{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:37:11Z","timestamp":1782970631944,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Background: Obesity is a global epidemic that remains inadequately addressed by healthcare systems. The gut microbiota offers a promising metabolic target, yet systematic reviews of clinical trials on microbiome modulators for obesity are scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the Trialtrove database (September 16, 2025), we performed a registry-based systematic review with the strategy: \u201c(Disease: Obesity) AND (Mechanism: Microbiome modulator).\u201d We included interventional trials targeting overweight\/obese populations with defined microbiome-modulating mechanisms; observational and withdrawn\/suspended trials were excluded. Extracted data covered phase, status, intervention type, sponsor, location, and participant characteristics. Descriptive analyses used R software (v4.4.3).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 217 included trials, 131 (60%) were completed and 37 (17%) ongoing., Academic institutions led sponsorship (157 trials), followed by commercial (45) and government (14). Trials rose sharply after 2011, peaking at 34 in 2023 (over 80% of Phase IV trials that year). Probiotics dominated (141 trials), followed by synbiotics (21) and FMT (22). China (52) and the US (24) led research. Probiotics prevailed in Phases III\/IV, whereas FMT concentrated in Phases II\/IV with a higher termination rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study reveals a rapidly growing yet uneven landscape. Probiotics remain the primary focus, academic institutions the main sponsors, and China\/US the core hubs. The field has entered a post-marketing evaluation phase dominated by Phase IV studies. Limitations include reliance on a single database and lack of efficacy data, but the study highlights rapid expansion and heterogeneity in this field. Future research should integrate multiple data sources and quality assessments for more comprehensive evidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1865785","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:24:37Z","timestamp":1782966277000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota as modulators of obesity and overweight: a registry-based systematic review of clinical trial evidence"],"prefix":"10.3389","volume":"13","author":[{"given":"Bolun","family":"Jiao","sequence":"first","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s00424-025-03066-8","article-title":"The obesity pandemic and its impact on non-communicable disease burden.","volume":"477","author":"Hildebrand","year":"2025","journal-title":"Pflugers Archiv"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/S0140-6736(23)02750-2","article-title":"Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults.","volume":"403","year":"2024","journal-title":"Lancet."},{"key":"B3","unstructured":"World Obesity Atlas 2025.\n          \n          2025"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e4523","DOI":"10.1128\/cmr.00045-23","article-title":"Role of the intestinal microbiota in contributing to weight disorders and associated comorbidities.","volume":"37","author":"Van Hul","year":"2024","journal-title":"Clin Microbiol Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"100010","DOI":"10.1016\/j.aspetd.2025.100010","article-title":"Pharmacological modulation of the gut microbiota and endotoxemia: a next-generation approach to treating metabolic syndrome.","volume":"1","author":"Dimeji","year":"2025","journal-title":"Aspet Discov."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e270","DOI":"10.1002\/imt2.270","article-title":"Gut-x axis.","volume":"4","author":"Lin","year":"2025","journal-title":"Imeta"},{"key":"B7","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1073\/pnas.0605374104","article-title":"Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.","volume":"104","author":"B\u00e4ckhed","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1241214","DOI":"10.1126\/science.1241214","article-title":"Gut microbiota from twins discordant for obesity modulate metabolism in mice.","volume":"341","author":"Ridaura","year":"2013","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","first-page":"C1723","DOI":"10.1152\/ajpcell.00704.2025","article-title":"From gut to blood: barrier dysfunction as a driver of systemic low-grade inflammation in cardiometabolic disease.","volume":"329","author":"Yang-Jensen","year":"2025","journal-title":"Am J Physiol Cell Physiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e23201","DOI":"10.1096\/fj.202300982R","article-title":"Microbial dietary protein metabolism regulates glp-1 mediated intestinal transit.","volume":"37","author":"Toft","year":"2023","journal-title":"FASEB J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.apsb.2025.12.006","article-title":"Gut microbiota drives the metabolic dysregulation in obesity-prone individuals by impairing GDCA-mediated activation of brown adipose thermogenesis and ileal GLP-1 secretion.","volume":"16","author":"Ma","year":"2026","journal-title":"Acta Pharm Sin B."