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Rukavina Mikusic NL, Prince PD, Choi MR, Chuffa LGA, Simão VA, Castro C, Manucha W, Quesada I. Microbiota, mitochondria, and epigenetics in health and disease: converging pathways to solve the puzzle. Pflugers Arch 2025; 477:635-655. [PMID: 40111427 DOI: 10.1007/s00424-025-03072-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 02/23/2025] [Accepted: 02/25/2025] [Indexed: 03/22/2025]
Abstract
Dysbiosis, which refers to an imbalance in the composition of the gut microbiome, has been associated with a range of metabolic disorders, including type 2 diabetes, obesity, and metabolic syndrome. Although the exact mechanisms connecting gut dysbiosis to these conditions are not fully understood, various lines of evidence strongly suggest a substantial role for the interaction between the gut microbiome, mitochondria, and epigenetics. Current studies suggest that the gut microbiome has the potential to affect mitochondrial function and biogenesis through the production of metabolites. A well-balanced microbiota plays a pivotal role in supporting normal mitochondrial and cellular functions by providing metabolites that are essential for mitochondrial bioenergetics and signaling pathways. Conversely, in the context of illnesses, an unbalanced microbiota can impact mitochondrial function, leading to increased aerobic glycolysis, reduced oxidative phosphorylation and fatty acid oxidation, alterations in mitochondrial membrane permeability, and heightened resistance to cellular apoptosis. Mitochondrial activity can also influence the composition and function of the gut microbiota. Because of the intricate interplay between nuclear and mitochondrial communication, the nuclear epigenome can regulate mitochondrial function, and conversely, mitochondria can produce metabolic signals that initiate epigenetic changes within the nucleus. Given the epigenetic modifications triggered by metabolic signals from mitochondria in response to stress or damage, targeting an imbalanced microbiota through interventions could offer a promising strategy to alleviate the epigenetic alterations arising from disrupted mitochondrial signaling.
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Affiliation(s)
- Natalia Lucia Rukavina Mikusic
- Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET) CONICET, Universidad de Buenos Aires, 1122, Buenos Aires, Argentina
- Departamento de Ciencias Biológicas, Cátedra de Anatomía E Histología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113, Buenos Aires, Argentina
| | - Paula Denise Prince
- Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET) CONICET, Universidad de Buenos Aires, 1122, Buenos Aires, Argentina
- Departamento de Ciencias Químicas, Cátedra de Fisicoquímica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113, Buenos Aires, Argentina
| | - Marcelo Roberto Choi
- Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET) CONICET, Universidad de Buenos Aires, 1122, Buenos Aires, Argentina.
- Departamento de Ciencias Biológicas, Cátedra de Anatomía E Histología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113, Buenos Aires, Argentina.
| | - Luiz Gustavo A Chuffa
- Department of Structural and Functional Biology, Institute of Biosciences, UNESP - São Paulo State University, P.O. Box 18618-689, Botucatu, São Paulo, Zip Code 510, Brazil
| | - Vinícius Augusto Simão
- Department of Structural and Functional Biology, Institute of Biosciences, UNESP - São Paulo State University, P.O. Box 18618-689, Botucatu, São Paulo, Zip Code 510, Brazil
| | - Claudia Castro
- Instituto de Medicina y Biología Experimental de Cuyo (IMBECU) CONICET-Universidad Nacional de Cuyo, Mendoza, Argentina
| | - Walter Manucha
- Instituto de Medicina y Biología Experimental de Cuyo (IMBECU) CONICET-Universidad Nacional de Cuyo, Mendoza, Argentina.
- Laboratorio de Farmacología Básica y Traslacional, Área de Farmacología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, 5500, Mendoza, Argentina.
| | - Isabel Quesada
- Instituto de Medicina y Biología Experimental de Cuyo (IMBECU) CONICET-Universidad Nacional de Cuyo, Mendoza, Argentina.
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Sahebi K, Arianejad M, Azadi S, Hosseinpour-Soleimani F, Kazemi R, Tajbakhsh A, Negahdaripour M. The Interplay between Gut Microbiome, Epigenetics, and Substance Use Disorders: from Molecular to Clinical Perspectives. Eur J Pharmacol 2025:177630. [PMID: 40252900 DOI: 10.1016/j.ejphar.2025.177630] [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: 12/26/2024] [Revised: 03/27/2025] [Accepted: 04/15/2025] [Indexed: 04/21/2025]
Abstract
Substance use disorders (SUDs) involve a complex series of central and peripheral pathologies, leading to impairments in cognitive, behavioral, and physiological processes. Emerging evidence indicates a more significant role for the microbiome-gut-brain axis (MGBA) in SUDs than previously recognized. The MGBA is interconnected with various body systems by producing numerous metabolites, most importantly short-chain fatty acids (SCFAs), cytokines, and neurotransmitters. These mediators influence the human body's epigenome and transcriptome. While numerous epigenetic alterations in different brain regions have been reported in SUD models, the intricate relationship between SUDs and the MGBA suggests that the gut microbiome may partially contribute to the underlying mechanisms of SUDs. Promising results have been observed with gut microbiome-directed interventions in patients with SUDs, including prebiotics, probiotics, antibiotics, and fecal transplantation. Nonetheless, the long-term epigenetic effects of these interventions remain unexplored. Moreover, various confounding factors and study limitations have hindered the identification of molecular mechanisms and clinical applications of gut microbiome interventions in SUDs. In the present review, we will (i) provide a comprehensive discussion on how the gut microbiome influences SUDs, with an emphasis on epigenetic alterations; (ii) discuss the current evidence on the bidirectional relationship of gut microbiome and SUDs, highlighting potential targets for intervention; and (iii) review recent advances in gut microbiome-directed therapies, along with their limitations and future directions.
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Affiliation(s)
- Keivan Sahebi
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mona Arianejad
- Department of Molecular Medicine, School of Advanced Technologies of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Soha Azadi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Hosseinpour-Soleimani
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Applied Cell Sciences and Tissue Engineering, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Radmehr Kazemi
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Manica Negahdaripour
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
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Xu Y, Huang Y, Wei S, Tian J, Huang Y, Nie Q, Zhang D. Changes in gut microbiota affect DNA methylation levels and development of chicken muscle tissue. Poult Sci 2025; 104:104869. [PMID: 39952142 PMCID: PMC11874558 DOI: 10.1016/j.psj.2025.104869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/17/2025] [Accepted: 01/30/2025] [Indexed: 02/17/2025] Open
Abstract
The intestinal microbiome is essential in regulating host muscle growth and development. Antibiotic treatment is commonly used to model dysbiosis of the intestinal microbiota, yet limited research addresses the relationship between gut microbes and muscle growth in yellow-feathered broilers. In this study, Xinghua chickens were administered broad-spectrum antibiotics for eight weeks to induce gut microbiome suppression. We investigated the relationships between the gut microbiome and muscle growth using 16S rRNA sequencing and transcriptomic analysis. Results indicated that antibiotic treatment significantly reduced body weight, dressed weight, eviscerated weight, and breast and leg muscle weight. Microbial diversity and richness in the duodenum, jejunum, ileum, and cecum were significantly decreased. The relative abundances of Firmicutes, Actinobacteria, and Bacteroidetes declined, while Proteobacteria increased. This microbial imbalance led to 298 differentially expressed genes (DEGs) in muscle tissue, of which 67 down-regulated genes were enriched in skeletal muscle development, including MYF6, MYBPC1 and METTL21C genes essential for muscle development. The DEGs were primarily involved in the MAPK signaling pathway, calcium signaling pathway, ECM-receptor interaction, actin cytoskeleton regulation, and nitrogen metabolism. Correlation analysis showed that dysregulation of the cecal microbiome had the most substantial effect on muscle growth and development. Furthermore, intestinal microbiome dysregulation reduced DNMT3b and METTL21C mRNA expression in muscle tissue, lowered overall DNA methylation and SAM levels, and induced methylation changes that impacted skeletal muscle development. This study demonstrates that gut microbiota influence DNA methylation in muscle tissue, thereby associated with muscle growth and development.
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Affiliation(s)
- Yibin Xu
- State Key Laboratory of· Livestock· and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, & Guangzhou Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, PR China
| | - Yunpeng Huang
- State Key Laboratory of· Livestock· and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, & Guangzhou Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, PR China
| | - Shenghua Wei
- State Key Laboratory of· Livestock· and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, & Guangzhou Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, PR China
| | - Jinghong Tian
- State Key Laboratory of· Livestock· and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, & Guangzhou Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, PR China
| | - Yulin Huang
- Wens Foodstuff Group Co. Ltd., Yunfu 527400, PR China
| | - Qinghua Nie
- State Key Laboratory of· Livestock· and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, & Guangzhou Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, PR China
| | - Dexiang Zhang
- State Key Laboratory of· Livestock· and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, South China Agricultural University, & Guangzhou Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou 510642, PR China; Wens Foodstuff Group Co. Ltd., Yunfu 527400, PR China.
