Definition and types of intermittent fasting
Intermittent Fasting (IF) refers to the voluntary abstinence or reduction of food intake for certain periods of time. Various eating patterns fall under this umbrella, including: time-restricted eating (TRE) or food in which meals are consumed within a limited daily window, such as eight to ten hours, alternate fasting where full fasting days alternate with eating days, modified protocols such as the well-known five-on-two approach where calorie intake is reduced on selected days each week, and religious fasting such as Ramadan, where abstinence occurs during the day. Although these approaches differ in structure, they all introduce repeated periods without nutrient intake, which induce coordinated physiological responses in the gut and metabolic systems.
Proposed mechanisms linking IF, intestinal function and metabolism
Instead of acting through a single path, IF initiates one sequence of physiological events that unfold during the fasting-feeding cyclestarting in the intestines and extending to systemic metabolism. Viewing IF as a cycle illuminates how digestive, microbial, immune, and metabolic processes interact over time.
The fasting phase: rhythm, motility, recovery and metabolic switch
The cycle begins with the absence of food, which acts as a powerful synchronizer circadian rhythms. Morning or early lunch improves glucose handling, lipid metabolism, and blood pressure patternswhile taking it late at night can weaken insulin sensitivity1.
As fasting continues, the intestine enters a motility phase characterized by intestinal activation migrating motor complexa pattern of cyclic contractions that only occurs in the absence of food. This housekeeping mechanism removes residual nutrients and bacteria from the small intestine and can help limit bacterial overgrowth2.
Prolonged fasting also initiates a recovery-oriented state. Decreased exposure to nutrients decreases endotoxin translocation and dampens inflammatory signaling. IF has indeed been demonstrated reduce pro-inflammatory cytokines and LPS-mediated monocyte activation³, while increasing regulatory cytokines that support lipid metabolism and immune balance. IL-6 can also increase transiently during fasting, but in this context appears to promote lipid mobilization rather than chronic inflammatory signaling4. This transient effect could benefit patients with IBD by supporting metabolic and immune regulation, although fasting should be approached cautiously in this population to avoid malnutrition or worsening of symptoms.5. At the cellular level fasting activates autophagy, improves mitochondrial efficiency and reduces oxidative stressto support tissue maintenance and metabolic flexibility6.
As the fast extends beyond 10 to 14 hours, the liver begins to run low on glycogen and the body switches from glucose to fat (ketone bodies) as its main fuel.7. In addition to the energy supply, ketones act as signaling molecules, influencing oxidative stress, inflammation and gene transcription linked to metabolic resilience. ALS often reduces postprandial insulin exposure simply by reducing the number of insulin-triggering eating events, which can improve insulin sensitivity.
Nutrients reaching the large intestine: microbial fermentation, hormones and satiety
When feeding is resumed, nutrients that escape digestion in the upper intestine reach the colon, where they are fermented by the gut microbiota into short-chain fatty acids (SCFAs). The gut microbiome itself follows a circadian rhythm, with daytime feeding favoring SCFA-producing Firmicutes and nighttime fasting supporting Bacteroidetes and bile acid turnover. ALS often increases microbial α-diversitywhich is usually higher during the day8while individuals with metabolic diseases, such as type 2 diabetes, often exhibit reduced diversity9. Higher microbial diversity inversely correlates with body fat, suggesting that some benefits may be secondary to weight loss10. ALS too enriches useful taxa like Faecalibacterium prausnitzii And Akkermansia muciniphila while reducing the number of pathogens6.
SCFAs play a central role in linking the microbiome to host metabolism. She strengthen the intestinal barrierreduce inflammation and stimulate the release of satiety hormones such as GLP-1 and PYY, which directly influence appetite regulation and glycemic control. These hormonal effects help explain why many people suffer from it snack less and spontaneous calorie reduction during IF7.
Breaking the fast: a crucial determinant of benefit
Breaking the fast can enhance or undermine the benefits of IF. Very large or very refined meals can overload the digestive system, delay gastric emptying and… reduce the absorption of important minerals such as iron, zinc and calciumespecially when phytate-rich foods are eaten without enhancers such as vitamin C or animal proteins. Repeated ingestion of high-sugar or low-fiber meals can also attenuate microbial fermentation and satiety signals. In addition, some individuals may overeat during feeding windowsespecially after long periods of fasting or whenever consuming extremely tasty food.
