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Hao X, Song H, Su X, Li J, Ye Y, Wang C, Xu X, Pang G, Liu W, Li Z, Luo T. Prophylactic effects of nutrition, dietary strategies, exercise, lifestyle and environment on nonalcoholic fatty liver disease. Ann Med 2025; 57:2464223. [PMID: 39943720 PMCID: PMC11827040 DOI: 10.1080/07853890.2025.2464223] [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: 08/14/2024] [Revised: 01/16/2025] [Accepted: 01/25/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and its prevalence has risen sharply. However, whether nutrition, dietary strategies, exercise, lifestyle and environment have preventive value for NAFLD remains unclear. METHODS Through searching 4 databases (PubMed, Web of Science, Embase and the Cochrane Library) from inception to January 2025, we selected studies about nutrition, dietary strategies, exercise, lifestyle and environment in the prevention of NAFLD and conducted a narrative review on this topic. RESULTS Reasonable nutrient intake encompassing macronutrients and micronutrients have an independent protective relationship with NAFLD. Besides, proper dietary strategies including mediterranean diet, intermittent fasting diet, ketogenic diet, and dietary approaches to stop hypertension diet have their inhibitory effects on the developmental process of NAFLD. Moreover, right exercises including walking, jogging, bicycling, and swimming are recommended for the prevention of NAFLD because they could effectively reduce weight, which is an important risk factor for NAFLD, and improve liver function. In addition, embracing a healthy lifestyle including reducing sedentary behavior, not smoking, sleeping well and brushing teeth regularly is integral since it not only could reduce the risk of NAFLD but also significantly contribute to overall prevention and control. Finally, the environment, including the social and natural environments, plays a potential role in NAFLD prevention. CONCLUSION Nutrition, dietary strategies, exercise, lifestyle and environment play an important role in the prevention of NAFLD. Moreover, this review offers comprehensive prevention recommendations for people at high risk of NAFLD.
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Affiliation(s)
- Xiangyong Hao
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Hao Song
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Xin Su
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Jian Li
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Youbao Ye
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Cailiu Wang
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Xiao Xu
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Guanglong Pang
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Wenxiu Liu
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Zihan Li
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Tian Luo
- The Institute for Clinical Research and Translational Medicine, Gansu Provincial Hospital, Lanzhou, China
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Ren T, Chen Q, Zhu C. The extrahepatic markers in postmenopausal women with metabolic dysfunction-associated steatotic liver disease: A systematic review. Clin Nutr ESPEN 2025; 68:22-31. [PMID: 40315986 DOI: 10.1016/j.clnesp.2025.04.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/25/2025] [Accepted: 04/24/2025] [Indexed: 05/04/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent, multifactorial systemic metabolic disorder, now recognized as the most common chronic liver disease globally. Female susceptibility to MASLD varies across menstrual states, influenced by genetic factors, age, menopausal status, and physical activity. Postmenopausal women, experiencing a significant reduction in estrogen, are particularly vulnerable to metabolic imbalances, increasing their risk of MASLD, disease progression, liver fibrosis, insulin resistance, and adverse cardiovascular events compared to premenopausal women and age-matched men. This review systematically synthesizes current research on extrahepatic abnormalities associated with MASLD in postmenopausal women. This review identifies key extrahepatic markers associated with MASLD in postmenopausal women, highlighting gaps in current research and proposing targeted screening and management strategies. (Graphical Abstract).
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Affiliation(s)
- Tingting Ren
- Department of Infectious Disease, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Qingling Chen
- Department of Infectious Disease, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
| | - Chuanlong Zhu
- Department of Infectious Disease, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; Department of Infectious and Tropical Diseases, The Second Affiliated Hospital, NHC Key Laboratory of Tropical Disease Control, Hainan Medical University, Haikou, China.
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Boulos M, Mousa RS, Jeries N, Simaan E, Alam K, Bulus B, Assy N. Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome. Int J Mol Sci 2025; 26:3448. [PMID: 40244398 PMCID: PMC11989262 DOI: 10.3390/ijms26073448] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/25/2025] [Accepted: 03/30/2025] [Indexed: 04/18/2025] Open
Abstract
Metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related, with rapidly increasing prevalence globally, driving significant public health concerns. Both conditions share common pathophysiological mechanisms such as insulin resistance (IR), adipose tissue dysfunction, oxidative stress, and gut microbiota dysbiosis, which contribute to their co-occurrence and progression. While the clinical implications of this overlap, including increased cardiovascular, renal, and hepatic risk, are well recognized, current diagnostic and therapeutic approaches remain insufficient due to the clinical and individuals' heterogeneity and complexity of these diseases. This review aims to provide an in-depth exploration of the molecular mechanisms linking MetS and MASLD, identify critical gaps in our understanding, and highlight existing challenges in early detection and treatment. Despite advancements in biomarkers and therapeutic interventions, the need for a comprehensive, integrated approach remains. The review also discusses emerging therapies targeting specific pathways, the potential of precision medicine, and the growing role of artificial intelligence in enhancing research and clinical management. Future research is urgently needed to combine multi-omics data, precision medicine, and novel biomarkers to better understand the complex interactions between MetS and MASLD. Collaborative, multidisciplinary efforts are essential to develop more effective diagnostic tools and therapies to address these diseases on a global scale.
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Affiliation(s)
- Mariana Boulos
- Internal Medicine Department, Galilee Medical Centre, Nahariya 221001, Israel; (R.S.M.); (N.J.); (E.S.); (K.A.); (B.B.); (N.A.)
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Rabia S. Mousa
- Internal Medicine Department, Galilee Medical Centre, Nahariya 221001, Israel; (R.S.M.); (N.J.); (E.S.); (K.A.); (B.B.); (N.A.)
| | - Nizar Jeries
- Internal Medicine Department, Galilee Medical Centre, Nahariya 221001, Israel; (R.S.M.); (N.J.); (E.S.); (K.A.); (B.B.); (N.A.)
| | - Elias Simaan
- Internal Medicine Department, Galilee Medical Centre, Nahariya 221001, Israel; (R.S.M.); (N.J.); (E.S.); (K.A.); (B.B.); (N.A.)
| | - Klode Alam
- Internal Medicine Department, Galilee Medical Centre, Nahariya 221001, Israel; (R.S.M.); (N.J.); (E.S.); (K.A.); (B.B.); (N.A.)
| | - Bulus Bulus
- Internal Medicine Department, Galilee Medical Centre, Nahariya 221001, Israel; (R.S.M.); (N.J.); (E.S.); (K.A.); (B.B.); (N.A.)
| | - Nimer Assy
- Internal Medicine Department, Galilee Medical Centre, Nahariya 221001, Israel; (R.S.M.); (N.J.); (E.S.); (K.A.); (B.B.); (N.A.)
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
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Yao Y, Hong Q, Ding S, Cui J, Li W, Zhang J, Sun Y, Yu Y, Yu M, Zhang C, Chen L, Jiang J, Hu Y. An umbrella review of meta-analyses on the effects of microbial therapy in metabolic dysfunction-associated steatotic liver disease. Clin Nutr 2025; 47:1-13. [PMID: 39978229 DOI: 10.1016/j.clnu.2025.02.007] [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: 11/08/2024] [Revised: 12/09/2024] [Accepted: 02/04/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND Current pharmacological treatments for metabolic dysfunction-associated steatotic liver disease (MASLD) are often accompanied by adverse side effects. Consequently, probiotics, prebiotics, and synbiotics, which are bioactive compounds from fermented foods and offer fewer side effects, have garnered significant attention as alternative therapeutic strategies. OBJECTIVE This study aims to assess the efficacy of microbial therapies-probiotics, prebiotics, and synbiotics-in managing MASLD and to identify the optimal treatment modality for various clinical indicators through a comprehensive umbrella review of meta-analyses. METHODS A thorough literature search was conducted across PubMed, Web of Science, EMBASE, Cochrane Library, and Scopus to identify 23 meta-analyses over 18,999 MASLD patients as of November 2024. RESULTS The findings indicate that microbial treatments positively influence levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), homeostasis model assessment of insulin resistance (HOMA-IR), insulin, tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and body mass index (BMI) in MASLD patients. Notably, probiotics were most effective in reducing TC, ALT, AST, GGT, insulin, TNF-α, and BMI; prebiotics were most effective in reducing TG; and synbiotics were most effective in reducing LDL-C, HOMA-IR, and CRP. CONCLUSION Our study provides robust evidence for microbial treatments of MASLD, enabling targeted interventions for different indicators.
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Affiliation(s)
- Yuanyue Yao
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Qing Hong
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, 200436, China
| | - Siqi Ding
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Jie Cui
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Wenhui Li
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Jian Zhang
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Ye Sun
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Yiyang Yu
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Mingzhou Yu
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Chengcheng Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, 214122, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, China
| | - Lianmin Chen
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Nanjing Medical University, Nanjing, 21100, China
| | - Jinchi Jiang
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China.
| | - Yonghong Hu
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
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Feng Y, Mei W, Chen Q, Chen X, Ni Y, Lei M, Liu J. Probiotic Supplementation Alleviates Corticosterone-Induced Fatty Liver Disease by Regulating Hepatic Lipogenesis and Increasing Gut Microbiota Diversity in Broilers. Microorganisms 2025; 13:200. [PMID: 39858968 PMCID: PMC11767375 DOI: 10.3390/microorganisms13010200] [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: 12/09/2024] [Revised: 12/19/2024] [Accepted: 01/15/2025] [Indexed: 01/27/2025] Open
Abstract
Emerging evidence indicates a close relationship between gut microbiota and fatty liver disease. It has been suggested that gut microbiota modulation with probiotics ameliorates fatty liver disease in rodents and humans, yet it remains unclear whether the same results will also be obtained in poultry. The aim of this study was to investigate whether a mixture of probiotics supplemented after hatching can prevent CORT-induced fatty liver disease in broilers, and to determine how such effects, if any, are associated with hepatic de novo lipogenesis and gut microbiota composition. Ninety-six one-day-old green-legged chickens were divided into a control group (CON) and probiotic group (PB). At 28 days of age, fatty liver was induced in 16 broilers that were randomly selected from the CON or PB group. At the end of the experiment, broilers from four groups, (i) the control group (CON), (ii) corticosterone group (CORT), (iii) probiotic group (PB), and (iv) PB plus CORT group (CORT&PB), were slaughtered for sampling and analysis. The results showed that probiotic administration significantly prevented CORT-induced body weight loss (p < 0.05) but did not alleviate the weight loss of immune organs caused by CORT. Compared to CON, the broilers in the CORT group exhibited a significant increase in triglyceride (TG) levels in plasma and liver (p < 0.01), as well as severe hepatocytic steatosis and hepatocellular ballooning, which was accompanied by the upregulation of hepatic lipogenesis gene expression. However, probiotic supplementation markedly decreased the intrahepatic lipid accumulation and steatosis histological score, which was associated with the downregulation of sterol regulatory element-binding protein-1 (SREBP1) and acetyl-CoA carboxylase (ACC) mRNA (p < 0.05) and the expression of its protein (p = 0.06). The cecal microbiota composition was determined by 16S rRNA high-throughput sequencing. The results showed that CORT treatment induced distinct gut microbiota alterations with a decrease in microbial diversity and an increase in Proteobacteria abundance (p < 0.05). In contrast, probiotic supplementation increased the beta diversity, the community richness, and the diversity index (p > 0.05), as well as the abundance of Intestinimonas (p < 0.05). Our results indicate that CORT treatment induced severe fatty liver disease and altered the gut microbiota composition in broilers. However, post-hatching probiotic supplementation had a beneficial effect on alleviating fatty liver disease by regulating lipogenic gene expression and increasing gut microbiota diversity and the abundance of beneficial bacteria. We demonstrate for the first time that the supplementation of probiotics to chicks had a beneficial effect on preventing fatty liver disease through regulating lipogenic gene expression and improving the gut microbial balance. Thus, our results indicate that probiotics are a potential nutritional agent for preventing fatty liver disease in chickens.
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Affiliation(s)
- Yuyan Feng
- Institute of Animal Husbandry, Jiangsu Academy of Agricultural Sciences, Nanjing 210094, China; (Y.F.); (X.C.)
- Key Laboratory of Animal Physiologic and Biochemistry, College of Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Nanjing Agricultural University, Nanjing 210094, China; (W.M.); (Q.C.); (Y.N.)
| | - Wenqing Mei
- Key Laboratory of Animal Physiologic and Biochemistry, College of Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Nanjing Agricultural University, Nanjing 210094, China; (W.M.); (Q.C.); (Y.N.)
| | - Qu Chen
- Key Laboratory of Animal Physiologic and Biochemistry, College of Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Nanjing Agricultural University, Nanjing 210094, China; (W.M.); (Q.C.); (Y.N.)
| | - Xiaojing Chen
- Institute of Animal Husbandry, Jiangsu Academy of Agricultural Sciences, Nanjing 210094, China; (Y.F.); (X.C.)
