Ruminococcus gnavus, a Member of the Human Gut Microbiome Associated with Crohn’s Disease, Produces an Inflammatory Polysaccharide

By Katie E. Golden

The microbial communities that live peacefully in our gut play a critical role in healthy metabolism and immunity. Evolving research on the microbiome has linked chronic disease, like Inflammatory Bowel Disease (IBD), to significant and characteristic disruptions in both the types and relative abundance of bacterial species that colonize the intestine. It has become an important research goal to not only characterize the relationship between microbiome changes and the development of disease, but also to understand the underlying molecular mechanisms that account for IBD pathology.

In a recent publication by Henke et.al1, scientists shed some light on the connection between microbial communities and IBD through investigations of the species Ruminococcus gnavus in Crohn’s disease (CD), a type of IBD. It has been observed that R. gnavus is not only more prevalent in the microbiome of CD patients, but also correlates with disease severity (blooms of the bacteria have been seen during times of disease flare). In this study, researchers describe a complex polysaccharide synthesized and secreted by the bacteria that induces an inflammatory cascade, revealing a potential physiologic mechanism that accounts for the relationship between the microbiome and CD progression.

In the first round of experiments, the authors cultured R. gnavus in a specifically designed media, and observed a dose-dependent relationship with levels of the pro-inflammatory cytokine TNFɑ (known to play an important role in the deleterious inflammation seen in autoimmune diseases). Through a series of subsequent biochemical and spectroscopic investigations, the researchers were able to identify and characterize the structure of a glucorhamnan polysaccharide responsible for the observed TNFɑ activity. They then showed that R.gnavus synthesizes and secretes the pro-inflammatory polysaccharide, which subsequently induces TNFɑ secretion by dendritic cells (through a pathway dependent on toll-like receptor 4). Finally, the authors identified a potential gene cluster with the necessary biosynthetic genes to code for the production of the glucorhamnan polysaccharide. Their work describes a breakthrough discovery of a plausible mechanism by which changes in microbiome characterics directly contribute to the pathophysiology of IBD.

1. Matthew T. Henke et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide, Proceedings of the National Academy of Sciences (2019).