{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:51:01Z","timestamp":1775152261829,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Camden Health Research Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Recent evidence suggests that Helicobacter pylori can act outside stomach by influencing the gut microbiome. We hypothesize that interactions between H. pylori and the gut microbiome, and the resulting changes in the gut chemicals (bile acids and bacterial signaling molecules involved in quorum sensing, e.g., autoinducer-2\/AI-2), influence pathogen survival, antibiotic response, and disease progression. Our gut microbiome, bile acid, and AI-2 analyses showed that H. pylori patients had decreased alpha diversity (p = 0.05), increased AI-2 concentration (p = 0.019), decreased taurine-conjugated bile acids, and increased unconjugated bile acids. A co-occurring module of Prevotella, Holdemanella, and Subdoligranulum, was higher in patients (p = 0.04) and relative abundance of Allisonella was positively associated with levels of unconjugated bile acids, chenodeoxycholic acid, and cholic acid (p = 0.05 and 0.02, respectively). Our study is the first to characterize the gut microbiome-metabolome signature (bile acids and AI-2) in H. pylori patients. Abundance of certain bacteria that deconjugate bile acids along with increased AI-2 possibly gives selective advantage for H. pylori growth, further reducing microbial diversity. Taurine-conjugated bile acids inhibit H. pylori growth. We propose a model describing interplay of these factors in H. pylori disease progression, suggesting therapeutic targets worth exploring with rising antibiotic resistance.<\/jats:p>","DOI":"10.3390\/microorganisms14040801","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:51:02Z","timestamp":1775148662000},"page":"801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Gut Signature of Microbiome, Bile Acid, and Quorum-Sensing Profiles Is Associated with Helicobacter pylori Infection and Disease Progression"],"prefix":"10.3390","volume":"14","author":[{"given":"Hyder","family":"Alikhan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Cooper University Health Care, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"White","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Sterrett","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Farag","sequence":"additional","affiliation":[{"name":"Cooper Medical School of Rowan University, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-5575","authenticated-orcid":false,"given":"Christopher A.","family":"Lowry","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1810-4927","authenticated-orcid":false,"given":"Lamya\u2019a M.","family":"Dawud","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Judge","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cooper University Health Care, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lark","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"DeSipio","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cooper University Health Care, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4388-6150","authenticated-orcid":false,"given":"Sangita","family":"Phadtare","sequence":"additional","affiliation":[{"name":"Cooper Medical School of Rowan University, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","first-page":"33","article-title":"The prevalence of Helicobacter pylori infection in different countries","volume":"9","author":"Pounder","year":"1995","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1053\/j.gastro.2016.01.028","article-title":"Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis","volume":"150","author":"Lee","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41572-023-00431-8","article-title":"Helicobacter pylori infection","volume":"9","author":"Malfertheiner","year":"2023","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1053\/j.gastro.2024.12.033","article-title":"Eradication Therapy to Prevent Gastric Cancer in Helicobacterpylori-Positive Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies","volume":"169","author":"Ford","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.14309\/ajg.0000000000002968","article-title":"ACG Clinical Guideline: Treatment of Helicobacter pylori Infection","volume":"119","author":"Chey","year":"2024","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"269","DOI":"10.14309\/ajg.0000000000002045","article-title":"Rates of Antimicrobial Resistance in Helicobacter pylori Isolates From Clinical Trial Patients Across the US and Europe","volume":"118","author":"Megraud","year":"2023","journal-title":"Am. