Project description:We used culturing of fecal sample enrichments on solid medium containing gastric mucin as the main carbon source to isolate a novel bacterium that is largely restricted to using the N-acetylglucosamine and N-acetylgalactosamine sugars from mucin. This butyrate-producing bacterium accesses these sugars from both polymeric gastric mucin and chemically released oligosaccharides and has a genome with correspondingly restricted carbohydrate-active enzyme content. Sequencing data was curated to determine gene expression profiles when comparing N-acetylgalactosamine, N-acetylglucosamine, gastric mucin oligosaccharides and cellobiose.
Project description:The personalized communities of microorganisms (microbiota) that inhabit the distal guts of humans have evolved to process a variety of complex carbohydrates. Many gut bacteria depolymerize and ferment dietary fiber polysaccharides, mutualistically providing short-chain fatty-acids to their host. Some human gut bacteria have evolved to utilize components of host mucin glycoproteins—the major component of protective mucus—and recent studies have implicated specific mucin-degrading commensal bacteria in the development of intestinal inflammation. Thus, identifying new gut bacteria that possess the ability to degrade host mucins and determining how these organisms might cooperate or compete for mucin components during health and disease is an important goal. Here, we used culture on solid medium containing gastric mucin as the main carbon source to isolate a novel bacterium that is largely restricted to using the N-acetylglucosamine and N-acetylgalactosamine sugars found in mucin O-glycans. This butyrate-producing bacterium accesses these sugars from both polymeric gastric mucin and chemically released oligosaccharides and has a genome with correspondingly restricted carbohydrate-active enzyme content. Surprisingly, strains related to this isolate appear to be rare in the now numerous sequence-based microbiota surveys with only 32/3781 (0.85%) human subjects containing this bacterium with an overall relative abundance ranging from 0.004-0.057%. This combination of low prevalence and abundance, suggests that this species could occupy an unknown niche in which access to mucin is important but otherwise render it difficult to detect in mostly feces-based microbiota surveys.
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited therapeutic options. The diversity and composition of intra-tumoral microbiota are associated with PDAC outcomes, and modulating the tumor microbiota has the potential to influence tumor growth and host-immune response. Here, we explore whether intervention with butyrate-producing probiotic can limit PDAC progression. By analyzing TCGA (PAAD) dataset, we found that tumoral butyrate-producing microbiota links to better prognosis and less aggressive features of PDAC. Intervention with Clostridium butyricum or its metabolite butyrate triggered superoxidative stress and intracellular lipid accumulation, which enhanced ferroptosis susceptibility of PDAC. Our study reveals a novel antitumor mechanism of butyrate, and suggests the therapeutic potential of butyrate-producing probiotics in PDAC.
