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Shu JZ, Huang YH, He XH, Liu FY, Liang QQ, Yong XT, Xie YF. Gut microbiota differences, metabolite changes, and disease intervention during metabolic - dysfunction - related fatty liver progression. World J Hepatol 2025; 17:103854. [DOI: 10.4254/wjh.v17.i3.103854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/17/2025] [Accepted: 02/12/2025] [Indexed: 03/26/2025] Open
Abstract
In the current era, metabolic dysfunction-associated steatotic liver disease (MASLD) has gradually developed into a major type of chronic liver disease that is widespread globally. Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD. Currently, the gut microbiota has become one of the important entry points for the research of this disease. Therefore, the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD, including the changes and differences in the microbiota between the healthy liver and the diseased liver. Meanwhile, considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis (such as mild fibrosis and severe fibrosis) during the disease progression, we also conduct a comparison of the microbiota in these states and use them as markers of disease progression. It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota, and the impact of lipopolysaccharide from Gram-negative bacteria on the disease. In addition, the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics (including new-generation probiotics) will be explored, which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota. This will achieve important progress in preventing and combating this disease.
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Affiliation(s)
- Jian-Zhong Shu
- Department of Encephalopathy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400015, China
- School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
- College of Integrated Traditional Chinese and Western Medicine, Chongqing University of Traditional Chinese Medicine, Chongqing 402760, China
| | - Yu-Han Huang
- School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
| | - Xiao-Hong He
- School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
| | - Feng-Ying Liu
- School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
| | - Qian-Qian Liang
- School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
| | - Xue-Tong Yong
- School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
| | - Yong-Fang Xie
- School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
- Institute of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
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Ou Y, Xie W, Wang H, Zheng Y, Guo Z, Zheng B. In vitro digestion of glycoproteins from Porphyra haitanensis: Effects on structure, hypoglycemic activity, and fermentation characteristics. Int J Biol Macromol 2025; 289:138699. [PMID: 39672441 DOI: 10.1016/j.ijbiomac.2024.138699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 11/23/2024] [Accepted: 12/10/2024] [Indexed: 12/15/2024]
Abstract
This study was to investigate the fundamental composition and structure, hypoglycemic activity and fermentation characteristics of Porphyra haitanensis glycoprotein (PG) following in vitro simulate gastrointestinal digestion. After in vitro digestion, PG was degraded into peptides, amino acids, and reducing sugars, and the digested PG structure evolved into functional aggregates that were more favorable for regulating intestinal flora. Such aggregated structure might inhibit the accessibility of digestive enzymes and significantly enhanced its hypoglycemic activity. Compared with undigested PG, the inhibition rate of digested PG on α-amylase and α-glucosidase was increased by 4.70 % and 7.69 %, respectively (P < 0.05). Furthermore, digested PG enhanced the abundances of Lactobacillus and Bifidobacterium, etc., which was positive related with the increased secretion of butyric acid, thereby playing a role in regulating intestinal homeostasis and blood glucose homeostasis in the host. Our findings can offer novel perspectives on the regulation of the intestinal flora by glycoproteins during gastrointestinal digestion.
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Affiliation(s)
- Yujia Ou
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; School of Marine Biology, Xiamen Ocean Vocational College, Xiamen 361100, China; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China
| | - Wen Xie
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China
| | - Haoyu Wang
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Yafeng Zheng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China
| | - Zebin Guo
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China.
| | - Baodong Zheng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China.
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Pan L, Wang L, Zeng Z, Zhang Z, Zheng B, Zhang Y. Chemical structure and prebiotic activity of a Dictyophora indusiata polysaccharide fraction. Food Chem 2025; 463:141086. [PMID: 39241418 DOI: 10.1016/j.foodchem.2024.141086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/19/2024] [Accepted: 08/29/2024] [Indexed: 09/09/2024]
Abstract
This study aimed to investigate the chemical structure and prebiotic activity of a Dictyophora indusiata polysaccharide fraction DIP0p. Our results indicated that DIP0p belongs to a heteropolysaccharide composed of glucose, galactose, mannose and xylose, accounting for 53.25 %, 24.18 %, 19.19 % and 3.37 %, respectively. Methylation and NMR results suggested that the main glycosidic bonds of DIP0p is →3)-Glcp-(1 → with →4)-Glcp-(1→, →3,4)-Glcp-(1→, →3,4)-Galp-(1 → and →6)-Manp-(1 → branches. In addition, DIP0p increased the abundance of benificial bacteria during the in vitro fecal fermentation, including Phascolarctobacterium, Parabacteroides and Bifidobacterium. It is remarkable that DIP0p improved the level of acetic acid, propionic acid, and butyric acid of the fermentation system, which were 1.31, 1.52, and 2.64 folds higher than the Controls, respectively. In summary, this study comprehensively analyzed the structure and probiotic activity of DIP0p, which providing a theoretical basis for the development of the functional foods.
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Affiliation(s)
- Lei Pan
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Integrated Scientific Research Base of Edible Fungi Processing and Comprehensive Utilization Technology, Ministry of Agriculture and Rural Affairs, Fuzhou, Fujian 350002, China.
| | - Lin Wang
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Integrated Scientific Research Base of Edible Fungi Processing and Comprehensive Utilization Technology, Ministry of Agriculture and Rural Affairs, Fuzhou, Fujian 350002, China
| | - Zhikun Zeng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Integrated Scientific Research Base of Edible Fungi Processing and Comprehensive Utilization Technology, Ministry of Agriculture and Rural Affairs, Fuzhou, Fujian 350002, China
| | - Zihao Zhang
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Integrated Scientific Research Base of Edible Fungi Processing and Comprehensive Utilization Technology, Ministry of Agriculture and Rural Affairs, Fuzhou, Fujian 350002, China
| | - Baodong Zheng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Integrated Scientific Research Base of Edible Fungi Processing and Comprehensive Utilization Technology, Ministry of Agriculture and Rural Affairs, Fuzhou, Fujian 350002, China
| | - Yi Zhang
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Integrated Scientific Research Base of Edible Fungi Processing and Comprehensive Utilization Technology, Ministry of Agriculture and Rural Affairs, Fuzhou, Fujian 350002, China.
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Ku J, Hsu J, Li Y, Wu L. Interplay among IL1R1, gut microbiota, and bile acids in metabolic dysfunction-associated steatotic liver disease: a comprehensive review. J Gastroenterol Hepatol 2025; 40:33-40. [PMID: 39343617 PMCID: PMC11771549 DOI: 10.1111/jgh.16750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 08/07/2024] [Accepted: 09/11/2024] [Indexed: 10/01/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by hepatic steatosis associated with metabolic abnormalities. Recent research has shed light on the intricate interplay among interleukin-1 receptor 1 (IL1R1), gut microbiota, and bile acids in the pathogenesis of MASLD. This review aims to provide a comprehensive overview of the current understanding of the role of IL1R1, gut microbiota, and bile acids in MASLD, exploring their interrelationships and potential mechanisms. We summarize the evidence supporting the involvement of IL1R1 in inflammation, discuss the influence of gut microbiota on bile acid metabolism and its influence on liver health, and elucidate the bidirectional interactions among IL1R1 signaling, gut microbiota composition, and bile acid homeostasis in MASLD. Furthermore, we highlight emerging therapeutic strategies targeting these interrelated pathways for the management of MASLD.
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Affiliation(s)
- Jie‐Lun Ku
- School of Medicine, College of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Jia‐Rou Hsu
- Department and Institute of Physiology, College of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Yung‐Tsung Li
- Graduate Institute of Clinical Medicine, College of MedicineNational Taiwan UniversityTaipei100Taiwan
| | - Li‐Ling Wu
- Department and Institute of Physiology, College of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Health Innovation CenterNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Microbiota Research CenterNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
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Park JE, Park HY, Kim YS, Park M. The Role of Diet, Additives, and Antibiotics in Metabolic Endotoxemia and Chronic Diseases. Metabolites 2024; 14:704. [PMID: 39728485 DOI: 10.3390/metabo14120704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/06/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024] Open
Abstract
Background/Objectives: Dietary patterns, including high-fat and high-carbohydrate diets (HFDs and HCDs), as well as non-dietary factors such as food additives and antibiotics, are strongly linked to metabolic endotoxemia, a critical driver of low-grade chronic inflammation. This review explores the mechanisms through which these factors impair intestinal permeability, disrupt gut microbial balance, and facilitate lipopolysaccharide (LPS) translocation into the bloodstream, contributing to metabolic disorders such as obesity, type 2 diabetes mellitus, and inflammatory bowel disease. Methods: The analysis integrates findings from recent studies on the effects of dietary components and gut microbiota interactions on intestinal barrier function and systemic inflammation. Focus is given to experimental designs assessing gut permeability using biochemical and histological methods, alongside microbiota profiling in both human and animal models. Results: HFDs and HCDs were shown to increase intestinal permeability and systemic LPS levels, inducing gut dysbiosis and compromising barrier integrity. The resulting endotoxemia promoted a state of chronic inflammation, disrupting metabolic regulation and contributing to the pathogenesis of various metabolic diseases. Food additives and antibiotics further exacerbated these effects by altering microbial composition and increasing gut permeability. Conclusions: Diet-induced alterations in gut microbiota and barrier dysfunction emerge as key mediators of metabolic endotoxemia and related disorders. Addressing dietary patterns and their impact on gut health is crucial for developing targeted interventions. Further research is warranted to standardize methodologies and elucidate mechanisms for translating these findings into clinical applications.
