{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:09:10Z","timestamp":1791770950340,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670486, 82070540"],"award-info":[{"award-number":["81670486, 82070540"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Bile reflux can cause inflammation, gastric mucosa atrophy, and diseases such as stomach cancer. Alkaline bile flowing back into the stomach affects the intragastric environment and can alter the gastric bacterial community. We sought to identify the characteristics of the stomach mucosal microbiota in patients with bile reflux.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gastric mucosal samples were collected from 52 and 40 chronic gastritis patients with and without bile reflux, respectively. The bacterial profile was determined using 16S rRNA gene analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the absence of H. pylori infection, the richness (based on the Sobs and Chao1 indices; P &amp;lt;0.05) and diversity (based on Shannon indices; P &amp;lt;0.05) of gastric mucosa microbiota were higher in patients with bile reflux patients than in those without. There was a marked difference in the microbiota structure between patients with and without bile reflux (ANOSIM, R=0.058, P=0.011). While the genera, <jats:italic>Comamonas<\/jats:italic>, <jats:italic>Halomonas<\/jats:italic>, <jats:italic>Bradymonas<\/jats:italic>, <jats:italic>Pseudomonas<\/jats:italic>, <jats:italic>Marinobacter<\/jats:italic>, <jats:italic>Arthrobacter<\/jats:italic>, and <jats:italic>Shewanella<\/jats:italic> were enriched in patients with bile reflux, the genera, <jats:italic>Haemophilus<\/jats:italic>, <jats:italic>Porphyromonas<\/jats:italic>, and <jats:italic>Subdoligranulum<\/jats:italic>, were enriched in those without bile reflux.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that bile reflux significantly alters the composition of the gastric microbiota.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2022.940687","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T05:51:59Z","timestamp":1662702719000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Bile reflux alters the profile of the gastric mucosa microbiota"],"prefix":"10.3389","volume":"12","author":[{"given":"Gang","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juexin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1159\/000517263","article-title":"The relationship between primary duodenogastric reflux and helicobacter pylori gastritis in children","volume":"40","author":"Arslan","year":"2021","journal-title":"Dig Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/mi.2016.131","article-title":"Helicobacter pylori infection is associated with an altered gastric microbiota in children","volume":"10","author":"Brawner","year":"2017","journal-title":"Mucosal Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/s0140-6736(80)92077-2","article-title":"Pyloric reflux and G-cell hyperfunction","volume":"2","author":"Calam","year":"1980","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"42","DOI":"10.18821\/0869-2084-2020-65-1-42-49","article-title":"[The state and role of esophagus, stomach, intestinal microbiota in patients with ulcer disease, chronic gastritis, esophagitis.]","volume":"65","author":"Chervinets","year":"2020","journal-title":"Klin Lab. Diagn."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.5152\/tjg.2017.10","article-title":"The role of lifestyle changes in gastroesophageal reflux diseases treatment","volume":"28","author":"Da\u011fl\u0131","year":"2017","journal-title":"Turk J. Gastroenterol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1038\/s41419-021-04396-y","article-title":"Interactions between gastric microbiota and metabolites in gastric cancer","volume":"12","author":"Dai","year":"2021","journal-title":"Cell Death Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"15438","DOI":"10.1038\/s41598-017-15510-6","article-title":"Gastric microbiome of Indian patients with helicobacter pylori infection, and their interaction networks","volume":"7","author":"Das","year":"2017","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/s1091-255x(98)80021-8","article-title":"Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen","volume":"2","author":"Fein","year":"1998","journal-title":"J. Gastrointest. Surg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.cell.2017.03.046","article-title":"Bacterial metabolism affects the c. elegans response to cancer chemotherapeutics","volume":"169","author":"Garc\u00eda-Gonz\u00e1lez","year":"2017","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1572-0241.2000.01704.x","article-title":"H. pylori in the pathogenesis of duodenal ulcer: interaction between duodenal acid load, bile and h. pylori","volume":"95","author":"Graham","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41420-022-00962-1","article-title":"Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review","volume":"8","author":"He","year":"2022","journal-title":"Cell Death Discovery"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12590","article-title":"The eradication of helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults","volume":"24","author":"He","year":"2019","journal-title":"Helicobacter"},{"key":"B13","first-page":"659","article-title":"A study on the roles of helicobacter pylori in bile reflux gastritis and gastric cancer","volume":"23","author":"Huang","year":"2018","journal-title":"J. buon"},{"key":"B14","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/hel.12260","article-title":"Gastric microbiota","author":"Ianiro","year":"2015","journal-title":"Helicobacter"},{"key":"B15","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3109\/1040841x.2012.726209","article-title":"The genus shewanella: from the briny depths below to human pathogen","volume":"40","author":"Janda","year":"2014","journal-title":"Crit. Rev. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s00432-016-2299-9","article-title":"Risk factors for intestinal metaplasia in a southeastern Chinese population: an analysis of 28,745 cases","volume":"143","author":"Jiang","year":"2017","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.jbiosc.2017.10.014","article-title":"Characterization of cellulolytic microbial consortium enriched on Napier grass using metagenomic approaches","volume":"125","author":"Kanokratana","year":"2018","journal-title":"J. Biosci. Bioeng."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.2217\/fmb.13.108","article-title":"Microbiology and epidemiology of halomonas species","volume":"8","author":"Kim","year":"2013","journal-title":"Future Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1365-2982.2004.00633.x","article-title":"Mechanisms underlying duodeno-gastric reflux in man","volume":"17","author":"Koek","year":"2005","journal-title":"Neurogastroenterol. Motil."