GUT MICROBIOTA AND PHARMACOLOGICAL TREATMENT RESPONSE IN OBESITY: IMPLICATIONS FOR PERSONALIZED MEDICINE
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.5930Keywords:
Obesity, Gut Microbiota, GLP-1 Receptor Agonists, Pharmacotherapy, Personalized Medicine, Gut–Brain AxisAbstract
Obesity is a chronic, multifactorial metabolic disease associated with significant morbidity, mortality, and increasing global prevalence. In recent years, the gut microbiota has emerged as an important regulator of host metabolism, energy homeostasis, inflammation, and appetite control (Gomes et al., 2018; Geng et al., 2022; Enache et al., 2024). At the same time, modern anti-obesity pharmacotherapy, particularly glucagon-like peptide-1 receptor agonists, has substantially improved therapeutic possibilities. However, considerable interindividual variability in treatment response remains a major clinical challenge.
This narrative review aimed to summarize current evidence regarding the relationship between gut microbiota and pharmacological treatment response in obesity, with particular emphasis on GLP-1 receptor agonists and implications for personalized medicine. Scientific literature including review articles, experimental studies, observational studies, and clinical investigations concerning obesity pharmacotherapy and microbiota-related mechanisms was qualitatively synthesized.
Current evidence suggests that gut microbiota may influence obesity treatment efficacy through modulation of incretin secretion, bile acid metabolism, short-chain fatty acid production, gut barrier integrity, inflammatory pathways, and the microbiota–gut–brain axis. GLP-1 receptor agonists may additionally modify microbial composition, suggesting a bidirectional relationship between incretin signaling and microbiota regulation (Gofron et al., 2025; Feng et al., 2024).
Overall, gut microbiota represents a promising therapeutic target and potential biomarker for precision obesity medicine. Further prospective human studies are required to validate microbiota-guided approaches to obesity pharmacotherapy.
References
Alissou, M., Demangeat, T., Folope, V., Van Elslande, H., Lelandais, H., Blanchemaison, J., Cailleaux, P.-E., Guney, S., Aupetit, A., Aubourg, A., Rapp, C., Petit, A., Godin, M., Vignal, L., Grigioni, S., Déchelotte, P., Colange, G., Coëffier, M., & Achamrah, N. (2025). Impact of semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study. Obesity Science & Practice, 11(2), e70109. https://doi.org/10.1002/osp4.70109
Angelini, G., Russo, S., & Mingrone, G. (2024). Incretin hormones, obesity and gut microbiota. Peptides, 178, 171216. https://doi.org/10.1016/j.peptides.2024.171216
Barakat, G. M., Ramadan, W., Assi, G., & El Khoury, N. B. (2024). Satiety: A gut–brain–relationship. The Journal of Physiological Sciences, 74(1), 11. https://doi.org/10.1186/s12576-024-00904-9
Cadena-Ullauri, S., Guevara-Ramírez, P., Ruiz-Pozo, V. A., Tamayo-Trujillo, R., Paz-Cruz, E., Zambrano-Villacres, R., Simancas-Racines, D., & Zambrano, A. K. (2024). The effect of intermittent fasting on microbiota as a therapeutic approach in obesity. Frontiers in Nutrition, 11, 1393292. https://doi.org/10.3389/fnut.2024.1393292
Cuevas-Sierra, A., Ramos-Lopez, O., Riezu-Boj, J. I., Milagro, F. I., & Martinez, J. A. (2019). Diet, gut microbiota, and obesity: Links with host genetics and epigenetics and potential applications. Advances in Nutrition, 10(Suppl. 1), S17–S30. https://doi.org/10.1093/advances/nmy078
Dreyer, J. L., & Liebl, A. L. (2018). Early colonization of the gut microbiome and its relationship with obesity. Human Microbiome Journal, 10, 1–5. https://doi.org/10.1016/j.humic.2018.08.002
