Butyrate-producing gut bacterium Faecalibacterium prausnitzii protects against bacterial pneumonia.

Abstract

BACKGROUND Gut microbiota play a protective role against pneumonia in mice, probably by producing the immunomodulatory short-chain fatty acid butyrate. Yet, butyrate has limited potential for clinical use due to its challenging handling in practice. We performed mouse experiments and translational analyses to determine whether butyrate-producing gut commensals, Faecalibacterium prausnitzii and Anaerobutyricum soehngenii, could provide protection against bacterial pneumonia and serve as next-generation probiotic. METHODS We pretreated C57BL/6J mice with butyrate, F. prausnitzii or A. soehngenii, and subsequently infected them intranasally with Klebsiella pneumoniae. To assess the relevance in humans, we assessed associations between rectal levels of Faecalibacterium, immune responses, and clinical outcomes in 115 patients with community-acquired pneumonia (CAP), and in a separate validation cohort. RESULTS Pretreatment with F. prausnitzii, but not A. soehngenii, protected mice against bacterial pneumonia, as reflected by reduced bacterial growth and dissemination, lessened organ damage and dampened inflammation. Similar to butyrate pretreatment, F. prausnitzii resulted in reduced pulmonary IL-6 and CXCL-1. In humans, gut Faecalibacterium was decreased during CAP compared to matched controls. CAP patients with higher gut Faecalibacterium levels had lower IL-6-producing capacity and downregulated inflammatory gene expression. Higher intestinal Faecalibacterium levels were associated with better clinical outcomes in independent cohorts of CAP and critically ill patients, which remained significant when controlled for potential confounders. CONCLUSION This is the first study showing that the gut commensal Faecalibacterium prausnitzii provides protection against bacterial pneumonia and has translational potential. This motivates future studies investigating the clinical potential of F. prausnitzii as novel probiotic for pneumonia.