Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production
Journal article, 2025

Excess amino acids from a protein-rich diet are mainly catabolized in the liver. However, it is still unclear to what extent the gut microbiota may be involved in the mechanisms governing this catabolism. Therefore, the aim of this study was to investigate whether consumption of different dietary protein concentrations induces changes in the taxonomy of the gut microbiota, which may contribute to the regulation of hepatic amino acid catabolism. Consumption of a high-protein diet caused overexpression of HIF-1 alpha in the colon and increase in mitochondrial activity, creating a more anaerobic environment that was associated with changes in the taxonomy of the gut microbiota promoting an increase in the synthesis of secondary bile acids, increased secretion of pancreatic glucagon. This effect was demonstrated in pancreatic islets, where secondary bile acids stimulated the expression of the PC2 enzyme that promotes glucagon formation. The increase in circulating glucagon was associated with an induction of the expression of hepatic amino acid-degrading enzymes, an effect attenuated by antibiotics. Thus, high protein intake in mice and humans induced the increase of different species in the gut microbiota with the capacity to produce secondary bile acids leading to an increase in secondary bile acids and glucagon levels, promoting amino acid catabolism.

amino acid catabolism

Gut microbiota

secondary bile acids

glucagon

high-protein diet

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Published in

Gut Microbes

1949-0976 (ISSN) 1949-0984 (eISSN)

Vol. 17 Issue 1 art. no 2465896

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Subject Categories (SSIF 2025)

Gastroenterology and Hepatology

Nutrition and Dietetics

Endocrinology and Diabetes

Identifiers

DOI

10.1080/19490976.2025.2465896

PubMed

39980327

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Latest update

3/14/2025