Nfil3 integrates circadian rhythm and microbial metabolite signaling to maintain gut–liver immune–metabolic homeostasis under high-fat diet stress

In mice on a high-fat diet, removing the Nfil3 gene results in less weight gain, less fat accumulation in the liver, lower blood sugar levels, and reduced leakage in the intestine.

In mice eating a high-fat diet, taking the probiotic VSL#3 leads to less weight gain, better blood sugar control, lower liver enzyme levels, and reduced intestinal leakage, and these changes require part of the Nfil3 signaling pathway.

In mice, a high-fat diet changes the gut bacteria by decreasing types that produce short-chain fatty acids and increasing types that produce endotoxins, which results in a leakier intestine and liver inflammation.

In people with obesity, immune cells in the blood show higher levels of Nfil3 protein and lower levels of circadian rhythm genes, alongside increased activity in inflammatory pathways and decreased levels of receptors that bind short-chain fatty acids.

In mice fed a high-fat diet, the probiotic VSL#3 changes gut bacteria activity to increase functions related to amino acid processing and redox balance while decreasing functions related to lipopolysaccharide production.

Gut microbes follow a daily rhythm, and prolonged periods without food are necessary for them to carry out repair processes in the lining of the intestine.