Good bacteria showing promise for the treatment of Crohn’s disease, ulcerative colitis

‘Good’ bacteria show promise for clinical treatment of Crohn’s disease, ulcerative colitis — ScienceDaily

“A new study published in Nature Communications demonstrates that a consortium of bacteria designed to complement missing or underrepresented functions in the imbalanced microbiome of inflammatory bowel disease (IBD) patients, prevented and treated chronic immune-mediated colitis in humanized mouse models”. The study’s senior author, Balfour Sartor, MD, Midget Distinguished Professor of Medicine, Microbiology and Immunology, Co-Director of the UNC Multidisciplinary IBD Center, said the results are encouraging for future use in treating Crohn’s disease and ulcerative colitis patients.

“The idea with this treatment is to restore the normal function of the protective bacteria in the gut, targeting the source of IBD, instead of treating its symptoms with traditional immunosuppressants that can cause side effects like infections or tumors,” Sartor said.


Chronic intestinal inflammation can be induced by multiple exogenous and endogenous signals and is mediated by immune and nonimmune cells in genetically susceptible hosts with defects in epithelial barrier function, immunoregulation, or bacterial killing. Exogenous substances including dietary products, pathogenic microorganisms, xenobiotics including antibiotics, or various combinations thereof, can trigger initial mucosal injury and/or dysbiosis to initiate acute intestinal inflammation that is perpetuated by the antigenic activities of a subset of resident microbiota1,2. Examples of these conditions are inflammatory bowel diseases (IBD), which encompass two main clinical disorders: Crohn’s disease and ulcerative colitis. Current IBD treatments primarily control inflammation through anti-inflammatory and immunosuppressive mechanisms. Some of the most successful drugs for treating IBD include infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib, which target specific immune components to control the inflammatory process. However, these and other immune modulating drugs induce sustained, steroid-free remission in only a small subset of patients and can have multiple serious side effects, including an increased risk for serious and potentially life-threatening infections and neoplasia. In addition, these drugs do not correct upstream conditions that contribute to the chronic inflammatory mechanisms, including the leaky mucosal barrier, a pro-inflammatory gut microbiome and immunoregulatory defects.

As an alternative to anti-inflammatory and immunosuppressive therapies, microbiome-inspired live biotherapeutic products (LBPs) are being developed to treat conditions linked to chronic intestinal inflammation and increased permeability. The traditional approach for LBP discovery has been to compare the microbiomes of healthy subjects and patients suffering from a specific condition, such as IBD, to identify microorganisms that are lacking or under-represented in large databases, such as the HMP2 project3. This information, further enforced by the results from microbial association studies, is used to propose a therapeutic formulation to replenish the microorganisms that are lacking or under-represented2,4. In the case of IBD, early efforts have focused on the use of strains belonging to the Clostridium clusters IV and XIVa, which were found to successfully decrease inflammation in rodent IBD models5,6,7. Using germ-free (GF) mice inoculated with healthy human fecal material pretreated with chloroform to enrich for spore-forming bacteria, a stable 17-strain consortium was enriched from a single donor based on their ability to induce colonic regulatory T cells (Tregs)7,8. This consortium was comprised of spore-forming Clostridium cluster IV, XIVa, and XVIII strains that produced butyrate and decreased the severity of several colitis models7.

Open label application of Fecal Microbiome Transplants and enrichment-based approaches have several disadvantages. The outcome is defined by the stool sample used for the enrichment, with different samples representing different consortia with variable efficacy;9 undesirable strains/functions associated with safety risks including virulence factors and transferable antibiotic resistance functions might be present, such as the presence of enteropathogenic and Shigatoxin-producing Escherichia coli strains10 and antibiotic-resistant E. coli strains11 in FMTs, or the presence of transferable vancomycin resistance elements as found in the genome of the VE202 consortium strain Blautia coccoides VE202-06 (GenBank Accession Number Accession: PRJDB525). Furthermore, consortium modeling, as presented in this study, shows that other bacterial species besides spore-forming Clostridium bacteria provide metabolic support and additional therapeutic functions required for optimal engraftment and therapeutic performance of live biotherapeutic products in the hostile gut environment of patients with intestinal inflammation. These shortcomings can be addressed by a bottom-up rational consortium design approach that is rigorously informed by mechanistic modeling and insights from microbiome ecology and disease pathogenesis. We used this approach to combine well-characterized strains isolated from many healthy human stool samples into a consortium of metabolically interdependent strains with a variety of therapeutic functionalities being distributed in a redundant way between strains. Initially a 17-strain consortium, GUT-103, was designed around publicly available strains. GUT-103 rapidly colonized mice, restored normal function to the inflamed colon, and prevented and reversed established experimental colitis in gnotobiotic mice. Based on these proof of concept studies, a refined 11-member consortium, GUT-108, was designed around a panel of proprietary human bacterial strains that strongly engrafted and provided similar redundant protective functions. Therapeutically applied GUT-108 corrected functional dysbiosis of the inflamed gut microbiome and treated established colitis in a humanized mouse colitis model while decreasing opportunistic pathogenic bacteria, increasing resident protective bacterial groups, and restoring immunologic and metabolic homeostasis.


Resident bacterial strains of the GUT-103 and GUT-108 consortia, designed to interdependently restore normal function to the inflamed colon, rapidly colonized gnotobiotic mice as well as ex-germ-free humanized mice that had developed a pro-inflammatory gut microbiome. These GUT-103 and 108-colonized mice exhibited the desired functional properties consistent with the rational design of the two consortia.

The two separate rationally designed consortia of intestinal bacterial strains with redundant functionalities that were previously found to be under-represented in the gut microbiome of IBD patients with active disease3 were shown to promote homeostatic immune functions and bacterial metabolism and prevent onset or progression of intestinal inflammation. We believe that this approach has the potential to maintain long term remission in a physiologic and safe manner, which should be tested in a Phase 1 clinical trial.

Testing GUT-103 against EER-induced colitis in gnotobiotic Il10−/− mice is clinically relevant to human Crohn’s disease because adherent-invasive Escherichia coli and Ruminococcus gnavus are increased in active Crohn’s disease3,31,32 and the adherent-invasive E. coli strain used was isolated from the ileum of a Crohn’s disease patient33. GUT-108 showed therapeutic efficacy to reverse established colitis in Il10−/− humanized mice by intervening 2 weeks after onset of moderate-severe intestinal inflammation, supporting a potential role for GUT-108 to treat active IBD. Moreover, the Il10−/− model of chronic pathobiont-driven T-cell-mediated chronic inflammation is more predictive of therapeutic responses in IBD patients than acute epithelial injury models such as dextran sodium sulfate2.

GUT-103 and GUT-108 were designed based on human data showing that protective functions provided by commensal bacteria are under-represented in the gut microbiome of IBD patients. These functions include the synthesis of SCFAs, indole and its derivatives, bile acid deconjugation and conversion, and competition for the critical nutrient iron and the synthesis of antagonistic molecules to control opportunistic pathogens3,34. Several animal studies have highlighted the role for SCFAs, especially propionate and butyrate, in regulatory T cell recruitment and function8,12,13,34,35,36. The recruitment in the colon and extrathymic conditioning of regulatory T cell response by SCFA make these molecules an important link in the crosstalk between the gut microbiome and the immune system. Therefore, commensal bacteria identified to produce propionate and butyrate were selected in the rational design of GUT-103 (Table 1) and GUT-108 (Table 2).

Several studies have shown the role of indole, a metabolite produced from tryptophan, and its metabolites in reducing attachment of pathogenic E. coli to epithelial cells37, strengthening the mucosal barrier and mucin stimulating production38. Therefore, commensal bacteria identified to produce indole and its derivatives were selected in the rational design of GUT-103 (Table 1) and GUT-108 (Table 2).

An inflammatory gut microbiota can result in the inefficient microbial conversion of bile salts into their primary and secondary bile acids3. IBD patients with an unbalanced gut microbiome due to inflammation have lower fecal and circulating concentrations of secondary bile acids and higher conjugated fecal bile acid concentrations than do healthy subjects39. Thus, activities essential for the conversion of primary bile acids, specifically the conversion of CA and TCDCA acid via a multistep process that includes 7-alpha-dehydroxylation by 7-alpha dehydratase (7-α-DH) or 7-alpha-hydroxy steroid dehydrogenase (7-α-HSD) activity15, are included in the strain selection for GUT-103 (Table 1) and GUT-108 (Table 2).

Competition for iron helps drive the competitiveness and establishment of microorganisms40. Therefore, GUT-103 (Table 1) and GUT-108 (Table 2) include several strains that synthesize one or more siderophores under iron-limiting conditions. Ideally, these siderophores are insensitive to inhibition by Lipocalin-2, a peptide that inhibits specific siderophores and their uptake, and is a major colonic defense system triggered by bacterial infections. Lipocalin-2 levels were increased after induction of inflammation in Il10−/− mice colonized with the EER consortium (Fig. 1c) or human fecal microbiota (Fig. 4c).

Bacteriocins, of which lantibiotics are considered a specific class, have shown great promise as new antibiotics for therapeutic application, as reviewed by Field et al.41. Thus, bacteriocin synthesis was included as a key functionality in strain selection as part the rational design process of GUT-103 (Table 1) and GUT-108 (Table 2).

