{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:41:40Z","timestamp":1787240500460,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Type 1 diabetes mellitus (T1DM) is a common autoimmune disease in children, characterized by the destruction of pancreatic \u03b2-cells. Despite treatment advancements, many patients struggle with glycemic control. Recent research suggests the gut microbiome plays a role in T1DM, with dysbiosis contributing to its onset. Probiotics may help improve glycemic control and reduce inflammation, but their effects in children with T1DM are unclear. This study systematically reviews the impact of probiotics and related supplements on glycemic control in pediatric T1DM patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study adhered to PRISMA guidelines and was registered in PROSPERO (CRD42025633971). We searched databases including PubMed and EMBASE until January 5, 2025. The focus was on randomized controlled trials (RCTs) involving participants under 18 with T1DM, examining the effects of probiotics, prebiotics, and synbiotics on glycemic control indexes like fasting blood glucose (FBG), hemoglobin A1c (HbA1c), C-peptide, and insulin needs. Two researcher extracted data, quality was assessed via the Cochrane Handbook, and STATA 16 was used for statistical analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight RCTs with 494 participants (246 intervention, 248 control) showed that probiotics and synbiotics significantly reduced HbA1c levels [Weighted Mean Difference (WMD)\u2009=\u2009\u22120.25%, 95% Confidence Interval (CI)\u2009=\u2009\u22120.45, \u22120.04;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019] with low heterogeneity [I-squared (I\n                      <jats:sup>2<\/jats:sup>\n                      )\u2009=\u200922%]. However, no significant changes were found in FBG, C-peptide levels, or insulin requirements. Sensitivity analyses yielded similar directions of effect for HbA1c. Subgroups suggested larger HbA1c reductions with longer intervention duration, shorter disease duration, and multi-strain formulations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Probiotic supplementation may achieve a small improvement in HbA1c in pediatric T1DM. Adequate dosing, longer intervention duration, and multi-strain formulations may be more likely to improve HbA1c, but the clinical importance is uncertain. However, our result shows no significant effects on fasting blood glucose, C-peptide, or insulin requirements; no routine clinical recommendations are proposed. The role of probiotics and related supplements in long-term glycemic control still requires confirmation through trials with extended follow-up. Large-scale, rigorously designed studies are needed to determine optimal intervention parameters, clarify underlying mechanisms, and evaluate the clinical applicability of probiotics in T1DM management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>identifier [CRD42025633971].<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2025.1633694","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T08:49:10Z","timestamp":1761209350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of probiotics and related supplements on glycemic control in pediatric patients with type 1 diabetes mellitus: a systematic review and meta-analysis of clinical trials"],"prefix":"10.3389","volume":"13","author":[{"given":"Hanyu","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/sctm.18-0150","article-title":"Bone morphogenetic protein-6 attenuates type 1 diabetes mellitus-associated bone loss","volume":"8","author":"Wang","year":"2019","journal-title":"Stem Cell Transl MED"},{"key":"B2","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.ecl.2012.08.001","article-title":"The epidemiology of type 1 diabetes in children","volume":"41","author":"Stanescu","year":"2012","journal-title":"Endocrin Metab Clin"},{"key":"B3","doi-asserted-by":"publisher","first-page":"112346","DOI":"10.1016\/j.diabres.2025.112346","article-title":"IDF diabetes atlas: a worldwide review of studies utilizing retinal photography to screen for diabetic retinopathy from 2017\u20132024 inclusive","volume":"226","author":"Owens","year":"2025","journal-title":"Diabetes Res Clin PR"},{"key":"B4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.12998\/wjcc.v12.i1.9","article-title":"Honeymoon phase in type 1 diabetes mellitus: a window of opportunity for diabetes reversal?","volume":"12","author":"Mittal","year":"2024","journal-title":"World J Clin Cases"},{"key":"B5","doi-asserted-by":"publisher","first-page":"737964","DOI":"10.3389\/fimmu.2021.737964","article-title":"Environmental determinants of type 1 diabetes: from association to proving causality","volume":"12","author":"Quinn","year":"2021","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/nyas.13508","article-title":"Host-microbiota interplay in mediating immune disorders","volume":"1417","author":"Felix","year":"2018","journal-title":"Ann NY Acad Sci"},{"key":"B7","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1097\/BOR.0000000000000628","article-title":"Microbiome and autoimmune diseases: cause and effect relationship","volume":"31","author":"Nogueira","year":"2019","journal-title":"Curr Opin Rheumatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.2337\/db08-0331","article-title":"The \"perfect storm\" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity","volume":"57","author":"Vaarala","year":"2008","journal-title":"Diabetes"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1016\/j.celrep.2017.02.027","article-title":"Circulating NOD1 activators and hematopoietic NOD1 contribute to metabolic inflammation and insulin