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Liu M, Ge Y, Xu E, Zhu T, Ruan H, Zheng J. The regulatory effects of epigallocatechin gallate on growth performance, systemic antioxidant status, immune response, and gut microbiota structure in geese. Poult Sci 2025; 104:105178. [PMID: 40267569 DOI: 10.1016/j.psj.2025.105178] [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: 03/18/2025] [Revised: 04/14/2025] [Accepted: 04/15/2025] [Indexed: 04/25/2025] Open
Abstract
The effects of dietary supplementation with epigallocatechin-3-gallate (EGCG) on growth performance, antioxidant capacity, immune function, and gut microbiota in geese were investigated. Seventy-two healthy 35-day-old male geese were randomly divided into a control group (basal diet) or an EGCG group (basal diet + 200 mg/kg EGCG), with 36 geese per group, which was further subdivided into 6 replicates (6 geese per replicate). The experiment lasted 21 days. Geese in the EGCG group exhibited significantly higher final body weight (2.93 kg vs. 2.28 kg, P < 0.01) and average daily gain (72.38 g/d vs. 41.4 g/d, P < 0.01) along with a 42.8 % reduction in the feed conversion ratio (3.95 vs. 6.91, P < 0.01) versus the control. Liver weights in the EGCG group were significantly elevated compared to the CON group on days 14 and 21 (P < 0.05) and a strong correlation between liver weight and body weight. EGCG significantly increased catalase, glutathione peroxidase, and superoxide dismutase activities, and the total antioxidant capacity in serum and jejunum while decreasing malondialdehyde (MDA) levels (P < 0.05). Immunological analyses revealed elevated serum immunoglobulin (Ig)A, IgG, and IgM and lysozyme in the EGCG group (P < 0.05), accompanied by a decrease in the pro-inflammatory cytokines interleukin-6 and interferon-γ. Intestinal morphology demonstrated increased villus height-to-crypt depth ratios in the duodenum and ileum (P < 0.05). 16S rRNA sequencing indicated that EGCG increased the relative abundance of Akkermansia and Verrucomicrobiota (P < 0.05) in the cecal content and enriched microbial functions related to inorganic ion transport and metabolism. Correlation analysis revealed positive associations between Akkermansia and IgA, and between Firmicutes and oxidative damage markers (MDA). Overall, dietary supplementation with 200 mg/kg EGCG could improve growth performance, antioxidant capacity, immune response, and gut microbiota structure in geese, supporting its potential as a plant-based feed additive.
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Affiliation(s)
- Mengyu Liu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University,163319, Daqing, Heilongjiang, PR China
| | - Yansong Ge
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University,163319, Daqing, Heilongjiang, PR China
| | - Enshuang Xu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University,163319, Daqing, Heilongjiang, PR China
| | - Tingting Zhu
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University,163319, Daqing, Heilongjiang, PR China
| | - Hongri Ruan
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University,163319, Daqing, Heilongjiang, PR China
| | - Jiasan Zheng
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University,163319, Daqing, Heilongjiang, PR China.
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Yakut A. Gut microbiota in the development and progression of chronic liver diseases: Gut microbiota-liver axis. World J Hepatol 2025; 17:104167. [PMID: 40177197 PMCID: PMC11959663 DOI: 10.4254/wjh.v17.i3.104167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/28/2025] [Accepted: 02/25/2025] [Indexed: 03/26/2025] Open
Abstract
The gut microbiota (GM) is a highly dynamic ecology whose density and composition can be influenced by a wide range of internal and external factors. Thus, "How do GM, which can have commensal, pathological, and mutualistic relationships with us, affect human health?" has become the most popular research issue in recent years. Numerous studies have demonstrated that the trillions of microorganisms that inhabit the human body can alter host physiology in a variety of systems, such as metabolism, immunology, cardiovascular health, and neurons. The GM may have a role in the development of a number of clinical disorders by producing bioactive peptides, including neurotransmitters, short-chain fatty acids, branched-chain amino acids, intestinal hormones, and secondary bile acid conversion. These bioactive peptides enter the portal circulatory system through the gut-liver axis and play a role in the development of chronic liver diseases, cirrhosis, and hepatic encephalopathy. This procedure is still unclear and quite complex. In this study, we aim to discuss the contribution of GM to the development of liver diseases, its effects on the progression of existing chronic liver disease, and to address the basic mechanisms of the intestinal microbiota-liver axis in the light of recent publications that may inspire the future.
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Affiliation(s)
- Aysun Yakut
- Department of Gastroenterology, İstanbul Medipol University Sefakoy Health Practice Research Center, İstanbul 38000, Türkiye.
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Zhou F, Deng S, Luo Y, Liu Z, Liu C. Research Progress on the Protective Effect of Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG) on the Liver. Nutrients 2025; 17:1101. [PMID: 40218859 PMCID: PMC11990830 DOI: 10.3390/nu17071101] [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: 02/24/2025] [Revised: 03/15/2025] [Accepted: 03/18/2025] [Indexed: 04/14/2025] Open
Abstract
The liver, as the primary metabolic organ, is susceptible to an array of factors that can harm liver cells and give rise to different liver diseases. Epigallocatechin gallate (EGCG), a natural compound found in green tea, exerts numerous beneficial effects on the human body. Notably, EGCG displays antioxidative, antibacterial, antiviral, anti-inflammatory, and anti-tumor properties. This review specifically highlights the pivotal role of EGCG in liver-related diseases, focusing on viral hepatitis, autoimmune hepatitis, fatty liver disease, and hepatocellular carcinoma. EGCG not only inhibits the entry and replication of hepatitis B and C viruses within hepatocytes, but also mitigates hepatocytic damage caused by hepatitis-induced inflammation. Furthermore, EGCG exhibits significant therapeutic potential against hepatocellular carcinoma. Combinatorial use of EGCG and anti-hepatocellular carcinoma drugs enhances the sensitivity of drug-resistant cancer cells to chemotherapeutic agents, leading to improved therapeutic outcomes. Thus, the combination of EGCG and anti-hepatocellular carcinoma drugs holds promise as an effective approach for treating drug-resistant hepatocellular carcinoma. In conclusion, EGCG possesses hepatoprotective properties against various forms of liver damage and emerges as a potential drug candidate for liver diseases.
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Affiliation(s)
- Fang Zhou
- School of Chemistry and Environmental Sciences, Xiangnan University, Chenzhou 423000, China;
| | - Sengwen Deng
- School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China; (S.D.); (C.L.)
| | - Yong Luo
- School of Chemistry and Environmental Sciences, Xiangnan University, Chenzhou 423000, China;
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China;
| | - Changwei Liu
- School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China; (S.D.); (C.L.)
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Esmaeili Z, Shavali Gilani P, Khosravani M, Motamedi M, Maleknejad S, Adabi M, Sadighara P. Nanotechnology-driven EGCG: bridging antioxidant and therapeutic roles in metabolic and cancer pathways. Nanomedicine (Lond) 2025; 20:621-636. [PMID: 39924937 PMCID: PMC11881875 DOI: 10.1080/17435889.2025.2462521] [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: 10/28/2024] [Accepted: 01/31/2025] [Indexed: 02/11/2025] Open
Abstract
Epigallocatechin-3-gallate (EGCG), the primary polyphenol in green tea, is renowned for its potent antioxidant properties. EGCG interacts with various cellular targets, inhibiting cancer cell proliferation through apoptosis and cell cycle arrest induction, while also modulating metabolic pathways. Studies have demonstrated its potential in addressing cancer development, obesity, and diabetes. Given the rising prevalence of metabolic diseases and cancers, EGCG is increasingly recognized as a promising therapeutic agent. This review provides a comprehensive overview of the latest findings on the effects of both free and nano-encapsulated EGCG on mechanisms involved in the management and prevention of hyperlipidemia, diabetes, and gastrointestinal (GI) cancers. The review highlights EGCG role in modulating key signaling pathways, enhancing bioavailability through nano-formulations, and its potential applications in clinical settings.
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Affiliation(s)
- Zahra Esmaeili
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Shavali Gilani
- Department of Environmental Health Engineering, Division of Food Safety and Hygiene, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Masood Khosravani
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maral Motamedi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shokofeh Maleknejad
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mahdi Adabi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Sadighara
- Department of Environmental Health Engineering, Division of Food Safety and Hygiene, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Lu Y, Li X, Ma S, Ding M, Yang F, Pang X, Sun J, Li X. Broccoli ( Brassica oleracea L. var. italica Planch) alleviates metabolic-associated fatty liver disease through regulating gut flora and lipid metabolism via the FXR/LXR signaling pathway. Food Funct 2025; 16:1218-1240. [PMID: 39903517 DOI: 10.1039/d4fo03731f] [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: 02/06/2025]
Abstract
The increased consumption of dietary fats contributes to the development of MAFLD (metabolic fatty liver disease). The ability of broccoli to enhance lipid metabolism has attracted researchers' attention. Researchers fed C57BL/6 mice a 12-week HFD to ensure the induction of MAFLD. The findings indicated that broccoli floret juice could effectively relieve MAFLD. Broccoli is helpful for reducing weight, blood glucose levels, fat accumulation, and insulin resistance associated with MAFLD and reduces the concentrations of TC, TG, LDL-C, GOT, GPT, IL-1β, IL-6, CCL4, and MCP1. Broccoli can increase the concentration of HDL-C, CAT, GSH-Px, SOD, and T-AOC, relieve inflammation and hepatic and ileum damage, and improve the antioxidant capacity of the body. Also, broccoli can optimize the structure of intestinal flora, promote the growth of Allobaculum, Muribaculaceae, Akkermansia, Eubacterium, and Bacteroides, and reduce bile acid deposition. In addition, the FXR/LXRα signaling system is impacted by broccoli, which is capable of raising the average levels of expression of the Fxr, SHP, and Cyp7a1 genes and proteins and reducing those of the genes for Fasn, Lpin 1, Dgat 2, Scd1, LXRα, and SREBP-1c.
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Affiliation(s)
- Yingjian Lu
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
| | - Xin Li
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
| | - Shaotong Ma
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
| | - Meng Ding
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
| | - Feiyu Yang
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Xinyi Pang
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
| | - Jing Sun
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
| | - Xiangfei Li
- College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing 210023, China.
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Andrei C, Zanfirescu A, Ormeneanu VP, Negreș S. Evaluating the Efficacy of Secondary Metabolites in Antibiotic-Induced Dysbiosis: A Narrative Review of Preclinical Studies. Antibiotics (Basel) 2025; 14:138. [PMID: 40001382 PMCID: PMC11852119 DOI: 10.3390/antibiotics14020138] [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: 12/19/2024] [Revised: 01/20/2025] [Accepted: 01/23/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate evidence from preclinical studies on the therapeutic effects of secondary metabolites in restoring gut microbial balance, emphasizing their mechanisms and efficacy. METHODS A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies were selected based on specific inclusion criteria, focusing on animal models treated with secondary metabolites for antibiotic-induced dysbiosis. The search terms included "gut microbiota", "antibiotics", and "secondary metabolites". Data extraction focused on microbial alterations, metabolite-specific effects, and mechanisms of action. Relevant findings were systematically analyzed and summarized. RESULTS Secondary metabolites demonstrated diverse effects in mitigating the impact of dysbiosis by modulating gut microbial composition, reducing inflammation, and supporting host biological markers. Polysaccharides and polyphenols restored the Firmicutes/Bacteroidetes ratio, increased beneficial taxa such as Lactobacillus and Bifidobacterium, and suppressed pathogenic bacteria like Escherichia-Shigella. Metabolites such as triterpenoid saponins enhanced gut barrier integrity by upregulating tight junction proteins, while alkaloids reduced inflammation by modulating proinflammatory cytokines (e.g., TNF-α, IL-1β). These metabolites also improved short-chain fatty acid production, which is crucial for gut and systemic health. While antibiotic-induced dysbiosis was the primary focus, other drug classes (e.g., PPIs, metformin) require further investigation. CONCLUSIONS Plant-derived secondary metabolites show promise in managing antibiotic-induced dysbiosis by restoring microbial balance, reducing inflammation, and improving gut barrier function. Future research should explore their applicability to other types of drug-induced dysbiosis and validate findings in human studies to enhance clinical relevance.
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Affiliation(s)
| | - Anca Zanfirescu
- Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania; (C.A.); (V.-P.O.); (S.N.)