The optimized 11-strain GUT-108 consortium was rationally designed to build on the proof-of-concept results obtained with GUT-103. GUT-108 went beyond members of the Clostridium clusters IV and XIVa strains, including Bacteroides and Akkermansia species. Furthermore, based on their genome analysis, strains with undesirable properties including the presence of transferable antibiotic resistances or putative virulence factors were excluded. We also omitted species that are fastidiously anaerobic, such as Faecalibacterium prausnitzii, from the GUT-108 consortium. Compared to GUT-103, GUT-108 strains provide additional redundancy for the synthesis of the protective secondary bile acids LCA and DCA, plus multiple mechanisms to compete with opportunistic pathogenic Enterobacteriaceae including synthesis of the siderophore yersiniabactin, and lantibiotics. In the inflammatory gut environment of humanized Il10−/− mice, beneficial Lachnospiraceae and Ruminococcaceae family members are decreased while opportunistic Enterobacteriaceae are increased42, as reported for Crohn’s disease patients32,43. Therapeutic application of GUT-108 reduced levels of colitogenic Enterobacteriaceae and increased beneficial resident Clostridium (Clusters IV and XIVa) species, especially Lachnospiraceae including Dorea species and Lachnoclostridium species that are not GUT-108 constituents (Fig. 4b). This altered community composition increased cecal luminal propionate concentrations, but not butyrate levels (Fig. 4f). Previous studies demonstrated that butyrate levels are not necessarily an indicator of a healthy gut microbiome, as butyrate synthesis from fermentation of amino acids such as lysine can contribute to inflammation under conditions associated with mucosal permeability44.

GUT-108 increased expression of Gpr41 and showed an upward trend for Gpr43 in Il10−/− mice humanized with a fecal transplant (Supplementary Fig. 5). As previously reported, SCFA produced by gut bacteria stimulate Tregs8 with propionate’s effect mediated through GPR4336. SCFA also mediate the function of GPR41, a key regulator that controls host energy balance45.

With its functional redundancy and metabolically interdependent auxotrophies, GUT-108 is designed to engraft and perform under a wide range of conditions. When applied to Il10−/− mice humanized with a fecal transplant, all GUT-108 strains except Clostridium scindens GGCC_0168 were established for at least 2 weeks. Clostridium scindens has been previously described as one of the essential strains necessary to convert primary bile acids into LCA and DCA. However, despite the absence of this strain, the established functional multi-strain network produced secondary bile acids, with Extibacter sp. GGCC_0201 providing the 7α-dehydratase activity required to convert CA and CDCA into the therapeutic secondary bile acids DCA and LCA, respectively. Normalizing the intestinal bile acid profile can restore intestinal epithelial stem cell function46, and increase colonic RORγ+ Treg cell counts that ameliorate host susceptibility to colitis47, while LCA stimulates Treg differentiation and inhibits Th17 cells48 consistent with GUT-108’s ability to restore secondary bile acid metabolism (Fig. 4f) and activate inducible IL-10+ RORγ FoxP3+ CD4+ Treg cells (Fig. 3f). GUT-108 stimulated regulatory (protective) immunity by increasing numbers of colonic LP IL-10-producing CD4+ T cells, B cells and DC and numbers and percentages of regulatory T cells, including inducible Tregs (IL-10+ RORγT+ FoxP3+ CD4+ cells) and IL-10+ Tregs (Fig. 3f). We further documented the anti-inflammatory effects of therapeutic GUT-108 in Il10−/− mice humanized with a fecal transplant by demonstrating that GUT-108 decreased IFN-ɣ+, IL-17α+, and IFN-ɣ+ IL-17α+ synthesizing colonic LP CD4+ TH1 and TH17 cells (Fig. 5a) and reduced expression levels of innate and Th1 and Th17 pathway cytokines, including IL-1β, IL-12p40, IL-13, IL-17α, IFNγ, and TNFα (Fig. 5b). Interestingly, GUT-108 treatment increased expression of IL-15 mRNA, a homeostatic cytokine that controls T cell inflammatory responses. Exogenous IL-15 treatment decreases IL-17α expression by Th17 cells in vitro through STAT5 enrichment at the IL-17 locus49, consistent with the ability of GUT-108 therapy to increase IL-15 gene expression and decrease IL-17α mRNA expression in colonic LP cells (Fig. 5b).

Increased intestinal bacterial metabolism of tryptophan, especially indole and its derivatives IAA and IPA, activates the Ahr pathway. AHR acts as a sensor of the microbiota community and, through its established role of modulating immune functions, maintains host-microbe homeostasis50. IPA is also a pregnane X receptor (PXR) agonist mediating its responses through TLR451. GUT-108 therapy increased both IAA and IPA levels in stool (Fig. 4f) and colonic Ahr gene expression (Fig. 5c). AHR is a critical mediator of anti-inflammatory responses to infection by bacterial pathogens and of the differentiation and function of immune cells including T cells, innate lymphoid cells, macrophages and DC28. AHR promotes the expression of the anti-inflammatory cytokine IL-10 and inhibits macrophage apoptosis, decreases the expression of inflammatory cytokines (IL-6 and TNF-α) and inhibits activation of NF-κB. Therefore, the Ahr pathway is critical to protect from excessive inflammatory cytokine expression and septic shock. In addition, Ahr pathway activation protects the mucosa during inflammation52.

Efficacy of GUT-108 in Il10−/− mice is mediated by IL-10-independent mechanisms. Further insights into these possible protective mechanisms include increased expression of metabolite sensors and mediators (Gpr41, Gpr43, Fxr, Pxr, Pparg, Fgf15, Fgf21) and pathways mediating differentiation of immune cells including Treg and Breg cells (cMaf, Il5, April, Aid, Bcl6) (Supplementary Fig. 5). For example, intestinal epithelial FGF15 is activated by bile acids serving as ligands for the nuclear receptor farnesoid X receptor (FXR). FXR/FGF15 signaling regulates bile acid homeostasis and protects against experimental colitis53. APRIL impacts immune regulatory T cells by stimulating their proliferation and survival, and directly contributing to their immune suppression54. Bcl6 induces IL-10 and follicular T helper cells and regulates the balance of innate lymphoid cells subsets55. Decreased expression of Nos2 (Supplementary Fig. 5), a part of the Ace2 -Nos2-IFNɣ biosynthesis gene cascade56, could lead to lower levels of ACE2, a key regulator to control intestinal inflammation induced by epithelial damage57. Certain viruses, including the coronaviruses SARS-CoV-1 and SARS-CoV-2, use the ACE2 protein for infecting respiratory and intestinal epithelial58. Therefore, chronic gut inflammation, as seen in type-2 diabetes and obesity59 might trigger elevated gut epithelial ACE2 levels, and therefore patients suffering from these conditions could be more sensitive for Coronavirus infection and at higher risk for complications, highlighting the importance of therapeutically targeting the pro-inflammatory gut microbiome as the underlying cause of chronic inflammation60.

In addition to analyzing fecal material, we measured cecal microbiota and in some cases cecal luminal metabolites to represent bacterial communities and function within the cecum/colon, since the cecum is one of the sites of most active inflammation (Fig. 4d). Previous rodent studies have shown broadly similar microbial patterns in cecal luminal and fecal samples61. Furthermore, we demonstrate similar cecal (Fig. 2) and fecal (Fig. 4f) secondary bile acid (LCA and DCA) responses to GUT-103 and GUT-108, respectively.

Although no animal model completely replicates all clinical features of human Crohn’s disease or ulcerative colitis, we believe that our use of a human fecal transplant in germ-free mice to initiate chronic TH1/TH17-mediated colitis and our treatment protocol of administering GUT-103 and 108 to mice with established mild to moderate inflammation replicates IBD as closely as feasible for preclinical studies. Proof of efficacy in human IBD will have to await a clinical trial.

GUT-103 and GUT-108 combine multiple modes of action to treat the upstream causes of inflammation by correcting the abnormal microbiome environment, activating various IL-10 synthesizing immune cells, lowering inflammatory responses, and restoring bacterial metabolic profiles to levels found in stool samples of healthy individuals. These overlapping protective mechanisms are predicted to maintain long term remission of IBD in a physiologic and safe manner, in contrast to most biologicals, which block downstream immune effector responses by neutralizing a single cytokine or molecule and induce immunosuppression that can be associated with increased infection and neoplasms. These integrated protective mechanisms make GUT-108 a promising novel therapy to treat a range of conditions whose pathogenesis is characterized by dysbiosis-mediated chronic intestinal inflammation and increased mucosal permeability. Besides IBD this could include graft versus host disease, hepatic encephalopathy, alcoholic liver disease, atherosclerosis, hypertension, obesity, metabolic syndrome, and type-2 diabetes mellitus.

Reference: van der Lelie, D., Oka, A., Taghavi, S. et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat Commun 12, 3105 (2021).

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A study has linked psychological stress to Crohn’s Disease Flare-up

McMaster-led study links stress to Crohn’s disease flare-ups “The main takeaway is that psychological stress impedes the body’s ability to fight off gut bacteria that may be implicated in Crohn’s disease. Innate immunity is designed to protect us from microbes that do not belong in the gut, like harmful bacteria,” said senior author Brian Coombes, professor and chair of biochemistry and biomedical sciences at McMaster.

“When our innate immune system functions properly, it prevents harmful bacteria from colonizing us, but when it breaks down, it leaves an opening for pathogens to colonize locations they normally cannot and cause illness.”

Below is the introduction and discussion of the study.


Crohn’s disease (CD) is an inflammatory disorder of the gastrointestinal tract triggered by microbial and environmental insults1,2,3. The global burden of disease associated with CD is rising, particularly in developed countries where an upward trend in incident cases has occurred for decades. Emergent disease is now appearing in Asia, Africa, and South America4. Current standards of care, including immunomodulatory biologics, are expensive and have high rates of primary and secondary non-responsiveness. Thus, there is an urgent unmet clinical need to better understand the microbial and environmental triggers of CD that will underpin new preventions and therapies.