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Affiliation(s)
- Ji-Eun Park
- Food Functionality Research Division, Korea Food Research Institute, Jeonju 55365, Republic of Korea
- Department of Food Science and Technology, Jeonbuk National University, Jeonju 54896, Republic of Korea
| | - Ho-Young Park
- Food Functionality Research Division, Korea Food Research Institute, Jeonju 55365, Republic of Korea
- Department of Food Biotechnology, Korea National University of Science and Technology, Daejeon 34113, Republic of Korea
| | - Young-Soo Kim
- Department of Food Science and Technology, Jeonbuk National University, Jeonju 54896, Republic of Korea
| | - Miri Park
- Food Functionality Research Division, Korea Food Research Institute, Jeonju 55365, Republic of Korea
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Pinheiro DF, Maciel GM, Lima NP, Lima NF, Ribeiro IS, Haminiuk CWI. Impact of fruit consumption on gut microbiota: Benefits, contaminants, and implications for human health. Trends Food Sci Technol 2024; 154:104785. [DOI: 10.1016/j.tifs.2024.104785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Zheng M, Zhai Y, Yu Y, Shen J, Chu S, Focaccia E, Tian W, Wang S, Liu X, Yuan X, Wang Y, Li L, Feng B, Li Z, Guo X, Qiu J, Zhang C, Hou J, Sun Y, Yang X, Zuo X, Heikenwalder M, Li Y, Yuan D, Li S. TNF compromises intestinal bile-acid tolerance dictating colitis progression and limited infliximab response. Cell Metab 2024; 36:2086-2103.e9. [PMID: 38971153 DOI: 10.1016/j.cmet.2024.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 03/28/2024] [Accepted: 06/07/2024] [Indexed: 07/08/2024]
Abstract
The intestine constantly encounters and adapts to the external environment shaped by diverse dietary nutrients. However, whether and how gut adaptability to dietary challenges is compromised in ulcerative colitis is incompletely understood. Here, we show that a transient high-fat diet exacerbates colitis owing to inflammation-compromised bile acid tolerance. Mechanistically, excessive tumor necrosis factor (TNF) produced at the onset of colitis interferes with bile-acid detoxification through the receptor-interacting serine/threonine-protein kinase 1/extracellular signal-regulated kinase pathway in intestinal epithelial cells, leading to bile acid overload in the endoplasmic reticulum and consequent apoptosis. In line with the synergy of bile acids and TNF in promoting gut epithelial damage, high intestinal bile acids correlate with poor infliximab response, and bile acid clearance improves infliximab efficacy in experimental colitis. This study identifies bile acids as an "opportunistic pathogenic factor" in the gut that would represent a promising target and stratification criterion for ulcerative colitis prevention/therapy.
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Affiliation(s)
- Mengqi Zheng
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China
| | - Yunjiao Zhai
- Advanced Medical Research Institute, Shandong University, Jinan 250012, China
| | - Yanbo Yu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Jing Shen
- Advanced Medical Research Institute, Shandong University, Jinan 250012, China
| | - Shuzheng Chu
- Advanced Medical Research Institute, Shandong University, Jinan 250012, China
| | - Enrico Focaccia
- Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Wenyu Tian
- Advanced Medical Research Institute, Shandong University, Jinan 250012, China
| | - Sui Wang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Xuesong Liu
- Advanced Medical Research Institute, Shandong University, Jinan 250012, China
| | - Xi Yuan
- Advanced Medical Research Institute, Shandong University, Jinan 250012, China
| | - Yue Wang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Lixiang Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Bingcheng Feng
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Zhen Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Xiaohuan Guo
- Institute for Immunology, School of Medicine, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing 100084, China
| | - Ju Qiu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Cuijuan Zhang
- Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan 250012, China; Department of Pathology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Jiajie Hou
- Cancer Centre, Faculty of Health Sciences University of Macau, Macau SAR, China; MOE Frontier Science Centre for Precision Oncology, University of Macau, Macau SAR, China
| | - Yiyuan Sun
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Xiaoyun Yang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Xiuli Zuo
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Mathias Heikenwalder
- Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; The M3 Research Center, Medical faculty, University Tübingen, Ottfried-Müller Strasse 37, Tübingen, Germany.
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan 250012, China.
| | - Detian Yuan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan 250012, China.
| | - Shiyang Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; Shandong Provincial Clinical Research Center for Digestive Diseases, Jinan, China; Advanced Medical Research Institute, Shandong University, Jinan 250012, China; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan 250012, China.
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Park CE, Jo YJ, Jung DR, Park HC, Shin JH. Comparative Analysis of Gut Microbiota between Captive and Wild Long-Tailed Gorals for Ex Situ Conservation. Microorganisms 2024; 12:1419. [PMID: 39065187 PMCID: PMC11278867 DOI: 10.3390/microorganisms12071419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/10/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
The long-tailed goral is close to extinction, and ex situ conservation is essential to prevent this phenomenon. Studies on the gut microbiome of the long-tailed goral are important for understanding the ecology of this species. We amplified DNA from the 16S rRNA regions and compared the microbiomes of wild long-tailed gorals and two types of captive long-tailed gorals. Our findings revealed that the gut microbiome diversity of wild long-tailed gorals is greatly reduced when they are reared in captivity. A comparison of the two types of captive long-tailed gorals confirmed that animals with a more diverse diet exhibit greater gut microbiome diversity. Redundancy analysis confirmed that wild long-tailed gorals are distributed throughout the highlands, midlands, and lowlands. For the first time, it was revealed that the long-tailed goral are divided into three groups depending on the height of their habitat, and that the gut bacterial community changes significantly when long-tailed gorals are raised through ex situ conservation. This provides for the first time a perspective on the diversity of food plants associated with mountain height that will be available to long-tailed goral in the future.
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Affiliation(s)
- Chang-Eon Park
- Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; (C.-E.P.); (Y.-J.J.); (D.-R.J.)
- Institute of Ornithology, Ex Situ Conservation Institution Designated by the Ministry of Environment, Gumi 39105, Republic of Korea;
| | - Young-Jae Jo
- Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; (C.-E.P.); (Y.-J.J.); (D.-R.J.)
| | - Da-Ryung Jung
- Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; (C.-E.P.); (Y.-J.J.); (D.-R.J.)
| | - Hee-Cheon Park
- Institute of Ornithology, Ex Situ Conservation Institution Designated by the Ministry of Environment, Gumi 39105, Republic of Korea;
| | - Jae-Ho Shin
- Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; (C.-E.P.); (Y.-J.J.); (D.-R.J.)
- NGS Core Facility, Kyungpook National University, Daegu 41566, Republic of Korea
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Li C, Liu Z, Wei W, Chen C, Zhang L, Wang Y, Zhou B, Liu L, Li X, Zhao C. Exploring the Regulatory Effect of LPJZ-658 on Copper Deficiency Combined with Sugar-Induced MASLD in Middle-Aged Mice Based on Multi-Omics Analysis. Nutrients 2024; 16:2010. [PMID: 38999758 PMCID: PMC11243161 DOI: 10.3390/nu16132010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 06/14/2024] [Accepted: 06/15/2024] [Indexed: 07/14/2024] Open
Abstract
Globally, metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), is one of the most common liver disorders and is strongly associated with copper deficiency. To explore the potential effects and mechanisms of Lactiplantibacillus plantarum LPJZ-658, copper deficiency combined with a high-sugar diet-induced MASLD mouse model was utilized in this study. We fed 40-week-old (middle-aged) male C57BL/6 mice a copper-deficient and high-sugar diet for 16 weeks (CuDS), with supplementary LPJZ-658 for the last 6 weeks (CuDS + LPJZ-658). In this study, we measured body weight, liver weight, and serum biochemical markers. Lipid accumulation, histology, lipidomics, and sphingolipid metabolism-related enzyme expression were investigated to analyze liver function. Untargeted metabolomics was used to analyze the serum and the composition and abundance of intestinal flora. In addition, the correlation between differential liver lipid profiles, serum metabolites, and gut flora at the genus level was measured. The results show that LPJZ-658 significantly improves abnormal liver function and hepatic steatosis. The lipidomics analyses and metabolic pathway analysis identified sphingolipid, retinol, and glycerophospholipid metabolism as the most relevant metabolic pathways that characterized liver lipid dysregulation in the CuDS group. Consistently, RT-qPCR analyses revealed that the enzymes catalyzing sphingolipid metabolism that were significantly upregulated in the CuDS group were downregulated by the LPJZ-658 treatment. In addition, the serum metabolomics results indicated that the linoleic acid, taurine and hypotaurine, and ascorbate and aldarate metabolism pathways were associated with CuDS-induced MASLD. Notably, we found that treatment with LPJZ-658 partially reversed the changes in the differential serum metabolites. Finally, LPJZ-658 effectively regulated intestinal flora abnormalities and was significantly correlated with differential hepatic lipid species and serum metabolites. In conclusion, we elucidated the function and potential mechanisms of LPJZ-658 in alleviating copper deficiency combined with sugar-induced middle-aged MASLD and hope this will provide possible treatment strategies for improving MASLD.
