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      Alteration of gut microbiota in association with cholesterol gallstone formation in mice

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          Abstract

          Background

          The gut microbiome exerts extensive roles in metabolism of nutrients, pharmaceuticals, organic chemicals. Little has been known for the role of gut microbiota in regulating cholesterol and bile acids in association with gallstone formation. This study investigated the changes in the composition of gut microbiota in mice fed with lithogenic diet (LD).

          Methods

          Adult male C57BL/6 J mice were fed with either lithogenic diet (1.25% cholesterol and 0.5% cholic acid) or chow diet as control for 56 days. The fecal microbiota were determined by 16S rRNA gene sequencing.

          Results

          LD led to formation of cholesterol gallstone in mice. The richness and alpha diversity of gut microbial reduced in mice fed with LD. Firmicutes was significantly decreased from 59.71% under chow diet to 31.45% under LD, P < 0.01, as well as the ratio of Firmicutes to Bacteroidetes. Differences in gut microbiota composition were also observed at phylum, family and genus levels between the two groups.

          Conclusion

          Our results suggested that gut microbiota dysbiosis might play an important role in the pathogenesis of cholesterol gallstone formation in mice.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12876-017-0629-2) contains supplementary material, which is available to authorized users.

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          Most cited references31

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          The burden of selected digestive diseases in the United States.

          Gastrointestinal (GI) and liver diseases inflict a heavy economic burden. Although the burden is considerable, current and accessible information on the prevalence, morbidity, and cost is sparse. This study was undertaken to estimate the economic burden of GI and liver disease in the United States for use by policy makers, health care providers, and the public. Data were extracted from a number of publicly available and proprietary national databases to determine the prevalence, direct costs, and indirect costs for 17 selected GI and liver diseases. Indirect cost calculations were purposefully very conservative. These costs were compared with National Institutes of Health (NIH) research expenditures for selected GI and liver diseases. The most prevalent diseases were non-food-borne gastroenteritis (135 million cases/year), food-borne illness (76 million), gastroesophageal reflux disease (GERD; 19 million), and irritable bowel syndrome (IBS; 15 million). The disease with the highest annual direct costs in the United States was GERD ($9.3 billion), followed by gallbladder disease ($5.8 billion), colorectal cancer ($4.8 billion), and peptic ulcer disease ($3.1 billion). The estimated direct costs for these 17 diseases in 1998 dollars were $36.0 billion, with estimated indirect costs of $22.8 billion. The estimated direct costs for all digestive diseases were $85.5 billion. Total NIH research expenditures were $676 million in 2000. GI and liver diseases exact heavy economic and social costs in the United States. Understanding the prevalence and costs of these diseases is important to help set priorities to reduce the burden of illness.
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            Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer.

            Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host.
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              Prevalence and ethnic differences in gallbladder disease in the United States.

              Gallbladder disease is one of the most common conditions in the United States, but its true prevalence is unknown. A national population-based survey was performed to determine the age, sex, and ethnic distribution of gallbladder disease in the United States. The third National Health and Nutrition Examination Survey (NHANES III) conducted gallbladder ultrasonography among a representative U.S. sample of more than 14, 000 persons. The diagnosis of gallbladder disease by detection of gallstones or cholecystectomy was made with excellent reproducibility. An estimated 6.3 million men and 14.2 million women aged 20-74 years had gallbladder disease. Age-standardized prevalence was similar for non-Hispanic white (8. 6%) and Mexican American (8.9%) men, and both were higher than non-Hispanic black men (5.3%). These relationships persisted with multivariate adjustment. Among women, age-adjusted prevalence was highest for Mexican Americans (26.7%) followed by non-Hispanic whites (16.6%) and non-Hispanic blacks (13.9%). Among women, multivariate adjustment reduced the risk of gallbladder disease for both Mexican Americans and non-Hispanic blacks compared with non-Hispanic whites. More than 20 million persons have gallbladder disease in the United States. Ethnic differences in gallbladder disease prevalence differed according to sex and were only partly explained by known risk factors.
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                Author and article information

                Contributors
                huhailc@sina.com
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                9 June 2017
                9 June 2017
                2017
                : 17
                : 74
                Affiliations
                [1 ]GRID grid.415869.7, Department of Surgery, Shanghai Institute of Digestive Surgery Ruijin Hospital, , Shanghai Jiaotong University School of Medicine, ; 200025 Shanghai, China
                [2 ]ISNI 0000000123704535, GRID grid.24516.34, Institute of Gallstone Disease, Center of Gallbladder Disease, Shanghai East Hospital, , Tongji University School of Medicine, ; #150 Jimo Road, Shanghai, 201200 China
                Article
                629
                10.1186/s12876-017-0629-2
                5466737
                28599622
                3fd24eb3-f6ed-48c1-80a5-d141019f0ad2
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 February 2017
                : 19 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81570577
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Gastroenterology & Hepatology
                gut microbiota,cholesterol gallstone,16s rrna gene sequencing

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