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Yao L, Zhou X, Jiang X, Chen H, Li Y, Xiong X, Tang Y, Zhang H, Qiao P. High-fat diet promotes gestational diabetes mellitus through modulating gut microbiota and bile acid metabolism. Front Microbiol 2025; 15:1480446. [PMID: 39935515 PMCID: PMC11810896 DOI: 10.3389/fmicb.2024.1480446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 12/27/2024] [Indexed: 02/13/2025] Open
Abstract
Introduction Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance during pregnancy, estimated to affect approximately 20% of the whole pregnancies and is increasing in prevalence globally. However, there is still a big gap in knowledge about the association between gut microbiota associated metabolism alterations and GDM development. Methods All the participants accomplished the validated internet-based dietary questionnaire for Chinese and serum, fecal samples were collected. HFD, control diet or colesevelam intervention was fed to GDM mice models or Fxr-/- mice models, with or without antibiotics cocktail treatment. Fecal microbiota transplantation were used for further validation. Gut microbiota and metabolites were detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Bile acids of serum, fecal samples from human and mice were analysised. Body weight, average feed intake, blood glucose, insulin levels and oral glucose tolerance test was performed among each groups. Expression levels of Fxr, Shp and Fgf15 mRNA and protein were detected by quantitative reverse transcription polymerase chain reaction and western blot, respectively. Results Our data indicated that high fat diet (HFD) was linked with higher prevalence of GDM, and HFD was positively associated with poor prognosis in GDM patients. Moreover, compared with normal diet (ND) group, GDM patients from HFD group performed a loss of gut microbiota diversity and enrichment of Alistipes onderdonkii, Lachnospiraceae bacterium 1_7_58FAA, and Clostridium aspaaragiforme while ruduction of Akkermansiaceae, Paraprevotell xylaniphila, and Prevotella copri. Additionally, HFD aggravated GDM in mice and gut microbiota depletion by antibiotics crippled the effect of excess fat intake. BAs profile altered in HFD GDM patients and mice models. Fecal microbiota transplantation (FMT) further confirmed that gut microbiota contributed to bile acids (BAs) metabolic dysfunction during HFD-associated GDM development. Mechanically, HFD-FMT administration activated Fxr, Shp, and Fgf15 activity, disturbed the glucose metabolism and aggravated insulin resistance but not in HFD-FMT Fxr-/- mice and ND-FMT Fxr-/- mice. Furthermore, colesevelam intervention alleviated HFD-associated GDM development, improved BAs metabolism, suppressed Fxr, Shp, and Fgf15 activity only in WT mice but not in the Fxr-/- HFD + Colesevelam group and Fxr-/- HFD group. HFD induced GDM and contributed to poor prognosis in GDM parturients through inducing gut microbial dysbiosis and metabolic alteration, especially appeared in BAs profile. Moreover, Fxr pathway participated in regulating HFD-associated gut microbiota disordered BAs metabolites and aggravating GDM in mice. Discussion Modulating gut microbiota and BAs metabolites could be a potential therapeutic strategy in the prevention and treatment of HFD-associated GDM.
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Affiliation(s)
- Lei Yao
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xuefei Zhou
- Department of Gynaecology and Obstetrics, The Center of Red Cross Hospital of Harbin, Harbin, China
| | - Xianqi Jiang
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hao Chen
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yuanliang Li
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiao Xiong
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yan Tang
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Haogang Zhang
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Pengfei Qiao
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Costa MADC, da Silva Duarte V, Fraiz GM, Cardoso RR, da Silva A, Martino HSD, Dos Santos D'Almeida CT, Ferreira MSL, Corich V, Hamaker BR, Giacomini A, Bressan J, Barros FARD. Regular Consumption of Black Tea Kombucha Modulates the Gut Microbiota in Individuals with and without Obesity. J Nutr 2024:S0022-3166(24)01239-2. [PMID: 39732435 DOI: 10.1016/j.tjnut.2024.12.013] [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: 08/26/2024] [Revised: 11/22/2024] [Accepted: 12/18/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND Kombucha, a fermented beverage obtained from a Symbiotic Culture of Bacteria and Yeast, has shown potential in modulating gut microbiota, although no clinical trials have been done. OBJECTIVES We aimed to evaluate the effects of regular black tea kombucha consumption on intestinal health in individuals with and without obesity. METHODS A pre-post clinical intervention study was conducted lasting 8 wk. Forty-six participants were allocated into 2 groups: normal weight + black tea kombucha (n = 23); and obese + black tea kombucha (n = 23). Blood, urine, and stool samples were collected at baseline (T0) and after 8 wk of intervention (T8). RESULTS A total of 145 phenolic compounds were identified in the kombucha, primarily flavonoids (81%) and phenolic acids (19%). Kombucha favored commensal bacteria such as Bacteroidota and Akkermanciaceae, especially in the obese group. Subdoligranulum, a butyrate producer, also increased in the obese group after kombucha consumption (P = 0.031). Obesity-associated genera Ruminococcus and Dorea were elevated in the obese group at baseline (P < 0.05) and reduced after kombucha consumption, becoming similar to the normal weight group (Ruminococcus: obese T8 × normal weight T8: P = 0.27; Dorea: obese T8 × normal weight T0: P = 0.57; obese T8 × normal weight T8: P = 0.32). Fungal diversity increased, with a greater abundance of Saccharomyces in both groups and reductions in Exophiala and Rhodotorula, particularly in the obese group. Pichia and Dekkera, key microorganisms in kombucha, were identified as biomarkers after the intervention. CONCLUSIONS Regular kombucha consumption positively influenced gut microbiota in both normal and obese groups, with more pronounced effects in the obese group, suggesting that it may be especially beneficial for those individuals. This trial was registered at Brazilian Clinical Trial Registry - ReBEC as UTN code U1111-1263-9550 (https://ensaiosclinicos.gov.br/rg/RBR-9832wsx).
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Affiliation(s)
- Mirian Aparecida de Campos Costa
- Bioactive Compounds and Carbohydrates (BIOCARB) Research Group, Department of Food Science and Technology, Universidade Federal de Viçosa, Viçosa, MG, Brazil; Whistler Center for Carbohydrate Research, Department of Food Science, Purdue University, West Lafayette, IN, United States
| | - Vinícius da Silva Duarte
- Faculty of Chemistry, Biotechnology, and Food Science, The Norwegian University of Life Sciences, Ås, Norway
| | - Gabriela Macedo Fraiz
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brazil; Department of Nutrition, Food Science and Physiology, Center for Nutrition Research, Universidad de Navarra, Pamplona, Spain
| | - Rodrigo Rezende Cardoso
- Bioactive Compounds and Carbohydrates (BIOCARB) Research Group, Department of Food Science and Technology, Universidade Federal de Viçosa, Viçosa, MG, Brazil
| | - Alessandra da Silva
- Public Health Epidemiology Graduate Program, Environmental and Health Education Laboratory, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ, Brazil
| | | | - Carolina Thomaz Dos Santos D'Almeida
- Laboratory of Bioactives, Food and Nutrition Graduate Program, Federal University of State of Rio de Janeiro - UNIRIO, Rio de Janeiro, RJ, Brazil
| | - Mariana Simões Larraz Ferreira
- Laboratory of Bioactives, Food and Nutrition Graduate Program, Federal University of State of Rio de Janeiro - UNIRIO, Rio de Janeiro, RJ, Brazil
| | - Viviana Corich
- Department of Agronomy, Food Natural Resources, Animals, and Environment, Università degli Studi di Padova, Legnaro, Padova, PD, Italy
| | - Bruce R Hamaker
- Whistler Center for Carbohydrate Research, Department of Food Science, Purdue University, West Lafayette, IN, United States
| | - Alessio Giacomini
- Department of Agronomy, Food Natural Resources, Animals, and Environment, Università degli Studi di Padova, Legnaro, Padova, PD, Italy
| | - Josefina Bressan
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, MG, Brazil
| | - Frederico Augusto Ribeiro de Barros
- Bioactive Compounds and Carbohydrates (BIOCARB) Research Group, Department of Food Science and Technology, Universidade Federal de Viçosa, Viçosa, MG, Brazil.
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Zheng L, Li B, Yuan A, Bi S, Puscher H, Liu C, Qiao L, Qiao Y, Wang S, Zhang Y. TFEB activator tanshinone IIA and derivatives derived from Salvia miltiorrhiza Bge. Attenuate hepatic steatosis and insulin resistance. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118662. [PMID: 39117022 DOI: 10.1016/j.jep.2024.118662] [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: 03/05/2024] [Revised: 07/03/2024] [Accepted: 08/01/2024] [Indexed: 08/10/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Salvia miltiorrhiza Bge. (SMB) is an herbal medicine extensively used for improving metabolic disorders, including Nonalcoholic fatty liver disease (NAFLD). However, the potential material basis and working mechanism still remained to be elucidated. AIM OF THE STUDY To find potential ingredients for therapy of NAFLD by high content screening and further verify the efficacy on restoring hepatic steatosis and insulin resistance, and clarify the potential working mechanism. MATERIALS AND METHODS The mouse transcription factor EB (Tfeb) in preadipocytes was knocked out by CRISPR-Cas9 gene editing. High content screening of TFEB nuclear translocation was performed to identify TFEB activators. The effect of candidate compounds on reducing lipid accumulation was evaluated using Caenorhabditis elegans (C. elegans). Then the role of Salvia miltiorrhiza extract (SMB) containing Tanshinone IIA and the derivatives were further investigated on high-fat diet (HFD) fed mice. RNA-seq was performed to explore potential molecular mechanism of SMB. Finally, the gut microbiota diversity was evaluated using 16S rRNA sequencing to investigate the protective role of SMB on regulating gut microbiota homeostasis. RESULTS Knockout of Tfeb led to excessive lipid accumulation in adipocytes while expression of TFEB homolog HLH-30 in C. elegans (MAH240) attenuated lipid deposition. Screening of TFEB activators identified multiple candidates from Salvia miltiorrhiza, all of them markedly induced lysosome biogenesis in HepG2 cells. One of the candidate compounds Tanshinone IIA significantly decreased lipid droplet deposition in HFD fed C. elegans. Administration of SMB on C57BL/6J mice via gastric irrigation at the dose of 15 g/kg/d markedly alleviated hepatic steatosis, restored serum lipid profile, and glucose tolerance. RNA-seq showed that gene expression profile was altered and the genes related to lipid metabolism were restored. The disordered microbiome was remodeled by SMB, Firmicutes and Actinobacteriotawere notably reduced, Bacteroidota and Verrucomicrobiota were significantly increased. CONCLUSION Taken together, the observations presented here help address the question concerning what were the main active ingredients in SMB for alleviating NAFLD, and established that targeting TFEB was key molecular basis for the efficacy of SMB.
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Affiliation(s)
- Lulu Zheng
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China
| | - Beiyan Li
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China
| | - Anlei Yuan
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China
| | - Shijie Bi
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China
| | - Harrison Puscher
- Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA
| | - Chaoqun Liu
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China
| | - Liansheng Qiao
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China
| | - Yanjiang Qiao
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China
| | - Shifeng Wang
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China.
| | - Yanling Zhang
- Key Laboratory of TCM-information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beisanhuan East Road No. 11, Chaoyang District, Beijing, 100029, China.
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10
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Riegelman E, Xue K, Wang JS, Tang L. Therapeutic potential of green tea catechins on the development of Parkinson's disease symptoms in a transgenic A53T mouse model. Nutr Neurosci 2024:1-17. [PMID: 39612295 DOI: 10.1080/1028415x.2024.2427753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2024]
Abstract
Objectives: This study aimed to evaluate the effects of green tea catechins on the prevention of Parkinson's disease neurobehavioral symptoms and α-synuclein blood plasma concentration in a hemizygous transgenic A53T mouse model.Methods: Thirty 6-month-old male mice were randomly assigned to three groups (n = 10/group): control, low-dose, and high-dose, receiving green tea polyphenol (GTP) treatment in their drinking water at 0%, 0.5%, and 1.5%, respectively, over a 90-day period. The efficacy of ad libitum dosing was assessed by analyzing the bioaccumulation of tea catechins in urine samples collected from metabolic cages on days 0, 30, 60, and 90, using LC/Q-TOF analysis. PD-related behavioral impairments were measured with open field and rotarod performance tests on days 0, 45, and 90. On day 90, plasma α-synuclein levels were analyzed via enzyme-linked immunosorbent assay (ELISA) to assess treatment effects.Results: Circulating tea catechin metabolites were detected in treated groups by day 30, with levels progressively increasing through day 90. By day 90, control mice exhibited significant deficits in rotarod performance, while both low- and high-dose groups maintained or improved their maximum time on the rotarod. Open field testing indicated reduced anxiety-related behavior in control mice compared to treated groups. ELISA analysis revealed significantly lower circulating α-synuclein levels in high-dose mice compared to controls.Conclusion: Our findings indicate that sustained administration of tea catechins significantly reduces circulating α-synuclein levels in blood plasma, improves motor coordination in a dose-dependent manner, and modulates anxiety-related behaviors in a PD mouse model.
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Affiliation(s)
- Elizabeth Riegelman
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, USA
| | - Kathy Xue
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, USA
| | - Jia-Sheng Wang
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, USA
| | - Lili Tang
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, USA
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11
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Yuan X, Fang X, Li Y, Yan Z, Zhai S, Yang Y, Song J. Effects of dietary protein level on liver lipid deposition, bile acid profile and gut microbiota composition of growing pullets. Poult Sci 2024; 103:104183. [PMID: 39216266 PMCID: PMC11402545 DOI: 10.1016/j.psj.2024.104183] [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: 03/06/2024] [Revised: 07/16/2024] [Accepted: 08/01/2024] [Indexed: 09/04/2024] Open
Abstract
The current study investigated the effects of dietary crude protein (CP) level on the liver lipid metabolism, gut microbiota, and bile acids (BA) profiles of growing pullets. Roman growing pullets (N = 180, 13-wk-old) were divided into 3 treatments groups with 6 replicates in each group and 10 hens in each replicate and provided 3 different dietary CP level diet treatments. The diet treatments included: a high-protein diet (15.5% CP, HP group), a medium-protein diet (14.5% CP, MP group), and a low-protein diet (13.5% CP, LP group). Compared with HP group, LP group significantly increased the lipid contents in the body (such as Breast intramuscular fat [BIMF], Leg intramuscular fat [LIMF], Percentage of abdominal fat [PAF], liver triglyceride [TG] and liver cholesterol [TC]), and the lipid metabolism-related parameters in serum (such as cholesterol (TC), high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], very low density lipoprotein [VLDL]), and the mRNA expression of lipid metabolism-related genes (such as fatty acid synthase [FAS], CCAAT/enhancer binding protein β [C/EBPβ], and fatty acid translocase [FAT/CD6]) (P < 0.05). In addition, LP group significantly reduced the contents of lithocholic acid (LCA), isoLCA, and ursodesoxycholic acid (UDCA), and increased the deoxycholic acid (DCA) content compared with HP group (P < 0.05). The effects of LCA on lipid deposition were confirmed in chicken preadipocyte cell line (CPI), in which LCA supplementation significantly decreased the relative expression of PPARγ, FAS, acyl-CoA carboxylase (ACC) and SREBP-1c (P < 0.05). Correlation analysis further revealed a significant association between BA profiles and lipid metabolism-related parameters. Furthermore, 16S rRNA gene sequencing indicated that dietary protein level can significantly affect the richness, diversity, and composition of cecal microbiota in growing pullets. LP group significantly increased the abundance of Bacteroidetes and significantly decreased the abundance of Firmicutesa compared with the HP group. In summary, low protein diet in growing pullets influence the liver lipid metabolism through changing the gut microbiota and liver BA metabolism.
