{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:22:43Z","timestamp":1787750563985,"version":"build-2784847793"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2026,8,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Organoids provide a useful model system to study interactions between gut microbes and the activity of host tissues, including gastrointestinal (GI) barrier function. However, most organoid models have limited capacity to mimic the physiological hypoxia experienced by the colonic epithelium\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . While oxygen is required to support respiration in the host cells, many gut microbes are anaerobes that require anoxic conditions to grow. Using an innovative anaerobe co-culture system that maintains constant oxygen concentrations on the basolateral side of colonic epithelial monolayers and anoxic conditions on the luminal side, we demonstrate that colonic monolayers derived from a primary human cell line behaved more like\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      epithelia when cultivated in the co-culture system than when cultured under ambient oxygen concentrations. We then identified interactions between the colonic epithelium and a strain of\n                      <jats:italic toggle=\"yes\">Bifidobacterium adolescentis<\/jats:italic>\n                      \u2014an oxygen-sensitive species that is prevalent and abundant in the adult gut microbiome. Co-culturing colonic monolayers with\n                      <jats:italic toggle=\"yes\">Bifidobacterium adolescentis<\/jats:italic>\n                      U269-1 in the anoxic apical chamber mitigated loss of the barrier function in monolayers exposed to inflammatory cytokines. We identified indole lactic acid (ILA) as one metabolite from\n                      <jats:italic toggle=\"yes\">B. adolescentis<\/jats:italic>\n                      that provides dose-dependent protection against inflammatory cytokines. Oral administration of ILA was well tolerated in mice and provided protection against immunotherapy-induced (anti-CTLA4) colitis in female, but not male mice. Together, we demonstrated the utility of the co-culture system for screening microbes and their metabolites for interactions with the colonic epithelium, as well as advancing our understanding of interactions between bifidobacteria and host barrier function.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>\n                        <jats:bold>IMPORTANCE<\/jats:bold>\n                      <\/jats:title>\n                      <jats:p>\n                        The present study yielded strong evidence for the beneficial effects of\n                        <jats:italic toggle=\"yes\">B. adolescentis<\/jats:italic>\n                        on the maintenance of colonic barrier function in an asymmetric oxygen system that mimics the colonic environment. The bifidobacterial metabolite indole lactic acid was implicated in this protection both\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and in a mouse model. We also refined and scaled the co-culture system to a 96-well plate format to provide the capacity for higher-throughput screening of microbes and microbial metabolites under physiologically relevant conditions.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00926-25","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:44:53Z","timestamp":1785509093000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["An innovative organoid model to screen for bacteria and their metabolites that protect against inflammation-induced colonic barrier disruption"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-1467","authenticated-orcid":false,"given":"Nicole","family":"Cady","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia R.","family":"Meyer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicinal Chemistry, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwi","family":"Kim","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine, University of Michigan","place":["Ann 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Y.","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine, University of Michigan","place":["Ann Arbor, USA"]},{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Rogel Cancer Center, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan P.","family":"Rosshart","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0030f2a11","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiome Research, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU)","place":["Erlangen, Germany"]},{"name":"Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU)","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yatrik M.","family":"Shah","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Internal Medicine, University of Michigan","place":["Ann Arbor, USA"]},{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Rogel Cancer Center, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, University of Michigan","place":["Ann Arbor, USA"]},{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Rogel Cancer Center, University of Michigan","place":["Ann Arbor, 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