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Zhang Z, Zheng Q, Liu Y, Chen G, Li Y. Association between periodontitis and mortality in participants with metabolic dysfunction-associated steatotic liver disease: results from NHANES. BMC Oral Health 2025; 25:567. [PMID: 40223086 PMCID: PMC11995466 DOI: 10.1186/s12903-025-05959-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 04/04/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND It has been reported that periodontitis was a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study is to investigate the impact of periodontitis on all-cause and cause-specific mortality of MASLD patients. METHODS We included 11,019 individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) from the National Health and Nutrition Examination Survey. Multivariable Cox proportional hazards models were utilized to analyze the estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality and cause-specific mortality among participants with different periods of periodontitis status. Additionally, we employed restricted cubic splines (RCS) curves to explore the dose-response relationship between clinical attachment level (CAL) and pocket probing depth (PPD) and mortality rates. Finally, a series of sensitivity analyses and stratification analyses were conducted to test the reliability and robustness of the results. RESULTS In this study, moderate to severe periodontitis significantly increased the all-cause mortality (HR 1.29, 95% CI 1.08-1.55; P = 0.003) and cardiovascular disease (CVD)-related mortality (HR 1.41, 95% CI 1.10-1.79; P = 0.006) among MASLD participants. However, no significant effects of different periodontal statuses on cancer mortality were observed among MASLD participants. CONCLUSIONS A nationwide large-sample longitudinal study indicated that MASLD patients with moderate to severe periodontitis experienced significantly higher all-cause and CVD-related mortality rates compared to those with no or mild periodontitis.
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Affiliation(s)
- Zhaofu Zhang
- Department of Infectious Diseases, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, PR China
| | - Qiuyun Zheng
- Department of Obstetrics and Gynecology, Zigui County People's Hospital, Zigui, 443200, PR China
| | - Yiheng Liu
- School of Medicine, Sun Yat-sen University, Shenzhen, 518107, PR China
| | - Guanhui Chen
- Department of Stomatology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, PR China.
| | - Yiming Li
- Department of Stomatology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, PR China.
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Rondanelli M, Borromeo S, Cavioni A, Gasparri C, Gattone I, Genovese E, Lazzarotti A, Minonne L, Moroni A, Patelli Z, Razza C, Sivieri C, Valentini EM, Barrile GC. Therapeutic Strategies to Modulate Gut Microbial Health: Approaches for Chronic Metabolic Disorder Management. Metabolites 2025; 15:127. [PMID: 39997751 PMCID: PMC11857149 DOI: 10.3390/metabo15020127] [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: 12/02/2024] [Revised: 01/17/2025] [Accepted: 01/28/2025] [Indexed: 02/26/2025] Open
Abstract
Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and metabolic disorders, as well as the role of probiotics in the modulation of the intestinal microbiota. The aim of this review was to summarize the reviews and individual articles on the state of the art regarding ideal therapy with probiotics and prebiotics in order to obtain the reversion of dysbiosis (alteration in microbiota) to eubiosis during metabolic diseases, such as diabetes, prediabetes, obesity, hyperhomocysteinemia, dyslipidemia, sarcopenia, and non-alcoholic fatty liver diseases. This review includes 245 eligible studies. In conclusion, a condition of dysbiosis, or in general, alteration of the intestinal microbiota, could be implicated in the development of metabolic disorders through different mechanisms, mainly linked to the release of pro-inflammatory factors. Several studies have already demonstrated the potential of using probiotics and prebiotics in the treatment of this condition, detecting significant improvements in the specific symptoms of metabolic diseases. These findings reinforce the hypothesis that a condition of dysbiosis can lead to a generalized inflammatory picture with negative consequences on different organs and systems. Moreover, this review confirms that the beneficial effects of probiotics on metabolic diseases are promising, but more research is needed to determine the optimal probiotic strains, doses, and administration forms for specific metabolic conditions.
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Affiliation(s)
- Mariangela Rondanelli
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy;
| | - Sara Borromeo
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessandro Cavioni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Ilaria Gattone
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Elisa Genovese
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessandro Lazzarotti
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Leonardo Minonne
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Alessia Moroni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Zaira Patelli
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Claudia Razza
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Claudia Sivieri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Eugenio Marzio Valentini
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
| | - Gaetan Claude Barrile
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, 27100 Pavia, Italy; (S.B.); (A.C.); (C.G.); (I.G.); (E.G.); (A.L.); (L.M.); (A.M.); (Z.P.); (C.R.); (C.S.); (E.M.V.)
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Augustijn QJJ, Grefhorst A, de Groen P, Wortelboer K, Seegers JFM, Gül IS, Suenaert P, Verheij J, de Vos WM, Herrema H, Nieuwdorp M, Holleboom AG. Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis. BMJ Open 2025; 15:e088290. [PMID: 39788762 PMCID: PMC11784342 DOI: 10.1136/bmjopen-2024-088290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 12/12/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world's population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD. METHODS AND ANALYSIS This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023. ETHICS AND DISSEMINATION Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER The trial is registered on clinicaltrials.gov (NCT05821010).
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Affiliation(s)
- Quinten J J Augustijn
- Department of Experimental Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands
- University of Amsterdam, Amsterdam, Netherlands
| | - Aldo Grefhorst
- Department of Experimental Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands
- University of Amsterdam, Amsterdam, Netherlands
| | - Pleun de Groen
- Department of Experimental Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands
- University of Amsterdam, Amsterdam, Netherlands
| | - Koen Wortelboer
- Department of Experimental Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, Netherlands
- University of Amsterdam, Amsterdam, Netherlands
| | | | | | | | | | | | - Hilde Herrema
- Amsterdam University Medical Centres, Amsterdam, Netherlands
| | - Max Nieuwdorp
- Department of Internal Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Academisch Medisch Centrum, Amsterdam, Netherlands
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Smith EE, Biessels GJ, Gao V, Gottesman RF, Liesz A, Parikh NS, Iadecola C. Systemic determinants of brain health in ageing. Nat Rev Neurol 2024; 20:647-659. [PMID: 39375564 PMCID: PMC11926994 DOI: 10.1038/s41582-024-01016-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2024] [Indexed: 10/09/2024]
Abstract
Preservation of brain health is a worldwide priority. The traditional view is that the major threats to the ageing brain lie within the brain itself. Consequently, therapeutic approaches have focused on protecting the brain from these presumably intrinsic pathogenic processes. However, an increasing body of evidence has unveiled a previously under-recognized contribution of peripheral organs to brain dysfunction and damage. Thus, in addition to the well-known impact of diseases of the heart and endocrine glands on the brain, accumulating data suggest that dysfunction of other organs, such as gut, liver, kidney and lung, substantially affects the development and clinical manifestation of age-related brain pathologies. In this Review, a framework is provided to indicate how organ dysfunction can alter brain homeostasis and promote neurodegeneration, with a focus on dementia. We delineate the associations of subclinical dysfunction in specific organs with dementia risk and provide suggestions for public health promotion and clinical management.
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Affiliation(s)
- Eric E Smith
- Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
| | - Geert Jan Biessels
- Department of Neurology, UMC Utrecht Brain Center, University Medical Centre Utrecht, Utrecht, Netherlands
| | - Virginia Gao
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
| | | | - Arthur Liesz
- Institute for Stroke and Dementia Research, University Medical Center Munich, Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Neal S Parikh
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
| | - Costantino Iadecola
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
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Bae J, Han E, Lee HW, Park CY, Chung CH, Lee DH, Cho EH, Rhee EJ, Yu JH, Park JH, Bae JC, Park JH, Choi KM, Kim KS, Seo MH, Lee M, Kim NH, Kim SH, Lee WY, Lee WJ, Choi YK, Lee YH, Hwang YC, Lyu YS, Lee BW, Cha BS. Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association. Diabetes Metab J 2024; 48:1015-1028. [PMID: 39610131 PMCID: PMC11621661 DOI: 10.4093/dmj.2024.0541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 10/23/2024] [Indexed: 11/30/2024] Open
Abstract
Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist's perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.
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Affiliation(s)
- Jaehyun Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
| | - Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hye Won Lee
- Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
| | - Cheol-Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hee Chung
- Department of Internal Medicine and Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dae Ho Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Eun-Hee Cho
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Eun-Jung Rhee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Ji-Cheol Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Jung Hwan Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kyung-Soo Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Mi Hae Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea
| | - Minyoung Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Nan-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - So Hun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Won-Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yeon-Kyung Choi
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yong-ho Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - You-Cheol Hwang
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Young Sang Lyu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - on Behalf of the Fatty Liver Research Group of the Korean Diabetes Association
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Internal Medicine and Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea
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Hakkak R, Korourian S, Li W, Spray B, Twaddle NC, Randolph CE, Børsheim E, Robeson II MS. Dietary soy protein reverses obesity-induced liver steatosis and alters fecal microbial composition independent of isoflavone level. Front Nutr 2024; 11:1487859. [PMID: 39529929 PMCID: PMC11551038 DOI: 10.3389/fnut.2024.1487859] [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: 08/28/2024] [Accepted: 10/09/2024] [Indexed: 11/16/2024] Open
Abstract
Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern that is exacerbated by the obesity pandemic. Dietary interventions have the potential to alleviate obesity-associated MASLD through variable mechanisms, including optimizing the gut microbiota. Previously, we reported that soy protein concentrate (SPC) with low or high levels of isoflavone (LIF or HIF) protected young obese Zucker rats from developing liver steatosis. The current study was designed to test whether SPC-LIF and SPC-HIF diets would reverse liver steatosis and alter fecal microbial composition in adult obese Zucker rats with existing steatosis. Methods Six-week-old male obese Zucker rats (n = 26) were fed a casein control diet (CAS) for 8 weeks and 7 rats were randomly selected and sacrificed to confirm liver steatosis. The remaining rats were randomly assigned to receive CAS, SPC-LIF, or SPC-HIF diet (n = 6-7/group) for an additional 10 weeks. Results Compared to CAS diet, feeding SPC-LIF and SPC-HIF diets resulted in significantly lower liver weight, liver steatosis score, and liver microvesicular score (p < 0.05), but did not lead to difference in body weight, liver macrovesicular score, serum ALT, or serum AST. Isoflavone levels (e.g., LIF vs. HIF) did not affect any of these measurements except in the SPC-HIF group, which had an additional decrease in liver weight (p < 0.05) compared to the SPC-LIF group. The SPC-HIF group also had significantly higher levels of the aglycone forms of daidzein, genistein, and equol as well as the total levels of daidzein, genistein, and equol compared to SPC-LIF or CAS diet fed rats (p < 0.05). The distribution of microbial communities based on measures of beta diversity of both SPC-LIF and SPC-HIF groups were significantly different to that of the CAS group (p ≤ 0.005). Alpha-diversity did not differ between any of the groups. Conclusion Taken together, dietary soy protein can reverse liver steatosis in adult Zucker rats, and the reversal of steatosis is accompanied by alterations in gut microbial composition.
