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
Author
Sandra Tobon-Cornejo
Instituto Nacional de la Nutricion Salvador Zubiran
Mónica Sánchez-Tapia
Instituto Nacional de la Nutricion Salvador Zubiran
Rocio Guizar-Heredia
Instituto Nacional de la Nutricion Salvador Zubiran
Laura Velazquez Villegas
Instituto Nacional de la Nutricion Salvador Zubiran
Lilia G. Noriega
Instituto Nacional de la Nutricion Salvador Zubiran
Janette Furuzawa-Carballeda
Instituto Nacional de la Nutricion Salvador Zubiran
Rogelio Hernandez-Pando
Instituto Nacional de la Nutricion Salvador Zubiran
Natalia Vazquez-Manjarrez
Instituto Nacional de la Nutricion Salvador Zubiran
Omar Granados-Portillo
Instituto Nacional de la Nutricion Salvador Zubiran
Adriana Lopez-Barradas
Instituto Nacional de la Nutricion Salvador Zubiran
Rosa Rebollar-Vega
Instituto Nacional de la Nutricion Salvador Zubiran
Universidad Nacional Autónoma de México
Otoniel Maya Lucas
Chalmers, Physics, E-commons
Aaron W. Miller
Cleveland Clinic Foundation
Aurora Serralde
Instituto Nacional de la Nutricion Salvador Zubiran
Martha Guevara-Cruz
Instituto Nacional de la Nutricion Salvador Zubiran
Nimbe Torres
Instituto Nacional de la Nutricion Salvador Zubiran
Armando R. Tovar
Instituto Nacional de la Nutricion Salvador Zubiran
Gut Microbes
1949-0976 (ISSN) 1949-0984 (eISSN)
Vol. 17 1 2465896Subject Categories (SSIF 2025)
Gastroenterology and Hepatology
Nutrition and Dietetics
Endocrinology and Diabetes
DOI
10.1080/19490976.2025.2465896
PubMed
39980327