{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:27:49Z","timestamp":1786512469051,"version":"build-2736575974"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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>Introduction<\/jats:title>\n                    <jats:p>Gastroesophageal reflux disease (GERD) and proton pump inhibitor (PPI) therapy have both been associated with alterations of the developing gastrointestinal microbiome and potential downstream clinical consequences in children. However, available evidence is fragmented across disease-related, treatment-related, and mechanistic studies, making the overall biological relationship difficult to interpret.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Web of Science, and Scopus databases were queried for the period January 2000 to May 2026 to synthesize evidence across the pathophysiological continuum linking pediatric GERD, microbiota alterations, inflammatory mechanisms, PPI exposure, and microbiota-associated clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The review included studies evaluating children with GERD as well as mechanistic studies involving pediatric upper gastrointestinal conditions requiring PPI therapy when microbiota-related outcomes were relevant to the review objective. Study selection was performed according to PRISMA guidelines, 31 of which were included in the final analysis. The data indicate that pediatric exposure to GERD and PPI is associated with changes in the gastrointestinal microbiota at multiple levels (oral, esophageal, gastric, and intestinal). These changes include reduced microbial diversity, changes in bacterial composition (particularly\n                      <jats:italic>Firmicutes<\/jats:italic>\n                      ,\n                      <jats:italic>Proteobacteria<\/jats:italic>\n                      ,\n                      <jats:italic>Bacteroidetes<\/jats:italic>\n                      , and\n                      <jats:italic>Actinobacteria<\/jats:italic>\n                      ), and increased similarity of microbiota between aerodigestive compartments, suggesting possible microbial transfer associated with reflux or aspiration. PPI exposure has been frequently associated with increased numbers of oropharyngeal bacteria in the gut, decreased beneficial taxa (e.g.,\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      ), and increased numbers of potentially pathogenic genera (e.g.,\n                      <jats:italic>Streptococcus<\/jats:italic>\n                      ,\n                      <jats:italic>Enterobacteriaceae<\/jats:italic>\n                      ). Several studies have reported an association between PPI and small intestinal bacterial overgrowth, but the results are inconsistent. PPI use has also been reported to be associated with an increased risk of infections, allergic diseases, and other systemic effects, coupled with the recognition of limited clinical benefit of PPI therapy in GERD in infants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pediatric GERD and PPI exposure are associated with alterations in the gastrointestinal microbiome and possible systemic clinical effects. Most evidence is heterogeneous and influenced by confounding factors, which limits the establishment of a causal relationship. Prospective longitudinal and mechanistic studies using standardized microbiome methodologies are required to clarify causality and better define the respective contributions of GERD and PPI therapy to microbiota alterations and their clinical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261405291<\/jats:ext-link>\n                      , identifier CRD420261405291.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1909690","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:39:13Z","timestamp":1786509553000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastrointestinal microbiota alterations associated with pediatric gastroesophageal reflux disease and proton pump inhibitor exposure: a systematic review of microbiome changes, dysbiosis markers, and associated clinical outcomes"],"prefix":"10.3389","volume":"13","author":[{"given":"Vasile Valeriu","family":"Lupu","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Jechel","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Adam Raileanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorana Caterina","family":"Anton","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Iulia","family":"Bozomitu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otilia Elena","family":"Frasinariu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana Raluca","family":"Temneanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Forna","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Cuciureanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin Horatiu","family":"Nedelcu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Rodica","family":"Anton","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Cristina","family":"Mitrofan","sequence":"additional","affiliation":[{"name":"Clinic of Pulmonary Disease","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Elena","family":"David","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Carmen","family":"Rusu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Vlase","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Anton","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancuta","family":"Lupu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy","place":["Iasi, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1097\/MPG.0b013e3181b7f563","article-title":"Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American