Intestinal host-microbe interactions fuel pulmonary inflammation in cigarette smoke exposed mice

The gut microbiota has been implicated in numerous aspects of host health and immune regulation. Specifically, recent studies have linked gut microbes to the pathogenesis of chronic obstructive pulmonary disease (COPD), primarily induced by excessive cigarette smoke, although the underlying mechanisms remain elusive. Here, we investigated the role of gastrointestinal (GI) host-microbe interactions on pulmonary health. Using two distinct means of modulating GI host-microbe relations, we dissected how gut microbes fuel pulmonary inflammation in mouse models of cigarette smoke (CS)-induced lung disease. We found that CS caused profound changes to the colonic mucosa, with reduced mucus and increased bacterial encroachment. Modulating host-microbe interactions using antibiotics and recombinant human β-defensin 2 restricted colonic bacterial encroachment, limiting interactions between host and microbe. These strategies resulted in substantial ~50% decrease in pulmonary neutrophil infiltration following both acute and chronic exposure to CS. The reported findings provide additional evidence of a gut-lung axis, offering novel insight into the role of the gut microbiota in pulmonary immune activation, which could represent a novel avenue for future therapeutic strategies.