Brain–Gut–Microbiome Interactions and Intermittent Fasting in Obesity
Open accessAbstract
The obesity epidemic and its metabolic consequences are a major public health problem both in the USA and globally. While the underlying causes are multifactorial, dysregulations within the brain–gut–microbiome (BGM) system play a central role. Normal eating behavior is coordinated by the tightly regulated balance between intestinal, extraintestinal and central homeostatic and hedonic mechanisms, resulting in stable body weight. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food has played a crucial role in shifting this balance towards hedonic eating through both central (disruptions in dopaminergic signaling) and intestinal (vagal afferent function, metabolic toxemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. The balance between homeostatic and hedonic eating behaviors is not only influenced by the amount and composition of the diet, but also by the timing and rhythmicity of food ingestion. Circadian rhythmicity affects both eating behavior and multiple gut functions, as well as the composition and interactions of the microbiome with the gut. Profound preclinical effects of intermittent fasting and time restricted eating on the gut microbiome and on host metabolism, mostly demonstrated in animal models and in a limited number of controlled human trials, have been reported. In this Review, we will discuss the effects of time-restricted eating on the BGM and review the promising effects of this eating pattern in obesity treatment.
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Interaction of such hormones in the periphery and hypothalamus plays a key role in regulation of appetite and satiety, and dysregulation has been implicated in obesity and food addiction.
“The interaction of such hormones in the periphery and in the hypothalamus play a key role in the regulation of appetite and satiety [23] and a dysregulation of these signaling systems has been implicated in obesity and food addiction [24].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [24]
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The role of the gut microbiota in multiple sclerosis
Correale, J., Hohlfeld, R., & Baranzini, S. E. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00697-8 · Cited by 207 · see citing works
Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders
Horn, J., Mayer, D. E., Chen, S., & Mayer, E. A. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01922-0 · Cited by 193 · see citing works
Self-citationMicrobiota and body weight control: Weight watchers within?
Boscaini, S., Leigh, S., Lavelle, A., García‐Cabrerizo, R., Lipuma, T., Clarke, G. A., Schellekens, H., & Cryan, J. F. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101427 · Cited by 66 · see citing works
Yarahmadi, A., Afkhami, H., Javadi, A., & Kashfi, M. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01561-z · Cited by 59 · see citing works
Timing is everything: Circadian rhythms and their role in the control of sleep
Pandi-Perumal, S. R., Cardinali, D. P., Zaki, N. F. W., Ramanujam, K., Spence, D. W., Reiter, R. J., & Brown, G. M. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2022.100978 · Cited by 50 · see citing works
Lavallee, C. M., Bruno, A., Ma, C., & Raman, M. (2022) · Nutrients · doi:10.3390/nu14214655 · Cited by 44 · see citing works
Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease
Nguyen, Y., Manis, J. R. Z., Ronczkowski, N. M., Bui, T., Oxenrider, A., Jadeja, R. N., & Thounaojam, M. C. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1377186 · Cited by 33 · see citing works
Zhang, H., Tong, T., Gao, Y., Liang, C., Yu, H., Li, S., Yan, X., & Wang, L. (2021) · Journal of Eating Disorders · doi:10.1186/s40337-021-00471-z · Cited by 33 · see citing works
Role of herbal medicine and gut microbiota in the prevention and treatment of obesity
Zhang, Q., Bai, Y., Wang, W., Li, J., Zhang, L., Tang, Y., & Yue, S. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.116127 · Cited by 33 · see citing works
Health Benefits of Intermittent Fasting
Reddy, B. L., Reddy, V. S., & Saier, M. H. (2024) · Microbial Physiology · doi:10.1159/000540068 · Cited by 32 · see citing works
Caron, J. P., Kreher, M. A., Mickle, A. M., Wu, S., Przkora, R., Estores, I. M., & Sibille, K. T. (2022) · Nutrients · doi:10.3390/nu14122536 · Cited by 27 · see citing works
The molecular signaling of exercise and obesity in the microbiota-gut-brain axis
Ribeiro, F. M., Silva, M. A., Lyssa, V., Marques, G., Lima, H. K., Franco, O. L., & Petriz, B. A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.927170 · Cited by 25 · see citing works
Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations
Barrea, L., Muscogiuri, G., Pugliese, G., Graziadio, C., Maisto, M., Pivari, F., Falco, A., Tenore, G. C., Colao, A., & Savastano, S. (2021) · Nutrients · doi:10.3390/nu13051671 · Cited by 25 · see citing works
Linkage of circadian rhythm disruptions with Alzheimer's disease and therapeutic interventions
Madhamanchi, K., Zhang, J., & Melkani, G. C. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.04.011 · Cited by 30 · see citing works
Gut microbiome: New perspectives for type 2 diabetes prevention and treatment
Li, S.-X., & Guo, Y. (2023) · World Journal of Clinical Cases · doi:10.12998/wjcc.v11.i31.7508 · Cited by 20 · see citing works
Time Restricted Eating: A Valuable Alternative to Calorie Restriction for Addressing Obesity?