Enache, R.-M., Profir, M., Roșu, O. A., Crețoiu, S. M., & Gaspar, B. S. (2024). The role of gut microbiota in the onset and progression of obesity and associated comorbidities. International Journal of Molecular Sciences, 25(22), 12321. https://doi.org/10.3390/ijms252212321
Feng, J., Teng, Z., Yang, Y., Liu, J., & Chen, S. (2024). Effects of semaglutide on gut microbiota, cognitive function and inflammation in obese mice. PeerJ, 12, e17891. https://doi.org/10.7717/peerj.17891
Gerard, P. (2016). Gut microbiota and obesity. Cellular and Molecular Life Sciences, 73(1), 147–162. https://doi.org/10.1007/s00018-015-2061-5
Geng, J., Ni, Q., Sun, W., Li, L., & Feng, X. (2022). The links between gut microbiota and obesity and obesity-related diseases. Biomedicine & Pharmacotherapy, 147, 112678. https://doi.org/10.1016/j.biopha.2022.112678
Gofron, K. K., Wasilewski, A., & Małgorzewicz, S. (2025). Effects of GLP-1 analogues and agonists on the gut microbiota: A systematic review. Nutrients, 17(8), 1303. https://doi.org/10.3390/nu17081303
Gomes, A. C., Hoffmann, C., & Mota, J. F. (2018). The human gut microbiota: Metabolism and perspective in obesity. Gut Microbes, 9(4), 308–325. https://doi.org/10.1080/19490976.2018.1465157
Gong, B., Li, C., Shi, Z., Wang, F., Dai, R., Chen, G., & Su, H. (2025). GLP-1 receptor agonists: Exploration of transformation from metabolic regulation to multi-organ therapy. Frontiers in Pharmacology, 16, 1675552. https://doi.org/10.3389/fphar.2025.1675552
Iqbal, M., Yu, Q., Tang, J., & Xiang, J. (2025). Unraveling the gut microbiota’s role in obesity: Key metabolites, microbial species, and therapeutic insights. Journal of Bacteriology, 207(5), e00479-24. https://doi.org/10.1128/jb.00479-24
Korpela, K., Flint, H. J., Johnstone, A. M., Lappi, J., Poutanen, K., Dewulf, E., Delzenne, N., de Vos, W. M., & Salonen, A. (2014). Gut microbiota signatures predict host and microbiota responses to dietary interventions in obese individuals. PLoS ONE, 9(3), e90702. https://doi.org/10.1371/journal.pone.0090702
Longo, S., Rizza, S., & Federici, M. (2023). Microbiota-gut-brain axis: Relationships among the vagus nerve, gut microbiota, obesity, and diabetes. Acta Diabetologica, 60(8), 1007–1017. https://doi.org/10.1007/s00592-023-02088-x
Nobrega, R., Costa, C. F. F. A., Cerqueira, O., Inês, A., Carrola, J. S., & Gonçalves, C. (2025). Association between gut microbiota and pediatric obesity: A systematic review. Nutrition, 140, 112875. https://doi.org/10.1016/j.nut.2025.112875
Puljiz, Z., Kumric, M., Vrdoljak, J., Martinovic, D., Ticinovic Kurir, T., Krnic, M. O., Urlic, H., Puljiz, Z., Zucko, J., Dumanic, P., Mikolasevic, I., & Bozic, J. (2023). Obesity, gut microbiota, and metabolome: From pathophysiology to nutritional interventions. Nutrients, 15(10), 2236. https://doi.org/10.3390/nu15102236
Wang, Q., Lin, H., Shen, C., Zhang, M., Wang, X., Yuan, M., Yuan, M., Jia, S., Cao, Z., Wu, C., Chen, B., Gao, A., Bi, Y., Ning, G., Wang, W., Wang, J., & Liu, R. (2023). Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling. Gut Microbes, 15(1), 2274124. https://doi.org/10.1080/19490976.2023.2274124
Zeng, Y., Wu, Y., Zhang, Q., & Xiao, X. (2024). Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio, 15(1), e02436-24. https://doi.org/10.1128/mbio.02436-24
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Copyright (c) 2026 Julia Burtowicz, Magdalena Kossmann, Laura Szalewska, Amin Abdulgater, Paulina Osuch-Tomaszewska, Wiktoria Urowska, Jędrzej Łysiak, Izabela Kazubek-Fuksiewicz

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