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      Preventive Effects and Mechanisms of Garlic on Dyslipidemia and Gut Microbiome Dysbiosis

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          Abstract

          Garlic ( Allium sativum L.) contains prebiotic components, fructans, antibacterial compounds, and organosulfur compounds. The complex ingredients of garlic seem to impart a paradoxical result on the gut microbiome. In this study, we used a mouse model to clarify the effects of whole garlic on the gut microbiome. C57BL/6N male mice were fed with or without whole garlic in normal diet (ND) or in high-fat diet (HFD) for 12 weeks. Supplementation with whole garlic attenuated HFD-enhanced ratio of serum GPT/GOT (glutamic-pyruvic transaminase/glutamic-oxaloacetic transaminase), levels of T-Cho (total cholesterol) and LDLs (low-density lipoproteins), and index of homeostatic model assessment for insulin resistance (HOMA-IR), but had no significant effect in the levels of serum HDL-c (high density lipoprotein cholesterol), TG (total triacylglycerol), and glucose. Moreover, garlic supplementation meliorated the HFD-reduced ratio of villus height/crypt depth, cecum weight, and the concentration of cecal organic acids. Finally, gut microbiota characterization by high throughput 16S rRNA gene sequencing revealed that whole garlic supplementation increased the α-diversity of the gut microbiome, especially increasing the relative abundance of f_ Lachnospiraceae and reducing the relative abundance of g_ Prevotella. Taken together, our data demonstrated that whole garlic supplementation could meliorate the HFD-induced dyslipidemia and disturbance of gut microbiome.

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          Most cited references36

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          Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation.

          Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are produced at high concentration by bacteria in the gut and subsequently released in the bloodstream. Basal acetate concentrations in the blood (about 100 microm) can further increase to millimolar concentrations following alcohol intake. It was known previously that SCFAs can activate leukocytes, particularly neutrophils. In the present work, we have identified two previously orphan G protein-coupled receptors, GPR41 and GPR43, as receptors for SCFAs. Propionate was the most potent agonist for both GPR41 and GPR43. Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41. The two receptors were coupled to inositol 1,4,5-trisphosphate formation, intracellular Ca2+ release, ERK1/2 activation, and inhibition of cAMP accumulation. They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxin-sensitive Gi/o family, whereas GPR43 displayed a dual coupling through Gi/o and Pertussis toxin-insensitive Gq protein families. The broad expression profile of GPR41 in a number of tissues does not allow us to infer clear hypotheses regarding its biological functions. In contrast, the highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection. The pharmacology of GPR43 matches indeed the effects of SCFAs on neutrophils, in terms of intracellular Ca2+ release and chemotaxis. Such a neutrophil-specific SCFA receptor is potentially involved in the development of a variety of diseases characterized by either excessive or inefficient neutrophil recruitment and activation, such as inflammatory bowel diseases or alcoholism-associated immune depression. GPR43 might therefore constitute a target allowing us to modulate immune responses in these pathological situations.
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            Preserving the evolutionary potential of floras in biodiversity hotspots.

            One of the biggest challenges for conservation biology is to provide conservation planners with ways to prioritize effort. Much attention has been focused on biodiversity hotspots. However, the conservation of evolutionary process is now also acknowledged as a priority in the face of global change. Phylogenetic diversity (PD) is a biodiversity index that measures the length of evolutionary pathways that connect a given set of taxa. PD therefore identifies sets of taxa that maximize the accumulation of 'feature diversity'. Recent studies, however, concluded that taxon richness is a good surrogate for PD. Here we show taxon richness to be decoupled from PD, using a biome-wide phylogenetic analysis of the flora of an undisputed biodiversity hotspot--the Cape of South Africa. We demonstrate that this decoupling has real-world importance for conservation planning. Finally, using a database of medicinal and economic plant use, we demonstrate that PD protection is the best strategy for preserving feature diversity in the Cape. We should be able to use PD to identify those key regions that maximize future options, both for the continuing evolution of life on Earth and for the benefit of society.
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              Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing.

              In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                29 May 2019
                June 2019
                : 11
                : 6
                : 1225
                Affiliations
                [1 ]The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0065, Japan; k4164345@ 123456kadai.jp (K.C.); k3591458@ 123456kadai.jp (K.X.); liuzhuying@ 123456gmail.com (Z.L.); sakaok24@ 123456chem.agri.kagoshima-u.ac.jp (K.S.) ; amzad@ 123456agr.u-ryukyu.ac.jp (M.A.H.)
                [2 ]Kenkoukazoku Co., Kagoshima 892-0848, Japan; yasushi.nakasone@ 123456kenkoukazoku.co.jp
                [3 ]Faculty of Agriculture, University of the Ryukyus, Okinawa 903-0213, Japan
                [4 ]Faculty of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan
                Author notes
                Author information
                https://orcid.org/0000-0003-2365-9302
                https://orcid.org/0000-0002-0449-8331
                Article
                nutrients-11-01225
                10.3390/nu11061225
                6627858
                31146458
                348f0eca-8a7c-4952-9605-7cee5a3b80d8
                © 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
                : 28 April 2019
                : 24 May 2019
                Categories
                Article

                Nutrition & Dietetics
                garlic,fructan,gut microbiome,16s rrna genes,high-fat diet
                Nutrition & Dietetics
                garlic, fructan, gut microbiome, 16s rrna genes, high-fat diet

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