Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders

Intermittent fasting (IF) has been reported to have beneficial effects on improving gut function via lowering gut inflammation and altering the gut microbiome diversity. In this study, we aimed to investigate the differential effects of three different common IF treatments, alternate day fasting (ADF), time-restricted fasting (TRF), and intermittent energy restriction (IER), on a dextran sodium sulfate (DSS)-induced colitis mouse model. The results indicated that TRF and IER, but not ADF improved the survival rates of the colitis mice. TRF and IER, but not ADF, reversed the colitis pathological development by improving the gut barrier integrity and colon length. Importantly, TRF and IER suppressed the inflammatory responses and oxidative stress in colon tissues. Interestingly, TRF and IER also attenuated colitis-related anxiety-like and obsessive-compulsive disorder behavior and alleviated the neuroinflammation and oxidative stress. TRF and IER also altered the gut microbiota composition, including the decrease of the enrichments of colitis-related microbes such as Shigella and Escherichia Coli, and increase of the enrichments of anti-inflammatory-related microbes. TRF and IER also improved the short chain fatty acid formation in colitis mice. In conclusion, the TRF and IER but not ADF exhibited the protective effects against colitis and related behavioral disorders, which could be partly explained by improving the gut microbiome compositions and preventing gut leak, and consequently suppressing the inflammation and oxidative damages in both colon and brain. The current research indicates that proper IF regimens could be effective strategies for nutritional intervention for the prevention and treatment of colitis.