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Tain YL, Lin YJ, Hsu CN. Animal Models for Studying Developmental Origins of Cardiovascular-Kidney-Metabolic Syndrome. Biomedicines 2025; 13:452. [PMID: 40002865 PMCID: PMC11853432 DOI: 10.3390/biomedicines13020452] [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: 01/24/2025] [Revised: 02/07/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
Cardiovascular-kidney-metabolic syndrome (CKMS) has become a significant global health challenge. Since CKMS often originates early in life, as outlined by the developmental origins of health and disease (DOHaD) concept, prevention is a more effective strategy than treatment. Various animal models, classified by environmental exposures or mechanisms, are used to explore the developmental origins of CKMS. However, no single model can fully replicate all aspects of CKMS or its clinical stages, limiting the advancement of preventive and therapeutic strategies. This review aims to assist researchers by comparing the strengths and limitations of common animal models used in CKMS programming studies and highlighting key considerations for selecting suitable models.
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Affiliation(s)
- You-Lin Tain
- Division of Pediatric Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan
| | - Ying-Jui Lin
- Division of Critical Care, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan;
- Division of Cardiology, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Department of Early Childhood Care and Education, Cheng Shiu University, Kaohsiung 833, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Depatrtment of Pharmacy, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan
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Gopal RK, Ganesh PS, Pathoor NN. Synergistic Interplay of Diet, Gut Microbiota, and Insulin Resistance: Unraveling the Molecular Nexus. Mol Nutr Food Res 2024; 68:e2400677. [PMID: 39548908 DOI: 10.1002/mnfr.202400677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/04/2024] [Indexed: 11/18/2024]
Abstract
This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet-induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet-induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short-chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome-based therapeutic strategies, it also investigates the effects of dietary components-fiber, polyphenols, and lipids-on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota-insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high-fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high-fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.
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Affiliation(s)
- Rajesh Kanna Gopal
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, Tamil Nadu, 600077, India
| | - Pitchaipillai Sankar Ganesh
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, Tamil Nadu, 600077, India
| | - Naji Naseef Pathoor
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, Tamil Nadu, 600077, India
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Enache RM, Profir M, Roşu OA, Creţoiu SM, Gaspar BS. The Role of Gut Microbiota in the Onset and Progression of Obesity and Associated Comorbidities. Int J Mol Sci 2024; 25:12321. [PMID: 39596385 PMCID: PMC11595101 DOI: 10.3390/ijms252212321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 11/06/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
Obesity, a global public health problem, is constantly increasing, so the concerns in preventing and combating it are increasingly focused on the intestinal microbiota. It was found that the microbiota is different in lean people compared to obese individuals, but the exact mechanisms by which energy homeostasis is influenced are still incompletely known. Numerous studies show the involvement of certain bacterial species in promoting obesity and associated diseases such as diabetes, hypertension, cancer, etc. Our aim is to summarize the main findings regarding the influence of several factors such as lifestyle changes, including diet and bariatric surgery, on the diversity of the gut microbiota in obese individuals. The second purpose of this paper is to investigate the potential effect of various microbiota modulation techniques on ameliorating obesity and its comorbidities. A literature search was conducted using the PubMed database, identifying articles published between 2019 and 2024. Most studies identified suggest that obesity is generally associated with alterations of the gut microbiome such as decreased microbial diversity, an increased Firmicutes-to-Bacteroidetes ratio, and increased SCFAs levels. Our findings also indicate that gut microbiota modulation techniques could represent a novel strategy in treating obesity and related metabolic diseases. Although some mechanisms (e.g., inflammation or hormonal regulation) are already considered a powerful connection between gut microbiota and obesity development, further research is needed to enhance the knowledge on this particular topic.
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Affiliation(s)
- Robert-Mihai Enache
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Monica Profir
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.P.); (O.A.R.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Oana Alexandra Roşu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.P.); (O.A.R.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Sanda Maria Creţoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.P.); (O.A.R.)
| | - Bogdan Severus Gaspar
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Surgery Clinic, Bucharest Emergency Clinical Hospital, 014461 Bucharest, Romania
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Hridayanka KSN, Duttaroy AK, Basak S. Bioactive Compounds and Their Chondroprotective Effects for Osteoarthritis Amelioration: A Focus on Nanotherapeutic Strategies, Epigenetic Modifications, and Gut Microbiota. Nutrients 2024; 16:3587. [PMID: 39519419 PMCID: PMC11547880 DOI: 10.3390/nu16213587] [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: 09/24/2024] [Revised: 10/20/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
In degenerative joint disease like osteoarthritis (OA), bioactive compounds like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin by executing epigenetic-modifying activities. Epigenetic modulation can target genes of disease pathophysiology via histone modification, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved in OA but have been less explored. OA patients often seek options that can improve the quality of their life in addition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bioactive and natural compounds exhibit therapeutic potential against OA, several disadvantages loom, like insolubility and poor bioavailability. Nanoformulated bioactive compounds promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive compounds as epigenetic and gut modulators in ameliorating OA. Moreover, it is not known whether the effects of polyphenolic bioactive compounds on gut microbial response are mediated by epigenetic modulatory activities in OA. This narrative review highlights the nanotherapeutic strategies utilizing bioactive compounds, reporting their effects on chondrocyte growth, metabolism, and epigenetic modifications in osteoarthritis amelioration.
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Affiliation(s)
- Kota Sri Naga Hridayanka
- Molecular Biology Division, National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500007, India;
| | - Asim K. Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway;
| | - Sanjay Basak
- Molecular Biology Division, National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500007, India;
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Chen W, Zou H, Xu H, Cao R, Zhang H, Zhang Y, Zhao J. The potential influence and intervention measures of gut microbiota on sperm: it is time to focus on testis-gut microbiota axis. Front Microbiol 2024; 15:1478082. [PMID: 39439945 PMCID: PMC11493703 DOI: 10.3389/fmicb.2024.1478082] [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: 08/09/2024] [Accepted: 09/23/2024] [Indexed: 10/25/2024] Open
Abstract
As the global male infertility rate continues to rise, there is an urgent imperative to investigate the underlying causes of sustained deterioration in sperm quality. The gut microbiota emerges as a pivotal factor in host health regulation, with mounting evidence highlighting its dual influence on semen. This review underscores the interplay between the Testis-Gut microbiota axis and its consequential effects on sperm. Potential mechanisms driving the dual impact of gut microbiota on sperm encompass immune modulation, inflammatory responses mediated by endotoxins, oxidative stress, antioxidant defenses, gut microbiota-derived metabolites, epigenetic modifications, regulatory sex hormone signaling. Interventions such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and Traditional natural herbal extracts are hypothesized to rectify dysbiosis, offering avenues to modulate gut microbiota and enhance Spermatogenesis and motility. Future investigations should delve into elucidating the mechanisms and foundational principles governing the interaction between gut microbiota and sperm within the Testis-Gut microbiota Axis. Understanding and modulating the Testis-Gut microbiota Axis may yield novel therapeutic strategies to enhance male fertility and combat the global decline in sperm quality.
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Affiliation(s)
- Wenkang Chen
- Graduate School of China Academy of Chinese Medical Sciences, Beijing, China
| | - Hede Zou
- Graduate School of China Academy of Chinese Medical Sciences, Beijing, China
| | - Haoran Xu
- Graduate School of Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Rui Cao
- Graduate School of Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Hekun Zhang
- Graduate School of Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Yapeng Zhang
- Graduate School of China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiayou Zhao
- Graduate School of China Academy of Chinese Medical Sciences, Beijing, China
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Wang M, Zhang Z, Liu Y, Jian E, Ye P, Jiang H, Yu X, Cai P. Research trends between childhood obesity and gut microbiota: a bibliometric analysis (2002-2023). Front Microbiol 2024; 15:1461306. [PMID: 39397792 PMCID: PMC11466780 DOI: 10.3389/fmicb.2024.1461306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/17/2024] [Indexed: 10/15/2024] Open
Abstract
Background In recent years, the prevalence of childhood obesity has escalated alarmingly, posing significant threats to the physical and mental well-being of children, with an elevated likelihood of persisting into adulthood. Notably, recent investigations have uncovered a profound association between intestinal microbiota, a crucial component of the internal milieu, and childhood obesity. Disturbances in intestinal microbiota and their by-products are now understood to be profoundly intertwined with the evolutionary pathway of childhood obesity. Bibliometric analysis offers a deep understanding of the current research landscape, so we apply it to a review of the emerging trends and patterns between childhood obesity and gut microbiota. Materials and methods We conducted a rigorous and extensive search of the Web of Science (WoS) Core Collection database, spanning the years from 1900 to 2023, to analyze scholarly articles pertaining to childhood obesity and gut microbiota. Utilizing VOSviewer, CiteSpace, the R package "bibliometrix," and the online bibliometric analysis platform (https://bibliometric.com/), we delved into the intricate details of research hotspots, academic collaborations, and emerging trends within this domain. Results The exhaustive search encompassed the globe, uncovering a cumulative total of 1,384 pertinent studies originating from 429 nations. The results were compelling, revealing a profound influence exerted by the United States and China in this specific field of research. Furthermore, it was observed that the volume of scholarly works pertaining to childhood obesity and gut microbiota is steadily growing year on year. The current hot topics in this field include "abuse," "maltreatment," "adverse childhood experiences," "students," and "food addiction". Conclusion This comprehensive review offers a meticulous exploration of the evolving trends and emerging research agendas pertaining to childhood obesity and gut microbiota over the past two decades. It strives to equip researchers with a thorough understanding of the key nations, institutions, journals, and potential collaborators in these specialized fields. Additionally, it sheds light on the current frontiers of research and strategic avenues for further exploration, thus serving as an invaluable resource for scholars delving deeper into the intricacies of childhood obesity and the gut microbiome.
