Time-restricted feeding causes irreversible metabolic disorders and gut microbiota shift in pediatric mice

BACKGROUND: Time-restricted feeding regimen (TRF), that is, no food consumption for 14–16 h during the light phase per day, attenuates the fattening traits and metabolic disorders in adults. This study aims to further investigate whether TRF would be protective against similar nutritional challenges in juvenile mice. METHODS: Mice in the experimental group were treated with TRF during the first 4 weeks (considered to be the childhood phase of mice) before switching to ad libitum (AD) feeding pattern as adults; the control group with all subjects sticks to AD mode. Body weight was monitored, and serum biochemistry, sexual maturity, immune function, and gut microbiota were assessed at a certain timing. RESULTS: Mice treated with TRF during the childhood period (from weaning age) but went through AD feeding pattern as adults demonstrated the tendency of higher body weight, higher levels of serum glucose, shrunken Langerhans islets, fatty liver disease, thickening of aortic walls, delayed sexual development, increased proportion of T regulatory cells, and unhealthy gut microbiota. CONCLUSION: Childhood TRF causes pleiotropic adverse effects, including severe irreversible metabolic disorders, depressed immune function, and retarded puberty. Microbiota set the stage for TRF to employ downstream reactions on the above changes.