• Caroline Chong-Nguyen, Bahtiyar Yilmaz, Bernadette Coles, Harry Sokol, Andrew MacPherson, Matthias Siepe, David Reineke, Selim Mosbahi, Daijiro Tomii, Masaaki Nakase, Sarah Atighetchi, Cyril Ferro, Christoph Wingert, Christoph Gräni, Thomas Pilgrim, Stephan Windecker, Hélène Blasco, Camille Dupuy, Patrick Emond, Yara Banz, Tereza Losmanovà, Yvonne Döring, and SiontisGeorge C MGCM0000-0003-2128-9205Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland..
• Department of Cardiology, Bern University Hospital, Inselspital, Bern, Switzerland.
• Eur. J. Clin. Invest. 2025 Jan 10: e14381e14381.

BackgroundThe human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.MethodsPeer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes.ResultsThirteen studies were included in the review: five human, three animal and five in vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E. coli.ConclusionsTMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.© 2025 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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