Effect of early-life gut microbiota on immune responses in a mouse model of multiple sclerosis

Multiple Sclerosis (MS) patients have distinct gut microbiota composition compared to healthy controls, and studies have highlighted the ability of various microbiota perturbations to exacerbate or ameliorate experimental autoimmune encephalomyelitis (EAE), an animal model of the disease. Accumulating evidence also suggests that the immune responses to gut microbiota are heavily influenced by early-life microbiota and its interactions with the developing immune system. Thus, we aimed to determine how early-life microbiota can modulate host immunity later in life and modulate susceptibility to EAE. We administered broad spectrum antibiotics during the weaning period to deplete gut microbiota and subsequently re-colonized antibiotic exposed mice. Mice exposed to antibiotics in early life exhibited significant changes in ileal lamina propria immune populations in adulthood compared to conventionally raised mice. Antibiotic-exposed mice also showed an increase in pro-inflammatory cytokine production from small intestinal CD11c+ dendritic cells (DCs) later in life. These changes also preceded higher EAE severity in antibiotic exposed mice. Post EAE induction, splenic DCs from antibiotic-treated mice increased the proliferation of autoreactive CD4+ T cells. Thus, our study highlights the critical role of early-life gut microbiota in shaping host immune responses and provides evidence that early-life gut microbiota perturbations can modulate the autoimmune response to EAE induction.