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During tumorigenesis, abnormal hypermethylation of the cytosine in CpG islands and hypomethylation of the whole genome result in genome instability and alterations in gene expression profile, including silencing of tumor suppressor genes, endogenous retro-elements, and tumor antigens, and activation of oncogenes (Liang and Weisenberger, 2017

The abundant ROS produced by MLPGA interfered with the transcription of genes related to antioxidants, extracellular polysaccharides, iron ions related pathway, biofilm development and virulence

1 Introduction 1.1 Relationship among gut microbiota, TMA and TMAO production, and human diseases Consolidated literature from over the last 20 years confirms the relationship between intestinal microbiota and a series of diseases ( 1.2 Biochemical mechanisms of TMA production Most of the TMA is synthesized in the intestine (colon) by the action of some anaerobic commensal gut bacteria containing choline- (or carnitine-) TMA lyase, an enzyme consisting of two units: a catalytic unit (CutC) and its activating enzyme (CutD) ( etc .), betaine, and L-carnitine and its metabolite -butyrobetaine (GBB), releasing TMA after the cleavage of the carbon (C)nitrogen (N) bond of choline/carnitine ( 1.3 Trimethylaminuria (TMAU): etiology, psychosocial impact, and incidence Trimethylaminuria (TMAU) is caused by TMA accumulation

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