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

Author:

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

Abstract

Abstract 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.

Funder

National Institute of Allergy and Infectious Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

Welch Foundation

Burroughs Wellcome Fund

American Cancer Society

Publisher

Springer Science and Business Media LLC

Subject

Microbiology (medical),Microbiology

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