Maintaining balance in the microverse: investigating microbial impacts on host gut inflammation

Abstract

Enteric microbes can impact digestion, maintain the immune system, and have implications for overall health. Microbial mechanisms driving and alleviating gut inflammation have been speculated but challenging to decipher specific microbial mechanism. Using multi-omics from a systematic to individual microbial populations level, we showed microbial pathways that were responsible for persistent gut inflammation, as well as potential microbial products that might alleviate inflammation. Enterobacteriaceae are known to promote gut inflammation and blooms during dysbiosis, with little speculation on how they drive inflammation. Through a holistic host-microbe approach, we showed that Enterobacteriaceae members can utilize L-cysteine for increased growth, fueling the growth needed to drive inflammation. We further isolated and cultured Enterobacteriaceae Klebsiella pneumoniae and revealed increased expression of membrane proteins and attachment proteins. With this knowledge, we synthesized a peptide to limit attachment of K. pneumoniae to the host, thereby limiting a proliferative and inflammatory response and providing a potential therapeutic alternative to antibiotics. Finally, when investigating dysbiotic murine recovery, we observed an increase in Lachnospiraceae. Using metabolomics, we investigated products that may aid in inflammation alleviation from five strains of Lachnospiraceae. One of the strains, Eubacterium rectale, produced several amino acids and antioxidants that is essential for gut repair. We also showed that microbial metabolites significantly lowered inflammation as well as lower expression of host repair and inflammatory genes. Overall, these findings help us to better understand the gut microbial landscape and the contributions of specific microbes and subpopulations in maintaining the balance of the gut microbiota and gut health.