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      Therapeutic Potential of Gut Microbiota and Its Metabolite Short-Chain Fatty Acids in Neonatal Necrotizing Enterocolitis

      Life
      MDPI AG

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          Abstract

          Short chain fatty acids (SCFAs), the principle end-products produced by the anaerobic gut microbial fermentation of complex carbohydrates (CHO) in the colon perform beneficial roles in metabolic health. Butyrate, acetate and propionate are the main SCFA metabolites, which maintain gut homeostasis and host immune responses, enhance gut barrier integrity and reduce gut inflammation via a range of epigenetic modifications in DNA/histone methylation underlying these effects. The infant gut microbiota composition is characterized by higher abundances of SCFA-producing bacteria. A large number of in vitro/vivo studies have demonstrated the therapeutic implications of SCFA-producing bacteria in infant inflammatory diseases, such as obesity and asthma, but the application of gut microbiota and its metabolite SCFAs to necrotizing enterocolitis (NEC), an acute inflammatory necrosis of the distal small intestine/colon affecting premature newborns, is scarce. Indeed, the beneficial health effects attributed to SCFAs and SCFA-producing bacteria in neonatal NEC are still to be understood. Thus, this literature review aims to summarize the available evidence on the therapeutic potential of gut microbiota and its metabolite SCFAs in neonatal NEC using the PubMed/MEDLINE database.

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          Most cited references146

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          From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

          A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.
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            The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism.

            Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.
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              Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

              The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                LBSIB7
                Life
                Life
                MDPI AG
                2075-1729
                February 2023
                February 16 2023
                : 13
                : 2
                : 561
                Article
                10.3390/life13020561
                36836917
                940aff66-e162-4b2b-9807-8a00ea066050
                © 2023

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

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