Unravelling the gut-lung axis: insights into microbiome interactions and Traditional Indian Medicine's perspective on optimal health

Abstract

The microbiome of the human gut is a complex assemblage of microorganisms that are in a symbiotic relationship with one another and profoundly influence every aspect of human health. According to converging evidence, the human gut is a nodal point for the physiological performance matrixes of the vital organs on several axes (i.e. gut-brain, gut-lung, etc). As a result of COVID-19, the importance of gut-lung dysbiosis (balance or imbalance) has been realised. In view of this, it is of utmost importance to develop a comprehensive understanding of the microbiome, as well as its dysbiosis. In this review, we provide an overview of the gut-lung axial microbiome and its importance in maintaining optimal health. Human populations have successfully adapted to geophysical conditions through traditional dietary practices from around the world. In this context, a section has been devoted to the traditional Indian system of medicine and its theories and practices regarding the maintenance of optimally customized gut health.

Keywords: COVID-19; Gut-lung axis; dysbiosis; microbiome; traditional medicine.

Figure 1.

Microbial composition among the physiological niches of the human respiratory and gastrointestinal tracts. The most abundant bacteria within the niches are denoted in blue text, the most abundant fungi in green, and the most abundant archaea in orange. Please note, the numbers presented in this figure represent the abundance of bacterial members in the human gastrointestinal and respiratory tracts. The focus of this figure is primarily on bacteria due to the limited knowledge available regarding the specific abundance of fungi and archaea in the human gastrointestinal tract. Created with BioRender.com.

Figure 2.

Schematic representation illustrating the concept of cross-talk between the gut and lung in the context of the human gut-lung axis. SFB: segmented filamentous bacteria, Ag: antigen, ILC: innate lymphoid cells, IFN: interferon, IEC: intestinal epithelial cells. Please note, this figure is not intended to provide an anatomically accurate depiction of the organs or their precise spatial arrangement. Rather, it serves to visually demonstrate the communication and interactions between these systems. The figure highlights the interplay between the gut and lung and their potential influence on each other's microbiomes. Please note that the spatial relationships and anatomical details are simplified for conceptual clarity. This figure is intended to support the discussion on the role of traditional medicines in managing the gut-lung axis, rather than providing detailed anatomical information. Created with BioRender.com.

Figure 3.

Molecular links between gut microbiota and host health in healthy and dysbiotic state. In a healthy gut, intestinal epithelial cells (IECs) utilise butyrate through mitochondrial beta-oxidation, maintaining an anaerobic environment. Butyrate binds to peroxisome proliferator-activated receptor gamma (PPARγ), reducing inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. G-protein-coupled receptor (GPR)109 serves as a major receptor for butyrate. In dysbiosis, low butyrate levels decrease PPARγ activity, increase glycolysis, and elevate iNOS expression, leading to an increased NO production and nitrates. Butyrate stimulates immune cells, like regulatory T cells (T_reg), through GPR109, exerting anti-inflammatory effects. Reduced aryl hydrocarbon receptor (AhR) activity disrupts gut barrier function. short-chain fatty acids (SCFAs: butyrate, propionate and acetate), endocannabinoids, and bile acids activate receptors on L-cells and IECs, promoting gut peptide secretion. SCFAs activate GPR41 and GPR43 on L-cells, promoting secretion of gut peptides including glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY). Endocannabinoids interact with cannabinoid receptors type 1 (CB1), CB2, PPARα, PPARγ, and transient receptor potential vanilloid type-1 (TRPV1) receptors, while bile acids activate farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) receptors. Gut pattern recognition receptors such as toll-like receptors (TLRs) detect pathogen-associated molecular patterns (PAMPs) and lipopolysaccharides (LPS) from the microbiota. These interactions reduce intestinal permeability, enhance insulin sensitivity and secretion, decrease food intake, lower plasma lipids, and mitigate hepatic steatosis and endotoxemia risk, associated with reduced inflammation. Dysbiosis leads to opposite effects. Overall, interactions among gut microbiota, IECs, immune cells, and molecular receptors maintain gut homeostasis and impact metabolism and inflammation. Created with BioRender.com.

Figure 4.

The microbiome-immune proteins-cellular interaction in the lungs. Created with BioRender.com.