The CD-associated microbiome has been intensely scrutinized as a source of inflammation in the gut5,6,7. General microbial features in CD include decreased community diversity, reduced levels of Clostridiales, and increased abundance of Proteobacteria7,8,9. Clinical observations consistently show bacteria in close association with the mucosal epithelium in Crohn’s patients, particularly members of the Enterobacteriaceae that are enriched in virulence and secretion pathways10,11,12. Adherent-invasive Escherichia coli (AIEC) is an abundant pathobiont at inflamed sites in the gut13,14. Numerous studies have confirmed that AIEC are enriched in humans with CD compared to healthy subjects and are often the dominant bacterial species present15,16. AIEC have a multiphasic lifestyle and can grow as extracellular planktonic cells, in biofilms, and intracellularly in epithelial cells and macrophages, where they induce host inflammatory pathways17,18,19,20. Thus, understanding the colonisation dynamics of AIEC is expected to yield insights into the progression of CD and may inform therapeutic intervention.

Several components of mucosal immunity are disrupted in CD. These include epithelial barrier integrity, mucous production and cell turnover, the production of antimicrobial peptides and proteins (AMPs), and the release of metal ion scavengers that contribute to nutritional immunity21,22,23. Nutritional immunity functions to limit bacterial growth by sequestering essential nutrients and metals required for bacterial replication22. Collectively, these elements of mucosal immunity work to spatially restrict bacteria largely to the gut lumen and to reduce the overgrowth of pathogens24. Interleukin (IL)-22 is a cytokine that regulates several aspects of mucosal immunity in the gut, including the production of AMPs and the activation of nutritional immunity25,26 Some enteric pathogens including Salmonella and Citrobacter can overcome IL-22-dependent host defenses through AMP resistance and metal acquisition systems that bypass the host defense proteins lipocalin (Lcn2) and calprotectin27,28. Similarly, IL-22 has been implicated in the induction of other iron scavengers, including hemopexin and haptoglobin, that can control the enteric pathogen Citrobacter rodentium29. The role of IL-22 in host control of CD-associated pathobionts has not been explored.

Disease expression in CD patients follows a relapsing and remitting course, where relatively asymptomatic periods are followed by heightened inflammation and disease activity30,31. A considerable body of clinical literature establishes psychological stress as a disease modifier in CD32,33,34,35,36. Episodes of acute psychological stress are associated with flares, relapse, and increased inflammatory markers in both the serum and mucosa of patients with CD and ulcerative colitis33,34,37. Rodent models of stress have extended these findings, demonstrating increased inflammation38, barrier disruption38,39,40, reactivation of disease induced by chemical exposure38,41, and increased susceptibility to enteric infection42. A previous study demonstrated that chronic stress coupled with DSS-induced colitis resulted in a modest alteration in inflammation and microbiome composition in the cecum and colon43. However, the mechanisms driving the mucosal and microbiological dysfunction associated with psychological stress remain unknown, particularly in the ileum.

Here we show in a pre-clinical model, designed to investigate the comorbid effects of psychological stress on microbial composition and immune pathways in the gut, that stress induces a multidimensional loss of host protection, provoking a dysbiotic shift in the ileal microbiome dominated by AIEC and other Enterobacteriaceae, with attendant immunological and barrier defects. These mucosal deficits are traced back to an apoptotic depletion of CD45+CD90+ cells resulting in the loss of protective IL-22 signaling that blunts AMP responses and barrier repair. The combined effects of nutritional immunity and stress-induced impairment of protective IL-22 responses create a favorable niche for AIEC expansion. These deficiencies are correctable using either exogenous IL-22, or by blocking stress-induced glucocorticoid signaling, which restores mucosal immunity and averts ileal dysbiosis including the expansion of AIEC. These data indicate that immunomodulation can normalize the dysbiotic shifts associated with CD in response to psychological stress, providing avenues for therapeutic interventions.


CD patients experiencing psychological stress are more likely to relapse and have increased disease activity, yet the mechanisms underlying this remain obscure33,65,66,67. Likewise, despite a higher frequency of AIEC colonization in CD patients, the host factors that influence the fluctuation of AIEC load in patients are not understood68. Current evidence indicates that AIEC is a pathobiont in the human gut and takes advantage of inflammatory niches derived from host insults, such as antibiotic use69, secondary enteric infections20, western diet70, and/or genetic predisposition71. In this study, we determined that psychological stress is associated with impaired IL-22-dependent mucosal antimicrobial defenses that result in profound small intestinal dysbiosis dominated by AIEC expansion.

Previous studies have demonstrated a link between intestinal dysbiosis and inflammation in mice47,72,73 and in IBD patients7. In our study, exposure to acute psychological stress resulted in a profound dysbiosis dominated by outgrowth of Enterobacteriaceae family members and genera commonly found to be enriched in CD patients7,8,9. For instance, an enrichment of Enterococcus faecalis is strongly associated with disease severity in CD patients74, and this species was also enriched following exposure to psychological stress. Bifidobacterium, which are commonly associated with intestinal health and generally have decreased abundance in CD, were also decreased following overnight stress.

Psychological stress has traditionally been considered anti-inflammatory in nature, owing to the production of glucocorticoids50,75,76. Our findings, in line with a recent publication43, demonstrate that stress induces a mixed inflammatory response. In our model of psychological stress, the pro-inflammatory features appear to play a dominant role in shaping the microenvironment that favors the expansion of AIEC. For example, mice exposed to stress had reduced expression of genes associated with barrier function, including tight junctions and mucins. The encroachment of AIEC towards the epithelium and dissemination to systemic sites that we observed following stress is likely facilitated by these weakened physical barriers, which further provokes the host inflammatory response. Indeed, we observed more pronounced barrier defects, increased pro-inflammatory cytokine expression, and dysbiosis in AIEC-colonized mice exposed to psychological stress compared to AIEC-naive mice exposed to the same stressor. Thus, the combination of inflammation-tolerant bacteria like AIEC, and the mucosal defects brought about by stress, appear to create a tipping point in gut homeostatic balance that favors inflammation.

Interestingly, while nutritional immunity was necessary, it was not sufficient to phenocopy the ileal dysbiosis induced by stress. Indeed, psychological stress independently impaired IL-22-driven protective mucosal immunity against AIEC. A pivotal role for IL-22 was revealed using IL-22 depletion and administration of IL-22-Fc to probe the functional consequences of this pathway during stress. Administration of IL-22-Fc functionally restored the expression of genes downstream of IL-22 signaling including fut2 and antimicrobial proteins which appeared to have a functional effect in preventing stress-induced AIEC expansion and in correcting the ileal dysbiosis that occurred following stress. Interestingly, recent clinical studies are evaluating the use of IL-22 in the treatment of IBD patients (Clinical Trial: NCT03558152, NCT02749630). When ileal explants taken from mice exposed to stress were stimulated with IL-23, these tissues failed to produce IL-22 whereas ileal tissues from unstressed mice showed a robust IL-22 signature, suggesting that the IL-22 producing cell population was depleted following psychological stress. Indeed, the gut of mice exposed to psychological stress had a significant reduction in the number of CD45+CD90+ cells in the small intestine following psychological stress, which we directly linked to stress because this cell population was restored by blocking glucocorticoid signaling.

Although psychological stress impaired IL-22-dependent host protection, nutritional immunity appeared to remain intact, and in fact was required for AIEC expansion. The host protein calprotectin sequesters zinc, manganese, calcium, and iron under states of inflammation59,77. In response to host nutritional immune pressure, some Enterobacteriaceae have evolved mechanisms to exploit nutrient limitation to outcompete commensal microbes27,28,78. For example, Salmonella expresses a high-affinity zinc transporter, ZnuABC, and can thrive in the presence of calprotectin-mediated nutritional immunity77. Interestingly, AIEC appears to also thrive in inflammatory environments13,14 and has acquired the ZnuABC transporter, likely providing a fitness advantage in states of nutritional immunity. Given the essentiality of iron for bacterial replication, the host has multiple mechanisms to limit the availability of iron in its various forms. Iron is typically transported complexed with heme and is a common target of bacterial species79,80. As such, the host sequesters free-heme in pathophysiological settings22,29. Accordingly, we found that both HPX and haptoglobin were upregulated during psychological stress exposure, potentially limiting iron availability to bacterial species22,29,81. Enhanced recruitment of neutrophil-like CD11b+Gr1+ cells in our model was accompanied by robust induction of neutrophil-derived Lcn2 following stress. The host releases Lcn2 to limit the acquisition of iron-bound enterobactin, preventing its reuptake by commensal strains of E. coli23. Unlike most commensal strains, many AIEC encode the biosynthetic and secretion machinery for salmochelin, a glycosylated variant of enterobactin that evades Lcn2 sequestration27,60,82 and provides a competitive advantage to Salmonella27,82. Indeed, AIEC derived a salmochelin-dependent competitive advantage in stressed mice, but not in unstressed mice, indicating that psychological stress creates a competitive gut environment that appears to benefit microbes that have evolved mechanisms to evade nutritional immunity. Interestingly, we found that neither LPS-mediated induction of iron limitation, nor CD90 depletion, in isolation, was sufficient to phenocopy the AIEC expansion seen during stress. Instead, our data are consistent with a combinatorial effect of psychological stress whereby the combined activation of nutritional immunity and immune cell attrition support the intestinal dysbiosis seen following psychological stress.