- Key Laboratory of Animal Physiologic and Biochemistry, College of Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Nanjing Agricultural University, Nanjing 210094, China; (W.M.); (Q.C.); (Y.N.)
| | - Yingdong Ni
- Key Laboratory of Animal Physiologic and Biochemistry, College of Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Nanjing Agricultural University, Nanjing 210094, China; (W.M.); (Q.C.); (Y.N.)
| | - Mingming Lei
- Institute of Animal Husbandry, Jiangsu Academy of Agricultural Sciences, Nanjing 210094, China; (Y.F.); (X.C.)
| | - Jie Liu
- Institute of Animal Husbandry, Jiangsu Academy of Agricultural Sciences, Nanjing 210094, China; (Y.F.); (X.C.)
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Nychas E, Marfil-Sánchez A, Chen X, Mirhakkak M, Li H, Jia W, Xu A, Nielsen HB, Nieuwdorp M, Loomba R, Ni Y, Panagiotou G. Discovery of robust and highly specific microbiome signatures of non-alcoholic fatty liver disease. MICROBIOME 2025; 13:10. [PMID: 39810263 PMCID: PMC11730835 DOI: 10.1186/s40168-024-01990-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 11/26/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND The pathogenesis of non-alcoholic fatty liver disease (NAFLD) with a global prevalence of 30% is multifactorial and the involvement of gut bacteria has been recently proposed. However, finding robust bacterial signatures of NAFLD has been a great challenge, mainly due to its co-occurrence with other metabolic diseases. RESULTS Here, we collected public metagenomic data and integrated the taxonomy profiles with in silico generated community metabolic outputs, and detailed clinical data, of 1206 Chinese subjects w/wo metabolic diseases, including NAFLD (obese and lean), obesity, T2D, hypertension, and atherosclerosis. We identified highly specific microbiome signatures through building accurate machine learning models (accuracy = 0.845-0.917) for NAFLD with high portability (generalizable) and low prediction rate (specific) when applied to other metabolic diseases, as well as through a community approach involving differential co-abundance ecological networks. Moreover, using these signatures coupled with further mediation analysis and metabolic dependency modeling, we propose synergistic defined microbial consortia associated with NAFLD phenotype in overweight and lean individuals, respectively. CONCLUSION Our study reveals robust and highly specific NAFLD signatures and offers a more realistic microbiome-therapeutics approach over individual species for this complex disease. Video Abstract.
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Affiliation(s)
- Emmanouil Nychas
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, Jena, 07745, Germany
| | - Andrea Marfil-Sánchez
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, Jena, 07745, Germany
| | - Xiuqiang Chen
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, Jena, 07745, Germany
| | - Mohammad Mirhakkak
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, Jena, 07745, Germany
| | - Huating Li
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai, 200233, China
| | - Weiping Jia
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai, 200233, China
| | - Aimin Xu
- The State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China
- Department of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
| | | | - Max Nieuwdorp
- Amsterdam UMC, Location AMC, Department of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands
| | - Rohit Loomba
- Department of Medicine, MASLD Research Center, University of California, San Diego, La Jolla, CA, 92093, USA
| | - Yueqiong Ni
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, Jena, 07745, Germany.
- Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai, 200233, China.
- Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany.
| | - Gianni Panagiotou
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11A, Jena, 07745, Germany.
- Faculty of Biological Sciences, Friedrich Schiller University, Jena, 07745, Germany.
- Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
- Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany.
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Jeon S, Lee H, Kim SY, Lee CH, Lim Y. Effects of Metabolites Derived from Guava ( Psidium guajava L.) Leaf Extract Fermented by Limosilactobacillus fermentum on Hepatic Energy Metabolism via SIRT1-PGC1α Signaling in Diabetic Mice. Nutrients 2024; 17:7. [PMID: 39796441 PMCID: PMC11722574 DOI: 10.3390/nu17010007] [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: 11/25/2024] [Revised: 12/20/2024] [Accepted: 12/22/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND/OBJECTIVES Type 2 diabetes mellitus (T2DM) is considered a serious risk to public health since its prevalence is rapidly increasing worldwide despite numerous therapeutics. Insulin resistance in T2DM contributes to chronic inflammation and other metabolic abnormalities that generate fat accumulation in the liver, eventually leading to the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Recently, the possibility that microbial-derived metabolites may alleviate MAFLD through enterohepatic circulation has emerged, but the underlying mechanism remains unclear. In this research, we utilized metabolites obtained from the fermentation of guava leaf extract, which is well-known for its antidiabetic activity, to investigate their effects and mechanisms on MAFLD. METHODS Diabetes was induced by a high-fat diet and streptozotocin injection (80 mg/kg body weight) twice in mice. Subsequently, mice whose fasting blood glucose levels were measured higher than 300 mg/dL were administered with metabolites of Limosilactobacillus fermentum (LF) (50 mg/kg/day) or guava leaf extract fermented by L. fermentum (GFL) (50 mg/kg/day) by gavage for 15 weeks. RESULTS GFL supplementation mitigated hyperglycemia and hepatic insulin resistance. Moreover, GFL regulated abnormal hepatic histological changes and lipid profiles in diabetic mice. Furthermore, GFL enhanced energy metabolism by activating the sirtuin1 (SIRT1)/proliferator-activated receptor γ coactivator 1α (PGC1α)/peroxisome proliferator-activated receptor (PPAR)-α pathway in diabetic mice. Meanwhile, GFL supplementation suppressed hepatic inflammation in diabetic mice. CONCLUSIONS Taken together, the current study elucidated that GFL could be a potential therapeutic to ameliorate hyperglycemia and hepatic steatosis by improving SIRT1/PGC-1α/ PPAR-α-related energy metabolism in T2DM.
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Affiliation(s)
- Sohyun Jeon
- Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea; (S.J.); (H.L.)
| | - Heaji Lee
- Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea; (S.J.); (H.L.)
| | - Sun-Yeou Kim
- College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea;
| | - Choong-Hwan Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea;
| | - Yunsook Lim
- Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea; (S.J.); (H.L.)
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Yaghmaei H, Bahanesteh A, Soltanipur M, Takaloo S, Rezaei M, Siadat SD. The Role of Gut Microbiota Modification in Nonalcoholic Fatty Liver Disease Treatment Strategies. Int J Hepatol 2024; 2024:4183880. [PMID: 39444759 PMCID: PMC11498984 DOI: 10.1155/2024/4183880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 08/25/2024] [Accepted: 10/05/2024] [Indexed: 10/25/2024] Open
Abstract
One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.
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Affiliation(s)
- Hessam Yaghmaei
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
| | | | - Masood Soltanipur
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sobhan Takaloo
- Biomedical Engineering Department, Hamedan University of Technology, Hamedan, Iran
| | - Mahdi Rezaei
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
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Ding S, Hong Q, Yao Y, Gu M, Cui J, Li W, Zhang J, Zhang C, Jiang J, Hu Y. Meta-analysis of randomized controlled trials of the effects of synbiotics, probiotics, or prebiotics in controlling glucose homeostasis in non-alcoholic fatty liver disease patients. Food Funct 2024; 15:9954-9971. [PMID: 39264166 DOI: 10.1039/d4fo02561j] [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: 09/13/2024]
Abstract
Background: Probiotics, prebiotics, and synbiotics have been suggested as a possible therapy for non-alcoholic fatty liver disease (NAFLD). However, their efficacy in improving blood glucose levels in NAFLD patients remains uncertain. Objective: The aim of this study was to assess the effects of supplementation with probiotics, prebiotics, or synbiotics on fasting blood glucose (FBG) levels in NAFLD patients. Methods: We searched PubMed, Web of Science, and Google Scholar for relevant trials published up to March 2024. Out of 3369 identified studies, 24 randomized controlled trials (RCTs) were included. Results: Probiotic, prebiotic, or synbiotic supplementation substantially reduced FBG (n = 23; standard mean difference (SMD) = -0.17; 95% confidence interval (CI): -0.30, -0.03; P = 0.02), fasting insulin levels (n = 12; SMD = -0.28; 95% CI: -0.49, -0.07; P = 0.01), and homeostatic model assessment for insulin resistance (HOMA-IR; n = 14; SMD = -0.28; 95% CI: -0.47, -0.09; P = 0.004). However, glycosylated hemoglobin (HbA1c; n = 3; SMD = -0.17; 95% CI: -0.48, 0.13; P = 0.27) was not significantly affected. The FBG-decreasing effect diminished as the body mass index (BMI) of volunteers increased in the baseline. Additionally, the number of probiotic strains and geographic region were shown to significantly affect FBG levels. Conclusion: This meta-analysis indicates that supplementation with probiotics, prebiotics, or synbiotics may aid in controlling glucose homeostasis in patients with NAFLD.
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Affiliation(s)
- Siqi Ding
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Qing Hong
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd, Shanghai, 200436, China
| | - Yuanyue Yao
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Minwen Gu
- College of Biological and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Jie Cui
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Wenhui Li
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Jian Zhang
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Chengcheng Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jinchi Jiang
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Yonghong Hu
- College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
- State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, China
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10
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Wang Y, Yang Z, Tang H, Sun X, Qu J, Lu S, Rao B. Faecal microbiota transplantation is better than probiotics for tissue regeneration of type 2 diabetes mellitus injuries in mice. Arch Physiol Biochem 2024; 130:333-341. [PMID: 35675471 DOI: 10.1080/13813455.2022.2080229] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 05/10/2022] [Accepted: 05/11/2022] [Indexed: 12/25/2022]
Abstract
CONTEXT Western diet and unhealthy lifestyle have contributed to the continued growth of type 2 diabetes mellitus (T2DM). T2DM is associated with dysbacteriosis, and studies have found that altering the gut microbiota has a positive effect on treatment. OBJECTIVE In addition to hyperglycaemia, T2DM often causes damage to multiple organs. However, there are few studies on organ damage from faecal microbiota transplantation (FMT). MATERIALS AND METHODS T2DM mice were divided into four groups and were given phosphate buffered saline (PBS) (T2DM group), FMT (FMT group), Lactobacillus (LAB group), and Bifidobacterium (BIO group) by gavage for six weeks, respectively. Mice on a normal diet (control group) were gavaged with PBS for six weeks. RESULTS After gavage treatment, FMT, LAB, and BIO groups were similar in lowering glucose, endotoxemia was slightly reduced, and the colonic mucus layer and liver lobules developed towards normal tissue. Surprisingly, we found that the FMT group had unique effects on islet cell regeneration, increased functional β cells, and insulin sensitivity. DISCUSSION AND CONCLUSION Lactobacillus has the best glucose-lowering effect, but FMT has obvious advantages in β-cell regeneration, which provides new treatment ideas for tissue damage caused by T2DM.
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Affiliation(s)
- Yuying Wang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
- Department of Gastrointestinal Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Zhenpeng Yang
- Department of Gastrointestinal Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Huazhen Tang
- Department of Gastrointestinal Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Xibo Sun
- Department of Gastrointestinal Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Jinxiu Qu
- Department of Gastrointestinal Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Shuai Lu
- Department of Gastrointestinal Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Benqiang Rao
- Department of Gastrointestinal Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
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11
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Banerjee G, Papri SR, Satapathy SK, Banerjee P. Akkermansia muciniphila - A Potential Next-generation Probiotic for Non-alcoholic Fatty Liver Disease. Curr Pharm Biotechnol 2024; 25:426-433. [PMID: 37724669 DOI: 10.2174/1389201025666230915103052] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 07/20/2023] [Accepted: 08/11/2023] [Indexed: 09/21/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions, and its growing prevalence is a serious concern worldwide, especially in Western countries. Researchers have pointed out several genetic mutations associated with NAFLD; however, the imbalance of the gut microbial community also plays a critical role in the progression of NAFLD. Due to the lack of approved medicine, probiotics gain special attention in controlling metabolic disorders like NAFLD. Among these probiotics, Akkermansia muciniphila (a member of natural gut microflora) is considered one of the most efficient and important bacterium in maintaining gut health, energy homeostasis, and lipid metabolism. In this perspective, we discussed the probable molecular mechanism of A. muciniphila in controlling the progression of NAFLD and restoring liver health. The therapeutic potential of A. muciniphila in NAFLD has been tested primarily on animal models, and thus, more randomized human trials should be conducted to prove its efficacy.