society for pediatric gastroenterology, hepatology, and nutrition (NASPGHAN) and the European society for pediatric gastroenterology, hepatology, and nutrition (ESPGHAN).","volume":"49","author":"Vandenplas","year":"2009","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1097\/MPG.0000000000001889","article-title":"Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American society for pediatric gastroenterology, hepatology, and nutrition and the european society for pediatric gastroenterology, hepatology, and nutrition.","volume":"66","author":"Rosen","year":"2018","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1097\/MPG.0000000000002280","article-title":"Prevalence of gastroesophageal reflux disease symptoms in infants and children: a systematic review.","volume":"68","author":"Singendonk","year":"2019","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1080\/20469047.2018.1489649","article-title":"Gastroesophageal reflux disease (GERD) in children.","volume":"39","author":"Poddar","year":"2019","journal-title":"Paediatr Int Child Health."},{"key":"B5","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1542\/peds.2010-2719","article-title":"Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review.","volume":"127","author":"van der Pol","year":"2011","journal-title":"Pediatrics."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1053\/j.gastro.2009.07.055","article-title":"Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury.","volume":"137","author":"Souza","year":"2009","journal-title":"Gastroenterology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.bpg.2010.08.008","article-title":"The integrity of the esophageal mucosa. Balance between offensive and defensive mechanisms.","volume":"24","author":"Orlando","year":"2010","journal-title":"Best Pract Res Clin Gastroenterol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1053\/j.gastro.2009.04.046","article-title":"Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome.","volume":"137","author":"Yang","year":"2009","journal-title":"Gastroenterology."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1158\/1055-9965.EPI-19-0008","article-title":"Alterations to the esophageal microbiome associated with progression from Barrett\u2019s esophagus to esophageal adenocarcinoma.","volume":"28","author":"Snider","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"11971","DOI":"10.1073\/pnas.1002601107","article-title":"Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.","volume":"107","author":"Dominguez-Bello","year":"2010","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B11","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41586-019-1560-1","article-title":"Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth.","volume":"574","author":"Shao","year":"2019","journal-title":"Nature."},{"key":"B12","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1542\/peds.2005-2824","article-title":"Factors influencing the composition of the intestinal microbiota in early infancy.","volume":"118","author":"Penders","year":"2006","journal-title":"Pediatrics."},{"key":"B13","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.chom.2015.04.004","article-title":"Dynamics and stabilization of the human gut microbiome during the first year of life.","volume":"17","author":"B\u00e4ckhed","year":"2015","journal-title":"Cell Host Microbe."},{"key":"B14","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-018-0617-x","article-title":"Temporal development of the gut microbiome in early childhood from the TEDDY study.","volume":"562","author":"Stewart","year":"2018","journal-title":"Nature."},{"key":"B15","doi-asserted-by":"publisher","first-page":"343ra81","DOI":"10.1126\/scitranslmed.aad0917","article-title":"Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability.","volume":"8","author":"Yassour","year":"2016","journal-title":"Sci Transl Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"10410","DOI":"10.1038\/ncomms10410","article-title":"Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children.","volume":"7","author":"Korpela","year":"2016","journal-title":"Nat Commun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1136\/gutjnl-2015-310376","article-title":"Proton pump inhibitors affect the gut microbiome.","volume":"65","author":"Imhann","year":"2016","journal-title":"Gut."},{"key":"B18","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/gutjnl-2015-310861","article-title":"Proton pump inhibitors alter the composition of the gut microbiota.","volume":"65","author":"Jackson","year":"2016","journal-title":"Gut."},{"key":"B19","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3389\/fimmu.2014.00427","article-title":"The intestinal microbiome in early life: health and disease.","volume":"5","author":"Arrieta","year":"2014","journal-title":"Front Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.tim.2018.09.008","article-title":"The human microbiome and child growth - first 1000 days and beyond.","volume":"27","author":"Robertson","year":"2019","journal-title":"Trends Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.","volume":"372","author":"Page","year":"2021","journal-title":"BMJ."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0216453","DOI":"10.1371\/journal.pone.0216453","article-title":"Aerodigestive sampling reveals altered microbial exchange between lung, oropharyngeal, and gastric microbiomes in children with impaired swallow function.","volume":"14","author":"Duvallet","year":"2019","journal-title":"PLoS One."