Homocysteine, Nutrition, and Gut Microbiota: A Comprehensive Review of Current Evidence and Insights

: Homocysteine, a sulfur-containing amino acid, is an intermediate product during the metabolism of methionine, a vital amino acid. An elevated concentration of homocysteine in the plasma, named hyperhomocysteinemia, has been significantly related to the onset of several diseases, including diabetes, multiple sclerosis, osteoporosis, cancer, and neurodegenerative disorders such as dementia, Alzheimer's and Parkinson's diseases. An interaction between metabolic pathways of homocysteine and gut microbiota has been reported, and specific microbial signatures have been found in individuals experiencing hyperhomocysteinemia. Furthermore, some evidence suggests that gut microbial modulation may exert an influence on homocysteine levels and related disease progression. Conventional approaches for managing hyperhomocysteinemia typically involve dietary interventions alongside the administration of supplements such as B vitamins and betaine. The present review aims to synthesize recent advancements in understanding interventions targeted at mitigating hyperhomocysteinemia, with a particular emphasis on the role of gut microbiota in these strategies. The emerging therapeutic potential of gut microbiota has been reported for several diseases. Indeed, a better understanding of the complex interaction between microbial species and homocysteine metabolism may help in finding novel therapeutic strategies to counteract hyperhomocysteinemia.