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

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.

Beneficial effect of ζ-carotene-like compounds on acute UVB irradiation by alleviating inflammation and regulating intestinal flora

“…54 In contrast, intestinal inflammation destroyed the composition of the microbiota, leading to the expansion of Enterobacteriaceae members. 55 Escherichia – Shigella is a member of Enterobacteriaceae and is proportional to the degree of skin itching and positively correlated with most pro-inflammatory factors in mice, 56 but negatively correlated with the integrity of the colonic barrier. Escherichia – Shigella causes macrophage apoptosis by penetrating epithelial cells and releasing IL-β to aggravate intestinal inflammation.…”

Allopurinol Disrupts Purine Metabolism to Increase Damage in Experimental Colitis

“…Accordingly, generation of purines is governed by two pathways that work in combination to maintain energy balance; namely the de novo purine biosynthesis pathway and the salvage pathway. De novo synthesis is an energetically intensive metabolic process requiring eleven catalytic steps, five enzymes requiring ATP, and three amino acids to generate one molecule of IMP from PRPP [ 39 ]. Conversely, salvage directly forms IMP from PRPP and Hpx, leaving energy available to fuel other cellular processes, such as nucleic acid synthesis [ 40 ].…”

Identification of cuproptosis-associated subtypes and signature genes for diagnosis and risk prediction of Ulcerative colitis based on machine learning

“…It has been shown that LDHD is involved in the regulation of copper apoptosis by controlling intracellular copper levels through involvement in the fatty acylation process of proteins in the TCA cycle ( 77 , 78 ). LDHD is expressed in intestinal epithelial cells and is involved in the regulation of oxidative stress and cellular metabolism, and it is believed that altered LDHD gene expression may lead to oxidative stress and altered cellular metabolism, resulting in increased intestinal inflammation ( 79 ), but the exact mechanism of its association with the development of UC is not fully understood.…”