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      Regulation of Gut Microbiota and Metabolic Endotoxemia with Dietary Factors

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          Abstract

          Metabolic endotoxemia is a condition in which blood lipopolysaccharide (LPS) levels are elevated, regardless of the presence of obvious infection. It has been suggested to lead to chronic inflammation-related diseases such as obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease (NAFLD), pancreatitis, amyotrophic lateral sclerosis, and Alzheimer’s disease. In addition, it has attracted attention as a target for the prevention and treatment of these chronic diseases. As metabolic endotoxemia was first reported in mice that were fed a high-fat diet, research regarding its relationship with diets has been actively conducted in humans and animals. In this review, we summarize the relationship between fat intake and induction of metabolic endotoxemia, focusing on gut dysbiosis and the influx, kinetics, and metabolism of LPS. We also summarize the recent findings about dietary factors that attenuate metabolic endotoxemia, focusing on the regulation of gut microbiota. We hope that in the future, control of metabolic endotoxemia using dietary factors will help maintain human health.

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          Most cited references126

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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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            Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function.

            Live probiotic bacteria are effective in reducing gut permeability and inflammation. We have previously shown that probiotics release peptide bioactive factors that modulate epithelial resistance in vitro. The objectives of this study were to determine the impact of factors released from Bifidobacteria infantis on intestinal epithelial cell permeability and tight junction proteins and to assess whether these factors retain their bioactivity when administered to IL-10-deficient mice. B. infantis conditioned medium (BiCM) was applied to T84 human epithelial cells in the presence and absence of TNF-alpha and IFN-gamma. Transepithelial resistance (TER), tight junction proteins [claudins 1, 2, 3, and 4, zonula occludens (ZO)-1, and occludin] and MAP kinase activity (p38 and ERK) were examined. Acute effects of BiCM on intestinal permeability were assessed in colons from IL-10-deficient mice in Ussing chambers. A separate group of IL-1-deficient mice was treated with BiCM for 4 wk and then assessed for intestinal histological injury, cytokine levels, epithelial permeability, and immune response to bacterial antigens. In T84 cells, BiCM increased TER, decreased claudin-2, and increased ZO-1 and occludin expression. This was associated with enhanced levels of phospho-ERK and decreased levels of phospho-p38. BiCM prevented TNF-alpha- and IFN-gamma-induced drops in TER and rearrangement of tight junction proteins. Inhibition of ERK prevented the BiCM-induced increase in TER and attenuated the protection from TNF-alpha and IFN-gamma. Oral BiCM administration acutely reduced colonic permeability in mice whereas long-term BiCM treatment in IL-10-deficient mice attenuated inflammation, normalized colonic permeability, and decreased colonic and splenic IFN-gamma secretion. In conclusion, peptide bioactive factors from B. infantis retain their biological activity in vivo and are effective in normalizing gut permeability and improving disease in an animal model of colitis. The effects of BiCM are mediated in part by changes in MAP kinases and tight junction proteins.
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              Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice

              Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis reveal pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation demonstrate the bacterium’s intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Administration of the probiotic Lactobacillus rhamnosus CNCM I-3690 limits B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results suggest a new avenue for interventions against western diet-driven inflammatory and metabolic diseases.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                23 September 2019
                October 2019
                : 11
                : 10
                : 2277
                Affiliations
                [1 ]Department of Nature & Wellness Research, Innovation Division, KAGOME CO., LTD., Nasushiobara 329-2762, Japan; Nobuo_Fuke@ 123456kagome.co.jp (N.F.); Hiroyuki_Suganuma@ 123456kagome.co.jp (H.S.)
                [2 ]Department of Cellular and Molecular Function Analysis, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan; nnagata@ 123456staff.kanazawa-u.ac.jp
                [3 ]Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan
                Author notes
                [* ]Correspondence: ota@ 123456asahikawa-med.ac.jp ; Tel.: +81-166-68-2450
                Author information
                https://orcid.org/0000-0002-2770-1355
                https://orcid.org/0000-0002-2389-2334
                https://orcid.org/0000-0001-6596-9881
                Article
                nutrients-11-02277
                10.3390/nu11102277
                6835897
                31547555
                887665e2-3e64-4796-bb00-dd5f6de73e0e
                © 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
                : 22 August 2019
                : 18 September 2019
                Categories
                Review

                Nutrition & Dietetics
                metabolic endotoxemia,lipopolysaccharide,gut microbiota,dietary factors
                Nutrition & Dietetics
                metabolic endotoxemia, lipopolysaccharide, gut microbiota, dietary factors

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