Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

Abstract

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut−lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut−lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

Respiratory diseases and gut microbiota: relevance, pathogenesis, and treatment

“…They are produced by fermenting dietary fiber with beneficial gut bacteria and play a vital role in energy metabolism, intestinal barrier integrity, immune function, and overall inflammation regulation. SCFA metabolism disorders are also closely related to the occurrence of allergic inflammation, asthma, and other respiratory diseases (Verma et al, 2024 ). Butyric acid, as one of the main members of short-chain fatty acids, has been shown to play an important role in different aspects of lung diseases such as allergic asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis (Kabel et al, 2016 ; Yip et al, 2021 ).…”