{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:33:38Z","timestamp":1787499218083,"version":"build-2736575974"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM131457"],"award-info":[{"award-number":["GM131457"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["OD010956"],"award-info":[{"award-number":["OD010956"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["OD010931-12"],"award-info":[{"award-number":["OD010931-12"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI123105"],"award-info":[{"award-number":["AI123105"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["OD011107"],"award-info":[{"award-number":["OD011107"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,12,3]]},"abstract":"<jats:p>\n                    Chronic gut inflammatory diseases are associated with disruption of intestinal epithelial barriers and impaired mucosal immunity. HIV-1 (HIV) causes depletion of mucosal CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells early in infection and disruption of gut epithelium, resulting in chronic inflammation and immunodeficiency. Although antiretroviral therapy (ART) is effective in suppressing viral replication, it is incapable of restoring the \u201cleaky gut,\u201d which poses an impediment for HIV cure efforts. Strategies are needed for rapid repair of the epithelium to protect intestinal microenvironments and immunity in inflamed gut. Using an in vivo nonhuman primate intestinal loop model of HIV\/AIDS, we identified the pathogenic mechanism underlying sustained disruption of gut epithelium and explored rapid repair of gut epithelium at the intersection of microbial metabolism. Molecular, immunological, and metabolomic analyses revealed marked loss of peroxisomal proliferator-activated receptor-\u03b1 (PPAR\u03b1) signaling, predominant impairment of mitochondrial function, and epithelial disruption both in vivo and in vitro. To elucidate pathways regulating intestinal epithelial integrity, we introduced probiotic\n                    <jats:italic>Lactobacillus plantarum<\/jats:italic>\n                    into Simian immunodeficiency virus (SIV)-inflamed intestinal lumen. Rapid recovery of the epithelium occurred within 5 h of\n                    <jats:italic>L. plantarum<\/jats:italic>\n                    administration, independent of mucosal CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell recovery, and in the absence of ART. This intestinal barrier repair was driven by\n                    <jats:italic>L. plantarum<\/jats:italic>\n                    -induced PPAR\u03b1 activation and restoration of mitochondrial structure and fatty acid \u03b2-oxidation. Our data highlight the critical role of PPAR\u03b1 at the intersection between microbial metabolism and epithelial repair in virally inflamed gut and as a potential mitochondrial target for restoring gut barriers in other infectious or gut inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1908977116","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T20:29:39Z","timestamp":1574108979000},"page":"24819-24829","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":77,"title":["PPAR\u03b1-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host\u2013microbe intersection during SIV infection"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7169-8504","authenticated-orcid":false,"given":"Katti R.","family":"Crakes","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Santos Rocha","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Grishina","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Hirao","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Napoli","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-7822","authenticated-orcid":false,"given":"Christopher A.","family":"Gaulke","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-3811","authenticated-orcid":false,"given":"Anne","family":"Fenton","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandipan","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Arredondo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Marco","sequence":"additional","affiliation":[{"name":"Department of Food Science &amp; Technology, University of California, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumathi","family":"Sankaran-Walters","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology, University of California Davis School of Medicine, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gino","family":"Cortopassi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Giulivi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616;"},{"name":"Medical Investigations of Neurodevelopmental Disorders Institute, University of California, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6346-8028","authenticated-orcid":false,"given":"Satya","family":"Dandekar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; 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