},{"key":"B23","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1007\/s10096-017-3178-2","article-title":"Characterization of the nasopharyngeal and middle ear microbiota in gastroesophageal reflux-prone versus gastroesophageal reflux non-prone children.","volume":"37","author":"Boers","year":"2018","journal-title":"Eur J Clin Microbiol Infect Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0128346","DOI":"10.1371\/journal.pone.0128346","article-title":"Esophageal microbiome in eosinophilic esophagitis.","volume":"10","author":"Harris","year":"2015","journal-title":"PLoS One."},{"key":"B25","doi-asserted-by":"publisher","first-page":"mgen000870","DOI":"10.1099\/mgen.0.000870","article-title":"Changes to the upper gastrointestinal microbiotas of children with reflux oesophagitis and oesophageal metaplasia.","volume":"8","author":"Luu","year":"2022","journal-title":"Microb Genom."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e109","DOI":"10.1097\/MPG.0000000000003413","article-title":"Esophageal microbiome in healthy children and esophageal eosinophilia.","volume":"74","author":"Parashette","year":"2022","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"701","DOI":"10.3390\/nu17040701","article-title":"Gut microbiota profile and functional gastrointestinal disorders in infants: a longitudinal study.","volume":"17","author":"Pantazi","year":"2025","journal-title":"Nutrients."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1267192","DOI":"10.3389\/fcimb.2023.1267192","article-title":"Analysis of the gut microbiota in children with gastroesophageal reflux disease using metagenomics and metabolomics.","volume":"13","author":"Ye","year":"2023","journal-title":"Front Cell Infect Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.1016\/j.clinthera.2006.11.012","article-title":"Pharmacokinetic properties of esomeprazole in children aged 1 to 11 years with symptoms of gastroesophageal reflux disease: a randomized, open-label study.","volume":"28","author":"Zhao","year":"2006","journal-title":"Clin Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"S16","DOI":"10.1097\/MPG.0b013e318176b2cb","article-title":"Safety and tolerability of esomeprazole in children with gastroesophageal reflux disease.","volume":"60","author":"Gilger","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1097\/MPG.0b013e3182496b35","article-title":"Esomeprazole for the treatment of GERD in infants ages 1-11 months.","volume":"60","author":"Winter","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1097\/MPG.0b013e31812e012f","article-title":"Pharmacokinetics and acid-suppressive effects of esomeprazole in infants 1-24 months old with symptoms of gastroesophageal reflux disease.","volume":"45","author":"Omari","year":"2007","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.14309\/ctg.0000000000000703","article-title":"Longitudinal microbiome changes in children exposed to proton pump inhibitors.","volume":"15","author":"Zhang","year":"2024","journal-title":"Clin Transl Gastroenterol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"504","DOI":"10.5863\/1551-6776-28.6.504","article-title":"Proton pump inhibitors modulate gene expression profile in esophageal mucosa and microbiome.","volume":"28","author":"Rajagopala","year":"2023","journal-title":"J Pediatr Pharmacol Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.5152\/tjg.2020.20245","article-title":"Gut microbiota characteristics in children after the use of proton pump inhibitors.","volume":"32","author":"Simakachorn","year":"2021","journal-title":"Turk J Gastroenterol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1254329","DOI":"10.3389\/fped.2023.1254329","article-title":"Gastroesophageal reflux and PPI exposure alter gut microbiota in very young infants.","volume":"11","author":"Francis","year":"2023","journal-title":"Front Pediatr."},{"key":"B37","doi-asserted-by":"publisher","first-page":"444","DOI":"10.3389\/fcimb.2017.00444","article-title":"The influence of proton pump inhibitors on the fecal microbiome of infants with gastroesophageal reflux-A prospective longitudinal interventional study.","volume":"7","author":"Castellani","year":"2017","journal-title":"Front Cell Infect Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1097\/MEG.0000000000000815","article-title":"Short article: Risk of small intestinal bacterial overgrowth with chronic use of proton pump inhibitors in children.","volume":"29","author":"Cares","year":"2017","journal-title":"Eur J Gastroenterol Hepatol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1016\/j.jpeds.2015.01.004","article-title":"Small bowel bacterial overgrowth associated with persistence of abdominal symptoms in children treated with a proton pump inhibitor.","volume":"166","author":"Sieczkowska","year":"2015","journal-title":"J Pediatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.jped.2012.12.005","article-title":"A double-blind placebo-controlled randomized trial on probiotics in small bowel bacterial overgrowth in children treated with omeprazole.","volume":"89","author":"Hegar","year":"2013","journal-title":"J Pediatr."},{"key":"B41","doi-asserted-by":"publisher","first-page":"51","DOI":"10.5056\/jnm17059","article-title":"Is it useful to administer probiotics together with proton pump inhibitors in children with gastroesophageal reflux?","volume":"24","author":"Belei","year":"2018","journal-title":"J Neurogastroenterol Motil."},{"key":"B42","doi-asserted-by":"publisher","first-page":"251","DOI":"10.5223\/pghn.2020.23.3.251","article-title":"Lactobacillus rhamnosus GG usage in the prevention of gastrointestinal and respiratory tract infections in children with gastroesophageal reflux disease treated with proton pump inhibitors: a randomized double-blinded placebo-controlled trial.","volume":"23","author":"Dziechciarz","year":"2020","journal-title":"Pediatr Gastroenterol Hepatol Nutr."