{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:43:26Z","timestamp":1777045406957,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Trimethylaminuria (TMAU), also known as \u201cfish-odor syndrome,\u201d is a rare metabolic disorder characterized by a body malodor that smells like a decaying fish. This syndrome is caused by a FMO3 liver enzyme malfunction, leading to trimethylamine (TMA) accumulation. To date, there is no definitive therapeutic treatment but only palliative care for TMAU, such as a controlled diet, taking antibiotics, or using acidic soaps to capture sweat-released TMA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we describe an innovative approach for the treatment of this disorder, where the use of postbiotics\/tyndallized probiotics is able to effectively inhibit the bacterial TMA lyase present, thus preventing the formation of TMA. We obtained a preparation (a mixture of tyndallized probiotics and their postbiotics) that was derived from the fermentation of <jats:italic>Lacticaseibacillus paracasei<\/jats:italic> in the presence of garlic extract and senna leaf. This preparation was used in <jats:italic>in vitro<\/jats:italic> assays on human fecal slurry while monitoring the levels of TMA released over time, and it was also tested <jats:italic>in vivo<\/jats:italic> in both <jats:italic>Mus musculus<\/jats:italic> C57BL\/6 (FMO3<jats:sup>+\/+<\/jats:sup>) strain WT and C57BL\/6<jats:sup>-Fmo3em1Smoc<\/jats:sup> (KO) mouse models to measure the trimethylamine N-oxide (TMAO) and TMA levels in the blood and urine, along with gut microbiota analysis in feces via next-generation sequencing (NGS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>L. paracasei<\/jats:italic> fermentation yielded 4.1 \u00d7 10<jats:sup>12<\/jats:sup>\u00a0CFU\/g lyophilized powder. <jats:italic>In vitro<\/jats:italic> assays involving fecal slurries supplemented with the fermentation product demonstrated a reduction in TMA levels, and the NGS analysis revealed that <jats:italic>Collinsella<\/jats:italic>, <jats:italic>Clostridium<\/jats:italic>, and <jats:italic>Streptococcus<\/jats:italic> were the most common bacterial genera that produced TMA. The <jats:italic>in vivo<\/jats:italic> study showed a significant reduction in TMAO levels in C57BL\/6(FMO3<jats:sup>+\/+<\/jats:sup>) strain WT mouse models and in TMA levels in C57BL\/6<jats:sup>-Fmo3em1Smoc<\/jats:sup> (KO) mouse models. In addition, bacteria belonging to the TMA-producing genera were still present after treatment with the tested compounds, excluding their bactericidal action. The postbiotics obtained may find a useful therapeutic application both in the prevention of cardiovascular events and as valid supports to reduce TMA production in TMAU patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1591825","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T05:41:58Z","timestamp":1759902118000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A mixture of postbiotics\/tyndallized probiotics reduces trimethylamine (TMA) in trimethylaminuria models: Evidence from in vitro and in vivo studies"],"prefix":"10.3389","volume":"16","author":[{"given":"Giuseppe","family":"Giannini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Soldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Elli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Sagheddu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Castagnetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Viciani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Salvini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Battistuzzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinando Maria","family":"Milazzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Alibrandi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonina","family":"Sidoti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7045","DOI":"10.3390\/molecules26227045","article-title":"Adaptive modelling of mutated FMO3 enzyme could unveil unexplored scenarios linking variant haplotypes to TMAU phenotypes","volume":"26","author":"Alibrandi","year":"2021","journal-title":"Molecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/bs.mie.2018.04.012","article-title":"Purification and characterization of the choline trimethylamine-lyase (CutC)-Activating protein CutD","volume":"606","author":"Bodea","year":"2018","journal-title":"Methods Enzymol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"711055","DOI":"10.3389\/fcimb.2021.711055","article-title":"Procedures for fecal microbiota transplantation in murine microbiome studies","volume":"11","author":"Bokoliya","year":"2021","journal-title":"Front. 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