Impaired systemic antibody response against gut microbiota pathobionts in critical illness and susceptibility to nosocomial infections.

backgroundCritically ill patients in intensive care units (ICUs) experience high rates of hospital-acquired (nosocomial) infections, commonly caused by translocation and dissemination of pathogenic microorganisms that colonize the intestinal tract (pathobionts). Multiple immune barriers protect the host against commensal and pathogenic colonizers, including a repertoire of circulating anti-commensal antibodies. The integrity of this systemic antibody-mediated defense system, its relationship with gut microbiota dysbiosis, and its impact on nosocomial infections in the ICU have not been explored.

resultsWe performed a longitudinal cohort study of 46 critically ill patients at day 1 and day 3 of their ICU admission compared to 28 healthy volunteer controls. Circulating IgM, IgG, and IgA responses against 10 common gut and extra-intestinal pathobionts were quantified by flow cytometry, together with high-dimensional analyses of circulating B cell populations, fecal microbiota composition, and clinical outcomes. We observed reduced plasma IgM and IgG reactivity against intestinal pathobionts such as Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis in ICU patients compared to healthy volunteers. Reduced gut pathobiont antibody responses in ICU patients was associated with B cell lymphopenia, and patients with gut microbiota dysbiosis had reduced levels of natural antibody producing B1-like B cells. Reduced IgG and IgM reactivity against gut Gram-negative pathobionts was associated with an increased risk of nosocomial infection or death.

conclusionsThese findings indicate that the systemic antibody barrier against microbiota pathobionts is compromised in critical illness and associated with increased risk of nosocomial infections.