{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:10:23Z","timestamp":1790010623883,"version":"4.0.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Observational studies have linked the gut microbiota (GM) to infectious diseases, but confounding, reverse causation, and disease-related microbiome changes limit causal interpretation. We combined Mendelian randomization (MR) with focused experimental analyses to investigate microbiota\u2013infection relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two-sample MR evaluated genetically predicted microbial taxa across 75 infectious outcomes. Inverse-variance weighted (IVW) estimates were used as the primary analysis, with weighted-median and MR-Egger estimates as complementary methods. Benjamini\u2013Hochberg false discovery rate (FDR) and Bonferroni corrections were applied across all IVW tests. Instrument strength, Cochran's Q, MR-Egger intercepts, leave-one-out analysis, MR-PRESSO, and Steiger directionality testing were used to assess robustness. Exploratory association patterns were used to prioritize a Coriobacteriia-related respiratory signal for experimental investigation using\n                      <jats:italic>Collinsella aerofaciens<\/jats:italic>\n                      cell-free supernatant and A549 epithelial cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 15,728 IVW tests, 659 associations had nominal\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05. After global correction, three taxonomically related associations with urinary tract infection (UTI) remained significant. Higher genetically predicted abundance of genus\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      was associated with lower UTI risk (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.17\u20130.49; FDR-adjusted\n                      <jats:italic>P<\/jats:italic>\n                      = 0.029), while order Bifidobacteriales and family Bifidobacteriaceae showed similar estimates (both OR 0.25, 95% CI 0.14\u20130.45) and met the Bonferroni threshold. Sensitivity analyses showed no significant heterogeneity or MR-PRESSO-detected outliers, and leave-one-out and Steiger analyses were supportive, although MR-Egger intercepts suggested possible directional pleiotropy. Exploratory analyses identified clustering between Coriobacteriia-lineage taxa and respiratory outcomes.\n                      <jats:italic>C. aerofaciens<\/jats:italic>\n                      cell-free supernatant altered 993 genes and enriched inflammatory pathways in A549 cells. qPCR supported increased CSF2, CXCL8, and CCL20 expression, while ELISA detected IL-8 and MIP-3\u03b1 but not quantifiable GM-CSF. Untargeted metabolomics identified 201 differential metabolites between bacterial supernatant samples and matched BHI controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The corrected\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      -related UTI association was the principal MR finding, while the broader analysis identified exploratory microbiota\u2013infection patterns. The\n                      <jats:italic>C. aerofaciens<\/jats:italic>\n                      model linked extracellular metabolic remodeling during bacterial growth with epithelial transcriptional and inflammatory responses, providing focused directions for further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1821422","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:33:37Z","timestamp":1790008417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering the gut microbiota's role in infection risk: Mendelian randomization analysis of microbial taxa and infectious outcomes"],"prefix":"10.3389","volume":"17","author":[{"given":"Fengning","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health and Health Management, Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyue","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Radiology, Shandong First Medical University","place":["Tai'an, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Clinical and Basic Medicine, Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1183\/09031936.03.00098803","article-title":"Innate immunity in the lung : how epithelial cells fight against respiratory pathogens","volume":"23","author":"Bals","year":"2004","journal-title":"Eur. 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