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Affiliation(s)
- Goutam Banerjee
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Suraya R Papri
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
| | - Sanjaya K Satapathy
- 2Department of Medicine, Northwell Health Center for Liver Disease & Transplantation, North Shore, University Hospital/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA
| | - Pratik Banerjee
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA
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12
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Velayati A, Kareem I, Sedaghat M, Sohrab G, Nikpayam O, Hedayati M, Abhari K, Hejazi E. Does symbiotic supplementation which contains Bacillus Coagulans Lactobacillus rhamnosus, Lactobacillus acidophilus and fructooligosaccharide has favourite effects in patients with type-2 diabetes? A randomised, double-blind, placebo-controlled trial. Arch Physiol Biochem 2023; 129:1211-1218. [PMID: 34077686 DOI: 10.1080/13813455.2021.1928225] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 05/04/2021] [Indexed: 12/15/2022]
Abstract
This study aimed to determine the effect of Bacillus Coagulans symbiotic supplementation on metabolic factors and inflammation in patients with type-2 diabetes. In this clinical trial, 50 patients with type-2 diabetes were randomly assigned to the symbiotic (containing Bacillus Coagulans + Lactobacillus rhamnosus + Lactobacillus acidophilus and fructooligosaccharide) or placebo groups to receive one sachet daily for 12 weeks. Glycaemic Index, lipid profile, and hs-CRP were measured at the beginning and end of the study. Analysis of covariance demonstrated that fasting blood glucose (FBG), insulin, homeostatic Model Assessment for Insulin Resistance (HOMA-IR), β-cell function (HOMA-β) (p <.05) and hs-CRP (p <.05) significantly declined in the treatment group compared with the placebo group. So, the current study indicated that Bacillus Coagulans symbiotic supplementation could improve metabolic factors and inflammation in patients with type-2 diabetes.
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Affiliation(s)
- Aynaz Velayati
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
| | - Iman Kareem
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
| | - Meghdad Sedaghat
- Depatment of Internal Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Golbon Sohrab
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
| | - Omid Nikpayam
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Nutrition, faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Khadijeh Abhari
- Food Sciences and Technology Department, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Hejazi
- Clinical Nutrition and dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences Tehran, Tehran, Iran
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13
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Mijangos-Trejo A, Nuño-Lambarri N, Barbero-Becerra V, Uribe-Esquivel M, Vidal-Cevallos P, Chávez-Tapia N. Prebiotics and Probiotics: Therapeutic Tools for Nonalcoholic Fatty Liver Disease. Int J Mol Sci 2023; 24:14918. [PMID: 37834367 PMCID: PMC10573697 DOI: 10.3390/ijms241914918] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 09/08/2023] [Accepted: 09/11/2023] [Indexed: 10/15/2023] Open
Abstract
Alterations in the gut-liver axis and changes in the gut microbiome are among the risk factors for the pathogenesis of non-alcoholic fatty liver disease (NAFLD). These patients show increased bacterial overgrowth in the small intestine and impaired intestinal permeability. Therefore, therapeutic options such as probiotics or prebiotics have been investigated to modulate intestinal microbiota composition to improve NAFLD. Most in vivo and in vitro probiotic studies have focused on reducing hepatic fat accumulation. The beneficial effects of probiotics on NAFLD have been demonstrated in animal models, and the most widely used microorganisms are those of the Lactobacillus and Bifidobacterium genera. In animal models, probiotics help restore the intestinal microbiota and improve the integrity of the intestinal barrier. This narrative review summarizes published evidence and the likely benefits of probiotics and prebiotics as a therapeutic option for patients with NAFLD.
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14
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Mahapatro A, Bawna F, Kumar V, Daryagasht AA, Gupta S, Raghuma N, Moghdam SS, Kolla A, Mahapatra SS, Sattari N, Amini-Salehi E, Nayak SS. Anti-inflammatory effects of probiotics and synbiotics on patients with non-alcoholic fatty liver disease: An umbrella study on meta-analyses. Clin Nutr ESPEN 2023; 57:475-486. [PMID: 37739694 DOI: 10.1016/j.clnesp.2023.07.087] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 07/28/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND AND AIM The impact of chronic low-grade inflammation in the development of non-alcoholic fatty liver disease (NAFLD) has been studied widely. Previous studies showed gut pathogens' effects on inflammation development in NAFLD patients; hence, hypothetically, gut microbial therapy by administration of probiotics, synbiotics, and prebiotics may alleviate inflammation in these individuals. Several studies were performed in this regard; however, conflicting results were obtained. In this study, we aimed to comprehensively evaluate the effects of gut microbial therapy on inflammatory markers in NAFLD patients in a meta-umbrella design. METHODS Two independent researchers investigated international databases, including PubMed, Web of Science, Scopus, and Cochrane Library, from inception until March 2023. Meta-analyses evaluating the impact of probiotics, synbiotics, or prebiotics on inflammatory markers of patients with NAFLD were eligible for our study. AMASTAR 2 checklist was used to evaluate the quality of included studies. Random effect model was performed for the analysis, and Egger's regression test was conducted to determine publication bias. RESULTS A total number of 12 studies were entered into our analysis. Our findings revealed that gut microbial therapy could significantly reduce serum C-reactive protein (CRP) levels among NAFLD patients (ES: -0.58; 95% CI: -0.73, -0.44, P < 0.001). In subgroup analysis, this reduction was observed with both probiotics (ES: -0.63; 95% CI: -0.81, -0.45, P < 0.001) and synbiotics (ES: -0.49; 95% CI: -0.74, -0.24, P < 0.001). In addition, gut microbial therapy could significantly decrease tumor necrosis factor-a (TNF-a) levels in NAFLD patients (ES: -0.48; 95% CI: -0.67 to -0.30, P < 0.001). In subgroup analysis, this decrease was observed with probiotics (ES: -0.32; 95% CI: -0.53, -0.11, P = 0.002) and synbiotics (ES: -0.96; 95% CI: -1.32, -0.60, P < 0.001). Not enough information was available for assessing prebiotics' impacts. CONCLUSION The results of this umbrella review suggest that probiotics and synbiotics have promising effects on inflammatory markers, including TNF-a and CRP; however, more research is needed regarding the effects of prebiotics. PROSPERO REGISTRATION CODE CRD42022346998.
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Affiliation(s)
| | - Fnu Bawna
- Dow University of Health Sciences, Karachi, Pakistan
| | | | | | - Siddharth Gupta
- Baptist Memorial Hospital, North Mississippi, Mississippi, USA
| | - Nakka Raghuma
- GSL Medical College and General Hospital, Rajamahendravaram, Andhra Pradesh, India
| | | | - Akshita Kolla
- SRM Medical College Hospital and Research Center, Chennai, India
| | | | - Nazila Sattari
- School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | | | - Sandeep S Nayak
- Department of Internal Medicine, Bridgeport Hospital, Bridgeport, USA
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15
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Lv H, Tao F, Peng L, Chen S, Ren Z, Chen J, Yu B, Wei H, Wan C. In Vitro Probiotic Properties of Bifidobacterium animalis subsp. lactis SF and Its Alleviating Effect on Non-Alcoholic Fatty Liver Disease. Nutrients 2023; 15:nu15061355. [PMID: 36986084 PMCID: PMC10053994 DOI: 10.3390/nu15061355] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 02/20/2023] [Accepted: 03/06/2023] [Indexed: 03/15/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with many influencing factors. With the increasing role of the gut–liver axis in various liver diseases, research on the prevention and treatment of NAFLD with probiotics is increasing. In the present study, a Bifidobacterium animalis subsp. strain, B. lactis SF, was isolated from the feces of healthy infants and characterized by sequencing of the 16S rDNA. A systematic probiotic evaluation was carried out, and a diet-induced mouse model was constructed to study the effect and mechanism of B. lactis SF on diet-induced NAFLD. Results show that B. lactis SF has excellent gastrointestinal fluid tolerance and intestinal colonization, and strong antibacterial and antioxidant capabilities. In vivo, B. lactis SF modulated intestinal flora, restored the intestinal barrier, and inhibited LPS entrance into the portal circulation, which subsequently inhibited the TLR4/NF-κB and modulated the PI3K-Akt/AMPK signaling pathway, attenuated the inflammatory response, and reduced lipid accumulation. In addition, B. lactis SF attenuated oxidative stress and further alleviated autophagy, resulting in an ameliorative effect on NAFLD. Therefore, our study provides a new dietary method for the treatment of NAFLD.
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Affiliation(s)
- Huihui Lv
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Feiyue Tao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Lingling Peng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Shufang Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Zhongyue Ren
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Jiahui Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
| | - Bo Yu
- Jiangxi-OAI Joint Research Institute, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China;
| | - Hua Wei
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; (H.L.); (F.T.); (L.P.); (S.C.); (Z.R.); (J.C.); (H.W.)
- Jiangxi-OAI Joint Research Institute, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China;
| | - Cuixiang Wan
- Jiangxi-OAI Joint Research Institute, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China;
- Correspondence: ; Tel.: +86-791-8833-4578; Fax: +86-791-8833-3708
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16
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Wu CS, Lin CC, Hsieh FC, Wu TY, Fang AH. Antiobesity Effect of Lacticaseibacillus paracasei LM-141 on High-Fat Diet-Induced Rats through Alleviation of Inflammation and Insulin Resistance. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2023; 2023:1011591. [PMID: 37114144 PMCID: PMC10129431 DOI: 10.1155/2023/1011591] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 03/10/2023] [Accepted: 03/18/2023] [Indexed: 04/29/2023]
Abstract
In this study, we set out to evaluate the antiobesity activities of our newly isolated Lacticaseibacillus paracasei LM-141 (LPLM141) using a high-fat diet (HFD)-fed rat model. Male Sprague-Dawley rats were fed with a HFD with or without low-dosage (2 × 107 CFU/day per rat) or high-dosage (2 × 109 CFU/day per rat) LPLM141 for 14 weeks. The results showed that administration of LPLM141 significantly decreased body weight gain, liver weight, adipose tissue weight, and epididymal white adipocyte size increased by HFD feeding. The abnormal serum lipid profile induced by HFD feeding was normalized by administration of LPLM141. The enhanced chronic low-grade inflammation in HFD-fed rats was reduced by LPLM141 supplementation, as reflected by decreased serum lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) levels, reduced macrophage infiltration in adipose tissue, and increased serum adiponectin concentration. In addition, the elevations of proinflammatory cytokine genes and suppression of PPAR-γ mRNA in adipose tissues of rats fed with a HFD were markedly reversed by LPLM141 administration. Oral administration of LPLM141 induced browning of epididymal white adipose tissue (eWAT) and activation of interscapular brown adipose tissue (iBAT) in rats fed with HFD. Consumption of LPLM141 exhibited a significant amelioration in insulin resistance, which were mechanistically caused by downregulation of the serum leptin level and upregulation of hepatic IRS-1 and p-Akt protein expressions, in HFD treated rats. LPLM141 consumption significantly decreased hepatic lipogenic gene expressions and preserved liver function stimulated by HFD treatment. Administration of LPLM141 obviously mitigated hepatic steatosis observed in HFD feeding rats. Our current findings shed light on LPLM141 supplementation that exhibited an antiobesity effect in HFD-fed rats by alleviating inflammation and insulin resistance, which further highlighted the potential of utilizing LPLM141 as a preventive/therapeutic probiotic agent for obesity.
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Affiliation(s)
- Ching-Shuang Wu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80708, Taiwan
| | - Chih-Chieh Lin
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | | | - Tai-Yun Wu
- Department of General Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11466, Taiwan
| | - Ai-Hui Fang
- Department of Microbiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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17
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Alshehhi MK, Nazir A. Microbial management of nonalcoholic fatty acid liver diseases. MICROBIOME THERAPEUTICS 2023:139-161. [DOI: 10.1016/b978-0-323-99336-4.00010-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Pan Z, Mao B, Zhang Q, Tang X, Yang B, Zhao J, Cui S, Zhang H. Postbiotics Prepared Using Lactobacillus paracasei CCFM1224 Prevent Nonalcoholic Fatty Liver Disease by Modulating the Gut Microbiota and Liver Metabolism. Int J Mol Sci 2022; 23:ijms232113522. [PMID: 36362307 PMCID: PMC9653709 DOI: 10.3390/ijms232113522] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 11/06/2022] Open
Abstract
Postbiotics are rich in a variety of bioactive components, which may have beneficial effects in inhibiting hepatic lipid accumulation. In this study, we investigated the preventive effects of postbiotics (POST) prepared from Lactobacillus paracasei on non-alcoholic fatty liver disease (NAFLD). Our results showed that when mice ingested a high-fat diet (HFD) and POST simultaneously, weight gain was slowed, epididymal white fat hypertrophy and insulin resistance were suppressed, serum biochemical indicators related to blood lipid metabolism were improved, and hepatic steatosis and liver inflammation decreased. Bacterial sequencing showed that POST modulated the gut microbiota in HFD mice, increasing the relative abundance of Akkermansia and reducing the relative abundance of Lachnospiraceae NK4A136 group, Ruminiclostridium and Bilophila. Spearman’s correlation analysis revealed significant correlations between lipid metabolism parameters and gut microbes. Functional prediction results showed that the regulation of gut microbiota was associated with the improvement of metabolic status. The metabolomic analysis of the liver revealed that POST-regulated liver metabolic pathways, such as glycerophospholipid and ether lipid metabolism, pantothenate and CoA biosynthesis, some parts of amino acid metabolism, and other metabolic pathways. In addition, POST regulated the gene expression in hepatocytes at the mRNA level, thereby regulating lipid metabolism. These findings suggest that POST plays a protective role against NAFLD and may exert its efficacy by modulating the gut microbiota and liver metabolism, and these findings may be applied to related functional foods.