Overall, our study shows that psychological stress creates a beneficial environment for AIEC, a CD-associated pathobiont in the gut. Given that the pathological changes observed following psychological stress are augmented in the presence of AIEC, this work establishes a rationale for future studies to dissect the relative contributions of the microbiome and psychological stress on the gut environment. In our current study, AIEC appears to derive this benefit by evading host nutritional immunity while taking advantage of an impaired induction of IL-22-mediated host defenses that rely on antimicrobial proteins and barrier maintenance. Thus, in the presence of pathobionts that efficiently evade nutritional immunity, this aberrant stress-induced host response provides a promiscuous niche for their unregulated expansion. The ability of IL-22 treatment to correct both mucosal host defenses and prevent E. coli-dominated ileal dysbiosis provides compelling rationale for continued investigation of this intervention. This work reveals insight into the role that psychological stress plays in disease expression of CD. Uncovering the interactions between microbes, the host immune system, and epithelial host defenses will lay the biological underpinnings that guide preventions and therapies that address unmet clinical needs for CD management.

Reference: Shaler, C.R., Parco, A.A., Elhenawy, W. et al. Psychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts. Nat Commun 12, 6664 (2021).

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Stress and Inflammatory Bowel Disease: Clear Mind, Happy Colon

The Authors

Joaquim Francisco Maria De Sousa, Smit Paghdar, Taheseen M. Khan, Nishant P. Patel, Savitri Chandrasekaran, Nicholas Tsouklidis


Inflammatory bowel disease (IBD) is a condition whose prevalence in the general population worldwide is increasing at an exponential pace. Many risk factors affect the incidence, progression, and overall outcome of IBD, one of them being psychological stress. This study examined the relationship between psychological stress and inflammatory bowel disease.

A search for relevant studies was conducted using PubMed, Google Scholar, ResearchGate, and SCOPUS. A systematic review was conducted on the relevant articles after critical appraisal.

This article mainly focused on studies that evaluated the presence of inflammatory markers observed in individuals who have been diagnosed with IBD and have high levels of psychological stress. It also assessed if lowering an individual’s psychological stress could help improve the outcomes of IBD.

Psychological stress can have a detrimental effect on individuals diagnosed with IBD. There is a need to conduct studies that can further confirm the association between psychological stressors, mental health conditions, and IBD. We should also encourage medical practitioners to educate patients who have been diagnosed with IBD regarding the benefits of stress reduction.

Introduction & Background

Inflammatory bowel disease (IBD) is an umbrella term that encompasses a group of inflammatory conditions that affect the small intestine and the colon. Crohn’s disease (CD) and ulcerative colitis (UC) are the two main subtypes of IBD [1].

UC is a chronic, inflammatory condition often limited to the colon and the rectum [2]. Patients with UC typically present with bloody diarrhea, tenesmus, and abdominal pain [3]. This was the first subtype of IBD to be discovered and serves as a starting point in the history of IBD. However, it is highly likely that the other forms were also present but not fully understood yet [4]. UC was first described in 1875 by two English physicians, Wilks and Moxon, who helped differentiate it from other diarrheal diseases caused by infectious agents [5]. In the following decades, the overall understanding of UC grew tremendously. Its role in causing cancer was better understood, and multiple treatment modalities followed soon after that.

CD is defined as “a chronic transmural inflammatory bowel disease, with skip lesions that may involve any part of the GI tract from the mouth to anus” [6]. Giovanni Battista Morgagni first described this condition. One of his case reports discussed a 20-year-old male patient who died following a prolonged spell of illness, including fever, abdominal pain, and bloody diarrhea. An autopsy was later performed, revealing perforations and transmural inflammation with ulceration, which extended from the terminal ileum to the colon. The report also suggested the presence of mesenteric lymphadenopathy and splenomegaly. Though Morgagni’s work was essential to introducing CD, it was an article written by Burrill B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer published in the Journal of the American Medical Association that gave us a better understanding of CD. The authors described a condition that affected the terminal part of the ileum. Its pathology included the presence of granulomas along with chronic necrotizing and cicatrizing inflammation in the ileum. There was also the presence of ulceration in the intestinal mucosa and connective tissue reactions, which repeatedly occurred, resulting in the obstruction of the intestinal lumen leading to the formation of fistulas. CD was recognized as a separate entity from UC in 1932 by Crohn et al. [4].

Due to the increasing number of newly diagnosed cases, there has also been a new interest in deciphering the risk factors that might be responsible for causing this disease [7]. Major risk factors such as high-fat diet, smoking (a risk factor for CD and a protective factor for UC), psychological stress, and appendectomy (a protective factor for UC and a risk factor for CD) have all been attributed to increasing the chances of being diagnosed with IBD in the future [8].

The relationship between the immune system, nervous system, and psychological processes is being established and has always been an area of considerable interest [9]. There is mounting evidence that associations between these systems play an essential role in IBD [10,11]. Psychological stressors affect the gut through various mechanisms, such as increased production of pro-inflammatory cytokines, activation of macrophages, and tumor necrosis factor through the hypothalamus-pituitary-adrenal axis [12].

IBD and psychological disorders share multiple pro-inflammatory pathways, such as the clinical expression of activated immune-inflammatory, oxidative, and nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT), autoimmune, and gut-brain pathways. These shared pathways are involved in the pathogenesis of IBD and psychological disorders, which can explain the concomitant flare-up of IBD in patients with depression as well as the worsening treatment outcomes of IBD patients who are diagnosed with psychological disorders [13].

In addition to the above-mentioned shared inflammatory pathways, the gut-brain axis has also been mentioned as one of the shared pathways between IBD and psychological disorders. This pathway involves bidirectional communication between the gut and the central nervous system. The principal component of this is the autonomic nervous system, of which the vagus nerve forms the core component. Stress is known to inhibit vagal nerve stimulation, which has anti-inflammatory properties, resulting in deleterious effects on the gastrointestinal tract. Early recognition and efforts to lower stress levels should help [14]. Figure 1 demonstrates the pathogenesis of IBD through the gut-brain axis.

Figure 1: Pathogenesis of IBD through the gut-brain axis.

IBD: inflammatory bowel disease

The United States had the highest age-standardized prevalence rate (464.5 [438.6-490.9]) per 100,000 population), followed by the United Kingdom (449.6 [420.6-481.6] per 100,000) [15]. As with any highly prevalent disease, there is a need to know the factors that trigger this condition. Psychological stress was a risk factor in many of these patients. It was also found that psychological stress caused a worsening of the quality of life in some IBD patients, and reducing stress levels in IBD patients helped in their remission [16]. Psychological stress is a risk factor that can be decreased if detected. Over time, various methods have been shown to help reduce stress, ranging from coping strategies to medications and lifestyle changes. Hence, gaining a better understanding of how psychological stress impacts the incidence and the outcomes of IBD has become paramount.

This review aims to explore the relationship between psychological stress on the incidence and outcomes of IBD. Further, this article aims to evaluate if reducing stress can help improve the chances of remission of IBD.

This article was previously presented as a poster at the International Virtual Medical Conference (IVMC): Spring Conference on April 23, 2022.


Effect of Psychological Stress on the Onset of IBD

Psychological stress can have a detrimental effect on our mental health and harm our physical well-being. In a study conducted in 2003 by Tuglu et al., 43 participants were chosen [17]. In total, 26 patients were diagnosed with major depressive disorder, and the remaining 17 were control subjects. This study aimed to examine the relationship between a psychological stressor such as major depressive disorder and an increase in pro-inflammatory cells such as IL-1, IL-6, and TNF-alpha. The measurement of these inflammatory markers was done at the start of the study and after six weeks of anti-depressant treatment. This study confirmed that psychological stressors have a role in increasing inflammatory markers as they were significantly higher in patients with major depressive disorders than in the control, and the levels of inflammatory markers markedly reduced after six weeks of anti-depressive treatment.

Another study by Mawdsley et al. aimed to study the rectal mucosa’s inflammatory response to psychological stress [18]. To assess this, serum IL-6 and IL-13 concentrations, TNF-alpha, and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, NK cell numbers, platelet activation, platelet-leukocyte aggregate (PLA) formation, substance P release, reactive oxygen metabolite (ROM) production, mucosal blood flow (RMBF), and histology were all actively measured in two groups of patients. One group underwent a stress test in which participants were asked to complete a 60-minute intelligent quotient (IQ) test in 50 minutes with music playing in the background and being repeatedly reminded to increase their efforts in completing the test. The second group underwent a control procedure and was asked to complete the same IQ test in 50 minutes but with background music of their choice. The inflammatory markers were measured before and after the process. This study also confirmed the presence of inflammatory response in individuals who experienced psychological stressors, which resulted in their relapses, further confirming that psychological stressors can cause an increase in inflammatory markers, which are seen in IBD.

Effect of Psychological Stress on the Disease Progression in IBD

Being diagnosed with IBD can be a traumatic experience for individuals from a physical and psychological standpoint. Patients diagnosed with IBD can present with various symptoms, such as abdominal pain, recurring bloody diarrhea, weight loss, and extreme tiredness. Many of these patients suffer from psychological stress due to being diagnosed with a chronic condition and from the symptoms they suffer. A few studies have shown that by reducing psychological stress, a patient’s quality of life is improved as a result of minimizing their psychological stress. One such study by Kuo et al. aimed to investigate the effect of stress reduction techniques on patients diagnosed with IBS and irritable bowel syndrome (IBS) [19]. This study enrolled 19 patients diagnosed with IBS and 29 IBD patients in a nine-week relaxation exercise called relaxation response-based mind-body group intervention (RR-MBI). A questionnaire regarding patients’ symptoms and inflammatory markers was used in a pre-post intervention study and after a short-term follow-up. This study showed that the patients’ pain scores and overall quality of life improved after the relaxation exercise.