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Affiliation(s)
- Mengping Wang
- School of Preclinical Medicine, Chengdu University, Chengdu, China
| | - Zhen Zhang
- School of Preclinical Medicine, Chengdu University, Chengdu, China
| | - Yuxuan Liu
- Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, China
| | - Enlin Jian
- Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu, China
| | - Peng Ye
- School of Preclinical Medicine, Chengdu University, Chengdu, China
| | - Hongjie Jiang
- School of Preclinical Medicine, Chengdu University, Chengdu, China
| | - Xiaoping Yu
- School of Preclinical Medicine, Chengdu University, Chengdu, China
| | - Peiling Cai
- School of Preclinical Medicine, Chengdu University, Chengdu, China
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Tain YL, Hsu CN. Maternal Polyphenols and Offspring Cardiovascular-Kidney-Metabolic Health. Nutrients 2024; 16:3168. [PMID: 39339768 PMCID: PMC11434705 DOI: 10.3390/nu16183168] [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: 08/19/2024] [Revised: 09/12/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND The convergence of cardiovascular, kidney, and metabolic disorders at the pathophysiological level has led to the recognition of cardiovascular-kidney-metabolic (CKM) syndrome, which represents a significant global health challenge. Polyphenols, a group of phytochemicals, have demonstrated potential health-promoting effects. METHODS This review highlights the impact of maternal polyphenol supplementation on the CKM health of offspring. RESULTS Initially, we summarize the interconnections between polyphenols and each aspect of CKM syndrome. We then discuss in vivo studies that have investigated the use of polyphenols during pregnancy and breastfeeding, focusing on their role in preventing CKM syndrome in offspring. Additionally, we explore the common mechanisms underlying the protective effects of maternal polyphenol supplementation. CONCLUSIONS Overall, this review underscores the potential of early-life polyphenol interventions in safeguarding against CKM syndrome in offspring. It emphasizes the importance of continued research to advance our understanding and facilitate the clinical translation of these interventions.
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Affiliation(s)
- You-Lin Tain
- Division of Pediatric Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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Ren Y, Huang P, Zhang L, Tang YF, Luo SL, She Z, Peng H, Chen YQ, Luo JW, Duan WX, Liu LJ, Liu LQ. Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora. Biomedicines 2024; 12:1633. [PMID: 39200098 PMCID: PMC11351752 DOI: 10.3390/biomedicines12081633] [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: 06/12/2024] [Revised: 07/15/2024] [Accepted: 07/18/2024] [Indexed: 09/01/2024] Open
Abstract
Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. Epigenetics, which involves the regulation of host gene expression without changing the nucleotide sequence, provides an exact direction for us to understand how the environment, lifestyle factors, and other risk factors contribute to obesity. DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. In this review, we examined recent advancements in research, focusing on the involvement of intestinal microbiota and DNA methylation in the etiology and progression of obesity, as well as potential interactions between the two factors, providing novel perspectives and avenues for further elucidating the pathogenesis, prevention, and treatment of obesity.
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Affiliation(s)
- Yi Ren
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
- Department of Pediatrics, Haikou Hospital of the Maternal and Child Health, Haikou 570100, China
- Department of Children’s Healthcare, Hainan Modern Women and Children’s Medical, Haikou 570100, China
| | - Peng Huang
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Lu Zhang
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Yu-Fen Tang
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Sen-Lin Luo
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Zhou She
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Hong Peng
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Yu-Qiong Chen
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Jin-Wen Luo
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Wang-Xin Duan
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Ling-Juan Liu
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Li-Qun Liu
- Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.R.); (P.H.); (L.Z.); (Y.-F.T.); (S.-L.L.); (Z.S.); (H.P.); (Y.-Q.C.); (J.-W.L.); (W.-X.D.); (L.-J.L.)
- Children’s Brain Development and Brain Injury Research Office, The Second Xiangya Hospital of Central South University, Changsha 410011, China
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12
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Kim B, Song A, Son A, Shin Y. Gut microbiota and epigenetic choreography: Implications for human health: A review. Medicine (Baltimore) 2024; 103:e39051. [PMID: 39029010 PMCID: PMC11398772 DOI: 10.1097/md.0000000000039051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/21/2024] Open
Abstract
The interwoven relationship between gut microbiota and the epigenetic landscape constitutes a pivotal axis in understanding human health and disease. Governed by a myriad of dietary, genetic, and environmental influences, the gut microbiota orchestrates a sophisticated metabolic interplay, shaping nutrient utilization, immune responses, and defenses against pathogens. Recent strides in genomics and metabolomics have shed light on the intricate connections between these microbial influencers and the host's physiological dynamics, presenting a dynamic panorama across diverse disease spectra. DNA methylation and histone modifications, as key players in epigenetics, intricately align with the dynamic orchestration of the gut microbiota. This seamless collaboration, notably evident in conditions like inflammatory bowel disease and obesity, has captured the attention of researchers, prompting an exploration of its nuanced choreography. Nevertheless, challenges abound. Analyzing data is intricate due to the multifaceted nature of the gut microbiota and the limitations of current analytical methods. This underscores the need for a multidisciplinary approach, where diverse disciplines converge to pave innovative research pathways. The integration of insights from microbiome and epigenome studies assumes paramount importance in unraveling the complexities of this intricate partnership. Deciphering the synchronized interactions within this collaboration offers a deeper understanding of these delicate interplays, potentially heralding revolutionary strides in treatment modalities and strategies for enhancing public health.
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Affiliation(s)
- Bailee Kim
- Crescenta Valley High School, La Crescenta, CA
| | - Angel Song
- Harvard-Westlake School, Studio City, CA
| | - Andrew Son
- Bellarmine College Preparatory, San Jose, CA
| | - Yonghwan Shin
- Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
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13
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Lin X, Han H, Wang N, Wang C, Qi M, Wang J, Liu G. The Gut Microbial Regulation of Epigenetic Modification from a Metabolic Perspective. Int J Mol Sci 2024; 25:7175. [PMID: 39000282 PMCID: PMC11241073 DOI: 10.3390/ijms25137175] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
Obesity is a global health challenge that has received increasing attention in contemporary research. The gut microbiota has been implicated in the development of obesity, primarily through its involvement in regulating various host metabolic processes. Recent research suggests that epigenetic modifications may serve as crucial pathways through which the gut microbiota and its metabolites contribute to the pathogenesis of obesity and other metabolic disorders. Hence, understanding the interplay between gut microbiota and epigenetic mechanisms is crucial for elucidating the impact of obesity on the host. This review primarily focuses on the understanding of the relationship between the gut microbiota and its metabolites with epigenetic mechanisms in several obesity-related pathogenic mechanisms, including energy dysregulation, metabolic inflammation, and maternal inheritance. These findings could serve as novel therapeutic targets for probiotics, prebiotics, and fecal microbiota transplantation tools in treating metabolic disruptions. It may also aid in developing therapeutic strategies that modulate the gut microbiota, thereby regulating the metabolic characteristics of obesity.
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Affiliation(s)
- Xingtong Lin
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (X.L.); (H.H.); (N.W.); (C.W.); (M.Q.)
- Yuelushan Laboratory, Changsha 410128, China
| | - Hui Han
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (X.L.); (H.H.); (N.W.); (C.W.); (M.Q.)
- Yuelushan Laboratory, Changsha 410128, China
| | - Nan Wang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (X.L.); (H.H.); (N.W.); (C.W.); (M.Q.)
- Yuelushan Laboratory, Changsha 410128, China
| | - Chengming Wang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (X.L.); (H.H.); (N.W.); (C.W.); (M.Q.)
- Yuelushan Laboratory, Changsha 410128, China
| | - Ming Qi
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (X.L.); (H.H.); (N.W.); (C.W.); (M.Q.)
- Yuelushan Laboratory, Changsha 410128, China
| | - Jing Wang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (X.L.); (H.H.); (N.W.); (C.W.); (M.Q.)
- Yuelushan Laboratory, Changsha 410128, China
| | - Gang Liu
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China; (X.L.); (H.H.); (N.W.); (C.W.); (M.Q.)
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
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Faienza MF, Urbano F, Anaclerio F, Moscogiuri LA, Konstantinidou F, Stuppia L, Gatta V. Exploring Maternal Diet-Epigenetic-Gut Microbiome Crosstalk as an Intervention Strategy to Counter Early Obesity Programming. Curr Issues Mol Biol 2024; 46:4358-4378. [PMID: 38785533 PMCID: PMC11119222 DOI: 10.3390/cimb46050265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/21/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024] Open
Abstract
Alterations in a mother's metabolism and endocrine system, due to unbalanced nutrition, may increase the risk of both metabolic and non-metabolic disorders in the offspring's childhood and adulthood. The risk of obesity in the offspring can be determined by the interplay between maternal nutrition and lifestyle, intrauterine environment, epigenetic modifications, and early postnatal factors. Several studies have indicated that the fetal bowel begins to colonize before birth and that, during birth and nursing, the gut microbiota continues to change. The mother's gut microbiota is primarily transferred to the fetus through maternal nutrition and the environment. In this way, it is able to impact the establishment of the early fetal and neonatal microbiome, resulting in epigenetic signatures that can possibly predispose the offspring to the development of obesity in later life. However, antioxidants and exercise in the mother have been shown to improve the offspring's metabolism, with improvements in leptin, triglycerides, adiponectin, and insulin resistance, as well as in the fetal birth weight through epigenetic mechanisms. Therefore, in this extensive literature review, we aimed to investigate the relationship between maternal diet, epigenetics, and gut microbiota in order to expand on current knowledge and identify novel potential preventative strategies for lowering the risk of obesity in children and adults.