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Affiliation(s)
- Reza Hakkak
- Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR, United States
- Arkansas Children’s Research Institute, Little Rock, AR, United States
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Soheila Korourian
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Wei Li
- Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Beverly Spray
- Division of Biostatistics Core, Arkansas Children’s Research Institute, Little Rock, AR, United States
| | - Nathan C. Twaddle
- Division of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, United States
| | | | - Elisabet Børsheim
- Arkansas Children’s Research Institute, Little Rock, AR, United States
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
- Arkansas Children’s Nutrition Center, Little Rock, AR, United States
| | - Michael S. Robeson II
- Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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Yuan H, Jung ES, Chae SW, Jung SJ, Daily JW, Park S. Biomarkers for Health Functional Foods in Metabolic Dysfunction-Associated Steatotic Liver Disorder (MASLD) Prevention: An Integrative Analysis of Network Pharmacology, Gut Microbiota, and Multi-Omics. Nutrients 2024; 16:3061. [PMID: 39339660 PMCID: PMC11434757 DOI: 10.3390/nu16183061] [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: 08/07/2024] [Revised: 09/01/2024] [Accepted: 09/05/2024] [Indexed: 09/30/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disorder (MASLD) is increasingly prevalent globally, highlighting the need for preventive strategies and early interventions. This comprehensive review explores the potential of health functional foods (HFFs) to maintain healthy liver function and prevent MASLD through an integrative analysis of network pharmacology, gut microbiota, and multi-omics approaches. We first examined the biomarkers associated with MASLD, emphasizing the complex interplay of genetic, environmental, and lifestyle factors. We then applied network pharmacology to identify food components with potential beneficial effects on liver health and metabolic function, elucidating their action mechanisms. This review identifies and evaluates strategies for halting or reversing the development of steatotic liver disease in the early stages, as well as biomarkers that can evaluate the success or failure of such strategies. The crucial role of the gut microbiota and its metabolites for MASLD prevention and metabolic homeostasis is discussed. We also cover state-of-the-art omics approaches, including transcriptomics, metabolomics, and integrated multi-omics analyses, in research on preventing MASLD. These advanced technologies provide deeper insights into physiological mechanisms and potential biomarkers for HFF development. The review concludes by proposing an integrated approach for developing HFFs targeting MASLD prevention, considering the Korean regulatory framework. We outline future research directions that bridge the gap between basic science and practical applications in health functional food development. This narrative review provides a foundation for researchers and food industry professionals interested in developing HFFs to support liver health. Emphasis is placed on maintaining metabolic balance and focusing on prevention and early-stage intervention strategies.
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Affiliation(s)
- Heng Yuan
- Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea;
| | - Eun-Soo Jung
- Clinical Trial Center for Functional Foods, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (E.-S.J.); (S.-W.C.); (S.-J.J.)
- Clinical Trial Center for K-FOOD Microbiome, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
| | - Soo-Wan Chae
- Clinical Trial Center for Functional Foods, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (E.-S.J.); (S.-W.C.); (S.-J.J.)
- Clinical Trial Center for K-FOOD Microbiome, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
| | - Su-Jin Jung
- Clinical Trial Center for Functional Foods, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (E.-S.J.); (S.-W.C.); (S.-J.J.)
- Clinical Trial Center for K-FOOD Microbiome, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
| | - James W. Daily
- Department of R&D, Daily Manufacturing Inc., Rockwell, NC 28138, USA;
| | - Sunmin Park
- Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea;
- Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, 20 Hoseoro79bungil, Asan 31499, Republic of Korea
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Vesković M, Pejović M, Šutulović N, Hrnčić D, Rašić-Marković A, Stanojlović O, Mladenović D. Exploring Fibrosis Pathophysiology in Lean and Obese Metabolic-Associated Fatty Liver Disease: An In-Depth Comparison. Int J Mol Sci 2024; 25:7405. [PMID: 39000518 PMCID: PMC11242866 DOI: 10.3390/ijms25137405] [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: 05/30/2024] [Revised: 06/21/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
While obesity-related nonalcoholic fatty liver disease (NAFLD) is linked with metabolic dysfunctions such as insulin resistance and adipose tissue inflammation, lean NAFLD more often progresses to liver fibrosis even in the absence of metabolic syndrome. This review aims to summarize the current knowledge regarding the mechanisms of liver fibrosis in lean NAFLD. The most commonly used lean NAFLD models include a methionine/choline-deficient (MCD) diet, a high-fat diet with carbon tetrachloride (CCl4), and a high-fructose and high-cholesterol diet. The major pro-fibrogenic mechanisms in lean NAFLD models include increased activation of the extracellular signal-regulated kinase (ERK) pathway, elevated expression of α-smooth muscle actin (α-SMA), collagen type I, and TGF-β, and modulation of fibrogenic markers such as tenascin-X and metalloproteinase inhibitors. Additionally, activation of macrophage signaling pathways promoting hepatic stellate cell (HSC) activation further contributes to fibrosis development. Animal models cannot cover all clinical features that are evident in patients with lean or obese NAFLD, implicating the need for novel models, as well as for deeper comparisons of clinical and experimental studies. Having in mind the prevalence of fibrosis in lean NAFLD patients, by addressing specific pathways, clinical studies can reveal new targeted therapies along with novel biomarkers for early detection and enhancement of clinical management for lean NAFLD patients.
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Affiliation(s)
- Milena Vesković
- Institute of Pathophysiology, Faculty of Medicine, University of Belgrade, Dr Subotića 9, 11000 Belgrade, Serbia
| | - Milka Pejović
- Primary Health Center “Vračar”, Velimira Bate Živojinovića 16, 11000 Belgrade, Serbia
| | - Nikola Šutulović
- Institute of Medical Physiology, Faculty of Medicine, University of Belgrade, Višegradska 26, 11000 Belgrade, Serbia
| | - Dragan Hrnčić
- Institute of Medical Physiology, Faculty of Medicine, University of Belgrade, Višegradska 26, 11000 Belgrade, Serbia
| | - Aleksandra Rašić-Marković
- Institute of Medical Physiology, Faculty of Medicine, University of Belgrade, Višegradska 26, 11000 Belgrade, Serbia
| | - Olivera Stanojlović
- Institute of Medical Physiology, Faculty of Medicine, University of Belgrade, Višegradska 26, 11000 Belgrade, Serbia
| | - Dušan Mladenović
- Institute of Pathophysiology, Faculty of Medicine, University of Belgrade, Dr Subotića 9, 11000 Belgrade, Serbia
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Xu H, Yuan M, Niu K, Yang W, Jiang M, Zhang L, Zhou J. Involvement of Bile Acid Metabolism and Gut Microbiota in the Amelioration of Experimental Metabolism-Associated Fatty Liver Disease by Nobiletin. Molecules 2024; 29:976. [PMID: 38474489 DOI: 10.3390/molecules29050976] [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: 01/09/2024] [Revised: 02/20/2024] [Accepted: 02/21/2024] [Indexed: 03/14/2024] Open
Abstract
Metabolism-associated fatty liver disease (MAFLD), a growing health problem worldwide, is one of the major risks for the development of cirrhosis and liver cancer. Oral administration of nobiletin (NOB), a natural citrus flavonoid, modulates the gut microbes and their metabolites in mice. In the present study, we established a mouse model of MAFLD by subjecting mice to a high-fat diet (HFD) for 12 weeks. Throughout this timeframe, NOB was administered to investigate its potential benefits on gut microbial balance and bile acid (BA) metabolism using various techniques, including 16S rRNA sequencing, targeted metabolomics of BA, and biological assays. NOB effectively slowed the progression of MAFLD by reducing serum lipid levels, blood glucose levels, LPS levels, and hepatic IL-1β and TNF-α levels. Furthermore, NOB reinstated diversity within the gut microbial community, increasing the population of bacteria that produce bile salt hydrolase (BSH) to enhance BA excretion. By exploring further, we found NOB downregulated hepatic expression of the farnesoid X receptor (FXR) and its associated small heterodimer partner (SHP), and it increased the expression of downstream enzymes, including cholesterol 7α-hydroxylase (CYP7A1) and cytochrome P450 27A1 (CYP27A1). This acceleration in cholesterol conversion within the liver contributes to mitigating MAFLD. The present findings underscore the significant role of NOB in regulating gut microbial balance and BA metabolism, revealing that long-term intake of NOB plays beneficial roles in the prevention or intervention of MAFLD.