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e180315","DOI":"10.1001\/jamapediatrics.2018.0315","article-title":"Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood.","volume":"172","author":"Mitre","year":"2018","journal-title":"JAMA Pediatr."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3872","DOI":"10.3390\/jcm14113872","article-title":"Association of acid-suppressive medication and antimicrobial use in infancy with food allergy and anaphylaxis.","volume":"14","author":"Chaaban","year":"2025","journal-title":"J Clin Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1001\/jamapediatrics.2023.2900","article-title":"Proton pump inhibitor use and risk of serious infections in young children.","volume":"177","author":"Lassalle","year":"2023","journal-title":"JAMA Pediatr."},{"key":"B46","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12887-018-0995-0","article-title":"Streptococcus agalactiae meningoencephalitis associated with gastroesophageal reflux disease and chronic proton pump inhibitors use, in a 9 month-old infant: a case report.","volume":"18","author":"B\u00eerlu\u0163iu","year":"2018","journal-title":"BMC Pediatr."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2003229","DOI":"10.1183\/13993003.03229-2020","article-title":"The risk of community-acquired pneumonia in children using gastric acid suppressants.","volume":"58","author":"van der Sande","year":"2021","journal-title":"Eur Respir J."},{"key":"B48","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1093\/cid\/civ432","article-title":"Use of acid suppression medication is associated with risk for C. difficile infection in infants and children: a population-based study.","volume":"61","author":"Freedberg","year":"2015","journal-title":"Clin Infect Dis."},{"key":"B49","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.jpeds.2022.04.030","article-title":"Association of early life prescriptions for antibiotics and acid suppressants with childhood psychotropic prescriptions.","volume":"246","author":"Stark","year":"2022","journal-title":"J Pediatr."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1111\/cts.13225","article-title":"Proton pump inhibitor use and risk of depression and anxiety in children: nationwide cohort study.","volume":"15","author":"Wang","year":"2022","journal-title":"Clin Transl Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/cpt.3679","article-title":"Prenatal and early childhood exposure to antibiotics or gastric acid inhibitors and increased risk of epilepsy: a nationwide population-based study.","volume":"118","author":"Gudnadottir","year":"2025","journal-title":"Clin Pharmacol Ther."},{"key":"B52","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s40264-024-01500-x","article-title":"Prenatal and early childhood exposure to proton pump inhibitors and antibiotics and the risk of childhood cancer: a nationwide population-based cohort study.","volume":"48","author":"Gudnadottir","year":"2025","journal-title":"Drug Saf."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1558414","DOI":"10.3389\/fimmu.2025.1558414","article-title":"The role of the esophageal and intestinal microbiome in gastroesophageal reflux disease: past, present, and future.","volume":"16","author":"Guan","year":"2025","journal-title":"Front Immunol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/dnares\/dst037","article-title":"Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers.","volume":"21","author":"Said","year":"2014","journal-title":"DNA Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"998","DOI":"10.3390\/gastroent15040069","article-title":"The esophageal microbiota in esophageal health and disease.","volume":"15","author":"Bonazzi","year":"2024","journal-title":"Gastroenterol Insights."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.3748\/wjg.v25.i18.2149","article-title":"Alteration of the esophageal microbiota in Barrett\u2019s esophagus and esophageal adenocarcinoma.","volume":"25","author":"Lv","year":"2019","journal-title":"World J Gastroenterol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/nrmicro2266","article-title":"The molecular basis of the host response to lipopolysaccharide.","volume":"8","author":"Bryant","year":"2010","journal-title":"Nat Rev Microbiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.jcmgh.2016.03.006","article-title":"NOD-like receptor protein 3 inflammasome priming and activation in Barrett\u2019s epithelial cells.","volume":"2","author":"Nadatani","year":"2016","journal-title":"Cell Mol Gastroenterol Hepatol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1158\/1078-0432.CCR-11-0934","article-title":"Molecular pathways: pathogenesis and clinical implications of microbiome alteration in esophagitis and Barrett esophagus.","volume":"18","author":"Yang","year":"2012","journal-title":"Clin Cancer Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"8115","DOI":"10.3390\/ijms26178115","article-title":"Tight junction proteins at the crossroads of inflammation. Barrier function, and disease modulation.","volume":"26","author":"Cha","year":"2025","journal-title":"Int J Mol Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1111\/1751-2980.12163","article-title":"ERK1\/2 participates in regulating the expression and distribution of tight junction proteins in the process of reflux esophagitis.","volume":"15","author":"Tan","year":"2014","journal-title":"J Dig Dis."