Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients
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 naive 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 IFNg, 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.
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