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Affiliation(s)
- Hongling Xu
- School of Traditional Chinese Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Mingming Yuan
- Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China
| | - Kailin Niu
- School of Traditional Chinese Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Wei Yang
- Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China
| | - Maoyuan Jiang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
| | - Lei Zhang
- School of Traditional Chinese Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China
| | - Jing Zhou
- Laboratory Animal Center Affiliate from Research Office, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China
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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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11
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Ahmadi Badi S, Bereimipour A, Rohani P, Khatami S, Siadat SD. Interplay between gut microbiota and the master iron regulator, hepcidin, in the pathogenesis of liver fibrosis. Pathog Dis 2024; 82:ftae005. [PMID: 38555503 PMCID: PMC10990161 DOI: 10.1093/femspd/ftae005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 02/12/2024] [Accepted: 03/28/2024] [Indexed: 04/02/2024] Open
Abstract
INTRODUCTION There is a proven role for hepcidin and the composition of gut microbiota and its derivatives in the pathophysiology of liver fibrosis. AREA COVERED This review focuses on the literature search regarding the effect of hepcidin and gut microbiota on regulating liver physiology. We presented the regulating mechanisms of hepcidin expression and discussed the possible interaction between gut microbiota and hepcidin regulation. Furthermore, we investigated the importance of the hepcidin gene in biological processes and bacterial interactions using bioinformatics analysis. EXPERT OPINION One of the main features of liver fibrosis is iron accumulation in hepatic cells, including hepatocytes. This accumulation can induce an oxidative stress response, inflammation, and activation of hepatic stellate cells. Hepcidin is a crucial regulator of iron by targeting ferroportin expressed on hepatocytes, macrophages, and enterocytes. Various stimuli, such as iron load and inflammatory signals, control hepcidin regulation. Furthermore, a bidirectional relationship exists between iron and the composition and metabolic activity of gut microbiota. We explored the potential of gut microbiota to influence hepcidin expression and potentially manage liver fibrosis, as the regulation of iron metabolism plays a crucial role in this context.
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Affiliation(s)
- Sara Ahmadi Badi
- Biochemistry Department, Pasteur Institute of Iran, Tehran, 1963737611, Iran
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, 1416753955, Iran
| | - Ahmad Bereimipour
- Department of Biological Sciences and BioDiscovery Institute, University of North Texas, Denton, TX 76203, USA
| | - Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, 1416753955, Iran
| | - Shohreh Khatami
- Biochemistry Department, Pasteur Institute of Iran, Tehran, 1963737611, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center, Pasteur Institute of Iran, Tehran, 1963737611, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran,1963737611, Iran
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12
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Kuraji R, Ye C, Zhao C, Gao L, Martinez A, Miyashita Y, Radaic A, Kamarajan P, Le C, Zhan L, Range H, Sunohara M, Numabe Y, Kapila YL. Nisin lantibiotic prevents NAFLD liver steatosis and mitochondrial oxidative stress following periodontal disease by abrogating oral, gut and liver dysbiosis. NPJ Biofilms Microbiomes 2024; 10:3. [PMID: 38233485 PMCID: PMC10794237 DOI: 10.1038/s41522-024-00476-x] [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: 04/17/2023] [Accepted: 01/02/2024] [Indexed: 01/19/2024] Open
Abstract
Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.
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Affiliation(s)
- Ryutaro Kuraji
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Changchang Ye
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontology, West China School of Stomatology, Sichuan University, Chengdu, China
| | - Chuanjiang Zhao
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Li Gao
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - April Martinez
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Yukihiro Miyashita
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Allan Radaic
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Pachiyappan Kamarajan
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
| | - Charles Le
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Ling Zhan
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
| | - Helene Range
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
- Department of Periodontology, University of Rennes, UFR of Odontology; Service d'Odontologie, CHU de Rennes, Rennes, France
- INSERM CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer); CIC 1414, Rennes, France
| | - Masataka Sunohara
- Department of Anatomy, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne L Kapila
- Orofacial Sciences Department, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA.
- Sections of Biosystems and Function and Periodontics, School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA.
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13
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Butt AS, Devi J. Polycystic ovary syndrome and nonalcoholic fatty liver disease. POLYCYSTIC OVARY SYNDROME 2024:92-99. [DOI: 10.1016/b978-0-323-87932-3.00021-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kim DY, Park JY, Gee HY. Lactobacillus plantarum ameliorates NASH-related inflammation by upregulating L-arginine production. Exp Mol Med 2023; 55:2332-2345. [PMID: 37907736 PMCID: PMC10689779 DOI: 10.1038/s12276-023-01102-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 07/16/2023] [Accepted: 08/02/2023] [Indexed: 11/02/2023] Open
Abstract
Lactobacillus is a probiotic with therapeutic potential for several diseases, including liver disease. However, the therapeutic effect of L. plantarum against nonalcoholic steatohepatitis (NASH) and its underlying mechanisms remain unelucidated. Therefore, we delineated the L. plantarum-mediated NASH regulation in a mouse model to understand its therapeutic effect. We used a choline-deficient high-fat diet (CD-HFD)-induced murine model that recapitulated the critical features of human metabolic syndrome and investigated the effect of L. plantarum on NASH pathogenesis using transcriptomic, metagenomic, and immunohistochemistry analyses. Validation experiments were performed using liver organoids and a murine model fed a methionine-choline-deficient (MCD) diet. L. plantarum treatment in mice significantly decreased liver inflammation and improved metabolic phenotypes, such as insulin tolerance and the hepatic lipid content, compared with those in the vehicle group. RNA-sequencing analysis revealed that L. plantarum treatment significantly downregulated inflammation-related pathways. Shotgun metagenomic analysis revealed that L-arginine biosynthesis-related microbial genes were significantly upregulated in the L. plantarum group. We also confirmed the elevated arginine levels in the serum of the L. plantarum group. We further used liver organoids and mice fed an MCD diet to demonstrate that L-arginine alone was sufficient to alleviate liver inflammation. Our data revealed a novel and counterintuitive therapeutic effect of L. plantarum on alleviating NASH-related liver inflammation by increasing circulating L-arginine.
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Affiliation(s)
- Dong Yun Kim
- Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of South Korea
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of South Korea
| | - Jun Yong Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of South Korea.
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of South Korea.
| | - Heon Yung Gee
- Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of South Korea.
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of South Korea.
- Woo Choo Lee Institute for Precision Drug Development, Seoul, Republic of South Korea.
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Lai C, Chen L, Zhong X, Tang Z, Zhang B, Luo Y, Li C, Jin M, Chen X, Li J, Shi Y, Sun Y, Guo L. Long-term effects on liver metabolism induced by ceftriaxone sodium pretreatment. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 335:122238. [PMID: 37506808 DOI: 10.1016/j.envpol.2023.122238] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/16/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023]
Abstract
Ceftriaxone is an emerging contaminant due to its potential harm, while its effects on liver are still need to be clarified. In this study, we first pretreated the 8-week-old C57BL/6J mice with high dose ceftriaxone sodium (Cef, 400 mg/mL, 0.2 mL per dose) for 8 days to prepare a gut dysbiosis model, then treated with normal feed for a two-month recovery period, and applied non-targeted metabolomics (including lipidomics) to investigate the variations of fecal and liver metabolome, and coupled with targeted determination of fecal short-chain fatty acids (SCFAs) and bile acids (BAs). Lastly, the correlations and mediation analysis between the liver metabolism and gut metabolism/microbes were carried, and the potential mechanisms of the mal-effects on gut-liver axis induced by Cef pretreatment were accordingly discussed. Compared to the control group, Cef pretreatment reduced the rate of weight gain and hepatosomatic index, induced bile duct epithelial cells proliferated around the central vein and appearance of binucleated hepatocytes, decreased the ratio of total branching chains amino acids (BCAAs) to total aromatic amino acids (AAAs) in liver metabolome. In fecal metabolome, the total fecal SCFAs and BAs did not change significantly while butyric acid decreased and the primary BAs increased after Cef pretreatment. Correlation and mediation analysis revealed one potential mechanism that Cef may first change the intestinal microbiota (such as destroying its normal structure, reducing its abundance and the stability of the microbial network or certain microbe abundance like Alistipes), and then change the intestinal metabolism (such as acetate, caproate, propionate), leading to liver metabolic disorder (such as spermidine, inosine, cinnamaldehyde). This study proved the possibility of Cef-induced liver damage, displayed the overall metabolic profile of the liver following Cef pretreatment and provided a theoretical framework for further research into the mechanism of Cef-induced liver damage.
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Affiliation(s)
- Chengze Lai
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Linkang Chen
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Xiaoting Zhong
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Zeli Tang
- Department of Pathology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China
| | - Bin Zhang
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Yu Luo
- Guangzhou Liwan District Center for Disease Control and Prevention, Guangzhou, Guangdong, China
| | - Chengji Li
- Yunfu Disease Control and Prevention Center, Guang Dong Province, China
| | - Mengcheng Jin
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Xu Chen
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Jinglin Li
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Yinying Shi
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Yanqin Sun
- Department of Pathology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China
| | - Lianxian Guo
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China.
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16
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Yang K, Song M. New Insights into the Pathogenesis of Metabolic-Associated Fatty Liver Disease (MAFLD): Gut-Liver-Heart Crosstalk. Nutrients 2023; 15:3970. [PMID: 37764755 PMCID: PMC10534946 DOI: 10.3390/nu15183970] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the gut-liver-heart crosstalk is crucial for unraveling the complexities of MAFLD and developing effective treatment and prevention strategies. The gut-liver crosstalk participates in the regulation of the metabolic and inflammatory processes through host-microbiome interactions. Gut microbiota have been associated with the development and progression of MAFLD, and its dysbiosis contributes to insulin resistance, inflammation, and oxidative stress. Metabolites derived from the gut microbiota enter the systemic circulation and influence both the liver and heart, resulting in the gut-liver-heart axis playing an important role in MAFLD. Furthermore, growing evidence suggests that insulin resistance, endothelial dysfunction, and systemic inflammation in MAFLD may contribute to an increased risk of cardiovascular disease (CVD). Additionally, the dysregulation of lipid metabolism in MAFLD may also lead to cardiac dysfunction and heart failure. Overall, the crosstalk between the liver and heart involves a complex interplay of molecular pathways that contribute to the development of CVD in patients with MAFLD. This review emphasizes the current understanding of the gut-liver-heart crosstalk as a foundation for optimizing patient outcomes with MAFLD.