Finally, a study by Gerbarg et al. evaluated the effect of a breath-body-mind workshop (a type of relaxation exercise) on various aspects of a patient who was diagnosed with IBD, such as their physical symptoms, inflammatory markers, and their psychological well-being [20]. In total, 29 patients diagnosed with IBD and enrolled in the Jill Roberts IBD centre were chosen and were randomly allocated to a group that would participate in the breath-body-mind workshop or an educational seminar. The IBD questionnaire, fecal calprotectin, C-reactive protein, perceived stress questionnaire, perceived disability scale, Beck anxiety inventory, and Beck depression inventory measures were obtained at baseline to measure the study outcomes and at weeks six and twenty-six. This study showed that patients enrolled in the breath-body-mind workshop were associated with significant improvements in their overall physical symptoms and psychological well-being and showed a drop in their C-reactive protein level. The studies mentioned above showed that stress reduction could benefit patients who have been diagnosed with IBD regarding their physical symptoms and psychological well-being and help improve their overall quality of life.

Effect of Psychological Stress and Mental Health Conditions on the Outcomes of IBD

Psychological stress and mental health conditions can also affect the disease outcomes, as described in a study by Persoons et al. in Belgium, whose aim was to study the effect of major depressive disorder on the outcomes of patients who were taking infliximab for luminal CD [21]. Major depressive disorder was diagnosed using the Patient Health Questionnaire. A total of 100 consecutive unselected patients were chosen for this prospective study. The patients were assessed at baseline and at four weeks after being treated with infliximab. Assessments included the patients’ clinical, psychosocial, and demographical disease-related biological parameters. The patients were then followed up clinically for the next nine months or had a flare-up. This study pointed out major depressive disorder as a risk factor for treatment failure with patients on infliximab and was responsible for earlier relapses in patients with CD.

A study by Bitton et al. aimed to identify if psychosocial, biological, and clinical parameters could predict relapse in inactive CD [22]. A total of 101 patients were recruited for this study, of whom 14 patients withdrew. Serum cytokines, anti-Saccharomyces cerevisiae antibodies, C-reactive protein, erythrocyte sedimentation rate, and intestinal permeability were measured every three months. Psychological distress was measured every month for a year. This study pointed out that patients under low stress or who did not engage in social diversion were less likely to relapse.

A large study conducted by Bernstein et al. aimed to study if stress, infections, antibiotics, or non-steroidal anti-inflammatory drugs trigger symptomatic flares in patients diagnosed with IBD [23]. A flare-up of the disease was identified using the Manitoba Inflammatory Bowel disease index. In total, 704 participants completed a baseline survey. These participants were selected from a population-based IBD register. They were followed up every three months for a year. This survey tracked the use of non-steroidal anti-inflammatory drugs, antibiotics, infections, major life events, and any forms of stressors faced by the participants. This study pointed out that stress was responsible for most symptomatic flare-ups in IBD.

Lastly, a study by Boye et al. aimed to test the theory that psychotherapy helped improve the overall disease progression and prevent relapses in patients diagnosed with IBD [24]. In total, 58 patients with UC and 56 patients with CD were selected and randomized to either receive treatment with standard medical management in one group or receive medical management and psychotherapy in the second group and were assessed at baseline, three, six, twelve, and eighteen months using the Inflammatory Bowel Disease Questionnaire to measure the outcomes. The study concluded that psychotherapy did not help improve the disease progression in patients diagnosed with IBD, nor did it reduce the chances of preventing relapse of the disease. Some of the studies mentioned above highlight that psychological stress and mental health conditions can contribute to relapses and symptomatic flare-ups in patients who have been diagnosed with IBD. Although some above-mentioned studies contradict this fact, this is an area that should be further investigated in the future. It can aid clinicians in formulating a follow-up plan that can help prevent relapses in patients diagnosed with IBD.

Limitations and future recommendations

Several studies and clinical trials did not have a large enough sample size. To better understand the relationship between psychological stress and IBD, much larger sample sizes would be needed in the future. Moreover, a few of the trials that were used are more than 15 years old. We need more studies in the future to confirm the extent to which psychological stress influences the disease course in IBD.

Recommendations for the future include allocating more resources toward further studying the link between IBD and psychological stressors and incorporating stress reduction techniques in the management plan for patients diagnosed with IBD.


While many risk factors can affect the overall course of disease for a patient who is yet to be diagnosed or has already been diagnosed with IBD, studies have found that stress and mental health conditions can increase inflammatory markers, thus increasing the probability of being diagnosed with IBD in the future. Studies have reported that stress can cause earlier relapses in patients with inactive IBD. In addition to affecting the incidence of IBD, stress reduction can reduce symptoms in patients who have already been diagnosed with IBD, hence improving the quality of their lives. We believe this article can further incite interest in investigating the relationship between IBD and psychological stressors. It can encourage medical practitioners to gauge stress levels in patients diagnosed with IBD during their consultation or with the help of questionnaires. They can then advise these patients of the benefits of stress reduction and recommend ways to do this using techniques such as mindfulness-based interventions, cognitive behavioral therapy, and similar stress alleviating processes.

Reference: De Sousa J, Paghdar S, Khan T M, et al. (May 15, 2022) Stress and Inflammatory Bowel Disease: Clear Mind, Happy Colon. Cureus 14(5): e25006. doi:10.7759/cureus.25006

Link to website: Cureus | Stress and Inflammatory Bowel Disease: Clear Mind, Happy Colon

A small taste of anti-inflammatory food

Learn about the real impacts that anti-inflammatory foods can have on managing your IBD and a few alternative ways to include nuts in your diet.

By Anne-Marie Stelluti

About the Author
Anne-Marie Stelluti is a registered dietitian in Vancouver and business owner of Modern Gut Health, a private practice with a special focus in digestive health nutrition. She is a graduate from McGill University and is a member of the College of Dietitians of British Columbia

Can anti-inflammatory foods have any benefits for
people with IBD?

Anti-inflammatory foods can definitely have benefits for people living with inflammatory bowel disease (IBD), and I recommend an anti-inflammatory diet to all of my clients with IBD. By eating more anti-inflammatory foods, like walnuts and extra-virgin olive oil, and less pro-inflammatory foods, like refined white sugars and processed foods, this can help reduce the levels of inflammation in the body.

Eating certain anti-inflammatory foods like turmeric has even been shown to help reduce CRP levels, an inflammatory marker in the blood and one that is elevated during a flare-up of IBD. Eating anti-inflammatory foods regularly may help promote remission and prevent flare-ups, thereby reducing the risk of surgery and/or use of medications.

Food is notoriously hard to study in IBD because there are so many confounding factors, including the type of IBD, location of the disease, diet, and all the different medications and supplements involved. Although we still need high-quality research in this area, it makes sense that eating more anti-inflammatory foods can only help, and it certainly isn’t harmful when you’re eating real and whole foods.

Food is an area that people can control, and I feel that people living with IBD want to do everything they can to reduce their risk of flare-ups, and an anti-inflammatory diet is a healthy and unrestrictive way to do it. There is no one anti-inflammatory diet, however, and the key is to eat plenty of anti-inflammatory foods daily, whether you’re following a Mediterranean diet, vegetarian diet, paleo diet, or no special diet at all. Nutrition plays a huge role in the prevention of disease and optimisation of health, and it’s never too early or too late to start eating an anti-inflammatory diet.

What should people with IBD know about consuming
solid nuts?

People with IBD should know that when they’re feeling well and in remission, they will likely tolerate solid nuts well. It’s important to chew them well however, at least fifteen chews per bite of solid food for optimal digestion and processing.

Nuts are a great source of protein, energy, fibre, and healthy anti-inflammatory fats, which is especially helpful for those who need to gain weight. They also make an easy and portable food to snack on. The exception to eating whole nuts during remission would be for people who have a stricture or narrowing of the intestine. They would have to avoid solid nuts in the long-term because of the risk of intestinal blockage.

Are there alternative ways to eat nuts?

During a flare-up of IBD, people living with IBD should know that they will likely not tolerate solid nuts in their whole form. I suggest having smooth nut butters instead to minimise any gut symptoms and give the gut some rest during this time. Smooth nut butters can also help to reduce diarrhea and maintain energy and protein levels during a flare. I suggest adding a tablespoon or two of smooth nut butter to sourdough bread, oatmeal, overnight oats, smoothies, energy balls, mild curries, and even certain soups (e.g. Moroccan, African).

Homemade Walnut Butter

You can also make your own nut butter (e.g. homemade walnut butter) if you have a high-powered blender or food processor, which is a lot cheaper than what you will find in the store, and it’s actually pretty easy to make.

It can be personalised to your taste and you can use a mix of your favourite nuts (raw or toasted), and/or coconut butter and even anti-inflammatory spices like
cinnamon, ginger, or turmeric, to make it unique and flavorful.

Walnuts are one of the most anti-inflammatory nuts out there, and I recommend them to everyone following an anti-inflammatory diet to optimise both gut and brain health, because let’s be honest, who doesn’t want that?

Salad dressing

Smooth nut butters can be used to make an easy nut butter dressing (e.g. in a glass jar shake together 3 tbsp smooth almond butter, 3 tbsp vinegar: balsamic, red wine or raw unpasteurised apple cider vinegar, and 3 tbsp water)

A small taste of the low fodmap diet

By Anne-Marie Stelluti

About the Author
Anne-Marie Stelluti is a registered dietitian in Vancouver and business owner of Modern Gut Health. She is a member of the College of Dietitians of British Columbia, and has completed FODMAP training with Monash University in 2019.

