THE GUT-BRAIN-MICROBIOME AXIS IN CHILDHOOD OBESITY: MECHANISMS AND CLINICAL IMPLICATIONS
DOI:
https://doi.org/10.63953/jisn.v3i4.69Keywords:
childhood obesity, gut microbiota, gut–brain axis, probioticAbstract
Background: Childhood obesity has become a global health crisis affecting 188 million children aged 5–19 years worldwide, with serious metabolic complications. The gut–brain–microbiome axis has emerged as a key mechanistic link and therapeutic target for obesity in children.
Methods: A narrative literature review was conducted using PubMed, Scopus, and Google Scholar and included studies published up to December 2025. Search terms, used in various combinations, included “childhood obesity,” “gut microbiota,” “gut–brain axis,” “targeted interventions,” “probiotic,” and “prebiotic”.
Results: Childhood obesity is associated with early-life gut dysbiosis characterized by reduced diversity, higher Firmicutes/Bacteroidetes ratios, and shifts in key taxa, driven by prenatal, postnatal, and lifestyle factors. This dysbiotic microbiota enhances energy harvest, promotes low-grade inflammation and barrier dysfunction, and disrupts gut–brain axis signaling via altered short-chain fatty acids, neurotransmitter, and gut hormone profiles, thereby impairing appetite regulation and favoring positive energy balance. Emerging evidence indicates that targeting the gut microbiota–brain axis with probiotics, prebiotics, synbiotics, and fecal microbiota transplantation may improve metabolic outcomes and body composition in children with obesity.
Conclusion: Gut microbiota dysbiosis contributes to childhood obesity via altered metabolism, inflammation, and gut–brain axis–mediated appetite regulation.
References
UNICEF. Feeding Profit. How food environments are failing children. Child Nutrition Report 2025. September 2025 2025. New York: UNICEF.
Muyulema SL, Carpio-Arias TV, Verdezoto N, Guanga Lara VE, Manzano AS, Pulgar H, et al. Worldwide trends in childhood overweight and obesity over the last 20 years. Clin Nutr ESPEN. 2025;65:453-460. https://doi.org/10.1016/j.clnesp.2024.12.013.
Lozano GB, Gil-Campos M and Trabazo RL. Health complications of obesity during childhood and beyond. Childhood Obesity. Elsevier, 2025, pp.223-244.
Wentzel A, Mabhida SE, Ndlovu M, Mokoena H, Esterhuizen B, Sekgala MD, et al. Prevalence of metabolic syndrome in children and adolescents with obesity: a systematic review and meta‐analysis. Obesity. 2025;33(1):12-32.
Asadi A, Shadab Mehr N, Mohamadi MH, Shokri F, Heidary M, Sadeghifard N, et al. Obesity and gut–microbiota–brain axis: A narrative review. Journal of Clinical Laboratory Analysis. 2022;36(5):e24420. https://doi.org/10.1002/jcla.24420.
Wang M, Zhang Z, Liu Y, Jian E, Ye P, Jiang H, et al. Research trends between childhood obesity and gut microbiota: a bibliometric analysis (2002–2023). Frontiers in Microbiology. 2024;Volume 15 - 2024. https://doi.org/10.3389/fmicb.2024.1461306.
Chen XP, You L and Jia Y. The role of probiotics in adolescents' obesity. Front Cell Infect Microbiol. 2025;15:1546627. https://doi.org/10.3389/fcimb.2025.1546627.
Sitorus NL, Dilantika C and Basrowi RW. Perspective of Indonesian Pediatricians On The Role of Prebiotic Supplemented Formula Towards Immunity, Growth and Development In Preterm Infants: A Preliminary Data. Amerta Nutr. 2021:34-42.
Kadim M and Masita BM. The importance of gut health in early life for long term health. World Nutrition Journal. 2022;5(S2):1-8.
Hrncir T. Gut Microbiota Dysbiosis: Triggers, Consequences, Diagnostic and Therapeutic Options. Microorganisms. 2022;10(3). https://doi.org/10.3390/microorganisms10030578.