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Affiliation(s)
- Xi Yuan
- College of Life Science, Yangtze University, Jingzhou, People's Republic of China
| | - Xiaoshuang Fang
- College of Animal Science and Technology, Yangtze University, Jingzhou, People's Republic of China
| | - Yongxia Li
- College of Life Science, Yangtze University, Jingzhou, People's Republic of China
| | - Zixing Yan
- College of Life Science, Yangtze University, Jingzhou, People's Republic of China
| | - Shuangshuang Zhai
- College of Life Science, Yangtze University, Jingzhou, People's Republic of China
| | - Ye Yang
- College of Life Science, Yangtze University, Jingzhou, People's Republic of China
| | - Jiao Song
- College of Animal Science and Technology, Yangtze University, Jingzhou, People's Republic of China.
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12
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Espín JC, Jarrín‐Orozco MP, Osuna‐Galisteo L, Ávila‐Gálvez MÁ, Romo‐Vaquero M, Selma MV. Perspective on the Coevolutionary Role of Host and Gut Microbiota in Polyphenol Health Effects: Metabotypes and Precision Health. Mol Nutr Food Res 2024; 68:e2400526. [PMID: 39538982 PMCID: PMC11605795 DOI: 10.1002/mnfr.202400526] [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: 07/08/2024] [Revised: 09/25/2024] [Indexed: 11/16/2024]
Abstract
"Personalized nutrition" aims to establish nutritional strategies to improve health outcomes for non-responders. However, it is utopian since most people share similar nutritional requirements. "Precision health," encompassing lifestyles, may be more fitting. Dietary (poly)phenols are "healthy" but non-nutritional molecules (thus, we can live without them). The gut microbiota influences (poly)phenol effects, producing metabolites with different activity than their precursors. Furthermore, producing distinctive metabolites, like urolithins, lunularin, and equol, leads to the term "polyphenol-related gut microbiota metabotypes," grouping individuals based on a genuine microbial metabolism of ellagic acid, resveratrol, and isoflavones, respectively. Additionally, (poly)phenols exert prebiotic-like effects through their antimicrobial activities, typically reducing microbial diversity and modulating microbiota functionality by impacting its composition and transcriptomics. Since the gut microbiota perceives (poly)phenols as a threat, (poly)phenol effects are mostly a consequence of microbiota adaptation through differential (poly)phenol metabolism (e.g., distinctive reductions, dehydroxylations, etc.). This viewpoint is less prosaic than considering (poly)phenols as essential nutritional players in human health, yet underscores their health significance in a coevolutionary partnership with the gut microbiota. In the perspective on the gut microbiota and (poly)phenols interplay, microbiota metabotypes could arbiter health effects. An innovative aspect is also emphasized: modulating the interacting microbial networks without altering the composition.
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Affiliation(s)
- Juan Carlos Espín
- Laboratory of Food & Health; Research Group on Quality, Safety and Bioactivity of Plant FoodsCEBAS‐CSIC30100 Campus de EspinardoMurciaSpain
| | - María Paula Jarrín‐Orozco
- Laboratory of Food & Health; Research Group on Quality, Safety and Bioactivity of Plant FoodsCEBAS‐CSIC30100 Campus de EspinardoMurciaSpain
| | - Leire Osuna‐Galisteo
- Laboratory of Food & Health; Research Group on Quality, Safety and Bioactivity of Plant FoodsCEBAS‐CSIC30100 Campus de EspinardoMurciaSpain
| | - María Ángeles Ávila‐Gálvez
- Laboratory of Food & Health; Research Group on Quality, Safety and Bioactivity of Plant FoodsCEBAS‐CSIC30100 Campus de EspinardoMurciaSpain
| | - María Romo‐Vaquero
- Laboratory of Food & Health; Research Group on Quality, Safety and Bioactivity of Plant FoodsCEBAS‐CSIC30100 Campus de EspinardoMurciaSpain
| | - María Victoria Selma
- Laboratory of Food & Health; Research Group on Quality, Safety and Bioactivity of Plant FoodsCEBAS‐CSIC30100 Campus de EspinardoMurciaSpain
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13
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Aoi W, Koyama T, Honda A, Takagi T, Naito Y. Association of Serum Bile Acid Profile with Diet and Physical Activity Habits in Japanese Middle-Aged Men. Nutrients 2024; 16:3381. [PMID: 39408348 PMCID: PMC11478694 DOI: 10.3390/nu16193381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/28/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND/OBJECTIVES Circulating bile acid (BA) profiles change with lifestyle and are closely related to intestinal BA metabolisms such as deconjugation and conversion to secondary BAs. The composition of BA in the blood is involved in systemic nutrient metabolism and intestinal health. Herein, we explored the associations of lifestyle and physical fitness with the circulating BA profile of middle-aged men. METHODS Data of 147 male participants (aged 50-64 years; BMI < 26 kg/m2; no medication for diabetes or dyslipidemia) from the Japan Multi-Institutional Collaborative Cohort study were analyzed. Serum concentrations of 15 types of BAs were examined for associations with variables on dietary habits, physical-activity habits, and physical fitness. RESULTS Green tea intake was positively associated with the deconjugation ratio of total BAs (p = 0.028) and negatively associated with secondary BA levels (free deoxycholic acid [DCA] (p = 0.078), glyco-DCA (p = 0.048), and tauro-DCA (p = 0.037)). In contrast, physical activity was negatively associated with the deconjugation ratio (p = 0.029) and secondary BA levels (free DCA (p = 0.098), and free lithocholic acid (p = 0.009)). Grip strength was also negatively associated with secondary BA levels (tauro-DCA (p = 0.041)) but was not associated with the deconjugation ratio. Energy and fat intake and skeletal muscle mass were not associated with the deconjugation ratio or secondary BA levels. CONCLUSIONS The study findings suggest that lifestyle-associated changes in serum deconjugated and secondary BAs indicate improvements in nutrient metabolism and the intestinal environment.
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Affiliation(s)
- Wataru Aoi
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto 6068522, Japan
| | - Teruhide Koyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
| | - Akira Honda
- Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Ibaraki 3000395, Japan;
| | - Tomohisa Takagi
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
- Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
| | - Yuji Naito
- Department of Human Immunology and Nutrition Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
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14
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Ma H, Wang Y, Wei J, Wang X, Yang H, Wang S. Stabilization of hypoxia-inducible factor 1α and regulation of specific gut microbes by EGCG contribute to the alleviation of ileal barrier disorder and obesity. Food Funct 2024; 15:9983-9994. [PMID: 39279449 DOI: 10.1039/d4fo02283a] [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: 09/18/2024]
Abstract
Tea polyphenols have a regulatory effect on metabolic-related diseases, however, the underlying mechanism remains elusive. Our study aims to explore the dietary intervention effect of Epigallocatechin gallate (EGCG), the major polyphenol in green tea, on obesity and intestinal barrier disorders in mice fed a high-fat diet. By supplementing with 50 mg kg-1 EGCG, we observed a significant amelioration in body weight gain, fat accumulation, and liver dysfunction. Furthermore, EGCG modulated the HFD-induced metabolomic alterations. In particular, EGCG intervention restored the ileal barrier by enhancing the expression of tight junction proteins and antimicrobial peptides. At the mechanistic level, EGCG treatment stabilized hypoxia-inducible factor 1α (HIF1α) both in vitro and in vivo. Meanwhile, EGCG significantly increased the abundance of Dubosiella and Akkermansia, along with the elevated SCFA contents. These findings suggest that the ability of EGCG to stabilize HIF1α and regulate specific gut microbes is pivotal in mitigating ileal barrier dysfunction and obesity. Moreover, serum metabolomics revealed potential biomarkers following EGCG intervention. This study supports the intake of EGCG or green tea in obesity management and offers a novel perspective for investigating the metabolic regulatory mechanism of other dietary polyphenols.
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Affiliation(s)
- Hui Ma
- College of Food Science, Shanxi Normal University, Taiyuan 030031, Shanxi, China.
| | - Yuanyifei Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.
| | - Jiayu Wei
- College of Food Science, Shanxi Normal University, Taiyuan 030031, Shanxi, China.
| | - Xiaochi Wang
- College of Food Science, Shanxi Normal University, Taiyuan 030031, Shanxi, China.
| | - Hui Yang
- College of Food Science, Shanxi Normal University, Taiyuan 030031, Shanxi, China.
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.
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15
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Mandal AK, Sahoo A, Almalki WH, Almujri SS, Alhamyani A, Aodah A, Alruwaili NK, Abdul Kadir SZBS, Mandal RK, Almalki RA, Lal JA, Rahman M. Phytoactives for Obesity Management: Integrating Nanomedicine for Its Effective Delivery. Nutr Rev 2024:nuae136. [PMID: 39331591 DOI: 10.1093/nutrit/nuae136] [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] [Indexed: 09/29/2024] Open
Abstract
Obesity is a global health concern that requires urgent investigation and management. While synthetic anti-obesity medications are available, they come with a high risk of side-effects and variability in their efficacy. Therefore, natural compounds are increasingly being used to treat obesity worldwide. The proposition that naturally occurring compounds, mainly polyphenols, can be effective and safer for obesity management through food and nutrient fortification is strongly supported by extensive experimental research. This review focuses on the pathogenesis of obesity while reviewing the efficacy of an array of phytoactives used for obesity treatment. It details mechanisms such as enzyme inhibition, energy expenditure, appetite suppression, adipocyte differentiation, lipid metabolism, and modulation of gut microbiota. Comprehensive in vitro, in vivo, and preclinical studies underscore the promise of phytoactives in combating obesity, which have been thoroughly reviewed. However, challenges, such as poor bioavailability and metabolism, limit their potential. Advances in nanomedicines may overcome these constraints, offering a new avenue for enhancing the efficacy of phytoactives. Nonetheless, rigorous and targeted clinical trials are essential before applying phytoactives as a primary treatment for obesity.
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Affiliation(s)
- Ashok Kumar Mandal
- Department of Pharmacology, Faculty of Medicine, University Malaya, Kuala Lumpur 50603, Malaysia
| | - Ankit Sahoo
- Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh 211007, India
| | - Waleed H Almalki
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Salem Salman Almujri
- Department of Pharmacology, College of Pharmacy, King Khalid University, Asir-Abha 61421, Saudi Arabia
| | - Abdulrahman Alhamyani
- Pharmaceuticals Chemistry Department, Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia
| | - Alhussain Aodah
- College of Pharmacy, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia
| | - Nabil K Alruwaili
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakakah 72341, Saudi Arabia
| | | | | | - Rami A Almalki
- Clinical Pharmacy Unit, Pharmaceutical Care Department, King Faisal Hospital, Makkah Health Cluster, Makkah 24382, Saudi Arabia
| | - Jonathan A Lal
- Department of Molecular and Cellular Engineering, Jacob Institute of Biotechnology and Bioengineering, Sam Higginbottom University of Agriculture, Technology, and Sciences, Prayagraj, Uttar Pradesh 211007, India
| | - Mahfoozur Rahman
- Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh 211007, India
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16
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Mohammadhasani K, Vahedi Fard M, Mottaghi Moghaddam Shahri A, Khorasanchi Z. Polyphenols improve non-alcoholic fatty liver disease via gut microbiota: A comprehensive review. Food Sci Nutr 2024; 12:5341-5356. [PMID: 39139973 PMCID: PMC11317728 DOI: 10.1002/fsn3.4178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/01/2024] [Accepted: 04/04/2024] [Indexed: 08/15/2024] Open
Abstract
Polyphenols, natural micronutrients derived from plants, are valued for their anti-inflammatory and antioxidant properties. The escalating global prevalence of non-alcoholic fatty liver disease (NAFLD) underscores its status as a chronic progressive liver condition. Furthermore, the dysregulation of gut microbiota (GM) is implicated in the onset and progression of NAFLD through the actions of metabolites such as bile acids (BAs), lipopolysaccharide (LPS), choline, and short-chain fatty acids (SCFAs). Additionally, GM may influence the integrity of the intestinal barrier. This review aims to evaluate the potential effects of polyphenols on GM and intestinal barrier function, and their subsequent impact on NAFLD. We searched through a wide range of databases, such as Web of Science, PubMed, EMBASE, and Scopus to gather information for our non-systematic review of English literature. GM functions and composition can be regulated by polyphenols such as chlorogenic acid, curcumin, green tea catechins, naringenin, quercetin, resveratrol, and sulforaphane. Regulating GM composition improves NAFLD by alleviating inflammation, liver fat accumulation, and liver enzymes. Furthermore, it improves serum lipid profile and gut barrier integrity. All of these components affect NAFLD through the metabolites of GM, including SCFAs, choline, LPS, and BAs. Current evidence indicates that chlorogenic acid, resveratrol, quercetin, and curcumin can modulate GM, improving intestinal barrier integrity and positively impacting NAFLD. More studies are necessary to evaluate the safety and efficacy of naringenin, sulforaphane, and catechin.
