Critically ill patients in intensive care units (ICUs) experience high rates of 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. We observed markedly impaired 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 against gut Gram-negative pathobionts was associated with an increased risk of nosocomial infection or death. These findings indicate that the systemic antibody barrier against microbiota pathobionts is compromised in critical illness and associated with increased risk of nosocomial infections, identifying a potential role for therapeutic antibody supplementation to prevent infections in the ICU.

The authors have declared no competing interest.

This study was funded by the Canadian Institutes of Health Research (CIHR) and Canadian Foundation for Innovation JR Evans Leaders Fund Grant.

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Health research ethics boards of the University of Calgary and Alberta Health Services gave ethical approval for this work (REB18-1294).

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Microbiome DNA sequence datasets available in the NCBI Sequence Read Archive under BioProject ID PRJNA851469. Additional datasets and code are available from the corresponding author upon reasonable request.