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      The Intestinal Fate of Citrus Flavanones and Their Effects on Gastrointestinal Health

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          Abstract

          Citrus flavanones, with hesperidin and naringin as the most abundant representatives, have various beneficial effects, including anti-oxidative and anti-inflammatory activities. Evidence also indicates that they may impact the intestinal microbiome and are metabolized by the microbiota as well, thereby affecting their bioavailability. In this review, we provide an overview on the current evidence on the intestinal fate of hesperidin and naringin, their interaction with the gut microbiota, and their effects on intestinal barrier function and intestinal inflammation. These topics will be discussed as they may contribute to gastrointestinal health in various diseases. Evidence shows that hesperidin and naringin are metabolized by intestinal bacteria, mainly in the (proximal) colon, resulting in the formation of their aglycones hesperetin and naringenin and various smaller phenolics. Studies have also shown that citrus flavanones and their metabolites are able to influence the microbiota composition and activity and exert beneficial effects on intestinal barrier function and gastrointestinal inflammation. Although the exact underlying mechanisms of action are not completely clear and more research in human subjects is needed, evidence so far suggests that citrus flavanones as well as their metabolites have the potential to contribute to improved gastrointestinal function and health.

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          Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health

          The colon is inhabited by a dense population of microorganisms, the so-called “gut microbiota,” able to ferment carbohydrates and proteins that escape absorption in the small intestine during digestion. This microbiota produces a wide range of metabolites, including short chain fatty acids (SCFA). These compounds are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids which can present straight or branched-chain conformation. Their production is influenced by the pattern of food intake and diet-mediated changes in the gut microbiota. SCFA have distinct physiological effects: they contribute to shaping the gut environment, influence the physiology of the colon, they can be used as energy sources by host cells and the intestinal microbiota and they also participate in different host-signaling mechanisms. We summarize the current knowledge about the production of SCFA, including bacterial cross-feedings interactions, and the biological properties of these metabolites with impact on the human health.
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            Phylogenetic relationships of butyrate-producing bacteria from the human gut.

            Butyrate is a preferred energy source for colonic epithelial cells and is thought to play an important role in maintaining colonic health in humans. In order to investigate the diversity and stability of butyrate-producing organisms of the colonic flora, anaerobic butyrate-producing bacteria were isolated from freshly voided human fecal samples from three healthy individuals: an infant, an adult omnivore, and an adult vegetarian. A second isolation was performed on the same three individuals 1 year later. Of a total of 313 bacterial isolates, 74 produced more than 2 mM butyrate in vitro. Butyrate-producing isolates were grouped by 16S ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism analysis. The results indicate very little overlap between the predominant ribotypes of the three subjects; furthermore, the flora of each individual changed significantly between the two isolations. Complete sequences of 16S rDNAs were determined for 24 representative strains and subjected to phylogenetic analysis. Eighty percent of the butyrate-producing isolates fell within the XIVa cluster of gram-positive bacteria as defined by M. D. Collins et al. (Int. J. Syst. Bacteriol. 44:812-826, 1994) and A. Willems et al. (Int. J. Syst. Bacteriol. 46:195-199, 1996), with the most abundant group (10 of 24 or 42%) clustering with Eubacterium rectale, Eubacterium ramulus, and Roseburia cecicola. Fifty percent of the butyrate-producing isolates were net acetate consumers during growth, suggesting that they employ the butyryl coenzyme A-acetyl coenzyme A transferase pathway for butyrate production. In contrast, only 1% of the 239 non-butyrate-producing isolates consumed acetate.
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              Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota.

              Tea is rich in polyphenols and other phenolics that have been widely reported to have beneficial health effects. However, dietary polyphenols are not completely absorbed from the gastrointestinal tract and are metabolized by the gut microflora so that they and their metabolites may accumulate to exert physiological effects. In this study, we investigated the influence of the phenolic components of a tea extract and their aromatic metabolites upon bacterial growth. Fecal homogenates containing bacteria significantly catalyzed tea phenolics, including epicatechin, catechin, 3-O-methyl gallic acid, gallic acid and caffeic acid to generate aromatic metabolites dependent on bacterial species. Different strains of intestinal bacteria had varying degrees of growth sensitivity to tea phenolics and metabolites. Growth of certain pathogenic bacteria such as Clostridium perfringens, Clostridium difficile and Bacteroides spp. was significantly repressed by tea phenolics and their derivatives, while commensal anaerobes like Clostridium spp., Bifidobacterium spp. and probiotics such as Lactobacillus sp. were less severely affected. This indicates that tea phenolics exert significant effects on the intestinal environment by modulation of the intestinal bacterial population, probably by acting as metabolic prebiotics. Our observations provide further evidence for the importance of colonic bacteria in the metabolism, absorption and potential activity of phenolics in human health and disease. The bioactivity of different phenolics may play an important role in the maintenance of gastrointestinal health.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                27 June 2019
                July 2019
                : 11
                : 7
                : 1464
                Affiliations
                [1 ]Department of Internal Medicine, Division of Gastroenterology-Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
                [2 ]BioActor BV, Gaetano Martinolaan 85, 6229 GS Maastricht, The Netherlands
                [3 ]Department of Food Technology, Safety and Health, Research Group Food Chemistry and Human Nutrition, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
                [4 ]ProDigest BVBA, Technologiepark 82, 9052 Ghent, Belgium
                Author notes
                Author information
                https://orcid.org/0000-0003-4671-7739
                Article
                nutrients-11-01464
                10.3390/nu11071464
                6683056
                31252646
                1a0208ed-98d6-406c-b76a-8d499957368b
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 June 2019
                : 24 June 2019
                Categories
                Review

                Nutrition & Dietetics
                citrus flavanones,intestinal microbiota,intestinal barrier function,intestinal inflammation,gastrointestinal health

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