Exploring the gut-lung-brain axis: Focus on endothelial dysfunction, impaired bioenergetics, and strategies to...

Dysbiosis has emerged as a major determinant in the pathogenesis of many human disorders and is a continuously expanding area of research. Identification of several microbial populations and their derived products marks an important milestone in microbiome research. Interestingly, there is evidence that gut microbiota-derived products affect distant organs such as the brain and lungs. Although the effect of gut dysbiosis on several lung- and brain-related disorders has been demonstrated, our knowledge of the mechanisms and consequences of individual microbiota-derived metabolites and products on specific cell types such as endothelial cells is still evolving. Endothelial dysfunction is a prominent feature in vascular dementia and several lung disorders. Specifically, alteration in endothelial bioenergetics is an emerging area of research. In this review, the evidence on the interconnection between dysbiosis in the gut and three lung disorders; asthma, COPD, and ARDS - is discussed. Additionally, the association between these respiratory disorders and cognitive impairment is examined with mechanistic insights. Moreover, data involving the direct impact of key microbial metabolites and their products on endothelial cells are synthesized and potential therapeutic modalities are highlighted. We identify the impact of microbial metabolites on endothelial dysfunction and bioenergetics as a potential gap in knowledge and a plausible avenue for future research.