Diet, Microbiota and Gut-Lung Connection

Abstract

The gut microbial community (Gut microbiota) is known to impact metabolic functions as well as immune responses in our body. Diet plays an important role in determining the composition of the gut microbiota. Gut microbes help in assimilating dietary nutrients which are indigestible by humans. The metabolites produced by them not only modulate gastro-intestinal immunity, but also impact distal organs like lung and brain. Micro-aspiration of gut bacteria or movement of sensitized immune cells through lymph or bloodstream can also influence immune response of other organs. Dysbiosis in gut microbiota has been implicated in several lung diseases, including allergy, asthma and cystic fibrosis. The bi-directional cross-talk between gut and lung (termed as Gut-Lung axis) is best exemplified by intestinal disturbances observed in lung diseases. Some of the existing probiotics show beneficial effects on lung health. A deeper understanding of the gut microbiome which comprises of all the genetic material within the gut microbiota and its role in respiratory disorders is likely to help in designing appropriate probiotic cocktails for therapeutic applications.

Th9 cells in allergic diseases: A role for the microbiota?

“…The composition of the gut microbiota is developing already in early life but it is dynamic and shaped by both genetic and non‐genetic factors . Previous research indicated strong associations between host immunity and the composition of the microbiota, not only in the gut, but also in organs such as the lung and skin . This connection between microbiota and immunity was already suggested by the ‘hygiene hypothesis’, which described early life infections and microbe encounters as important to balance the Th1 and Th2 cell responses and consequently to prevent allergy development .…”

“…45,46 Previous research indicated strong associations between host immunity and the composition of the microbiota, not only in the gut, but also in organs such as the lung and skin. 46,47 This connection between microbiota and immunity was already suggested by the 'hygiene hypothesis', which described early life infections and microbe encounters as important to balance the Th1 and Th2 cell responses and consequently to prevent allergy development. 46,48 Nowadays, CD4 T cells are considered to have high plasticity, being able to switch between subtypes and functional capacity depending on received environmental triggers.…”

“…However, evidence is accumulating that effects of gut‐derived microbial factors are not limited to the gut microenvironment, but also signals to immune cells in other organs such as the lung and brain, via the so‐called gut‐lung and gut‐brain axes. These broad effects might be mediated by the release of gut‐derived microbial and dietary factors, such as short‐chain fatty acids (SCFAs), into the circulation, or due to traffic of gut‐derived activated T cells towards other compartments of the body . Consequently, the gut microbiota might influence the immune system in the entire organism.…”

The role of innate immunity in asthma development and protection: Lessons from the environment

“…G‐protein‐coupled receptors (GPCRs or GPRs), particularly GPR41 (FFAR3), GPR43 (FFAR2) and GPR109A located on innate immune cells, play an important role in immune modulation by binding microbial short‐chain fatty acids (SCFA) such as acetate, propionate and butyrate. These small molecules are produced by anaerobic bacteria in the gut as metabolic byproducts of dietary fibre fermentation and can either stimulate innate immunity in the gut directly or enter the blood stream, in both cases eliciting systemic effects that extend to the lung—a critical scenario effectively captured by the recently developed notion of a gut‐lung axis . Mechanistically, SCFAs bind to GPR41 and GPR43, which induce immune regulation and suppress airway inflammation by promoting the expansion of colonic Tregs or influencing hematopoiesis and the function of DCs recruited to the lung .…”

“…These small molecules are produced by anaerobic bacteria in the gut as metabolic byproducts of dietary fibre fermentation and can either stimulate innate immunity in the gut directly or enter the blood stream, in both cases eliciting systemic effects that extend to the lung-a critical scenario effectively captured by the recently developed notion of a gut-lung axis. 109 Mechanistically, SCFAs bind to GPR41 and GPR43, which induce immune regulation and suppress airway inflammation by promoting the expansion of colonic Tregs 108,110 or influencing hematopoiesis and the function of DCs recruited to the lung. 105 For instance, despite an absence of SCFAs in the lungs of HDM-sensitized and challenged mice, systemic levels of propionate enhanced the development of DCs impaired in their ability to activate a Th2 immune response.…”