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Affiliation(s)
- Chunhua Li
- College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China; (C.L.); (Z.L.); (C.C.); (L.Z.); (L.L.)
| | - Ziqi Liu
- College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China; (C.L.); (Z.L.); (C.C.); (L.Z.); (L.L.)
| | - Wei Wei
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;
| | - Chen Chen
- College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China; (C.L.); (Z.L.); (C.C.); (L.Z.); (L.L.)
| | - Lichun Zhang
- College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China; (C.L.); (Z.L.); (C.C.); (L.Z.); (L.L.)
| | - Yang Wang
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China;
| | - Bo Zhou
- Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Changchun Veterinary Research Institute, Chinese Academy of Medical Sciences, Changchun 130122, China;
| | - Liming Liu
- College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China; (C.L.); (Z.L.); (C.C.); (L.Z.); (L.L.)
| | - Xiao Li
- Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Changchun Veterinary Research Institute, Chinese Academy of Medical Sciences, Changchun 130122, China;
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Cuiqing Zhao
- College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City 132101, China; (C.L.); (Z.L.); (C.C.); (L.Z.); (L.L.)
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Ghani I, An Y, Qiao Q, He S, Li Z. Polyphenols from Foxtail Millet Improve Non-Alcoholic Fatty Liver Disease by Regulating Intestinal Microbiome in Mice. Foods 2024; 13:1683. [PMID: 38890912 PMCID: PMC11172357 DOI: 10.3390/foods13111683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/18/2024] [Accepted: 05/19/2024] [Indexed: 06/20/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic manifestation of metabolic dysfunction for which effective interventions are lacking. The burden of NAFLD is increasing at an alarming rate. NAFLD is frequently associated with morbidities such as dyslipidemia, type 2 diabetes mellitus and obesity, etc. The current study explored the potential role of bound polyphenols from foxtail millet (BPIS) in treating mice with NAFLD induced by a high-fat diet (HFD). The results indicated the critical role of BPIS in treating NAFLD by effectively restoring the gut microbiota in C57BL/6 mice that received a high-fat diet (HFD) for 12 weeks. At the same time, 16S rRNA analysis demonstrated that BPIS remodeled the overall structure of the gut microbiota from fatty liver diseases towards that of normal counterparts, including ten phylum and twenty genus levels. Further study found that the expression of tight junction proteins was upregulated in the BPIS-treated group. This study provides new insights into the potential NAFLD protective effects induced by polyphenols of foxtail millet.
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Affiliation(s)
| | | | | | | | - Zhuoyu Li
- Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China; (I.G.); (Y.A.); (Q.Q.); (S.H.)
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11
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He S, Li L, Lei S, Su J, Zhang Y, Zeng H. Effect of lotus seed resistant starch on the bioconversion pathway of taurocholic acid by regulating the intestinal microbiota. Int J Biol Macromol 2024; 266:131174. [PMID: 38552699 DOI: 10.1016/j.ijbiomac.2024.131174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 02/19/2024] [Accepted: 03/26/2024] [Indexed: 04/02/2024]
Abstract
Taurocholic acid (TCA) is abundant in the rat intestine and has multiple health benefits. In the gut, intestinal microbiota can transform TCA into different bile acid (BA) derivatives, with the composition of microbiota playing a crucial role in the transformation process. This study aims to investigate how lotus seed resistant starch (LRS) can regulate microbiota to influence BA transformation. A fecal fermentation study was conducted in vitro, using either LRS, high-amylose maize starch (HAMS), or glucose (GLU) to analyze microbiota composition, BA content, and metabolic enzyme activities over different fermentation times. Bioinformatics analysis found that LRS increased the relative abundance of Enterococcus, Bacillus, and Lactobacillus, and decreased Escherichia-Shigella, compared with HAMS and GLU. LRS also reduced total BA content and accelerated the conversion of TCA to cholic acid, deoxycholic acid, and other derivatives. These results reveal that LRS and GLU tend to mediate the dehydroxy pathway, whereas HAMS tends to secrete metabolic enzymes in the epimerization pathway. Therefore, the evidence that LRS may regulate TCA bioconversion may benefit human colon health research and provide an important theoretical basis, as well as offer new concepts for the development of functional foods.
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Affiliation(s)
- Shuqi He
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Lanxin Li
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Suzhen Lei
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Jinhan Su
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Yi Zhang
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fujian Agriculture and Forestry University, Fuzhou 350002, China; China-Ireland International Cooperation Centre for Food Material Science and Structure Design, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
| | - Hongliang Zeng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Fujian Provincial Key Laboratory of Quality Science and Processing Technology in Special Starch, Fujian Agriculture and Forestry University, Fuzhou 350002, China; China-Ireland International Cooperation Centre for Food Material Science and Structure Design, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
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12
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Wang Y, Wang S, Wang TL, Chang LK, Zhou JH, Yang K, Guo LP. Structure of crude polysaccharides from Atractylodes lancea rhizome and treatment of diarrhea owing to spleen deficiency through intestinal flora. Biomed Chromatogr 2024; 38:e5818. [PMID: 38230827 DOI: 10.1002/bmc.5818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/27/2023] [Accepted: 12/05/2023] [Indexed: 01/18/2024]
Abstract
To optimize the extraction process of crude polysaccharides from Atractylodes and elaborate the mechanism of Atractylodes polysaccharides in treating diarrhea owing to spleen deficiency, so as to lay a foundation for further development and utilization of Atractylodes lancea, we used an orthogonal test to optimize the extraction process and established a model of spleen deficiency. It was further combined with histopathology and intestinal flora to elaborate the mechanism of Atractylodes polysaccharides in the treatment of spleen-deficiency diarrhea. The optimized extraction conditions were as follows: the ratio of material to liquid was 1:25; the rotational speed was 150 rpm; the extraction temperature was 60°C; the extraction time was 2 h; and the extraction rate was about 23%. The therapeutic effect of Atractylodes polysaccharides on a spleen-deficiency diarrhea model in mice showed that the water content of stools and diarrhea grade in the treatment group were alleviated, and the levels of gastrin, motilin and d-xylose were improved. The analysis results based on gut microbiota showed that the model group had a higher diversity of gut microbiota than the normal group and treatment group, and the treatment group could correct the diversity of gut microbiota in model mice. Analysis based on the level of phylum and genus showed that the treatment group could inhibit the abundance of Helicobacter pylori genus and increase beneficial bacteria genera. The conclusion was that the optimized extraction process of Atractylodes polysaccharides was reasonable and feasible, and had a good therapeutic effect on spleen deficiency diarrhea.
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Affiliation(s)
- Yue Wang
- Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, College of Life Science, China Jiliang University, Hangzhou, China
| | - Sheng Wang
- State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tie-Lin Wang
- State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Li-Kun Chang
- State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun-Hui Zhou
- State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ke Yang
- Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, College of Life Science, China Jiliang University, Hangzhou, China
| | - Lan-Ping Guo
- State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
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13
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Wang S, Li X, Zhang B, Li Y, Chen K, Qi H, Gao M, Rong J, Liu L, Wan Y, Dong X, Yan M, Ma L, Li P, Zhao T. Tangshen formula targets the gut microbiota to treat non-alcoholic fatty liver disease in HFD mice: A 16S rRNA and non-targeted metabolomics analyses. Biomed Pharmacother 2024; 173:116405. [PMID: 38484559 DOI: 10.1016/j.biopha.2024.116405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 02/24/2024] [Accepted: 03/06/2024] [Indexed: 03/27/2024] Open
Abstract
BACKGROUND Tangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown. METHOD We conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body. RESULTS TSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota. CONCLUSION TSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.
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Affiliation(s)
- Shaopeng Wang
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China; College of Pharmacy, Shandong Second Medical University, Weifang, PR China
| | - Xin Li
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Bo Zhang
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Yuxi Li
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Kexu Chen
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China; College of Pharmacy, Shandong Second Medical University, Weifang, PR China
| | - Huimin Qi
- College of Pharmacy, Shandong Second Medical University, Weifang, PR China
| | - Mengqi Gao
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Jin Rong
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Lin Liu
- Zoucheng Market Supervision Administration, Jining, PR China
| | - Yuzhou Wan
- Research and Development Department, Nanjing Denovo Pharma Co., Ltd, Nanjing, PR China
| | - Xi Dong
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Meihua Yan
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Liang Ma
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China
| | - Ping Li
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China.
| | - Tingting Zhao
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, State Key Laboratory of Rsepiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, PR China.
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14
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Miranda CS, Santana-Oliveira DA, Vasques-Monteiro IL, Dantas-Miranda NS, Glauser JSDO, Silva-Veiga FM, Souza-Mello V. Time-dependent impact of a high-fat diet on the intestinal barrier of male mice. World J Methodol 2024; 14:89723. [PMID: 38577199 PMCID: PMC10989404 DOI: 10.5662/wjm.v14.i1.89723] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/26/2023] [Accepted: 02/18/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa, leading to low-grade inflammation, impaired mucosal integrity, and increased intestinal permeability, resulting in the migration of lipopolysaccharide (LPS) to other tissues. AIM To evaluate the chronic effects (at 10 and 16 wk) of a high-fat diet (HFD) (with 50% energy as fat) on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice. METHODS Forty adult male mice were divided into four nutritional groups, where the letters refer to the type of diet (control and HFD or HF) and the numbers refer to the period (in weeks) of diet administration: Control diet for 10 wk, HFD for 10 wk, control diet for 16 wk, and HFD for 16 wk. After sacrifice, biochemical, molecular, and stereological analyses were performed. RESULTS The HF groups were overweight, had gut dysbiosis, had a progressive decrease in occludin immunostaining, and had increased LPS concentrations. Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group, consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake. CONCLUSION Chronic HFD intake causes overweight, gut dysbiosis, and morphological and functional alterations of the intestinal barrier after 10 or 16 wk. Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.