Aulia B, Ermamilia A, Sundjaya T and Pratiwi D. Maternal Gut Microbiome and Its Impact on Fetal Outcomes: A Focus on Maternal Nutrition. Journal of Indonesian Specialized Nutrition. 2025;3(2):125-146.
Vandenplas Y, Carnielli VP, Ksiazyk J, Luna MS, Migacheva N, Mosselmans JM, et al. Factors affecting early-life intestinal microbiota development. Nutrition. 2020;78:110812. https://doi.org/10.1016/j.nut.2020.110812.
Nunez H, Nieto PA, Mars RA, Ghavami M, Sew Hoy C and Sukhum K. Early life gut microbiome and its impact on childhood health and chronic conditions. Gut Microbes. 2025;17(1):2463567. https://doi.org/10.1080/19490976.2025.2463567.
Suárez-Martínez C, Santaella-Pascual M, Yagüe-Guirao G and Martínez-Graciá C. Infant gut microbiota colonization: influence of prenatal and postnatal factors, focusing on diet. Front Microbiol. 2023;14:1236254. https://doi.org/10.3389/fmicb.2023.1236254.
Riva A, Borgo F, Lassandro C, Verduci E, Morace G, Borghi E, et al. Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol. 2017;19(1):95-105. https://doi.org/10.1111/1462-2920.13463.
Indiani CMdSP, Rizzardi KF, Castelo PM, Ferraz LFC, Darrieux M and Parisotto TM. Childhood Obesity and Firmicutes/Bacteroidetes Ratio in the Gut Microbiota: A Systematic Review. Childhood Obesity. 2018;14(8):501-509. https://doi.org/10.1089/chi.2018.0040.
Bervoets L, Van Hoorenbeeck K, Kortleven I, Van Noten C, Hens N, Vael C, et al. Differences in gut microbiota composition between obese and lean children: a cross-sectional study. Gut Pathog. 2013;5(1):10. https://doi.org/10.1186/1757-4749-5-10.
Cho KY. Association of gut microbiota with obesity in children and adolescents. Clinical and experimental pediatrics. 2022;66(4):148.
Li R, Kurilshikov A, Yang S, van Oortmerssen JAE, van Hilten A, Ahmadizar F, et al. Association between gut microbiome profiles and host metabolic health across the life course: a population-based study. The Lancet Regional Health – Europe. 2025;50. https://doi.org/10.1016/j.lanepe.2024.101195.
Cuevas-Sierra A, Ramos-Lopez O, Riezu-Boj JI, Milagro FI and Martinez JA. Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications. Adv Nutr. 2019;10(suppl_1):S17-s30. https://doi.org/10.1093/advances/nmy078.
Nóbrega R, Costa CFFA, Cerqueira Ó, Inês A, Carrola JS and Gonçalves C. Association between gut microbiota and pediatric obesity: A systematic review. Nutrition. 2025;140:112875. https://doi.org/10.1016/j.nut.2025.112875.
Morgado MC, Sousa M, Coelho AB, Costa JA and Seabra A. Exploring gut microbiota and the influence of physical activity interventions on overweight and obese children and adolescents: a systematic review. In: Healthcare 2023, p.2459. MDPI.
Longo S, Rizza S and Federici M. Microbiota-gut-brain axis: relationships among the vagus nerve, gut microbiota, obesity, and diabetes. Acta Diabetol. 2023;60(8):1007-1017. https://doi.org/10.1007/s00592-023-02088-x.
Yu KB and Hsiao EY. Roles for the gut microbiota in regulating neuronal feeding circuits. J Clin Invest. 2021;131(10). https://doi.org/10.1172/jci143772.
Barrett E, Ross RP, O'Toole PW, Fitzgerald GF and Stanton C. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 2012;113(2):411-417. https://doi.org/10.1111/j.1365-2672.2012.05344.x.