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Affiliation(s)
- Zhenghao Pan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Bingyong Mao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Qiuxiang Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xin Tang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Bo Yang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Shumao Cui
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Correspondence: ; Tel.: +86-0510-85912155
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
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Lin YC, Lin HF, Wu CC, Chen CL, Ni YH. Pathogenic effects of Desulfovibrio in the gut on fatty liver in diet-induced obese mice and children with obesity. J Gastroenterol 2022; 57:913-925. [PMID: 35976494 DOI: 10.1007/s00535-022-01909-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 07/24/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD. METHODS C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L. reuteri) or Lactobacillus rhamnosus GG plus Bifidobacterium animalis subsp. lactis BB12 (LGG plus BB12). Their fecal microbiomes identified by 16S rRNA sequencing were correlated with the severity of fatty liver. We then used a human cohort to confirm the role of the microbe(s). The HFD-fed mice were administrated with the identified bacterium, Desulfovibrio. The histopathological changes in the liver and ileum were analyzed. RESULTS Lactobacillus and Bifidobacterium improved hepatic steatosis and fibrosis in HFD-fed mice, which was related to the decreased abundance of Desulfovibrio in feces. Further human study confirmed the amount of D. piger in the fecal microbiota of obese children with NAFLD was increased. We then administered D. piger and found aggravated hepatic steatosis and fibrosis in HFD-fed mice. Hepatic expression of CD36 was significantly increased in HFD-fed mice gavaged with D. piger. In HepG2 cells, overexpression of CD36 increased lipid droplets, whereas knockdown of CD36 decreased lipid droplets. HFD-fed mice gavaged with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 density in the ileum tissue. CONCLUSIONS Our findings provide novel insights into the role of Desulfovibrio dysregulation in NAFLD. Modulation of Desulfovibrio may be a potential target for the treatment of NAFLD.
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Affiliation(s)
- Yu-Cheng Lin
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Asia Eastern University of Science and Technology, New Taipei City, Taiwan
| | - Hsueh-Fang Lin
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Chi-Chien Wu
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Chun-Liang Chen
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Yen-Hsuan Ni
- Departments of Pediatrics, College of Medicine, National Taiwan University, No.8, Chung Shan S. Rd., Taipei City, 10002, Taiwan.
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20
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Hany NM, Eissa S, Basyouni M, Hasanin AH, Aboul-Ela YM, Elmagd NMA, Montasser IF, Ali MA, Skipp PJ, Matboli M. Modulation of hepatic stellate cells by Mutaflor ® probiotic in non-alcoholic fatty liver disease management. J Transl Med 2022; 20:342. [PMID: 35907883 PMCID: PMC9338485 DOI: 10.1186/s12967-022-03543-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/17/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients. OBJECTIVE To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor® on this network. METHODS First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-β, were estimated by ELISA. RESULTS Mutaflor® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-β effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression. CONCLUSION Mutaflor® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.
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Affiliation(s)
- Noha M. Hany
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, P.O. box, Cairo, 11381 Egypt
| | - Sanaa Eissa
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, P.O. box, Cairo, 11381 Egypt
- MASRI Research Institue, Ain Shams University, Cairo, Egypt
| | - Manal Basyouni
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, P.O. box, Cairo, 11381 Egypt
| | - Amany H. Hasanin
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Yasmin M. Aboul-Ela
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Nagwa M. Abo Elmagd
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Iman F. Montasser
- Department of Gastroenterology, Hepatology and Infectious Diseases, Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud A. Ali
- Department of Molecular Microbiology, Military Medical Academy, Cairo, Egypt
| | - Paul J. Skipp
- Centre for Proteomic Research, School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK
| | - Marwa Matboli
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, P.O. box, Cairo, 11381 Egypt
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21
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Li S, Liu J, Wang Z, Duan F, Jia Z, Chen X, Li S. The promising role of probiotics/prebiotics/synbiotics in energy metabolism biomarkers in patients with NAFLD: A systematic review and meta-analysis. Front Public Health 2022; 10:862266. [PMID: 35958869 PMCID: PMC9358257 DOI: 10.3389/fpubh.2022.862266] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 07/01/2022] [Indexed: 11/13/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide, seriously harming human health, and its pathogenesis remains unclear. In recent years, increasing evidence has indicated that intestinal microbiota plays an important role in the occurrence and development of NAFLD. The regulation method of probiotics/prebiotics/synbiotics can alter the intestinal microbiota and has been suggested as an option in the treatment of NAFLD. Methods Five databases of PubMed, Embase, the Cochrane Library, clinicaltrails.gov, and China National Knowledge Infrastructure were searched initially, and then the eligible studies were screened. Finally, the data of included studieswere extracted, combined and analyzed Results A total of 29 randomized controlled trials involving 2,110 patients were included in this study. The results showed that using probiotics/prebiotics/synbiotics in the intervention group could reduce the levels of glucose (SMD = −0.23, 95% CI [−0.45, −0.01], P = 0.04), HOMA-IR (SMD = −0.47, 95% CI [−0.63, −0.31], P < 0.00001) and insulin (SMD = −0.46, 95% CI [−0.76, −0.16], P = 0.002) in sugar metabolism; in terms of lipid metabolism, the levels of TC (SMD = −0.62, 95%CI [−0.87, −0.36], P < 0.00001), and LDL-C (SMD = −0.57, 95%CI [−0.85, −0.28], P < 0.00001) were decreased; and the level of ALB was decreased in protein metabolism (SMD = −0.34, 95%CI [−0.61, −0.06], P = 0.02). Conclusions Based on the current evidence, probiotics/prebiotics/synbiotics may improve energy metabolism biomarkers in the NAFLD population, but these effects still need to be confirmed by further research. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/#aboutpage.
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Affiliation(s)
- Shudi Li
- Henan University of Chinese Medicine, Zhengzhou, China
| | - Jiangkai Liu
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Zhen Wang
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Fei Duan
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Zi Jia
- Henan University of Chinese Medicine, Zhengzhou, China
| | - Xinju Chen
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
| | - Suling Li
- The First Affiliated Hospital of Henan University of TCM, Zhengzhou, China
- *Correspondence: Suling Li
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22
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Ebrahimi-Mousavi S, Alavian SM, Sohrabpour AA, Dashti F, Djafarian K, Esmaillzadeh A. The effect of daily consumption of probiotic yogurt on liver enzymes, steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized clinical trial. BMC Gastroenterol 2022; 22:102. [PMID: 35255811 PMCID: PMC8899796 DOI: 10.1186/s12876-022-02176-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 02/21/2022] [Indexed: 02/08/2023] Open
Abstract
Background Given the increasing prevalence of non-alcoholic fatty liver disease, it is necessary to find an easy and cost-effective method in its management and treatment. Probiotics are a group of living microorganisms that might affect NAFLD through the intestinal-liver axis. The present clinical trial aims to examine the effect of probiotic yogurt consumption on liver enzymes, steatosis and liver fibrosis in patients with NAFLD. Methods Sixty-eight patients with NAFLD will be recruited in this study. After block matching for sex, BMI and age, patients will be randomly assigned to receive 300 g/d probiotic yogurt containing 106 cfu/g of Lactobacillus acidophilus and Bifidobacterium lactis strains or 300 g/d plain yogurt daily for 12 weeks and those in the control group would receive similar amounts of plain yogurts. Weight, height, and waist circumference will be measured at study baseline and after the intervention. Biochemical indicators including plasma glucose, serum insulin, lipid profile, liver markers (ALT, AST and GGT) will be examined at study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equation. The degree of steatosis and hepatic fibrosis will also be assessed at the beginning and end of the intervention by the same gastroenterologist using elastography with fibroscan. Discussion Probiotics have been suggested as a new strategy in the management of NAFLD. Their effects might be mediated through intestinal microbiota modification and production of short-chain fatty acids. Consumption of probiotic-enriched foods, rather than their supplements, might be a cost-effective method for long-term use in these patients. In case of finding the beneficial effects of probiotic yogurt consumption in the current clinical trial, its inclusion in the dietary plan of NAFLD patients can be recommended. Trial registration This clinical trial was registered in Iranian Registry of Clinical Trials (www.irct.ir) at 2021-04-19 with code number of IRCT20210201050210N1.
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Affiliation(s)
- Sara Ebrahimi-Mousavi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqyiatallah University of Medical Sciences, Tehran, Iran
| | - Amir Ali Sohrabpour
- The Liver, Pancreatic, and Biliary Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Dashti
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Kurosh Djafarian
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, P.O. Box 14155-6117, Tehran, Iran. .,Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. .,Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
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23
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Fan M, Choi YJ, Wedamulla NE, Tang Y, Han KI, Hwang JY, Kim EK. Heat-Killed Enterococcus faecalis EF-2001 Attenuate Lipid Accumulation in Diet-Induced Obese (DIO) Mice by Activating AMPK Signaling in Liver. Foods 2022; 11:575. [PMID: 35206052 PMCID: PMC8870772 DOI: 10.3390/foods11040575] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 02/09/2022] [Accepted: 02/10/2022] [Indexed: 02/04/2023] Open
Abstract
To explore the inhibitory mechanism of heat-killed Enterococcus faecalis, EF-2001 on hepatic lipid deposition, a diet-induced obese (DIO) animal model was established by high-fat diet (HFD). The DIO C57BL/6 mice were divided into four groups: the normal group without HFD (ND, n = 8), obesity group (HFD, n = 8), experimental group (HFD + EF-2001, 200 mg/kg, n = 8), and positive control group (HFD + Orlistat, 60 mg/kg, n = 8). After 4 weeks, liver and adipose tissue were fixed in 10% paraformaldehyde, followed by embedding in paraffin for tissue sectioning. The differences in body mass, body fat ratio, fatty cell area, and lipid profiling of the liver (TC, LDL, and HDL) were also determined. Moreover, Western blot was performed to analyze the expression of lipid accumulation-related proteins, including AMPK, PPARγ, SREBP-1, ACC, and FAS. Compared with the HFD group, the HFD + EF-2001 group exhibited decreased fat mass, liver index, adipocyte area, TC, and LDL, and an increased level of HDL. The results of liver hematoxylin and eosin (H&E), and oil red O staining showed that the mice in each intervention group were improved on hepatic lipid accumulation, and the mice in the HFD + EF-2001 group were the most similar to those in the normal group when compared with the HFD group. From the Western blot results, we proved that EF-2001 activated the AMPK signaling pathway. EF-2001 significantly upregulated the expressions of p-AMPK and p-ACC and downregulated PPARγ, SREBP-1, and FAS in murine liver. Taken together, these results suggest that EF-2001 decrease lipid accumulation in the DIO model mice through the AMPK pathway and ameliorate liver damage by HFD.
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Affiliation(s)
- Meiqi Fan
- Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju 27478, Korea;
| | - Young-Jin Choi
- Department of Food Science and Nutrition, College of Health Science, Dong-A University, Busan 49315, Korea; (Y.-J.C.); (N.E.W.)
- Center for Silver-Targeted Biomaterials, Brain Busan 21 Plus Program, Dong-A University, Busan 49315, Korea
- Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Korea
| | - Nishala Erandi Wedamulla
- Department of Food Science and Nutrition, College of Health Science, Dong-A University, Busan 49315, Korea; (Y.-J.C.); (N.E.W.)
- Center for Silver-Targeted Biomaterials, Brain Busan 21 Plus Program, Dong-A University, Busan 49315, Korea
- Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Korea
- Department of Export Agriculture, Faculty of Animal Science and Export Agriculture, Uva Wellassa University, Badulla 90000, Sri Lanka
| | - Yujiao Tang
- School of Bio-Science and Food Engineering, Changchun University of Science and Technology, Changchun 130600, China;
| | | | - Ji-Young Hwang
- Department of Food Science & Technology, Dong-Eui University, Busan 47340, Korea;
| | - Eun-Kyung Kim
- Department of Food Science and Nutrition, College of Health Science, Dong-A University, Busan 49315, Korea; (Y.-J.C.); (N.E.W.)
