{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T10:42:52Z","timestamp":1786272172919,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,6]]},"group-title":"Microbiology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Tuberculosis (TB) is a life-threatening disease with heterogenous presentation. Approximately one-quarter of the global population is infected with\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (Mtb), yet a much smaller fraction develops active TB disease. Host genetics, immune system function, and environmental factors have all been implicated in susceptibility to Mtb, yet no one factor fully explains TB heterogeneity. Strikingly, many of these same factors are linked to gut microbiome composition, which is intimately linked to systemic development of the immune system. Antibiotic treated mouse models suggest that increased gut microbiota diversity is protective against Mtb infection. In contrast,\n                  <jats:italic>Helicobacter hepaticus<\/jats:italic>\n                  colonization is correlated with exacerbated Mtb burden. However, antibiotics can have both microbial and nonmicrobial targets and studies to date have not deconvoluted these effects. Focused testing of specific microbiome members has been impossible without a gnotobiotic model for Mtb. Here, we develop the first gnotobiotic mouse model for Mtb infection and test how microbial diversity in the gut microbiome impacts host susceptibility to Mtb. Surprisingly, after intranasal challenge with Mtb, germ-free wild type mice had no difference in lung burden when compared to mice born with either a defined gut microbiome community (OMM-12) or a diverse, conventional microbiota.\n                  <jats:italic>H. hepaticus<\/jats:italic>\n                  gut colonization of OMM-12 and conventional mice also did not impact Mtb burden in the lungs in this controlled setting.\n                  <jats:italic>H. hepaticus<\/jats:italic>\n                  colonization of the gut did perturb lung immune responses associated with TB infection control. CD4+ T cells were decreased, CD8+ T cells were increased, and IL-6 production was decreased. While the gut microbiome may yet play a role in immune compromised mouse models or human disease, comparing drastically different gut microbiotas in gnotobiotically controlled C57BL\/6 mice did not yield any evidence of alteration in Mtb lung burden. The host\u2019s unique immune response to Mtb may in part make the pathogen resistant to immune disruption caused by gut microbiome changes.\n                <\/jats:p>","DOI":"10.64898\/2026.08.05.743129","type":"posted-content","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:50:46Z","timestamp":1786078246000},"source":"Crossref","is-referenced-by-count":0,"title":["Host control of\n                  <i>Mycobacterium tuberculosis<\/i>\n                  infection is not influenced by the gut microbiome"],"prefix":"10.64898","author":[{"given":"Carolina","family":"Agudelo","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Balakhmet","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel B.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas M.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Stanley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley R.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley"},{"name":"Center for Computational Biology, University of California, Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026080903000708000_2026.08.05.743129v1.1","doi-asserted-by":"crossref","unstructured":"Khan, N. et al. Alteration in the Gut Microbiota Provokes Susceptibility to Tuberculosis. Front. Immunol. 7, (2016).","DOI":"10.3389\/fimmu.2016.00529"},{"key":"2026080903000708000_2026.08.05.743129v1.2","unstructured":"Global Tuberculosis Report 2025. (World Health Organization, Geneva, 2025)."},{"key":"2026080903000708000_2026.08.05.743129v1.3","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16-0581"},{"key":"2026080903000708000_2026.08.05.743129v1.4","doi-asserted-by":"crossref","unstructured":"Li, W. , Zhu, Y. , Liao, Q. , Wang, Z. & Wan, C . Characterization of gut microbiota in children with pulmonary tuberculosis. BMC Pediatr. 19, 445 (2019).","DOI":"10.1186\/s12887-019-1782-2"},{"key":"2026080903000708000_2026.08.05.743129v1.5","doi-asserted-by":"crossref","unstructured":"Ding, X. et al. A metagenomic study of the gut microbiome in PTB\u2019S disease. Microbes Infect. 24, 104893 (2022).","DOI":"10.1016\/j.micinf.2021.104893"},{"key":"2026080903000708000_2026.08.05.743129v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.14015"},{"key":"2026080903000708000_2026.08.05.743129v1.7","doi-asserted-by":"crossref","first-page":"e2534432123","DOI":"10.1073\/pnas.2534432123","article-title":"The intestinal microbiota impacts nutritional immunity and resistance to Acinetobacter baumannii pneumonia","volume":"123","year":"2026","journal-title":"Proc. Natl. Acad. Sci"},{"key":"2026080903000708000_2026.08.05.743129v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01803-x"},{"key":"2026080903000708000_2026.08.05.743129v1.9","doi-asserted-by":"crossref","unstructured":"Jiang, Q. , Xu, Q. , Ken\u00e9z, \u00c1. , Chen, S. & Yang, G . Klebsiella pneumoniae infection is associated with alterations in the gut microbiome and lung metabolome. Microbiol. 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