Parrotta, M. E., Colangeli, L., Scipione, V., Vitale, C., Sbraccia, P., & Guglielmi, V. (2025) · Current Obesity Reports · doi:10.1007/s13679-025-00609-z · Cited by 19 · see citing works
Qi, Z., Zhou, L., Dai, S., Zhang, P., Zhong, H., Zhou, W., Zhao, X., Xu, H., Zhao, G., Wu, H., et al. (2025) · Life Metabolism · doi:10.1093/lifemeta/loaf002 · Cited by 16 · see citing works
Metabolomics Profiling of Nephrotic Syndrome towards Biomarker Discovery
Jacob, M., Nimer, R. M., Alabdaljabar, M. S., Sabi, E. M., Al‐Ansari, M. M., Housien, M., Sumaily, K. M., Dahabiyeh, L. A., & Rahman, A. M. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012614 · Cited by 16 · see citing works
Correlates of Food Addiction and Eating Behaviours in Patients with Morbid Obesity
Schankweiler, P., Raddatz, D., Ellrott, T., & Hauck, C. (2023) · Obesity Facts · doi:10.1159/000531528 · Cited by 14 · see citing works
Oliveira, L. D. C., Morais, G. P., Ropelle, E. R., de Moura, L. P., Cintra, D. E., Pauli, J. R., de Freitas, E. C., Rorato, R. C., & da Silva, A. S. R. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.858320 · Cited by 14 · see citing works
Shao, X., Tan, L. H., & He, L. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1019129 · Cited by 12 · see citing works
The link between gut microbiota and multiple sclerosis from the perspective of barrier function
Ren, J., Niu, Z., Wang, J., Guo, J., Hao, H.-J., Gao, F., Liu, R., & Wang, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1652796 · Cited by 11 · see citing works
Metabolic Consequences Of Weight Reduction
Farhana, A., & Rehman, A. U. (2021) · Cited by 11 · see citing works
Intermittent Fasting on Human Health and Disease
Margina, D. M., & Drăgoi, C. M. (2023) · Nutrients · doi:10.3390/nu15214491 · Cited by 11 · see citing works
Wang, J., Rang, Y., & Liu, C. (2024) · Current Nutrition Reports · doi:10.1007/s13668-024-00570-8 · Cited by 10 · see citing works
Song, H., Pang, R., Chen, Z., Wang, L., Hu, X., Feng, J., Wang, W., Liu, J., & Zhang, A. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1466125 · Cited by 9 · see citing works
Ou, Y., Chen, K., Guo, J. Q., Ye, C., Zhou, X., Chen, D., Bian-sheng, L., Liu, C., & Liu, J. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.145679 · Cited by 9 · see citing works
Gut microbiota modulation and health benefits of various fasting regimens
Ashique, S., Debnath, B., Mojgani, N., Tariq, M., Haider, T., Shorog, E., Yasmin, S., Islam, A., Sharma, H., Hussain, M. S., et al. (2025) · Current Research in Biotechnology · doi:10.1016/j.crbiot.2025.100311 · Cited by 9 · see citing works
Are the Modern Diets for the Treatment of Obesity Better than the Classical Ones?
