Alternate-day fasting increases the risk of decreased immune cells and anemia in DSS-induced colitis mice.

Intermittent fasting (IF) is a widely adopted dietary strategy with well-documented benefits in the management of metabolic diseases. However, its effects in pathological settings characterized by severe tissue injury, such as inflammatory bowel disease (IBD), remain controversial. In this study, we investigated the impact of alternate-day fasting (ADF) on disease activity and immune responses in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Mice were subjected to a 35-day ADF protocol, and acute colitis was induced using 3% DSS initiated 7 days prior to the conclusion of the fasting regimen. Multiple indicators were assessed, including body weight, survival rate, colonic tissue damage and barrier integrity, immune cell profile alterations in the bone marrow and spleen, as well as changes in peripheral blood cell counts. Our results showed that ADF significantly exacerbated colonic inflammation, leading to more severe body weight loss and reduced survival. Histopathological examination revealed that ADF impaired the structural integrity of the colonic mucus layer. Flow cytometric analysis further demonstrated that ADF markedly reduced specific innate immune cell populations in the bone marrow and reduced lymphocyte counts in the spleen. Furthermore, ADF-treated mice exhibited signs of anemia. Taken together, these findings indicate that, in acute DSS-induced colitis, strict ADF intervention does not alleviate intestinal injury but instead exacerbates disease progression by suppressing tissue repair, weakening systemic immune function, and promoting anemia. Therefore, the use of intermittent fasting should be carefully evaluated based on the specific pathological context, and caution is strongly recommended for patients with active inflammatory bowel disease.