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Affiliation(s)
| | - Myeongjun Song
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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17
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Han H, Sun Y, Zhang W, Zhang Z, Yuan T. The Effect of Nanobubble Water Containing Cordyceps Extract and Withaferin A on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:2265. [PMID: 37570582 PMCID: PMC10421312 DOI: 10.3390/nano13152265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/31/2023] [Accepted: 08/01/2023] [Indexed: 08/13/2023]
Abstract
Cordyceps extract and withaferin A (Wi-A) are natural compounds that have therapeutic effects on non-alcoholic fatty liver disease (NAFLD). However, their efficacy is limited and a long treatment duration is usually required. To enhance their efficiency, the synergistic effects of nanobubble water (NBW) derived from nitrogen, hydrogen, and oxygen gases were investigated. Results showed that the physical properties of all three NBWs, including nanobubble density (108 particles/mL) and zeta potential (below -22 mV), were stable during 48 h of storage. Hydrogen and nitrogen NBWs did not reduce, but instead promoted, free fatty acid-induced lipid accumulation in HepG2 cells. In contrast, oxygen NBW synergistically enhanced the effects of cordyceps extract and Wi-A. The lipid content decreased by 29% and 33% in the oxygen NBW + cordyceps extract and oxygen NBW + Wi-A groups, respectively, compared to reductions of 22% and 16% by aqueous extracts without NB. This study found that NBW may enhance the lipid-reducing effects of natural compounds, such as cordyceps extract and withaferin A, in hepatic cells. Further studies in animal experiments are needed to determine whether NBW has a potential application in NAFLD.
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Affiliation(s)
| | | | | | | | - Tian Yuan
- Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Ibaraki, Japan; (H.H.); (Y.S.); (W.Z.); (Z.Z.)
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18
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Perlin CM, Longo L, Keingeski MB, Picon RV, Álvares-da-Silva MR. Gut mycobiota changes in liver diseases: A systematic review. Med Mycol 2023; 61:myad071. [PMID: 37463798 DOI: 10.1093/mmy/myad071] [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: 02/08/2023] [Revised: 06/27/2023] [Accepted: 07/16/2023] [Indexed: 07/20/2023] Open
Abstract
Intestinal fungi play an important role in the health-disease process. We observed that in liver diseases, fungal infections lead to high mortality. In this review, we were able to gather and evaluate the available scientific evidence on intestinal mycobiota and liver diseases. We searched PubMed and Embase, using a combination of several entry terms. Only studies in adults ≥ 18 years old with liver disease and published after 2010 were included. We observed that individuals with liver disease have an altered intestinal mycobioma, which accompanies the progression of these diseases. In cirrhotic patients, there are a high number of Candida sp. strains, especially Candida albicans. In early chronic liver disease, there is an increase in alpha diversity at the expense of Candida sp. and conversely, in advanced liver disease, there is a negative correlation between alpha diversity and model for end-stage liver disease score. On the other hand, patients with non-alcoholic fatty liver disease demonstrate greater diversity compared to controls. Our study concluded that the evidence on the subject is sparse, with few studies and a lack of standardization of outcome measures and reporting, and it was not possible to perform a meta-analysis capable of synthesizing relevant parameters of the human mycobiotic profile. However, certain fungal genera such as Candida play an important role in the context of liver disease and that adults with liver disease have a distinct gut mycobiotic profile from healthy controls.
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Affiliation(s)
- Cássio Marques Perlin
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035-002, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035-903, Brazil
| | - Larisse Longo
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035-002, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035-903, Brazil
| | - Melina Belén Keingeski
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035-002, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035-903, Brazil
| | - Rafael V Picon
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035-002, Brazil
- School of Medicine, Department of Internal Medicine, Universidade Federal do Rio Grande do Sul; Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035-903, Brazil
| | - Mário Reis Álvares-da-Silva
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90035-002, Brazil
- Experimental Laboratory of Hepatology and Gastroenterology, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035-903, Brazil
- School of Medicine, Department of Internal Medicine, Universidade Federal do Rio Grande do Sul; Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035-903, Brazil
- CNPq researcher
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19
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Guo GJ, Yao F, Lu WP, Xu HM. Gut microbiome and metabolic-associated fatty liver disease: Current status and potential applications. World J Hepatol 2023; 15:867-882. [PMID: 37547030 PMCID: PMC10401411 DOI: 10.4254/wjh.v15.i7.867] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 06/11/2023] [Accepted: 06/30/2023] [Indexed: 07/21/2023] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. In recent years, the occurrence rate of MAFLD has been on the rise, mainly due to lifestyle changes, high-calorie diets, and imbalanced dietary structures, thereby posing a threat to human health and creating heavy social and economic burdens. With the development of 16S sequencing and integrated multi-omics analysis, the role of the gut microbiota (GM) and its metabolites in MAFLD has been further recognized. The GM plays a role in digestion, energy metabolism, vitamin synthesis, the prevention of pathogenic bacteria colonisation, and immunoregulation. The gut-liver axis is one of the vital links between the GM and the liver. Toxic substances in the intestine can enter the liver through the portal vascular system when the intestinal barrier is severely damaged. The liver also influences the GM in various ways, such as bile acid circulation. The gut-liver axis is essential in maintaining the body's normal physiological state and plays a role in the onset and prognosis of many diseases, including MAFLD. This article reviews the status of the GM and MAFLD and summarizes the GM characteristics in MAFLD. The relationship between the GM and MAFLD is discussed in terms of bile acid circulation, energy metabolism, micronutrients, and signalling pathways. Current MAFLD treatments targeting the GM are also listed.
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Affiliation(s)
- Gong-Jing Guo
- Gastroenterology Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen 518172, Guangdong Province, China
| | - Fei Yao
- Department of Science and Education, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, Guangdong Province, China
| | - Wei-Peng Lu
- The First Clinical School, Guangzhou Medical University, Guangzhou 510120, Guangdong Province, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong Province, China.
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20
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Nysather J, Kaya E, Manka P, Gudsoorkar P, Syn WK. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease Cross Talk. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:315-335. [PMID: 37657879 DOI: 10.1053/j.akdh.2023.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 12/14/2022] [Accepted: 04/04/2023] [Indexed: 09/03/2023]
Abstract
Nonalcoholic fatty liver disease is a multisystem condition with effects beyond the liver. The identification of chronic kidney disease as an independent mediator of nonalcoholic fatty liver disease or associated entity with shared cardiometabolic risk factors remains controversial and continues to draw scientific interest. With increasing prevalence of nonalcoholic fatty liver disease and lack of Food and Drug Administration approved therapies, these shared cardiometabolic risk factors have drawn significant attention. In this article, we review shared pathophysiological mechanisms between nonalcoholic fatty liver disease and chronic kidney disease along with current treatment strategies that might be useful for both disease processes.
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Affiliation(s)
- Jacob Nysather
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Eda Kaya
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Paul Manka
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Prakash Gudsoorkar
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Wing-Kin Syn
- Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Euskal Herriko Unibertsitatea/Universidad del País Vasco, Leioa, Spain.
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21
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Yang R, Yang Y, Yang L, Chen H, Zhong W, Zhu L. First insight into the sex-dependent accumulation, tissue distribution and potential toxicities of 2-ethylhexyl diphenyl phosphate and its metabolites in adult zebrafish. JOURNAL OF HAZARDOUS MATERIALS 2023; 452:131299. [PMID: 37027911 DOI: 10.1016/j.jhazmat.2023.131299] [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: 01/17/2023] [Revised: 03/05/2023] [Accepted: 03/24/2023] [Indexed: 05/03/2023]
Abstract
The 2-ethylhexyl diphenyl phosphate (EHDPHP), a primary organophosphorus flame retardant used in various industrial products, is prone to biotransformation. However, there is a knowledge gap on the sex- and tissue-specific accumulation and potential toxicities of EHDPHP (M1) and its metabolites (M2-M16). In this study, adult zebrafish (Danio rerio) were exposed to EHDPHP (0, 5, 35 and 245 µg/L) for 21-day, which was followed by 7-day depuration. The bioconcentration factor (BCF) of EHDPHP in female zebrafish was 26.2 ± 7.7% lower than in males due to the lower uptake rate (ku) while higher depuration rate (kd) in the females. The regular ovulation and higher metabolic efficiency promoted elimination from female zebrafish, thus leading to much less (28-44%) accumulation of ∑(M1-M16) in female zebrafish. They exhibited the highest accumulation in the liver and intestine in both sexes, which might be regulated by tissue-specific transporters and histones evidenced by molecular docking results. Intestine microbiota analysis further revealed that female zebrafish were more susceptible to EHDPHP exposure, with more significant changes in phenotype number and KEGG pathways in female than male fish. Disease prediction results suggested that EHDPHP exposure might cause cancers, cardiovascular diseases as well as endocrine disorders in both sexes. These results provide a comprehensive understanding of the sex-dependent accumulation and toxicity of EHDPHP and its metabolites.
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Affiliation(s)
- Rongyan Yang
- Key Laboratory of Pollution Processes and Environmental Criteria of Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China
| | - Yi Yang
- Key Laboratory of Pollution Processes and Environmental Criteria of Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China
| | - Liping Yang
- Key Laboratory of Pollution Processes and Environmental Criteria of Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China
| | - Hao Chen
- Key Laboratory of Pollution Processes and Environmental Criteria of Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China
| | - Wenjue Zhong
- Key Laboratory of Pollution Processes and Environmental Criteria of Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China.
| | - Lingyan Zhu
- Key Laboratory of Pollution Processes and Environmental Criteria of Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering of Nankai University, Tianjin 300350, China
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22
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Kirundi J, Moghadamrad S, Urbaniak C. Microbiome-liver crosstalk: A multihit therapeutic target for liver disease. World J Gastroenterol 2023; 29:1651-1668. [PMID: 37077519 PMCID: PMC10107210 DOI: 10.3748/wjg.v29.i11.1651] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/05/2023] [Accepted: 03/07/2023] [Indexed: 03/17/2023] Open
Abstract
Liver disease has become a leading cause of death, particularly in the West, where it is attributed to more than two million deaths annually. The correlation between gut microbiota and liver disease is still not fully understood. However, it is well known that gut dysbiosis accompanied by a leaky gut causes an increase in lipopolysaccharides in circulation, which in turn evoke massive hepatic inflammation promoting liver cirrhosis. Microbial dysbiosis also leads to poor bile acid metabolism and low short-chain fatty acids, all of which exacerbate the inflammatory response of liver cells. Gut microbial homeostasis is maintained through intricate processes that ensure that commensal microbes adapt to the low oxygen potential of the gut and that they rapidly occupy all the intestinal niches, thus outcompeting any potential pathogens for available nutrients. The crosstalk between the gut microbiota and its metabolites also guarantee an intact gut barrier. These processes that protect against destabilization of gut microbes by potential entry of pathogenic bacteria are collectively called colonization resistance and are equally essential for liver health. In this review, we shall investigate how the mechanisms of colonization resistance influence the liver in health and disease and the microbial-liver crosstalk potential as therapeutic target areas.
