E0253 - Altered Fecal Microbiome in Patients With Irritable Bowel Syndrome With Diarrhea Is Related to Bile Acid Synthesis, Not to Rapid Colonic Transit

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Joelle BouSaba, MD

Mayo Clinic
Rochester, MN

Joelle BouSaba, MD, Stephen Johnson, MS, Jun Chen, PhD, Irene Busciglio, BS, Paula Carlson, BS, Michael Camilleri, MD
Mayo Clinic, Rochester, MN

Introduction: Bile acid (BA) diarrhea (BAD) affects up to 30% of patients with irritable bowel syndrome with diarrhea (IBS-D). In a cohort of 194 patients with IBS-D, 43 had BAD (serum 7αC4 >52ng/mL) and, as a group, had faster colonic transit, lower microbial α diversity, and a different microbial compositional profile based on β diversity compared to IBS-D without altered BA metabolism (ABAM); 70 microbial species were differentially abundant between the two groups, with 61/70 decreased in BAD (PMID: 35580964). However, the effect of colonic transit on the relationship between BAs and the microbiome was not evaluated. Our aim was to compare the microbiome composition in the same cohort of patients with IBS-D (total 183) with and without rapid colonic transit as measured by the geometric center at 24 hours (GC24) before and after adjusting for ABAM (elevated serum 7αC4).

Methods: Participants with Rome III positive IBS-D provided a random single stool sample and measurements of fasting serum 7αC4 and colonic transit by scintigraphy as part of an institutional review board approved study. Patients with GC >3.45 (90^th percentile of normal) were considered to have rapid transit. SHOGUN was used to perform taxonomic assignment of reads passing quality control. Microbiome analysis included α diversity, β diversity, and differential abundance.

Results: Patients with rapid colonic transit had borderline lower α diversity (InvSimpson, p=0.07) and a borderline different compositional profile based on β diversity (Jaccard, p=0.07) compared to patients without rapid transit. There were 6 genera and 14 species (table) including Clostridium polynesiense and species belonging to the Ruminococcaciae and Lachnospiraceae families that were decreased in patients with rapid colonic transit. After adjustment of the analysis for age, sex, BMI, and serum 7αC4, there was no significant difference in α or β diversity (figure) between the two groups. Moreover, these differences in differential abundance of microbiota at the genus and species levels were not maintained after adjustment, except for Clostridium polynesiense which was decreased with rapid colonic transit.

Discussion: Altered fecal microbiome composition in patients with IBS-D and rapid colonic transit are significantly impacted by a biomarker of bile acid synthesis, serum 7αC4, rather than resulting from the rapid transit.

Figure: Microbial alpha (left) and beta (right) diversity in patients with IBS-D with and without rapid colonic transit after adjustment for age, sex, BMI, and serum 7αC4.

	Log 2-Fold Change ± Standard Error
	Before adjustment
Mobiluncus mulieris	-0.60 ± 0.17
Intestinimonas butyriciproducens	-1.12 ± 0.28
Intestinimonas massiliensis	-0.82 ± 0.21
Pseudoflavonifractor capillosus	-0.75 ± 0.20
Anaerosalibacter massiliensis	-0.92 ± 0.27
Anaerofustis stercorihominis	-1.79 ± 0.48
Lachnospiraceae bacterium MC2017	-0.99 ± 0.28
Oscillibacter sp. KLE 1745	-1.13 ± 0.35
Anaerotruncus colihominis	-0.75 ± 0.20
Megasphaera genomosp. Type 1	-1.32 ± 0.38
Clostridium polynesiense	-1.62 ± 0.32
Clostridium cellulosi	-0.94 ± 0.29
Ruminococcaceae bacterium AE2021	-0.61 ± 0.17
Caloramator australicus	-0.35 ± 0.11
	After adjustment
Clostridium polynesiense	-1.34 ± 0.33

Table: Differentially abundant species in patients with IBS-D with or without rapid transit before and after adjustment for age, sex, BMI, and serum 7αC4

Disclosures:

Joelle BouSaba indicated no relevant financial relationships.

Stephen Johnson indicated no relevant financial relationships.

Jun Chen indicated no relevant financial relationships.

Irene Busciglio indicated no relevant financial relationships.

Paula Carlson indicated no relevant financial relationships.

Michael Camilleri: Aclipse Therapeutics – Consultant. Aditum Bio – Consultant. AEON Pharma – Consultant. Allergan – Grant/Research Support. Arena – Consultant. Bilayer Therapeutics – Stock Options. BioKier – Consultant. Coloplast – Consultant. Coloplast – Consultant. Colospan – Consultant. Cosmo Pharmaceuticals – Consultant. Dignify Therapeutics – Stock Options. Enterin – Stock Options. Fauna Bio – Consultant. GlaxoSmithKline – Consultant. Invea Therapeutics – Consultant. InveniAI – Consultant. Ironwood – Consultant. Kallyope – Consultant. NGM Biopharmaceuticals – Grant/Research Support. Novome – Consultant. Pfizer – Consultant. Protagonist Therapeutics – Consultant. Protagonist Therapeutics – Consultant. QED Therapeutics – Consultant. Sunovion Pharmaceuticals – Consultant. Takeda – Consultant. Thelium Therapeutics – Stock Options. Vanda – Grant/Research Support. VIPUN Medical – Consultant. Virios – Consultant. Zealand Biopharma – Consultant.

Joelle BouSaba, MD, Stephen Johnson, MS, Jun Chen, PhD, Irene Busciglio, BS, Paula Carlson, BS, Michael Camilleri, MD. E0253 - Altered Fecal Microbiome in Patients With Irritable Bowel Syndrome With Diarrhea Is Related to Bile Acid Synthesis, Not to Rapid Colonic Transit, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.