Frontiers in nutritionOct 17, 2026

How intermittent fasting may affect metabolism through gut bacteria, body clocks, and cell cleanup

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 18, 2026

Abstract

Intermittent fasting (IF) may improve metabolic health through various mechanisms.

Four main patterns of intermittent fasting are examined: time-restricted feeding, alternate day fasting, the 5:2 fasting, and the 4:3 fasting.
Intermittent fasting is associated with improvements in body weight, glucose management, insulin sensitivity, and lipid profiles.
Mechanisms include enhancing the intestinal barrier and reducing inflammation, which may alleviate insulin resistance.
Restoration of circadian rhythms in metabolism-related gene expression could correct metabolic dysregulation.
Increased energy expenditure and fat burning may occur through the action of short-chain fatty acids on white adipose tissue.
Cellular autophagy may be enhanced via the activation of specific signaling pathways, potentially improving metabolic function.

Simplified

The global obesity epidemic has increased the burden of metabolic diseases. Dietary interventions are key to managing obesity and improving metabolic health. Intermittent fasting (IF) has emerged as a promising chrononutritional intervention that may modulate metabolic metabolic homeostasis through timed eating-fasting cycles. This review examines four main IF patterns:time-restricted feeding (TRF), alternate day fasting (ADF), the 5:2 fasting, and the 4:3 fasting, and evaluates their effects on body weight, glucose homeostasis, insulin sensitivity, and lipid profiles. Furthermore, it delineates the mechanistic pathways through which IF confers metabolic benefits beyond caloric restriction alone: (1) alleviating insulin resistance by enhancing the intestinal mucosal barrier and upregulating GLP-1 expression suppressing endotoxemia-related inflammation; (2) restoring circadian rhythmicity in the expression of metabolism-related genes to correct metabolic dysregulation; (3) increasing energy expenditure and lipid oxidation via short-chain fatty acid-mediated browning of white adipose tissue (WAT); and (4) enhancing cellular autophagy through activation of the SIRT3-AMPK-mTOR signaling pathway, thereby improving overall metabolic function. Evidence supports IF as a potentially effective alternative for obesity and metabolic disorders through chronobiological mechanisms. However, potential adverse effects like hypoglycemia and adherence challenges highlight the need for individualized approaches in clinical practice.

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How intermittent fasting may affect metabolism through gut bacteria, body clocks, and cell cleanup

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