Control of lupus nephritis by changes of gut microbiota

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dc.contributor.authorMu, Qinghuien
dc.contributor.authorZhang, Husenen
dc.contributor.authorLiao, Xiaofengen
dc.contributor.authorLin, Kaisenen
dc.contributor.authorLiu, Hualanen
dc.contributor.authorEdwards, Michael R.en
dc.contributor.authorAhmed, Sattar Ansaren
dc.contributor.authorYuan, Ruoxien
dc.contributor.authorLi, Liwuen
dc.contributor.authorCecere, Thomas E.en
dc.contributor.authorBranson, David B.en
dc.contributor.authorKirby, Jay L.en
dc.contributor.authorGoswami, Poornaen
dc.contributor.authorLeeth, Caroline M.en
dc.contributor.authorRead, Kaitlin A.en
dc.contributor.authorOestreich, Kenneth J.en
dc.contributor.authorVieson, Miranda D.en
dc.contributor.authorReilly, Christopher M.en
dc.contributor.authorLuo, Xin M.en
dc.date.accessioned2017-07-28T18:39:24Zen
dc.date.available2017-07-28T18:39:24Zen
dc.date.issued2017-07-11en
dc.description.abstractBackground: Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Results: Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a “leaky” gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. Conclusions: This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupusassociated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.orcidLeeth, CM [0000-0002-5909-7623]en
dc.identifier.orcidLuo, XM [0000-0002-2809-5836]en
dc.identifier.urihttp://hdl.handle.net/10919/78465en
dc.language.isoenen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000405193600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderThe Author(s)en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMicrobiologyen
dc.subjectGut microbiotaen
dc.subjectLupusen
dc.subjectLeaky guten
dc.subjectAutoimmunityen
dc.subjectINTESTINAL ALKALINE-PHOSPHATASEen
dc.subjectIMMUNE-COMPLEXESen
dc.subjectNZB/W MICEen
dc.subjectCELLSen
dc.subjectAUTOIMMUNITYen
dc.subjectLIPOPOLYSACCHARIDEen
dc.subjectDIFFERENTIATIONen
dc.subjectBACTERIAen
dc.subjectDISEASEen
dc.subjectERYTHEMATOSUSen
dc.titleControl of lupus nephritis by changes of gut microbiotaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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