Am J Gastroenterol. 2022 Oct 27. doi: 10.14309/ajg.0000000000001997. Online ahead of print.

Maria J Villanueva-Millan ¹, Gabriela Leite ¹, Jiajing Wang ¹, Walter Morales ¹, Gonzalo Parodi ¹, Maya L Pimentel ¹, Gillian M Barlow ¹, Ruchi Mathur ^1 2, Ali Rezaie ^1 3, Maritza Sanchez ¹, Sarah Ayyad ¹, Daniel Cohrs ¹, Christine Chang ¹, Mohamad Rashid ¹, Ava Hosseini ¹, Alyson Fiorentino ¹, Stacy Weitsman ¹, Brennan Chuang ¹, Bianca Chang ³, Nipaporn Pichetshote ⁴, Mark Pimentel ^1 3

Author information

¹Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California, USA.

²Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai, Los Angeles, California, USA.

³Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai, Los Angeles, California, USA.

⁴Vatche and Tamar Vamoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California, USA.

Abstract

Introduction: Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome sequencing to identify potential microbial drivers of IBS subtypes.

Methods: IBS-C and IBS-D subjects from 2 randomized controlled trials (NCT03763175 and NCT04557215) were included. Baseline breath carbon dioxide, hydrogen (H 2 ), methane (CH 4 ), and hydrogen sulfide (H 2 S) levels were measured by gas chromatography, and baseline stool microbiome composition was analyzed by 16S rRNA sequencing. Microbial metabolic pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes collection databases.

Results: IBS-C subjects had higher breath CH 4 that correlated with higher gut microbial diversity and higher relative abundance (RA) of stool methanogens, predominantly Methanobrevibacter , as well as higher absolute abundance of Methanobrevibacter smithii in stool. IBS-D subjects had higher breath H 2 that correlated with lower microbial diversity and higher breath H 2 S that correlated with higher RA of H 2 S-producing bacteria, including Fusobacterium and Desulfovibrio spp. The predominant H 2 producers were different in these distinct microtypes, with higher RA of Ruminococcaceae and Christensenellaceae in IBS-C/CH 4 + (which correlated with Methanobacteriaceae RA) and higher Enterobacteriaceae RA in IBS-D. Finally, microbial metabolic pathway analysis revealed enrichment of Kyoto Encyclopedia of Genes and Genomes modules associated with methanogenesis and biosynthesis of methanogenesis cofactor F420 in IBS-C/CH 4 + subjects, whereas modules associated with H 2 S production, including sulfate reduction pathways, were enriched in IBS-D.

Discussion: Our findings identify distinct gut microtypes linked to breath gas patterns in IBS-C and IBS-D subjects, driven by methanogens such as M. smithii and H 2 S producers such as Fusobacterium and Desulfovibrio spp, respectively.