},{"key":"B12","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1136\/postgradmedj-2015-133285","article-title":"Gut microbiota, obesity and diabetes.","volume":"92","author":"Patterson","year":"2016","journal-title":"Postgrad Med J"},{"key":"B13","doi-asserted-by":"publisher","first-page":"152822","DOI":"10.1016\/j.bbrc.2025.152822","article-title":"GLP-1 receptor agonists and inflammatory pathway modulation: dual targeting of metabolic and immune dysfunction in insulin resistance.","volume":"789","author":"Ngabea","year":"2025","journal-title":"Biochem Biophys Res Commun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"720","DOI":"10.3390\/antibiotics13080720","article-title":"Exploring therapeutic advances: a comprehensive review of intestinal microbiota modulators.","volume":"13","author":"Pires","year":"2024","journal-title":"Antibiotics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12986-025-00969-2","article-title":"Multi-omics analyses the effect of Bifidobacterium longum subsp. Longum BL21 supplementation on overweight and obese subjects: a randomized, double-blind, placebo-controlled study.","volume":"22","author":"Wang","year":"2025","journal-title":"Nutr Metab"},{"key":"B16","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.clnu.2024.11.042","article-title":"Effects of synbiotics surpass probiotics alone in improving type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial.","volume":"44","author":"Zhang","year":"2025","journal-title":"Clinical Nutr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"687","DOI":"10.3109\/09637486.2013.775224","article-title":"The effects of synbiotic supplementation on some cardio-metabolic risk factors in overweight and obese children: a randomized triple-masked controlled trial.","volume":"64","author":"Safavi","year":"2013","journal-title":"Int J Food Sci Nutr"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1695329","DOI":"10.3389\/fmedt.2025.1695329","article-title":"Microbiome-based therapeutics for metabolic disorders: harnessing microbial intrusions for treatment.","volume":"7","author":"Ahmed","year":"2025","journal-title":"Front Med Technol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e432322","DOI":"10.1128\/spectrum.04323-22","article-title":"Membrane protein amuc_1100 derived from Akkermansia muciniphila facilitates lipolysis and browning via activating the AC3\/PKA\/HSL pathway.","volume":"11","author":"Zheng","year":"2023","journal-title":"Microbiol Spectr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"100082","DOI":"10.70389\/PJS.100082","article-title":"Transparency in the reporting of artificial intelligence \u2013 the titan guideline.","volume":"10","author":"Agha","year":"2025","journal-title":"Prem J Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"15718","DOI":"10.1073\/pnas.0407076101","article-title":"The gut microbiota as an environmental factor that regulates fat storage.","volume":"101","author":"B\u00e4ckhed","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1038\/s42255-022-00687-6","article-title":"High-protein diet prevents fat mass increase after dieting by counteracting lactobacillus-enhanced lipid absorption.","volume":"4","author":"Zhong","year":"2022","journal-title":"Nat Metab"},{"key":"B23","doi-asserted-by":"publisher","first-page":"100359","DOI":"10.1016\/j.shj.2024.100359","article-title":"Implementation: the final step in translating innovation.","volume":"8","author":"DeMaria","year":"2024","journal-title":"Structural Heart"},{"key":"B24","doi-asserted-by":"publisher","first-page":"S166","DOI":"10.14309\/01.ajg.0001130556.74421.96","article-title":"S774 the effect of gut microbiome-modulating therapies on anthropometric parameters and blood pressure in metabolic syndrome: a systematic review, meta-analysis and meta-regression.","volume":"120","author":"Kaul","year":"2025","journal-title":"Am J Gastroenterol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.3390\/life14111485","article-title":"Impact of gut microbiome interventions on glucose and lipid metabolism in metabolic diseases: a systematic review and meta-analysis.","volume":"14","author":"Mederle","year":"2024","journal-title":"Life"},{"key":"B26","first-page":"193","article-title":"Consensus on intestinal microecological preparations and fecal microbiota transplantation in the treatment of obesity.","volume":"39","author":"Yuan","year":"2025","journal-title":"Chin J Pract Diag Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e317202","DOI":"10.1371\/journal.pone.0317202","article-title":"The efficacy of Lacticaseibacillus paracasei MSMC39-1 and Bifidobacterium animalis TA-1 probiotics in modulating gut microbiota and reducing the risk of the characteristics of metabolic syndrome: a randomized, double-blinded, placebo-controlled study.","volume":"20","author":"Luangphiphat","year":"2025","journal-title":"Plos