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cgh.2008.10.024","article-title":"Efficient identification and evaluation of effective Helicobacter pylori therapies","volume":"7","author":"Graham","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ebiom.2018.08.028","article-title":"The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial","volume":"35","author":"Chen","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dewayani, A., Afrida Fauzia, K., Alfaray, R.I., Waskito, L.A., Doohan, D., Rejeki, P.S., Alshawsh, M.A., Rezkitha, Y.A.A., Yamaoka, Y., and Miftahussurur, M. (2023). Gastric microbiome changes in relation with Helicobacter pylori resistance. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0284958"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20100","DOI":"10.1038\/s41598-019-56631-4","article-title":"Helicobacter pylori infection associates with fecal microbiota composition and diversity","volume":"9","author":"Frost","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_11","first-page":"13","article-title":"Is duodenal biopsy appropriate in areas endemic for Helicobacter pylori?","volume":"4","author":"Sahin","year":"2017","journal-title":"N. Clin. Istanb."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Butt, J., and Epplein, M. (2019). Helicobacter pylori and colorectal cancer\u2014A bacterium going abroad?. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007861"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7480620","DOI":"10.1155\/2019\/7480620","article-title":"Association between Helicobacter pylori Infection and Colorectal Adenomatous Polyps","volume":"2019","author":"Yang","year":"2019","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dash, N.R., Khoder, G., Nada, A.M., and Al Bataineh, M.T. (2019). Exploring the impact of Helicobacter pylori on gut microbiome composition. PLoS ONE, 14, Erratum in PLoS ONE 2021, 16, e0256274.","DOI":"10.1371\/journal.pone.0256274"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1572-0241.2000.01704.x","article-title":"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":"ref_16","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1099\/jmm.0.45636-0","article-title":"Chemotactic response of Helicobacter pylori to human plasma and bile","volume":"53","author":"Worku","year":"2004","journal-title":"J. Med. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"a012427","DOI":"10.1101\/cshperspect.a012427","article-title":"Bacterial quorum sensing: Its role in virulence and possibilities for its control","volume":"2","author":"Rutherford","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature24624","article-title":"Progress in and promise of bacterial quorum sensing research","volume":"551","author":"Whiteley","year":"2017","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.1038\/s41467-020-19243-5","article-title":"Sensing of autoinducer-2 by functionally distinct receptors in prokaryotes","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1128\/JB.00246-07","article-title":"The quorum-sensing molecule autoinducer 2 regulates motility and flagellar morphogenesis in Helicobacter pylori","volume":"189","author":"Rader","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev-genet-102108-134304","article-title":"Bacterial quorum-sensing network architectures","volume":"43","author":"Ng","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5575","DOI":"10.3748\/wjg.v27.i33.5575","article-title":"Characterization of gut microbiome and metabolome in Helicobacter pylori patients in an underprivileged community in the United States","volume":"27","author":"White","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.chom.2016.02.020","article-title":"A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing","volume":"19","author":"Ismail","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_24","first-page":"27663","article-title":"Analysis of composition of microbiomes: A novel method for studying microbial composition","volume":"26","author":"Mandal","year":"2015","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/1755-0998.13704","article-title":"SCNIC: Sparse correlation network investigation for compositional data","volume":"23","author":"Shaffer","year":"2023","journal-title":"Mol. Ecol. Resour."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Friedman, J., and Alm, E.J. (2012). Inferring correlation networks from genomic survey data. PLoS Comput. Biol., 8.","DOI":"10.1371\/journal.pcbi.1002687"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1093\/bioinformatics\/bty734","article-title":"FastSpar: Rapid and scalable correlation estimation for compositional data","volume":"35","author":"Watts","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41592-023-02092-7","article-title":"Multigroup analysis of compositions of microbiomes with covariate adjustments and repeated measures","volume":"21","author":"Lin","year":"2024","journal-title":"Nat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1136\/gutjnl-2019-319696","article-title":"Effect of Helicobacter pylori on gastrointestinal microbiota: A population-based study in Linqu, a high-risk area of gastric cancer","volume":"69","author":"Guo","year":"2020","journal-title":"Gut"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12753","DOI":"10.1111\/hel.12753","article-title":"Duodenal microbiome in patients with or without Helicobacter pylori infection","volume":"25","author":"Baldeon","year":"2020","journal-title":"Helicobacter"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Huang, G., Wang, S., Wang, J., Tian, L., Yu, Y., Zuo, X., and Li, Y. (2022). Bile reflux alters the profile of the gastric mucosa microbiota. