Systematic Investigations on the Metabolic and Transcriptomic Regulation of Lactate in the Human Colon Epithelial Cells

Lactate, primarily produced by the gut microbiota, performs as a necessary information transmission carrier between the gut and the microbiota. To investigate the role of lactate in the gut epithelium cell-microbiota interactions as a metabolic signal, we performed a combinatory, global, and unbiased analysis of metabolomic and transcriptional profiling in human colon epithelial cells (Caco-2), using a lactate treatment at the physiological concentration (8 mM). The data demonstrated that most of the genes in oxidative phosphorylation were significantly downregulated in the Caco-2 cells due to lactate treatment. Consistently, the levels of fumarate, adenosine triphosphate (ATP), and creatine significantly decreased, and these are the metabolic markers of OXPHOS inhibition by mitochondria dysfunction. The one-carbon metabolism was affected and the polyol pathway was activated at the levels of gene expression and metabolic alternation. In addition, lactate significantly upregulated the expressions of genes related to self-protection against apoptosis. In conclusion, lactate participates in gut-gut microbiota communications by remodeling the metabolomic and transcriptional signatures, especially for the regulation of mitochondrial function. This work contributes comprehensive information to disclose the molecular mechanisms of lactate-mediated functions in human colon epithelial cells that can help us understand how the microbiota communicates with the intestines through the signaling molecule, lactate.

Automated summary

Lactate, produced by gut microbiota, serves as an important information carrier between the gut and microbiota. This study investigates the role of lactate in the interactions between gut epithelial cells and microbiota by analyzing the metabolomic and transcriptional profiles in human colon epithelial cells. The findings suggest that lactate remolds the metabolomic and transcriptional signatures, particularly in regulating mitochondrial function. This work provides comprehensive information on the molecular mechanisms of lactate-mediated functions in human colon epithelial cells, contributing to our understanding of how microbiota communicates with the intestines through lactate.