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Affiliation(s)
- Kimia Mohammadhasani
- Department of Nutrition, Food Sciences and Clinical Biochemistry, School of Medicine, Social Determinants of Health Research CenterGonabad University of Medical SciencesGonabadIran
| | - Mohammad Vahedi Fard
- Department of Nutrition, Food Sciences and Clinical Biochemistry, School of Medicine, Social Determinants of Health Research CenterGonabad University of Medical SciencesGonabadIran
| | - Ali Mottaghi Moghaddam Shahri
- International UNESCO Center for Health‐Related Basic Sciences and Human NutritionMashhad University of Medical SciencesMashhadIran
| | - Zahra Khorasanchi
- Department of Nutrition, School of MedicineMashhad University of Medical SciencesMashhadIran
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17
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Fujisaka S, Watanabe Y, Toume K, Morinaga Y, Nawaz A, Kado T, Nishimura A, Bilal M, Aslam MR, Igarashi Y, Nakagawa Y, Tobe K. Identification of herbal drug extracts that promote growth of Akkermansia muciniphila in high-fat diet fed mice. Diabetol Int 2024; 15:495-506. [PMID: 39101187 PMCID: PMC11291798 DOI: 10.1007/s13340-024-00713-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 03/12/2024] [Indexed: 08/06/2024]
Abstract
Disruption of the gut microbiota causes metabolic dysfunction, and intervention in the gut microbiota has the potential to improve host glucose metabolism. Akkermanisa muciniphila is an intestinal bacterium involved in anti-obesity and insulin resistance. Developing interventions to increase A. muciniphla would be useful for new treatment strategies. In this study, we screened herbal drug extracts that promoted the growth of A. muciniphila. Among the 123 herbal drugs, five herbal drug extracts significantly increased A. muciniphila DNA levels compared with that in controls. In particular, Dioscoreae rhizoma extract increased the growth of A. muciniphila in the intestines of mice fed a high-fat diet and improved obesity. It significantly reduced body weight gain, improved glucose tolerance even when the administration was initiated after the induction of dietary obesity. These results suggest that herbal drug extracts, such as Dioscoreae rhizome, that increase A. muciniphila could be a new therapeutic strategy for metabolic syndrome. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-024-00713-w.
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Affiliation(s)
- Shiho Fujisaka
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
| | - Yoshiyuki Watanabe
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
| | - Kazufumi Toume
- Institute of Natural Medicine, University of Toyama, Toyama, 9300194 Japan
| | - Yoshitomo Morinaga
- Department of Microbiology, Faculty of Medicine, University of Toyama, Toyama, 9300194 Japan
| | - Allah Nawaz
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
- Section of Integrative Physiology and Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215 USA
| | - Tomonobu Kado
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
| | - Ayumi Nishimura
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
| | - Muhammad Bilal
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
| | - Muhammad Rahil Aslam
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
| | - Yoshiko Igarashi
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
| | - Yoshimi Nakagawa
- Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama, 9300194 Japan
| | - Kazuyuki Tobe
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 9300194 Japan
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18
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Zuo G, Chen M, Zuo Y, Liu F, Yang Y, Li J, Zhou X, Li M, Huang JA, Liu Z, Lin Y. Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024. [PMID: 38607257 DOI: 10.1021/acs.jafc.3c04832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/13/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the "gut microbiota-barrier-liver axis" are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman's correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.
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Affiliation(s)
- Gaolong Zuo
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
| | - Meiyan Chen
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
| | - Yingpeng Zuo
- National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
| | - Fen Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
| | - Yuzhu Yang
- National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
| | - Jie Li
- Co-Innovation Centre of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
| | - Xirui Zhou
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
| | - Menghua Li
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
| | - Jian-An Huang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
- National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
- National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
- Co-Innovation Centre of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
| | - Yong Lin
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, PR China
- National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
- Co-Innovation Centre of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, PR China
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19
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Shoji T, Masumoto S, Miura T. Mechanism of procyanidins for health functionality by improving the intestinal environment. Biosci Biotechnol Biochem 2024; 88:345-351. [PMID: 38059864 DOI: 10.1093/bbb/zbad174] [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: 09/29/2023] [Accepted: 11/27/2023] [Indexed: 12/08/2023]
Abstract
Procyanidins are one of the polyphenols consisting of multiple flavan-3-ols (eg epicatechin). They have a complex chemical structure, with the degree of polymerization and linked position of flavan-3-ols varying among various foods, such as apples and chocolate. Physiological functional studies of procyanidins have investigated their mechanisms in cells and animals based on their antioxidant effects. Recently, the intestinal environment, including the intestinal microflora, has played an important role in the energy metabolism and health status of the host. Regulation of the intestinal environment by dietary polyphenols is becoming a new concept in health functions, and we have begun to investigate the mechanism of apple procyanidins, focusing on the gut microbiota and metabolites in our functional research. In this minireview, we will discuss the effects of procyanidin ingestion on the gut microbiota and metabolites.
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Affiliation(s)
- Toshihiko Shoji
- Food Research Institute, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki, Japan
| | - Saeko Masumoto
- Faculty of Food and Agricultural Sciences, Fukushima University, 1, Kanayagawa, Fukushima-shi, Fukushima, Japan
| | - Tomisato Miura
- Institute of Radiation Emergency Medicine, Hirosaki University, 66-1, Hon-cho, Hirosaki-shi, Aomori, Japan
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Liu M, Kang Z, Cao X, Jiao H, Wang X, Zhao J, Lin H. Prevotella and succinate treatments altered gut microbiota, increased laying performance, and suppressed hepatic lipid accumulation in laying hens. J Anim Sci Biotechnol 2024; 15:26. [PMID: 38369510 PMCID: PMC10874536 DOI: 10.1186/s40104-023-00975-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 12/12/2023] [Indexed: 02/20/2024] Open
Abstract
BACKGROUND This work aimed to investigate the potential benefits of administering Prevotella and its primary metabolite succinate on performance, hepatic lipid accumulation and gut microbiota in laying hens. RESULTS One hundred and fifty 58-week-old Hyline Brown laying hens, with laying rate below 80% and plasma triglyceride (TG) exceeding 5 mmol/L, were used in this study. The hens were randomly allocated into 5 groups and subjected to one of the following treatments: fed with a basal diet (negative control, NC), oral gavage of 3 mL/hen saline every other day (positive control, PC), gavage of 3 mL/hen Prevotella melaninogenica (107 CFU/mL, PM) or 3 mL/hen Prevotella copri (107 CFU/mL, P. copri) every other day, and basal diet supplemented with 0.25% sodium succinate (Succinate). The results showed that PM and P. copri treatments significantly improved laying rate compared to the PC (P < 0.05). The amount of lipid droplet was notably decreased by PM, P. copri, and Succinate treatments at week 4 and decreased by P. copri at week 8 (P < 0.05). Correspondingly, the plasma TG level in Succinate group was lower than that of PC (P < 0.05). Hepatic TG content, however, was not significantly influenced at week 4 and 8 (P > 0.05). PM treatment increased (P < 0.05) the mRNA levels of genes PGC-1β and APB-5B at week 4, and ACC and CPT-1 at week 8. The results indicated enhanced antioxidant activities at week 8, as evidenced by reduced hepatic malondialdehyde (MDA) level and improved antioxidant enzymes activities in PM and Succinate groups (P < 0.05). Supplementing with Prevotella or succinate can alter the cecal microbiota. Specifically, the abundance of Prevotella in the Succinate group was significantly higher than that in the other 4 groups at the family and genus levels (P < 0.05). CONCLUSIONS Oral intake of Prevotella and dietary supplementation of succinate can ameliorate lipid metabolism of laying hens. The beneficial effect of Prevotella is consistent across different species. The finding highlights that succinate, the primary metabolite of Prevotella, represents a more feasible feed additive for alleviating fatty liver in laying hens.
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Affiliation(s)
- Min Liu
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271018, China
| | - Zeyue Kang
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271018, China
| | - Xikang Cao
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271018, China
| | - Hongchao Jiao
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271018, China
| | - Xiaojuan Wang
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271018, China
| | - Jingpeng Zhao
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271018, China
| | - Hai Lin
- College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an, 271018, China.
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Sidhu D, Vasundhara M, Dey P. The intestinal-level metabolic benefits of green tea catechins: Mechanistic insights from pre-clinical and clinical studies. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 123:155207. [PMID: 38000106 DOI: 10.1016/j.phymed.2023.155207] [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: 07/25/2023] [Revised: 10/11/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND The intestinal-level host-microbiota interaction has been implicated in the pathogenesis of chronic diseases. The current review is intended to provide a comprehensive insight into deciphering whether intestinal-level bioactivities mediate the overall metabolic health benefits of green tea catechins. PURPOSE We have comprehensively discussed pre-clinical and clinical evidences of intestinal-level changes in metabolism, microbiota, and metabolome due to catechin-rich green tea treatments, ultimately limiting metabolic diseases. Exclusive emphasis has been given to purified catechins and green tea, and discussions on extraintestinal mechanisms of metabolic health benefits were avoided. METHODS A literature search for relevant pre-clinical and clinical studies was performed in various online databases (e.g., PubMed) using specific keywords (e.g., catechin, intestine, microbiota). Out of all the referred literature, ∼15% belonged to 2021-2023, ∼51% were from 2011-2020, and ∼32% from 2000-2010. RESULT The metabolic health benefits of green tea catechins are indeed influenced by the intestinal-level bioactivities, including reduction of mucosal inflammation and oxidative stress, attenuation of gut barrier dysfunction, decrease in intestinal lipid absorption and metabolism, favorable modulation of mucosal nuclear receptor signaling, alterations of the luminal global metabolome, and mitigation of the gut dysbiosis. The results from the recent clinical studies support the pre-clinical evidences. The challenges and pitfalls of the currently available knowledge on catechin bioactivities have been discussed, and constructive directions to harness the translational benefits of green tea through future interventions have been provided. CONCLUSION The metabolism, metabolome, and microbiota at the intestinal epithelia play critical roles in catechin metabolism, pharmacokinetics, bioavailability, and bioactivities. Especially the reciprocal interaction between the catechins and the gut microbiota dictates the metabolic benefits of catechins.
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Affiliation(s)
- Dwinder Sidhu
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala 147004, India
| | - M Vasundhara
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala 147004, India.
| | - Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala 147004, India.
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Ren G, Bai C, Yi S, Cong Q, Zhu Y. Mechanisms and Therapeutic Strategies for MAFLD Targeting TLR4 Signaling Pathways. J Innate Immun 2023; 16:45-55. [PMID: 38128497 PMCID: PMC10783892 DOI: 10.1159/000535524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/23/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases. The underlying pathophysiological mechanisms are intricate and involve various factors. Unfortunately, there is currently a lack of available effective treatment options. Toll-like receptors (TLRs) are a group of pattern-recognition receptors that are responsible for activating the innate immune system. Research has demonstrated that TLR4 plays a pivotal role in the progression of MAFLD by facilitating the pathophysiological mechanisms. SUMMARY Lipid peroxidation, pro-inflammatory factors, insulin resistance (IR), and dysbiosis of intestinal microbiota are considered as the pathogenic mechanisms of MAFLD. This review summarizes the impact of TLR4 signaling pathways on the progression of MAFLD, specifically in relation to lipid metabolic disorders, IR, oxidative stress, and gut microbiota disorders. Additionally, we emphasize the potential therapeutic approaches for MAFLD that target TLR4 signaling pathways, including the use of plant extracts, traditional Chinese medicines, probiotics, pharmaceuticals such as peroxisome proliferator-activated receptor antagonists and farnesol X agonists, and lifestyle modifications such as dietary changes and exercise also considered. Furthermore, TLR4 signaling pathways have also been linked to the lean MAFLD. KEY MESSAGES TLR4 plays a crucial role in MAFLD by triggering IR, buildup of lipids, imbalance in gut microbiota, oxidative stress, and initiation of immune responses. The mitigation of MAFLD can be accomplished by suppressing the TLR4 signaling pathway. In the future, it could potentially emerge as a therapeutic target for the condition.
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Affiliation(s)
- Guanghui Ren
- Department of Infectious Disease, Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China,
| | - Changchuan Bai
- Dalian Hospital of Traditional Chinese Medicine, Dalian, China
| | - Sitong Yi
- Department of Infectious Disease, Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qingwei Cong
- Department of Infectious Disease, Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ying Zhu
- Department of Infectious Disease, Liver Disease Center of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Açar Y, Ağagündüz D, De Cicco P, Capasso R. Flavonoids: Their putative neurologic roles, epigenetic changes, and gut microbiota alterations in Parkinson's disease. Biomed Pharmacother 2023; 168:115788. [PMID: 37913731 DOI: 10.1016/j.biopha.2023.115788] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/25/2023] [Accepted: 10/25/2023] [Indexed: 11/03/2023] Open
Abstract
Parkinson's Disease (PD), a neurodegenerative disorder, is characterized by the degeneration of progressive dopaminergic (DA) neurons in the substantia nigra region of the human midbrain. Although just what causes PD remains a mystery, it is known that oxidative stress (OS) as well as mitochondrial dysfunction, neuro-inflammation, and insufficient neurotrophic support play a role in the disease's pathophysiology. Phytochemicals are a diverse small molecule group derived from plants that can be classified into numerous classes on the basis of their biological activities and chemical structure. Of these groups of phytochemicals, the most abundant, which has well-established anti-Parkinson's effects, are polyphenols. Flavonoids, including naringin and naringenin, genistein, kaempferol, anthocyanins, epigallocatechin-3-gallate, and baicalein are plant-based biologically active polyphenols, which have been shown to exhibit therapeutic potential when used as treatment for a variety of pathological illnesses, such as neurodegenerative diseases (NDs) and PD. Recently, it was reported that flavonoids have beneficial effects on PD, such as the protection of DA neurons, improvement of motor and cognitive abilities, regulation of signaling pathways, and modulation of OS and neuro-inflammation. In addition, by changing the composition of bacteria in gut microbiota, flavonoids reduce pathogenic strains and promote the growth of beneficial strains. In this context, the current paper will provide a literature review on the neurological roles that flavonoids play, as one of the most abundant phytochemical families, in PD.
