Enhancing Recovery from Gut Microbiome Dysbiosis and Alleviating DSS-Induced Colitis in Mice with a Consortium of Rare Short-Chain Fatty Acid-Producing Bacteria

Abstract

AbstractThe human gut microbiota is a complex community comprised of hundreds of species, with a few present in high abundance and the vast majority in low abundance. The biological functions and effects of these low-abundant species on the host are not yet fully understood. In this study, we assembled a bacterial consortium (SC-4) consisting ofB. paravirosa, C. comes, M. indica, andA. butyriciproducens, which are low-abundant, short-chain fatty acid (SCFA) producing bacteria isolated from healthy human gut and tested its effect on host health using germfree and human microbiota associated mice models of colitis. Our findings demonstrate that SC-4 can colonize in Germ-free (GF) mice, increasing mucin thickness by activating the MUC-1 and MUC-2 genes, thereby protecting GF mice from Dextran Sodium Sulfate (DSS)-induced colitis. Moreover, SC-4 aided in the recovery of human microbiota-associated mice from DSS-induced colitis, and intriguingly, its administration enhanced the alpha diversity of the gut microbiome, shifting the community composition closer to control levels. We also show a functional redundancy existing in the gut microbiome, resulting in the low abundant SCFA producers acting as a form of insurance, which in turn accelerates recovery from dysbiotic state upon the administration of SC-4. SC-4 colonization also upregulated iNOS gene expression, further supporting its ability to enhance mucin thickness upon colonization. A metagenomic analysis of Inflammatory Bowel Disease (IBD) patient samples revealed a decrease in the abundance of SC-4 bacteria in both Ulcerative Colitis (UC) and Crohn’s Disease (CD), highlighting the potential importance of these species in the human gut. Collectively, our results provide evidence that low-abundant SCFA-producing species in the gut may offer a novel therapeutic approach for IBD.