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Affiliation(s)
| | | | | | | | | | | | - Vanessa Souza-Mello
- Department of Anatomy, Rio de Janeiro State University, Rio de Janeiro 20551030, Brazil
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15
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Xu Q, Cheng X, Wen C, Wu X, Ye M, Li M, Liu S, Wen L, Liu Z, Wang J. An Ilex latifolia‐containing compound tea regulates glucose–lipid metabolism and modulates gut microbiota in high‐fat diet‐fed mice. FOOD FRONTIERS 2024; 5:802-819. [DOI: 10.1002/fft2.362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2024] Open
Abstract
AbstractKuding Tea (Ilex latifolia) is a bitter‐tasting herbal tea that was used for the treatment of symptoms related with diabetes mellitus, hypertension, and hyperlipidemia. However, Kuding Tea is also difficultly accepted by people in daily life because of its poor palatability. In this study, Kuding Tea, green tea (GT) (Camellia sinensis L.), and Luohan (Siraitia grosvenorii) fruits were formulated into a compound Kuding Tea (CKT) to improve the taste and health benefits of this beverage. High‐fat diet‐fed male C57BL/6J mice were used as animal models to explore the effects of CKT (6 or 12 mg/mL, water ad libitum) on body weight, food intake, liver function, blood glucose and lipids, and gene expression. L02 and 3T3‐L1 cells were used to further demonstrate the effects of CKT on fat accumulation and hepatic lipid deposition. Our results suggest that CKT can regulate glucose and lipid metabolism by decreasing body weight, reducing white adipose deposition, improving glucose tolerance, increasing the expression of brown adipose genes, and reducing fat accumulation in the liver, and CKT inhibited fat accumulation better than GT. In addition, a low dose (6 mg/mL) of CKT reduced the abundance of Desulfovibrio bacteria, positively associated with obesity, and increased that of norank_f__Muribaculaceae, Lachnospiraceae_NK4A136_group, and Alloprevotella, which are beneficial to glucose and lipid metabolism. This study suggests that CKT not only has a better palatability but also has potential preventive effects on high‐fat diet‐induced glucose–lipid metabolic diseases.
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Affiliation(s)
- Qiurong Xu
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
| | - Xianyu Cheng
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
| | - Chi Wen
- Hunan Chu Ming Tea Industry Co., Ltd. Changsha China
| | - Xiaoran Wu
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
| | - Mengke Ye
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
| | - Mengyao Li
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
| | - Sha Liu
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
| | - Lixin Wen
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Education, National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, College of Horticulture Hunan Agricultural University Changsha China
| | - Ji Wang
- Hunan Engineering Research Center of Livestock and Poultry Health Care Colleges of Veterinary Medicine, Hunan Agricultural University Changsha China
- Animal Nutritional Genome and Germplasm Innovation Research Center, College of Animal Science and Technology Hunan Agricultural University Changsha China
- Changsha Lvye Biotechnology Co., Ltd. Changsha China
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16
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Thilakarathna WPDW, Rupasinghe HPV. Proanthocyanidins-Based Synbiotics as a Novel Strategy for Nonalcoholic Fatty Liver Disease (NAFLD) Risk Reduction. Molecules 2024; 29:709. [PMID: 38338453 PMCID: PMC10856248 DOI: 10.3390/molecules29030709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 01/29/2024] [Accepted: 02/01/2024] [Indexed: 02/12/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, is a spectrum of liver abnormalities ranging from steatosis to nonalcoholic steatohepatitis (NASH) characterized by excessive lipid accumulation. The prevalence of NAFLD is predicted to increase rapidly, demanding novel approaches to reduce the global NAFLD burden. Flavonoids, the most abundant dietary polyphenols, can reduce the risk of NAFLD. The majority of dietary flavonoids are proanthocyanidins (PACs), which are oligomers and polymers of the flavonoid sub-group flavan-3-ols. The efficacy of PAC in reducing the NAFLD risk can be significantly hindered by low bioavailability. The development of synbiotics by combining PAC with probiotics may increase effectiveness against NAFLD by biotransforming PAC into bioavailable metabolites. PAC and probiotic bacteria are capable of mitigating steatosis primarily through suppressing de novo lipogenesis and promoting fatty acid β-oxidation. PAC and probiotic bacteria can reduce the progression of steatosis to NASH mainly through ameliorating hepatic damage and inflammation induced by hepatic oxidative stress, endoplasmic reticulum stress, and gut microbiota dysbiosis. Synbiotics of PAC are superior in reducing the risk of NAFLD compared to independent administration of PAC and probiotics. The development of PAC-based synbiotics can be a novel strategy to mitigate the increasing incidence of NAFLD.
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Affiliation(s)
- Wasitha P. D. W. Thilakarathna
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada;
| | - H. P. Vasantha Rupasinghe
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada;
- Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4H7, Canada
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Hu D, Hou M, Song P, Chen Q, Feng Y, Wu X, Ni Y. Dietary bile acids supplementation improves the growth performance and alleviates fatty liver in broilers fed a high-fat diet via improving the gut microbiota. Poult Sci 2024; 103:103270. [PMID: 38056054 PMCID: PMC10746564 DOI: 10.1016/j.psj.2023.103270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 12/08/2023] Open
Abstract
This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3-7 d), middle stage (17-21 d), and late stage (31-35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers.
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Affiliation(s)
- Dan Hu
- Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China
| | - Manman Hou
- Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China
| | - Pin Song
- Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China
| | - Qu Chen
- Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China
| | - Yuyan Feng
- Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaoting Wu
- Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China
| | - Yingdong Ni
- Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China.
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18
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Ge J, Ye L, Cheng M, Xu W, Chen Z, Guan F. Preparation of microgels loaded with lycopene/NMN and their protective mechanism against acute liver injury. Food Funct 2024; 15:809-822. [PMID: 38131354 DOI: 10.1039/d3fo03293k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
This study aimed to enhance the stability and bioavailability of lycopene (LYC) and nicotinamide mononucleotide (NMN) by incorporating them into porous microgels after loading LYC into liposomes. The particle size, zeta potential, encapsulation rate (%), scanning electron microscopy images, and stability and release kinetics characteristics in simulating digestion confirmed that the microgels had high LYC and NMN encapsulation rates (99.11% ± 0.12% and 68.98% ± 0.26%, respectively) and good stability and release characteristics. The protective effect and potential mechanism of microgels loaded with LYC and NMN on lipopolysaccharide (LPS)-induced acute liver injury in C57BL/6 mice were investigated by intragastric administration for 28 days prior to LPS exposure. The results showed that the microgels loaded with LYC and NMN significantly ameliorated LPS-induced liver injury and reduced the inflammatory response and oxidative stress. In addition, LYC and NMN can not only act on the Toll-like receptor 4 (TLR4)/MD2 complex but also regulate TLR4-related miRNAs (miR-145a-5p and miR-217-5p) in serum extracellular vesicles, thereby synergistically inhibiting the TLR4/NF-κB signaling pathway. In addition, the microgels loaded with LYC and NMN were able to enrich beneficial bacteria that produced short-chain fatty acids and reduce harmful bacteria. In conclusion, LYC and NMN protected against LPS-induced acute liver injury via inhibition of oxidative stress and inflammation, as well as regulating the gut microbiota.
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Affiliation(s)
- Jian Ge
- College of Life Sciences, China Jiliang University, 258 XueYuan Street, XiaSha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, People's Republic of China.
| | - Luting Ye
- College of Life Sciences, China Jiliang University, 258 XueYuan Street, XiaSha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, People's Republic of China.
| | - Min Cheng
- College of Life Sciences, China Jiliang University, 258 XueYuan Street, XiaSha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, People's Republic of China.
| | - Weijia Xu
- College of Life Sciences, China Jiliang University, 258 XueYuan Street, XiaSha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, People's Republic of China.
| | - Zhaowen Chen
- College of Life Sciences, China Jiliang University, 258 XueYuan Street, XiaSha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, People's Republic of China.
| | - Feng Guan
- College of Life Sciences, China Jiliang University, 258 XueYuan Street, XiaSha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, People's Republic of China.
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19
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Abdollahiyan S, Nabavi-Rad A, Keshavarz Azizi Raftar S, Monnoye M, Salarieh N, Farahanie A, Asadzadeh Aghdaei H, Zali MR, Hatami B, Gérard P, Yadegar A. Characterization of gut microbiome composition in Iranian patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Sci Rep 2023; 13:20584. [PMID: 37996480 PMCID: PMC10667333 DOI: 10.1038/s41598-023-47905-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 11/20/2023] [Indexed: 11/25/2023] Open
Abstract
Gut microbiota dysbiosis is intimately associated with development of non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Nevertheless, the gut microbial community during the course of NAFLD and NASH is yet to be comprehensively profiled. This study evaluated alterations in fecal microbiota composition in Iranian patients with NAFLD and NASH compared with healthy individuals. This cross-sectional study enrolled 15 NAFLD, 15 NASH patients, and 20 healthy controls, and their clinical parameters were examined. The taxonomic composition of the fecal microbiota was determined by sequencing the V3-V4 region of 16S rRNA genes of stool samples. Compared to the healthy controls, NAFLD and NASH patients presented reduced bacterial diversity and richness. We noticed a reduction in the relative abundance of Bacteroidota and a promotion in the relative abundance of Proteobacteria in NAFLD and NASH patients. L-histidine degradation I pathway, pyridoxal 5'-phosphate biosynthesis I pathway, and superpathway of pyridoxal 5'-phosphate biosynthesis and salvage were more abundant in NAFLD patients than in healthy individuals. This study examined fecal microbiota dysbiosis in NAFLD and NASH patients and presented consistent results to European countries. These condition- and ethnicity-specific data could provide different diagnostic signatures and therapeutic targets.
