Gut microbiota mediate the FGF21 adaptive stress response to chronic dietary protein-restriction in mice

Chronic dietary protein-restriction can create essential amino acid deficiencies and induce metabolic adaptation through the hepatic FGF21 pathway which serves to maintain host fitness during prolonged states of nutritional imbalance. Similarly, the gut microbiome undergoes metabolic adaptations when dietary nutrients are added or withdrawn. Here we confirm previous reports that dietary protein-restriction triggers the hepatic FGF21 adaptive metabolic pathway and further demonstrate that this response is mediated by the gut microbiome and can be tuned through dietary supplementation of fibers that alter the gut microbiome. In the absence of a gut microbiome, we discover that FGF21 is de-sensitized to the effect of protein-restriction. These data suggest that host-intrinsic adaptive pathways to chronic dietary protein-restriction, such as the hepatic FGF21 pathway, may in-fact be responding first to adaptive metabolic changes in the gut microbiome. Dietary protein restriction induces a hepatic stress response mediated by the endocrine molecule FGF21, which triggers host adaptive pathways. Here the authors demonstrate that the gut microbiome is required to trigger the FGF21 response and can be manipulated through dietary fiber supplementation.

Automated summary

Dietary protein restriction triggers the hepatic FGF21 adaptive metabolic pathway, which is influenced by the gut microbiome and can be regulated by dietary fiber supplementation. In the absence of gut microbiome, FGF21 loses sensitivity to protein restriction.