Discover more about how the low-FODMAP diet is relevant to you and what you need to be mindful of when committing to the regimen.

What would you say most motivates you as a dietitian?

 Helping others in a meaningful and fulfilling way is what motivates me most as a dietitian. It’s very rewarding to see the impact food and nutrition can have, especially when it comes to digestive health and diseases like IBD. When I see how people substantially improve their quality of life and start to feel better and get their life back, that really motivates me to keep going. I’m also really happy when they can reduce and/or even get off their medications.

What led you to work in the field of diet and nutrition?  

I always loved science, and food and nutrition has always been a passion of mine that I wanted to pursue. The field of dietetics was a way where I could encompass all of this. My dad was a great teacher, and I felt that nutrition was also an area that I could work in where I could teach and help others. It’s a field that’s always changing and you can always challenge yourself to learn more and become better. I don’t think I’ll ever get bored. Also, I wanted to work in the health field, but not in one that involved cutting or cleaning people up. Nutrition is a great way to do that!

What is a low FODMAP diet?

 A low FODMAP diet is a short-term elimination diet that involves avoiding high FODMAP foods for 2-6 weeks and then reintroducing them back in to see what you as an individual can tolerate. FODMAPs are a group of sugars that can cause bloating, gas, abdominal pain, and diarrhea in people with IBS and/or other gastrointestinal conditions like IBD. Examples of FODMAPs include lactose, beans, and prunes.

The diet has been shown to help reduce and improve gut symptoms in about seventy per cent of people with IBS, and most people notice an improvement within the first one to two weeks. I have seen it help and improve the quality of life of so many of my clients. It’s very rewarding to see someone go from being unable to travel or hike because they need to be close to a bathroom, to feeling better and not needing to worry about that at all. It’s like they have their life back.

The diet is much easier than it looks like at first glance, and with the help of a registered dietitian trained in FODMAPs, it can be made a lot easier and nutritionally sound.

Can a low FODMAP diet help people living with IBD and what kind of outcomes could they expect from following it?

A low FODMAP diet could help people with IBD who have IBS-like symptoms of abdominal pain, bloating, gas, and diarrhea, as well as the chronic diarrhea characteristic of microscopic colitis, or the bloating characteristic of small intestinal bacterial overgrowth (SIBO), which people with IBD may also have. The goal of the diet is symptom control.

FODMAPs themselves do not cause damage to the gut and they are found in healthy foods and are considered prebiotics, but they can cause gastrointestinal symptoms and distress in certain quantities.

It can really help to try the diet to identify your personal triggers so that you know what does and does not bother your gut. Your personal tolerances can also change over time, and it’s important to be aware of that.

What should people be careful or aware of when considering a low FODMAP diet?

People should be aware that it takes some time to prepare before starting the diet, and I recommend at The greatest challenge people will likely face will be eating out on a low FODMAP diet because of onion and garlic, which are two particularly high FODMAP foods that tend to be added to many foods (soups, sauces, marinades, stocks, etc). A registered dietitian can give you plenty of tips and meal ideas so that you don’t feel like you’re missing out and lacking in variety.

The other thing to be careful of when doing the low FODMAP diet is to avoid doing it in the long-term. This is relevant for some people who feel so much better that they are reluctant or afraid to reintroduce foods back in that may have triggered severe symptoms in the past. The elimination part of the diet is too restrictive to be followed long term, and it may be harmful to the healthy gut microbiome, which we could not live well without.

Our healthy gut bacteria do everything from digesting food to making vitamins, and they keep our intestinal lining strong and healthy, and that is not something you want to compromise through diet. A dietitian can help you go slowly in reintroducing foods back in if you are reluctant to do so, including starting with ones that are more likely to be well tolerated.

least a week to get ready and do that. I also recommend waiting until after a vacation or time of increased stress (e.g. moving) to do the elimination diet, as stress can impact our gut symptoms as well and the goal of the diet is to figure out if it helps reduce your gut symptoms. It is not recommended to start any new probiotics or supplements at the same time as the low FODMAP diet, because you want to see if the diet is working, not if it is the effect of probiotics or supplements.

A Potential New Dietary Therapy For Crohn’s Disease

Dr. Emma Halmos shares details on the emerging Crohn’s Disease Exclusion Diet and its future potential for managing Crohn’s.

About the Author

Dr. Emma P. Halmos is an Accredited Practising Dietitian and works with the Department of Gastroenterology at both The Alfred Hospital and Monash University in Melbourne

The first known diet therapy to treat active Crohn’s disease was exclusive enteral nutrition (EEN), which induces remission in up to 80% of patients.

Unfortunately, this process of removing all food and replacing it with a liquid nutritional formula for 6-8 weeks is difficult and strict adherence is key for the treatment to be effective.  Furthermore, ongoing EEN is unrealistic, so this treatment is not used to maintain remission.  Alternative dietary therapies with good evidence for inducing and possibly maintaining remission are needed.

Paediatrician and researcher Dr Arie Levine together with colleagues from Israel have developed a diet called the Crohn’s Disease Exclusion Diet (CDED) and assessed its potential to treat Crohn’s in a controlled trial of children with mild to moderate Crohn’s.  The trial showed that CDED combined with partial enteral nutrition (PEN) for six weeks was similar to EEN in gut healing but when CDED and PEN was extended to 12 weeks, remission was maintained whereas many people lost remission if they started eating freely after the usual 6 week EEN program.

This study has indicated that CDED with PEN may be a suitable replacement for EEN and its extended use may maintain remission.

The diet involves eating five foods daily, claiming to provide fibre and starches that are thought good for gut health, while removing certain food components thought bad for the gut.

While more varied than EEN, the CDED is very restrictive and does require the use of PEN to ensure nutritional adequacy. The idea is that the diet may become less restrictive in time under dietitian guidance, but how this impacts on Crohn’s activity is unknown.

Additionally, due to the very strict nature of the diet, we do not know the specific food components involved in Crohn’s activity, or whether it is effective in adults, but we are one step closer to a potential targeted diet for treatment as research continues.

The CDED should be completed in conjunction with a gastroenterologist and dietitian well versed in the diet to ensure that it is applied appropriately and that overall health, including response to medications and nutritional adequacy are not compromised.

How to best support an exercise routine with IBD

By Claudia Cramer

About the Author

Claudia Cramer holds a Bachelor of Nutrition and Exercise Science and a Masters of Dietetics from the University of Queensland. Claudia has also completed her Sports Nutrition qualifications. An area of particular interest and passion for Claudia is helping people optimise their gut health, ignited after she was diagnosed with an auto-immune disease (UC) in 2014. Her practice focuses on using food functionally to ease anxiety, depression and other mental health issues, plus improving the body’s overall wellbeing. Claudia likes to practice what she preaches; you’ll often find her at the gym, getting creative in the kitchen or brunching at a local cafe.

Having an inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease, has its challenges. Many of the challenges may be more physical, such as bowel may be more physical, such as bowel discomfort and urgency, lack of appetite, and general malaise and fatigue.

There are also other challenges with having IBD which may be more invisible to the outside eye, and that is the mental toll of having a chronic disease. Mental
health conditions such as depression and anxiety are more common in people with UC and Crohn’s disease than the normal population.

This makes sense from a biological perspective, as most of our serotonin(feel-good chemical) is made in our gut (digestive system), and UC and Crohn’s disease are inflammatory disorders that affect the digestive system. With that said, one thing we know that can help to manage IBD is regular exercise.

There are many benefits of physical activity when you have IBD, such as maintaining a healthy weight (which may help other comorbidities) and improving bowel regularly (if you are more prone to constipation). There are also mental health benefits. Regular exercise can improve our psychological health by reducing feelings of anxiety and depression and relieving stress. Despite the challenges that come with having an IBD, it can be reasonable to recommend incorporating regular physical activity into our weekly routines. When we are exercising, we can also utilise nutrition principles, to maximise our exercise efforts.

So, what are some things we can do to help support our exercise routine? Let’s look into some of the nutrition-exercise fundamentals.

Pre-workout nutrition
Before we exercise, we have a few goals. They include making sure we have enough energy for the exercising muscle to sustain the activity and that we are adequately hydrated. The primary fuel we use for our exercising muscle is carbohydrates. Therefore, our strategy will look at including a source of carbohydrate prior to exercise. Overall, we want to choose a food that is:

• Rich in carbohydrate to prime your fuel stores
• Low in fibre, especially if you have issues with your gut or feel very nervous
• Easy to digest – avoid foods overly high in fat or protein as these are slower to digest
• Familiar – practise your options in training and do not try anything new on an event day!

By including a small, carbohydraterich snack in the hour leading up to exercise, it can help to provide us with some immediate fuel (while not leaving us feeling too full, which would be uncomfortable during exercise).

Some ideas for pre-workout snacks
• A piece of fruit (for example a whole banana or an apple)
• Some yoghurt and berries
• A muesli bar
• Rice cakes with some honey
• Fruit smoothie
• Raisin toast with jam
• Tub of creamed rice with canned fruit

It is worth keeping in mind your individual tolerance to foods, and what might work for you in helping to manage your individual IBD condition.

Post-workout nutrition
We know the period after exercise is important nutritionally, and paying particular attention to nutrition recovery immediately after a training session or event has been shown to positively affect subsequent exercise performance.

We’re looking to:
• Replenish fuel (glycogen) stores used during the training session or competition with a carbohydrate rich food
• Deliver some lean protein to assist with muscle repair and synthesis
• Restore fluid and electrolytes lost in sweat.