- Center for Silver-Targeted Biomaterials, Brain Busan 21 Plus Program, Dong-A University, Busan 49315, Korea
- Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Korea
- Department of Export Agriculture, Faculty of Animal Science and Export Agriculture, Uva Wellassa University, Badulla 90000, Sri Lanka
- Center for Food & Bio Innovation, Dong-A University, Busan 49315, Korea
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24
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Rong L, Zou J, Ran W, Qi X, Chen Y, Cui H, Guo J. Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD). Front Endocrinol (Lausanne) 2022; 13:1087260. [PMID: 36726464 PMCID: PMC9884828 DOI: 10.3389/fendo.2022.1087260] [Citation(s) in RCA: 114] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/28/2022] [Indexed: 01/17/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the liver and is often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, and other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD in 2020 as metabolic (dysfunction) associated with fatty liver disease (MAFLD). The changes in diet and lifestyle are recognized the non-drug treatment strategies; however, due to the complex pathogenesis of NAFLD, the current drug therapies are mainly focused on its pathogenic factors, key links of pathogenesis, and related metabolic disorders as targets. There is still a lack of specific drugs. In clinical studies, the common NAFLD treatments include the regulation of glucose and lipid metabolism to protect the liver and anti-inflammation. The NAFLD treatments based on the enterohepatic axis, targeting gut microbiota, are gradually emerging, and various new metabolism-regulating drugs are also under clinical development. Therefore, this review article has comprehensively discussed the research advancements in NAFLD treatment in recent years.
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Affiliation(s)
- Li Rong
- Department of Gastroenterology, Bishan Hospital of Chongqing Medical University, Bishan Hospital of Chongqing, Chongqing, China
| | - Junyan Zou
- Medical Research Institute, Southwest University, Chongqing, China
- Medical Research Institute, Southwest University, Public Health Hospital Affiliated to Southwest University, Chongqing, China
| | - Wei Ran
- Medical Research Institute, Southwest University, Public Health Hospital Affiliated to Southwest University, Chongqing, China
| | - Xiaohong Qi
- Department of General surgery, Baoshan People’s Hospital of Yunnan Province, Baoshan, Yunnan, China
| | - Yaokai Chen
- Medical Research Institute, Southwest University, Public Health Hospital Affiliated to Southwest University, Chongqing, China
| | - Hongjuan Cui
- Medical Research Institute, Southwest University, Chongqing, China
| | - Jinjun Guo
- Department of Gastroenterology, Bishan Hospital of Chongqing Medical University, Bishan Hospital of Chongqing, Chongqing, China
- *Correspondence: Jinjun Guo,
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25
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Wang L, Jiao T, Yu Q, Wang J, Wang L, Wang G, Zhang H, Zhao J, Chen W. Bifidobacterium bifidum Shows More Diversified Ways of Relieving Non-Alcoholic Fatty Liver Compared with Bifidobacterium adolescentis. Biomedicines 2021; 10:biomedicines10010084. [PMID: 35052765 PMCID: PMC8772902 DOI: 10.3390/biomedicines10010084] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/20/2021] [Accepted: 12/30/2021] [Indexed: 12/22/2022] Open
Abstract
The occurrence of non-alcoholic fatty liver disease (NAFLD) is closely related to intestinal microbiota disturbance, and probiotics has become a new strategy to assist in alleviating NAFLD. In order to investigate the effect of Bifidobacterium on NAFLD and the possible pathway, a NAFLD model was established by using a high-fat diet (HFD) for 18 weeks. Fourteen strains of Bifidobacterium were selected (seven Bifidobacterium adolescentis and seven Bifidobacterium bifidum) for intervention. The effects of different bifidobacteria on NAFLD were evaluated from liver cell injury, liver fat deposition, liver inflammatory state and liver histopathology, and were taken as entry points to explore the mitigation approaches of bifidobacteria through energy intake, lipid metabolism, glucose metabolism and intestinal permeability. The results showed that Bifidobacterium exerts species-specific effects on NAFLD. B. bifidum exerted these effects mainly through regulating the intestinal microbiota, increasing the relative abundance of Faecalibaculum and Lactobacillus, decreasing the relative abundance of Tyzzerella, Escherichia-Shigella, Intestinimonas, Osillibacter and Ruminiclostridium, and further increasing the contents of propionic acid and butyric acid, regulating lipid metabolism and intestinal permeability, and ultimately inhibiting liver inflammation and fat accumulation to alleviate NAFLD. B. adolescentis exerted its effects mainly through changing the intestinal microbiota, increasing the content of propionic acid, regulating lipid metabolism and ultimately inhibiting liver inflammation to alleviate NAFLD.
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Affiliation(s)
- Linlin Wang
- State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai 200436, China;
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Ting Jiao
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Qiangqing Yu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Jialiang Wang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Luyao Wang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- Wuxi Translational Medicine Research Center, Jiangsu Translational Medicine Research Institute, Wuxi Branch, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
- Correspondence: ; Tel./Fax: +86-510-8591-2155
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (T.J.); (Q.Y.); (J.W.); (L.W.); (G.W.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
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Michels M, Jesus GFA, Voytena APL, Rossetto M, Ramlov F, Córneo E, Feuser P, Gelain D, Dal-Pizzol F. Immunomodulatory Effect of Bifidobacterium, Lactobacillus, and Streptococcus Strains of Paraprobiotics in Lipopolysaccharide-Stimulated Inflammatory Responses in RAW-264.7 Macrophages. Curr Microbiol 2021; 79:9. [PMID: 34905100 DOI: 10.1007/s00284-021-02708-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 10/11/2021] [Indexed: 12/17/2022]
Abstract
The discovery of the potential of paraprobiotics to exert different immunological benefits suggests that further studies should be carried out to determine their potential and mechanisms of action in modulating the immune system. The objective of this study was to investigate the immune response of several microbial-associated molecular patterns (MAMPS) used at different doses in macrophage cell lines RAW-264.7 stimulated with lipopolysaccharide (LPS). Two experiments were conducted. The first was performed to determine a dose response curve for each paraprobiotic (Bifidobacterium lactis, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus paracasei, and Streptococcus thermophilus). Further experiments were carried using only two doses (0.01 g/ml and 0.1 g/ml). RAW-264.7 cells were cultivated in Dubelcco's Modified Eagle's medium supplemented with fetal bovine serum and penicillin/streptomycin. Cells were incubated with LPS (1 μg/ml) and six concentrations of MAMPs were added. RAW-264.7 viability, myeloperoxidase activity, nitrite/nitrate concentration, reactive oxygen species production, oxidative damage, and inflammatory parameters were measured. In the LPS group, there was a significant reduction in cell viability. Myeloperoxidase and nitrite/nitrate concentrations demonstrated a better effect at 0.01 and 0.1 g/ml doses. There was a significant reduction in interleukin-6 (IL-6) levels at 0.1 g/ml dose in all paraprobiotics. IL-10 levels decreased in the LPS group and increased at 0.1 g/ml dose in all paraprobiotics. The dichlorofluorescin diacetate results were reinforced by the observed in oxidative damage. Paraprobiotics are likely to contribute to the improvement of intestinal homeostasis, immunomodulation, and host metabolism.
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Affiliation(s)
- Monique Michels
- Gabbia Biotechnology, Barra Velha, SC, Brazil. .,Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil. .,Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Avenida Universitária, 1105 - Bairro Universitário, Criciúma, SC, CEP: 888006-000, Brazil.
| | | | | | | | | | - Emily Córneo
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Paulo Feuser
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
| | - Daniel Gelain
- Departament of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Felipe Dal-Pizzol
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Brazil
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Abstract
Several products consist of probiotics that are available in markets, and their potential uses are growing day by day, mainly because some strains of probiotics promote the health of gut microbiota, especially Furmicutes and Bacteroidetes, and may prevent certain gastrointestinal tract (GIT) problems. Some common diseases are inversely linked with the consumption of probiotics, i.e., obesity, type 2 diabetes, autism, osteoporosis, and some immunological disorders, for which the disease progression gets delayed. In addition to disease mitigating properties, these microbes also improve oral, nutritional, and intestinal health, followed by a robust defensive mechanism against particular gut pathogens, specifically by antimicrobial substances and peptides producing probiotics (AMPs). All these positive attributes of probiotics depend upon the type of microbial strains dispensed. Lactic acid bacteria (LAB) and Bifidobacteria are the most common microbes used, but many other microbes are available, and their use depends upon origin and health-promoting properties. This review article focuses on the most common probiotics, their health benefits, and the alleviating mechanisms against chronic kidney diseases (CKD), type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), and obesity.
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Tang C, Tao J, Sun J, Lv F, Lu Z, Lu Y. Regulatory mechanisms of energy metabolism and inflammation in oleic acid-treated HepG2 cells from Lactobacillus acidophilus NX2-6 extract. J Food Biochem 2021; 45:e13925. [PMID: 34486133 DOI: 10.1111/jfbc.13925] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 07/12/2021] [Accepted: 08/26/2021] [Indexed: 12/12/2022]
Abstract
In this study, the cell-free extracts (CFE) of Lactobacillus acidophilus NX2-6 were utilized to treat oleic acid (OA)-induced hepatic steatosis. It was found that CFE treatment improved lipid metabolism in OA-induced hepatic steatosis model by downregulating several lipogenic genes but increasing expression levels of lipolysis-related genes. In addition, gene expression analysis revealed that CFE treatment promoted mitochondrial biogenesis and fission by upregulating the mRNA levels of PGC-1α, PGC-1β, Sirt1, NRF1, and Fis1. CFE treatment also increased protein expression of p-AMPKα, PGC-1α, ACOX1, and Sirt1 in OA-treated cells, suggesting that CFE possessed ability to improve energy metabolism. Furthermore, CFE treatment also reversed OA-induced oxidative stress by increasing CAT activity and protein level of Nrf-2 as well as reducing protein expression of ATF6, XBP1, GRP78, p50, and p-ERK, indicating that CFE could inhibit endoplasmic reticulum stress and sterile inflammation. Thus, L. acidophilus NX2-6 had potential to fight against NAFLD. PRACTICAL APPLICATIONS: Diet-induced hepatic steatosis is one of major public health concerns all over the world. Hepatic steatosis is accompanied by disregulation of lipid metabolism and energy metabolism, endoplasmic reticulum stress, oxidative stress as well as chronic inflammation. It is reported that probiotics are considered as emerging therapeutic strategy to alleviate hepatic steatosis. This study indicated potential applications of dead probiotics in the prevention of hepatic steatosis and development of functional foods.
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Affiliation(s)
- Chao Tang
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Jia Tao
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Jing Sun
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, China
| | - Fengxia Lv
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Zhaoxin Lu
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Yingjian Lu
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, China
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Guerra JVS, Dias MMG, Brilhante AJVC, Terra MF, García-Arévalo M, Figueira ACM. Multifactorial Basis and Therapeutic Strategies in Metabolism-Related Diseases. Nutrients 2021; 13:nu13082830. [PMID: 34444990 PMCID: PMC8398524 DOI: 10.3390/nu13082830] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/09/2021] [Accepted: 08/11/2021] [Indexed: 12/11/2022] Open
Abstract
Throughout the 20th and 21st centuries, the incidence of non-communicable diseases (NCDs), also known as chronic diseases, has been increasing worldwide. Changes in dietary and physical activity patterns, along with genetic conditions, are the main factors that modulate the metabolism of individuals, leading to the development of NCDs. Obesity, diabetes, metabolic associated fatty liver disease (MAFLD), and cardiovascular diseases (CVDs) are classified in this group of chronic diseases. Therefore, understanding the underlying molecular mechanisms of these diseases leads us to develop more accurate and effective treatments to reduce or mitigate their prevalence in the population. Given the global relevance of NCDs and ongoing research progress, this article reviews the current understanding about NCDs and their related risk factors, with a focus on obesity, diabetes, MAFLD, and CVDs, summarizing the knowledge about their pathophysiology and highlighting the currently available and emerging therapeutic strategies, especially pharmacological interventions. All of these diseases play an important role in the contamination by the SARS-CoV-2 virus, as well as in the progression and severity of the symptoms of the coronavirus disease 2019 (COVID-19). Therefore, we briefly explore the relationship between NCDs and COVID-19.
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Affiliation(s)
- João V. S. Guerra
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Graduate Program in Pharmaceutical Sciences, Faculty Pharmaceutical Sciences, University of Campinas, Campinas 13083-970, Brazil
| | - Marieli M. G. Dias
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas 13083-970, Brazil;
| | - Anna J. V. C. Brilhante
- Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas 13083-970, Brazil;
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biorenewables National Laboratory (LNBR), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil
| | - Maiara F. Terra
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Graduate Program in Functional and Molecular Biology, Institute of Biology, State University of Campinas (Unicamp), Campinas 13083-970, Brazil;
| | - Marta García-Arévalo
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Correspondence: or (M.G.-A.); (A.C.M.F.)
| | - Ana Carolina M. Figueira
- Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Polo II de Alta Tecnologia—R. Giuseppe Máximo Scolfaro, Campinas 13083-100, Brazil; (J.V.S.G.); (M.M.G.D.); (M.F.T.)
- Correspondence: or (M.G.-A.); (A.C.M.F.)