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Affiliation(s)
- Yasemin Açar
- Department of Nutrition and Dietetics, Gazi University, Ankara, Turkey.
| | - Duygu Ağagündüz
- Department of Nutrition and Dietetics, Gazi University, Ankara, Turkey
| | - Paola De Cicco
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, Portici, 80055 Naples, Italy.
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Liu Y, Huang K, Zhang Y, Cao H, Guan X. Dietary polyphenols maintain homeostasis via regulating bile acid metabolism: a review of possible mechanisms. Food Funct 2023; 14:9486-9505. [PMID: 37815149 DOI: 10.1039/d3fo02471g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
The synthesis and metabolism of bile acids (BAs) have been implicated in various metabolic diseases, including obesity and diabetes. Dietary polyphenols, as natural antioxidants, play a vital role in synthesizing and metabolizing bile acids. This paper reviews the mechanism of dietary polyphenols involved in bile acid (BA) synthesis and metabolism. The impact of different gut microorganisms on BA profiles is discussed in detail. The regulation of BA metabolism by dietary polyphenols can be divided into two modes: (1) dietary polyphenols directly activate/inhibit farnesol X receptor (FXR) and Takeda G protein-coupled receptor (TGR5); (2) dietary polyphenols regulate BA synthesis and metabolism through changes in intestinal microorganisms. Research on direct activation/inhibition of FXR and TGR5 by polyphenols should be ramped up. In addition, the effect of dietary polyphenols on intestinal microorganisms has been paid more and more attention and has become a target that cannot be ignored.
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Affiliation(s)
- Yongyong Liu
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
| | - Kai Huang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
| | - Yu Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
| | - Hongwei Cao
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
| | - Xiao Guan
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
- National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, PR China
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Zhao N, Kong Y, Yuan Q, Wei Z, Gu J, Ji C, Jin H, Zhao M. The toxic mechanism of 6:2 Cl-PFESA in adolescent male rats: Endocrine disorders and liver inflammation regulated by the gut microbiota-gut-testis/liver axis. JOURNAL OF HAZARDOUS MATERIALS 2023; 459:132155. [PMID: 37517236 DOI: 10.1016/j.jhazmat.2023.132155] [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: 05/15/2023] [Revised: 07/18/2023] [Accepted: 07/25/2023] [Indexed: 08/01/2023]
Abstract
In previous studies, 6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), a perfluorooctanesulfonate alternative, has been demonstrated to be toxic to mammals. However, the toxic mechanism of 6:2 Cl-PFESA in mammals is unknown. Herein, adolescent male rats were administered 50 μg/kg/Day 6:2 Cl-PFESA for 28 days (oral gavage) to estimate the toxicity of 6:2 Cl-PFESA and investigate its toxic mechanism. Significant changes in some hematological indicators (e.g., aspartate transaminase and neutrophils) and liver sections (inflammatory cell infiltration) indicated that 6:2 Cl-PFESA exposure caused rat hepatotoxicity. Six steroid hormones (e.g., testosterone, progesterone, and cortisol) in serum and thirteen genes in testicles (related to the pathway of steroid hormone biosynthesis) were significantly regulated in 6:2 Cl-PFESA-treated rats. This suggested that 6:2 Cl-PFESA induced rat endocrine disorders. Compared to the controls, the mean relative abundance of Ruminococcaceae, Pasteurellaceae, Micrococcaceae, and Desulfovibrionaceae was significantly regulated by 1.3-, 0.40-, 0.32-, and 3.2-fold in the 6:2 Cl-PFESA rats, respectively. The 6:2 Cl-PFESA treatment also significantly disturbed 47 gut metabolites (29 upregulated and 18 downregulated), mainly bile acids, short-chain fatty acids, and amino acids. In summary, 6:2 Cl-PFESA induced endocrine disorders and liver inflammation in rats by altering the gut microbiota-gut-testis/liver axis. This study first reveals the toxic mechanism of 6:2 Cl-PFESA in mammals through a multiomics approach and provides comprehensive insight into the toxic mechanism of 6:2 Cl-PFESA.
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Affiliation(s)
- Nan Zhao
- Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, PR China
| | - Yuan Kong
- Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, PR China
| | - Qixian Yuan
- Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, PR China
| | - Zihao Wei
- Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, PR China
| | - Jinping Gu
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, PR China
| | - Chenyang Ji
- Zhejiang Provincial Key Laboratory of Pollution Exposure and Health Intervention, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou 310015, PR China.
| | - Hangbiao Jin
- Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, PR China.
| | - Meirong Zhao
- Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, PR China
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Cheng H, Zhang D, Wu J, Liu J, Zhou Y, Tan Y, Feng W, Peng C. Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 119:154979. [PMID: 37552899 DOI: 10.1016/j.phymed.2023.154979] [Citation(s) in RCA: 50] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 06/30/2023] [Accepted: 07/15/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time. In recent years, interaction with gut microbiota is hypothesized to be a reasonable explanation of the potential mechanisms for natural compounds especially polyphenols. OBJECTIVES This review aims to present a persuasive explanation for the contradiction between the limited bioavailability and the remarkable bioactivities of polyphenols by examining their interactions with gut microbiota. METHODS We assessed literatures published before April 10, 2023, from several databases, including Scopus, PubMed, Google Scholar, and Web of Science. The keywords used include "polyphenols", "gut microbiota", "short-chain fatty acids", "bile acids", "trimethylamine N-oxide", "lipopolysaccharides" "tryptophan", "dopamine", "intestinal barrier", "central nervous system", "lung", "anthocyanin", "proanthocyanidin", "baicalein", "caffeic acid", "curcumin", "epigallocatechin-3-gallate", "ferulic acid", "genistein", "kaempferol", "luteolin", "myricetin", "naringenin", "procyanidins", "protocatechuic acid", "pterostilbene", "quercetin", "resveratrol", etc. RESULTS: The review first demonstrates that polyphenols significantly alter gut microbiota diversity (α- and β-diversity) and the abundance of specific microorganisms. Polyphenols either promote or inhibit microorganisms, with various factors influencing their effects, such as dosage, treatment duration, and chemical structure of polyphenols. Furthermore, the review reveals that polyphenols regulate several gut microbiota metabolites, including short-chain fatty acids, dopamine, trimethylamine N-oxide, bile acids, and lipopolysaccharides. Polyphenols affect these metabolites by altering gut microbiota composition, modifying microbial enzyme activity, and other potential mechanisms. The changed microbial metabolites induced by polyphenols subsequently trigger host responses in various ways, such as acting as intestinal acid-base homeostasis regulators and activating on specific target receptors. Additionally, polyphenols are transformed into microbial derivatives by gut microbiota and these polyphenols' microbial derivatives have many potential advantages (e.g., increased bioactivity, improved absorption). Lastly, the review shows polyphenols maintain intestinal barrier, central nervous system, and lung function homeostasis by regulating gut microbiota. CONCLUSION The interaction between polyphenols and gut microbiota provides a credible explanation for the exceptional bioactivities of polyphenols. This review aids our understanding of the underlying mechanisms behind the bioactivity of polyphenols.
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Affiliation(s)
- Hao Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Dandan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Jing Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Juan Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, PR China
| | - Yaochuan Zhou
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Yuzhu Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China
| | - Wuwen Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
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Stojic J, Kukla M, Grgurevic I. The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status. Diagnostics (Basel) 2023; 13:2960. [PMID: 37761327 PMCID: PMC10528663 DOI: 10.3390/diagnostics13182960] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/06/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.
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Affiliation(s)
- Josip Stojic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, 10000 Zagreb, Croatia;
| | - Michał Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagellonian University Medical College, 31-688 Kraków, Poland;
- Department of Endoscopy, University Hospital, 30-688 Kraków, Poland
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, 10000 Zagreb, Croatia;
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
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Tveter KM, Mezhibovsky E, Wu Y, Roopchand DE. Bile acid metabolism and signaling: Emerging pharmacological targets of dietary polyphenols. Pharmacol Ther 2023; 248:108457. [PMID: 37268113 PMCID: PMC10528343 DOI: 10.1016/j.pharmthera.2023.108457] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 04/03/2023] [Accepted: 05/22/2023] [Indexed: 06/04/2023]
Abstract
Beyond their role as emulsifiers of lipophilic compounds, bile acids (BAs) are signaling endocrine molecules that show differential affinity and specificity for a variety of canonical and non-canonical BA receptors. Primary BAs (PBAs) are synthesized in the liver while secondary BAs (SBAs) are gut microbial metabolites of PBA species. PBAs and SBAs signal to BA receptors that regulate downstream pathways of inflammation and energy metabolism. Dysregulation of BA metabolism or signaling has emerged as a feature of chronic disease. Dietary polyphenols are non-nutritive plant-derived compounds associated with decreased risk of metabolic syndrome, type-2 diabetes, hepatobiliary and cardiovascular disease. Evidence suggests that the health promoting effects of dietary polyphenols are linked to their ability to alter the gut microbial community, the BA pool, and BA signaling. In this review we provide an overview of BA metabolism and summarize studies that link the cardiometabolic improvements of dietary polyphenols to their modulation of BA metabolism and signaling pathways, and the gut microbiota. Finally, we discuss approaches and challenges in deciphering cause-effect relationships between dietary polyphenols, BAs, and gut microbes.
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Affiliation(s)
- Kevin M Tveter
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA
| | - Esther Mezhibovsky
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA
| | - Yue Wu
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA
| | - Diana E Roopchand
- Rutgers, The State University of New Jersey, Department of Food Science, Institute for Food Nutrition and Health [Center for Microbiome, Nutrition and Health & Rutgers Center for Lipid Research], 61 Dudley Road, New Brunswick, NJ 08901, USA.
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de la Rubia Ortí JE, Moneti C, Serrano-Ballesteros P, Castellano G, Bayona-Babiloni R, Carriquí-Suárez AB, Motos-Muñoz M, Proaño B, Benlloch M. Liposomal Epigallocatechin-3-Gallate for the Treatment of Intestinal Dysbiosis in Children with Autism Spectrum Disorder: A Comprehensive Review. Nutrients 2023; 15:3265. [PMID: 37513683 PMCID: PMC10383799 DOI: 10.3390/nu15143265] [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: 06/12/2023] [Revised: 07/18/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system. In individuals with ASD, there is an increase in bacterial genera such as Clostridium, as well as species involved in the synthesis of branched-chain amino acids (BCAA) like Prevotella copri. Conversely, decreased amounts of Akkermansia muciniphila and Bifidobacterium spp. are observed. Epigallocatechin-3-gallate (EGCG) is one of the polyphenols with the greatest beneficial activity on microbial growth, and its consumption is associated with reduced psychological distress. Therefore, the objective of this review is to analyze how EGCG and its metabolites can improve the microbial dysbiosis present in ASD and its impact on the pathology. The analysis reveals that EGCG inhibits the growth of pathogenic bacteria like Clostridium perfringens and Clostridium difficile. Moreover, it increases the abundance of Bifidobacterium spp. and Akkermansia spp. As a result, EGCG demonstrates efficacy in increasing the production of metabolites involved in maintaining epithelial integrity and improving brain function. This identifies EGCG as highly promising for complementary treatment in ASD.
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Affiliation(s)
| | - Costanza Moneti
- Doctoral School, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain
| | | | - Gloria Castellano
- Centro de Investigación Traslacional San Alberto Magno (CITSAM), Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain
| | - Raquel Bayona-Babiloni
- Department of Basic Medical Sciences, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain
| | - Ana Belén Carriquí-Suárez
- Department of Basic Medical Sciences, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain
| | - María Motos-Muñoz
- Department of Personality Psychology, Treatment and Methodology, Catholic University of Valencia San Vicente Mártir, 46100 Valencia, Spain
- Child Neurorehabilitation Unit, Manises Hospital, 46940 Valencia, Spain
| | - Belén Proaño
- Department of Basic Medical Sciences, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain
| | - María Benlloch
- Department of Basic Medical Sciences, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain
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Abdolmaleky HM, Sheng Y, Zhou JR. Bioactive nutraceuticals oligo-lactic acid and fermented soy extract alleviate cognitive decline in mice in part via anti-neuroinflammation and modulation of gut microbiota. Front Nutr 2023; 10:1116278. [PMID: 36969810 PMCID: PMC10034322 DOI: 10.3389/fnut.2023.1116278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 02/10/2023] [Indexed: 03/12/2023] Open
Abstract
IntroductionCognition decline is associated with aging and certain diseases, such as neurodegenerative or neuropsychiatric disorders, diabetes and chronic kidney disease. Inflammation/neuroinflammation is considered an important causal factor, and experimental evidence suggests that anti-inflammatory natural compounds may effectively prevent cognitive decline. The goal of this study was to evaluate the effects of two natural bioactive agents, oligo-lactic acid (LAP) and fermented soy extract (ImmunBalance, IMB), on cognition in an adenine-induced cognitive impairment mouse model and to investigate the modulation of related biomarkers.MethodsMale C57 black mice were randomly assigned into the following experimental groups and received the corresponding treatments for 2 weeks before the use of adenine for model development: (1) negative control; (2) model control: injection of adenine at 50 mg/kg daily for 4 weeks; (3, 4) IMB groups: adenine injection and IMB oral gavage at 250 and 1,000 mg/kg BW, respectively; and (5) LAP group: adenine injection and LAP oral gavage at 1,000 mg/kg BW. One week after the model was developed, mice were evaluated for cognitive performances by using Y maze test, novel object recognition test, open field test, and Barnes maze tests. At the end of the experiment, brain tissues and cecum fecal samples were collected for analysis of gene expression and gut microbiota.ResultsMice treated with LAP or IMB had significantly improved spatial working memory, spatial recognition memory (LAP only), novel object recognition, and spatial learning and memory, compared with those in the model group. Gene expression analysis showed that, among a panel of cognition related genes, six of them (ELOVL2, GLUT4, Nestein, SNCA, TGFB1, and TGFB2) were significantly altered in the model group. LAP treatment significantly reversed expression levels of inflammatory/neuroinflammatory genes (SNCA, TGFB1), and IMB significantly reversed expression levels of genes related to inflammation/neuroinflammation, neurogenesis, and energy metabolism (ELOVL2, GLUT4, Nestin, TGFB1, and TGFB2). The altered microbiome was attenuated only by IMB.DiscussionIn conclusion, our data showed that LAP improved cognition associated with regulating biomarkers related to neuroinflammation and energy metabolism, whereas IMB improved cognition associated with regulating biomarkers related to neuroinflammation, energy metabolism, and neurogenesis, and modulating gut microbiota. Our results suggest that LAP and IMB may improve cognitive performance in mice via distinct mechanisms of action.