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Affiliation(s)
- Jorum Kirundi
- Department of Biomedical Research, University of Bern, Bern 3014, Switzerland
| | - Sheida Moghadamrad
- Department of Gastroenterology/Hepatology, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona and Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano 6900, Switzerland
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23
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Kuraji R, Shiba T, Dong TS, Numabe Y, Kapila YL. Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis. World J Gastroenterol 2023; 29:967-996. [PMID: 36844143 PMCID: PMC9950865 DOI: 10.3748/wjg.v29.i6.967] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 11/14/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-0071, Japan
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
| | - Takahiko Shiba
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, United States
- Department of Periodontology, Tokyo Medical and Dental University, Tokyo 113-8549, Japan
| | - Tien S Dong
- The Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo 102-8159, Japan
| | - Yvonne L Kapila
- Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94143, United States
- Sections of Biosystems and Function and Periodontics, Professor and Associate Dean of Research, Felix and Mildred Yip Endowed Chair in Dentistry, University of California Los Angeles, Los Angeles, CA 90095, United States
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24
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Huang PY, Chen CH, Tsai MJ, Yao CC, Wang HM, Kuo YH, Chang KC, Hung CH, Chuah SK, Tsai MC. Effects of direct anti-viral agents on the gut microbiota in patients with chronic hepatitis C. J Formos Med Assoc 2023; 122:157-163. [PMID: 36155707 DOI: 10.1016/j.jfma.2022.08.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 08/21/2022] [Accepted: 08/30/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND/PURPOSE Gut microbiology is associated with liver disease due to gut-liver circulation via the gut microbial-liver axis. There is a paucity of data regarding the effects of treatment to cure hepatitis C virus (HCV) infection on the gut microbiota. The aim of this study was to evaluate the fecal microbiota before and after treatment with direct antiviral agents (DAA) in patients with HCV infection. METHODS This prospective study was conducted at Kaohsiung Chung-Gung Memorial Hospital, Taiwan, between December 2019 and November 2020. We recruited patients with chronic hepatitis C (CHC) receiving DAA treatment. Fecal samples were collected twice: at baseline (before DAA treatment; CHC group) and 24 weeks after the end of treatment (EOT; SVR24 group), and once from healthy controls at baseline (control group). The taxonomic composition of the gut microbiota was determined using 16 S ribosomal RNA gene sequencing of stool samples. RESULTS A total of 60 patients with CHC and 60 healthy controls matched by age and gender were enrolled. All patients achieved a sustained virologic response (SVR). Alpha diversity was not significantly difference between any groups. Analysis of similarities (ANOSIM) revealed minor differences in the microbial community structure between the control group and CHC group (R = 0.0146, P = 0.098) and less significant differences between the CHC group and SVR24 group (R = -0.0139; P = 0.94). Three phyla and eight genera were differentially abundant between the control group and CHC group. CONCLUSION Individuals with CHC do not exhibit significant gut microbiota alterations and eradication of HCV by DAA is not associated with significant modification of the gut microbiota.
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Affiliation(s)
- Pao-Yuan Huang
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Mu-Jung Tsai
- Kaohsiung Municipal Kaohsiung Senior High School, Kaohsiung 807, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Hsin-Ming Wang
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
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25
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Multifactorial Diseases of the Heart, Kidneys, Lungs, and Liver and Incident Cancer: Epidemiology and Shared Mechanisms. Cancers (Basel) 2023; 15:cancers15030729. [PMID: 36765688 PMCID: PMC9913123 DOI: 10.3390/cancers15030729] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/05/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
Within the aging population, the frequency of cancer is increasing dramatically. In addition, multiple genetic and environmental factors lead to common multifactorial diseases, including cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and metabolic-associated fatty liver disease. In recent years, there has been a growing awareness of the connection between cancer and multifactorial diseases, as well as how one can affect the other, resulting in a vicious cycle. Although the exact mechanistic explanations behind this remain to be fully explored, some progress has been made in uncovering the common pathologic mechanisms. In this review, we focus on the nature of the link between cancer and common multifactorial conditions, as well as specific shared mechanisms, some of which may represent either preventive or therapeutic targets. Rather than organ-specific interactions, we herein focus on the shared mechanisms among the multifactorial diseases, which may explain the increased cancer risk. More research on this subject will highlight the significance of developing new drugs that target multiple systems rather than just one disease.
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26
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Yoshikawa S, Taniguchi K, Sawamura H, Ikeda Y, Asai T, Tsuji A, Matsuda S. Metabolic Associated Fatty Liver Disease as a Risk Factor for the Development of Central Nervous System Disorders. LIVERS 2023; 3:21-32. [DOI: 10.3390/livers3010002] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
MAFLD/NAFLD is the most ordinary liver disease categorized by hepatic steatosis with the increase of surplus fat in the liver and metabolic liver dysfunction, which is associated with bigger mortality and a high medical burden. An association between MAFLD/NAFLD and central nervous system disorders including psychological disorders has been demonstrated. Additionally, MAFLD/NAFLD has been correlated with various types of neurodegenerative disorders such as amyotrophic lateral sclerosis or Parkinson’s disease. Contrasted to healthy controls, patients with MAFLD/NAFLD have a greater prevalence risk of extrahepatic complications within multiple organs. Dietary interventions have emerged as effective strategies for MAFLD/NAFLD. The PI3K/AKT/mTOR signaling pathway involved in the regulation of Th17/Treg balance might promote the pathogenesis of several diseases including MAFLD/NAFLD. As extrahepatic complications may happen across various organs including CNS, cooperative care with individual experts is also necessary for managing patients with MAFLD/NAFLD.
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Affiliation(s)
- Sayuri Yoshikawa
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Kurumi Taniguchi
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Haruka Sawamura
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Yuka Ikeda
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Tomoko Asai
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Ai Tsuji
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Satoru Matsuda
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
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Chen Z, Ding C, Gu Y, He Y, Chen B, Zheng S, Li Q. Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends. Front Oncol 2023; 13:1120515. [PMID: 37064156 PMCID: PMC10098157 DOI: 10.3389/fonc.2023.1120515] [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: 12/10/2022] [Accepted: 03/20/2023] [Indexed: 04/18/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a primary malignant tumor responsible for approximately 90% of all liver cancers in humans, making it one of the leading public health problems worldwide. The gut microbiota is a complex microbial ecosystem that can influence tumor formation, metastasis, and resistance to treatment. Therefore, understanding the potential mechanisms of gut microbiota pathogenesis is critical for the prevention and treatment of HCC. Materials and methods A search was conducted in the Web of Science Core Collection (WoSCC) database for English literature studies on the relationship between gut microbiota and HCC from 2011 to 2022. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were used to analyze global trends and research hotspots in this field. Results A total of 739 eligible publications, comprising of 383 articles and 356 reviews, were analyzed. Over the past 11 years, there has been a rapid increase in the annual number of publications and average citation levels, especially in the last five years. The majority of published articles on this topic originated from China (n=257, 34.78%), followed by the United States of America (n=203, 27.47%), and Italy (n=85, 11.50%). American scholars demonstrated high productivity, prominence, and academic environment influence in the research of this subject. Furthermore, the University of California, San Diego published the most papers (n=24) and had the highest average citation value (value=152.17) in the study of the relationship between gut microbiota and HCC. Schnabl B from the USA and Ohtani N from Japan were the authors with the highest number of publications and average citation value, respectively. Conclusion In recent years, research on the gut microbiota's role in HCC has made rapid progress. Through a review of published literature, it has been found that the gut microbiota is crucial in the pathogenesis of HCC and in oncotherapy.
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Affiliation(s)
- Zhitao Chen
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| | - Chenchen Ding
- Affiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yangjun Gu
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| | - Yahui He
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- School of Medicine, Zhejiang Chinese Medical University, Zhejiang Shuren College, Hangzhou, China
| | - Bing Chen
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- School of Medicine, Zhejiang Chinese Medical University, Zhejiang Shuren College, Hangzhou, China
| | - Shusen Zheng
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- *Correspondence: Qiyong Li, ; Shusen Zheng,
| | - Qiyong Li
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China
- *Correspondence: Qiyong Li, ; Shusen Zheng,
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Cojocariu C, Popa C, Muzica C, Stanciu C, Cuciureanu T, Trifan A. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease. ESSENTIALS OF NON-ALCOHOLIC FATTY LIVER DISEASE 2023:171-181. [DOI: 10.1007/978-3-031-33548-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Bhat MH, Hajam YA, Neelam, Kumar R, Diksha. Microbial Diversity and Their Role in Human Health and Diseases. ROLE OF MICROBES IN SUSTAINABLE DEVELOPMENT 2023:1-33. [DOI: 10.1007/978-981-99-3126-2_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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30
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Guo G, Wu Y, Liu Y, Wang Z, Xu G, Wang X, Liang F, Lai W, Xiao X, Zhu Q, Zhong S. Exploring the causal effects of the gut microbiome on serum lipid levels: A two-sample Mendelian randomization analysis. Front Microbiol 2023; 14:1113334. [PMID: 36876057 PMCID: PMC9978097 DOI: 10.3389/fmicb.2023.1113334] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 01/27/2023] [Indexed: 02/18/2023] Open
Abstract
Background The gut microbiome was reported to be associated with dyslipidemia in previous observational studies. However, whether the composition of the gut microbiome has a causal effect on serum lipid levels remains unclear. Objective A two-sample Mendelian randomization (MR) analysis was conducted to investigate the potential causal relationships between gut microbial taxa and serum lipid levels, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and log-transformed triglyceride (TG) levels. Materials and methods Summary statistics of genome-wide association studies (GWASs) for the gut microbiome and four blood lipid traits were obtained from public datasets. Five recognized MR methods were applied to assess the causal estimates, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates. Results The combined results from the five MR methods and sensitivity analysis showed 59 suggestive causal associations and four significant causal associations. In particular, genus Terrisporobacter was associated with higher LDL-C (P IVW = 3.01 × 10-6) and TC levels (P IVW = 2.11 × 10-4), phylum Actinobacteria was correlated with higher LDL-C level (P IVW = 4.10 × 10-4), and genus Oscillospira was associated with lower TG level (P IVW = 2.19 × 10-6). Conclusion This research may provide novel insights into the causal relationships of the gut microbiome on serum lipid levels and new therapeutic or prevention strategies for dyslipidemia.