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Ileal Bile Acid Transporter Inhibitor Improves Hepatic Steatosis by Ameliorating Gut Microbiota Dysbiosis in NAFLD Model Mice. mBio 2021; 12:e0115521. [PMID: 34225483 PMCID: PMC8406289 DOI: 10.1128/mbio.01155-21] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat deposition in the liver unrelated to alcohol consumption, is highly prevalent worldwide. However, effective therapeutic agents approved for NAFLD treatment are lacking. An ileal bile acid transporter inhibitor (IBATi), which represents a new mode of treatment of chronic idiopathic constipation, leads to increased delivery of bile acids to the colon. We investigated the effect of IBATi against NAFLD through modification of the gut microbiota in mice. IBATi treatment significantly suppressed body weight gain, liver dysfunction, and serum low-density lipoprotein levels and significantly decreased NAFLD activity scores in high-fat diet (HFD) mice. Treatment with IBATi ameliorated the decreased hepatic cholesterol 7-a-monooxygenase (Cyp7a1) and increased ileal fibroblast growth factor 15 (Fgf15) mRNA expression in HFD mice. Further, IBATi treatment changed the α-diversity in the gut microbiota reduced by HFD, which was analyzed in feces using 16S rRNA sequencing. To establish the mechanism underlying improvement in NAFLD induced by IBATi, we recolonized antibiotic solution-treated mice by fecal microbiome transplantation (FMT) using stool from HFD or HFD plus IBATi mice. This is the first report that fecally transplanted gut microbiota from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. In conclusion, IBATi improved hepatic steatosis by ameliorating gut microbiota dysbiosis in NAFLD model mice, suggesting a potential therapeutic agent for NAFLD treatment. IMPORTANCE NAFLD is an increasingly recognized condition that may progress to liver cirrhosis and hepatocellular carcinoma, and community surveys have assessed that the prevalence is 14 to 32% worldwide. The first line of treatment for NAFLD is lifestyle modification to achieve weight reduction, particularly through diet and exercise. However, weight reduction is difficult to achieve and maintain, and pharmacological agents approved for the treatment of NAFLD are lacking. This study investigated the influence of the gut microbiota and the effect of an IBATi on NAFLD using a murine model. Treatment with IBATi significantly improved NAFLD in HFD mice. Further, fecal microbiome transplantation using stool from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. Our study makes a significant contribution to the literature because the study findings suggest a potential treatment strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.
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Gupta M, Krishan P, Kaur A, Arora S, Trehanpati N, Singh TG, Bedi O. Mechanistic and physiological approaches of fecal microbiota transplantation in the management of NAFLD. Inflamm Res 2021; 70:765-776. [PMID: 34212214 DOI: 10.1007/s00011-021-01480-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2021] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease allied with various metabolic disorders, obesity and dysbiosis. Gut microbiota plays an influential role in the pathogenesis of NAFLD and other metabolic disorders. However, recent scientific upsurge emphasizes on the utility of beneficial gut microbiota and bacteriotherapy in the management of NAFLD. Fecal microbiota transplantation (FMT) is the contemporary therapeutic approach with state-of-the-art methods for the treatment of NAFLD. Other potential therapies include probiotics and prebiotics supplements which are based on alteration of gut microbes to treat NAFLD. In this review, our major focus is on the pathological association of gut microbiota with progression of NAFLD, historical aspects and recent advances in FMT with possible intervention to combat NAFLD and its associated metabolic dysfunctions.
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Affiliation(s)
- Manisha Gupta
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway (NH-64), Rajpura, 140401, Punjab, India
| | - Pawan Krishan
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
| | - Amarjot Kaur
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway (NH-64), Rajpura, 140401, Punjab, India
| | - Sandeep Arora
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway (NH-64), Rajpura, 140401, Punjab, India
| | - Nirupma Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway (NH-64), Rajpura, 140401, Punjab, India
| | - Onkar Bedi
- Chitkara College of Pharmacy, Chitkara University, Chandigarh-Patiala National Highway (NH-64), Rajpura, 140401, Punjab, India.
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
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Mularczyk M, Bourebaba Y, Kowalczuk A, Marycz K, Bourebaba L. Probiotics-rich emulsion improves insulin signalling in Palmitate/Oleate-challenged human hepatocarcinoma cells through the modulation of Fetuin-A/TLR4-JNK-NF-κB pathway. Biomed Pharmacother 2021; 139:111560. [PMID: 33839491 DOI: 10.1016/j.biopha.2021.111560] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 03/29/2021] [Accepted: 03/31/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Fetuin-A, also known as α2-Heremans-Schmid glycoprotein (AHSG), is an abundant plasmatic serum protein synthesized predominantly in liver and adipose tissue. This glycoprotein is known to negatively regulate insulin signaling through the inhibition of insulin receptor (IR) autophosphorylation and tyrosine kinase activity, which participates in insulin resistance (IR) and metabolic syndrome development. Recent studies demonstrated that IR and associated metabolic disorders, are closely related to the gut microbiota and modulating it by probiotics could be effective in metabolic diseases management. OBJECTIVE In this present work we aimed to evaluate the effects of a probiotics-rich emulsion on reducing the IR induced by free fatty acids accumulation in human hepatocarcinoma cell line, and to elucidate the implicated molecular pathways, with a specific emphasis on the hepatokin Fetuin-A-related axis. RESULTS Here we showed, that probiotics improve HepG2 viability, protect against apoptosis under normal and IR conditions. Moreover, the emulsion was successful in attenuating oxidative stress as well as improving mitochondrial metabolism and dynamics. Interestingly, application of the probiotics to lipotoxic HepG2 cells resulted in significant reduction of Fetuin-A/TLR4/JNK/NF-κB pathway activation, which suggests a protective effect against inflammation, obesity as well as liver related insulin resistant. CONCLUSION Overall, the presented data reports clearly on the potent potential of probiotics formulated in an emulsion vehicle to enhance metabolic functions of affected IR HepG2 cells, and suggest the possibility of using such preparations as insulin sensitizing therapy, playing at the same time protective role for the development of liver related insulin resistant.
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Affiliation(s)
- Malwina Mularczyk
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375 Wrocław, Poland; International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114 Wisznia Mała, Poland
| | - Yasmina Bourebaba
- International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114 Wisznia Mała, Poland; Département du Tronc Commun, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000 Bejaia, Algeria
| | - Anna Kowalczuk
- National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland
| | - Krzyzstof Marycz
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375 Wrocław, Poland; International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114 Wisznia Mała, Poland
| | - Lynda Bourebaba
- Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375 Wrocław, Poland; International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114 Wisznia Mała, Poland.
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Khan A, Ding Z, Ishaq M, Bacha AS, Khan I, Hanif A, Li W, Guo X. Understanding the Effects of Gut Microbiota Dysbiosis on Nonalcoholic Fatty Liver Disease and the Possible Probiotics Role: Recent Updates. Int J Biol Sci 2021; 17:818-833. [PMID: 33767591 PMCID: PMC7975705 DOI: 10.7150/ijbs.56214] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/24/2020] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is leading chronic liver syndrome worldwide. Gut microbiota dysbiosis significantly contributes to the pathogenesis and severity of NAFLD. However, its role is complex and even unclear. Treatment of NAFLD through chemotherapeutic agents have been questioned because of their side effects on health. In this review, we highlighted and discussed the current understanding on the importance of gut microbiota, its dysbiosis and its effects on the gut-liver axis and gut mucosa. Further, we discussed key mechanisms involved in gut dysbiosis to provide an outline of its role in progression to NAFLD and liver cirrhosis. In addition, we also explored the potential role of probiotics as a treatment approach for the prevention and treatment of NAFLD. Based on the latest findings, it is evident that microbiota targeted interventions mostly the use of probiotics have shown promising effects and can possibly alleviate the gut microbiota dysbiosis, regulate the metabolic pathways which in turn inhibit the progression of NAFLD through the gut-liver axis. However, very limited studies in humans are available on this issue and suggest further research work to identify a specific core microbiome association with NAFLD and to discover its mechanism of pathogenesis, which will help to enhance the therapeutic potential of probiotics to NAFLD.
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Affiliation(s)
- Ashiq Khan
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
- Department of Microbiology, Balochistan University of Information Technology Engineering & Management Sciences Quetta 87300, Pakistan
| | - Zitong Ding
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Muhammad Ishaq
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Ali Sher Bacha
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Israr Khan
- School of Life Sciences, Institute of Microbiology Lanzhou University, Lanzhou 730000, PR China
| | - Anum Hanif
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Wenyuan Li
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
| | - Xusheng Guo
- School of Life Sciences, Probiotics and Biological Feed Research Centre, Lanzhou University, Lanzhou 730000, PR China
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Morvaridzadeh M, Nachvak SM, Mohammadi R, Moradi S, Mostafai R, Pizarro AB, Abdollahzad H. Probiotic Yogurt Fortified with Vitamin D Can Improve Glycemic Status in Non-Alcoholic Fatty Liver Disease Patients: a Randomized Clinical Trial. Clin Nutr Res 2021; 10:36-47. [PMID: 33564651 PMCID: PMC7850818 DOI: 10.7762/cnr.2021.10.1.36] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 12/20/2020] [Accepted: 01/04/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant public health problem globally and the most notable chronic liver disease in Asian countries. Various dietary supplements have been assessed as potential methods to alleviate the metabolic damages related to NAFLD, but the results of these works have been equivocal. This study aimed to evaluate the effects of probiotic yogurt fortified with vitamin D (Pro-YFD) on glycemic and anthropometric indices in patients with NAFLD. One hundred and four NAFLD patients of both sexes were randomly allocated to 2 groups: group A (Pro-YFD) and group B (unfortified yogurt). The intervention period was 3 months. Fasting blood samples were obtained for measuring fasting blood sugar (FBS) and insulin level. Food intake was measured using a validated food frequency questionnaire. Body composition was estimated by bio-impedance. Eighty-eight patients completed the study. The mean serum level of 25(OH)D3 was elevated significantly (p < 0.001), while insulin level decreased significantly (p < 0.003) in group A at the end of the study. FBS levels showed no significant differences between the groups at the end of the trial. Also, there were no significant changes in diet caloric intake, physical activity, or anthropometric indices in the 2 groups during the interventions. Pro-YFD in the diets of patients with NAFLD may attenuate insulin resistance and improve serum level of 25(OH)D3.
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Affiliation(s)
- Mojgan Morvaridzadeh
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah 6719851351, Iran
| | - Seyed Mostafa Nachvak
- Department of Nutrition, Research Center for Environmental Determinants of Health (RCEDH), Kermanshah University of Medical Sciences, Kermanshah 6719851351, Iran
| | - Reza Mohammadi
- Department of Food Science and Technology, Research Center for Environmental Determinants of Health (RCEDH), Kermanshah University of Medical Sciences, Kermanshah 6719851351, Iran
| | - Shima Moradi
- Department of Nutrition, Research Center for Environmental Determinants of Health (RCEDH), Kermanshah University of Medical Sciences, Kermanshah 6719851351, Iran
| | - Roghayeh Mostafai
- Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah 6719851351, Iran
| | | | - Hadi Abdollahzad
- Department of Nutrition, Research Center for Environmental Determinants of Health (RCEDH), Kermanshah University of Medical Sciences, Kermanshah 6719851351, Iran
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Wang YH. Current progress of research on intestinal bacterial translocation. Microb Pathog 2020; 152:104652. [PMID: 33249165 DOI: 10.1016/j.micpath.2020.104652] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 10/19/2020] [Accepted: 11/24/2020] [Indexed: 02/07/2023]
Abstract
Under normal conditions, the intestinal flora and the body are in dynamic equilibrium. When the barrier function of the intestinal tract is damaged due to various reasons, changes in the number and proportion of bacteria or spatial displacement result in bacterial translocation (BT), which ultimately leads to multiple organ dysfunction syndrome (MODS). Endogenous infections and endotoxemia caused by intestinal flora and endotoxin translocation are the origins of inflammatory responses, and the intestinal tract is the organ in which MODS both initiates and targets. Only by ensuring the integrity of the intestinal mucosal barrier can intestinal BT be effectively prevented. Elimination of the primary disease and maintaining blood and oxygen supply to the intestine is the most basic treatment. Early initiation of the intestinal tract, establishment of enteral nutrition, and selective digestive decontamination are also highly effective treatments. Early diagnosis, intervention, or prevention of BT may be a new avenue or important connection in the treatment of various diseases. The mechanism of BT, detection techniques, prevention and treatment, and its interaction with parenteral diseases were reviewed.