resistance","volume":"18","author":"Chan","year":"2017","journal-title":"Cell Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1007\/s00125-008-0941-z","article-title":"Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies","volume":"51","author":"Cardwell","year":"2008","journal-title":"Diabetologia"},{"key":"B12","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/s41390-020-0761-5","article-title":"Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort","volume":"88","author":"Korpela","year":"2020","journal-title":"Pediatr Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1080\/1744666X.2023.2150612","article-title":"Gut microbiome in type 1 diabetes: the immunological perspective","volume":"19","author":"Rampanelli","year":"2023","journal-title":"Expert Rev Clin Immu"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.3390\/ijms21041542","article-title":"Acetate and butyrate improve \u03b2-cell metabolism and mitochondrial respiration under oxidative stress","volume":"21","author":"Hu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"638470","DOI":"10.1155\/2015\/638470","article-title":"Th17 cells in type 1 diabetes: role in the pathogenesis and regulation by gut microbiome","volume":"2015","author":"Li","year":"2015","journal-title":"Mediat Inflamm"},{"key":"B16","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1007\/s11892-011-0191-1","article-title":"Gut microbiota and the pathogenesis of insulin resistance","volume":"11","author":"Delzenne","year":"2011","journal-title":"Curr Diabetes Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"65","DOI":"10.12998\/wjcc.v11.i1.65","article-title":"Role of natural products and intestinal flora on type 2 diabetes mellitus treatment","volume":"11","author":"Aydin","year":"2023","journal-title":"World J Clin Cases"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.clnu.2024.03.006","article-title":"Probiotics and synbiotics for glycemic control in diabetes: a systematic review and meta-analysis of randomized controlled trials","volume":"43","author":"Baroni","year":"2024","journal-title":"Clin Nutr"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e3655","DOI":"10.1002\/dmrr.3655","article-title":"Probiotics, prebiotics, and synbiotics in type 1 diabetes mellitus: a systematic review and meta-analysis of clinical trials","volume":"40","author":"Moravejolahkami","year":"2024","journal-title":"Diabetes-Metab Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.3390\/nu16162629","article-title":"Impact of probiotics on the glycemic control of pediatric and adolescent individuals with type 1 diabetes: a systematic review and meta-analysis","volume":"16","author":"Stefanaki","year":"2024","journal-title":"Nutrients"},{"key":"B21","doi-asserted-by":"publisher","first-page":"W65","DOI":"10.7326\/0003-4819-151-4-200908180-00136","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration","volume":"151","author":"Liberati","year":"2009","journal-title":"Ann Intern Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/jrsm.1429","article-title":"Optimally estimating the sample standard deviation from the five-number summary","volume":"11","author":"Shi","year":"2020","journal-title":"Res Synth Methods"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1177\/0962280216669183","article-title":"Optimally estimating the sample mean from the sample size, median, mid-range, and\/or mid-quartile range","volume":"27","author":"Luo","year":"2018","journal-title":"Stat Methods Med Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1037\/1082-989X.11.2.193","article-title":"Assessing heterogeneity in meta-analysis: Q statistic or I2 index?","volume":"11","author":"Huedo-Medina","year":"2006","journal-title":"Psychol Methods"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4427","DOI":"10.1210\/jc.2019-00481","article-title":"Effect of prebiotic on microbiota, intestinal permeability, and glycemic control in children with type 1 diabetes","volume":"104","author":"Ho","year":"2019","journal-title":"J Clin Endocr Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1080\/21645515.2019.1633877","article-title":"Effects of probiotic administration on immune responses of children and adolescents with type 1 diabetes to a quadrivalent inactivated influenza vaccine","volume":"16","author":"Bianchini","year":"2020","journal-title":"Hum Vacc Immunother"},{"key":"B27","doi-asserted-by":"publisher","first-page":"607","DOI":"10.2147\/DMSO.S238867","article-title":"The effects of synbiotic supplementation on glycemic Status, lipid profile, and biomarkers of oxidative stress in type 1 diabetic patients. A placebo-controlled, double-blind, randomized clinical trial","volume":"13","author":"Zare","year":"2020","journal-title":"Diabet Metab Synd Obes"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1111\/pedi.13244","article-title":"A high potency multi-strain probiotic improves glycemic control in children with new-onset type 1 diabetes mellitus: a randomized, double-blind, and placebo-controlled pilot study","volume":"22","author":"Kumar","year":"2021","journal-title":"Pediatr Diabetes"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e001523","DOI":"10.1136\/bmjdrc-2020-001523","article-title":"Lack of effect of lactobacillus rhamnosus GG and bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial","volume":"9","author":"Groele","year":"2021","journal-title":"BMJ Open Diab Res Care"},{"key":"B30","doi-asserted-by":"publisher","first-page":"754401","DOI":"10.3389\/fendo.2022.754401","article-title":"Adjuvant probiotics of lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 attenuate glycemic levels and inflammatory cytokines in patients with type 1 diabetes mellitus","volume":"13","author":"Wang","year":"2022","journal-title":"Front Endocrinol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"128","DOI":"10.5114\/pedm.2023.132025","article-title":"The effect of oral probiotics on glycated haemoglobin levels in children with type 1 diabetes mellitus\u2014a randomized clinical trial","volume":"29","author":"Shabani-Mirzaee","year":"2023","journal-title":"Pediatr