Diet-Microbiome Interactions Influence Lung Function in Chronic Obstructive Pulmonary Disease

Abstract

Chronic Obstructive Pulmonary Disease (COPD) affects 30 million Americans. Previous epidemiologic work has shown that diet can impact pulmonary function in those with and without COPD. Diet is also a major driver of gut microbiome composition and function. Importantly, the gut microbiome has also been associated with lung health (i.e., the gut-lung axis) in both preclinical and clinical studies. Despite this growing body of evidence, many questions remain regarding the gut-lung axis. Specifically, how the microbiome impacts the relationship between diet factors and spirometry or stage of disease in people with COPD is little understood. We hypothesize that there are taxonomic differences in the gut microbiome among the different stages of COPD and that diet microbiome interactions influence pulmonary function. This study aimed to identify how the GI microbiota correlated with the severity of respiratory disease in COPD patients and how the microbiome may mediate the relationship between diet, including fiber and omega-3 fatty acids, and lung function outcomes.

Keywords: COPD; Diet; Fiber; Lungs; Microbiome; Omega-3 Fatty Acid.

Figure 1.. Differentially abundant taxa between different COPD Gold stages.

Differentially abundant taxa at the (A) genus level and (B) order level in COPD Gold Stage 2 v 1 (left panel), COPD Gold Stage 3 v 1 (middle panel), and COPD Gold Stage 4 v 1 (right panel) using the corncob method with Benjamini-Hochberg (BH) correction for multiple comparisons. Blue lines indicate taxa that are significantly different between the compared GOLD Stages. Specifically, if the blue line is positive, then the indicated taxa is increased in GOLD Stage 2,3,4 compared to Stage 1; however, if the blue line is negative, then the indicated taxa is decreased in GOLD Stage 2,3,4 when compared to Stage 1.

Figure 2.. The GI microbial community partially mediates diet and lung function interactions in COPD subjects.

Mediation analysis was performed with dietary parameters as the exposure and lung function parameters FEV1, FVC, and FEV1 % predicted as the outcome, and community composition as the mediator using the MODIMA method. Mediation analysis was performed using FEV1 % predicted as the outcome and (A) Omega, (B) Omega-3, and (C) Omega-6 as the exposures. Mediation analysis was performed using FEV1 as the outcome and (D) Omega, (E) Omega-3, and (F) Omega-6 as the exposures. Finally, mediation analysis was performed using FVC as the outcome and (G) Fiber, (H) Omega, and (I) Omega-3 as the exposures.

Figure 3. Diet and lung function interaction in COPD subjects is partially mediated via specific bacterial taxa.

Mediation analysis was performed with dietary parameters as the exposure and lung function parameters FEV1, FVC, and FEV1 % predicted as the outcome, and individual bacterial taxa as the mediator using the CCMM method. Mediation analysis was performed using Fiber, total omega, omega-3, omega-6, and n6:n3 ratio (from top to bottom) as the dietary exposure parameters.