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Affiliation(s)
- Yan-Hua Wang
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
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Yan X, Wang F, Weng P, Wu Z. The effect of fermented Huyou juice on intestinal microbiota in a high-fat diet-induced obesity mouse model. J Food Biochem 2020; 44:e13480. [PMID: 33103254 DOI: 10.1111/jfbc.13480] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 08/21/2020] [Accepted: 08/29/2020] [Indexed: 12/17/2022]
Abstract
This study mainly discussed the effect of fermented Huyou juice (FHJ) on modulating the intestinal microbiota of human, and anti-obesity mechanisms. Through the way of metagenomics, the effect of FHJ on gut flora has been summarized with a mice model of obesity induced by human flora-associated (HFA) high-fat diet. The results showed that the FHJ ameliorated the gut dysbiosis caused by obesity. When receiving FHJ treatment, a dramatic decrease in Firmicutes/Bacteroidetes occurred. What's more, having experienced 8 weeks of FHJ intervention, KEGG pathways of two-component system, ATP-binding cassette (ABC) transporters, and biosynthesis of amino acids made the most differentially expressed genes more abundant, the unigene numbers are 16781,480, and 1,221, respectively. Our results may be of great significance to the use of FHJ which serves as a functional fermented beverage product with the underlying effect of treating the obesity induced by high-fat diet. The FHJ helps to improve the host health by regulating the intestinal flora and affecting some metabolic pathways. PRACTICAL APPLICATIONS: The fermentation of Huyou juice is one of the important ways to develop and utilize fruit resources. It is a common way of fruit and vegetable juice fermentation with mixed strains. After fermentation, the juice produces a large number of bioactive peptides, and sugar, toxic substances, and antinutritional material will be reduced, the nutritional value of the fruits and vegetables were improved. At the same time, the fermented juice industry could develop various functional health products, which is conducive to the transformation, upgrading, and sustainable development of Changshan Huyou.
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Affiliation(s)
- Xu Yan
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China
| | - Fangjie Wang
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China
| | - Peifang Weng
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China
| | - Zufang Wu
- College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China
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Abhari K, Saadati S, Yari Z, Hosseini H, Hedayati M, Abhari S, Alavian SM, Hekmatdoost A. The effects of Bacillus coagulans supplementation in patients with non-alcoholic fatty liver disease: A randomized, placebo-controlled, clinical trial. Clin Nutr ESPEN 2020; 39:53-60. [PMID: 32859329 DOI: 10.1016/j.clnesp.2020.06.020] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 05/02/2020] [Accepted: 06/29/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND The aim of this study was to evaluate the effects of supplementation with 109 spores of Bacillus coagulans (GBI-30) plus inulin in patients with non-alcoholic fatty liver disease (NAFLD). METHODS In a randomized, double-blind, placebo-controlled clinical trial, fifty three patients with NAFLD were randomly assigned to receive either a synbiotic or a placebo capsule for 12 weeks. The primary outcome was reduction in steatosis score in Fibroscan exam. RESULTS At the end of study, serum alanine aminotransferase and γ glutamine transaminase decreased significantly more in synbiotic group compared to placebo group (p = 0.001, and p = 0.004, respectively). Synbiotic supplementation significantly reduced serum tumor necrosis factor-α (p = 0.03) and nuclear factor-κB activity (p = 0.04). Moreover, hepatic steatosis reduced significantly more in synbiotic group compared to placebo group (p < 0.001). CONCLUSION Our results indicate that 12 weeks supplementation with B. coagulans plus inulin is beneficial for treatment of NAFLD and its related inflammation without any significant effects on related cardiovascular risk factors. CLINICAL TRIALS This trial was registered at irct.ir with number of IRCT20100524004010N23.
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Affiliation(s)
- Khadijeh Abhari
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeede Saadati
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Yari
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hedayat Hosseini
- Department of Food Technology, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahabeddin Abhari
- Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
| | - Seyyed Moayyed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Wang G, Jiao T, Xu Y, Li D, Si Q, Hao J, Zhao J, Zhang H, Chen W. Bifidobacterium adolescentis and Lactobacillus rhamnosus alleviate non-alcoholic fatty liver disease induced by a high-fat, high-cholesterol diet through modulation of different gut microbiota-dependent pathways. Food Funct 2020; 11:6115-6127. [PMID: 32573567 DOI: 10.1039/c9fo02905b] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) has increased year on year, and the increasing appreciation of the importance of gut microbiota provides novel therapeutic avenues for the treatment of NAFLD. To explore the similarities and differences between lactic acid bacteria (LAB) known to alleviate NAFLD, we selected three strains of Bifidobacterium adolescentis and three strains of Lactobacillus rhamnosus to administer to C57BL/6J mice on a high-fat, high-cholesterol diet (HFHCD) for 23 weeks. Subsequently, the effects of the LAB were evaluated through various measures. The six LAB strains were found to have varying degrees of efficacy in the prevention of NAFLD. We found that there were interspecific and intraspecific differences in the beneficial effects, mainly with respect to energy metabolism, lipid metabolism and short-chain fatty acid concentration. Three strains of B. adolescentis and one strain of L. rhamnosus were found to relieve NAFLD by increasing the concentration of short-chain fatty acids in the intestine of NAFLD mice. The other two strains of L. rhamnosus, LGG and L10-1, relieved NAFLD through different ways, LGG modulated energy metabolism and lipid metabolism, and L10-1 reduced liver inflammation. Examination of gut microbiota indicated that the six LAB strains could block the HFHCD-induced elevation of Firmicutes/Bacteroidetes and alter the dominant species within the gut. These results suggest that B. adolescentis and L. rhamnosus can inhibit the development of NAFLD by regulating gut microbiota, and their use is thus a promising therapeutic strategy.
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Affiliation(s)
- Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China.
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Zhou J, Zhou F, Wang W, Zhang XJ, Ji YX, Zhang P, She ZG, Zhu L, Cai J, Li H. Epidemiological Features of NAFLD From 1999 to 2018 in China. Hepatology 2020; 71:1851-1864. [PMID: 32012320 DOI: 10.1002/hep.31150] [Citation(s) in RCA: 438] [Impact Index Per Article: 87.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 01/06/2020] [Indexed: 12/12/2022]
Abstract
With dramatic changes in lifestyles over the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disorder in China but has not received sufficient attention. NAFLD-related advanced liver disease and its mortality along with its overall disease burden are expected to increase substantially. There is thus an imperative need to clarify the epidemiological features of NAFLD to guide a holistic approach to management. We summarize eight epidemiological features of NAFLD in China over the past two decades using systematic review and meta-analysis methodology. Our data reveal a rapid growth in the NAFLD population, especially among younger individuals. Importantly, there is a strong ethnic difference in body mass index (BMI) and genetic risk of NAFLD compared with the US population. The etiology of advanced liver disease and its complications (e.g., hepatocellular carcinoma) has been altered because of a Westernized lifestyle and the implementation of effective vaccination strategies against viral hepatitis. Regional epidemiological patterns of NAFLD indicate that economics, environment, and lifestyle are critical factors in disease progression. The analysis also indicates that a large number of patients remain undiagnosed and untreated because of the inadequacy of diagnostic tools and the absence of effective pharmacologic therapies. Given the burden of NAFLD, future policy and research efforts need to address knowledge gaps to mitigate the risk burden.
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Affiliation(s)
- Jianghua Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Feng Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
- Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wenxin Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Xiao-Jing Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Yan-Xiao Ji
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Peng Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Lihua Zhu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
| | - Jingjing Cai
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Institute of Model Animal of Wuhan University, Wuhan, China
- Basic Medical School, Wuhan University, Wuhan, China
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Liraglutide Attenuates Nonalcoholic Fatty Liver Disease by Modulating Gut Microbiota in Rats Administered a High-Fat Diet. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2947549. [PMID: 32149099 PMCID: PMC7049398 DOI: 10.1155/2020/2947549] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 12/15/2019] [Accepted: 01/04/2020] [Indexed: 12/16/2022]
Abstract
This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.
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Shen SH, Zhong TY, Peng C, Fang J, Lv B. Structural modulation of gut microbiota during alleviation of non-alcoholic fatty liver disease with Gynostemma pentaphyllum in rats. BMC Complement Med Ther 2020; 20:34. [PMID: 32024509 PMCID: PMC7076883 DOI: 10.1186/s12906-020-2835-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 01/27/2020] [Indexed: 02/06/2023] Open
Abstract
Background The current work aimed to assess whether Gynostemma pentaphyllum (GP), a Chinese herbal medicine, structurally modifies the gut microbiota in rats during non-alcoholic fatty liver disease (NAFLD) treatment. Methods High-fat diet (HFD)-induced NAFLD rats were orally administered water decoction of GP or equal amounts of distilled water per day for 4 weeks. Liver tissues were examined by histopathological observation, while intestinal tissues were examined by both histopathological and ultrastructural observations. The levels of fasting blood glucose (FBG), fasting serum insulin (FINS), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) were measured by enzymatic method. The levels of toll-like receptor 4 (TLR-4), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and interleukin-6 (IL-6) in both serum and hepatic tissues were measured by RT-qPCR. The protein expression level of TLR-4 in hepatic tissues was detected by western blot. The gut microbiota was assessed by 16S rRNA-based microbiota analysis. Results GP maintained intestinal integrity and reversed gut dysbiosis in high-fat diet (HFD)-induced NAFLD rats. This also reduced the ratio of Firmicutes to Bacteroidetes, enriching the abundance of beneficial bacteria (Lactococcus spp.) and inhibiting the abundance of pathogenic bacteria (Ruminococcus spp.) in the gut. The levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and the expression of TLR4 were downregulated (P < 0.05), while the insulin resistance index, HOMA-IR showed improvement by GP treatment (P < 0.05). Liver function indicators (ALT and AST) were remarkably decreased (P < 0.01). Besides, GP treatment reduced TG and LDL-C levels (P < 0.05), and increased HDL-C level (P < 0.05) compared with NAFLD group. Conclusion The structural alterations of gut microbiota induced by GP are associated with NAFLD alleviation.
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Affiliation(s)
- Shu-Hua Shen
- Department of Healthcare Management, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China
| | - Ting-Yan Zhong
- School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Cui Peng
- School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Jie Fang
- Laboratory Animal Centre, Zhejiang Academy of Medical Science, Hangzhou, 310000, China
| | - Bin Lv
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Zhejiang, 310006, Hangzhou, China.
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Yan T, Yan N, Wang P, Xia Y, Hao H, Wang G, Gonzalez FJ. Herbal drug discovery for the treatment of nonalcoholic fatty liver disease. Acta Pharm Sin B 2020; 10:3-18. [PMID: 31993304 PMCID: PMC6977016 DOI: 10.1016/j.apsb.2019.11.017] [Citation(s) in RCA: 159] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/23/2019] [Accepted: 10/31/2019] [Indexed: 12/11/2022] Open
Abstract
Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease (NAFLD) and its progressive stage, nonalcoholic steatohepatitis (NASH). Traditional herbal medicines (THM) have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and mechanisms. In modern times, NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/NASH pathology and progression. THM have garnered increased attention for providing therapeutic candidates for treating NAFLD. In this review, a new model called “multiple organs-multiple hits” is proposed to explain mechanisms of NASH progression. Against this proposed model, the effects and mechanisms of the frequently-studied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed, among which silymarin and berberine are already under U.S. FDA-sanctioned phase 4 clinical studies. Furthermore, experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are discussed. The opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are highlighted. Increasing mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.
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Affiliation(s)
- Tingting Yan
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Corresponding authors.
| | - Nana Yan
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Ping Wang
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yangliu Xia
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China
| | - Haiping Hao
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Guangji Wang
- State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
| | - Frank J. Gonzalez
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Corresponding authors.
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Hu H, Lin A, Kong M, Yao X, Yin M, Xia H, Ma J, Liu H. Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives. J Gastroenterol 2020; 55:142-158. [PMID: 31845054 PMCID: PMC6981320 DOI: 10.1007/s00535-019-01649-8] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 11/19/2019] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest "gut-liver axis"-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of "gut-liver axis" manipulation and efficacy of these therapeutic strategies for NAFLD treatment.
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Affiliation(s)
- Haiming Hu
- grid.257143.60000 0004 1772 1285Hubei University of Chinese Medicine, Wuhan, Hubei China
| | - Aizhen Lin
- grid.477392.cHubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei China
| | - Mingwang Kong
- grid.257143.60000 0004 1772 1285Hubei University of Chinese Medicine, Wuhan, Hubei China
| | - Xiaowei Yao
- grid.257143.60000 0004 1772 1285Hubei University of Chinese Medicine, Wuhan, Hubei China
| | - Mingzhu Yin
- grid.257143.60000 0004 1772 1285Hubei University of Chinese Medicine, Wuhan, Hubei China
| | - Hui Xia
- grid.257143.60000 0004 1772 1285Hubei University of Chinese Medicine, Wuhan, Hubei China
| | - Jun Ma
- grid.257143.60000 0004 1772 1285Hubei University of Chinese Medicine, Wuhan, Hubei China
| | - Hongtao Liu
- grid.257143.60000 0004 1772 1285Hubei University of Chinese Medicine, Wuhan, Hubei China
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Non-alcoholic fatty liver diseases: from role of gut microbiota to microbial-based therapies. Eur J Clin Microbiol Infect Dis 2019; 39:613-627. [PMID: 31828683 DOI: 10.1007/s10096-019-03746-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 10/23/2019] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the well-known disease of the liver in adults and children throughout the world. The main manifestations related to NAFLD are an unusual storage of lipid in hepatocytes (hepatic steatosis) and progression of inflammation for non-alcoholic steatohepatitis (NASH). NAFLD is described as a multifactorial complication due to the genetic predisposition, metabolic functions, inflammatory, gut microbiota (GM), and environmental factors. The GM dysregulation among these factors is correlated to NAFLD development. In recent decades, advanced microbial profiling methods are continuing to shed light on the nature of the changes in the GM caused by NASH and NAFLD. In the current review, we aim to perform a literature review in different library databases and electronic searches (Science Direct, PubMed, and Google Scholar) which were randomly obtained. This will be done in order to provide an overview of the relation between GM and NAFLD, and the role of prebiotics, probiotics, and fecal microbiota transplantation (FMT), as potential therapeutic challenges for NAFLD.
