Gut microbiome functionality might be associated with exercise tolerance and recurrence of resected early-stage lung cancer patients

Brenda A Wilson,Glen J Weiss,Edit Dulka,Virag Hollosi,Gianni Panagiotou,Gabriella Galffy,Janos Varga,Andrea Marfil-Sánchez,Balazs Dome,Zsolt Megyesfalvi,Bastian Seelbinder,Yueqiong Ni,Judit Berta,Zoltan Lohinai

doi:10.1371/journal.pone.0259898

Abstract

Impaired exercise tolerance and lung function is a marker for increased mortality in lung cancer patients undergoing lung resection surgery. Recent data suggest that the gut-lung axis regulates systemic metabolic and immune functions, and microbiota might alter exercise tolerance. Here, we aimed to evaluate the associations between gut microbiota and outcomes in lung cancer patients who underwent lung resection surgery. We analysed stool samples, from 15 early-stage lung cancer patients, collected before and after surgical resection using shotgun metagenomic and Internal Transcribed Spacer (ITS) sequencing. We analysed microbiome and mycobiome associations with post-surgery lung function and cardiopulmonary exercise testing (CPET) to assess the maximum level of work achieved. There was a significant difference, between pre- and post-surgical resection samples, in microbial community functional profiles and several species from Alistipes and Bacteroides genus, associated with the production of SCFAs, increased significantly in abundance. Interestingly, an increase in VO2 coincides with an increase in certain species and the "GABA shunt" pathway, suggesting that treatment outcome might improve by enriching butyrate-producing species. Here, we revealed associations between specific gut bacteria, fungi, and their metabolic pathways with the recovery of lung function and exercise capacity.

Highlights

The ethology or progression of lung cancer has been linked to numerous factors, including the gut microflora [1]
Barton et al [9] showed that athletes have greater faecal short-chain fatty acid (SCFA) concentrations and altered abundance of bacterial pathways related to the biosynthesis of amino acids and the metabolism of carbohydrates
There were no significant changes in bacterial species alpha diversity over time (Shannon P = 0.98, Simpson P = 0.56, Chao1 P = 0.53; Wilcoxon signed-rank test) (Fig 1A)

Summary

Introduction

The ethology or progression of lung cancer has been linked to numerous factors, including the gut microflora [1]. Butyrate is a short-chain fatty acid (SCFA) that can regulate proliferation of epithelial cells in the gut, improve the integrity of the gut barrier, and alter the immune system and gene expression of the host [6]. A decrease in the abundance of Firmicutes has been repeatedly reported in lung cancer patients [2, 7] and has been previously associated with dysbiosis of gut metabolism, resulting in lower SCFAs concentration [2]. Others found that exercise training can alter the gut microbiota, at the taxonomic and functional level, in obese and non-obese humans [10] and reduce the expression of genes associated to metabolism of fructose and amino acids [11]. Others showed that physical activity decreases the risk for colorectal cancer by 24% [15]

Objectives

Methods

Results

Conclusion