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Affiliation(s)
- Sara Abdollahiyan
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrbanoo Keshavarz Azizi Raftar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Magali Monnoye
- Micalis Institute, INRAE, AgroParisTech, Paris-Saclay University, Jouy-en-Josas, France
| | - Naghmeh Salarieh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Farahanie
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Philippe Gérard
- Micalis Institute, INRAE, AgroParisTech, Paris-Saclay University, Jouy-en-Josas, France.
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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20
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Guney C, Bal NB, Akar F. The impact of dietary fructose on gut permeability, microbiota, abdominal adiposity, insulin signaling and reproductive function. Heliyon 2023; 9:e18896. [PMID: 37636431 PMCID: PMC10447940 DOI: 10.1016/j.heliyon.2023.e18896] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/24/2023] [Accepted: 08/02/2023] [Indexed: 08/29/2023] Open
Abstract
The excessive intake of fructose in the regular human diet could be related to global increases in metabolic disorders. Sugar-sweetened soft drinks, mostly consumed by children, adolescents, and young adults, are the main source of added fructose. Dietary high-fructose can increase intestinal permeability and circulatory endotoxin by changing the gut barrier function and microbial composition. Excess fructose transports to the liver and then triggers inflammation as well as de novo lipogenesis leading to hepatic steatosis. Fructose also induces fat deposition in adipose tissue by stimulating the expression of lipogenic genes, thus causing abdominal adiposity. Activation of the inflammatory pathway by fructose in target tissues is thought to contribute to the suppression of the insulin signaling pathway producing systemic insulin resistance. Moreover, there is some evidence that high intake of fructose negatively affects both male and female reproductive systems and may lead to infertility. This review addresses dietary high-fructose-induced deteriorations that are obvious, especially in gut permeability, microbiota, abdominal fat accumulation, insulin signaling, and reproductive function. The recognition of the detrimental effects of fructose and the development of relevant new public health policies are necessary in order to prevent diet-related metabolic disorders.
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Affiliation(s)
| | | | - Fatma Akar
- Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
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21
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Parunyakul K, Chuchoiy A, Kooltueon S, Puttagamnerd P, Srisuksai K, Santativongchai P, Pongchairerk U, Tulayakul P, E-kobon T, Fungfuang W. Effect of the oil from the fatty tissues of Crocodylus siamensis on gut microbiome diversity and metabolism in mice. PLoS One 2023; 18:e0289073. [PMID: 37506097 PMCID: PMC10381048 DOI: 10.1371/journal.pone.0289073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
Dietary fat can alter host metabolism and gut microbial composition. Crocodile oil (CO) was extracted from the fatty tissues of Crocodylus siamensis. CO, rich in monounsaturated- and polyunsaturated fatty acids, has been reported to reduce inflammation, counter toxification, and improve energy metabolism. The aim of this study was to investigate the effect of CO on gut microbiota (GM) in laboratory mice as well as the accompanying metabolic changes in the animals. Forty-five C57BL/6 male mice were randomly divided into five groups and orally administrated either sterile water (control [C]); 1 or 3% (v/w) CO (CO-low [CO-L] and CO-high [CO-H], respectively); or 1 or 3% (v/w) palm oil (PO-low and PO-high, respectively) for 11 weeks. Body weight gain, food intake, energy intake, blood glucose levels, and blood lipid profiles were determined. Samples from colon tissue were collected and the 16S rRNA genes were pyrosequenced to clarify GM analyses. The results showed that there were no differences in body weight and blood glucose levels. Food intake by the mice in the CO-L and CO-H groups was statistically significantly less when compared to that by the animals in the C group. However, neither CO treatment had a statistically significant effect on calorie intake when compared to the controls. The CO-H exhibited a significant increase in serum total cholesterol and low-density lipoprotein but showed a downward trend in triglyceride levels compared to the control. The GM analyses revealed that both CO treatments have no significant influence on bacterial diversity and relative abundance at the phylum level, whereas increases of Choa1 and abundance-based coverage estimator indexes, distinct β-diversity, and Proteobacteria abundance were observed in the PO-high group compared with the C group. Furthermore, the abundance of Azospirillum thiophilum and Romboutsia ilealis was significantly higher in the CO-L and CO-H groups which could be associated with energy metabolic activity. Thus, CO may be an alternative fat source for preserving host metabolism and gut flora.
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Affiliation(s)
- Kongphop Parunyakul
- Faculty of Science, Department of Zoology, Kasetsart University, Bangkok, Thailand
| | - Aphisara Chuchoiy
- Faculty of Science, Department of Zoology, Kasetsart University, Bangkok, Thailand
| | - Sasiporn Kooltueon
- Faculty of Science, Department of Zoology, Kasetsart University, Bangkok, Thailand
| | | | - Krittika Srisuksai
- Faculty of Science, Department of Zoology, Kasetsart University, Bangkok, Thailand
| | - Pitchaya Santativongchai
- Faculty of Veterinary Medicine, Bio-Veterinary Sciences (International Program), Kasetsart University, Bangkok, Thailand
| | - Urai Pongchairerk
- Faculty of Veterinary Medicine, Department of Anatomy, Kasetsart University, Bangkok, Thailand
| | - Phitsanu Tulayakul
- Faculty of Veterinary Medicine, Department of Veterinary Public Health, Kasetsart University, Nakhon Pathom, Thailand
| | - Teerasak E-kobon
- Faculty of Science, Department of Genetics, Kasetsart University, Bangkok, Thailand
| | - Wirasak Fungfuang
- Faculty of Science, Department of Zoology, Kasetsart University, Bangkok, Thailand
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22
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Miranda CS, Silva-Veiga FM, Santana-Oliveira DA, Fernandes-da-Silva A, Brito GC, Martins FF, Souza-Mello V. Chronic Excessive Fructose Intake Maximizes Brown Adipocyte Whitening but Causes Similar White Adipocyte Hypertrophy Than a High-Fat Diet in C57BL/6 Mice. JOURNAL OF THE AMERICAN NUTRITION ASSOCIATION 2023; 42:435-444. [PMID: 35822844 DOI: 10.1080/07315724.2022.2062686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/29/2023]
Abstract
Objective: This study aimed to evaluate the differential role of a high-fat diet (HF) or high-fructose diet (HFRU) on white adipose tissue and brown adipose tissue remodeling in C57BL/6 mice.Methods: The animals were randomly assigned to receive HF (50% of energy as lipids), HFRU (50% of energy as fructose), or a control diet (C, 10% of energy as lipids) for 12 weeks. Results: The HF group became overweight from the 7th week onwards, but both HF and HFRU groups showed hyperinsulinemia, oral glucose intolerance, and adverse adipose tissue remodeling. HF and HFRU groups showed interscapular brown adipose tissue whitening, tough the reduced QA [nuclei] suggested maximized brown adipocyte dysfunction due to the HFRU diet. In contrast, HF and HFRU diets exerted similar effects upon subcutaneous white adipocytes, with a similar average cross-sectional area. Immunohistochemistry confirmed the whitening enhancement with reduced UCP1 immunodensity in the HFRU group. Conclusion: In conclusion, HF and HFRU diets had indistinguishable effects upon white adipocyte morphology, but the HFRU diet provoked a more pronounced whitening than the HF diet after a 12-week protocol. These results point to the silent and harmful impact that excessive fructose has upon the metabolism of lean mice.
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Affiliation(s)
- Carolline Santos Miranda
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Flávia Maria Silva-Veiga
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Daiana Araujo Santana-Oliveira
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Aline Fernandes-da-Silva
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gabrielle Carvalho Brito
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fabiane Ferreira Martins
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vanessa Souza-Mello
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
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23
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Jin Y, Heo KS. Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2023; 27:299-310. [PMID: 37386828 PMCID: PMC10316197 DOI: 10.4196/kjpp.2023.27.4.299] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 05/18/2023] [Accepted: 05/19/2023] [Indexed: 07/01/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.
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Affiliation(s)
- Yujin Jin
- College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 34134, Korea
| | - Kyung-Sun Heo
- College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 34134, Korea
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24
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Liu Y, Zhong W, Li X, Shen F, Ma X, Yang Q, Hong S, Sun Y. Diets, Gut Microbiota and Metabolites. PHENOMICS (CHAM, SWITZERLAND) 2023; 3:268-284. [PMID: 37325710 PMCID: PMC10260722 DOI: 10.1007/s43657-023-00095-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 06/17/2023]
Abstract
The gut microbiota refers to the gross collection of microorganisms, estimated trillions of them, which reside within the gut and play crucial roles in the absorption and digestion of dietary nutrients. In the past decades, the new generation 'omics' (metagenomics, transcriptomics, proteomics, and metabolomics) technologies made it possible to precisely identify microbiota and metabolites and describe their variability between individuals, populations and even different time points within the same subjects. With massive efforts made, it is now generally accepted that the gut microbiota is a dynamically changing population, whose composition is influenced by the hosts' health conditions and lifestyles. Diet is one of the major contributors to shaping the gut microbiota. The components in the diets vary in different countries, religions, and populations. Some special diets have been adopted by people for hundreds of years aiming for better health, while the underlying mechanisms remain largely unknown. Recent studies based on volunteers or diet-treated animals demonstrated that diets can greatly and rapidly change the gut microbiota. The unique pattern of the nutrients from the diets and their metabolites produced by the gut microbiota has been linked with the occurrence of diseases, including obesity, diabetes, nonalcoholic fatty liver disease, cardiovascular disease, neural diseases, and more. This review will summarize the recent progress and current understanding of the effects of different dietary patterns on the composition of gut microbiota, bacterial metabolites, and their effects on the host's metabolism.