Research has shown that co-ingestion of protein with a small amount of carbohydrate is a sweet spot in playing a critical role in muscle glycogen synthesis post exercise. What we would be looking for is around 14-28g protein and 56g carbohydrate in a post-workout meal.

What this might look like, specifically, is:
• 2 tubs of yoghurt and 2 cups of fruit salad
• A salad roll with 60g lean sandwich meat and a banana
• Lean chicken and salad roll
• A bowl of muesli with yoghurt and berries
• Spaghetti with lean beef bolognese sauce
• Chicken burrito with salad and cheese
• Spinach quiche with sweet potato crust
• A small tin of tuna on crackers, plus a banana

While I have provided some general recommendations for nutrition around exercise, it is important to tailor these recommendations to suit you and your condition. If you are experiencing a flare up of your IBD symptoms, perhaps choosing foods that you know are safe is more important than following a stricter nutrition plan. Similarly, at those times, perhaps you might reduce your exercise routine to some gentle exercise for your mental health. You can always pick it back up when your symptoms are more controlled.

Dietary Therapy for IBD

By Dr Emma P. Halmos

About the Author

Dr Emma P. Halmos is an Accredited Practising Dietitian, and Adjunct Senior Research Fellow, Department of Gastroenterology, The Alfred Hospital and Monash University.

Almost every person diagnosed with inflammatory bowel disease (IBD) will ask the question: “What should I eat?”

Historically, diet was dismissed by healthcare professionals, with the exception of using it to treat malnutrition or prevent bowel obstruction.  However, research over the last 10 years has brought to light how valuable diet is throughout different stages of IBD.  From research we have learnt that diet can be manipulated to target different aspects of IBD and should be considered part of routine IBD management. 

There are four ways in which diet may be used to treat IBD, as detailed below:

  1. Nutritional adequacy: Malnutrition, which describes both under- and over-nutrition, is very common in IBD, particularly in people with active Crohn’s disease, due to increased requirements from inflammation and possible impairment of nutrient absorption with small bowel involvement.  Malnutrition is not a trivial problem and can cause fatigue, poor quality of life, depression and may even weaken response to certain medications.  Furthermore, people with malnutrition are more likely to become sick and take a longer time to recover.  This is of particular concern for those undergoing surgery, as malnutrition contributes to risk of post-surgical complications.  Unfortunately, weight is not the best indicator of malnutrition, but unintentional weight loss of more than 5% body weight within three months is a sign of undernutrition.  If you are malnourished, it is recommended that you see a dietitian who can help change your diet to achieve good nutritional status. 
  2. Dietary treatment for inflammation:  Treatment of an active disease is mainly done with medications.  The only dietary therapy that has shown to effectively treat adults and children with active Crohn’s disease is exclusive enteral nutrition (EEN).  This is a short-term treatment that involves drinking nutritional supplements in place of food, usually for six weeks.  EEN must be used under the guidance of both a gastroenterologist and IBD dietitian to ensure it is done correctly and that there is a plan in place for when EEN is stopped.  Since the emergence of EEN, there are many other diets being developed and formally investigated in research trials for their effectiveness to treat Crohn’s disease and/or ulcerative colitis.  It is likely there will be more valid evidence-based dietary therapies available in the future.  On the other hand, some diets that are often promoted on the internet without undergoing formal research trials also claim to treat IBD.  Many of these diets can be extremely restrictive and cause malnutrition and they use only symptoms as a marker of inflammation, which is not always accurate (see below).  Your gastroenterologist and dietitian can discuss options of dietary management with you. 
  3. Complications of IBD:  Sometimes dietary therapies may be used to treat other problems resulting from IBD.  Many people with IBD also develop irritable bowel syndrome (IBS), which means symptoms are related to how the bowel is functioning rather than from inflammation.  This is why it is important to not rely on only symptoms to determine inflammation, but also objective markers.  Medications for IBD target inflammation, so they tend not to work on IBS.  Alternatively, certain diets, such as a FODMAP diet, can improve symptoms, but not inflammation.  Other IBD complications that may need specialty diets include strictures (intestinal narrowing), fat malabsorption, oxalate kidney stones or for symptoms from altered bowel anatomy (e.g., ileostomy, colostomy or j-pouch). 
  4. Preventing IBD:  Most research into IBD and diet have looked at very large studies that link dietary components to development of IBD in healthy people.  Evidence suggests that features of a Mediterranean diet, such as large amounts of plant-based foods (grains, vegetables and fruit), moderate amounts of dairy and fish, and limited meat is protective against Crohn’s disease and less meat also protective against ulcerative colitis.  On the other hand, discretionary food (i.e., ‘junk food’) increases risk of developing IBD.  While these dietary factors are recommended for those at risk of getting IBD, such as family members of those with known IBD, we do not know if these suggestions treat established IBD. 

Dietary therapy in IBD is used now more than ever before.  As dietary recommendations for IBD patients are individual and depend on the purpose, guidance through an IBD dietitian is advised.  Indeed, access to a gastrointestinal dietitian is now recommended as part of IBD management by Australian and global IBD quality of care standards.  To ensure that you are adapting diet effectively and safely, discuss with your IBD treating team the need of involving a suitable dietitian. See, an Australian network of IBD dietitians for further information. 

Erin Russell shares her insights into the various sources of dietary protein and emerging trends in plant-based meat alternatives.

With a large movement towards plant-based diets for ethical, sustainability, cost or perceived health benefi ts, it can be difficult to navigate the most appropriate protein source for your diet, especially if you have infl ammatory bowel disease. We spoke with dietitian Erin Russell to learn more about the potential benefi ts and concerns in sourcing protein from the diff erent options available.

Discovering protein: What is it and what are the suggested requirements?

Protein is one of the three macronutrients in our diet (protein, carbohydrates and fats). Protein has an important role in maintaining muscle mass and is used for building and repairing cells in the body. Guidelines suggest that people with IBD who are in remission have no increased protein needs compared to the rest
of the population. The Australian Guide to Healthy Eating recommends adults consume 2-3 serves of lean meat or alternatives per day (see below). This is slightly higher for males.

How much is a serve of lean meat and poultry, fish, eggs, nuts and seeds, and legumes/beans?

65g cooked lean red meats such as beef, lamb,
veal, pork, goat or kangaroo (about 90-100g raw)

100g cooked fish fillet (about
115g raw) or one small can of fish

2 large (120g) eggs

80g cooked lean poultry such as chicken or turkey (100g raw)

1 cup (150g) cooked or canned legumes/beans such as lentils, chick peas or split peas (preferably with no added salt)

On the other hand, during a severe flare of IBD, protein requirements may increase by 20 to 50 per cent due to the body’s active inflammatory state and catabolic response. It can be difficult for you to estimate this increase yourselves, and clinical symptoms such as bowel habits, nausea and feeling unwell may decrease your intake. Dietitians use many clinical factors to estimate a person’s protein requirements, so it is recommended you seek a referral to an Accredited Practising Dietitian if you need further support in working out your protein needs.

What protein source is best when taking IBD into consideration?

a. meat and animal products
b. meat alternatives (i.e. processed vegetable protein to mimic meat)
c. whole plant-based protein

a. Meat and animal products (beef, lamb, pork, chicken, fish, seafood, etc. as well as dairy products and eggs)

Importantly, this group can be quite varied – from processed salami, to lean chicken breast, to eggs, to tuna – it’s difficult to comment on these as a group.

However, in general, processed meats, e.g. sausages, bacon, ham and salami, are categorised as ‘discretionary’ foods and it’s recommended that they should not be consumed every day. With current research trends in IBD and for general health, it is suggested these foods are avoided in large quantities. Meat and animal products are the most traditional source of protein in the Australian diet, and are a rich source of iron, B12 and zinc. These vitamins and minerals are also most easily absorbed from an animal-based source.

The link between animal protein intake and IBD has been explored but it is not well established. There is no convincing evidence to suggest that patients with IBD need to avoid animal protein, or that a vegetarian/plant-based diet is more beneficial.

b. Meat alternatives – ‘fake’ or ‘mock’ meat

Recent trends in plant-based diets has led to an increase in meat alternatives on the market. This includes products such as quorn, facon (fake bacon), mince, fake sausages/burgers/schnitzels/chicken pieces etc. These products can seem appealing as they are often easy to cook, have a meat like taste and texture, and are also a protein source.

The products may be made from various base ingredients such as soy, eggs, mushrooms, gluten, legumes and nuts. Often the products also need a number of preservatives, emulsifiers, salt and processing to achieve a meat like texture and flavour.

There have not been any specific studies for meat alternatives and their direct impact for patients with IBD, however some assumptions can be made based on their nutrition composition. Current research in Victoria around the impact of emulsifiers and sulphates suggest they may be having a negative impact for people with ulcerative colitis. For example, emulsifiers have only been studied in mice with IBD, but initial outcomes suggest that emulsifiers may have an adverse effect on gut bacteria and increase inflammation.

At present, there are no regulations for vitamin and mineral fortification in these plant-based meat alternatives. Therefore, the products may not reflect similar content of iron, B12 and zinc found in animal products. If plant-based meat alternatives become a direct substitute for animal products, then without supplementation, there is a risk of micronutrient deficiencies.

c. Plant-based protein – whole forms (lentils, beans, chickpeas, soy, tofu, tempeh, nuts and seeds)

Vegetarian and vegan diets have not been shown to be better for people with IBD, but there may be other reasons to choose these diets, such as environmental or ethical concerns.