Pizzi A, Parolin C, Gottardi D, Ricci A, Parpinello GP, Lanciotti R, et al. A Novel GABA-Producing Levilactobacillus brevis Strain Isolated from Organic Tomato as a Promising Probiotic. Biomolecules. 2025;15(7). https://doi.org/10.3390/biom15070979.
Fock E and Parnova R. Mechanisms of Blood-Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids. Cells. 2023;12(4). https://doi.org/10.3390/cells12040657.
Huwart SJP, Fayt C, Gangarossa G, Luquet S, Cani PD and Everard A. TLR4-dependent neuroinflammation mediates LPS-driven food-reward alterations during high-fat exposure. J Neuroinflammation. 2024;21(1):305. https://doi.org/10.1186/s12974-024-03297-z.
Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC, et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond). 2015;39(3):424-429. https://doi.org/10.1038/ijo.2014.153.
Wachsmuth HR, Weninger SN and Duca FA. Role of the gut–brain axis in energy and glucose metabolism. Experimental & Molecular Medicine. 2022;54(4):377-392. https://doi.org/10.1038/s12276-021-00677-w.
Agustí A, García-Pardo MP, López-Almela I, Campillo I, Maes M, Romaní-Pérez M, et al. Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function. Frontiers in Neuroscience. 2018;Volume 12 - 2018. https://doi.org/10.3389/fnins.2018.00155.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER and Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-1031. https://doi.org/10.1038/nature05414.
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480-484. https://doi.org/10.1038/nature07540.
Huwart SJP, Morales-Puerto N and Everard A. Gut microbiota-related neuroinflammation at the crossroad of food reward alterations: implications for eating disorders. Gut. 2025;74(10):1728-1740. https://doi.org/10.1136/gutjnl-2024-333397.
Noor J, Chaudhry A, Batool S, Noor R and Fatima G. Exploring the Impact of the Gut Microbiome on Obesity and Weight Loss: A Review Article. Cureus. 2023;15(6):e40948. https://doi.org/10.7759/cureus.40948.
Schwiertz A, Taras D, Schäfer K, Beijer S, Bos NA, Donus C, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190-195. https://doi.org/10.1038/oby.2009.167.
He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, et al. Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism. Int J Mol Sci. 2020;21(17). https://doi.org/10.3390/ijms21176356.
Li S, Ma X, Mei H, Chang X, He P, Sun L, et al. Association between gut microbiota and short-chain fatty acids in children with obesity. Scientific Reports. 2025;15(1):483. https://doi.org/10.1038/s41598-024-84207-4.
Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature. 2016;534(7606):213-217. https://doi.org/10.1038/nature18309.
Tang R and Li L. Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus. Can J Infect Dis Med Microbiol. 2021;2021:6632266. https://doi.org/10.1155/2021/6632266.
Jyoti and Dey P. Mechanisms and implications of the gut microbial modulation of intestinal metabolic processes. NPJ Metab Health Dis. 2025;3(1):24. https://doi.org/10.1038/s44324-025-00066-1.
Mohr AE, Crawford Ms, Jasbi P, Fessler S and Sweazea KL. Lipopolysaccharide and the gut microbiota: considering structural variation. FEBS Letters. 2022;596(7):849-875. https://doi.org/10.1002/1873-3468.14328.
Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761-1772. https://doi.org/10.2337/db06-1491.
Varma MC, Kusminski CM, Azharian S, Gilardini L, Kumar S, Invitti C, et al. Metabolic endotoxaemia in childhood obesity. BMC Obes. 2015;3:3. https://doi.org/10.1186/s40608-016-0083-7.
Koller AM, Săsăran MO and Mărginean CO. The Role of Gut Microbiota in Pediatric Obesity and Metabolic Disorders: Insights from a Comprehensive Review. Nutrients 17: 1883. DOI: 10.3390/nu17111883.
Roth CL, Melhorn SJ, De Leon MRB, Rowland MG, Elfers CT, Huang A, et al. Impaired Brain Satiety Responses After Weight Loss in Children With Obesity. The Journal of Clinical Endocrinology & Metabolism. 2022;107(8):2254-2266. https://doi.org/10.1210/clinem/dgac299.