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Affiliation(s)
- Yilian Liu
- State Key Laboratory of Genetic Engineering and School of Life Sciences, Human Phenome Institute, Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200433 China
| | - Wanglei Zhong
- State Key Laboratory of Genetic Engineering and School of Life Sciences, Human Phenome Institute, Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200433 China
| | - Xiao Li
- State Key Laboratory of Genetic Engineering and School of Life Sciences, Human Phenome Institute, Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200433 China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Dongfeng Hospital, Hubei University of Medicine, Shiyan, 442001 Hubei China
| | - Xiaonan Ma
- State Key Laboratory of Genetic Engineering and School of Life Sciences, Human Phenome Institute, Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200433 China
| | - Qi Yang
- State Key Laboratory of Genetic Engineering and School of Life Sciences, Human Phenome Institute, Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200433 China
| | - Shangyu Hong
- State Key Laboratory of Genetic Engineering and School of Life Sciences, Human Phenome Institute, Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200433 China
| | - Yan Sun
- Masonic Medical Research Institute, 2150 Bleecker St, Utica, NY 13501 USA
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25
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Jing Y, Su Z, Zhang S, Han Q, Wang Z, Hu B, Zhang D, Sun S, Wu L. Structural Characterization, Simulated Digestion and Anti-Aging Activities of an Acidic Polysaccharide from Salvia Miltiorrhiza. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2023:10.1007/s11130-023-01070-w. [PMID: 37249735 DOI: 10.1007/s11130-023-01070-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Accepted: 04/30/2023] [Indexed: 05/31/2023]
Abstract
An acidic polysaccharide (SMP) with a molecular weight (Mw) of 1.28 × 106 Da was isolated from Salvia miltiorrhiza. The monosaccharide composition in molar percentages was rhamnose (Rha): galacturonic acid (GalA): galactose (Gal): arabinose (Ara) = 6.15: 55.98: 21.27: 16.69. The results of simulated digestion in vitro showed that SMP was not degraded in saliva, gastric juice or intestinal juice. The Y maze test and new object recognition test showed that SMP could improve the working memory impairment of aging mice. SMP could also increase the activity of superoxide dismutase (SOD) and catalase (CAT) in serum and brain tissue, decrease the content of malondialdehyde (MDA), decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue, and increase the content of short-chain fatty acids (SCFA) in the intestine. In addition, SMP could also regulate the intestinal flora structure, including increasing the relative abundance of Firmicutes and Bacteroidetes and decreasing the relative abundance of Proteobacteria. This work lays a foundation for the development of functional foods related to Salvia miltiorrhiza.
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Affiliation(s)
- Yongshuai Jing
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Ziteng Su
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Shilin Zhang
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Qiyuan Han
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Ziying Wang
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Beibei Hu
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Danshen Zhang
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Shiguo Sun
- College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, 26 Yuxiang Street, Shijiazhuang, 050018, China
| | - Lanfang Wu
- College of Pharmacy, Hebei University of Chinese Medicine, No. 3 Xingyuan Road, Shijiazhuang, 050200, China.
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26
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The Effects of Probiotics on Small Intestinal Microbiota Composition, Inflammatory Cytokines and Intestinal Permeability in Patients with Non-Alcoholic Fatty Liver Disease. Biomedicines 2023; 11:biomedicines11020640. [PMID: 36831176 PMCID: PMC9953317 DOI: 10.3390/biomedicines11020640] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/02/2023] [Accepted: 02/13/2023] [Indexed: 02/22/2023] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p < 0.05). This group significantly reduced three unclassifiable species: unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (-7.9 ± 0.44, p < 0.0001) and TNF-α (-0.96 ± 0.25, p < 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p < 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: -34.51 ng/mL ± 18.38, p < 0.0001 vs. placebo: -33.34 ng/mL ± 16.62, p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes.
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27
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Yang Z, Su H, Lv Y, Tao H, Jiang Y, Ni Z, Peng L, Chen X. Inulin intervention attenuates hepatic steatosis in rats via modulating gut microbiota and maintaining intestinal barrier function. Food Res Int 2023; 163:112309. [PMID: 36596207 DOI: 10.1016/j.foodres.2022.112309] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 12/01/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022]
Abstract
Increasing evidence has suggested the mitigatory efficacy of prebiotic inulin on nonalcoholic fatty liver disease (NAFLD), nevertheless, its action mechanisms remain elusive. Herein, inulin consumption effectively ameliorated high-sucrose diet-induced hepatic steatosis and inflammation, and rehabilitated liver lipogenesis regulators, including carbohydrate response element-binding protein, stearoyl-CoA desaturase-1 and peroxisome proliferator-activated receptor alpha. Furthermore, inulin supplementation restored the intestinal barrier integrity and function by up-regulating expressions of tight junction proteins (zonula occludens-1, claudin-1 and occludin). High-throughput sequencing demonstrated that inulin administration regulated the gut microbiota composition, wherein abundance of short-chain fatty acid (SCFA)-producers, including Bifidobacterium, Phascolarctobacterium and Blautia, was significantly enhanced in the inulin-treated rats, conversely, opportunistic pathogens, such as Acinetobacter and Corynebacterium_1, were suppressed. SCFA quantitative analysis showed that dietary inulin suppressed faecal acetate levels, but improved propionate and butyrate concentrations in rats with NAFLD. Functional prediction showed that tryptophan metabolism was one of the key metabolic pathways affected by gut microbiota changes. A targeted metabolomics profiling of tryptophan metabolism demonstrated that inulin intervention up-regulated faecal contents of indole-3-acetic acid and kynurenic acid, whereas down-regulated levels of kynurenine and 5-hydoxyindoleacetic acid in NAFLD rats. Therefore, this study demonstrated that inulin intake alleviated hepatic steatosis likely by regulating the gut microbiota composition and function and restoring the intestinal barrier integrity, which may provide a novel notion for the prevention and treatment of NAFLD in future.
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Affiliation(s)
- Zhandong Yang
- Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
| | - Huihui Su
- Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China; Guangdong Engineering Research Center for Sugar Technology, Guangzhou 510316, China
| | - Yunjuan Lv
- KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, China
| | - Heqing Tao
- Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
| | - Yonghong Jiang
- Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
| | - Ziyan Ni
- Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
| | - Liang Peng
- Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
| | - Xueqing Chen
- Department of Gastroenterology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
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28
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Yan JK, Wang C, Chen TT, Zhu J, Chen X, Li L, Liu X, Zhang H, Li L. A pectic polysaccharide from fresh okra (Abelmoschus esculentus L.) beneficially ameliorates CCl 4-induced acute liver injury in mice by antioxidation, inhibition of inflammation and modulation of gut microbiota. Food Chem Toxicol 2023; 171:113551. [PMID: 36481254 DOI: 10.1016/j.fct.2022.113551] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 11/21/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022]
Abstract
Okra [Abelmoschus esculentus (Linn.) Moench], as a well-known medicinal and food plant, has important physiological activities and health benefits, and polysaccharide is its main bioactive component. In this study, a pectic polysaccharide (OPS-50) prepared from fresh okra pods by three-phase partitioning and gradient (NH4)2SO4 precipitation at a saturation of 50% was employed in carbon tetrachloride (CCl4)-caused acute liver damage in mice to evaluate the hepatoprotective potential. Results indicated that OPS-50 was mainly composed of a limited linear homogalacturonan backbone and abundant rhamnogalacturonan-I domains as side chains. OPS-50 exerted positively protective effects on acute liver damage induced by CCl4 in mice through relieving weight reduction and organ damage, ameliorating liver function and dyslipidemia, alleviating oxidative stress, suppressing pro-inflammatory cytokines, modulating gut microbiota, and promoting short-chain fatty acid secretion. Moreover, liver histopathology demonstrated the protective benefit of OPS-50 on CCl4-caused acute liver damage in mice. Therefore, our data suggested that the pectic OPS-50, as a dietary supplement, have great potential in preventing and treating chemical liver damages.
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Affiliation(s)
- Jing-Kun Yan
- Engineering Research Center of Health Food Design & Nutrition Regulation, Dongguan Key Laboratory of Typical Food Precision Design, China National Light Industry Key Laboratory of Healthy Food Development and Nutrition Regulation, School of Life and Health Technology, Dongguan University of Technology, Dongguan, 523808, China; School of Food & Biological Engineering, Institute of Food Physical Processing, Jiangsu University, Zhenjiang, 212013, China.
| | - Chun Wang
- School of Food & Biological Engineering, Institute of Food Physical Processing, Jiangsu University, Zhenjiang, 212013, China
| | - Ting-Ting Chen
- School of Food & Biological Engineering, Institute of Food Physical Processing, Jiangsu University, Zhenjiang, 212013, China
| | - Jie Zhu
- Engineering Research Center of Health Food Design & Nutrition Regulation, Dongguan Key Laboratory of Typical Food Precision Design, China National Light Industry Key Laboratory of Healthy Food Development and Nutrition Regulation, School of Life and Health Technology, Dongguan University of Technology, Dongguan, 523808, China
| | - Xu Chen
- Engineering Research Center of Health Food Design & Nutrition Regulation, Dongguan Key Laboratory of Typical Food Precision Design, China National Light Industry Key Laboratory of Healthy Food Development and Nutrition Regulation, School of Life and Health Technology, Dongguan University of Technology, Dongguan, 523808, China
| | - Longqing Li
- Engineering Research Center of Health Food Design & Nutrition Regulation, Dongguan Key Laboratory of Typical Food Precision Design, China National Light Industry Key Laboratory of Healthy Food Development and Nutrition Regulation, School of Life and Health Technology, Dongguan University of Technology, Dongguan, 523808, China
| | - Xiaozhen Liu
- Engineering Research Center of Health Food Design & Nutrition Regulation, Dongguan Key Laboratory of Typical Food Precision Design, China National Light Industry Key Laboratory of Healthy Food Development and Nutrition Regulation, School of Life and Health Technology, Dongguan University of Technology, Dongguan, 523808, China
| | - Henan Zhang
- Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, National Engineering Research Center of Edible Fungi, Key Laboratory of Edible Fungi Resources and Utilization (South), Ministry of Agriculture, Shanghai, 200000, China.
| | - Lin Li
- Engineering Research Center of Health Food Design & Nutrition Regulation, Dongguan Key Laboratory of Typical Food Precision Design, China National Light Industry Key Laboratory of Healthy Food Development and Nutrition Regulation, School of Life and Health Technology, Dongguan University of Technology, Dongguan, 523808, China.