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Affiliation(s)
- Gongjie Guo
- School of Medicine, South China University of Technology, Guangzhou, China.,Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Yonglin Wu
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
| | - Yingjian Liu
- School of Medicine, South China University of Technology, Guangzhou, China.,Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Zixian Wang
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Guifeng Xu
- School of Medicine, South China University of Technology, Guangzhou, China.,Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Xipei Wang
- Laboratory of Phase I Clinical Trials, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Feiqing Liang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
| | - Weihua Lai
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiao Xiao
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Qian Zhu
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Shilong Zhong
- School of Medicine, South China University of Technology, Guangzhou, China.,Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.,Laboratory of Phase I Clinical Trials, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
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Lützhøft DO, Sinioja T, Christoffersen BØ, Jakobsen RR, Geng D, Ahmad HFB, Straarup EM, Pedersen KM, Kot W, Pedersen HD, Cirera S, Hyötyläinen T, Nielsen DS, Hansen AK. Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model. BMC Microbiol 2022; 22:287. [DOI: 10.1186/s12866-022-02704-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 11/11/2022] [Indexed: 12/03/2022] Open
Abstract
Abstract
Background
Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.
Results
Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.
Conclusions
Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
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Polyphenol-Rich Liupao Tea Extract Prevents High-Fat Diet-Induced MAFLD by Modulating the Gut Microbiota. Nutrients 2022; 14:nu14224930. [PMID: 36432617 PMCID: PMC9697786 DOI: 10.3390/nu14224930] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/17/2022] [Accepted: 11/18/2022] [Indexed: 11/23/2022] Open
Abstract
The modulation of gut microbiota dysbiosis might regulate the progression of metabolic-associated fatty liver disease (MAFLD). Here, we found that polyphenol-rich Liupao tea extract (PLE) prevents high-fat diet (HFD)-induced MAFLD in ApoE-/- male mice accompanied by protection of the intestinal barrier and downregulation of lipopolysaccharide (LPS)-related Toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) signaling in the liver. Fecal microbiome transplantation (FMT) from PLE-and-HFD-treated mice delayed MAFLD development significantly compared with FMT from HFD-treated mice. In this case, 16S rRNA gene sequencing revealed that Rikenellaceae and Odoribacter were significantly enriched and that Helicobacter was significantly decreased in not only the HFD+PLE group but also the HFD+PLE-FMT group. Furthermore, the level of 3-sulfodeoxycholic acid was significantly decreased in the HFD+PLE-FMT group compared with the HFD-FMT group. In conclusion, our data demonstrate that PLE could modulate the MAFLD phenotype in mice and that this effect is partly mediated through modulation of the gut microbiota.
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Deng Y, Chen H, Huang Y, Zhang Y, Ren H, Fang M, Wang Q, Chen W, Hale RC, Galloway TS, Chen D. Long-Term Exposure to Environmentally Relevant Doses of Large Polystyrene Microplastics Disturbs Lipid Homeostasis via Bowel Function Interference. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2022; 56:15805-15817. [PMID: 36282942 DOI: 10.1021/acs.est.1c07933] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
The question of whether long-term chronic exposure to microplastics (MPs) could induce dose- and size-dependent adverse effects in mammals remains controversial and poorly understood. Our study explored potential health risks from dietary exposure to environmentally relevant doses of polystyrene (PS) MPs, through a mouse model and integrated analyses of the interruptions of fecal microbial metagenomes and plasma lipidomes. After 21 weeks of exposure to the MPs (40-100 μm), mice mainly exhibited gut microbiota dysbiosis, tissue inflammation, and plasma lipid metabolism disorder, although no notable accumulation of MPs was observed in the gut or liver. The change of the relative abundance of microbiota was strongly associated with the exposure dose and size of MPs while less significant effects were observed in gut damage and abnormal lipid metabolism. Moreover, multiomics data suggested that the host abnormal lipid metabolism was closely related to bowel function disruptions, including gut microbiota dysbiosis, increased gut permeability, and inflammation induced by MPs. We revealed for the first time that even without notable accumulation in mouse tissues, long-term exposure to MPs at environmentally relevant doses could still induce widespread health risks. This raises concern on the health risks from the exposure of humans and other mammals to environmentally relevant dose MPs.
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Affiliation(s)
- Yongfeng Deng
- School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China
| | - Hexia Chen
- School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China
| | - Yichao Huang
- School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China
| | - Yan Zhang
- State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China
| | - Hongqiang Ren
- State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China
| | - Mingliang Fang
- School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore
| | - Qing Wang
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Wen Chen
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Robert C Hale
- Virginia Institute of Marine Science, William & Mary, P.O. Box 1346, Gloucester Point, Virginia 23062, United States
| | - Tamara S Galloway
- Biosciences, College of Life and Environmental Sciences, Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter, Devon EX4 4QD, United Kingdom
| | - Da Chen
- School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China
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Xing W, Gao W, Lv X, Zhao Z, Mao G, Dong X, Zhang Z. The effects of supplementation of probiotics, prebiotics, or synbiotics on patients with non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials. Front Nutr 2022; 9:1024678. [PMID: 36386939 PMCID: PMC9640999 DOI: 10.3389/fnut.2022.1024678] [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: 08/22/2022] [Accepted: 10/03/2022] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Research on the efficacy of probiotics, prebiotics, and synbiotics on NAFLD patients continues to be inconsistent. The purpose of this study is to evaluate the effectiveness of these microbial therapies on NAFLD. METHODS Eligible randomized-controlled trials reporting the effect of probiotics, prebiotics, or synbiotics in NAFLD were searched in PubMed, Web of Science, Embase, Google scholar, and CNKI databases from 2020 to Jul 2022. The changes in the outcomes were analyzed using standard mean difference (SMD) and 95% confidence intervals (CIs) with a random- or fixed-effects model to examine the effect of microbial therapies. Subgroup analysis, influence and publication bias analysis were also performed. The quality of the eligible studies was evaluated using the Cochrane Risk of Bias Tool. RESULTS Eleven studies met the inclusion criteria involving 741 individuals. Microbial therapies could improve liver steatosis, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-c), alanine aminotransferase (ALT), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), and homeostasis model assessment-insulin resistance (HOMAI-R) (all P < 0.05). But microbial therapies could not ameliorate body mass index (BMI), energy, carbohydrate, fat intake, fasting blood sugar, HbA1c, insulin, high-sensitivity C-reactive protein (hs-CRP), and hepatic fibrosis of patients with NAFLD. CONCLUSION Probiotics, prebiotics, and synbiotics supplementation can potentially improve liver enzymes, lipid profiles, and liver steatosis in patients with NAFLD.
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Affiliation(s)
- Wenmin Xing
- Zhejiang Provincial Key Laboratory of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou, China
| | - Wenyan Gao
- School of Pharmacy, Hangzhou Medical College, Hangzhou, China
| | - Xiaoling Lv
- Zhejiang Provincial Key Laboratory of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou, China
| | - Zhenlei Zhao
- Zhejiang Provincial Key Laboratory of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou, China
| | - Genxiang Mao
- Zhejiang Provincial Key Laboratory of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou, China
| | - Xiaoyan Dong
- College of Pharmacy and Traditional Chinese Medicine, Jiangsu College of Nursing, Huaian, China
| | - Zuyong Zhang
- The Third People’s Hospital of Hangzhou, Hangzhou, China
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Ho AHY, Wong S, Lui R. Topic: Nutrition and the Gut-Liver-Brain Axis. CURRENT HEPATOLOGY REPORTS 2022; 21:99-110. [DOI: 10.1007/s11901-022-00589-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/24/2022] [Indexed: 04/14/2025]
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36
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Ortiz-López N, Fuenzalida C, Dufeu MS, Pinto-León A, Escobar A, Poniachik J, Roblero JP, Valenzuela-Pérez L, Beltrán CJ. The immune response as a therapeutic target in non-alcoholic fatty liver disease. Front Immunol 2022; 13:954869. [PMID: 36300120 PMCID: PMC9589255 DOI: 10.3389/fimmu.2022.954869] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/21/2022] [Indexed: 08/25/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public health problem worldwide. The clinical progression of NAFLD is associated with advanced forms of liver injury such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). As such, diverse pharmacological strategies have been implemented over the last few years, principally focused on metabolic pathways involved in NAFLD progression. However, a variable response rate has been observed in NAFLD patients, which is explained by the interindividual heterogeneity of susceptibility to liver damage. In this scenario, it is necessary to search for different therapeutic approaches. It is worth noting that chronic low-grade inflammation constitutes a central mechanism in the pathogenesis and progression of NAFLD, associated with abnormal composition of the intestinal microbiota, increased lymphocyte activation in the intestine and immune effector mechanisms in liver. This review aims to discuss the current knowledge about the role of the immune response in NAFLD development. We have focused mainly on the impact of altered gut-liver-microbiota axis communication on immune cell activation in the intestinal mucosa and the role of subsequent lymphocyte homing to the liver in NAFLD development. We further discuss novel clinical trials that addressed the control of the liver and intestinal immune response to complement current NAFLD therapies.