O'Mahony SM, Clarke G, Borre YE, Dinan TG and Cryan JF. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res. 2015;277:32-48. https://doi.org/10.1016/j.bbr.2014.07.027.
Lukić I, Ivković S, Mitić M and Adžić M. Tryptophan metabolites in depression: modulation by gut microbiota. Frontiers in behavioral neuroscience. 2022;16:987697.
Belelli D, Lambert JJ, Wan MLY, Monteiro AR, Nutt DJ and Swinny JD. From bugs to brain: unravelling the GABA signalling networks in the brain-gut-microbiome axis. Brain. 2025;148(5):1479-1506. https://doi.org/10.1093/brain/awae413.
Schneider E, Leigh SJ, Lynch CMK, Hilbert A, Clarke G, Higgs S, et al. Microbiota-gut-brain axis in binge-eating disorder: Towards microbiome-based therapies. Neurosci Appl. 2024;3:104088. https://doi.org/10.1016/j.nsa.2024.104088.
Hamamah S, Aghazarian A, Nazaryan A, Hajnal A and Covasa M. Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling. Biomedicines. 2022;10(2). https://doi.org/10.3390/biomedicines10020436.
Gupta A, Osadchiy V and Mayer EA. Brain-gut-microbiome interactions in obesity and food addiction. Nat Rev Gastroenterol Hepatol. 2020;17(11):655-672. https://doi.org/10.1038/s41575-020-0341-5.
Novelle MG. Decoding the Role of Gut-Microbiome in the Food Addiction Paradigm. Int J Environ Res Public Health. 2021;18(13). https://doi.org/10.3390/ijerph18136825.
Morys F, García-García I and Dagher A. Is obesity related to enhanced neural reactivity to visual food cues? A review and meta-analysis. Soc Cogn Affect Neurosci. 2020;18(1). https://doi.org/10.1093/scan/nsaa113.
Gearhardt AN, Yokum S, Orr PT, Stice E, Corbin WR and Brownell KD. Neural Correlates of Food Addiction. Archives of General Psychiatry. 2011;68(8):808-816. https://doi.org/10.1001/archgenpsychiatry.2011.32.
Forcina G, Di Filippo P, De Biasio D, Cesaro FG, Frattolillo V, Massa A, et al. Targeting the Gut Microbiota in Pediatric Obesity: A Paradigm Shift in Prevention and Treatment? A Comprehensive Review. Nutrients 17: 2942. DOI: 10.3390/nu17182942.
Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology & Hepatology. 2017;14(8):491-502. https://doi.org/10.1038/nrgastro.2017.75.
Yadav M, Sehrawat N, Sharma AK, Kumar S, Singh R, Kumar A, et al. Synbiotics as potent functional food: recent updates on therapeutic potential and mechanistic insight. J Food Sci Technol. 2024;61(1):1-15. https://doi.org/10.1007/s13197-022-05621-y.
Chen A-C, Fang T-J, Ho H-H, Chen J-F, Kuo Y-W, Huang Y-Y, et al. A multi-strain probiotic blend reshaped obesity-related gut dysbiosis and improved lipid metabolism in obese children. Front Nutr. 2022;9:922993.
Balas RB, Meliț LE, Lupu A, Lupu VV and Mărginean CO. Prebiotics, probiotics, and synbiotics—a research hotspot for pediatric obesity. Microorganisms. 2023;11(11):2651.
Yildirim GK, Dinleyici M, Vandenplas Y and Dinleyici EC. Effects of synbiotic supplementation on intestinal microbiota composition in children and adolescents with exogenous obesity:(Probesity-2 trial). Gut pathogens. 2023;15(1):36.
Yildirim GK, Dinleyici M, Vandenplas Y and Dinleyici EC. Effects of multispecies Synbiotic supplementation on anthropometric measurements, glucose and lipid parameters in children with exogenous obesity: a Randomized, double blind, placebo-controlled clinical trial (Probesity-2 trial). Front Nutr. 2022;9:898037.
