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      Gut microbiota-derived metabolites: implications for metabolic syndrome and therapeutic interventions

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          Abstract

          Background

          The gut microbiota (GM) and their metabolites have garnered significant attention for their roles in metabolic syndrome (MetS) and associated conditions. MetS, characterized by a cluster of metabolic abnormalities, significantly increases the risk of cardiovascular disease (CVD), obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The dysbiosis of gut microbiota, marked by changes in microbial composition and function, has been implicated in the pathogenesis of MetS.

          Main body

          This review synthesizes recent findings elucidating the influence of GM composition and microbiota-derived metabolites on MetS pathogenesis and progression. Notably, alterations in GM composition and dysregulation of metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), polyamines, amino acids, and indole derivatives have been implicated in MetS development. These metabolites play crucial roles in metabolic processes, and their imbalance can trigger or exacerbate metabolic disturbances associated with MetS. Various therapeutic approaches, including dietary interventions, probiotics, prebiotics, and precision medicine targeting specific metabolites, offer promising strategies for managing MetS. These interventions aim to restore a healthy GM balance and regulate the production of beneficial metabolites.

          Conclusion

          The complexity of GM interactions and their systemic effects necessitate more standardized research methodologies. Future investigations focusing on personalized therapeutic interventions and non-invasive diagnostic tools are warranted to address the complexities of MetS management. Advancing our understanding of the GM-metabolite-MetS axis will be crucial for developing effective, targeted treatments and improving patient outcomes in MetS.

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          Most cited references125

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          Akkermansia muciniphila -derived extracellular vesicles influence gut permeability through the regulation of tight junctions

          The gut microbiota has an important role in the gut barrier, inflammation and metabolic functions. Studies have identified a close association between the intestinal barrier and metabolic diseases, including obesity and type 2 diabetes (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial bacterium that reduces gut barrier disruption and insulin resistance. Here we evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in the regulation of gut permeability. We found that there are more AmEVs in the fecal samples of healthy controls compared with those of patients with T2D. In addition, AmEV administration enhanced tight junction function, reduced body weight gain and improved glucose tolerance in high-fat diet (HFD)-induced diabetic mice. To test the direct effect of AmEVs on human epithelial cells, cultured Caco-2 cells were treated with these vesicles. AmEVs decreased the gut permeability of lipopolysaccharide-treated Caco-2 cells, whereas Escherichia coli-derived EVs had no significant effect. Interestingly, the expression of occludin was increased by AmEV treatment. Overall, these results imply that AmEVs may act as a functional moiety for controlling gut permeability and that the regulation of intestinal barrier integrity can improve metabolic functions in HFD-fed mice.
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            Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health

            ABSTRACT Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new ‘generation’ of potentially beneficial microbes to have been recognized are members of the genus Eubacterium, who form a part of the core human gut microbiome. The genus consists of phylogenetically, and quite frequently phenotypically, diverse species, making Eubacterium a taxonomically unique and challenging genus. Several members of the genus produce butyrate, which plays a critical role in energy homeostasis, colonic motility, immunomodulation and suppression of inflammation in the gut. Eubacterium spp. also carry out bile acid and cholesterol transformations in the gut, thereby contributing to their homeostasis. Gut dysbiosis and a consequently modified representation of Eubacterium spp. in the gut, have been linked with various human disease states. This review provides an overview of Eubacterium species from a phylogenetic perspective, describes how they alter with diet and age and summarizes its association with the human gut and various health conditions.
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              Bile acids and the gut microbiota: metabolic interactions and impacts on disease

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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                The Egyptian Journal of Internal Medicine
                Egypt J Intern Med
                Springer Science and Business Media LLC
                2090-9098
                December 2024
                July 25 2024
                : 36
                : 1
                Article
                10.1186/s43162-024-00342-4
                1f4031b1-6fd4-46d3-8fea-98f9ab4ebe8e
                © 2024

                https://creativecommons.org/licenses/by/4.0

                https://creativecommons.org/licenses/by/4.0

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