Andrew Brantley Hall：A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

Andrew Brantley Hall

时长：10:21 分会场：2019中国肠道大会 - 肠道菌群与健康大会

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that has been linked to deviations in the composition of the gut microbiome. Using taxonomic profiling and reference genomes, we inferred an increased abundance of oxidative stress pathways in IBD, for which one of the main contributors was the organism Ruminococcus gnavus. To better understand the mechanisms underlying the changes between gut metagenomes of individuals with IBD relative to non-IBD controls, we performed whole metagenome sequencing (WMS) on monthly stool samples from 32 subjects (n=20 IBD; 12 control), resulting in 266 total longitudinal samples. Combining taxonomic and functional profiling, increased disease activity was characterized by a loss of strict anaerobes coupled with an increased abundance of facultative anaerobes (such as R. gnavus) that are typically found only in very low abundance in healthy individuals (nested anova + p-value = 0.0478, validation cohort nested anova + p-value = 0.005). One of the major factors in the response to increased oxidative stress shaping microbial dysbiosis in IBD was dramatic, but transient increases in the relative abundance of R. gnavus in IBD. Strain-level analysis supports the existence of an IBD-specific strain of R. gnavus with a distinct functional repertoire compared R. gnavus from healthy individuals. The IBD-specific strain contains adherence-related genes and genes involved in glycine-betaine transport which are involved in the response to stress. Pangenome analysis of R. gnavus revealed that genes for mucus utilization are widespread in our samples suggesting this organism occupies the mucogenic niche and is therefore closely-associated with the host epithelia. Increases in the abundance of mucus-utilizing, epithelial-associated strains of R. gnavus are a part of the dysbiotic consortia that may contribute to the excessive response of the host immune system to the gut microbiome in IBD.

Andrew Brantley Hall

麻省理工-哈佛大学博德研究所

"Dr. Hall is a Merck Fellow of the Helen Hay Whitney Postdoctoral Foundation in Ramnik Xavier's lab at the Broad Institute of Harvard and MIT as well as the Center for Computational and Integrative Biology at Massachusetts General Hospital and Harvard Medical School. He combines bioinformatics, microbiology, and genetics to unravel the complexities of the human gut microbiome. His current project focuses on understanding the factors underlying alterations to the gut microbiome in Inflammatory Bowel Disease (IBD) and determining whether dysbiosis of the gut microbiome is a cause or consequence of gut inflammation. "

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