Journal Article

Colonocyte-derived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis

Jimenez, Angel G., Winter, Maria G., Gillis, Caroline C., Zhu, Wenhan, Winter, Sebastian E., Llano, Ernesto M., Taylor, Savannah J., Kim, Jiwoong, Santos, Renato L., Spiga, Luisella, Rojas, Vivian K., Silva, Laice Alves da, Muramatsu, Matthew K., Chanin, Rachael B., Dobbins, Amanda L.

2022

Overview

Background Intestinal inflammation disrupts the microbiota composition leading to an expansion of Enterobacteriaceae family members (dysbiosis). Associated with this shift in microbiota composition is a profound change in the metabolic landscape of the intestine. It is unclear how changes in metabolite availability during gut inflammation impact microbial and host physiology. Results We investigated microbial and host lactate metabolism in murine models of infectious and non-infectious colitis. During inflammation-associated dysbiosis, lactate levels in the gut lumen increased. The disease-associated spike in lactate availability was significantly reduced in mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells. Commensal E. coli and pathogenic Salmonella , representative Enterobacteriaceae family members, utilized lactate via the respiratory L-lactate dehydrogenase LldD to increase fitness. Furthermore, mice lacking the lactate dehydrogenase A subunit in intestinal epithelial cells exhibited lower levels of inflammation in a model of non-infectious colitis. Conclusions The release of lactate by intestinal epithelial cells during gut inflammation impacts the metabolism of gut-associated microbial communities. These findings suggest that during intestinal inflammation and dysbiosis, changes in metabolite availability can perpetuate colitis-associated disturbances of microbiota composition. 4h64TYW6e28QusiMD-BunN Video Abstract

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Animal models / Animals / Antibiotics / Bacteria / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Colitis / Colitis - pathology / Colorectal cancer / Digestive system / Dysbacteriosis / Dysbiosis / E coli / Enterobacteriaceae / Enterobacteriaceae - metabolism / Epithelial cells / Escherichia coli - metabolism / Experiments / Fitness / Gastrointestinal Microbiome / Gastrointestinal tract / Genes / Gut inflammation / Gut microbiota / Host-microbe interactions / Inflammation / Inflammation - pathology / Inflammatory bowel disease / Intestinal microflora / Intestine / L-Lactate dehydrogenase / Laboratories / Lactate Dehydrogenase 5 / Lactate metabolism / Lactic acid / Lactic Acid - metabolism / Medical Microbiology / Metabolism / Metabolites / Mice / Mice, Inbred C57BL / Microbial Ecology / Microbial Genetics and Genomics / Microbiology / Microbiota / Plasmids / Sodium / Virology