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Affiliation(s)
- Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “A. Moro”, 70124 Bari, Italy
| | - Flavia Urbano
- Giovanni XXIII Pediatric Hospital, 70126 Bari, Italy; (F.U.); (L.A.M.)
| | - Federico Anaclerio
- Department of Psychological Health and Territorial Sciences, School of Medicine and Health Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; (F.A.); (F.K.); (L.S.); (V.G.)
- Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | | | - Fani Konstantinidou
- Department of Psychological Health and Territorial Sciences, School of Medicine and Health Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; (F.A.); (F.K.); (L.S.); (V.G.)
- Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Liborio Stuppia
- Department of Psychological Health and Territorial Sciences, School of Medicine and Health Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; (F.A.); (F.K.); (L.S.); (V.G.)
- Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Valentina Gatta
- Department of Psychological Health and Territorial Sciences, School of Medicine and Health Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; (F.A.); (F.K.); (L.S.); (V.G.)
- Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
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15
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Tain YL, Hsu CN. Interplay between maternal nutrition and epigenetic programming on offspring hypertension. J Nutr Biochem 2024; 127:109604. [PMID: 38373508 DOI: 10.1016/j.jnutbio.2024.109604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 01/19/2024] [Accepted: 02/15/2024] [Indexed: 02/21/2024]
Abstract
Recent human and animal studies have delineated hypertension can develop in the earliest stage of life. A lack or excess of particular nutrients in the maternal diet may impact the expression of genes associated with BP, leading to an increased risk of hypertension in adulthood. Modulations in gene expression could be caused by epigenetic mechanisms through aberrant DNA methylation, histone modification, and microRNAs (miRNAs). Several molecular mechanisms for the developmental programming of hypertension, including oxidative stress, dysregulated nutrient-sensing signal, aberrant renin-angiotensin system, and dysbiotic gut microbiota have been associated with epigenetic programming. Conversely, maternal nutritional interventions such as amino acids, melatonin, polyphenols, resveratrol or short chain fatty acids may work as epigenetic modifiers to trigger protective epigenetic modifications and prevent offspring hypertension. We present a current perspective of maternal malnutrition that can cause fetal programming and the potential of epigenetic mechanisms lead to offspring hypertension. We also discuss the opportunities of dietary nutrients or nutraceuticals as epigenetic modifiers to counteract those adverse programming actions for hypertension prevention. The extent to which aberrant epigenetic changes can be reprogrammed or reversed by maternal dietary interventions in order to prevent human hypertension remains to be established. Continued research is necessary to evaluate the interaction between maternal malnutrition and epigenetic programming, as well as a greater focus on nutritional interventions for hypertension prevention towards their use in clinical translation.
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Affiliation(s)
- You-Lin Tain
- Division of Pediatric Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Tang R, Liu R, Zha H, Cheng Y, Ling Z, Li L. Gut microbiota induced epigenetic modifications in the non-alcoholic fatty liver disease pathogenesis. Eng Life Sci 2024; 24:2300016. [PMID: 38708414 PMCID: PMC11065334 DOI: 10.1002/elsc.202300016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/29/2023] [Accepted: 05/22/2023] [Indexed: 05/07/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents a growing global health concern that can lead to liver disease and cancer. It is characterized by an excessive accumulation of fat in the liver, unrelated to excessive alcohol consumption. Studies indicate that the gut microbiota-host crosstalk may play a causal role in NAFLD pathogenesis, with epigenetic modification serving as a key mechanism for regulating this interaction. In this review, we explore how the interplay between gut microbiota and the host epigenome impacts the development of NAFLD. Specifically, we discuss how gut microbiota-derived factors, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), can modulate the DNA methylation and histone acetylation of genes associated with NAFLD, subsequently affecting lipid metabolism and immune homeostasis. Although the current literature suggests a link between gut microbiota and NAFLD development, our understanding of the molecular mechanisms and signaling pathways underlying this crosstalk remains limited. Therefore, more comprehensive epigenomic and multi-omic studies, including broader clinical and animal experiments, are needed to further explore the mechanisms linking the gut microbiota to NAFLD-associated genes. These studies are anticipated to improve microbial markers based on epigenetic strategies and provide novel insights into the pathogenesis of NAFLD, ultimately addressing a significant unmet clinical need.
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Affiliation(s)
- Ruiqi Tang
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
| | - Rongrong Liu
- Center of Pediatric Hematology‐oncologyPediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang ProvinceNational Clinical Research Center for Child HealthChildren's HospitalZhejiang University School of MedicineHangzhouChina
| | - Hua Zha
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
| | - Yiwen Cheng
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
| | - Zongxin Ling
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
- Jinan Microecological Biomedicine Shandong LaboratoryJinanChina
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
- Jinan Microecological Biomedicine Shandong LaboratoryJinanChina
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Liversidge BD, Gomez DE, Dodd SAS, MacNicol JL, Adolphe JL, Blois SL, Verbrugghe A. Comparison of the fecal microbiota of adult healthy dogs fed a plant-based (vegan) or an animal-based diet. Front Microbiol 2024; 15:1367493. [PMID: 38694809 PMCID: PMC11061427 DOI: 10.3389/fmicb.2024.1367493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 04/02/2024] [Indexed: 05/04/2024] Open
Abstract
Purpose Pet guardians are increasingly seeking vegan dog foods. However, research on the impact of these diets on gastrointestinal (GI) physiology and health is limited. In humans, vegan diets modify the GI microbiota, increasing beneficial digestive microorganisms. This study aimed to examine the canine fecal microbiota in response to a vegan diet compared to an animal-based diet. Methods Sixty-one client-owned healthy adult dogs completed a randomized, double-blinded longitudinal study. Dogs were randomly assigned into two groups that were fed either a commercial extruded animal-based diet (MEAT, n = 30) or an experimental extruded vegan diet (PLANT, n = 31) for 12 weeks. Fecal collections occurred at the start of the experimental period and after 3 months of exclusively feeding either diet. Bacterial DNA was extracted from the feces, and the V4 region of the 16S rRNA gene was amplified using PCR and sequenced on Illumina MiSeq. Beta-diversity was measured using Jaccard and Bray-Curtis distances, and the PERMANOVA was used to assess for differences in fecal microbiota within and between groups. Alpha-diversity indices for richness, evenness, and diversity, as well as relative abundance, were calculated and compared between groups. Results Beta-diversity differences occurred between diet groups at exit time-point with differences on Bray-Curtis distances at the family and genus levels (p = 0.007 and p = 0.001, respectively), and for the Jaccard distance at the family and genus level (p = 0.006 and p = 0.011, respectively). Significant differences in alpha-diversity occurred when comparing the PLANT to the MEAT group at the exit time-point with the PLANT group having a lower evenness (p = 0.012), but no significant differences in richness (p = 0.188), or diversity (p = 0.06). At exit-timepoint, compared to the MEAT group, the relative abundance of Fusobacterium, Bacteroides, and Campylobacter was lower in the PLANT group. The relative abundance of Fusobacterium decreased over time in the PLANT group, while no change was observed in the MEAT group. Conclusion These results indicate that vegan diets may change the canine gut microbiota. Future studies are warranted to confirm our results and determine long-term effects of vegan diets on the canine gut microbiome.
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Affiliation(s)
- Brooklynn D. Liversidge
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
| | - Diego E. Gomez
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
| | - Sarah A. S. Dodd
- Department of Population Medicine, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
| | - Jennifer L. MacNicol
- Department of Animal Biosciences, Ontario Agricultural College, University of Guelph, Guelph, ON, Canada
| | - Jennifer L. Adolphe
- Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
- Petcurean Pet Nutrition, Chilliwack, BC, Canada
| | - Shauna L. Blois
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
| | - Adronie Verbrugghe
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
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18
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Kopczyńska J, Kowalczyk M. The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity. Front Immunol 2024; 15:1380476. [PMID: 38605957 PMCID: PMC11008232 DOI: 10.3389/fimmu.2024.1380476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 03/18/2024] [Indexed: 04/13/2024] Open
Abstract
Obesity and chronic low-grade inflammation, often occurring together, significantly contribute to severe metabolic and inflammatory conditions like type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. A key player is elevated levels of gut dysbiosis-associated lipopolysaccharide (LPS), which disrupts metabolic and immune signaling leading to metabolic endotoxemia, while short-chain fatty acids (SCFAs) beneficially regulate these processes during homeostasis. SCFAs not only safeguard the gut barrier but also exert metabolic and immunomodulatory effects via G protein-coupled receptor binding and epigenetic regulation. SCFAs are emerging as potential agents to counteract dysbiosis-induced epigenetic changes, specifically targeting metabolic and inflammatory genes through DNA methylation, histone acetylation, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). To assess whether SCFAs can effectively interrupt the detrimental cascade of obesity and inflammation, this review aims to provide a comprehensive overview of the current evidence for their clinical application. The review emphasizes factors influencing SCFA production, the intricate connections between metabolism, the immune system, and the gut microbiome, and the epigenetic mechanisms regulated by SCFAs that impact metabolism and the immune system.