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Sun M, Li D, Hua M, Miao X, Su Y, Chi Y, Li Y, Sun R, Niu H, Wang J. Analysis of the alleviating effect of black bean peel anthocyanins on type 2 diabetes based on gut microbiota and serum metabolome. J Funct Foods 2023. [DOI: 10.1016/j.jff.2023.105456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
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Dietary Supplementation of Cedryl Acetate Ameliorates Adiposity and Improves Glucose Homeostasis in High-Fat Diet-Fed Mice. Nutrients 2023; 15:nu15040980. [PMID: 36839338 PMCID: PMC9967006 DOI: 10.3390/nu15040980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 02/11/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023] Open
Abstract
Cedryl acetate (CA), also called acetyl cedrene, is approved by the FDA as a flavoring or adjuvant to be added to foods. In this study, we aimed to investigate the preventive benefits of CA on obesity and obesity-related metabolic syndrome caused by a high-fat diet (HFD). Three groups of C57BL/6J mice (ten-week-old) were fed Chow, an HFD, or an HFD with CA supplementation (100 mg/kg) for 19 weeks. We observed that CA supplementation significantly reduced weight gain induced by an HFD, decreased the weight of the visceral fat pads, and prevented adipocyte hypertrophy in mice. Moreover, mice in the CA group showed significant improvements in hepatic lipid accumulation, glucose intolerance, insulin resistance, and gluconeogenesis compared with the mice in the HFD group. Since 16S rRNA analysis revealed that the gut microbiota in the CA and HFD groups were of similar compositions at the phylum and family levels, CA may have limited effects on gut microbiota in HFD-fed mice. The beneficial effects on the metabolic parameters of CA were reflected by CA's regulation of metabolism-related gene expression in the liver (including Pepck, G6Pase, and Fbp1) and the epididymal white adipose tissues (including PPARγ, C/EBPα, FABP4, FAS, Cytc, PGC-1α, PRDM16, Cidea, and COX4) of the mice. In summary, a potent preventive effect of CA on HFD-induced obesity and related metabolic syndrome was highlighted by our results, and CA could be a promising dietary component for obesity intervention.
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Xu J, Wei Y, Huang Y, Wei X. Regulatory Effects and Molecular Mechanisms of Tea and Its Active Compounds on Nonalcoholic Fatty Liver Disease. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:3103-3124. [PMID: 36773311 DOI: 10.1021/acs.jafc.2c07702] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is a multifactorial disease resulting from the interaction between environment, genetic background, and metabolic stress. Most treatments for NAFLD include dietary intervention and exercise show limited efficacy due to the complex mechanisms involved in NAFLD. Meanwhile, drug therapy is accompanied by serious side effects. The development of high-efficiency natural supplements is a sustainable strategy for the prevention and treatment of NAFLD. As the second most consumed beverage, tea has health benefits that have been widely recognized. Nevertheless, the intervention of tea active compounds in NAFLD has received limited attention. Tea contains abundant bioactive compounds with potential effects on NAFLD, such as catechins, flavonoids, theanine, tea pigments, and tea polysaccharides. We reviewed the intrinsic and environmental factors and pathogenic mechanisms that affect the occurrence and development of NAFLD, and summarized the influences of exercise, drugs, diet, and tea drinking on NAFLD. On this basis, we further analyzed the potential effects and molecular regulatory mechanisms of tea active compounds on NAFLD and proposed future development directions. This review hopes to provide novel insights into the development and application of tea active compounds in the prevention and treatment of NAFLD.
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Affiliation(s)
- Jia Xu
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
- School of Environmental and Chemical Engineering, Shanghai University, 333 Nanchen Road, Shanghai 200240, PR China
| | - Yang Wei
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
| | - Yi Huang
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
| | - Xinlin Wei
- School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
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Research progress on the lipid-lowering and weight loss effects of tea and the mechanism of its functional components. J Nutr Biochem 2023; 112:109210. [PMID: 36395969 DOI: 10.1016/j.jnutbio.2022.109210] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 07/13/2022] [Accepted: 09/23/2022] [Indexed: 11/16/2022]
Abstract
Obesity caused by poor eating habits has become a great challenge faced by public health organizations worldwide. Optimizing dietary intake and ingesting special foods containing biologically active substances (such as polyphenols, alkaloids, and terpenes) is a safe and effective dietary intervention to prevent the occurrence and development of obesity. Tea contains several active dietary factors, and daily tea consumption has been shown to have various health benefits, especially in regulating human metabolic diseases. Here, we reviewed recent advances in research on tea and its functional components in improving obesity-related metabolic dysfunction, and gut microbiota homeostasis and related clinical research. Furthermore, the potential mechanisms by which the functional components of tea could promote lipid-lowering and weight-loss effects by regulating fat synthesis/metabolism, glucose metabolism, gut microbial homeostasis, and liver function were summarized. The research results showing a "positive effect" or "no effect" objectively evaluates the lipid-lowering and weight-loss effects of the functional components of tea. This review provides a new scientific basis for further research on the functional ingredients of tea for lipid lowering and weight loss and the development of lipid-lowering and weight-loss functional foods and beverages derived from tea.
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Zhou F, Yang L, Sun W, Wang X, Guo N, Ma H, Yang L. The PPARα/CYP4A14 bile acid pathway is associated with lipid metabolism disorders caused by low birth weight with high-fat diet. Food Nutr Res 2023; 67:8994. [PMID: 36794015 PMCID: PMC9899044 DOI: 10.29219/fnr.v67.8994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/14/2022] [Accepted: 11/04/2022] [Indexed: 01/25/2023] Open
Abstract
Purpose To investigate possible mechanisms underlying the greater susceptibility of lipid metabolism disorders in low birth weight (LBW) mice fed with high-fat diets (HFDs). Methods LBW mice model was established by using the pregnancy malnutrition method. Male pups were selected from LBW and normal-birth weight (NBW) offspring at random. After 3 weeks of weaning, all offspring mice were fed with HFD. Serum triglycerides (TGs), cholesterol (TC), low density lipoprotein (LDL-C), total bile acid (TAB), non-esterified fatty acid (NEFA), and mice fecal bile acid profiles were measured. Lipid deposition in liver sections was visualized by Oil Red O staining. The weight ratio of liver, muscle, and adiposity was calculated. Tandem mass tag (TMT) combined with LC-MS/MS was used to determine the differentially expressed proteins (DEPs) of liver tissue in two groups. Bioinformatics was used for further analysis of DEPs to screen key target proteins, and then Western Blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to validate the expressions of DEPs. Results LBW mice fed with HFD showed more severe lipid metabolism disorders in the childhood. In contrast to the NBW group, the serum bile acids and fecal ω-muricholic acid (ω-MCA) levels in the LBW group were significantly lower. LC-MS/MS analysis showed that downregulated proteins were associated with lipid metabolism, and further analysis found that these proteins are mainly concentrated in peroxisome proliferation-activated receptor (PPAR) and primary bile acid synthesis signaling pathways and are involved in cellular processes and metabolic processes through binding and catalytic functions. Bioinformatics analysis indicated that the level of Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1), PPARα, key factors of cholesterol metabolism and bile acid synthesis, as well as downstream molecules Cytochrome P450 Family 4 Subfamily A Member 14 (CYP4A14), and Acyl-Coenzyme A Oxidase 2 (ACOX2) are markedly different in the liver of LBW individuals fed with HFD, and confirmed by WB and RT-qPCR. Conclusion LBW mice are more prone to dyslipidemia probably due to downregulated bile acid metabolism-related PPARα/CYP4A14 pathway, resulting in insufficient metabolism of cholesterol to bile acids, which, in turn, leads to elevated blood cholesterol.
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Affiliation(s)
- Fei Zhou
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China,Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China
| | - Linquan Yang
- Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China
| | - Wenwen Sun
- Department of Internal Medicine, North China University of Science and Technology, Tangshan, China
| | - Xing Wang
- Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China
| | - Na Guo
- Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China
| | - Huijuan Ma
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China,Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China,Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China,Huijuan Ma Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, China.
| | - Linlin Yang
- Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, China,Linlin Yang Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, China.
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Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man. Int J Mol Sci 2022; 24:ijms24010045. [PMID: 36613488 PMCID: PMC9820369 DOI: 10.3390/ijms24010045] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Akkermansia muciniphila is a mucosal symbiont considered a gut microbial marker in healthy individuals, as its relative abundance is significantly reduced in subjects with gut inflammation and metabolic disturbances. Dietary polyphenols can distinctly stimulate the relative abundance of A. muciniphila, contributing to the attenuation of several diseases, including obesity, type 2 diabetes, inflammatory bowel diseases, and liver damage. However, mechanistic insight into how polyphenols stimulate A. muciniphila or its activity is limited. This review focuses on dietary interventions in rodents and humans and in vitro studies using different phenolic classes. We provide critical insights with respect to potential mechanisms explaining the effects of polyphenols affecting A. muciniphila. Anthocyanins, flavan-3-ols, flavonols, flavanones, stilbenes, and phenolic acids are shown to increase relative A. muciniphila levels in vivo, whereas lignans exert the opposite effect. Clinical trials show consistent findings, and high intervariability relying on the gut microbiota composition at the baseline and the presence of multiple polyphenol degraders appear to be cardinal determinants in inducing A. muciniphila and associated benefits by polyphenol intake. Polyphenols signal to the AhR receptor and impact the relative abundance of A. muciniphila in a direct and indirect fashion, resulting in the restoration of intestinal epithelial integrity and homeostatic crosstalk with the gut microbiota by affecting IL-22 production. Moreover, recent evidence suggests that A. muciniphila participates in the initial hydrolysis of some polyphenols but does not participate in their complete metabolism. In conclusion, the consumption of polyphenol-rich foods targeting A. muciniphila as a pivotal intermediary represents a promising precision nutritional therapy to prevent and attenuate metabolic and inflammatory diseases.
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Wang M, Wang B, Zhou S, Liu J, Lu H, Wu H, Ding M, Li Y. Quercetin ameliorates chicken quality by activating the PI3K/PKB/AMPK signaling pathway in broilers. Front Vet Sci 2022; 9:951512. [PMID: 36578440 PMCID: PMC9791930 DOI: 10.3389/fvets.2022.951512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 11/14/2022] [Indexed: 12/14/2022] Open
Abstract
This study was conducted to investigate the effects and mechanism of quercetin on chicken quality in broilers. We selected 480 AA broilers (1 day old) and randomly allotted those to four treatments (negative control and 0.2, 0.4, or 0.6 g of quercetin per kg of diet) for 42 days. Compared with the control group, the supplementation with 0.4 g of quercetin significantly increased the pH45min and L * value of the thigh muscle and decreased the shearing force of the thigh muscle and breast muscle and drip loss of the thigh muscle (P < 0.05). The supplementation with 0.6 g/kg of quercetin significantly increased the pH45min and L * value of the thigh muscle, and pH45min of breast muscle and decreased the drip loss of the thigh muscle (P < 0.05). Sensory scores of meat color, tenderness, and juiciness also were improved with increasing quercetin concentration (P < 0.05). The inosinic acid (IMP) content of the breast and thigh muscles of broilers was significantly increased by supplementation with 0.6 g/kg of quercetin (P < 0.05). Supplementation with 0.2, 0.4, and 0.6 g of quercetin significantly reduced mRNA expression of L-FABP (P < 0.05, P < 0.05, and P < 0.05); supplementation with 0.4 and 0.6 g/kg of quercetin significantly increased mRNA expression of PKB and AMPKα1 (P < 0.05 and P < 0.05); supplementation with 0.6 g/kg of quercetin in the diet significantly reduced mRNA expression of SREBP1 and HMGR (P < 0.05 and P < 0.05) and significantly increased mRNA expression of CPT1 and PPARγ (P < 0.05 and P < 0.05); and supplementation with 0.2, 0.4, and 0.6 g/kg of quercetin significantly increased mRNA expression of PI3K, LPL, and Apo A1 and significantly reduced mRNA expression of ACC and FATP1 in the breast muscle of broilers (P > 0.05). PI3k, PKB, AMPK, SREBP1, and L-FABP were significantly and positively correlated with pH45min (P < 0.05); PPARγ was significantly and positively correlated with shear force (P < 0.05); CPT1 was significantly and positively correlated with the L * value (P < 0.05); and HMGR was significantly and positively correlated with drip loss (P < 0.05). In conclusion, quercetin improved the meat quality, protecting it against lipid oxidation and deposition by regulating the PI3K/PKB/AMPKα1 signaling pathway in the breast muscle of broilers.
