title: Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients.
abstract: Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from naïve CD4(+) lymphocytes to a greater extent than healthy control-microbiota. Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4(+) lymphocyte over-activation, thus supporting a possible therapeutic benefit of probiotics containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3(+) IL-17(+) populations, suggesting a possible Treg-Th17 trans-differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL-17(+) populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNγ, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti-dsDNA titers were increased and showed a strong negative correlation with IL-6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine.
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Asturias, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Asturias, Spain.|Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain.
authors.forename: Banesa
authors.initials: B
authors.lastname: de Paz
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Asturias, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Carrio
authors.affiliation: Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Hevia
authors.affiliation: Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: Sánchez
authors.affiliation: Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain.
authors.forename: Abelardo
authors.initials: A
authors.lastname: Margolles
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Asturias, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000368:Aged; D000069985:Bifidobacterium bifidum; D016022:Case-Control Studies; D002454:Cell Differentiation; D003013:Clostridium / Q000472:pathogenicity; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D058504:Th17 Cells / Q000166:cytology*
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020381:Interleukin-17; D015850:Interleukin-6