It has been previously reported that systemic lupus erythematosus (SLE) patients show intestinal ‘dysbiosis’, characterized by a reduced Firmicutes/Bacteroidetes ratio. The overall bacterial load and diversity is similar between those with SLE and controls.
A new study, led by Dr. Ana Suárez from the Department of Functional Biology at Faculty of Medicine in the University of Oviedo (Asturias, Spain), has found that intestinal microbiota changes promote a pro-inflammatory environment in SLE patients.
The researchers investigated the influence of faecal microbiota obtained from SLE patients and healthy controls in in vitro differentiation of regulatory T cells (Treg) as well as Th1 and Th17 effector cells from naïve CD4+ T lymphocytes (T helper-Th- cells). Th17 cells act as primary drivers of autoimmune and inflammatory responses and are involved in local inflammation and tissue destruction in SLE. Microbiota isolated from SLE patients’ stool samples induced lymphocyte activation and Th17 cell differentiation to a greater extent than those from healthy controls. Specifically, there was an increased frequency of Th17 cells in SLE patients with anti-double stranded DNA antibodies, whereas no significant differences were observed in the Th1 subset. In addition, it has been found that enriching SLE gut microbiota with two Clostridia strains (Ruminococcus obeum DSM25238 and Blautia coccoides DSM935) along with Bifidobacterium bifidum LMG13195, which have a Treg-inducing function, reduced the Th17/Th1 balance and prevented Th over-activation. This contributed to preventing excessive inflammation and restoring the Treg/Th17/Th1 imbalance present in SLE. These results suggest that rescuing gut microbiota with specific Treg-inducer bacterial strains seem to improve patients’ inflammatory profile.
Researchers in this study also assessed the relationship between several immune parameters and SLE-associated gut ‘dysbiosis’. Peripheral blood samples were obtained in 37 SLE patients and 36 healthy controls (HC) for immune analysis and 20 SLE patients and 20 HC were included in the intestinal microbiota analysis. In SLE patients there was a positive correlation between Firmicutes (and Firmicutes to Bacteroidetes ratio) with serum levels of interferon gamma (IFN-g), whereas there was a negative correlation between IL-17 producing cells and Firmicutes in HC.
Finally, the team found a negative correlation between the frequency of Synergistetes, a little known intestinal bacterium, and both the titer of anti-double stranded DNA antibodies (anti-ds DNA antibiodies: a specific marker for SLE) and serum levels of IL-6 (a proinflammatory cytokine increased in SLE) in SLE patients. These results suggest a possible relationship between this bacterial group and disease activity or antibody production. Both the amount of total IgM and IgM antibodies that recognize phosphorylcholine (PC) (anti-PC IgM antibodies), which are natural protective antibodies against inflammatory pathways in autoimmunity and atherosclerosis, were positively correlated with the proportion of Synergistetes, whereas serum levels of IL-6 showed a negative association. These results point out a possible role of intestinal Synergistetes in the generation of natural protective anti-PC IgM antibodies, which could be of relevance in SLE patients with high IL-6 and/or anti-dsDNA levels since they present with a low frequency of these bacteria.
In conclusion, intestinal ‘dysbiosis’ in SLE patients could enhance lymphocyte activation and Th17 differentiation, therefore contributing to patients’ local inflammation and tissue destruction. Supplementing with beneficial bacterial strains may rescue intestinal dysbiosis and its associated over-activated immune responses through inducing the production of Treg cells. Intestinal Synergistetes may have a protective role in SLE patients by inducing natural protective anti-PC IgM antibodies.
López P, de Paz B, Rodríguez-Carrio J, et al. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep. 2016; 6:24072. doi:10.1038/srep24072.