The Gut-Liver-Lung Axis. Modulation of the Innate Immune Response and Its Possible Role in Chronic Obstructive Pulmonary Disease

Evidence from epidemiological studies suggests that a diet high in fiber is associated with better lung function and reduced risk of chronic obstructive pulmonary disease (COPD). The mechanism for this benefit remains unknown, but, as fiber is not absorbed by the gut, this finding suggests that the gut may play an active role in pathogenic pathways underlying COPD. There is a growing awareness that aberrant activity of the innate immune system, characterized by increased neutrophil and macrophage activation, may contribute to the development or progression of COPD. Innate immunity is modulated in large part by the liver, where hepatic cells function in immune surveillance of the portal circulation, as well as providing a rich source of systemic inflammatory cytokines and immune mediators (notably, IL-6 and C-reactive protein). We believe that the beneficial effect of dietary fiber on lung function is through modulation of innate immunity and subsequent attenuation of the pulmonary response to inflammatory stimuli, most apparent in current or former smokers. We propose that the "gut-liver-lung axis" may play a modifying role in the pathogenesis of COPD. In this review, we summarize lines of evidence that include animal models, large prospective observational studies, and clinical trials, supporting the hypothesis that the gut-liver-lung axis plays an integral part in the pathogenic mechanisms underlying the pathogenesis of COPD.