Plant-based protein – largely from legumes, nuts, and seeds – has always been present in vegetarian and vegan diets. They are known to be high in fibre and protein, low in saturated fats and generally quite affordable. In terms of micronutrients, B12 is difficult to find, iron is not as easily absorbed and large portions are required to satisfy zinc requirements. Supplements may be required.

A few other considerations for plant-based proteins are that they:

  • Are high in insoluble fibre, and may not be appropriate for patients following a modified fibre diet (e.g. stricturing Crohn’s disease)
  • Have variable FODMAP (Fermentable Oligo-, Di-, Mono-saccharides And Polyols) content and large portions may not be tolerated well by people with IBS (irritable bowel syndrome) symptoms.
Chicken breast (100g cooked)Mock chicken breast (100g)Firm tofu (100g)
Cost$1.20 $3.80$0.80

So, perhaps another option is more suitable:

d. It depends!

Avoiding whole food groups may leave you at risk of micronutrient deficiencies.

Risk and prevalence of missing out on vital nutrients is outlined on the CCA website:

Erin’s recommendations:

  • Protein needs in IBD patients varies, depending on the disease state.
  • There is no need to avoid meat or animal products but try to avoid processed meats.
  • Meat alternatives provide little benefit to the diet – they are higher in preservatives, lack micronutrients, and are expensive. However, they can provide a protein source and may be convenient.
  • Plant-based protein can be higher in FODMAPs, and portions need to be considered for IBS symptoms. They are high in fibre, and affordable.
  • Some variety is ideal – this means including a variety of different nutrients and fibres for gut health.

As always, please seek assistance from an Accredited Practising Dietitian if you have any questions or concerns with your diet, or if you are planning to make a large change to your diet.

Ask your gastroenterologist or GP for a referral, otherwise you can search the Dietitians Association of Australia.

About the author

Erin Russell is an Accredited Practising Dietitian within the Gastroenterology Department at Eastern Health in Melbourne. Working with hospital inpatients and outpatients, Erin has a
particular interest in the relationship between IBD and diet.

Biosimilars And Biologics: What It Means For you

kaboompics.com_Medicines & thermometer

A biosimilar drug for the anti-TNF drug infliximab has just been approved for the PBS in Australia.  What does this mean for those living with Crohn’s disease or colitis?

Biologic medicines are complex drugs made using a biological source such as a cell and are many times larger than conventional small molecule drugs such as aspirin, for example. They can very accurately target specific molecules in the body that are critical in how diseases cause damage and have been a major advancement in the care of many conditions.

Infliximab (Remicade®) was the first biologic medicine in IBD, and has been used in Australia since 2001. It was also the first biologic to become available on the PBS for Crohn’s disease in 2007. Since then, adalimumab (Humira®) was listed in 2008 for Crohn’s disease, infliximab was also listed for ulcerative colitis and vedolizumab (Entyvio®) was listed for both Crohn’s disease and ulcerative colitis in November 2015. These medicines have made a significant difference in the treatment of inflammatory bowel disease in Australia.

The patents for the original biologic drugs are starting to expire, opening up the way for copies, known as biosimilars, to enter the market. Due to the large size and complexity of biologic agents, biosimlars are not identical copies like generic drugs that can be made for small molecules, but have highly similar effects both in the laboratory and in human trials on diseases.

Overall, biosimilars have been welcomed due to the high costs of biologic medicines. Biosimilars can result in cost savings for the Government due to price competition, but will be the same price to the patient.

Inflectra®, a biosimilar for infliximab, is now available on the PBS. Other biosimilars are expected to come onto the market in the coming years.

Currently, there is limited information on the effects of switching from one biologic drug to a biosimilar, and no trial data on the effects of switching back and forth multiple times between them.

Substitution at pharmacy level


The Australian government has decided that these drugs can be substituted at the point of dispensing in a pharmacy despite the opposition of the peak doctors and patient groups who use these drugs. This means that your pharmacist may be able to offer you the biosimilar brand instead of your usual brand of medicine, just as this can be done with other generic medicines. This would not require going back to your prescribing doctor.

Substitution at pharmacy level is a measure taken to encourage more people to use biosimilars. There are, however, still reasons to be wary about the implications for consumers.

What should we know about pharmacy level substitution of biologics?

CCA Board Director and Chair of the Australian IBD Association Dr Gregory Moore says Australia is the only jurisdiction in the world where repeated substitutions can be carried out in this way, despite a lack of long term safety and efficacy data for this strategy,

This is despite the Therapeutic Goods Association’s ruling that “it is not currently possible to determine a degree of similarity, between a biosimilar and an already registered biological medicine sufficient to support a designation by the TGA of ‘bioequivalence’.”

There are concerns the unknown safety and possible development of a patient’s own antibodies against the biologic drugs that can lead to loss of their effectiveness or infusion reactions, which could be a result of switching medication multiple times.

This needs to be discussed with your medical team.

Overall, Dr Moore recommends a patient who has started their treatment on one version of infliximab (either Remicade® or Inflectra®) to remain on that drug until we have more information on the long-term effects of switching.

At present, the best way to ensure consistent treatment for IBD patients is to list the drug by its generic name and its trade name, such as “infliximab Remicade” or “infliximab Inflectra” and to have the prescribing doctor tick the “Brand Substitution Not Permitted” box on prescriptions, Dr Moore says.

In cases where a patient is new to therapy, a full discussion with their treatment team is recommended on whether to use biosimilars that are available.

At present, only Remicade® (infliximab) is affected by these changes, but Humira® (adalimumab) will also be off patent in the near future..

How to make sure your medicine is the right one for you

Prescribers and patients both have the right to choose the brand of medicine they will receive at pharmacy level, but it is a choice that should be an informed one.

  1. Talk to your treatment team about your medication, and whether a biosimilar is available as an alternative to your current biologic treatment
  2. Decide in consultation with your gastroenterologist whether you should stay on your current biologic, or consider substituting it for a biosimilar
  3. If you will stay on your current biologic, ensure your doctor ticks the “Brand Substitution Not Permitted” box on your script. This will ensure no substitutions happen at pharmacy level
  4. Keep records of your medication, and immediately advise your treatment team if there is any change to the brand you receive from the pharmacy. This can simply be done by keeping the packaging, or taking photographs.
  5. Make sure you keep up to date on any changes to biologics or biosimilars available for the treatment of IBD by visiting or following us on Facebook.

Finding your trigger foods

When you are newly diagnosed with Crohn’s or colitis, there is a flood of information about how to control symptoms, what medication could assist, and a million different opinions on food that you should or shouldn’t eat.


“Don’t eat pizza, don’t drink milk, stay away from curry, eat lots of kale even if you don’t like it…”

The simple response is that IBD is a very personal disease, and what acts as a trigger for one person may be well tolerated by another. So how do you begin the process of working out what your body reacts poorly to?

The first step to consider is whether you are currently in flare, or are assessing your diet during a period of relative health. These two different states may produce different reactions to certain foods, or complicate assessing what your bowel can tolerate.

As we have noted in our IBD Toolkit, during flare-ups of disease some people find that a bland, low fibre diet is easier to tolerate than one that contains high fibre or spicy foods. Low fibre diets are those that restrict the harsh skins and seeds found in some fruits, vegetables and dried fruit, in addition to nuts, seeds and wholegrains.

These diets tend to stimulate less secretion of intestinal fluids and cause less contraction in the small and large intestines and may help to control symptoms such as abdominal cramps and diarrhoea.

While this can be helpful in the first instance, individual experience is the most useful guide to finding your food tolerances. Imagine if you followed the advice of every different internet article on IBD – you would probably be left on a diet of dust and the occasional dry cracker!

But if you are trying to figure out good nutrition that suits your body and lifestyle, here are a few tips on starting that process:

Remember, any significant changes to your diet or nutrition should be discussed with your treatment team.

What To Do When Stuck In The Bathroom

 Those of us living with Crohn’s or colitis are more than familiar with spending too much time in the bathroom. But the upside is we have so much extra time for activities!

Here are just a few ideas for how you could make use of the time spent on the porcelain throne.

Serenade your intestines
Ever dreamed of winning Australian Idol or The Voice? Everybody knows the acoustics in the bathroom make for a great singing spot. Why not put your creativity to work and come up with a love song to your colon?

Read the classics
If you missed out on that English class due to time off from school or university and therefore never quite finished Pride and Prejudice, we have great news for you! Keep a copy in the bathroom and you’ll be loving (or hating) Mr Darcy in no time!

Work on your zombie escape plan
Are you going to head for the hills, barricade yourself in a mall, or take them on yourself? Everybody needs a plan, so why not use your time to finesse the finer details?

Write some letters
Putting pen to paper has become something of a lost art. Your grandmother or a family friend overseas would probably love to hear from you while they decipher your handwriting. Just make sure you don’t call and tell them everything that’s in the letter before it eventually arrives!

Become an expert in an obscure field of study
The power of the smartphone means you can fit in some serious research time while on public transport, lying in bed, or even in the bathroom. If you’ve always been curious about ancient Peruvian artefacts or the truth about the Loch Ness monster, now is your time to shine!

Brush up on the news
If you are someone who doesn’t manage to catch the 6pm bulletin every evening, there is plenty of time throughout the day to keep yourself in the loop. If sports or politics isn’t your thing, you could always head to the Research section of our website and see if there’s any new IBD information out there!

Read shampoo bottles
Well, it’s the classic fallback isn’t it? Perhaps it’s time to move to organic, just so there’s some different ingredients to memorise.

How do you keep yourself entertained when you find yourself with time to kill?