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Affiliation(s)
- Julia Kopczyńska
- Laboratory of Lactic Acid Bacteria Biotechnology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
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19
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Siddiqui R, Qaisar R, Al-Dahash K, Altelly AH, Elmoselhi AB, Khan NA. Cardiovascular changes under the microgravity environment and the gut microbiome. LIFE SCIENCES IN SPACE RESEARCH 2024; 40:89-96. [PMID: 38245353 DOI: 10.1016/j.lssr.2023.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/31/2023] [Accepted: 09/04/2023] [Indexed: 01/22/2024]
Abstract
In view of the critical role the gut microbiome plays in human health, it has become clear that astronauts' gut microbiota composition changes after spending time in space. Astronauts are exposed to several risks in space, including a protracted period of microgravity, radiation, and mechanical unloading of the body. Several deleterious effects of such an environment are reported, including orthostatic intolerance, cardiovascular endothelial dysfunction, cellular and molecular changes, and changes in the composition of the gut microbiome. Herein, the correlation between the gut microbiome and cardiovascular disease in a microgravity environment is evaluated. Additionally, the relationship between orthostatic hypotension, cardiac shrinkage and arrhythmias during spaceflight, and cellular alterations during spaceflight is reviewed. Given its impact on human health in general, modifying the gut microbiota may significantly promote astronaut health and performance. This is merited, given the prospect of augmented human activities in future space missions.
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Affiliation(s)
- Ruqaiyyah Siddiqui
- Microbiota Research Center, Istinye University, Istanbul 34010, Turkey; College of Arts and Sciences, American University of Sharjah, University City, Sharjah 26666, United Arab Emirates
| | - Rizwan Qaisar
- Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Cardiovascular Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Khulood Al-Dahash
- Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Ahmad Hashem Altelly
- Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Adel B Elmoselhi
- Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Cardiovascular Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Naveed Ahmed Khan
- Microbiota Research Center, Istinye University, Istanbul 34010, Turkey.
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20
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Khalil H, Nada AH, Mahrous H, Hassan A, Rijo P, Ibrahim IA, Mohamed DD, AL-Salmi FA, Mohamed DD, Elmaksoud AIA. Amelioration effect of 18β-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine. Front Immunol 2024; 14:1206990. [PMID: 38322013 PMCID: PMC10844948 DOI: 10.3389/fimmu.2023.1206990] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 11/27/2023] [Indexed: 02/08/2024] Open
Abstract
Aim suppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid. Method In the current work, we investigated the effect of sole GA combined with different agents such as doxorubicin (DOX) or probiotic bacteria (Lactobacillus rhamanosus) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats' liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats' liver tissue. Results Our results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively. Conclusion GA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.
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Affiliation(s)
- Hany Khalil
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
| | - Alaa H. Nada
- Department of Industrial Biotechnology, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
| | - Hoda Mahrous
- Department of Industrial Biotechnology, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
| | - Amr Hassan
- Department of Bioinformatics, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
| | - Patricia Rijo
- Research Center for Biosciences & Health Technologies (CBIOS), Universidade Lusófona de Humanidades e Tecnologias, Lisboa, Portugal
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
| | - Ibrahim A. Ibrahim
- Department of Plant Biotechnology, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
| | - Dalia D. Mohamed
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
| | - Fawziah A. AL-Salmi
- Department of Biology, Faculty of Sciences, Taif University, Taif, Saudi Arabia
| | - Doaa D. Mohamed
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
| | - Ahmed I. Abd Elmaksoud
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI) University of Sadat City, Sadat, Egypt
- College of Biotechnology, Misr University of Science and Technology, Giza, Egypt
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21
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Sun A, Park P, Cole L, Vaidya H, Maegawa S, Keith K, Calendo G, Madzo J, Jelinek J, Jobin C, Issa JPJ. Non-pathogenic microbiota accelerate age-related CpG Island methylation in colonic mucosa. Epigenetics 2023; 18:2160568. [PMID: 36572998 PMCID: PMC9980687 DOI: 10.1080/15592294.2022.2160568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 11/11/2022] [Indexed: 12/28/2022] Open
Abstract
DNA methylation is an epigenetic process altered in cancer and ageing. Age-related methylation drift can be used to estimate lifespan and can be influenced by extrinsic factors such as diet. Here, we report that non-pathogenic microbiota accelerate age-related methylation drift in the colon when compared with germ-free mice. DNA methylation analyses showed that microbiota and IL10KO were associated with changes in 5% and 4.1% of CpG sites, while mice with both factors had 18% alterations. Microbiota, IL10KO, and their combination altered 0.4%, 0.4%, and 4% of CpG island methylation, respectively. These are comparable to what is seen in colon cancer. Ageing changes were accelerated in the IL10KO mice with microbiota, and the affected genes were more likely to be altered in colon cancer. Thus, the microbiota affect DNA methylation of the colon in patterns reminiscent of what is observed in ageing and colorectal cancer.
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Affiliation(s)
- Ang Sun
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
| | - Pyounghwa Park
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
- Coriell Institute for Medical Research, Camden, NJ, United States
| | - Lauren Cole
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
| | - Himani Vaidya
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
- Coriell Institute for Medical Research, Camden, NJ, United States
| | - Shinji Maegawa
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
- Research Department of Pediatrics, University of Texas, MD Anderson Cancer Center Department of Pediatrics, University of Texas, MD Anderson Cancer CenterHouston, TX, USA
| | - Kelsey Keith
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
- Coriell Institute for Medical Research, Camden, NJ, United States
| | - Gennaro Calendo
- Coriell Institute for Medical Research, Camden, NJ, United States
| | - Jozef Madzo
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
- Coriell Institute for Medical Research, Camden, NJ, United States
| | - Jaroslav Jelinek
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
- Coriell Institute for Medical Research, Camden, NJ, United States
| | - Christian Jobin
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Jean-Pierre J. Issa
- Fels Cancer Institute for Personalized Medicine, Temple University School of Medicine, Philadelphia, PA, United States
- Coriell Institute for Medical Research, Camden, NJ, United States
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22
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Ren Y, Zeng Y, Wu Y, Yu J, Zhang Q, Xiao X. The Role of Gut Microbiota in Gestational Diabetes Mellitus Affecting Intergenerational Glucose Metabolism: Possible Mechanisms and Interventions. Nutrients 2023; 15:4551. [PMID: 37960204 PMCID: PMC10648599 DOI: 10.3390/nu15214551] [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: 09/15/2023] [Revised: 10/21/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open
Abstract
The incidence of type 2 diabetes is increasing every year and has become a serious public health problem. In addition to genetic factors, environmental factors in early life development are risk factors for diabetes. There is growing evidence that the gut microbiota plays an important role in glucose metabolism, and the gut microbiota of pregnant women with gestational diabetes mellitus (GDM) differs significantly from that of healthy pregnant women. This article reviews the role of maternal gut microbiota in offspring glucose metabolism. To explore the potential mechanisms by which the gut microbiota affects glucose metabolism in offspring, we summarize clinical studies and experimental animal models that support the hypothesis that the gut microbiota affects glucose metabolism in offspring from dams with GDM and discuss interventions that could improve glucose metabolism in offspring. Given that adverse pregnancy outcomes severely impact the quality of survival, reversing the deleterious effects of abnormal glucose metabolism in offspring through early intervention is important for both mothers and their offspring.
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Affiliation(s)
- Yaolin Ren
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.R.); (Y.Z.); (Y.W.); (J.Y.)
| | - Yuan Zeng
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.R.); (Y.Z.); (Y.W.); (J.Y.)
| | - Yifan Wu
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.R.); (Y.Z.); (Y.W.); (J.Y.)
| | - Jie Yu
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.R.); (Y.Z.); (Y.W.); (J.Y.)
| | - Qian Zhang
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.R.); (Y.Z.); (Y.W.); (J.Y.)
| | - Xinhua Xiao
- Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; (Y.R.); (Y.Z.); (Y.W.); (J.Y.)
- State Key Laboratory of Complex Severe and Rare Diseases, The Translational Medicine Center of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
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23
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Xinyuan T, Lei Y, Jianping S, Rongwei Z, Ruiwen S, Ye Z, Jing Z, Chunfang T, Hongwei C, Haibin G. Advances in the role of gut microbiota in the regulation of the tumor microenvironment (Review). Oncol Rep 2023; 50:181. [PMID: 37615187 PMCID: PMC10485805 DOI: 10.3892/or.2023.8618] [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: 03/16/2023] [Accepted: 08/01/2023] [Indexed: 08/25/2023] Open
Abstract
As a protector of human health, the gut microbiota plays an important role in the development of the immune system during childhood, and the regulation of dietary habits, metabolism and immune system during adulthood. Dysregulated gut flora is not pathogenic, but it can weaken the protective effect of the immune system and cause various diseases. The tumor microenvironment is a physiological environment formed during tumor growth, which provides nutrients and growth factors necessary for tumor growth. As an important factor affecting the tumor microenvironment, the intestinal microflora affects the development of tumors through the mechanisms of gut and microflora metabolites, gene toxins and signaling pathways. The present article aimed to review the components and mechanisms of action, clinical applications, and biological targets of gut microbiota in the regulation of the tumor microenvironment. The present review provides novel insights for the future use of intestinal flora, to regulate the tumor microenvironment, to intervene in the occurrence, development, treatment and prognosis of tumors.
