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The latter, not only promotes the transport of nutrients, ions, and fluids from the lumen to the internal environment but is linked with the development of diseases including coronary artery disease, heart failure, and lung diseases. The exact mechanism of how the microbiota achieves crosstalk between itself and distant organs\/tissues is not clear, but factors released to other organs may play a role, like inflammatory and genetic factors, and now we highlight melatonin as a novel mediator of the gut\u2010lung crosstalk. Melatonin is present in high concentrations in the gut and the lung and has recently been linked to the pathogenesis of pulmonary hypertension (PH). In this comprehensive review of the literature, we suggest that melatonin is an important link between the gut microbiota and the development of PH (where suppressed melatonin\u2010crosstalk between the gut and lungs could promote the development of PH). More studies are needed to investigate the link between the gut microbiota, melatonin and PH. Studies could also investigate whether microbiota genes play a role in the epigenetic aspects of PH. This is relevant because, for example, dysbiosis (caused by epigenetic factors) could reduce melatonin signaling between the gut and lungs, reduce subcellular melatonin concentrations in the gut\/lungs, or reduce melatonin serum levels secondary to epigenetic factors. This area of research is largely unexplored and further studies are warranted.<\/jats:p>","DOI":"10.1002\/pul2.12277","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T04:58:10Z","timestamp":1691989090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota crosstalk mechanisms are key in pulmonary hypertension: The involvement of melatonin is instrumental too"],"prefix":"10.1002","volume":"13","author":[{"given":"Steve","family":"Jacobs","sequence":"first","affiliation":[{"name":"CARMA: Centre for Cardio\u2010Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine &amp; Health Sciences Stellenbosch University Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Payne","sequence":"additional","affiliation":[{"name":"CARMA: Centre for Cardio\u2010Metabolic 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