Endocrinol Diabetes Metab"},{"key":"B32","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s12098-024-05074-5","article-title":"Supplementation of high-strength oral probiotics improves immune regulation and preserves beta cells among children with new-onset type 1 diabetes mellitus: a randomised, double-blind placebo control trial","volume":"92","author":"Lokesh","year":"2025","journal-title":"Indian J Pediatr"},{"key":"B33","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/S2213-8587(22)00113-9","article-title":"Cross-sectional associations between the gut microbe Ruminococcus gnavus and features of the metabolic syndrome","volume":"10","author":"Grahnemo","year":"2022","journal-title":"Lancet Diabetes Endo"},{"key":"B34","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2337\/dc08-9025","article-title":"Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American diabetes association and the European association for the study of diabetes","volume":"32","author":"Nathan","year":"2009","journal-title":"Diabetes Care"},{"key":"B35","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1093\/advances\/nmaa133","article-title":"Probiotics contribute to glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis","volume":"12","author":"Rittiphairoj","year":"2021","journal-title":"Adv Nutr"},{"key":"B36","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s00404-023-07346-5","article-title":"Effect of probiotics on pregnancy outcomes in gestational diabetes: systematic review and meta-analysis","volume":"310","author":"Wu","year":"2024","journal-title":"Arch Gynecol Obstet"},{"key":"B37","doi-asserted-by":"publisher","first-page":"110162","DOI":"10.1016\/j.diabres.2022.110162","article-title":"The effect of probiotic and synbiotic use on glycemic control in women with gestational diabetes: a systematic review and meta-analysis","volume":"194","author":"\u00c7etinkaya","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e46741","DOI":"10.7759\/cureus.46741","article-title":"Probiotics and their role in the management of type 2 diabetes mellitus (short-term versus long-term effect): a systematic review and meta-analysis","volume":"15","author":"Ayesha","year":"2023","journal-title":"Cureus J Med Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1392306","DOI":"10.3389\/fendo.2024.1392306","article-title":"Effect of probiotics at different intervention time on glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis","volume":"15","author":"Wang","year":"2024","journal-title":"Front Endocrinol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"106397","DOI":"10.1016\/j.phrs.2022.106397","article-title":"Probiotic therapy, a novel and efficient adjuvant approach to improve glycemic status: an umbrella meta-analysis","volume":"183","author":"Zarezadeh","year":"2022","journal-title":"Pharmacol Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"986","DOI":"10.3892\/or.2020.7463","article-title":"Treatment with a probiotic combination reduces abdominal adhesion in rats by decreasing intestinal inflammation and restoring microbial composition","volume":"43","author":"Deng","year":"2020","journal-title":"Oncol Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1159\/000492853","article-title":"Short-chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of NLRP3 inflammasome and autophagy","volume":"49","author":"Feng","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"B43","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12865-022-00495-3","article-title":"Three important short-chain fatty acids (SCFAs) attenuate the inflammatory response induced by 5-FU and maintain the integrity of intestinal mucosal tight junction","volume":"23","author":"Yue","year":"2022","journal-title":"BMC Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1007\/s10620-023-07835-2","article-title":"Effect of clostridium butyricum on high-fat diet-induced intestinal inflammation and production of short-chain fatty acids","volume":"68","author":"Choi","year":"2023","journal-title":"Digest Dis Sci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.3389\/fimmu.2017.01345","article-title":"Clostridium butyricum CGMCC0313.1 protects against autoimmune diabetes by modulating intestinal immune homeostasis and inducing pancreatic regulatory T cells","volume":"8","author":"Jia","year":"2017","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"2423024","DOI":"10.1080\/19490976.2024.2423024","article-title":"Intestinal flora: a potential pathogenesis mechanism and treatment strategy for type 1 diabetes mellitus","volume":"16","author":"Huang","year":"2024","journal-title":"Gut Microbes"},{"key":"B47","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/nrendo.2017.137","article-title":"Microbiota: FMT transiently improves insulin sensitivity","volume":"13","author":"Greenhill","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.3390\/foods13172719","article-title":"The role and mechanism of probiotics supplementation in blood glucose regulation: a review","volume":"13","author":"Shen","year":"2024","journal-title":"Foods"},{"key":"B49","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.jcjd.2019.10.006","article-title":"Interplay between gut microbiota and gastrointestinal peptides: potential outcomes on the regulation of glucose control","volume":"44","author":"Lupien-Meilleur","year":"2020","journal-title":"Can J Diabetes"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1633694\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T08:49:11Z","timestamp":1761209351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1633694\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":49,"alternative-id":["10.3389\/fped.2025.1633694"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1633694","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"article-number":"1633694"}}