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Affiliation(s)
- Tian Xinyuan
- School of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010107, P.R. China
| | - Yu Lei
- Department of Pharmacy, Traditional Chinese Medicine Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia Autonomous Region 010020, P.R. China
| | - Shi Jianping
- School of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010107, P.R. China
| | - Zhao Rongwei
- Department of Obstetrics and Gynecology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
| | - Shi Ruiwen
- School of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010107, P.R. China
| | - Zhang Ye
- School of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010107, P.R. China
| | - Zhao Jing
- School of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010107, P.R. China
| | - Tian Chunfang
- Department of Oncology, Traditional Chinese Medicine Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia Autonomous Region 010020, P.R. China
| | - Cui Hongwei
- Department of Scientific Research, Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010020, P.R. China
| | - Guan Haibin
- School of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010107, P.R. China
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24
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Dias S, Pheiffer C, Adam S. The Maternal Microbiome and Gestational Diabetes Mellitus: Cause and Effect. Microorganisms 2023; 11:2217. [PMID: 37764061 PMCID: PMC10535124 DOI: 10.3390/microorganisms11092217] [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: 05/10/2023] [Revised: 08/27/2023] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is a growing public health concern that affects many pregnancies globally. The condition is associated with adverse maternal and neonatal outcomes including gestational hypertension, preeclampsia, placental abruption, preterm birth, stillbirth, and fetal growth restriction. In the long-term, mothers and children have an increased risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease. Accumulating evidence suggest that alterations in the maternal microbiome may play a role in the pathogenesis of GDM and adverse pregnancy outcomes. This review describes changes in the maternal microbiome during the physiological adaptations of pregnancy, GDM and adverse maternal and neonatal outcomes. Findings from this review highlight the importance of understanding the link between the maternal microbiome and GDM. Furthermore, new therapeutic approaches to prevent or better manage GDM are discussed. Further research and clinical trials are necessary to fully realize the therapeutic potential of the maternal microbiome and translate these findings into clinical practice.
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Affiliation(s)
- Stephanie Dias
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa; (S.D.); (C.P.)
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa; (S.D.); (C.P.)
- Centre for Cardio-Metabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, Cape Town 7505, South Africa
- Department of Obstetrics and Gynaecology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa
| | - Sumaiya Adam
- Department of Obstetrics and Gynaecology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa
- Diabetes Research Centre, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa
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25
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Abstract
Epigenetics has transformed our understanding of the molecular basis of complex diseases, including cardiovascular and metabolic disorders. This review offers a comprehensive overview of the current state of knowledge on epigenetic processes implicated in cardiovascular and metabolic diseases, highlighting the potential of DNA methylation as a precision medicine biomarker and examining the impact of social determinants of health, gut bacterial epigenomics, noncoding RNA, and epitranscriptomics on disease development and progression. We discuss challenges and barriers to advancing cardiometabolic epigenetics research, along with the opportunities for novel preventive strategies, targeted therapies, and personalized medicine approaches that may arise from a better understanding of epigenetic processes. Emerging technologies, such as single-cell sequencing and epigenetic editing, hold the potential to further enhance our ability to dissect the complex interplay between genetic, environmental, and lifestyle factors. To translate research findings into clinical practice, interdisciplinary collaborations, technical and ethical considerations, and accessibility of resources and knowledge are crucial. Ultimately, the field of epigenetics has the potential to revolutionize the way we approach cardiovascular and metabolic diseases, paving the way for precision medicine and personalized health care, and improving the lives of millions of individuals worldwide affected by these conditions.
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Affiliation(s)
- Andrea A Baccarelli
- Department of Environmental Health Sciences, Mailman School of Public Health, New York (A.A.B.)
| | - José Ordovás
- Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, at Tufts University, Boston, MA (J.O.)
- IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain (J.O.)
- Consortium CIBERObn, Instituto de Salud Carlos III (ISCIII), Madrid, Spain (J.O.)
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26
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Rosas M, Liu C, Hong MY. Effects of Mixed Nut Consumption on Blood Glucose, Insulin, Satiety, and the Microbiome in a Healthy Population: A Pilot Study. J Med Food 2023; 26:342-351. [PMID: 37083461 PMCID: PMC11534022 DOI: 10.1089/jmf.2022.0121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2023] Open
Abstract
Nuts contain many health-promoting nutrients, fiber, and phytochemicals. Nut consumption has been reported to improve several chronic disease risk factors. Most studies to date have investigated single variety nut consumption. A nut mixture may offer a more diverse array of nutrients over single variety nuts. The primary outcome of this study was to examine the effects of mixed nut consumption on postprandial glucose, insulin, and satiety in healthy young adults. Exploratory outcomes include the effects of daily nut consumption on stool microbiome and bowel movement patterns. Twenty participants were randomized to consume either 42 g of mixed nuts or 46 g of potato chips daily for 3 weeks. Mixed nut consumption did not alter postprandial blood glucose and insulin, while potato chip consumption increased glucose and insulin (P < .05). There were no significant differences in fasting blood glucose or insulin for either snack after 3 weeks of daily consumption. Both snacks increased satiety while there were no significant differences in body weight, body fat, blood pressure, waist-to-hip ratio, or anxiety. After 3 weeks of snack consumption, both groups significantly reduced straining during bowel movements while the mixed nut group slightly increased stool amount. There were no significant changes in microbiome composition for either group; however, there was a nonsignificant trend toward increased Firmicutes to Bacteroidetes ratio in the potato chip group and an opposite trend in the mixed nut group. The results of this study suggest that mixed nuts are a healthy alternative for blood sugar control. The study was registered at ClinicalTrials.gov, Number: NCT03375866.
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Affiliation(s)
- Martin Rosas
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Changqi Liu
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Mee Young Hong
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
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27
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Salas-Perez F, Assmann TS, Ramos-Lopez O, Martínez JA, Riezu-Boj JI, Milagro FI. Crosstalk between Gut Microbiota and Epigenetic Markers in Obesity Development: Relationship between Ruminococcus, BMI, and MACROD2/ SEL1L2 Methylation. Nutrients 2023; 15:nu15071550. [PMID: 37049393 PMCID: PMC10097304 DOI: 10.3390/nu15071550] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/09/2023] [Accepted: 03/20/2023] [Indexed: 04/14/2023] Open
Abstract
Changes in gut microbiota composition and in epigenetic mechanisms have been proposed to play important roles in energy homeostasis, and the onset and development of obesity. However, the crosstalk between epigenetic markers and the gut microbiome in obesity remains unclear. The main objective of this study was to establish a link between the gut microbiota and DNA methylation patterns in subjects with obesity by identifying differentially methylated DNA regions (DMRs) that could be potentially regulated by the gut microbiota. DNA methylation and bacterial DNA sequencing analysis were performed on 342 subjects with a BMI between 18 and 40 kg/m2. DNA methylation analyses identified a total of 2648 DMRs associated with BMI, while ten bacterial genera were associated with BMI. Interestingly, only the abundance of Ruminococcus was associated with one BMI-related DMR, which is located between the MACROD2/SEL1L2 genes. The Ruminococcus abundance negatively correlated with BMI, while the hypermethylated DMR was associated with reduced MACROD2 protein levels in serum. Additionally, the mediation test showed that 19% of the effect of Ruminococcus abundance on BMI is mediated by the methylation of the MACROD2/SEL1L2 DMR. These findings support the hypothesis that a crosstalk between gut microbiota and epigenetic markers may be contributing to obesity development.
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Affiliation(s)
| | - Taís Silveira Assmann
- Graduate Program in Medical Sciences, Endocrinology, Department of Internal Medicine, Faculty of Medicine, Federal University of do Rio Grande do Sul, Porto Alegre 90035-003, Brazil
| | - Omar Ramos-Lopez
- Medicine and Psychology School, Autonomous University of Baja California, Tijuana 22390, Mexico
| | - J Alfredo Martínez
- Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
- Department of Nutrition, Food Science and Physiology, University of Navarra, 31008 Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Carlos III Health Institute, 28029 Madrid, Spain
| | - Jose Ignacio Riezu-Boj
- Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain
| | - Fermín I Milagro
- Center for Nutrition Research, University of Navarra, 31008 Pamplona, Spain
- Department of Nutrition, Food Science and Physiology, University of Navarra, 31008 Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Carlos III Health Institute, 28029 Madrid, Spain
- Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain
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28
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Giannella L, Grelloni C, Quintili D, Fiorelli A, Montironi R, Alia S, Delli Carpini G, Di Giuseppe J, Vignini A, Ciavattini A. Microbiome Changes in Pregnancy Disorders. Antioxidants (Basel) 2023; 12:463. [PMID: 36830021 PMCID: PMC9952029 DOI: 10.3390/antiox12020463] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/08/2023] [Accepted: 02/10/2023] [Indexed: 02/16/2023] Open
Abstract
The human microbiota comprises all microorganisms, such as bacteria, fungi, and viruses, found within a specific environment that live on our bodies and inside us. The last few years have witnessed an explosion of information related to the role of microbiota changes in health and disease. Even though the gut microbiota is considered the most important in maintaining our health, other regions of the human body, such as the oral cavity, lungs, vagina, and skin, possess their own microbiota. Recent work suggests a correlation between the microbiota present during pregnancy and pregnancy complications. The aim of our literature review was to provide a broad overview of this growing and important topic. We focused on the most significant changes in the microbiota in the four more common obstetric diseases affecting women's health. Thus, our attention will be focused on hypertensive disorders, gestational diabetes mellitus, preterm birth, and recurrent miscarriage. Pregnancy is a unique period in a woman's life since the body undergoes different adaptations to provide an optimal environment for fetal growth. Such changes also involve all the microorganisms, which vary in composition and quantity during the three trimesters of gestation. In addition, special attention will be devoted to the potential and fundamental advances in developing clinical applications to prevent and treat those disorders by modulating the microbiota to develop personalized therapies for disease prevention and tailored treatments.
