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      Genoprotective Properties and Metabolites of β-Glucan-Rich Edible Mushrooms Following Their In Vitro Fermentation by Human Faecal Microbiota

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          Abstract

          A variety of bioactive compounds, constituents of edible mushrooms, in particular β-glucans, i.e., a group of β- d-glucose polysaccharides abundant in the fungal cell walls, have been linked to immunomodulating, anticancer and prebiotic activities. The aim of the study was the investigation of the genoprotective effects of edible mushrooms produced by Pleurotus eryngii, Pleurotus ostreatus and Cyclocybe cylindracea (Basidiomycota). Mushrooms from selected strains of the species mentioned above were fermented in vitro using faecal inocula from healthy volunteers. The cytotoxic and anti-genotoxic properties of the fermentation supernatants (FSs) were investigated in Caco-2 human colon adenocarcinoma cells. The FSs were cytotoxic in a dose-dependent manner. Non-cytotoxic concentrations were used for the genotoxicity studies, which revealed that mushrooms’ FSs have the ability to protect Caco-2 cells against tert-butyl hydroperoxide ( t-BOOH), a known genotoxic agent. Their global metabolic profiling was assessed by 1H-NMR spectroscopy. A total of 37 metabolites were identified with the use of two-dimensional (2D) homo- and hetero-nuclear NMR experiments. Multivariate data analysis monitored the metabolic variability of gut microbiota and probed to biomarkers potentially associated with the health-promoting effects of edible mushrooms.

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          Concentrations of choline-containing compounds and betaine in common foods.

          Choline is important for normal membrane function, acetylcholine synthesis and methyl group metabolism; the choline requirement for humans is 550 mg/d for men (Adequate Intake). Betaine, a choline derivative, is important because of its role in the donation of methyl groups to homocysteine to form methionine. In tissues and foods, there are multiple choline compounds that contribute to total choline concentration (choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin). In this study, we collected representative food samples and analyzed the choline concentration of 145 common foods using liquid chromatography-mass spectrometry. Foods with the highest total choline concentration (mg/100 g) were: beef liver (418), chicken liver (290), eggs (251), wheat germ (152), bacon (125), dried soybeans (116) and pork (103). The foods with the highest betaine concentration (mg/100 g) were: wheat bran (1339), wheat germ (1241), spinach (645), pretzels (237), shrimp (218) and wheat bread (201). A number of epidemiologic studies have examined the relationship between dietary folic acid and cancer or heart disease. It may be helpful to also consider choline intake as a confounding factor because folate and choline methyl donation can be interchangeable.
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            The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling

            Gut microbiota provides the host with multiple functions (e.g., by contributing to food digestion, vitamin supplementation, and defense against pathogenic strains) and interacts with the host organism through both direct contact (e.g., through surface antigens) and soluble molecules, which are produced by the microbial metabolism. The existence of the so-called gut–brain axis of bi-directional communication between the gastrointestinal tract and the central nervous system (CNS) also supports a communication pathway between the gut microbiota and neural circuits of the host, including the CNS. An increasing body of evidence has shown that gut microbiota is able to modulate gut and brain functions, including the mood, cognitive functions, and behavior of humans. Nonetheless, given the extreme complexity of this communication network, its comprehension is still at its early stage. The present contribution will attempt to provide a state-of-the art description of the mechanisms by which gut microbiota can affect the gut–brain axis and the multiple cellular and molecular communication circuits (i.e., neural, immune, and humoral). In this context, special attention will be paid to the microbial strains that produce bioactive compounds and display ascertained or potential probiotic activity. Several neuroactive molecules (e.g., catecholamines, histamine, serotonin, and trace amines) will be considered, with special focus on Glu and GABA circuits, receptors, and signaling. From the basic science viewpoint, “microbial endocrinology” deals with those theories in which neurochemicals, produced by both multicellular organisms and prokaryotes (e.g., serotonin, GABA, glutamate), are considered as a common shared language that enables interkingdom communication. With regards to its application, research in this area opens the way toward the possibility of the future use of neuroactive molecule-producing probiotics as therapeutic agents for the treatment of neurogastroenteric and/or psychiatric disorders.
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              Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease

              Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. On a daily basis, however, we are exposed to one of the most abundant substrates of the enzyme trimethylamine (TMA), which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous TMA to nonodorous TMA N-oxide (TMAO), which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria (TMAU). Affected individuals cannot produce TMAO and, consequently, excrete large amounts of TMA. A dysbiosis in gut bacteria can give rise to secondary TMAU. Recently, there has been much interest in FMO3 and its catalytic product, TMAO, because TMAO has been implicated in various conditions affecting health, including cardiovascular disease, reverse cholesterol transport, and glucose and lipid homeostasis. In this review, we consider the dietary components that can give rise to TMA, the gut bacteria involved in the production of TMA from dietary precursors, the metabolic reactions by which bacteria produce and use TMA, and the enzymes that catalyze the reactions. Also included is information on bacteria that produce TMA in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the TMA/TMAO microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of TMA, the involvement of TMAO and FMO3 in disease, and the implications of the host-microbiome axis for management of TMAU.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                04 August 2020
                August 2020
                : 25
                : 15
                : 3554
                Affiliations
                [1 ]Institute of Chemical Biology, National Hellenic Research Foundation, 11634 Athens, Greece; aboulaka@ 123456eie.gr (A.B.); pchristodoulou@ 123456eie.gr (P.C.); mvlassopoulou@ 123456eie.gr (M.V.); mzervou@ 123456eie.gr (M.Z.)
                [2 ]Department of Nutrition and Dietetics, Harokopio University, 17676 Kallithea, Greece; emitsou@ 123456hua.gr (E.K.M.); gsaxami@ 123456hua.gr (G.S.); kyriacou@ 123456hua.gr (A.K.)
                [3 ]Laboratory of General and Agricultural Microbiology, Department of Crop Science, Agricultural University of Athens, 11855 Athens, Greece; georgioskoutrotsios@ 123456gmail.com (G.K.); giorgosbekiaris@ 123456yahoo.gr (G.B.); zervakis@ 123456aua.gr (G.I.Z.)
                Author notes
                [* ]Correspondence: panosg@ 123456eie.gr (P.G.); vpletsa@ 123456eie.gr (V.P.); Tel.: +30-2107273733 (P.G.); +30-2107273754 (V.P.)
                Author information
                https://orcid.org/0000-0002-8685-7632
                https://orcid.org/0000-0002-2892-098X
                https://orcid.org/0000-0001-5963-4954
                Article
                molecules-25-03554
                10.3390/molecules25153554
                7435999
                32759726
                be466b5e-1e28-4072-a55d-f9935dbdf02b
                © 2020 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
                : 07 July 2020
                : 02 August 2020
                Categories
                Article

                edible mushrooms,β-glucans,faecal microbiota,in vitro fermentation,genoprotection,nmr-based metabolomics

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