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Affiliation(s)
- Mi Wang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China,College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, China
| | - Bo Wang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Shuaishuai Zhou
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Jiayan Liu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Han Lu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Hao Wu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Manyi Ding
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
| | - Yao Li
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, China,*Correspondence: Yao Li
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Monma T, Iwamoto J, Ueda H, Tamamushi M, Kakizaki F, Konishi N, Yara S, Miyazaki T, Hirayama T, Ikegami T, Honda A. Evaluation of gut dysbiosis using serum and fecal bile acid profiles. World J Clin Cases 2022; 10:12484-12493. [PMID: 36579096 PMCID: PMC9791502 DOI: 10.12998/wjcc.v10.i34.12484] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/25/2022] [Accepted: 11/04/2022] [Indexed: 12/02/2022] Open
Abstract
Dysbiosis in the intestinal microflora can affect the gut production of microbial metabolites, and toxic substances can disrupt the barrier function of the intestinal wall, leading to the development of various diseases. Decreased levels of Clostridium subcluster XIVa (XIVa) are associated with the intestinal dysbiosis found in inflammatory bowel disease (IBD) and Clostridium difficile infection (CDI). Since XIVa is a bacterial group responsible for the conversion of primary bile acids (BAs) to secondary BAs, the proportion of intestinal XIVa can be predicted by determining the ratio of deoxycholic acid (DCA)/[DCA + cholic acid (CA)] in feces orserum. For example, serum DCA/(DCA+CA) was significantly lower in IBD patients than in healthy controls, even in the remission period. These results suggest that a low proportion of intestinal XIVa in IBD patients might be a precondition for IBD onset but not a consequence of intestinal inflammation. Another report showed that a reduced serum DCA/(DCA + CA) ratio could predict susceptibility to CDI. Thus, the BA profile, particularly the ratio of secondary to primary BAs, can serve as a surrogate marker of the intestinal dysbiosis caused by decreased XIVa.
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Affiliation(s)
- Tadakuni Monma
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Junichi Iwamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Hajime Ueda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Makoto Tamamushi
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Fumio Kakizaki
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Naoki Konishi
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Shoichiro Yara
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Teruo Miyazaki
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Takeshi Hirayama
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Tadashi Ikegami
- Department of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
| | - Akira Honda
- Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Inashiki-Gun 300-0395, Japan
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Shansky Y, Bespyatykh J. Bile Acids: Physiological Activity and Perspectives of Using in Clinical and Laboratory Diagnostics. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27227830. [PMID: 36431930 PMCID: PMC9692537 DOI: 10.3390/molecules27227830] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022]
Abstract
Bile acids play a significant role in the digestion of nutrients. In addition, bile acids perform a signaling function through their blood-circulating fraction. They regulate the activity of nuclear and membrane receptors, located in many tissues. The gut microbiota is an important factor influencing the effects of bile acids via enzymatic modification. Depending on the rate of healthy and pathogenic microbiota, a number of bile acids may support lipid and glucose homeostasis as well as shift to more toxic compounds participating in many pathological conditions. Thus, bile acids can be possible biomarkers of human pathology. However, the chemical structure of bile acids is similar and their analysis requires sensitive and specific methods of analysis. In this review, we provide information on the chemical structure and the biosynthesis of bile acids, their regulation, and their physiological role. In addition, the review describes the involvement of bile acids in various diseases of the digestive system, the approaches and challenges in the analysis of bile acids, and the prospects of their use in omics technologies.
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Affiliation(s)
- Yaroslav Shansky
- Department of Molecular Medicine, Center of Molecular Medicine and Diagnostics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya Str., 1a, 119435 Moscow, Russia
- Correspondence:
| | - Julia Bespyatykh
- Department of Molecular Medicine, Center of Molecular Medicine and Diagnostics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya Str., 1a, 119435 Moscow, Russia
- Department of Expertise in Doping and Drug Control, Mendeleev University of Chemical Technology of Russia, Miusskaya Square, 9, 125047 Moscow, Russia
- Department of Public Health and Health Care, Federal Scientific State Budgetary Institution «N.A. Semashko National Research Institute of Public Health», Vorontsovo Pole Str., 12-1, 105064 Moscow, Russia
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Hidalgo I, Ortiz-Flores M, Villarreal F, Fonseca-Coronado S, Ceballos G, Meaney E, Nájera N. Is it possible to treat nonalcoholic liver disease using a flavanol-based nutraceutical approach? Basic and clinical data. J Basic Clin Physiol Pharmacol 2022; 33:703-714. [PMID: 35119232 DOI: 10.1515/jbcpp-2021-0285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 01/15/2022] [Indexed: 01/05/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by a spectrum of diseases, ranging from simple steatosis to hepatocellular carcinoma. The main factors for NAFLD are closely related to obesity, insulin resistance, intestinal microbiota alterations, hyperinsulinism, low-grade systemic inflammation, nitroxidative stress, lipid peroxidation, and mitochondrial dysfunction. Currently, the treatment of NAFLD is based on diet and exercise because, to date, there is no specific pharmacological agent, already approved, that raises the need for new therapeutic strategies. Nutraceuticals, such as polyphenols, have potential beneficial effects for health. In this article, the beneficial effects of epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EC) are discussed. EGCG is the main catechin in green tea, which has shown in various studies its potential effect preventing and treating NAFLD since it has shown antihyperlipidemic, anti-inflammatory, antifibrotic, antioxidant, and improvement of liver lipid metabolism. However, it has been found that excessive consumption may cause hepatotoxicity. EC is widely distributed in nature (fruits and vegetables). This flavanol has shown many beneficial effects, including antihypertensive, anti-inflammatory, anti-hyperglycemic, antithrombotic, and antifibrotic properties. It increases mitochondrial biogenesis, and it also has effects on the regulation of synthesis and metabolism of lipids. This flavanol is a nontoxic substance; it has been classified by the United States Food and Drug Administration as harmless. The EC-induced effects can be useful for the prevention and/or treatment of NAFLD.
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Affiliation(s)
- Isabel Hidalgo
- Unidad de Investigación Laboratorio de Investigación en Inmunología y Salud Publica, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Estado de México, Mexico
| | - Miguel Ortiz-Flores
- Laboratorio de investigación integral cardiometabólica, Escuela Superior de Medicina, Instituto Politécnico Nacional, CDMX, Mexico
| | | | - Salvador Fonseca-Coronado
- Unidad de Investigación Laboratorio de Investigación en Inmunología y Salud Publica, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Estado de México, Mexico
| | - Guillermo Ceballos
- Laboratorio de investigación integral cardiometabólica, Escuela Superior de Medicina, Instituto Politécnico Nacional, CDMX, Mexico
| | - Eduardo Meaney
- Laboratorio de investigación integral cardiometabólica, Escuela Superior de Medicina, Instituto Politécnico Nacional, CDMX, Mexico
| | - Nayelli Nájera
- Laboratorio de investigación integral cardiometabólica, Escuela Superior de Medicina, Instituto Politécnico Nacional, CDMX, Mexico
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Li JY, Gillilland M, Lee AA, Wu X, Zhou SY, Owyang C. Secondary bile acids mediate high-fat diet-induced upregulation of R-spondin 3 and intestinal epithelial proliferation. JCI Insight 2022; 7:e148309. [PMID: 36099053 PMCID: PMC9675439 DOI: 10.1172/jci.insight.148309] [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: 02/04/2021] [Accepted: 08/31/2022] [Indexed: 11/17/2022] Open
Abstract
A high-fat diet (HFD) contributes to the increased incidence of colorectal cancer, but the mechanisms are unclear. We found that R-spondin 3 (Rspo3), a ligand for leucine-rich, repeat-containing GPCR 4 and 5 (LGR4 and LGR5), was the main subtype of R-spondins and was produced by myofibroblasts beneath the crypts in the intestine. HFD upregulated colonic Rspo3, LGR4, LGR5, and β-catenin gene expression in specific pathogen-free rodents, but not in germ-free mice, and the upregulations were prevented by the bile acid (BA) binder cholestyramine or antibiotic treatment, indicating mediation by both BA and gut microbiota. Cholestyramine or antibiotic treatments prevented HFD-induced enrichment of members of the Lachnospiraceae and Rumincoccaceae, which can transform primary BA into secondary BA. Oral administration of deoxycholic acid (DCA), or inoculation of a combination of the BA deconjugator Lactobacillus plantarum and 7α-dehydroxylase-containing Clostridium scindens with an HFD to germ-free mice increased serum DCA and colonic Rspo3 mRNA levels, indicating that formation of secondary BA by gut microbiota is responsible for HFD-induced upregulation of Rspo3. In primary myofibroblasts, DCA increased Rspo3 mRNA via TGR5. Finally, we showed that cholestyramine or conditional deletion of Rspo3 prevented HFD- or DCA-induced intestinal proliferation. We conclude that secondary BA is responsible for HFD-induced upregulation of Rspo3, which, in turn, mediates HFD-induced intestinal epithelial proliferation.
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Magni G, Riboldi B, Petroni K, Ceruti S. Flavonoids bridging the gut and the brain: intestinal metabolic fate, and direct or indirect effects of natural supporters against neuroinflammation and neurodegeneration. Biochem Pharmacol 2022; 205:115257. [PMID: 36179933 DOI: 10.1016/j.bcp.2022.115257] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 09/14/2022] [Accepted: 09/14/2022] [Indexed: 11/02/2022]
Abstract
In recent years, experimental evidence suggested a possible role of the gut microbiota in the onset and development of several neurodegenerative disorders, such as AD and PD, MS and pain. Flavonoids, including anthocyanins, EGCG, the flavonol quercetin, and isoflavones, are plant polyphenolic secondary metabolites that have shown therapeutic potential for the treatment of various pathological conditions, including neurodegenerative diseases. This is due to their antioxidant and anti-inflammatory properties, despite their low bioavailability which often limits their use in clinical practice. In more recent years it has been demonstrated that flavonoids are metabolized by specific bacterial strains in the gut to produce their active metabolites. On the other way round, both naturally-occurring flavonoids and their metabolites promote or limit the proliferation of specific bacterial strains, thus profoundly affecting the composition of the gut microbiota which in turn modifies its ability to further metabolize flavonoids. Thus, understanding the best way of acting on this virtuous circle is of utmost importance to develop innovative approaches to many brain disorders. In this review, we summarize some of the most recent advances in preclinical and clinical research on the neuroinflammatory and neuroprotective effects of flavonoids on AD, PD, MS and pain, with a specific focus on their mechanisms of action including possible interactions with the gut microbiota, to emphasize the potential exploitation of dietary flavonoids as adjuvants in the treatment of these pathological conditions.
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Affiliation(s)
- Giulia Magni
- Department of Pharmacological and Biomolecular Sciences - Università degli Studi di Milano - via Balzaretti, 9 - 20133 MILAN (Italy)
| | - Benedetta Riboldi
- Department of Pharmacological and Biomolecular Sciences - Università degli Studi di Milano - via Balzaretti, 9 - 20133 MILAN (Italy)
| | - Katia Petroni
- Department of Biosciences - Università degli Studi di Milano - via Celoria, 26 - 20133 MILAN (Italy)
| | - Stefania Ceruti
- Department of Pharmacological and Biomolecular Sciences - Università degli Studi di Milano - via Balzaretti, 9 - 20133 MILAN (Italy).
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Zhou C, Zhang W, Lin H, Zhang L, Wu F, Wang Y, Yu S, Peng X, Cheng W, Li M, Pan X, Huang Z, Zhang W. Effect of theaflavin-3,3′-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota. Front Pharmacol 2022; 13:925264. [PMID: 36105184 PMCID: PMC9464872 DOI: 10.3389/fphar.2022.925264] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 07/13/2022] [Indexed: 11/13/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), one of the risk factors for hepatitis, cirrhosis, and even hepatic carcinoma, has been a global public health problem. The polyphenol compound theaflavin-3,3′-digallate (TF3), mainly extracted from black tea, has been reported to produce an effect on hypoglycemic and antilipid deposition in vitro. In our study, we further investigated the function and novel mechanisms of TF3 in protecting NAFLD in vivo. By using leptin-deficient obese (ob/ob) mice with NAFLD symptoms, TF3 treatment prevented body weight and waistline gain, reduced lipid accumulation, and alleviated liver function injury, as well as decreased serum lipid levels and TG levels in livers in ob/ob mice, observing no side effects. Furthermore, the transcriptome sequencing of liver tissue showed that TF3 treatment corrected the expression profiles of livers in ob/ob mice compared with that of the model group. It is interesting to note that TF3 might regulate lipid metabolism via the Fads1/PPARδ/Fabp4 axis. In addition, 16S rRNA sequencing demonstrated that TF3 increased the abundance of Prevotellaceae_UCG-001, norank_f_Ruminococcaceae, and GCA-900066575 and significantly decreased that of Parvibacter. Taken together, the effect of TF3 on NAFLD might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota. TF3 might be a promising candidate for NAFLD therapy.
