Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice

Abstract

Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro. Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1β and interleukin-17 in the colon than in mice fed ad libitum. Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro. In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation.

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

“…Short, water-only fasting has been shown to prevent and help treat intestinal inflammation in acute DSS models (a single, 5-day DSS treatment) (Savendahl et al, 1997; Okada et al, 2017). Our study, using the chronic DSS model that more closely reflects the symptoms and pathology associated with IBD, indicates that fasting alone is not sufficient to reverse the pathology associated with IBD, but it is its combination with certain ingredients that is effective.…”

Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses

“…Given that mTOR serves as a nutrient sensor, the whole-body nutritional status in response to energy intake and starvation may considerably affect the immune response. Indeed, fasting or fasting-mimic diet exerts a protective effect on bacterial sepsis and colitis by alleviating expression of proinflammatory cytokines (Okada et al, 2017;Rangan et al, 2019), whereas glucose supplementation protects against influenza viral infection (Wang et al, 2016). However, the impact of nutritional signals on mucosal barriers, lymphocyte dynamics, and effector functions in the context of fasting and feeding remains unknown.…”

Peroxisome Proliferator-Activated Receptors and Caloric Restriction—Common Pathways Affecting Metabolism, Health, and Longevity

“…The beneficial impact of several restrictive approaches including multiple models of intermittent fasting [ 801 , 802 , 803 , 804 ] and fasting-mimicking diet [ 805 , 806 , 807 ] has been proven. These diets imply temporal restriction without long-term energy deprivation or prolonged hunger making them less restrictive than CR, easier to apply in everyday life, more flexible for various lifestyles, and therefore more plausible for a wide population.…”