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      Supplemental Clostridium butyricum Modulates Lipid Metabolism Through Shaping Gut Microbiota and Bile Acid Profile of Aged Laying Hens

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          Abstract

          Probiotic Clostridium butyricum could affect lipid metabolism in broilers. However, it is not clear whether C. butyricum could improve lipid metabolism through shaping gut microbiota and bile acid (BA) profile of laying hens. We aimed to evaluate the contributions of gut microbiota and BA profile to the potential effect of C. butyricum on lipid metabolism of aged laying hens. A total of 192 60-week-old Hy-Line Brown laying hens were divided into two groups (eight replicates per group). Birds were fed a basal diet supplemented with 0 or 2.7 g/kg C. butyricum (1.0 × 10 9 CFU/g). Samples were collected at the end of week 8 of the experiment. The results showed elevated ( P < 0.05) concentrations of glucagon-like peptide 1, insulin and thyroid hormones in serum responded to C. butyricum addition, which also decreased ( P < 0.05) hepatic free fatty acids contents, as well as increased ( P < 0.05) the expression of hepatic acyl-CoA oxidase, farnesoid X receptor (FXR) and PPARα. C. butyricum addition increased ( P < 0.05) Bacteroidetes abundance but tended to decrease ( P < 0.10) Firmicutes abundance in the ileum. Besides, C. butyricum addition resulted in higher ( P < 0.05) abundances of Clostridia ( Clostridiales) and Prevotellaceae, concurrent with an increasing trend ( P < 0.10) of Bifidobacteriaceae abundance and decreased the abundances of several harmful bacteria such as Klebsiella ( P < 0.05). Regarding ileal BA profile, there was a reduced ( P < 0.05) content of tauro-α-muricholic acid, increased ( P < 0.05) contents of tauroursodeoxycholic acid and lithocholic acid, along with increasing trends ( P < 0.10) of glycochenodeoxycholic acid and hyodeoxycholic acid contents due to C. butyricum addition, which also increased ( P < 0.05) ileal FXR expression. Collectively, supplemental C. butyricum accelerated hepatic fatty acid oxidation, and shaped gut microbiota and BA profile, thus reducing fat deposition in the liver of aged laying hens.

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          Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis.

          Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly identical to wild-type littermates. FXR/BAR null mice were distinguished from wild-type mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR null mice also had reduced bile acid pools and reduced fecal bile acid excretion due to decreased expression of the major hepatic canalicular bile acid transport protein. Bile acid repression and induction of cholesterol 7alpha-hydroxylase and the ileal bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing the regulatory role of FXR/BAR for the expression of these genes in vivo. These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor.
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            Liver X receptors in lipid signalling and membrane homeostasis

            Liver X receptors α and β (LXRα and LXRβ) are nuclear receptors with pivotal roles in the transcriptional control of lipid metabolism. Transcriptional activity of LXRs is induced in response to elevated cellular levels of cholesterol. LXRs bind to and regulate the expression of genes that encode proteins involved in cholesterol absorption, transport, efflux, excretion and conversion to bile acids. The coordinated, tissue-specific actions of the LXR pathway maintain systemic cholesterol homeostasis and regulate immune and inflammatory responses. LXRs also regulate fatty acid metabolism by controlling the lipogenic transcription factor sterol regulatory element-binding protein 1c and regulate genes that encode proteins involved in fatty acid elongation and desaturation. LXRs exert important effects on the metabolism of phospholipids, which, along with cholesterol, are major constituents of cellular membranes. LXR activation preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids by inducing transcription of the remodelling enzyme lysophosphatidylcholine acyltransferase 3. The ability of the LXR pathway to couple cellular sterol levels with the saturation of fatty acids in membrane phospholipids has implications for several physiological processes, including lipoprotein production, dietary lipid absorption and intestinal stem cell proliferation. Understanding how LXRs regulate membrane composition and function might provide new therapeutic insight into diseases associated with dysregulated lipid metabolism, including atherosclerosis, diabetes mellitus and cancer.
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              Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance.

              The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver. However, unlike systemic agonism, we find that Fex reduces diet-induced weight gain, body-wide inflammation and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue (WAT). These pronounced metabolic improvements suggest tissue-restricted FXR activation as a new approach in the treatment of obesity and metabolic syndrome.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                15 April 2020
                2020
                : 11
                : 600
                Affiliations
                Risk Assessment Laboratory of Feed Derived Factors to Animal Product Quality Safety of Ministry of Agriculture & Rural Affairs, and National Engineering Research Center of Biological Feed, Feed Research Institute, Chinese Academy of Agricultural Sciences , Beijing, China
                Author notes

                Edited by: Spyridon Ntougias, Democritus University of Thrace, Greece

                Reviewed by: Ahmed Ali Saleh, Kafrelsheikh University, Egypt; Robert Gordan Nichols, Pennsylvania State University (PSU), United States

                *Correspondence: Guang-hai Qi, qiguanghai@ 123456caas.cn

                This article was submitted to Systems Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.00600
                7176355
                32351471
                33f8bd31-ee12-4f21-ba59-7e2d861b05b2
                Copyright © 2020 Wang, Wang, Zhang, Wu and Qi.

                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
                : 15 December 2019
                : 18 March 2020
                Page count
                Figures: 4, Tables: 6, Equations: 0, References: 58, Pages: 12, Words: 0
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                clostridium butyricum,laying hen,lipid metabolism,gut microbiota,bile acid
                Microbiology & Virology
                clostridium butyricum, laying hen, lipid metabolism, gut microbiota, bile acid

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