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Affiliation(s)
- Cheng Zhou
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Wenji Zhang
- Guangdong Provincial Engineering & Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Key Laboratory of Crop Genetic Improvement of Guangdong Province, Crops Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Hui Lin
- Department of Radiation Oncology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Luyun Zhang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Fan Wu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Yan Wang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Susu Yu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Xinyue Peng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Wenli Cheng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Min Li
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Xiaoying Pan
- Guangdong Provincial Engineering & Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Key Laboratory of Crop Genetic Improvement of Guangdong Province, Crops Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Zhenrui Huang
- Guangdong Provincial Engineering & Technology Research Center for Tobacco Breeding and Comprehensive Utilization, Key Laboratory of Crop Genetic Improvement of Guangdong Province, Crops Research Institute, Guangdong Academy of Agricultural Sciences, Guangzhou, China
- *Correspondence: Zhenrui Huang, ; Wenjuan Zhang,
| | - Wenjuan Zhang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
- *Correspondence: Zhenrui Huang, ; Wenjuan Zhang,
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de Freitas PL, Miranda JPN, França LM, Paes AMDA. Plant-Derived (Poly)phenols and Their Metabolic Outcomes: The Pursuit of a Role for the Gut Microbiota. Nutrients 2022; 14:nu14173510. [PMID: 36079768 PMCID: PMC9460414 DOI: 10.3390/nu14173510] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/12/2022] [Accepted: 08/14/2022] [Indexed: 12/13/2022] Open
Abstract
Plant-derived (poly)phenolic compounds have been undoubtedly shown to promote endocrine homeostasis through the improvement of diverse metabolic outcomes. Amongst diverse potential mechanisms, the prebiotic modulatory effects exerted by these compounds on the gut microbiota have supported their nutraceutical application in both experimental and clinical approaches. However, the comprehension of the microbiota modulatory patterns observed upon (poly)phenol-based dietary interventions is still in its infancy, which makes the standardization of the metabolic outcomes in response to a given (poly)phenol a herculean task. Thus, this narrative review sought to gather up-to-date information on the relationship among (poly)phenols intake, their modulatory effect on the gut microbiota diversity, and consequent metabolic outcomes as a supportive tool for the future design of experimental approaches and even clinical trials.
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Affiliation(s)
- Perla Lopes de Freitas
- Laboratory of Experimental Physiology, Department of Physiological Sciences, Biological and Health Sciences Center, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
- Health Sciences Graduate Program, Biological and Health Sciences Center, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
| | - João Paulo Nascimento Miranda
- Laboratory of Experimental Physiology, Department of Physiological Sciences, Biological and Health Sciences Center, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
| | - Lucas Martins França
- Laboratory of Experimental Physiology, Department of Physiological Sciences, Biological and Health Sciences Center, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
| | - Antonio Marcus de Andrade Paes
- Laboratory of Experimental Physiology, Department of Physiological Sciences, Biological and Health Sciences Center, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
- Health Sciences Graduate Program, Biological and Health Sciences Center, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
- Correspondence:
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Kan J, Wu F, Wang F, Zheng J, Cheng J, Li Y, Yang Y, Du J. Phytonutrients: Sources, bioavailability, interaction with gut microbiota, and their impacts on human health. Front Nutr 2022; 9:960309. [PMID: 36051901 PMCID: PMC9424995 DOI: 10.3389/fnut.2022.960309] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/11/2022] [Indexed: 12/13/2022] Open
Abstract
Phytonutrients are natural bioactive components present in the daily diet that can exert a positive impact on human health. Studies have shown that phytonutrients may act as antioxidants and improve metabolism after being ingested, which help to regulate physiological processes and prevent metabolic disorders and diseases. However, their efficacy is limited by their low bioavailability. The gut microbiota is symbiotic with humans and its abundance and profile are related to most diseases. Interestingly, studies have shown that the gut microbiota is associated with the metabolism of phytonutrients by converting them into small molecules that can be absorbed by the body, thereby enhancing their bioavailability. Furthermore, phytonutrients can modulate the composition of the gut microbiota, and therefore improve the host's health. Here, we focus on uncovering the mechanisms by which phytonutrients and gut microbiota play roles in health, and the interrelationships between phytonutrients and gut microbiota were summarized. We also reviewed the studies that reported the efficacy of phytonutrients in human health and the future directions.
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Affiliation(s)
- Juntao Kan
- Nutrilite Health Institute, Shanghai, China
| | - Feng Wu
- Sequanta Technologies Co., Ltd., Shanghai, China
| | | | | | - Junrui Cheng
- Department of Molecular and Structural Biochemistry, North Carolina State University, Kannapolis, NC, United States
| | - Yuan Li
- Sequanta Technologies Co., Ltd., Shanghai, China
| | - Yuexin Yang
- Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, China
- Yuexin Yang
| | - Jun Du
- Nutrilite Health Institute, Shanghai, China
- *Correspondence: Jun Du
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Feng W, Liu J, Cheng H, Zhang D, Tan Y, Peng C. Dietary compounds in modulation of gut microbiota-derived metabolites. Front Nutr 2022; 9:939571. [PMID: 35928846 PMCID: PMC9343712 DOI: 10.3389/fnut.2022.939571] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/24/2022] [Indexed: 11/29/2022] Open
Abstract
Gut microbiota, a group of microorganisms that live in the gastrointestinal tract, plays important roles in health and disease. One mechanism that gut microbiota in modulation of the functions of hosts is achieved through synthesizing and releasing a series of metabolites such as short-chain fatty acids. In recent years, increasing evidence has indicated that dietary compounds can interact with gut microbiota. On one hand, dietary compounds can modulate the composition and function of gut microbiota; on the other hand, gut microbiota can metabolize the dietary compounds. Although there are several reviews on gut microbiota and diets, there is no focused review on the effects of dietary compounds on gut microbiota-derived metabolites. In this review, we first briefly discussed the types of gut microbiota metabolites, their origins, and the reasons that dietary compounds can interact with gut microbiota. Then, focusing on gut microbiota-derived compounds, we discussed the effects of dietary compounds on gut microbiota-derived compounds and the following effects on health. Furthermore, we give our perspectives on the research direction of the related research fields. Understanding the roles of dietary compounds on gut microbiota-derived metabolites will expand our knowledge of how diets affect the host health and disease, thus eventually enable the personalized diets and nutrients.
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Affiliation(s)
- Wuwen Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Juan Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hao Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Dandan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuzhu Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Wei F, Yang X, Zhang M, Xu C, Hu Y, Liu D. Akkermansia muciniphila Enhances Egg Quality and the Lipid Profile of Egg Yolk by Improving Lipid Metabolism. Front Microbiol 2022; 13:927245. [PMID: 35928144 PMCID: PMC9344071 DOI: 10.3389/fmicb.2022.927245] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
Akkermansia muciniphila (A. muciniphila) has shown potential as a probiotic for the prevention and treatment of non-alcoholic fatty liver disease in both humans and mice. However, relatively little is known about the effects of A. muciniphila on lipid metabolism, productivity, and product quality in laying hens. In this study, we explored whether A. muciniphila supplementation could improve lipid metabolism and egg quality in laying hens and sought to identify the underlying mechanism. In the first experiment, 80 Hy-Line Brown laying hens were divided into four groups, one of which was fed a normal diet (control group), while the other three groups were administered a high-energy, low-protein diet to induce fatty liver hemorrhagic syndrome (FLHS). Among the three FLHS groups, one was treated with phosphate-buffered saline, one with live A. muciniphila, and one with pasteurized A. muciniphila. In the second experiment, 140 Hy-Line Brown laying hens were divided into two groups and respectively fed a basal diet supplemented or not with A. muciniphila lyophilized powder. The results showed that, in laying hens with FLHS, treatment with either live or pasteurized A. muciniphila efficiently decreased body weight, abdominal fat deposition, and lipid content in both serum and the liver; downregulated the mRNA expression of lipid synthesis-related genes and upregulated that of lipid transport-related genes in the liver; promoted the growth of short-chain fatty acids (SCFAs)-producing microorganisms and increased the cecal SCFAs content; and improved the yolk lipid profile. Additionally, the supplementation of lyophilized powder of A. muciniphila to aged laying hens reduced abdominal fat deposition and total cholesterol (TC) levels in both serum and the liver, suppressed the mRNA expression of cholesterol synthesis-related genes in the liver, reduced TC content in the yolk, increased eggshell thickness, and reshaped the composition of the gut microbiota. Collectively, our findings demonstrated that A. muciniphila can modulate lipid metabolism, thereby, promoting laying hen health as well as egg quality and nutritive value. Live, pasteurized, and lyophilized A. muciniphila preparations all have the potential for use as additives for improving laying hen production.
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Hong T, Jiang X, Zou J, Yang J, Zhang H, Mai H, Ling W, Feng D. Hepatoprotective effect of curcumin against bisphenol A-induced hepatic steatosis via modulating gut microbiota dysbiosis and related gut-liver axis activation in CD-1 mice. J Nutr Biochem 2022; 109:109103. [PMID: 35780999 DOI: 10.1016/j.jnutbio.2022.109103] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 03/14/2022] [Accepted: 06/08/2022] [Indexed: 11/18/2022]
Abstract
Chronic exposure to low-dose bisphenol A (BPA) has become a global problem of public health. Our previous work showed that low-dose BPA exposure caused gut microbial dysbiosis and hepatic steatosis. Curcumin, a polyphenol extracted from turmeric, has an inhibitory effect on liver lipid accumulation, whether curcumin can alleviate BPA-induced hepatic steatosis through improving intestinal flora and modulating gut-liver axis remains to be elucidated. Male CD-1 mice were fed with BPA-contaminated diet supplemented with or not with curcumin for 24 weeks. Curcumin supplementation markedly ameliorated liver fat accumulation and hepatic steatosis induced by BPA. Gut microbiota analysis via 16S rRNA sequencing revealed that the relative abundance of Proteobacteria and Firmicutes/Bacteroidetes ratio were increased in BPA-fed mice, and this alteration was reversed by curcumin treatment. Akkermansia, which was recognized as a potential probiotic, was significantly reduced after BPA exposure and was restored to the control level with curcumin addition. Furthermore, curcumin supplementation reversed the down-regulation of intestinal tight junction protein expressions (zona occludens-1 and occludin), improved increased gut permeability, reduced serum lipopolysaccharide level and suppressed the activation of hepatic toll-like receptor 4 / nuclear factor-κB (TLR4/NF-κB) pathway induced by BPA. These results indicated that the protective effect of curcumin against hepatic steatosis induced by BPA and further revealed that its mechanism might be its prebiotic effect on maintaining intestinal flora homeostasis and improving intestinal barrier function, consequently reducing serum lipopolysaccharide-triggered inflammatory response in the liver. Our work provides evidence for curcumin as a potential nutritional therapy for BPA-mediated hepatic steatosis.
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Affiliation(s)
- Ting Hong
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Xin Jiang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Jun Zou
- Department of Cardiology, The Sixth Affiliated Hospital of South China University of Technology, Foshan 528200, China
| | - Jie Yang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Hongmin Zhang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Haiyan Mai
- Department of Clinical Nutrition, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Wenhua Ling
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Dan Feng
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
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Huang T, Che Q, Chen X, Chen D, Yu B, He J, Chen H, Yan H, Zheng P, Luo Y, Huang Z. Apple Polyphenols Improve Intestinal Antioxidant Capacity and Barrier Function by Activating the Nrf2/Keap1 Signaling Pathway in a Pig Model. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:7576-7585. [PMID: 35679090 DOI: 10.1021/acs.jafc.2c02495] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
In recent years, the function of plant polyphenols to improve the intestinal barrier has been fully demonstrated. However, the exact mechanisms linking plant polyphenols with the intestinal barrier function have not yet been established. Apple polyphenols (APs) are safe and healthy nutrients, which are extracted from apples and their byproducts. Using pig and IPEC-J2 cell models, this study investigated the effects of dietary AP supplementation on intestinal antioxidant capacity and barrier function. Then, we further explored the role of the Nrf2/Keap1 signaling pathway in maintaining intestinal antioxidant capacity and barrier function. Our study found that dietary AP supplementation improved the intestinal mechanical barrier by promoting the intestinal morphology and intestinal tight junction protein expression, improved the intestinal immune barrier by increasing intestinal secretory immunoglobulin A production, and improved the intestinal biological barrier by increasing probiotics and decreasing the Escherichia coli population. Further research found that dietary AP supplementation increased the intestinal antioxidant capacity and activated the Nrf2/Keap1 signaling pathway. Finally, after treatment with Nrf2-specific inhibitor ML-385, the upregulation effect of APs on antioxidant capacity and tight junction protein expression was reduced in IPEC-J2 cells. Our results suggested that APs promoted intestinal antioxidant capacity and barrier function via the Nrf2/Keap1 signaling pathway.
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Affiliation(s)
- Tengteng Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Qiangjun Che
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Xiaoling Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Daiwen Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Bing Yu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Jun He
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Hong Chen
- College of Food Science, Sichuan Agricultural University, Yaan, Sichuan 625014, P. R. China
| | - Hui Yan
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Ping Zheng
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Yuheng Luo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
| | - Zhiqing Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China
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Cheng H, Liu J, Zhang D, Tan Y, Feng W, Peng C. Gut microbiota, bile acids, and nature compounds. Phytother Res 2022; 36:3102-3119. [PMID: 35701855 DOI: 10.1002/ptr.7517] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 05/09/2022] [Accepted: 05/17/2022] [Indexed: 11/09/2022]
Abstract
Natural compounds (NPs) have historically made a major contribution to pharmacotherapy in various diseases and drug discovery. In the past decades, studies on gut microbiota have shown that the efficacy of NPs can be affected by the interactions between gut microbiota and NPs. On one hand, gut microbiota can metabolize NPs. On the other hand, NPs can influence the metabolism and composition of gut microbiota. Among gut microbiota metabolites, bile acids (BAs) have attracted widespread attention due to their effects on the body homeostasis and the development of diseases. Studies have also confirmed that NPs can regulate the metabolism of BAs and ultimately regulate the physiological function of the body and disease progresses. In this review, we comprehensively summarize the interactions among NPs, gut microbiota, and BAs. In addition, we also discuss the role of microbial BAs metabolism in understanding the toxicity and efficacy of NPs. Furthermore, we present personal insights into the future research directions of NPs and BAs.
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Affiliation(s)
- Hao Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Juan Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Dandan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuzhu Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wuwen Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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