},{"key":"B20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1136\/gut.38.1.15","article-title":"Helicobacter pylori may induce bile reflux: link between h pylori and bile induced injury to gastric epithelium","volume":"38","author":"Ladas","year":"1996","journal-title":"Gut"},{"key":"B21","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jss.2018.03.055","article-title":"Exposure to bile acids alters the intracellular location and function of MnSOD in barrett's esophagus","volume":"229","author":"Li","year":"2018","journal-title":"J. Surg. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1136\/gutjnl-2017-315318","article-title":"MicroRNA-92a-1-5p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia","volume":"68","author":"Li","year":"2019","journal-title":"Gut"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00533","article-title":"Regulatory T cells and plasmacytoid dendritic cells within the tumor microenvironment in gastric cancer are correlated with gastric microbiota dysbiosis: A preliminary study","volume":"10","author":"Ling","year":"2019","journal-title":"Front. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1111\/1751-2980.12858","article-title":"The relationship between gastric cancer, its precancerous lesions and bile reflux: A retrospective study","volume":"21","author":"Li","year":"2020","journal-title":"J. Dig Dis."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s13099-021-00460-2","article-title":"Impact of helicobacter pylori eradication on the gastric microbiome","volume":"13","author":"Mao","year":"2021","journal-title":"Gut Pathog."},{"key":"B26","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1111\/j.1365-2036.1991.tb00533.x","article-title":"The effect of bile acids on the growth and adherence of helicobacter pylori","volume":"5","author":"Mathai","year":"1991","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/j.cgh.2018.02.034","article-title":"New causes for the old problem of bile reflux gastritis","volume":"16","author":"McCabe","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1186\/s40064-016-3641-z","article-title":"Cholecystectomy and duodenogastric reflux: interacting effects over the gastric mucosa","volume":"5","author":"Mercan","year":"2016","journal-title":"Springerplus"},{"key":"B29","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0304-3835(83)90174-x","article-title":"Promoting effect of intestinal pseudomonas aeruginosa on gastric tumorigenesis in rats with n-methyl-N'-nitro-N-nitrosoguanidine","volume":"17","author":"Morishita","year":"1983","journal-title":"Cancer Lett."},{"key":"B30","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1136\/jcp.39.5.531","article-title":"Campylobacter like organisms and reflux gastritis","volume":"39","author":"O'Connor","year":"1986","journal-title":"J. Clin. Pathol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1136\/gut.30.11.1552","article-title":"Prospective comparative study of the influence of postoperative bile reflux on gastric mucosal histology and campylobacter pylori infection","volume":"30","author":"Offerhaus","year":"1989","journal-title":"Gut"},{"key":"B32","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1002\/cam4.1965","article-title":"Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development","volume":"8","author":"Pearson","year":"2019","journal-title":"Cancer Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"13817","DOI":"10.1038\/s41598-018-31738-2","article-title":"The gastric mucosal-associated microbiome in patients with gastric polyposis","volume":"8","author":"Ren","year":"2018","journal-title":"Sci. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.1002\/cncr.32369","article-title":"Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications","volume":"125","author":"Sasaki","year":"2019","journal-title":"Cancer"},{"key":"B35","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1136\/jcp.46.3.235","article-title":"Bile reflux and intestinal metaplasia in gastric mucosa","volume":"46","author":"Sobala","year":"1993","journal-title":"J. Clin. Pathol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"864","DOI":"10.18699\/vj21.100","article-title":"Taxonomic composition and biodiversity of the gut microbiome from patients with irritable bowel syndrome, ulcerative colitis, and asthma","volume":"25","author":"Tikunov","year":"2021","journal-title":"Vavilovskii Zhurnal Genet. Selektsii"},{"key":"B37","doi-asserted-by":"publisher","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":"B38","doi-asserted-by":"publisher","DOI":"10.3892\/or.2021.8195","article-title":"Bile reflux and hypopharyngeal cancer (Review)","volume":"46","author":"Vageli","year":"2021","journal-title":"Oncol. Rep."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202200263","article-title":"Bile acid-microbiome interaction promotes gastric carcinogenesis","volume":"9","author":"Wang","year":"2022","journal-title":"Adv. Sci. (Weinh)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"391","DOI":"10.3892\/etm.2021.9822","article-title":"Intestinal mucosal microbiota composition of patients with acquired immune deficiency syndrome in guangzhou, China","volume":"21","author":"Xu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1111\/jgh.14946","article-title":"Microbiological evidences for gastric cardiac microflora dysbiosis inducing the progression of inflammation","volume":"35","author":"Yan","year":"2020","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.835310","article-title":"The spatial landscape of the bacterial community and bile acids in the digestive tract of patients with bile reflux","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12848","article-title":"The impact of helicobacter pylori infection, eradication therapy, and probiotics intervention on gastric microbiota in young adults","volume":"26","author":"Yuan","year":"2021","journal-title":"Helicobacter"},{"key":"B44","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.omtn.2021.08.019","article-title":"Essential role of ALKBH5-mediated RNA demethylation modification in bile acid-induced gastric intestinal metaplasia","volume":"26","author":"Yue","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.559148","article-title":"Alterations of gastric microbiota in gastric cancer and precancerous stages","volume":"11","author":"Zhang","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.625586","article-title":"The effects of helicobacter pylori infection on microbiota associated with gastric mucosa and immune factors in children","volume":"12","author":"Zheng","year":"2021","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.940687\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T05:52:07Z","timestamp":1662702727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.940687\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":46,"alternative-id":["10.3389\/fcimb.2022.940687"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.940687","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]},"article-number":"940687"}}