Koliaki, C. C., & Katsilambros, N. L. (2022) · Endocrines · doi:10.3390/endocrines3040052 · Cited by 8 · see citing works
A nexus of dietary restriction and gut microbiota: Recent insights into metabolic health
Wang, L., Wang, F., Xiong, L. H., Song, H., Ren, B., & Shen, X. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2202750 · Cited by 9 · see citing works
Understanding Microbial Mediation of the Brain-Gut Axis
Horn, J. V., Delgadillo, D. R., & Mayer, E. A. (2025) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2024.12.004 · Cited by 7 · see citing works
Self-citationMei, H., Yang, S., Peng, A., Li, R., Xiang, F., Zheng, H., Tan, Y., Zhang, Y., Zhou, A., Zhang, J., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.891679 · Cited by 7 · see citing works
Chronodisruption and Gut Microbiota: Triggering Glycemic Imbalance in People with Type 2 Diabetes
Moreno-Cortés, M. L., Meza, E., Garcı́a-Mena, J., & Hernández-Rodríguez, A. (2024) · Nutrients · doi:10.3390/nu16050616 · Cited by 8 · see citing works
Ullah, Z., Tao, Y., Mehmood, A., & Huang, J. (2024) · Bioengineering · doi:10.3390/bioengineering11111063 · Cited by 6 · see citing works
Yalçın, T., & Öztürk, E. E. (2023) · Galician Medical Journal · doi:10.21802/gmj.2023.1.2 · Cited by 6 · see citing works
Intermittent Fasting and Probiotics: Synergistic Modulation of Gut Health for Therapeutic Advantages
Shehbaz, A., Afzaal, M., Akram, N., Saeed, F., Khan, W., Ahmed, F., Ahmed, A., Asghar, A., & Faisal, Z. (2024) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-024-10358-5 · Cited by 6 · see citing works
The research progress and prospects of circadian rhythm in obesity: a bibliometric analysis
Dou, Y., Guo, X., Wang, X., He, A., Li, F., & Gao, K. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1499984 · Cited by 6 · see citing works
Minnebo, Y., Paepe, K. D., Raes, J., & de Wiele, T. V. (2023) · FEMS Microbiology Ecology · doi:10.1093/femsec/fiad149 · Cited by 5 · see citing works
Xie, H., Chen, Y., Tang, J., Ma, Y., Liu, Y., & Ren, X. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-06541-9 · Cited by 5 · see citing works
Eating Disorders in the Workplace
Magnavita, N., Meraglia, I., & Isolani, L. (2025) · Nutrients · doi:10.3390/nu17142300 · Cited by 5 · see citing works
Violence in Healthcare Workers Is Associated with Disordered Eating
Magnavita, N., & Isolani, L. (2025) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph22081221 · Cited by 5 · see citing works
Association between intestinal microflora and obesity
Savytska, M., Kozyk, M., Strubchevska, K., YOSYPENKO, K., Falalyeyeva, T. M., Kobyliak, N. M., Boccuto, L., Pellicano, R., Fagoonee, S., Scarpellini, E., et al. (2023) · Minerva Gastroenterology · doi:10.23736/s2724-5985.23.03379-x · Cited by 4 · see citing works
Dynamical alterations of brain function and gut microbiome in weight loss
Zhou, J., Wu, X., Xiang, T., Liu, F., Gao, H., Tong, L., Yan, B., Li, Z., Zhang, C., Wang, L., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1269548 · Cited by 4 · see citing works
Restoring gut biome balance for weight loss: clinical applications
Bhat, N., Bhat, J., Bhat, K., Junaid, I., Bhat, A., & Bhat, J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822238-6.00022-4 · Cited by 3 · see citing works
The gut microbiome: an overview of current trends and risks for paediatric populations
Sangiuolo, K., Cheng, E., Terala, A., Dubrosa, F., & Milanaik, R. L. (2022) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001186 · Cited by 3 · see citing works