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Affiliation(s)
- Nicolás Ortiz-López
- Laboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
- School of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Catalina Fuenzalida
- Laboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
- School of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - María Soledad Dufeu
- Laboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
- School of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Araceli Pinto-León
- Laboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
| | | | - Jaime Poniachik
- Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Juan Pablo Roblero
- Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Lucía Valenzuela-Pérez
- Laboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
- School of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Caroll J. Beltrán
- Laboratory of Immunogastroenterology, Unit of Gastroenterology, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile
- School of Medicine, Faculty of Medicine, Universidad de Chile, Santiago, Chile
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Potential link between high FIB-4 score and chronic kidney disease in metabolically healthy men. Sci Rep 2022; 12:16638. [PMID: 36198747 PMCID: PMC9535017 DOI: 10.1038/s41598-022-21039-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 09/22/2022] [Indexed: 11/08/2022] Open
Abstract
Although the association between non-alcoholic fatty liver disease and chronic kidney disease (CKD) has been well known, it is unclear whether Fibrosis-4 (FIB-4) score is a predictor of CKD development. We performed this retrospective cohort study, with a longitudinal analysis of 5-year follow-up data from Japanese annual health check-ups. Participants with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and/or proteinuria) and a habit of alcohol consumption were excluded. The cut-off FIB-4 score was 1.30, indicating increased risk of liver fibrosis. Overall, 5353 participants (men only) were analyzed without exclusion criteria. After propensity score matching, high FIB-4 score (≥ 1.30) was not an independent risk factor for incident CKD (odds ratio [OR] 1.57; 95% confidence interval [CI] 0.97-2.56). However, high FIB-4 score was a significant risk factor for CKD in non-obese (OR 1.92; 95% CI 1.09-3.40), non-hypertensive (OR 2.15; 95% CI 1.16-3.95), or non-smoking (OR 1.88; 95% CI 1.09-3.23) participants. In these participants, FIB-4 score was strongly associated with eGFR decline in the multiple linear regression analysis (β = - 2.8950, P = 0.011). Therefore, a high FIB-4 score may be significantly associated with CKD incidence after 5 years in metabolically healthy participants.
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Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention. Cells 2022; 11:cells11182827. [PMID: 36139402 PMCID: PMC9497179 DOI: 10.3390/cells11182827] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/26/2022] [Accepted: 09/08/2022] [Indexed: 11/24/2022] Open
Abstract
Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.
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Kuraji R, Kapila Y, Numabe Y. Periodontal Disease and Nonalcoholic Fatty Liver Disease: New Microbiome-Targeted Therapy Based on the Oral–Gut–Liver Axis Concept. CURRENT ORAL HEALTH REPORTS 2022; 9:89-102. [DOI: 10.1007/s40496-022-00312-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 01/03/2025]
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Mohammadi Z, Poustchi H, Hekmatdoost A, Etemadi A, Eghtesad S, Sharafkhah M, Stewart D, Ghanbari R, Chlipala GE, Bishehsari F, Merat S, Malekzadeh R. Gut microbiota profile in patients with nonalcoholic fatty liver disease and presumed nonalcoholic steatohepatitis. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2022; 27:54. [PMID: 36092483 PMCID: PMC9450256 DOI: 10.4103/jrms.jrms_673_21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 01/06/2022] [Accepted: 01/31/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND The main composition of intestinal microbiota in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients has not yet been elucidated. In this, case-control study, we identified differences of intestinal microbiota in male patients with NAFLD, presumed NASH, and healthy controls. MATERIALS AND METHODS We compared gut microbial composition of 25 patients with NAFLD, 13 patients with presumed NASH, and 12 healthy controls. Demographic information as well as clinical, nutritional, and physical activity data was gathered. Stool and blood samples were collected to perform the laboratory analysis. The taxonomic composition of gut microbiota was assessed using V4 regions of microbial small subunit ribosomal Ribonucleic acid genes sequencing of stool samples. RESULTS Firmicutes, Actinobacteria, and Bacteroidetes were the most frequently phyla in all groups. Our results revealed that Veillonella was the only genus with significantly different amounts in presumed NASH patients compared with patients with NAFLD (P = 2.76 × 10-6, q = 2.07 × 10-4, logFC = 5.52). CONCLUSION This pilot study was the first study to compare gut microbial composition in patients with NAFLD and presumed NASH in the Middle East. Given the potential effects of gut microbiota on the management and prevention of NAFLD, larger, prospective studies are recommended to confirm this study's findings.
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Affiliation(s)
- Zahra Mohammadi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arash Etemadi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Sareh Eghtesad
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Sharafkhah
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Delisha Stewart
- Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, USA
| | - Reza Ghanbari
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - George Edward Chlipala
- Research Informatics Core, Research Resources Center, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Faraz Bishehsari
- Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois, USA
| | - Shahin Merat
- Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Cannabis Extract Effects on Metabolic Parameters and Gut Microbiota Composition in a Mice Model of NAFLD and Obesity. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:7964018. [PMID: 35795290 PMCID: PMC9251106 DOI: 10.1155/2022/7964018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/26/2022] [Accepted: 05/28/2022] [Indexed: 11/23/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver abnormalities and has been linked with metabolic syndrome hallmarks. Unfortunately, current treatments are limited. This work aimed to elucidate the effects of three cannabis extracts on metabolic alteration and gut microbiota composition in a mouse model of NAFLD and obesity. Male mice were fed with a high-fat diet (HFD) for 12 weeks. Following the establishment of obesity, the HFD-fed group was subdivided into HFD or HFD that was supplemented with one of three cannabis extracts (CN1, CN2, and CN6) for additional 8 weeks. Metabolic parameters together with intestinal microbiota composition were evaluated. Except for several minor changes in gene expression, no profound metabolic effect was found due to cannabis extracts addition. Nevertheless, marked changes were observed in gut microbiota diversity and composition, with CN1 and CN6 exhibiting microbial abundance patterns that are associated with more beneficial outcomes. Taken together, specific cannabis extracts' addition to an HFD results in more favorable modifications in gut microbiota. Although no marked metabolic effect was disclosed, longer treatments duration and/or higher extracts concentrations may be needed. More research is required to ascertain this conjecture and to establish the influence of various cannabis extracts on host health in general and NAFLD in particular.
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Yao N, Yang Y, Li X, Wang Y, Guo R, Wang X, Li J, Xie Z, Li B, Cui W. Effects of Dietary Nutrients on Fatty Liver Disease Associated With Metabolic Dysfunction (MAFLD): Based on the Intestinal-Hepatic Axis. Front Nutr 2022; 9:906511. [PMID: 35782947 PMCID: PMC9247350 DOI: 10.3389/fnut.2022.906511] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/26/2022] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has recently become the most common liver disease with a global prevalence of over 25% and is expected to increase. Recently, experts have reached a consensus that “fatty liver disease associated with metabolic dysfunction or MAFLD” may be a more appropriate and inclusive definition than NAFLD. Like the former name NAFLD, MAFLD, as a manifestation of multiple system metabolic disorders involving the liver, has certain heterogeneity in its pathogenesis, clinical manifestations, pathological changes and natural outcomes. We found that there is a delicate dynamic balance among intestinal microflora, metabolites and host immune system to maintain a healthy intestinal environment and host health. On the contrary, this imbalance is related to diseases such as MAFLD. However, there are no clear studies on how dietary nutrients affect the intestinal environment and participate in the pathogenesis of MAFLD. This review summarizes the interactions among dietary nutrients, intestinal microbiota and MAFLD in an attempt to provide evidence for the use of dietary supplements to regulate liver function in patients with MAFLD. These dietary nutrients influence the development and progression of MAFLD mainly through the hepatic-intestinal axis by altering dietary energy absorption, regulating bile acid metabolism, changing intestinal permeability and producing ethanol. Meanwhile, the nutrients have the ability to combat MAFLD in terms of enriching abundance of intestinal microbiota, reducing Firmicutes/Bacteroidetes ratio and promoting abundance of beneficial gut microbes. Therefore, family therapy with MAFLD using a reasonable diet could be considered.
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Affiliation(s)
- Nan Yao
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yixue Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Xiaotong Li
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yuxiang Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Ruirui Guo
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Xuhan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Jing Li
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Zechun Xie
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Bo Li
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
- *Correspondence: Bo Li
| | - Weiwei Cui
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, China
- Weiwei Cui
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43
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Lee JH, Kwon YJ. Reply - Letter to the Editor. Clin Nutr 2022; 41:1461-1462. [PMID: 35504771 DOI: 10.1016/j.clnu.2022.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 04/11/2022] [Indexed: 11/22/2022]
Affiliation(s)
- Jun-Hyuk Lee
- Department of Family Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, 01830, Republic of Korea.
| | - Yu-Jin Kwon
- Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Gyeonggi-do, 16995, Republic of Korea.
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Ogresta D, Mrzljak A, Cigrovski Berkovic M, Bilic-Curcic I, Stojsavljevic-Shapeski S, Virovic-Jukic L. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications. J Clin Transl Hepatol 2022; 10:339-355. [PMID: 35528987 PMCID: PMC9039716 DOI: 10.14218/jcth.2021.00268] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/24/2021] [Accepted: 10/08/2021] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, type 2 diabetes mellitus and obesity. It is considered a multisystem disease and there is a strong association with cardiovascular disease and arterial hypertension, which interfere with changes in the coagulation system. Coagulation disorders are common in patients with hepatic impairment and are dependent on the degree of liver damage. Through a review of the literature, we consider and discuss possible disorders in the coagulation cascade and fibrinolysis, endothelial dysfunction and platelet abnormalities in patients with NAFLD.