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Affiliation(s)
- Luca Giannella
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
| | - Camilla Grelloni
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
| | - Dayana Quintili
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
| | - Alessia Fiorelli
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
| | - Ramona Montironi
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
| | - Sonila Alia
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Via Tronto 10/A, 60126 Ancona, Italy
| | - Giovanni Delli Carpini
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
| | - Jacopo Di Giuseppe
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
| | - Arianna Vignini
- Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Università Politecnica delle Marche, Via Tronto 10/A, 60126 Ancona, Italy
| | - Andrea Ciavattini
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Via Filippo Corridoni, 16, 60123 Ancona, Italy
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29
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Naseri K, Dabiri H, Olfatifar M, Shahrbaf MA, Yadegar A, Soheilian-Khorzoghi M, Sadeghi A, Saadati S, Rostami-Nejad M, Verma AK, Zali MR. Evaluation of gut microbiota of iranian patients with celiac disease, non-celiac wheat sensitivity, and irritable bowel syndrome: are there any similarities? BMC Gastroenterol 2023; 23:15. [PMID: 36647022 PMCID: PMC9841652 DOI: 10.1186/s12876-023-02649-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 01/11/2023] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND AND AIMS Individuals with celiac disease (CD), non-celiac wheat sensitivity (NCWS), and irritable bowel syndrome (IBS), show overlapping clinical symptoms and experience gut dysbiosis. A limited number of studies so far compared the gut microbiota among these intestinal conditions. This study aimed to investigate the similarities in the gut microbiota among patients with CD, NCWS, and IBS in comparison to healthy controls (HC). MATERIALS AND METHODS In this prospective study, in total 72 adult subjects, including CD (n = 15), NCWS (n = 12), IBS (n = 30), and HC (n = 15) were recruited. Fecal samples were collected from each individual. A quantitative real-time PCR (qPCR) test using 16S ribosomal RNA was conducted on stool samples to assess the relative abundance of Firmicutes, Bacteroidetes, Bifidobacterium spp., and Lactobacillus spp. RESULTS In all groups, Firmicutes and Lactobacillus spp. had the highest and lowest relative abundance respectively. The phylum Firmicutes had a higher relative abundance in CD patients than other groups. On the other hand, the phylum Bacteroidetes had the highest relative abundance among healthy subjects but the lowest in patients with NCWS. The relative abundance of Bifidobacterium spp. was lower in subjects with CD (P = 0.035) and IBS (P = 0.001) compared to the HCs. Also, the alteration of Firmicutes to Bacteroidetes ratio (F/B ratio) was statistically significant in NCWS and CD patients compared to the HCs (P = 0.05). CONCLUSION The principal coordinate analysis (PCoA), as a powerful multivariate analysis, suggested that the investigated gut microbial profile of patients with IBS and NCWS share more similarities to the HCs. In contrast, patients with CD had the most dissimilarity compared to the other groups in the context of the studied gut microbiota.
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Affiliation(s)
- Kaveh Naseri
- School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia
| | - Hossein Dabiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Meysam Olfatifar
- Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Mohammad Amin Shahrbaf
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mona Soheilian-Khorzoghi
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeede Saadati
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Anil K Verma
- Celiac Disease Research Laboratory, Department of Pediatrics, Università Politecnica Delle Marche, 60123, Ancona, Italy
| | - Mohammad Reza Zali
- Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Watson MM, van der Giezen M, Søreide K. Gut Microbiome Influence on Human Epigenetics, Health, and Disease. HANDBOOK OF EPIGENETICS 2023:669-686. [DOI: 10.1016/b978-0-323-91909-8.00012-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Epigenetics and Gut Microbiota Crosstalk: A potential Factor in Pathogenesis of Cardiovascular Disorders. BIOENGINEERING (BASEL, SWITZERLAND) 2022; 9:bioengineering9120798. [PMID: 36551003 PMCID: PMC9774431 DOI: 10.3390/bioengineering9120798] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/09/2022] [Accepted: 12/12/2022] [Indexed: 12/15/2022]
Abstract
Cardiovascular diseases (CVD) are the leading cause of mortality, morbidity, and "sudden death" globally. Environmental and lifestyle factors play important roles in CVD susceptibility, but the link between environmental factors and genetics is not fully established. Epigenetic influence during CVDs is becoming more evident as its direct involvement has been reported. The discovery of epigenetic mechanisms, such as DNA methylation and histone modification, suggested that external factors could alter gene expression to modulate human health. These external factors also influence our gut microbiota (GM), which participates in multiple metabolic processes in our body. Evidence suggests a high association of GM with CVDs. Although the exact mechanism remains unclear, the influence of GM over the epigenetic mechanisms could be one potential pathway in CVD etiology. Both epigenetics and GM are dynamic processes and vary with age and environment. Changes in the composition of GM have been found to underlie the pathogenesis of metabolic diseases via modulating epigenetic changes in the form of DNA methylation, histone modifications, and regulation of non-coding RNAs. Several metabolites produced by the GM, including short-chain fatty acids, folates, biotin, and trimethylamine-N-oxide, have the potential to regulate epigenetics, apart from playing a vital role in normal physiological processes. The role of GM and epigenetics in CVDs are promising areas of research, and important insights in the field of early diagnosis and therapeutic approaches might appear soon.
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Begum N, Mandhare A, Tryphena KP, Srivastava S, Shaikh MF, Singh SB, Khatri DK. Epigenetics in depression and gut-brain axis: A molecular crosstalk. Front Aging Neurosci 2022; 14:1048333. [PMID: 36583185 PMCID: PMC9794020 DOI: 10.3389/fnagi.2022.1048333] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/23/2022] [Indexed: 12/15/2022] Open
Abstract
Gut-brain axis is a dynamic, complex, and bidirectional communication network between the gut and brain. Changes in the microbiota-gut-brain axis are responsible for developing various metabolic, neurodegenerative, and neuropsychiatric disorders. According to clinical and preclinical findings, the gut microbiota is a significant regulator of the gut-brain axis. In addition to interacting with intestinal cells and the enteric nervous system, it has been discovered that microbes in the gut can modify the central nervous system through metabolic and neuroendocrine pathways. The metabolites of the gut microbiome can modulate a number of diseases by inducing epigenetic alteration through DNA methylation, histone modification, and non-coding RNA-associated gene silencing. Short-chain fatty acids, especially butyrate, are well-known histone deacetylases inhibitors. Similarly, other microbial metabolites such as folate, choline, and trimethylamine-N-oxide also regulate epigenetics mechanisms. Furthermore, various studies have revealed the potential role of microbiome dysbiosis and epigenetics in the pathophysiology of depression. Hence, in this review, we have highlighted the role of gut dysbiosis in epigenetic regulation, causal interaction between host epigenetic modification and the gut microbiome in depression and suggest microbiome and epigenome as a possible target for diagnosis, prevention, and treatment of depression.
