Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide.
Matthew T HenkeDouglas J KennyChelsi D CassillyHera VlamakisRamnik J XavierJon ClardyPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
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.
Keyphrases
- toll like receptor
- blood glucose
- dendritic cells
- endothelial cells
- immune response
- inflammatory response
- rheumatoid arthritis
- nuclear factor
- genome wide
- induced pluripotent stem cells
- molecular docking
- dna methylation
- pluripotent stem cells
- metabolic syndrome
- adipose tissue
- skeletal muscle
- transcription factor
- water soluble