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      Dietary fermented products using koji mold and sweet potato- shochu distillery by-product promotes hepatic and serum cholesterol levels and modulates gut microbiota in mice fed a high-cholesterol diet

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          Abstract

          It has been reported that fermented products (FPs) prepared from sweet potato- shochu distillery by-product suppressed weight gain and decreased serum cholesterol levels in mice under normal dietary conditions. Furthermore, from the information gained from the above data regarding health benefits of the FPs, the aim of this study was evaluating the effects of dietary FPs on lipid accumulation and gut microbiota in mice with or without cholesterol-load in the diet. C57BL/6N mice were fed normal (CO) diet, CO with 10% FPs (CO + FPs) diet, cholesterol loaded (HC) diet, or HC with 10% FPs (HC + FPs) diet for 8 weeks. The mice were then euthanized, and blood samples, tissue samples, and feces were collected. The adipose tissue weight and liver triglyceride levels in the HC + FPs diet groups were significantly reduced compared to that in the HC diet groups. However, FPs significantly increased the serum non-high-density lipoprotein cholesterol (HDL-C) levels, the ratio of non-HDL-C to HDL-C and hepatic total cholesterol levels in mice fed cholesterol-loaded diet compared with that of the HC diet group. Since dietary FPs significantly decreased the protein expression levels of cholesterol 7 alpha-hydroxylase 1 in the HC + FPs diet groups, the cholesterol accumulation in FPs group may be explained by insufficient catabolism from cholesterol to bile acid. In addition, the dietary FPs tended to increase Clostridium cluster IV and XIVa, which are butyrate-producing bacteria. Related to the result, n-butyrate was significantly increased in the CO + FPs and the HC + FPs diet groups compared to their respective control groups. These findings suggested that dietary FPs modulated the lipid pool and gut microbiota.

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          Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

          The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.
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            High-Fat Diet Reduces the Formation of Butyrate, but Increases Succinate, Inflammation, Liver Fat and Cholesterol in Rats, while Dietary Fibre Counteracts These Effects

            Introduction Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. Objective To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks. Material and Methods Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin – acetic acid; guar gum – propionic acid; or a mixture – butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. Results and Discussion Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet.
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              A next-generation beneficial microbe: Akkermansia muciniphila

              There have been many reports on the roles of intestinal flora and intestinal environment in health promotion and disease prevention. Beneficial bacteria such as Bifidobacterium and lactic acid-producing bacteria have been shown to improve the intestinal environment, and yield a good effect on metabolism, immunity and nerve response. In this review, in addition to these beneficial bacteria, we introduced Akkermansia muciniphila as a next-generation beneficial microbe. Several reports indicate that Akkermansia muciniphila affects glucose metabolism, lipid metabolism, and intestinal immunity, and that certain food ingredients such as polyphenols may increase the abundance of Akkermansia muciniphila in the gut.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ
                PeerJ Inc. (San Diego, USA )
                2167-8359
                12 September 2019
                2019
                : 7
                : e7671
                Affiliations
                [1 ] Interdisciplinary Graduate School of Agriculture and Engineering, University of Miyazaki , Miyazaki, Miyazaki, Japan
                [2 ] Kirishima Shuzo Co., Ltd. , Miyakonojo, Miyazaki, Japan
                [3 ] Graduate School of Agriculture, University of Miyazaki , Miyazaki, Miyazaki, Japan
                [4 ] Organization for Promotion of Tenure Track, University of Miyazaki , Miyazaki, Miyazaki, Japan
                Author information
                http://orcid.org/0000-0003-2252-2582
                Article
                7671
                10.7717/peerj.7671
                6745188
                da1a289a-a701-4f74-aa07-fdbc07d1a560
                © 2019 Kosakai et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 23 May 2019
                : 13 August 2019
                Funding
                Funded by: Kirishima Shuzo Co., Ltd
                All research funding for this study was provided by Kirishima Shuzo Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Food Science and Technology
                Microbiology
                Nutrition

                sweet potato-shochu,distillery by-product,dietary fiber,short chain fatty acids,gut microbiota,koji,cholesterol

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