Solito A, Cionci NB, Calgaro M, Caputo M, Vannini L, Hasballa I, et al. Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial. Clinical Nutrition. 2021;40(7):4585-4594.
Oswari H, Widodo AD, Handayani F, Juffrie M, Sundjaya T, Bindels J, et al. Dosage-Related Prebiotic Effects of Inulin in Formula-Fed Infants. Pediatr Gastroenterol Hepatol Nutr. 2019;22(1):63-71. https://doi.org/10.5223/pghn.2019.22.1.63.
Visuthranukul C, Leelahavanichkul A, Tepaamorndech S, Chamni S, Mekangkul E and Chomtho S. Inulin supplementation exhibits increased muscle mass via gut-muscle axis in children with obesity: double evidence from clinical and in vitro studies. Scientific Reports. 2024;14(1):11181. https://doi.org/10.1038/s41598-024-61781-1.
Panichsillaphakit E, Visuthranukul C, Chongpison Y, Chuaypen N, Kwanbunbumpen T, Uaariyapanichkul J, et al. The effects of inulin supplementation on eating behaviours in children and adolescents with obesity: a randomized double-blinded placebo-controlled study. Nutrition & Metabolism. 2025;22(1):97.
Khongtan S, Sivamaruthi BS, Thangaleela S, Kesika P, Bharathi M, Sirilun S, et al. The Influence of Probiotic Supplementation on the Obesity Indexes, Neuroinflammatory and Oxidative Stress Markers, Gut Microbial Diversity, and Working Memory in Obese Thai Children. Foods 12: 3890. DOI: 10.3390/foods12213890.
Verma A, Nelson MT, DePaolo WR, Hampe C and Roth CL. A randomized double-blind placebo controlled pilot study of probiotics in adolescents with severe obesity. J Diabetes Metab Disord. 2021;20(2):1289-1300. https://doi.org/10.1007/s40200-021-00855-7.
Visuthranukul C, Chamni S, Kwanbunbumpen T, Saengpanit P, Chongpison Y, Tepaamorndech S, et al. Effects of inulin supplementation on body composition and metabolic outcomes in children with obesity. Scientific Reports. 2022;12(1):13014. https://doi.org/10.1038/s41598-022-17220-0.
Liber A and Szajewska H. Effect of oligofructose supplementation on body weight in overweight and obese children: a randomised, double-blind, placebo-controlled trial. British Journal of Nutrition. 2014;112(12):2068-2074. https://doi.org/10.1017/S0007114514003110.
Leong KS, Jayasinghe TN, Wilson BC, Derraik JG, Albert BB, Chiavaroli V, et al. Effects of fecal microbiome transfer in adolescents with obesity: the gut bugs randomized controlled trial. JAMA network open. 2020;3(12):e2030415-e2030415.
Wilson BC, Zuppi M, Derraik JG, Albert BB, Tweedie-Cullen RY, Leong KS, et al. Long-term health outcomes in adolescents with obesity treated with faecal microbiota transplantation: 4-year follow-up. Nature Communications. 2025;16(1):7786.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Bianda Aulia, Tonny Sundjaya
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors retain copyright and grant the journal the right of first publication with the work simultaneously licensed under a Creative Commons Attribution-ShareAlike 4.0 International (CC-BY-SA) that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
LICENSE TO PUBLISH
- All material published by the Journal of Indonesian Specialized Nutrition is protected under International copyright and intellectual property laws. Journal of Indonesian Specialized Nutrition is licensed under a Creative Commons Attribution-ShareAlike 4.0 International (CC-BY-SA) or an equivalent license as the optimal license for the publication, distribution, use, and reuse of scholarly works.
- This license permits anyone to compose, repair, and make derivative creations even for commercial purposes, as long as appropriate credit and proper acknowledgment of the original publication from a journal are made to allow users to trace back to the original manuscript and author.
- You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. If you remix, transform or build upon the material, you must distribute your contributions under the same license as the original.
