High-fiber diets attenuate emphysema development via modulation of gut microbiota and metabolism

Abstract

Dietary fiber functions as a prebiotic to determine the gut microbe composition. The gut microbiota influences the metabolic functions and immune responses in human health. The gut microbiota and metabolites produced by various dietary components not only modulate immunity but also impact various organs. Although recent findings have suggested that microbial dysbiosis is associated with several respiratory diseases, including asthma, cystic fibrosis, and allergy, the role of microbiota and metabolites produced by dietary nutrients with respect to pulmonary disease remains unclear. Therefore, we explored whether the gut microbiota and metabolites produced by dietary fiber components could influence a cigarette smoking (CS)-exposed emphysema model. In this study, it was demonstrated that a high-fiber diet including non-fermentable cellulose and fermentable pectin attenuated the pathological changes associated with emphysema progression and the inflammatory response in CS-exposed emphysema mice. Moreover, we observed that different types of dietary fiber could modulate the diversity of gut microbiota and differentially impacted anabolism including the generation of short-chain fatty acids, bile acids, and sphingolipids. Overall, the results of this study indicate that high-fiber diets play a beneficial role in the gut microbiota-metabolite modulation and substantially affect CS-exposed emphysema mice. Furthermore, this study suggests the therapeutic potential of gut microbiota and metabolites from a high-fiber diet in emphysema via local and systemic inflammation inhibition, which may be useful in the development of a new COPD treatment plan.

Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae

“…Recent mouse studies have demonstrated the importance of the metabolome, including short chain fatty acid output, in susceptibility to smoking-induced pathology (15,16,35). Given the lack of butyrate production found in conventionally raised zebrafish larvae (27), we think it is unlikely that exposure to control mouse faecal microbiota produces anti-inflammatory short chain fatty acids as the protective mechanism against 1% CSE exposure compared to the pro-inflammatory CS-exposed mouse faecal microbiota.…”

“…The failure of single bacterial species that could be cultured from the guts of zebrafish to recapitulate the pro-inflammatory effects of CS-exposed mouse microbiota in the context of 1% CSE co-exposure suggest either the presence of multiple microbial species and/or other microbiota or factors present in the faecal homogenate. This was not unexpected as the aerobic conditions of the larval zebrafish gut does not facilitate sustained colonisation by some members of the mammalian microbiota (33), and recent mouse studies have demonstrated the importance of the metabolome, including short chain fatty acid output, in susceptibility to smoking-induced pathology (15, 16, 35). Given the lack of butyrate production found in conventionally raised zebrafish larvae (27), we think it is unlikely that exposure to control mouse faecal microbiota produces anti-inflammatory short chain fatty acids as the protective mechanism against 1% CSE exposure compared to the pro-inflammatory CS-exposed mouse faecal microbiota.…”

“…This is suggested to occur through alterations to the immune system (5), mucin production (6) or through direct antimicrobial effects of the toxins within the smoke (14). Shifts in gut microbiome and the profile of gut metabolites and pathology are associated with chronic obstructive pulmonary disease (COPD) in humans and CS-induced emphysema in mice (4,10,11,15,16). Microbiomes and metabolites associated with COPD and CS exacerbate lung inflammation via the gut-lung axis of shared mucosal immunity contributing to lung pathology in mammals (4,11,17).…”

Anti-Inflammatory Function of Fatty Acids and Involvement of Their Metabolites in the Resolution of Inflammation in Chronic Obstructive Pulmonary Disease

“…Patients with chronic diseases show changes in the composition of the gut microflora with an increase in the number of harmful bacteria [ 249 ]. Interestingly, the proportion of Bacteroidetes is significantly reduced in COPD, which may contribute to the course of the disease [ 250 , 251 ]. In addition, the species diversity of the intestinal microflora and the number of Bacteroides decreases in the elderly [ 252 , 253 ].…”

SARS-CoV-2 triggered excessive inflammation and abnormal energy metabolism in gut microbiota

“…Sphingolipids are progressively recognized as critical mediators in participation with inflammatory responses and multiple pulmonary diseases [66]. The biosynthesis of polyketide sugar unit and lipopolysaccharide could be related to oxidative stress state and risk of microbial translocation to systemic inflammation, respectively [67].…”