Sex-specific effects of intermittent fasting on hippocampal neurogenesis via the gut-brain axis
Luo, Y., Wang, H. Z., Chen, Z., Deng, Y., Zhang, Y., & Hu, W. (2024) · Food & Function · doi:10.1039/d4fo00318g · Cited by 3 · see citing works
Chronotype is associated with Mediterranean dietary adherence and environmental footprints
İnan, C. M., Kahraman, C. Ş., Özçelik, A. Ö., & Ayhan, N. Y. (2024) · International Journal of Environmental Health Research · doi:10.1080/09603123.2024.2334785 · Cited by 2 · see citing works
The impact of food addiction on the treatment of eating disorders and obesity: A systematic review
Amato, A. L., Gualtieri, P., Cirillo, M., Placa, G. L., Frank, G., Cianci, R., & Renzo, L. D. (2026) · Physiology & Behavior · doi:10.1016/j.physbeh.2026.115248 · Cited by 2 · see citing works
Bieńko, M., Rutkowska, M., Król, T., Toborek, M., Marchaj, M., Korta, K., Putra, A., Niedziela, N., & Margas, M. (2024) · Quality in Sport · doi:10.12775/qs.2024.16.52500 · Cited by 3 · see citing works
Rabiei, S. (2025) · International Journal of Preventive Medicine · doi:10.4103/ijpvm.ijpvm_312_24 · Cited by 1 · see citing works
Silverii, G. A., & Turrini, A. (2025) · Current Obesity Reports · doi:10.1007/s13679-025-00663-7
Gut microbiota as a novel therapeutic target for eating disorders and obesity
Samulenaite, S., Mathis, V., Darcq, E., Burokas, A., Martín‐García, E., & Maldonado, R. J. (2026) · British Journal of Pharmacology · doi:10.1111/bph.70547 · Cited by 1 · see citing works
Paltsyn, A. A., & Sviridkina, N. B. (2021) · Zhurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» · doi:10.25557/0031-2991.2021.04.116-120 · Cited by 1 · see citing works
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Lifestyle and eye care 4: Eye care professionals - an approach to disease prevention
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Introductory Chapter: Insights into the Therapeutic Applications of Fasting
Drăgoi, C. M., Ungurianu, A., Dumitrescu, I.-B., & Nicolae, A. C. (2025) · Food science and nutrition · doi:10.5772/intechopen.1009338
Alimentos ultraprocesados y su relación con la obesidad: Aportes desde la neuroeducación
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Segment-Specific Functional Responses of Swine Intestine to Time-Restricted Feeding Regime
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- Authors
- Frank, J., Gupta, A., Osadchiy, V., & Mayer, E. A.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Mayer, Emeran A.
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2021-02-10
- Volume
- 13
- Issue
- 2
- Pages
- 584
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC7916460
- OpenAlex
- W3129023812
- Cited by
- 68
- References
- 90
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 12 · 2023: 9 · 2022: 16 · 2021: 8
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 041301, DK048351, R01DK048351, K23DK106528, R03DK121025)
- National Institute on Minority Health and Health Disparities (R01MD015904)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- intermittent fasting, time-restricted eating, obesity, dietary habits, hedonic eating, dopaminergic signaling, systemic immune activation, gut microbiota, metabolome, circadian rhythm, meal timing, obesity treatment
- MeSH terms
- Gastrointestinal Microbiome, Food Addiction, Animals, Brain, Circadian Rhythm, Diet, Fasting, Feeding Behavior, Humans, Obesity, Stress, Psychological, Vagus Nerve, Gastrointestinal Tract, Metabolome, Dysbiosis
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