},{"key":"B62","doi-asserted-by":"publisher","first-page":"2077620","DOI":"10.1080\/21688370.2022.2077620","article-title":"Tight junctions: from molecules to gastrointestinal diseases.","volume":"11","author":"Moonwiriyakit","year":"2023","journal-title":"Tissue Barriers."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites.","volume":"165","author":"Koh","year":"2016","journal-title":"Cell."},{"key":"B64","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/1462-2920.13589","article-title":"Formation of propionate and butyrate by the human colonic microbiota.","volume":"19","author":"Louis","year":"2017","journal-title":"Environ Microbiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1093\/nutrit\/nuw067","article-title":"Role of short-chain fatty acids in colonic inflammation, carcinogenesis, and mucosal protection and healing.","volume":"75","author":"van der Beek","year":"2017","journal-title":"Nutr Rev."},{"key":"B66","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.bpg.2017.09.011","article-title":"Action and function of Faecalibacterium prausnitzii in health and disease.","volume":"31","author":"Ferreira-Halder","year":"2017","journal-title":"Best Pract Res Clin Gastroenterol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.3390\/nu11071565","article-title":"Dietary factors and modulation of bacteria strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: a systematic review.","volume":"11","author":"Verhoog","year":"2019","journal-title":"Nutrients."},{"key":"B68","doi-asserted-by":"publisher","first-page":"e89","DOI":"10.1038\/ctg.2015.20","article-title":"Influence of proton-pump inhibitors on the luminal microbiota in the gastrointestinal tract.","volume":"6","author":"Tsuda","year":"2015","journal-title":"Clin Transl Gastroenterol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.3390\/biomedicines12102271","article-title":"Proton pump inhibitors and oral-gut microbiota: from mechanism to clinical significance.","volume":"12","author":"Zhang","year":"2024","journal-title":"Biomedicines."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1136\/gutjnl-2023-330168","article-title":"Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial.","volume":"73","author":"Zhu","year":"2024","journal-title":"Gut."},{"key":"B71","doi-asserted-by":"publisher","first-page":"e8860","DOI":"10.7759\/cureus.8860","article-title":"Small intestinal bacterial overgrowth: comprehensive review of diagnosis, prevention, and treatment methods.","volume":"12","author":"Achufusi","year":"2020","journal-title":"Cureus."},{"key":"B72","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1136\/flgastro-2022-102163","article-title":"Aetiology, diagnosis and management of small intestinal bacterial overgrowth.","volume":"14","author":"Ahmed","year":"2022","journal-title":"Frontline Gastroenterol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"e00078","DOI":"10.14309\/ctg.0000000000000078","article-title":"Small intestinal bacterial overgrowth: clinical features and therapeutic management.","volume":"10","author":"Rao","year":"2019","journal-title":"Clin Transl Gastroenterol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.cgh.2012.12.011","article-title":"Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis.","volume":"11","author":"Lo","year":"2013","journal-title":"Clin Gastroenterol Hepatol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease.","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.phrs.2012.09.002","article-title":"Gut microbiota, immune development and function.","volume":"69","author":"Bengmark","year":"2013","journal-title":"Pharmacol Res."},{"key":"B77","first-page":"203","article-title":"The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems.","volume":"28","author":"Carabotti","year":"2015","journal-title":"Ann Gastroenterol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.1038\/s41598-020-59550-x","article-title":"The effects of a multispecies synbiotic on microbiome-related side effects of long-term proton pump inhibitor use: a pilot study.","volume":"10","author":"Horvath","year":"2020","journal-title":"Sci Rep."},{"key":"B79","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fmed.2018.00124","article-title":"Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis.","volume":"5","author":"McFarland","year":"2018","journal-title":"Front Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41575-019-0173-3","article-title":"Probiotics and prebiotics in intestinal health and disease: from biology to the clinic.","volume":"16","author":"Sanders","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document. The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic.","volume":"11","author":"Hill","year":"2014","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1038\/s41591-019-0439-x","article-title":"The pros, cons, and many unknowns of probiotics.","volume":"25","author":"Suez","year":"2019","journal-title":"Nat Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1017\/S0007114516002026","article-title":"Importance of strain subgroup analysis in probiotic meta-analyses.","volume":"116","author":"McFarland","year":"2016","journal-title":"Br J Nutr."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1909690\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:39:28Z","timestamp":1786509568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1909690\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":83,"alternative-id":["10.3389\/fnut.2026.1909690"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1909690","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"article-number":"1909690"}}