Introduction

Limiting fermentable carbohydrates (FODMAPs) is an evidence-based irritable bowel syndrome (IBS) management approach and food antigen avoidance is common in IBS (1). The gut microbiota degrades undigested food and specific microbes may produce antigens that trigger IBS symptoms (2). Correlations between the gut microbiota and whole-of-diet intakes of specific microbiota-degradable food compounds and food antigens by people with IBS have not been elucidated.

Aims & Methods

The aim of this study was to compare dietary intakes and the gut microbiota of adults with IBS to healthy controls to inform personalised diet intervention-based research. This cross-sectional study used data and samples from a digestive health biobank. Demographic, psychological and symptom data were analysed against dietary data from a food frequency questionnaire (FFQ) and 24-hour diet recall (24-HR) aligned with biobanked stool samples. Dietary data were compared using independent and paired t-tests. Stool sample gDNA was extracted using the Promega Maxwell DNA recovery system and shotgun metagenomic sequencing performed to a depth of 3Gb. Taxonomic profiling was completed with MetaPhlAn4 and results analysed using R packages phyloseq, MicroEco and Maaslin2.

Results

Thirty-four adults with IBS (23 IBS-D, 11 IBS-C) and 39 healthy controls were included. Demographic and clinical characteristics were not significantly different between IBS and controls except for psychological distress (p<0.001), anxiety and depression (p<0.05) and gastrointestinal symptom burden (p<0.001). Usual dietary intake of participants with IBS was significantly lower than controls for total FODMAPs (p<0.05) and lactose (both p<0.05). In the 24-48 hours prior to stool sampling, participants with IBS consumed significantly lower total fibre (p<0.01), fruit serves (p<0.01) and gluten (0<0.05). Energy, macro- and micronutrients did not differ between groups (FFQ or 24-HR) and were consistent between FFQ and 24-HR for most dietary variables. Microbial beta diversity differed between IBS and controls (p<0.01 PERMANOVA) and IBS-C and IBS-D subtypes (p<0.001). Microbiota profiles differed between IBS and controls. Two microbial species (sp.) were positively associated with gluten (24-HR) intake (1 unclassified Clostridia sp., 1 unclassified sp. from Actinomycetaceae family, both p<0.01) in the IBS cohort. Strong positive correlations were evident in controls for saturated fat (12 bacterial species, all p<0.001) and total energy (15 species, all p<0.05), with strong negative correlations evident between Akkermansia muciniphila and saturated fat (p<0.001), total energy (p<0.01), total fat, and caffeine (both p<0.05). Bacterial species with significant correlations to dietary variables across both usual and 24-HR dietary data were Akkermansia muciniphila and unclassified Firmicutes GGB14025.

Conclusion

Microbiota differences between adults with IBS and controls were associated with diet and clinical characteristics. Differences in relationships between specific FODMAPs (lactose) and food antigens (gluten) and microbiota associations has clinical relevance for IBS dietary management. Future translation-focussed research investigating personalisation of dietary intervention for microbiota-targeted symptom management in IBS is warranted.

References

1. Black CJ, Staudacher HM, Ford AC. Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. Gut. 2022;71(6):1117-26.
2. Wang Y, Ma W, Mehta R, Nguyen LH, Song M, Drew DA, et al. Diet and gut microbial associations in irritable bowel syndrome according to disease subtype. Gut Microbes. 2023;15(2):2262130.

Disclosure

Nicholas J Talley's disclosures include Intrinsic Medicine (2022) (human milk oligosaccharide), Alimentry (2023) (gastric mapping), Agency for Health Care Research and Quality (fiber and laxation) (2024), outside the submitted work. In addition, Dr. Talley has a patent Nepean Dyspepsia Index (NDI) 1998, a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, “Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Patent Application No. 63/537,725.

Clinical Case Summary

We report a case of chronic gastrointestinal graft versus host disease (GVHD) in a 59-year-old male underwent orthotopic liver transplant (OLTx) for toxic liver cirrhosis in 2012. Effective anti-rejection therapy with Tacrolimus has been mantained to date. In December 2021, he presented with persistent hematochezia and diarrhea, up to 10 evcauations per day, nocturnal diarrhea, fecal urgency, and abdominal pain. Investigations including serology for celiac disease, stool cultures, CMV blood and stool tests were negative. As post-OLT follow-up investigations, esophagogastroduodenoscopy revealed no significant findings except for Helicobacter pylori related gastritis, while colonoscopy showed a tubular colon with erythematous mucosa, loss of vascular pattern and small ulcerations all along; rectal involvement with mild erythema and thinned vascular pattern was also described. Histological examination revealed chronic colitis consistent with GVHD, Lerner grade 2. Systemic corticosteroid therapy (oral Prednisone) was started in June 2022, resulting in clinical improvement. However, steroid tapering led to symptom recurrence and raising in fecal calprotectin levels up to 1200 mcg/g. Subsequent colonoscopy in November 2022 confirmed GVHD colitis, prompting a trial of immunosuppressive therapy escalation with Tacrolimus together with a cicle of Budesonide, yielding transitory clinical and laboratory improvement. In June 2023, following treatment with Amoxicillin and Ketorolac due to dental cures, diarrhea with blood in stools againg recurred with new increase in fecal calprotectin levels (2100 ug/g). Vedolizumab "off-label" therapy was thus started in December 2023, resulting in clinical response. Latest fecal calprotectin level, at the end of the induction phase, at the beginning of march 2024, was 135 mcg/g. Follow-up colonscopy will be soon performed.

References

Vikrant Rai, Nicholas Edward Dietz & Devendra K. Agrawal (2016) Immunological basis for treatment of graft versus host disease after liver transplant, Expert Review of Clinical Immunology, 12:5, 583-593, DOI: 10.1586/1744666X.2016.1145056

Yngvar Fløisand, Vladimir Lj Lazarevic, Johan Maertens, Jonas Mattsson, Nirav N. Shah, Pierre Zachée, Aliki Taylor, Mona Akbari, Syed Quadri, Andrejus Parfionovas, Yi-Bin Chen (2018) Safety and Effectiveness of Vedolizumab in Patients with

Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review, Biology of Blood and Marrow Transplantation, DOI:https://doi.org/10.1016/j.bbmt.2018.11.013