Conclusion:
Clinical evidence remains limited, but current evidence suggests this early TRlimiting food intake to earlier hours of the day produces the most consistent results benefits for glucose regulation, lipid metabolism and circadian alignment1. However, intermittent fasting is not a therapeutic shortcut, nor a one-size-fits-all solution. Its potential benefits depend on careful implementation, gradual adaptation and overall diet quality, and not just the duration of the fast. For long-term health, the most effective approach is one that can be sustained over time and integrated into a balanced lifestyle. Extended fasting protocols should only be performed under medical or dietary supervision11and intermittent fasting isn’t for everyone. People with diabetes, eating disorders12hypotension, during pregnancy or lactation, or those undergoing intense exercise should seek professional guidance or avoid fasting altogether.
Keywords: Gut microbiota, metabolism, intermittent fasting (IF), time-restricted eating (TRE), alternate-day fasting (ADF)
References:
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- Mohr, E., Jasbi, P., Bowes, D. A., Dirks, B., Whisner, C. M., Arciero, K. M., Poe, M., Gu, H., Gumpricht, E., Sweazea, K. L., & Arciero, P. J. (2022). Exploratory analysis of one- and two-day intermittent fasting protocols on the gut microbiome and plasma metabolome in overweight/obese adults. Limits in nutrition9, 1036080. https://doi.org/10.3389/fnut.2022.1036080
- Haskey, N., Lewis, A. G., Lavallee, C., Yousuf, M., Taylor, L., Jilani, S., Gold, S., Lu, C., Ghosh, S., Panaccione, R., & Raman, M. (2025). Time-restricted feeding improves inflammatory and metabolic biomarkers in overweight Crohn’s disease: a randomized, placebo-controlled pilot study. Journal of the Canadian Society of Gastroenterology8(Suppl 1), i31. https://doi.org/10.1093/jcag/gwae059.080
- Pérez-Gerdel, T., Camargo, M., Alvarado, M., and RamÃrez, J. D. (2023). Impact of intermittent fasting on the gut microbiota: a systematic review. Advanced Biology, 7(8), article 2200337. https://doi.org/10.1002/adbi.202200337
- Paukkonen, I., Törrönen, E.-N., Lok, Schwab, U., & El-Nezami, H. (2024). The impact of intermittent fasting on the gut microbiota: a systematic review of human studies. Frontiers in Nutrition, 11, 1342787. https://doi.org/10.3389/fnut.2024.1342787
- Ashique, S., Debnath, B., Mojgani, N., Tariq, M., Haider, T., Shorog, E., Yasmin, S., Islam, A., Sharma, H., Hussain, M. S., Madan, A., Malik, T., & Ansari, M. Y. (2025). Modulation of the gut microbiota and health benefits of different fasting regimens. Current research in biotechnology10, 100311. https://doi.org/10.1016/j.crbiot.2025.100311
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- Mohr, A. E., Sweazea, K. L., Bowes, D. A., Jasby, P., Whisner, C. M., Sears, D. D., Krajmalnik-Brown, R., Jin, Y., Gu, H., Klein-Seetharaman, J., Arciero, K. M., Gumpricht, E., & Arciero, P. J. (2024). Gut microbiome remodeling and metabolomic profile improve in response to protein stimulation with intermittent fasting versus continuous caloric restriction. Nature Communication, 15, 4155. https://doi.org/10.1038/s41467-024-48355-5#
- Mikhael-Moussa, H., Bertrand, V., Lejeune, E., Dupont, C., Aupetit, A., Achamrah, N., and Melchior, C. (2025). The association of avoidant/restrictive food intake disorders (ARFID) and neurogastroenterological disorders (including gut-brain interaction disorders [DGBI]): An exploratory overview. Neurogastroenterology and motility37(9), e70039. https://doi.org/10.1111/nmo.70039
- Mikhael-Moussa, H., Bertrand, V., Lejeune, E., Dupont, C., Aupetit, A., Achamrah, N., and Melchior, C. (2025). The association of avoidant/restrictive food intake disorders (ARFID) and neurogastroenterological disorders (including gut-brain interaction disorders [DGBI]): An exploratory overview. Neurogastroenterology and motility37(9), e70039. https://doi.org/10.1111/nmo.70039
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