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Chen X, Tan XR, Li SJ, Zhang XX. LncRNA NEAT1 promotes hepatic lipid accumulation via regulating miR-146a-5p/ROCK1 in nonalcoholic fatty liver disease. Life Sci 2019; 235:116829. [PMID: 31484042 DOI: 10.1016/j.lfs.2019.116829] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/26/2019] [Accepted: 08/31/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the specific mechanism of the disease remains unknown, and effective treatments are still lacking. It was reported that Nuclear enriched abundant transcript 1 (NEAT1) obviously was up-regulated in NAFLD model. But the role and underlying mechanism of NEAT1 in NAFLD is unclear. METHODS HepG2 cells were treated by free fatty acids (FFA) and C57BL/6J mice were treated by high-fat diet to establish NAFLD in vitro and in vivo models, respectively. Cell transfection was applied to regulate the expression of NEAT1, ROCK1, and miR-146a-5p. Western blotting and qRT-PCR were used for measuring expression of protein and mRNA level, respectively. Dual luciferase assay was used to detect the target relationship. Oil Red O staining was used to measure the lipid accumulation. HE staining was used for observing pathological feature of liver tissues. RESULTS High levels of NEAT1 and ROCK1, and low level of miR-146a-5p were identified in NAFLD models. NEAT1 could target miR-146a-5p to promote ROCK1 expression. Knockdown of NEAT1, overexpression of miR-146a-5p and knockdown of ROCK1 inhibited lipid accumulation through activating AMPK pathway. CONCLUSION NEAT1 may regulate NAFLD through miR-146a-5p targeting ROCK1, and further affect AMPK/SREBP pathway. This study may provide a new thought for the treatment of NAFLD.
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Affiliation(s)
- Xi Chen
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China
| | - Xin-Rui Tan
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China
| | - Shi-Jun Li
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China
| | - Xing-Xing Zhang
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China.
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Sun Y, Song Y, Liu C, Geng J. LncRNA NEAT1-MicroRNA-140 axis exacerbates nonalcoholic fatty liver through interrupting AMPK/SREBP-1 signaling. Biochem Biophys Res Commun 2019; 516:584-590. [PMID: 31239155 DOI: 10.1016/j.bbrc.2019.06.104] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 06/18/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the mechanism modulating the pathogenesis of NAFLD remains elusive. It was reported that nuclear enriched abundant transcript 1 (NEAT1) and microRNA-140 (miR-140) could regulate lipogenesis, but whether they could influence NAFLD are still unknown. METHODS HepG2 cells were treated by free fatty acids (FFA) to establish the model of NAFLD in vitro, and C57 mice were treated by high-fat diet to establish the model of NAFLD in vivo. Cell transfection was applied to regulate the expression of NEAT1 and miR-140. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. HE staining and Oil Red O staining were used for observing liver tissues. RESULTS NEAT1 and miR-140 are upregulated in hepacytes under the NAFLD conditions. NEAT1 directly binds to miR-140 and acts synergistically with miR-140 to exacerbate the progression of NAFLD. Reciprocally, silence of miR-140 or NEAT1 alleviates the severity of NAFLD. The mechanistical study shows that the axis of NEAT1-miR-140 inactivates AMPK/SREBP-1 signaling during the NAFLD. . CONCLUSION The NEAT1-miR-140 axis play a crucial role in modulation of NAFLD via inactivation of AMPK/SREBP1 signaling. This study may provide a novel insight for the treatment of NAFLD.
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Affiliation(s)
- Yunfu Sun
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China.
| | - Yu Song
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China
| | - Changsheng Liu
- The Second Department of General Surgery, Southern Ward of Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China
| | - Jianli Geng
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China
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The promising role of probiotic and synbiotic therapy in aminotransferase levels and inflammatory markers in patients with nonalcoholic fatty liver disease - a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2019; 31:703-715. [PMID: 31009401 DOI: 10.1097/meg.0000000000001371] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. The pathogenesis of NAFLD is complex and multifactorial. There is growing evidence that altered gut microbiota plays a key role in NAFLD progression. Probiotics/synbiotics, by modifying gut microbiota, may be a promising treatment choice for NAFLD management. AIM The aim of this study was to study the effect of probiotics/synbiotics on various laboratory and radiographic parameters in NAFLD management. MATERIALS AND METHODS A systematic review and meta-analysis were carried out according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We searched PubMed, Medline, and Google Scholar for randomized-controlled trials that studied the role of probiotics/synbiotics in NAFLD. The primary outcome was change in baseline alanine aminotransferase and aspartate aminotransferase in the treatment arm. We used a random-effects model and inverse variance for the continuous data to estimate the mean difference (MD) and the standard mean difference (SMD) in RevMan Version 5.3. RESULTS We included 12 randomized-controlled trials for analysis. The intervention arm, which comprised of the probiotic and/or the synbiotic arm, showed a significant improvement in alanine aminotransferase levels, MD=-13.93, confidence interval (CI)=-20.20 to -7.66, P value of less than 0.0001, I=92% and aspartate aminotransferase levels MD=-11.45, CI=-15.15 to -7.74, P value of less than 0.00001, I=91%. There was a reduction in high-sensitivity C-reactive protein levels in the intervention arm, SMD=-0.68, CI=-1.10 to -0.26, P value of 0.001, I=0%. The liver fibrosis score improved in the intervention arm, MD=-0.71, CI=-0.81 to -0.61, P value less than 0.00001, I=0%. CONCLUSION Probiotic/synbiotic use improves aminotransaminase levels and reduces proinflammatory marker high-sensitivity C-reactive protein and liver fibrosis in NAFLD patients.
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Zhou AL, Ward RE. Milk polar lipids modulate lipid metabolism, gut permeability, and systemic inflammation in high-fat-fed C57BL/6J ob/ob mice, a model of severe obesity. J Dairy Sci 2019; 102:4816-4831. [PMID: 30981495 DOI: 10.3168/jds.2018-15949] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 02/22/2019] [Indexed: 12/14/2022]
Abstract
Dynamic interactions between lipid metabolism, gut permeability, and systemic inflammation remain unclear in the context of obesity. Milk polar lipids, lipids derived from the milk fat globule membrane, could positively affect the aforementioned obesity-related endpoints. This study aimed to test the hypotheses that milk polar lipids will reduce gut permeability, systemic inflammation, and liver lipid levels, and differentially affect the hepatic expression of genes associated with fatty acid synthesis and cholesterol regulation in preexisting obesity. We fed 3 groups of C57BL/6J ob/ob mice (n = 6 per group) for 2 wk: (1) a modified AIN-93G diet (CO) with 34% fat by energy; (2) CO with milk gangliosides (GG) at 0.2 g/kg of diet; and (3) CO with milk phospholipids (PL) at 10 g/kg of diet. The GG and PL were provided as semi-purified concentrates and replaced 2.0% and 7.2% of dietary fat by energy. The GG and PL did not affect total food intake, weight gain, fasting glucose, or gut permeability. The PL decreased liver mass and the mesenteric fat depot compared with the CO. The GG increased tight junction protein occludin in colon mucosa compared with the CO. The GG and PL decreased tight junction protein zonula occludens-1 in jejunum mucosa compared with the CO. Plasma endotoxin increased during the study but was unaffected by the treatments. Compared with the CO and GG, the PL increased plasma sphingomyelin and plasma IL-6. The GG and PL differentially regulated genes associated with lipid metabolism in the liver compared with the CO. Regarding general effects on lipid metabolism, the GG and PL decreased lipid levels in the liver and the mesenteric depot, and increased lipid levels in the plasma. Diet consumption decreased significantly when the ob/ob mice were kept in metabolic cages, which were not big enough and resulted in unwanted animal deaths. Future studies may keep this in mind and use better metabolic equipment for ob/ob mice. In conclusion, dietary milk polar lipids may have limited beneficial effects on gut barrier integrity, systemic inflammation, and lipid metabolism in the context of severe obesity.
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Affiliation(s)
- A L Zhou
- Nutrition, Dietetics and Food Sciences, Utah State University, 8700 Old Main Hill, Logan 84322
| | - R E Ward
- Nutrition, Dietetics and Food Sciences, Utah State University, 8700 Old Main Hill, Logan 84322.
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Campo L, Eiseler S, Apfel T, Pyrsopoulos N. Fatty Liver Disease and Gut Microbiota: A Comprehensive Update. J Clin Transl Hepatol 2019; 7:56-60. [PMID: 30944821 PMCID: PMC6441642 DOI: 10.14218/jcth.2018.00008] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Revised: 09/17/2018] [Accepted: 10/03/2018] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the accumulation of fat in the liver in the absence of secondary causes. NAFLD is a multifactorial disease that results from the interaction of genetic predisposition and metabolic, inflammatory and environmental factors. Among these factors, dysregulation of gut microbiome has been linked to the development of fatty liver disease. The microbiome composition can be modified by dietary habits leading to gut microbiome dysbiosis, especially when a diet is rich in saturated fats, animal products and fructose sugars. Different species of bacteria in the gut metabolize nutrients differently, triggering different pathways that contribute to the accumulation of fat within the liver and triggering inflammatory cascades that promote liver damage. In this review, we summarize the current understanding of the roles of gut microbiota in mediating NAFLD development and discuss possible gut microbiota-targeted therapies for NAFLD. We summarize experimental and clinical evidence, and draw conclusions on the therapeutic potential of manipulating gut microbiota to decrease the incidence and prevalence of fatty liver disease.
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Affiliation(s)
- Lyna Campo
- Division of Gastroenterology and Hepatology, University Hospital, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Sara Eiseler
- Division of Gastroenterology and Hepatology, University Hospital, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Tehilla Apfel
- Division of Gastroenterology and Hepatology, University Hospital, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, University Hospital, Rutgers New Jersey Medical School, Newark, NJ, USA
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Wu J, Shao H, Zhang J, Ying Y, Cheng Y, Zhao D, Dou X, Lv H, Li S, Liu F, Ling P. Mussel polysaccharide α-D-glucan (MP-A) protects against non-alcoholic fatty liver disease via maintaining the homeostasis of gut microbiota and regulating related gut-liver axis signaling pathways. Int J Biol Macromol 2019; 130:68-78. [PMID: 30797009 DOI: 10.1016/j.ijbiomac.2019.02.097] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 02/09/2019] [Accepted: 02/15/2019] [Indexed: 12/14/2022]
Abstract
We isolated and characterized a Mussel polysaccharide, α-D-glucan (MP-A), from Mytilus coruscus earlier. In this work, the pharmacological activity and mechanisms of MP-A as an oral supplement for non-alcoholic fatty liver disease (NAFLD) were explored. High fat diet (HFD) was utilized to induce NAFLD in Sprague Dawley male rats and MP-A (0.6 g/kg) was supplemented for 4 weeks. The results showed that MP-A supplementation reduced blood lipid levels, intrahepatic lipid accumulation and NAFLD activity score in HFD-fed rats. Additionally, the analysis of 16S rDNA sequencing on gut microbiota samples revealed that HFD could induce microbial dysbiosis. However, MP-A supplementation could remodel gut microbiota structure, inhibit LPS-TLR4-NF-κB pathway activation, and restrain subsequent inflammation factors secretion. Furthermore, MP-A regulated the lipid metabolism by promoting the production of short chain fatty acids and suppressing PPAR γ and SREBP-1c expression. Our results support that MP-A can prevent against NAFLD and act as an oral supplementation for hepatoprotection via modulating gut microbiota and related gut-liver axis signaling pathways.
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Affiliation(s)
- Jixu Wu
- School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China; Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
| | - Huarong Shao
- Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China.
| | - Jinhua Zhang
- Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
| | - Yong Ying
- Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
| | - Yanling Cheng
- Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
| | - Dan Zhao
- Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
| | - Xixi Dou
- Shandong Freda Pharmaceutical Group Company, Jinan 250101, China
| | - Huimin Lv
- Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
| | - Shuaiguang Li
- School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China; Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China
| | - Fei Liu
- School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China; Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China.
| | - Peixue Ling
- School of Pharmaceutical Sciences, Shandong University, Jinan 250101, China; Shandong Academy of Pharmaceutical Sciences, Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China; Shandong Freda Pharmaceutical Group Company, Jinan 250101, China.
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