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.940687"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s005350050374","article-title":"Antibacterial action of bile acids against Helicobacter pylori and changes in its ultrastructural morphology: Effect of unconjugated dihydroxy bile acid","volume":"34","author":"Itoh","year":"1999","journal-title":"J. Gastroenterol."},{"key":"ref_33","first-page":"879","article-title":"Bile acids promote gastric intestinal metaplasia by upregulating CDX2 and MUC2 expression via the FXR\/NF-\u03baB signalling pathway","volume":"54","author":"Yu","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","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":"ref_35","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s40168-021-01101-1","article-title":"Review: Microbial transformations of human bile acids","volume":"9","author":"Guzior","year":"2021","journal-title":"Microbiome"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1158\/1055-9965.EPI-12-0730","article-title":"Bile acid promotes intestinal metaplasia and gastric carcinogenesis","volume":"21","author":"Tatsugami","year":"2012","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/pathogens3010014","article-title":"Metabolism of cholesterol and bile acids by the gut microbiota","volume":"3","author":"Gerard","year":"2013","journal-title":"Pathogens"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13580","DOI":"10.1073\/pnas.0804437105","article-title":"Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome","volume":"105","author":"Jones","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrgastro.2017.119","article-title":"Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis","volume":"15","author":"Jia","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e12778","DOI":"10.1111\/hel.12778","article-title":"AI-2 represses CagA expression and bacterial adhesion, attenuating the Helicobacter pylori-induced inflammatory response of gastric epithelial cells","volume":"26","author":"Wen","year":"2021","journal-title":"Helicobacter"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, H., Huang, X., Zhang, X., Zhang, X., Xu, X., She, F., and Wen, Y. (2022). AI-2 Induces Urease Expression Through Downregulation of Orphan Response Regulator HP1021 in Helicobacter pylori. Front. Med., 9.","DOI":"10.3389\/fmed.2022.790994"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108274","DOI":"10.1016\/j.bioorg.2025.108274","article-title":"Manipulation and quantification of the levels of Autoinducer-2 quorum sensing signal in the mouse gut","volume":"157","author":"Rodrigues","year":"2025","journal-title":"Bioorganic Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s40168-022-01367-z","article-title":"Exploring AI-2-mediated interspecies communications within rumen microbial communities","volume":"10","author":"Liu","year":"2022","journal-title":"Microbiome"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.anaerobe.2017.08.009","article-title":"Dipeptidyl peptidase IV and quorum sensing signaling in biofilm-related virulence of Prevotella aurantiaca","volume":"48","author":"Fteita","year":"2017","journal-title":"Anaerobe"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.anaerobe.2005.03.003","article-title":"Bacteroides species produce Vibrio harveyi autoinducer 2-related molecules","volume":"11","author":"Antunes","year":"2005","journal-title":"Anaerobe"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/jobm.201300311","article-title":"Production of AI-2 is mediated by the S-ribosylhomocystein lyase gene luxS in Bacteroides fragilis and Bacteroides vulgatus","volume":"54","author":"Peixoto","year":"2014","journal-title":"J. Basic Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s12223-008-0030-1","article-title":"Detection of possible AI-2-mediated quorum sensing system in commensal intestinal bacteria","volume":"53","author":"Lukas","year":"2008","journal-title":"Folia Microbiol."},{"key":"ref_48","unstructured":"(2026, March 24). Data USA: Camden City, N.J.Q.U.S.C.B, Available online: https:\/\/www.census.gov\/quickfacts\/fact\/table\/camdencitynewjersey\/PST045224."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/4\/801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:03:00Z","timestamp":1775149380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/4\/801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["microorganisms14040801"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14040801","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}