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The failure of immunomodulatory mechanisms to regulate this inflammation further exacerbates the condition ( 3 Microbial-host interplay in TMAO synthesis and metabolism TMAO originates from dietary precursors metabolized through a tightly coordinated interplay between gut microbiota and host hepatic enzymes ( 3.1 Gut microbiota: primary producers of trimethylamine Gut microbiota, particularly Firmicutes and Proteobacteria , are key mediators of TMA production through distinct enzymatic pathways ( Firmicutes , Actinobacteria , and Proteobacteria utilize the CutC/D enzyme system to cleave cholineabundant in eggs, meat, and fish ( Bacteroidetes ( Proteobacteria and some Firmicutes via the CntA/B system ( Gammaproteobacteria ( Burkholderia through ergothionease to generate TMA ( Different gut microbes vary in their ability to generate TMA

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These findings were supported by a cohort of 29 HCC patients, where selenium levels had an inverse correlation with VEGF and IL-8 (113)