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Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases

Journal

CHEMICO-BIOLOGICAL INTERACTIONS
Volume 368, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2022.110231

Keywords

Short -chain fatty acids; Gut microbiota metabolites; Gut -lung axis; Respiratory diseases; Potential therapeutics

Funding

  1. Rebecca L Cooper Medical Research Foundation
  2. Maridulu Budyari Gumal Sydney Partnership for Health, Education, Research and Enterprise (SPHERE) RSEOH CAG Seed grant, fellowship and extension grant
  3. Faculty of Health MCR/ECR Mentorship Support Grant
  4. UTS Global Strategic Partnerships Seed Funding Scheme
  5. UTS International Research Scholarship
  6. UTS President's Scholarship
  7. Prevent Cancer Foundation (PCF)
  8. International Association for the Study of Lung Cancer (IASLC)

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The human microbiota plays a crucial role in immune system development and balance. Dysbiosis in the gut and respiratory tract is associated with immune system dysfunction and the development of lung diseases. Short-chain fatty acids (SCFAs) produced by the gut microbiota have a significant impact on the homeostasis, susceptibility, and outcome of various lung diseases.
The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated with immune system dysfunction and lung disease development. The microbiota's influence on human health and disease is exerted through the abundance of metabolites produced by resident microorganisms, where short-chain fatty acids (SCFAs) represent the fundamental class. SCFAs are mainly produced by the gut microbiota through anaerobic fermentation of dietary fibers, and are known to influence the homeostasis, susceptibility to and outcome of many lung diseases. This article explores the microbial species found in healthy human gastrointestinal and respiratory tracts. We investigate factors contributing to dysbiosis in lung illness, and the gut-lung axis and its association with lung diseases, with a particular focus on the functions and mechanistic roles of SCFAs in these processes. The key focus of this review is a discussion of the main metabolites of the intestinal microbiota that contribute to host-pathogen interactions: SCFAs, which are formed by anaerobic fermentation. These metabolites include propionate, acetate, and butyrate, and are crucial for the preservation of immune homeostasis. Evidence suggests that SCFAs prevent infections by directly affecting host immune signaling. This review covers the various and intricate ways through which SCFAs affect the immune system's response to infections, with a focus on pulmonary diseases including chronic obstructive pulmonary diseases, asthma, lung cystic fibrosis, and tuberculosis. The findings reviewed

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