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      Lactobacillus plantarum ZJUIDS14 alleviates non-alcoholic fatty liver disease in mice in association with modulation in the gut microbiota

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          Abstract

          This present study was designed to explore the protective role of Lactobacillus plantarum ZJUIDS14 against Non-alcoholic Fatty Liver Disease (NAFLD) in a high-fat-diet (HFD)-induced C57BL/6 mice model. The probiotic (10 9 CFU/every other day) was administered by oral gavage for 12 weeks. We found that L. plantarum ZJUIDS14 intervention significantly alleviated HFD related hepatic steatosis, liver damage, insulin resistance, and increased hepatic expression of peroxisome proliferator activated receptor α (PPAR-α) while stimulating the activation of AMP-activated protein kinase (AMPK). Furthermore, L. plantarum ZJUIDS14 improved mitochondrial function as reflected by an increase in dynamin related protein 1 (DRP1) and a decrease of proteins associated with oxidative phosphorylation (OXPHOS) after the treatment. Additionally, mice from the L. plantarum ZJUIDS14 group had a restored intestinal flora and homeostasis involving Coprostanoligenes group, Ruminococcaceae UCG- 014, Allobaculum, Ruminiclostridium 1, and Roseburia. Meanwhile, these five genera exhibited a significant (negative or positive) association with ileum inflammation mRNA levels and SCFA contents, by Spearman’s correlation analysis. In general, our data demonstrated that L. plantarum ZJUIDS14 mitigates hepatic steatosis and liver damage induced by HFD. Specifically, they strengthened the integrity of the intestinal barrier, regulated gut microbiota, and improved mitochondrial function. Our data provide an experimental basis for L. plantarum ZJUIDS14 as a promising candidate to prevent NAFLD.

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          Mechanisms of NAFLD development and therapeutic strategies

          There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression.
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            The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

            Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.
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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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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                09 January 2023
                2022
                : 9
                : 1071284
                Affiliations
                [1] 1College of Animal Sciences, Institute of Dairy Science, Zhejiang University , Hangzhou, China
                [2] 2School of Public Health, Zhejiang Chinese Medical University , Hangzhou, China
                [3] 3School of Life Sciences, Zhejiang Chinese Medical University , Hangzhou, China
                Author notes

                Edited by: Anandh Babu Pon Velayutham, The University of Utah, United States

                Reviewed by: Xiang Gao, Qingdao University, China; Madan Kumar Perumal, Central Food Technological Research Institute (CSIR), India

                *Correspondence: Songtao Li, isongtao@ 123456zcmu.edu.cn

                These authors have contributed equally to this work

                This article was submitted to Nutrition and Metabolism, a section of the journal Frontiers in Nutrition

                Article
                10.3389/fnut.2022.1071284
                9868733
                36698477
                efb77a71-6d1f-41ad-a365-d617036d597f
                Copyright © 2023 Cao, Ding, Zhuge, Lai, Chang, Le, Yang, Valencak, Li and Ren.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 October 2022
                : 23 December 2022
                Page count
                Figures: 8, Tables: 1, Equations: 0, References: 77, Pages: 16, Words: 8433
                Funding
                This work was supported by the Key R&D Program Projects in Zhejiang Province, China (Grant number 2019C02091), the Natural Science Foundation of China (81973041), and Zhejiang Natural Science Foundation for Distinguished Young Scholars (LR20H260001).
                Categories
                Nutrition
                Original Research

                lactobacillus plantarum zjuids14,non-alcoholic fatty liver disease,hepatic steatosis,mitochondrial function,intestinal microbiota

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