Maternal Gut Dysbiosis Exacerbates Offspring Susceptibility to Collagen-Induced Arthritis in Mice
TL;DR
It is demonstrated that the maternal gut microbiota plays a critical role in the pathogenesis of autoimmune arthritis and that FMT may represent a potential therapeutic approach.
Abstract
Objective: The gut microbiota plays a critical role in immune system development and the maintenance of immune tolerance. Dysbiosis, particularly during the maternal period, has been implicated in autoimmune diseases. This study investigated whether maternal antibiotic-induced dysbiosis exacerbates collagen-induced arthritis (CIA) in offspring and whether fecal microbiota transplantation (FMT) can reverse this effect. Materials and Methods: To establish a dysbiosis model, pregnant BALB/c mice were administered a combination of amoxicillin (40 mg/kg) and vancomycin (30 mg/kg) from the last week of pregnancy until the male pups used in the experiment (n=5 per group) reached 8 weeks of age (total treatment duration, 9 weeks). In the FMT group, oral FMT was administered after completion of antibiotic therapy. The bacterial profiles of the mice gut microbiota were analyzed by sequencing, and CIA was subsequently induced in all groups. Results: Maternal dysbiosis significantly reduced bacterial populations in the gut microbiota, whereas FMT restored these populations. Additionally, dysbiosis was associated with increased arthritis severity in the CIA model, whereas FMT appeared to reduce it. These results demonstrate that the maternal gut microbiota plays a critical role in the pathogenesis of autoimmune arthritis and that FMT may represent a potential therapeutic approach. Conclusion: Maternal dysbiosis in the gut microbiota and its treatment with FMT affected body weight in mice, particularly causing low birth weight. Dysbiosis increased disease severity in the CIA model, whereas FMT treatment reduced it.