Gut microbiota structure and metabolites, before and ater treatment in early rheumatoid arthritis patients. A pilot study

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. Modifications ofgut microbiota seem to be associated with the disease, but the impact of gut microbiotaon therapies’ outcome remains unclear. A role of T cells in RA pathogenesis has beenaddressed, particularly on the Th17/Treg cells balance. Our study aimed to evaluate inearly RA (ERA) patients compared to a control group, fecal gut microbiota composition,short-chain fatty acids concentrations, and the levels of circulating Th17/Treg andtheir own cytokines, before and after 3 months of standard treatment (Methotrexate(MTX) plus glucocorticoids). Fecal microbiota characterization was carried out on19 ERA patients and 20 controls matched for sex and age. Significant decreasedbiodiversity levels, and a partition on the base of the microbiota composition, betweenthe ERA patients at baseline compared to controls, were observed. The co-occurrentanalysis of interactions revealed a characteristic clustered structure of the microbialnetwork in controls that is lost in ERA patients where an altered connection betweenmicrobes and clinical parameters/metabolites has been reported. Microbial markerssuch as Acetanaerobacterium elongatum, Cristiansella massiliensis, and Gracilibacterthermotolerans resulted significantly enriched in control group while the species Blautiagnavus emerged to be more abundant in ERA patients. Our results showed an alterationin Th17/Treg balance with higher Th17 levels and lower Treg levels in ERA group respectto control at baseline, those data improved after therapy. Treatment administration andthe achievement of a low disease activity/remission appear to exert a positive pressureon the structure of intestinal microbiota with the consequent restoration of biodiversity,of the structure of microbial network, and of the abundance of taxa that became closerto those presented by the subject without the disease. We also found an associationbetween Blautia gnavus and ERA patients characterized by a significant reduction of propionic acid level. Furthermore significant differences highlighted at baseline amongcontrols and ERA patients are no more evident after treatment. These data corroboratethe role played by gut microbiota in the disease and suggest that therapy aimed torestore gut microbiota would improve treatment outcome.