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Synbiotic Intervention Ameliorates Oxidative Stress and Gut Permeability in an In Vitro and In Vivo Model of Ethanol-Induced Intestinal Dysbiosis. Biomedicines 2022; 10:biomedicines10123285. [PMID: 36552041 PMCID: PMC9816946 DOI: 10.3390/biomedicines10123285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022] Open
Abstract
Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD's pathophysiology is unknown. However, acetaldehyde's toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome's shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.
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Li A, Wang J, Zhang X, Kou R, Chen M, Zhang B, Liu J, Peng B, Zhang Y, Wang S. Cold-Brewed Jasmine Tea Attenuates High-Fat Diet-Induced Obesity and Gut Microbial Dysbiosis. Nutrients 2022; 14:nu14245359. [PMID: 36558518 PMCID: PMC9784320 DOI: 10.3390/nu14245359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/13/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Cold-brewed jasmine tea (CB-JT) is regarded to possess characteristic flavors and health benefits as a novel resource of functional tea beverages. To investigate the molecular mechanisms underlying CB-JT-mediated protective effects on obesity, we evaluated the serum biochemistry, histological condition, glucose tolerance, gene expression profile and intestinal microbial diversity in high-fat diet (HFD)-fed mice. Our results demonstrate that cold-brewed jasmine tea can significantly attenuate HFD-induced body weight gain, abnormal serum lipid levels, fat deposition, hepatic injury, inflammatory processes as well as metabolic endotoxemia. CB-JT also modified the microbial community composition in HFD-fed mice and altered the balance to one closely resembled that of the control group. The differential abundance of core microbes in obese mice was reversed by CB-JT treatment, including an increment in the abundance of Blautia, Mucispirillum, and Bilophila as well as a decrease in the abundance of Alloprevotella. CB-JT was proved to regulate the mRNA expression levels of lipid metabolism-related genes such as Leptin, Pgc1a Il6, and Il1b in the adipose tissue coupled with Cyp7a1, Lxra, Srebp1c, and Atgl in the liver. These findings indicate that cold-brewed jasmine tea might be served as a potential functional tea beverage to prevent obesity and gut microbiota dysbiosis.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Shuo Wang
- Correspondence: ; Tel.: +86-22-8535-8445
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31
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Chua D, Low ZS, Cheam GX, Ng AS, Tan NS. Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm. Int J Mol Sci 2022; 23:14762. [PMID: 36499091 PMCID: PMC9737809 DOI: 10.3390/ijms232314762] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/15/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022] Open
Abstract
Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.
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Affiliation(s)
- Damien Chua
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
| | - Zun Siong Low
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
| | - Guo Xiang Cheam
- School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, Singapore
| | - Aik Seng Ng
- Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
| | - Nguan Soon Tan
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
- School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, Singapore
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32
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Grabacka M, Płonka PM, Pierzchalska M. The PPARα Regulation of the Gut Physiology in Regard to Interaction with Microbiota, Intestinal Immunity, Metabolism, and Permeability. Int J Mol Sci 2022; 23:ijms232214156. [PMID: 36430628 PMCID: PMC9696208 DOI: 10.3390/ijms232214156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/11/2022] [Accepted: 11/14/2022] [Indexed: 11/19/2022] Open
Abstract
Peroxisome proliferator-activated receptor alpha (PPARα) is expressed throughout the mammalian gut: in epithelial cells, in the villi of enterocytes and in Paneth cells of intestinal crypts, as well as in some immune cells (e.g., lamina propria macrophages, dendritic cells) of the mucosa. This review examines the reciprocal interaction between PPARα activation and intestinal microbiota. We refer to the published data confirming that microbiota products can influence PPARα signaling and, on the other hand, PPARα activation is able to affect microbiota profile, viability, and diversity. PPARα impact on the broad spectrum of events connected to metabolism, signaling (e.g., NO production), immunological tolerance to dietary antigens, immunity and permeability of the gut are also discussed. We believe that the phenomena described here play a prominent role in gut homeostasis. Therefore, in conclusion we propose future directions for research, including the application of synthetic activators and natural endogenous ligands of PPARα (i.e., endocannabinoids) as therapeutics for intestinal pathologies and systemic diseases assumed to be related to gut dysbiosis.
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Affiliation(s)
- Maja Grabacka
- Department of Biotechnology and General Technology of Foods, Faculty of Food Technology, University of Agriculture, ul. Balicka 122, 30-149 Cracow, Poland
- Correspondence: ; Tel.: +48-12-662-4701
| | - Przemysław M. Płonka
- Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Cracow, Poland
| | - Małgorzata Pierzchalska
- Department of Biotechnology and General Technology of Foods, Faculty of Food Technology, University of Agriculture, ul. Balicka 122, 30-149 Cracow, Poland
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33
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Xu P, Hong Y, Chen P, Wang X, Li S, Wang J, Meng F, Zhou Z, Shi D, Li Z, Cao S, Xiao Y. Regulation of the cecal microbiota community and the fatty liver deposition by the addition of brewers’ spent grain to feed of Landes geese. Front Microbiol 2022; 13:970563. [PMID: 36204629 PMCID: PMC9530188 DOI: 10.3389/fmicb.2022.970563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
The effects of brewers’ spent grain (BSG) diets on the fatty liver deposition and the cecal microbial community were investigated in a total of 320 healthy 5-day-old Landes geese. These geese were randomly and evenly divided into 4 groups each containing 8 replicates and 10 geese per replicate. These four groups of geese were fed from the rearing stage (days 5–60) to the overfeeding stage (days 61–90). The Landes geese in group C (control) were fed with basal diet (days 5–90); group B fed first with basal diet in the rearing stage and then basal diet + 4% BSG in the overfeeding stage; group F first with basal diet + 4% BSG during the rearing stage and then basal diet in the overfeeding stage; and group W with basal diet + 4% BSG (days 5–90). The results showed that during the rearing stage, the body weight (BW) and the average daily gain (ADG) of Landes geese were significantly increased in groups F and W, while during the overfeeding stage, the liver weights of groups W and B were significantly higher than that of group C. The taxonomic structure of the intestinal microbiota revealed that during the overfeeding period, the relative abundance of Bacteroides in group W was increased compared to group C, while the relative abundances of Escherichia–Shigella and prevotellaceae_Ga6A1_group were decreased. Results of the transcriptomics analysis showed that addition of BSG to Landes geese diets altered the expression of genes involved in PI3K-Akt signaling pathway and sphingolipid metabolism in the liver. Our study provided novel experimental evidence based on the cecal microbiota to support the application of BSG in the regulation of fatty liver deposition by modulating the gut microbiota in Landes geese.
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Affiliation(s)
- Ping Xu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Yuxuan Hong
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Pinpin Chen
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Xu Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Shijie Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Jie Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Fancong Meng
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Zutao Zhou
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Deshi Shi
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Zili Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Shengbo Cao
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
| | - Yuncai Xiao
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China
- *Correspondence: Yuncai Xiao,
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van der Vossen EWJ, de Goffau MC, Levin E, Nieuwdorp M. Recent insights into the role of microbiome in the pathogenesis of obesity. Therap Adv Gastroenterol 2022; 15:17562848221115320. [PMID: 35967920 PMCID: PMC9373125 DOI: 10.1177/17562848221115320] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 07/06/2022] [Indexed: 02/04/2023] Open
Abstract
Obesity is a risk factor for many chronic diseases and its rising prevalence the last couple of decades is a healthcare concern in many countries. Obesity is a multifactorial problem that is not only limited in its causation by diet and lack of exercise. Genetics but also environmental factors such as the gut microbiome should similarly be taken into account. A plethora of articles have been published, that from various different angles, attempt to disentangle the complex interaction between gut microbiota and obesity. Examples range from the effect of the gut microbiota on the host immune system to the pathophysiological pathways in which microbial-derived metabolites affect obesity. Various discordant gut microbiota findings are a result of this complexity. In this review, in addition to summarizing the classical role of the gut microbiome in the pathogenesis of obesity, we attempt to view both the healthy and obesogenic effects of the gut microbiota as a consequence of the presence or absence of collective guilds/trophic networks. Lastly, we propose avenues and strategies for the future of gut microbiome research concerning obesity.
