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Title: Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
ORCiD logo [1];  [2];  [1];  [2];  [3]; ORCiD logo [1]
  1. Harvard Medical School, Boston, MA (United States)
  2. Broad Inst. of MIT and Harvard, Cambridge, MA (United States)
  3. Broad Inst. of MIT and Harvard, Cambridge, MA (United States); Massachusetts General Hospital, Boston, MA (United States)
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A substantial and increasing number of human diseases are associated with changes in the gut microbiota, and discovering the molecules and mechanisms underlying these associations represents a major research goal. Multiple studies associate Ruminococcus gnavus, a prevalent gut microbe, with Crohn’s disease, a major type of inflammatory bowel disease. We have found that R. gnavus synthesizes and secretes a complex glucorhamnan polysaccharide with a rhamnose backbone and glucose sidechains. Chemical and spectroscopic studies indicated that the glucorhamnan was largely a repeating unit of five sugars with a linear backbone formed from three rhamnose units and a short sidechain composed of two glucose units. The rhamnose backbone is made from 1,2- and 1,3-linked rhamnose units, and the sidechain has a terminal glucose linked to a 1,6-glucose. This glucorhamnan potently induces inflammatory cytokine (TNFα) secretion by dendritic cells, and TNFα secretion is dependent on toll-like receptor 4 (TLR4). We also identify a putative biosynthetic gene cluster for this molecule, which has the four biosynthetic genes needed to convert glucose to rhamnose and the five glycosyl transferases needed to build the repeating pentasaccharide unit of the inflammatory glucorhamnan.

Research Organization:
Univ. of Georgia, Athens, GA (United States); Univ. of Georgia, Athens, GA (United States). Complex Carbohydrate Research Center
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division; USDOE
Grant/Contract Number:
SC0015662
OSTI ID:
1612314
Alternate ID(s):
OSTI ID: 1964089
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, Issue 26; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 273 works
Citation information provided by
Web of Science

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Cited By (7)

Coronary artery disease is associated with an altered gut microbiome composition journal January 2020
Relationship between gut microbiota and circulating metabolites in population-based cohorts journal December 2019
Gut Microbiome: Profound Implications for Diet and Disease journal July 2019
A dual-chain assembly pathway generates the high structural diversity of cell-wall polysaccharides in Lactococcus lactis journal October 2019
Influence of Maternal Inulin-Type Prebiotic Intervention on Glucose Metabolism and Gut Microbiota in the Offspring of C57BL Mice journal October 2019
Do the Bugs in Your Gut Eat Your Memories? Relationship between Gut Microbiota and Alzheimer’s Disease journal November 2020
Beneficial Effects of Linseed Supplementation on Gut Mucosa-Associated Microbiota in a Physically Active Mouse Model of Crohn’s Disease journal May 2022

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Related Subjects

60 APPLIED LIFE SCIENCES
science & technology - other topics
inflammatory bowel disease
microbiome
polysaccharide
inflammatory bowel disease
microbiome
polysaccharide