One"},{"key":"B28","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12986-023-00739-y","article-title":"Effect of different doses of Lacticaseibacillus paracasei K56 on body fat and metabolic parameters in adult individuals with obesity: a pilot study.","volume":"20","author":"Kadeer","year":"2023","journal-title":"Nutr Metab"},{"key":"B29","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.clnesp.2022.09.005","article-title":"The effect of synbiotic and vitamin d co-supplementation on body composition and quality of life in middle-aged overweight and obese women: a randomized controlled trial.","volume":"52","author":"Jamshidi","year":"2022","journal-title":"Clin Nutr Espen"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1002\/fsn3.3899","article-title":"Inulin-type fructans with different degrees of polymerization improve insulin resistance, metabolic parameters, and hormonal status in overweight and obese women with polycystic ovary syndrome: a randomized double-blind, placebo-controlled clinical trial.","volume":"12","author":"Ziaei","year":"2023","journal-title":"Food Sci Nutr"},{"key":"B31","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41421-024-00725-5","article-title":"Sodium oligomannate disrupts the adherence of rib(high) bacteria to gut epithelia to block SAA-triggered TH1 inflammation in 5XFAD transgenic mice.","volume":"10","author":"Wang","year":"2024","journal-title":"Cell Discov"},{"key":"B32","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/s41422-019-0216-x","article-title":"Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer\u2019s disease progression.","volume":"29","author":"Wang","year":"2019","journal-title":"Cell Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1007\/s11695-024-07437-5","article-title":"Effects of probiotic supplementation added to a weight loss program on anthropometric measures, body composition, eating behavior, and related hormone levels in patients with food addiction and weight regain after bariatric surgery: a randomized clinical trial.","volume":"34","author":"Ghafouri-Taleghani","year":"2024","journal-title":"Obes Surg"},{"key":"B34","doi-asserted-by":"publisher","first-page":"CD15875","DOI":"10.1002\/14651858.CD015875","article-title":"Gut microbiome-based interventions for the management of obesity in children and adolescents aged up to 19 years.","volume":"7","author":"Fahim","year":"2025","journal-title":"Cochrane Database Syst Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.cmet.2024.12.010","article-title":"Akkermansia muciniphila supplementation in patients with overweight\/obese type 2 diabetes: efficacy depends on its baseline levels in the gut.","volume":"37","author":"Zhang","year":"2025","journal-title":"Cell Metab"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2559032","DOI":"10.1080\/19490976.2025.2559032","article-title":"The challenges and opportunities in the expanding horizons of microbiota transplant therapies.","volume":"17","author":"Khoruts","year":"2025","journal-title":"Gut Microbes"},{"key":"B37","doi-asserted-by":"publisher","first-page":"113","DOI":"10.25259\/IJMR_818_2024","article-title":"Faecal microbiota transplantation for recurrent Clostridiodes difficile infection & its global regulatory landscape.","volume":"161","author":"Deepti","year":"2025","journal-title":"Indian J Med Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1177\/2050640620910313","article-title":"Towards an EU-wide suitable regulatory framework for faecally derived, industrially manufactured medicinal products.","volume":"8","author":"Mikkelsen","year":"2020","journal-title":"Unit Eur Gastroenterol J"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1080\/19490976.2018.1502537","article-title":"Regulating stool for microbiota transplantation.","volume":"10","author":"Ossorio","year":"2019","journal-title":"Gut Microbes"},{"key":"B40","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1007\/s00284-026-04865-7","article-title":"Postbiotics: definitions, manufacturing, analytical characterization, and clinical evidence for human and animal health.","volume":"83","author":"Mokashe","year":"2026","journal-title":"Curr Microbiol"},{"key":"B41","unstructured":"Amends EU Novel Food Rules to Extend Use of Pasteurised Akkermansia muciniphila in Food Supplements and Foods for Special Medical Purposes for Adolescents. Regulation (EU) 2026\/391.\n          \n          2026"},{"key":"B42","unstructured":"Postbiotic Supplements Market - Size, Share &amp; Growth Analysis 2025-2034. Report No. GMI7076.\n          \n          2025"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1865785\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:24:43Z","timestamp":1782966283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1865785\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":42,"alternative-id":["10.3389\/fnut.2026.1865785"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1865785","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"article-number":"1865785"}}