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Affiliation(s)
- Eduard W. J. van der Vossen
- Department of Experimental Vascular Medicine,
Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The
Netherlands
| | - Marcus C. de Goffau
- Department of Experimental Vascular Medicine,
Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The
Netherlands
| | - Evgeni Levin
- Department of Experimental Vascular Medicine,
Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The
Netherlands,Horaizon BV, Delft, The Netherlands
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35
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A polysaccharide from Inonotus obliquus ameliorates intestinal barrier dysfunction in mice with type 2 diabetes mellitus. Int J Biol Macromol 2022; 214:312-323. [PMID: 35714869 DOI: 10.1016/j.ijbiomac.2022.06.071] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 06/05/2022] [Accepted: 06/10/2022] [Indexed: 12/31/2022]
Abstract
Type 2 diabetes mellitus is a global disease that endangers human health, and the need for the development of nontoxic treatment candidates is urgent. In the present work, one homogeneous polysaccharide from Inonotus obliquus (IN) was isolated, and the protective effect and mechanism of IN on type 2 diabetes mellitus were investigated from the aspects of the intestinal barrier. IN mainly consisted of 9 monosaccharides with a Mw of 373 kDa. IN attenuated body weight loss, alleviated pathological damage, and suppressed the production of proinflammatory cytokines. Additionally, IN repaired the intestinal barrier by upregulating the expression of Ki-67, ZO-1 and MUC2. Furthermore, the abundance of Firmicutes was significantly increased with IN treatment, while the levels of Bacteroidetes were significantly inhibited. In conclusion, IN protected against type 2 diabetes mellitus by ameliorating intestinal barrier dysfunction and might serve as a novel drug candidate for type 2 diabetes mellitus.
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36
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Effects of in vitro digestion and fermentation of Nostoc commune Vauch. polysaccharides on properties and gut microbiota. Carbohydr Polym 2022; 281:119055. [DOI: 10.1016/j.carbpol.2021.119055] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/05/2021] [Accepted: 12/24/2021] [Indexed: 01/11/2023]
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37
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Xie H, Fang J, Farag MA, Li Z, Sun P, Shao P. Dendrobium officinale leaf polysaccharides regulation of immune response and gut microbiota composition in cyclophosphamide-treated mice. Food Chem X 2022; 13:100235. [PMID: 35499019 PMCID: PMC9039934 DOI: 10.1016/j.fochx.2022.100235] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 01/23/2022] [Accepted: 01/24/2022] [Indexed: 01/16/2023] Open
Abstract
Polysaccharides extracted from Dendrobium officinale leaves could make better use of production waste. DOLP reduces gut barrier damage and cure inflammation. DOLP alleviated liver damage caused by drugs. DOLP regulated gut micorbiota and metabolism and increases the abundance of probiotics. In this study, the polysaccharides extracted from Dendrobium officinale leaf (DOLP) was used in immune deficiency mice to evaluate the bioactivity. Thymus and spleen indices were calculated while the alleviation of the colon and liver histopathological progression was evaluated by H&E staining. The data indicated that DOLP improved immunity status by restoring the gut barrier and atrophy of immune organs. Cytokines levels as marker of inflammation were determined using ELISA in serum and colon. Which proved that DOLP inhibited the expression of pro-inflammatory cytokines (TNF-α, TGF- β1, IL-6, IL-1β) and promoted the expression of anti-inflammatory cytokines (IL-10). Short chain fatty acids (SCFAs) levels and microbial composition in feces were determined using GS and high-throughput sequencing. DOLP improved gut microbiota by increasing the relative abundance of total bacteria and probiotics such as Bacteroides, Lactobacillus and Lachnospiraceae. Therefore, DOLP has potential effect for the treatment of chronic immune diseases.
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Affiliation(s)
- Hualing Xie
- College of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, PR China
| | - Jingyu Fang
- College of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, PR China
| | - Mohamed A. Farag
- Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr El Aini St. P.B, Cairo, Egypt
- Department of Chemistry, School of Science & Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Zhenhao Li
- Zhejiang ShouXianGu Botanical Drug Institute Co. Ltd, Zhejiang, Hangzhou 321200, China
| | - Peilong Sun
- College of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, PR China
- Corresponding authors.
| | - Ping Shao
- College of Food Science and Technology, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, PR China
- Corresponding authors.
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38
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Effects of Fumonisin B and Hydrolyzed Fumonisin B on Growth and Intestinal Microbiota in Broilers. Toxins (Basel) 2022; 14:toxins14030163. [PMID: 35324660 PMCID: PMC8954478 DOI: 10.3390/toxins14030163] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/18/2022] [Accepted: 02/21/2022] [Indexed: 02/01/2023] Open
Abstract
Fumonisins are mainly produced by Fusarium verticillioides and proliferatum, which causes a variety of toxicities in humans and animals, including fumonisin Bs (FBs) as the main form. After they are metabolized by plants or microorganisms, modified fumonisins are difficult to detect by conventional methods, which result in an underestimation of their contamination level. Fumonisins widely contaminate maize and maize products, especially in broiler feed. As an economically important food, broilers are often adversely affected by mycotoxins, leading to food safety hazards and high economic losses. However, there are few studies regarding the adverse effects of FBs on broiler growth and health, especially modified FBs. Our data shows that after exposure to FBs or hydrolyzed fumonisin Bs (HFBs), the body weight and tissue weight of broilers decreased significantly, especially the testes. Moreover, they significantly affect the intestinal microbiota and the relative abundance of bacteria from phylum-to-species levels, with the differentially affected bacteria mainly belonging to Firmicutes and Proteobacteria. Our findings suggest that both the parent and hydrolyzed FBs could induce growth retardation, tissue damage and the imbalance of intestinal microbiota in broilers. This indicated that the harmful effects of HFBs cannot be ignored during food safety risk assessment.
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Teng Y, Yang X, Li G, Zhu Y, Zhang Z. Habitats Show More Impacts Than Host Species in Shaping Gut Microbiota of Sympatric Rodent Species in a Fragmented Forest. Front Microbiol 2022; 13:811990. [PMID: 35197954 PMCID: PMC8859092 DOI: 10.3389/fmicb.2022.811990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/05/2022] [Indexed: 11/13/2022] Open
Abstract
Gut microbiota play a significant role for animals to adapt to the changing environment. Host species and habitats are key drivers in shaping the diversity and composition of the microbiota, but the determinants of composition of the sympatric host gut microbiome remain poorly understood within an ecosystem. In this study, we examined the effects of habitats of different succession stages and host species on the diversity and composition of fecal gut microbiota in four sympatric rodent species (Apodemus draco, Leopoldamys edwardsi, Niviventer confucianus, and Niviventer fulvescens) in a subtropical forest. We found, as compared to the differences between species, habitat types showed a much larger effect on the gut microbiota of rodents. Alpha diversity of the microbial community of A. draco, N. fulvescens, and N. confucianus was highest in farmland, followed by primary forest and shrubland, and lowest in secondary forest. Beta diversity of the three rodent species showed significant different among habitats. The alpha diversity of gut microbiota of L. edwardsi was significantly higher than those of A. draco and N. confucianus, and its beta diversity showed significant difference from A. draco. Our results suggested that gut microbiota were important for animals in responding to diet changes in different habitats under human disturbances.
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Affiliation(s)
- Yuwei Teng
- State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China
| | - Xifu Yang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Guoliang Li
- State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China
| | - Yunlong Zhu
- State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China
| | - Zhibin Zhang
- State Key Laboratory of Integrated Management of Pest Insects and Rodents in Agriculture, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China
- *Correspondence: Zhibin Zhang,
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Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future. Int J Mol Sci 2022; 23:ijms23010498. [PMID: 35008925 PMCID: PMC8745668 DOI: 10.3390/ijms23010498] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 02/05/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. In this sense, this study aimed to perform a review of the role of organokines in NASH. Thus, by combining descriptors such as NASH, organokines, oxidative stress, inflammation, insulin resistance, and dyslipidemia, a search was carried out in the EMBASE, MEDLINE-PubMed, and Cochrane databases of articles published in the last ten years. Insulin resistance, inflammation and mitochondrial dysfunction, fructose, and intestinal microbiota were factors identified as participating in the genesis and progression of NASH. Changes in the pattern of organokines secretion (adipokines, myokines, hepatokines, and osteokines) directly or indirectly contribute to aggravating the condition or compromise homeostasis. Thus, further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.
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Zhao Z, Guo Z, Yin Z, Qiu Y, Zhou B. Gut Microbiota Was Involved in the Process of Liver Injury During Intra-Abdominal Hypertension. Front Physiol 2021; 12:790182. [PMID: 34955896 PMCID: PMC8703017 DOI: 10.3389/fphys.2021.790182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/12/2021] [Indexed: 11/22/2022] Open
Abstract
Background: Intestinal damage caused by intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) can lead to the ectopic gut microbiota, which can contribute to liver injury via portal veins. Therefore, it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury. The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study. Methods: A model of IAH was established in rats, and 16S rRNA sequencing was analyzed for gut microbiota in the feces of rats. The elimination of gut microbiota was completed by antibiotics gavage, and fecal microbiota transplantation (FMT) was used to change the composition of gut microbiota in rats. Results: In addition to the traditional cause of liver blood vessel compression, liver injury caused by IAH was also associated with gut microbiota dysbiosis. Gut microbiota clearance can relieve liver injury caused by IAH, while FMT from IAH-intervened rats can aggravate IAH-related liver injury. Conclusion: The gut microbiota was one of the most important factors contributing to the IAH-related liver injury, and the JNK/p38 signaling pathway was activated in this process.
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Affiliation(s)
- Zeyu Zhao
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhengchang Guo
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhengliang Yin
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yue Qiu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Bo Zhou
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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