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Affiliation(s)
- Doris Ogresta
- Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
- Department of Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Maja Cigrovski Berkovic
- Department for Endocrinology, Diabetes and Pharmacology, University Hospital Dubrava, Zagreb, Croatia
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb
- Department of Pharmacology, Faculty of Medicine, University of JJ Strossmayer, Osijek, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of JJ Strossmayer, Osijek, Croatia
- Department of Diabetes, Endocrinology and Metabolism Disorders, University Hospital Osijek, Osijek, Croatia
| | | | - Lucija Virovic-Jukic
- Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
- Department of Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
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Tsai HY, Shih YY, Yeh YT, Huang CH, Liao CA, Hu CY, Nagabhushanam K, Ho CT, Chen YK. Pterostilbene and Its Derivative 3'-Hydroxypterostilbene Ameliorated Nonalcoholic Fatty Liver Disease Through Synergistic Modulation of the Gut Microbiota and SIRT1/AMPK Signaling Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:4966-4980. [PMID: 35416649 DOI: 10.1021/acs.jafc.2c00641] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a recent chronic liver disease common in many developed countries and is closely associated with metabolic syndrome, such as obesity and insulin resistance. The present study was performed to investigate the effects of pterostilbene (Pt) and its derivative 3'-hydroxypterostilbene (OHPt) on free fatty acids (FFA)-induced lipid accumulation in HepG2 cells and high-fat diet (HFD)-induced NAFLD in C57BL/6J mice. The results showed that Pt and OHPt significantly ameliorated FFA-induced steatosis in HepG2 cells and enhanced lipolysis through the upregulation of SIRT1/AMPK and insulin signaling pathways. In the in vivo study, Pt and OHPt treatment resulted in reduced hepatic lipid droplets accumulation. The data showed that Pt and OHPt upregulated the SIRT1/AMPK pathway and subsequently downregulated the protein expression of SREBP-1 to activate fatty acid (FA) β-oxidation to inhibit FA synthesis. Pt and OHPt administration activated the insulin signaling pathway and further ameliorated the insulin resistance and liver function in the HFD-fed mice. Furthermore, Pt and OHPt markedly increased the numbers of Oscillospira and decreased the numbers of Allobaculum, Phascolarctobacterium, and Staphylococcus compared with those in the HFD group. These robust results indicate that Pt and OHPt are able to possess potential health benefits in improving insulin resistance and hepatic steatosis by promoting healthy populations or abundances of considered vital microbiota. Besides, OHPt is more effective than Pt, which might have promising chemotherapeutic effects for future clinical application.
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Affiliation(s)
- Hui-Yun Tsai
- Department of Nutrition and Health Science, Fooyin University, Kaohsiung 83102, Taiwan
- Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan
| | - Yu-Yuan Shih
- Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
| | - Yao-Tsung Yeh
- Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan
- Biomedical Analysis Center, Fooyin University Hospital, Pingtung 92849, Taiwan
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan
| | - Cheng-Hsieh Huang
- Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan
- Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chorng-An Liao
- Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan
- Biomedical Analysis Center, Fooyin University Hospital, Pingtung 92849, Taiwan
| | - Chun-Yi Hu
- Department of Food Science and Nutrition, Meiho University, Pingtung 912009, Taiwan
| | | | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, United States
| | - Yu-Kuo Chen
- Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
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46
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Peng HL, Liu LN, Liu DL, Tan YY. Depression and non-alcoholic fatty liver disease: Association and potential mechanisms. Shijie Huaren Xiaohua Zazhi 2022; 30:295-302. [DOI: 10.11569/wcjd.v30.i7.295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Hai-Ling Peng
- Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China,Research Center of Digestive Diseases, Central South University, Changsha 410011, Hunan Province, China
| | - Li-Ni Liu
- Department of Psychosomatic Medicine, Hunan Brain Hospital, Changsha 410011, Hunan Province, China
| | - De-Liang Liu
- Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China,Research Center of Digestive Diseases, Central South University, Changsha 410011, Hunan Province, China
| | - Yu-Yong Tan
- Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China,Research Center of Digestive Diseases, Central South University, Changsha 410011, Hunan Province, China
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Michels N, Zouiouich S, Vanderbauwhede B, Vanacker J, Indave Ruiz BI, Huybrechts I. Human microbiome and metabolic health: An overview of systematic reviews. Obes Rev 2022; 23:e13409. [PMID: 34978141 DOI: 10.1111/obr.13409] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 10/05/2021] [Accepted: 11/28/2021] [Indexed: 12/16/2022]
Abstract
To summarize the microbiome's role in metabolic disorders (insulin resistance, hyperglycemia, type 2 diabetes, obesity, hyperlipidemia, hypertension, nonalcoholic fatty liver disease [NAFLD], and metabolic syndrome), systematic reviews on observational or interventional studies (prebiotics/probiotics/synbiotics/transplant) were searched in MEDLINE and Embase until September 2020. The 87 selected systematic reviews included 57 meta-analyses. Methodological quality (AMSTAR2) was moderate in 62%, 12% low, and 26% critically low. Observational studies on obesity (10 reviews) reported less gut bacterial diversity with higher Fusobacterium, Lactobacillus reuteri, Bacteroides fragilis, and Staphylococcus aureus, whereas lower Methanobrevibacter, Lactobacillus plantarum, Akkermansia muciniphila, and Bifidobacterium animalis compared with nonobese. For diabetes (n = 1), the same was found for Fusobacterium and A. muciniphila, whereas higher Ruminococcus and lower Faecalibacterium, Roseburia, Bacteroides vulgatus, and several Bifidobacterium spp. For NAFLD (n = 2), lower Firmicutes, Rikenellaceae, Ruminococcaceae, whereas higher Escherichia and Lactobacillus were detected. Discriminating bacteria overlapped between metabolic disorders, those with high abundance being often involved in inflammation, whereas those with low abundance being used as probiotics. Meta-analyses (n = 54) on interventional studies reported 522 associations: 54% was statistically significant with intermediate effect size and moderate between-study heterogeneity. Meta-evidence was highest for probiotics and lowest for fecal transplant. Future avenues include better methodological quality/comparability, testing functional differences, new intervention strategies, and considerating other body habitats and kingdoms.
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Affiliation(s)
- Nathalie Michels
- Department of Public Health and Primary Care, Ghent University, Ghent, Belgium
| | - Semi Zouiouich
- International Agency for Research on Cancer, Lyon, France
| | - Bert Vanderbauwhede
- Department of Public Health and Primary Care, Ghent University, Ghent, Belgium
| | - Judith Vanacker
- Department of Public Health and Primary Care, Ghent University, Ghent, Belgium
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Wang T, Ishikawa T, Sasaki M, Chiba T. Oral and Gut Microbial Dysbiosis and Non-alcoholic Fatty Liver Disease: The Central Role of Porphyromonas gingivalis. Front Med (Lausanne) 2022; 9:822190. [PMID: 35308549 PMCID: PMC8924514 DOI: 10.3389/fmed.2022.822190] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/19/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota play many important roles, such as the regulation of immunity and barrier function in the intestine, and are crucial for maintaining homeostasis in living organisms. The disruption in microbiota is called dysbiosis, which has been associated with various chronic inflammatory conditions, food allergies, colorectal cancer, etc. The gut microbiota is also affected by several other factors such as diet, antibiotics and other medications, or bacterial and viral infections. Moreover, there are some reports on the oral-gut-liver axis indicating that the disruption of oral microbiota affects the intestinal biota. Non-alcoholic fatty liver disease (NAFLD) is one of the systemic diseases caused due to the dysregulation of the oral-gut-liver axis. NAFLD is the most common liver disease reported in the developed countries. It includes liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. Recently, accumulating evidence supports an association between NAFLD and dysbiosis of oral and gut microbiota. Periodontopathic bacteria, especially Porphyromonas gingivalis, have been correlated with the pathogenesis and development of NAFLD based on the clinical and basic research, and immunology. P. gingivalis was detected in the liver, and lipopolysaccharide from this bacteria has been shown to be involved in the progression of NAFLD, thereby indicating a direct role of P. gingivalis in NAFLD. Moreover, P. gingivalis induces dysbiosis of gut microbiota, which promotes the progression of NAFLD, through disrupting both metabolic and immunologic pathways. Here, we review the roles of microbial dysbiosis in NAFLD. Focusing on P. gingivalis, we evaluate and summarize the most recent advances in our understanding of the relationship between oral-gut microbiome symbiosis and the pathogenesis and progression of non-alcoholic fatty liver disease, as well as discuss novel strategies targeting both P. gingivalis and microbial dysbiosis.
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Affiliation(s)
- Ting Wang
- Division of Internal Medicine, Department of Oral Medicine, Iwate Medical University, Morioka, Japan
| | - Taichi Ishikawa
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Morioka, Japan
| | - Minoru Sasaki
- Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, Morioka, Japan
| | - Toshimi Chiba
- Division of Internal Medicine, Department of Oral Medicine, Iwate Medical University, Morioka, Japan
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Valentini F, Rocchi G, Vespasiani-Gentilucci U, Guarino MPL, Altomare A, Carotti S. The Origins of NAFLD: The Potential Implication of Intrauterine Life and Early Postnatal Period. Cells 2022; 11:562. [PMID: 35159371 PMCID: PMC8834011 DOI: 10.3390/cells11030562] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 01/30/2022] [Accepted: 02/02/2022] [Indexed: 02/04/2023] Open
Abstract
Fetal life and the first few months after birth represent a plastic age, defined as a "window of opportunity", as the organism is particularly susceptible to environmental pressures and has to adapt to environmental conditions. Several perturbations in pregnancy, such as excessive weight gain, obesity, gestational diabetes mellitus and an inadequate or high-fat diet, have been associated with long-term metabolic consequences in offspring, even without affecting birth weight. Moreover, great interest has also been focused on the relationship between the gut microbiome of early infants and health status in later life. Consistently, in various epidemiological studies, a condition of dysbiosis has been associated with an increased inflammatory response and metabolic alterations in the host, with important consequences on the intestinal and systemic health of the unborn child. This review aims to summarize the current knowledge on the origins of NAFLD, with particular attention to the potential implications of intrauterine life and the early postnatal period. Due to the well-known association between gut microbiota and the risk of NAFLD, a specific focus will be devoted to factors affecting early microbiota formation/composition.
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Affiliation(s)
- Francesco Valentini
- Pediatric Unit, Sant’Andrea Hospital, Faculty of Medicine and Psychology, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy;
| | - Giulia Rocchi
- Unit of Food Science and Human Nutrition, Campus Biomedico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Umberto Vespasiani-Gentilucci
- Unit of Internal Medicine and Hepatology, Fondazione Policlinico Campus Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Michele Pier Luca Guarino
- Gastroenterology Unit, Fondazione Policlinico Campus Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Annamaria Altomare
- Gastroenterology Unit, Fondazione Policlinico Campus Biomedico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Simone Carotti
- Unit of Microscopic and Ultrastructural Anatomy, Campus Biomedico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
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50
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Gut Microbiome and Organ Fibrosis. Nutrients 2022; 14:nu14020352. [PMID: 35057530 PMCID: PMC8781069 DOI: 10.3390/nu14020352] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/07/2022] [Accepted: 01/08/2022] [Indexed: 02/07/2023] Open
Abstract
Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.
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