Modulating the Microbiome to Treat GI Disease

Educational Objectives

The goal of this program is to improve the management of gastrointestinal diseases by modulation of the microbiome. After hearing and assimilating this program, the clinician will be better able to:

1. Manipulate the microbiome using evidence-based strategies.

Summary

Introduction: the microbiome helps digest complex carbohydrates and fiber and creates beneficial metabolites that promote health and prevent gastrointestinal (GI) disease

Prebiotics (fiber): a substance that promotes the growth of beneficial bacteria; lack of complex plant-based fibers in the diet results in the loss of diversity of the microbiome and of microbial metabolites that promote health and homeostasis (similar to effects of inflammation and GI disease)

Microbiome dysbiosis: high levels of harmful microbes and low levels of beneficial microbes; occurs with most GI disease processes

Management: the main therapeutic approach is to eliminate the harmful microbes; however, treatment targets all microbes in the GI tract and does not address the specific cause of the dysbiosis; administering beneficial microbes through microbial therapeutics is emerging via, eg, fecal microbiota transplantation (FMT)

Probiotics: current probiotics are not microbiome-derived therapeutics and are non-native to the microbiome; do not reverse dysbiosis (may reinforce it); Spencer et al (2021) — found that fiber augments, and probiotics inhibit, effects of cancer immunotherapy

FODMAP intolerance: microbial dysbiosis causes GI symptoms related to disordered fermentation; patients with irritable bowel syndrome (IBS) benefit from a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet; the low-FODMAP diet consists of 3 phases (the restriction phase, lasting ≈1 mo, followed by reintroduction and personalization)

Mechanism: FODMAP intolerance is mediated by poor absorption and inappropriate microbial fermentation (dysbiosis mediated) that causes symptoms

Low-FODMAP and gluten-free grains: eg, teff, millet, buckwheat, oats, rice, quinoa; to further diversify the diet, include well-tolerated foods that support the microbiome, eg, spices, nuts, seeds (ie, additive food advice rather than restrictive food advice)

Gluten and fructan sensitivity: recent pivotal studies suggest that non-celiac gluten sensitivity (NCGS) is not a clinical entity; recent randomized, controlled trials (Skodje et al [2018]; Mohseni et al [2022]) found that IBS symptoms after wheat consumption are related to the fructan content, rather than their gluten content (microbiome-mediated non-celiac wheat intolerance); low-fructan wheat or ancient wheats (eg, spelt, kamut, einkorn) subjected to traditional sourdough fermentation are well tolerated by patients with IBS

Promoting a healthy microbiome: reintroduce fiber; empower patients to make healthy, microbiome-friendly food choices that do not cause GI symptoms

Permanent loss of fiber-degrading bacteria: patients with IBD report fiber intolerance; purified prebiotic fibers show a bimodal response in clinical trials; Kedia et al (2022) found that FMT plus dietary intervention was superior to standard medical therapy, particularly for mild ulcerative colitis

Final points: better assessment of the microbiome for fiber-degrading capacity is needed; treatment in the form of FMT or a microbial therapeutic is possible; future strategies may involve a symbiotic approach, in which next-generation probiotics with fiber-degrading capacity are followed by appropriately matched fiber to produce beneficial microbial metabolites

Readings

Kedia S, Virmani S, K Vuyyuru S, et al. Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial. Gut. 2022;71(12):2401-2413. doi:10.1136/gutjnl-2022-327811; Magge S, Lembo A. Low-FODMAP diet for treatment of irritable bowel syndrome. Gastroenterol Hepatol (N Y). 2012;8(11):739-745; Mohseni F, Agah S, Ebrahimi-Daryani N, et al. The effect of low FODMAP diet with and without gluten on irritable bowel syndrome: A double blind, placebo controlled randomized clinical trial. Clin Nutr ESPEN. 2022;47:45-50. doi:10.1016/j.clnesp.2021.12.019; Skodje GI, Sarna VK, Minelle IH, et al. Fructan, rather than gluten, induces symptoms in patients with self-reported non-celiac gluten sensitivity. Gastroenterology. 2018;154(3):529-539.e2. doi:10.1053/j.gastro.2017.10.040; Spencer CN, McQuade JL, Gopalakrishnan V, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632-1640. doi:10.1126/science.aaz7015; Yan F, Polk DB. Probiotics and probiotic-derived functional factors-mechanistic insights into applications for intestinal homeostasis. Front Immunol. 2020;11:1428. Published 2020 Jul 3. doi:10.3389/fimmu.2020.01428.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Spencer was recorded at the 2023 Updates in Gastroenterology and Hepatology, held on April 13-15, 2023, in Redwood City, CA, and presented by Stanford University School of Medicine. For information on upcoming CME activities from this presenter, please visit med.stanford.edu/cme. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

Lecture ID:

GE372202

Qualifies for:

ABIM MOC

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.