Cerebral ischaemic stroke results in altered mucosal antibody responses and host-commensal microbiota interactions.

Stroke is a devastating neurological event with a high risk of mortality that results in long-term sequalae that extend beyond the central nervous system. Notably these include gastrointestinal dysfunction and altered composition of the commensal microbiota in both patients and mouse models, which have been suggested to contribute to secondary infection and poor clinical outcomes following stroke. Strikingly, changes in commensal microbial community composition occur rapidly following stroke and correlate with disease severity. Despite these observations, the underpinning mechanisms that drive perturbation of the microbiota post-stroke remain poorly understood. The gastrointestinal tract is home to a complex network of tissue-resident immune cells that maintain homeostatic interactions with commensal microbes and prevent bacterial-driven inflammation. Here we demonstrate mice subjected to ischaemic stroke exhibit alterations in the intestinal immune system, most notably in class switched germinal centre B cells and the production of Immunoglobulin A (IgA) - a major effector response against commensal microbes. Mice lacking secretory antibodies, including IgA, exhibited a partial reversion of stroke-induced changes in microbiota composition. Together these findings demonstrate stroke is associated with dysregulation of antibody producing immune responses, which may in part explain changes in the intestinal microbiota. A mechanistic understanding of the immunological basis of stroke-associated pathologies in the periphery may open new avenues to manage the secondary complications and long-term prognosis of patients suffering from neurological disease.