Control of lupus nephritis by changes of gut microbiota.

Autor: Mu Q; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Zhang H; Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, VA, USA.; Present Address: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA., Liao X; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Lin K; Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, VA, USA., Liu H; Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, VA, USA.; Present Address: Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA., Edwards MR; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Ahmed SA; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Yuan R; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.; Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA., Li L; Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA., Cecere TE; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Branson DB; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Kirby JL; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Goswami P; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Leeth CM; Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA., Read KA; Virginia Tech Carilion Research Institute and School of Medicine, Roanoke, VA, USA., Oestreich KJ; Virginia Tech Carilion Research Institute and School of Medicine, Roanoke, VA, USA., Vieson MD; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA., Reilly CM; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.; Edward Via College of Osteopathic Medicine, Blacksburg, VA, USA., Luo XM; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA. xinluo@vt.edu.
Jazyk: angličtina
Zdroj: Microbiome [Microbiome] 2017 Jul 11; Vol. 5 (1), pp. 73. Date of Electronic Publication: 2017 Jul 11.
DOI: 10.1186/s40168-017-0300-8
Abstrakt: Background: 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 lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.
Databáze: MEDLINE
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