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Affiliation(s)
- Nusrat Begum
- Cellular and Molecular Neuroscience Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India
| | - Aniket Mandhare
- Cellular and Molecular Neuroscience Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India
| | - Kamatham Pushpa Tryphena
- Cellular and Molecular Neuroscience Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India
| | - Saurabh Srivastava
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India,*Correspondence: Saurabh Srivastava,
| | - Mohd Farooq Shaikh
- Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia,Mohd Farooq Shaikh,
| | - Shashi Bala Singh
- Cellular and Molecular Neuroscience Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India
| | - Dharmendra Kumar Khatri
- Cellular and Molecular Neuroscience Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India,Dharmendra Kumar Khatri,
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Hong J, Fu T, Liu W, Du Y, Min C, Lin D. Specific alterations of gut microbiota in diabetic microvascular complications: A systematic review and meta-analysis. Front Endocrinol (Lausanne) 2022; 13:1053900. [PMID: 36545341 PMCID: PMC9761769 DOI: 10.3389/fendo.2022.1053900] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 11/11/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The role of gut microbiota in diabetes mellitus (DM) and its complications has been widely accepted. However, the alternation of gut microbiota in diabetic microvascular complications (DC) remains to be determined. METHODS Publications (till August 20th, 2022) on gut microbiota in patients with DC were retrieved from PubMed, Web of Science, Embase and Cochrane. Review Manager 5.3 was performed to estimate the standardized mean difference (SMD) and 95% confidence interval (CI) and calculate alpha diversity indices and the relative abundance of gut microbiota between patients in DC v.s. DM and DC v.s. healthy controls (HC). RESULTS We included 13 studies assessing 329 patients with DC, 232 DM patients without DC, and 241 HC. Compared to DM, patients with DC shared a significantly lower Simpson index (SMD = -0.59, 95% CI [-0.82, -0.36], p < 0.00001), but a higher ACE index (SMD = 0.42, 95% CI[0.11, 0.74], p = 0.009). Compared to HC, DC patients held a lower ACE index (SMD = -0.61, 95% CI[-1.20, -0.02], p = 0.04). The relative abundances of phylum Proteobacteria (SMD = 0.03, 95% CI[0.01, 0.04], p = 0.003, v.s. HC) and genus Klebsiella (SMD = 0.00, 95% CI[0.00, 0.00], p < 0.00001, v.s. HC) were enriched, accompanying with depleted abundances of phylum Firmicutes (SMD = -0.06, 95% CI[-0.11, -0.01], p = 0.02, v.s. HC), genera Bifidobacterium (SMD = -0.01, 95% CI[-0.02,-0.01], p < 0.0001, v.s. DM), Faecalibacterium (SMD = -0.01, 95% CI[-0.02, -0.00], p = 0.009, v.s. DM; SMD = -0.02, 95% CI[-0.02, -0.01], p < 0.00001, v.s. HC) and Lactobacillus (SMD = 0.00, 95% CI[-0.00, -0.00], p < 0.00001, v.s. HC) in DC. CONCLUSIONS Gut microbiota perturbations with the depletion of alpha diversity and certain short-chain fatty acids (SCFAs)-producing bacteria were associated with the pathology of DC. Therefore, gut microbiota might serve as a promising approach for the diagnosis and treatment of DC. Further investigations are required to study the mechanisms by which gut dysbiosis acts on the onset and progression of DC.
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Affiliation(s)
- Jinni Hong
- Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of Traditional Chinese Medicine Guangdong Provincial Institute of Geriatric, Guangzhou, China
| | - Tingting Fu
- Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of Traditional Chinese Medicine Guangdong Provincial Institute of Geriatric, Guangzhou, China
| | - Weizhen Liu
- Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of Traditional Chinese Medicine Guangdong Provincial Institute of Geriatric, Guangzhou, China
| | - Yu Du
- Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of Traditional Chinese Medicine Guangdong Provincial Institute of Geriatric, Guangzhou, China
| | - Cunyun Min
- Department of Traditional Chinese Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of Traditional Chinese Medicine Guangdong Provincial Institute of Geriatric, Guangzhou, China
| | - Datao Lin
- Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
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Giannini C, Mastromauro C, Scapaticci S, Gentile C, Chiarelli F. Role of bile acids in overweight and obese children and adolescents. Front Endocrinol (Lausanne) 2022; 13:1011994. [PMID: 36531484 PMCID: PMC9747777 DOI: 10.3389/fendo.2022.1011994] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 11/07/2022] [Indexed: 12/05/2022] Open
Abstract
Bile acids (BAs) are amphipathic molecules synthetized in the liver. They are primarily involved in the digestion of nutrients. Apart from their role in dietary lipid absorption, BAs have progressively emerged as key regulators of systemic metabolism and inflammation. In the last decade, it became evident that BAs are particularly important for the regulation of glucose, lipid, and energy metabolism. Indeed, the interest in role of BA in metabolism homeostasis is further increased due to the global public health increase in obesity and related complications and a large number of research postulating that there is a close mutual relationship between BA and metabolic disorders. This strong relationship seems to derive from the role of BAs as signaling molecules involved in the regulation of a wide spectrum of metabolic pathways. These actions are mediated by different receptors, particularly nuclear farnesoid X receptor (FXR) and Takeda G protein coupled receptor 5 (TGR5), which are probably the major effectors of BA actions. These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in BA, lipid and carbohydrate metabolism, energy expenditure, and inflammation. The large correlation between BAs and metabolic disorders offers the possibility that modulation of BAs could be used as a therapeutic approach for the treatment of metabolic diseases, including obesity itself. The aim of this review is to describe the main physiological and metabolic actions of BA, focusing on its signaling pathways, which are important in the regulation of metabolism and might provide new BA -based treatments for metabolic diseases.
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Affiliation(s)
- Cosimo Giannini
- Department of Pediatrics, University of Chieti, Chieti, Italy
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Singh A, Ambaru B, Bandsode V, Ahmed N. Panomics to decode virulence and fitness in Gram-negative bacteria. Front Cell Infect Microbiol 2022; 12:1061596. [PMID: 36478674 PMCID: PMC9719987 DOI: 10.3389/fcimb.2022.1061596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 10/26/2022] [Indexed: 11/22/2022] Open
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Zhang C, Chen F, Shen Y, Chen Y, Ma J. Sleep apnea is associated with the increase of certain genera of Ruminococcaceae and Lachnospiraceae in the gut microbiome of hypertensive patients. Expert Rev Respir Med 2022; 16:1247-1256. [PMID: 36369876 DOI: 10.1080/17476348.2022.2147509] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
BACKGROUND Obstructive sleep apnea (OSA) and hypertension are interrelated diseases linked to gut dysbiosis. This study aimed to investigate the effect of OSA on the gut microbiome in the context of hypertension and vice versa. RESEARCH DESIGN AND METHODS Of 211 consecutively screened patients, 52 completed polysomnography study, medical history questionnaires, and fecal sample collection. 16S rRNA gene sequencing was performed on fecal samples, and diversity, richness, and microbial taxa were analyzed using bioinformatics. RESULTS Alpha diversity showed slightly decreased diversity in OSA and hypertension groups without significant difference, and the hypoxia burden index (HBI) showed a weak positive correlation with Chao1 index (r = 0.342, p < 0.05) in OSA patients. Firmicutes-to-Bacteroidetes ratio was higher in patients with than without OSA. In hypertensive patients, those with OSA had higher Ruminococcus_1, Lachnoclostridium, Lachnospira, [Ruminococcus]_torques_group, and unidentified Lachnospiraceae levels than those without OSA. Conversely, in OSA patients, hypertensive patients had lower Faecalibacterium and Lachnospiraceae_NK4A136_group levels. CONCLUSION The present study suggests a possible compensatory mechanism for gut microbiome changes in sleep apnea pathophysiology. The positive correlation between HBI and alpha diversity, and increase in certain genera of Ruminococcaceae and Lachnospiraceae in OSA patients may represent an adaptive response to hypoxia.
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Affiliation(s)
- Cheng Zhang
- The Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, China
| | - Fengwei Chen
- The Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, China
| | - Yane Shen
- The Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, China
| | - Yuqing Chen
- Nephrology Department, Peking University First Hospital, Beijing, China
| | - Jing Ma
- The Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, China
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Fabozzi G, Rebuzzini P, Cimadomo D, Allori M, Franzago M, Stuppia L, Garagna S, Ubaldi FM, Zuccotti M, Rienzi L. Endocrine-Disrupting Chemicals, Gut Microbiota, and Human (In)Fertility-It Is Time to Consider the Triad. Cells 2022; 11:3335. [PMID: 36359730 PMCID: PMC9654651 DOI: 10.3390/cells11213335] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/12/2022] [Accepted: 10/17/2022] [Indexed: 07/29/2023] Open
Abstract
The gut microbiota (GM) is a complex and dynamic population of microorganisms living in the human gastrointestinal tract that play an important role in human health and diseases. Recent evidence suggests a strong direct or indirect correlation between GM and both male and female fertility: on the one hand, GM is involved in the regulation of sex hormone levels and in the preservation of the blood-testis barrier integrity; on the other hand, a dysbiotic GM is linked to the onset of pro-inflammatory conditions such as endometriosis or PCOS, which are often associated with infertility. Exposure to endocrine-disrupting chemicals (EDCs) is one of the main causes of GM dysbiosis, with important consequences to the host health and potential transgenerational effects. This perspective article aims to show that the negative effects of EDCs on reproduction are in part due to a dysbiotic GM. We will highlight (i) the link between GM and male and female fertility; (ii) the mechanisms of interaction between EDCs and GM; and (iii) the importance of the maternal-fetal GM axis for offspring growth and development.
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Affiliation(s)
- Gemma Fabozzi
- B-Woman, Via dei Monti Parioli 6, 00197 Rome, Italy
- Clinica Valle Giulia, GeneraLife IVF, Via De Notaris 2B, 00197 Rome, Italy
| | - Paola Rebuzzini
- Laboratory of Developmental Biology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
| | - Danilo Cimadomo
- Clinica Valle Giulia, GeneraLife IVF, Via De Notaris 2B, 00197 Rome, Italy
| | | | - Marica Franzago
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Medicine and Aging Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Liborio Stuppia
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Silvia Garagna
- Laboratory of Developmental Biology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
- Centre for Health Technologies (CHT), University of Pavia, Via Ferrata 5, 27100 Pavia, Italy
| | | | - Maurizio Zuccotti
- Laboratory of Developmental Biology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
- Centre for Health Technologies (CHT), University of Pavia, Via Ferrata 5, 27100 Pavia, Italy
| | - Laura Rienzi
- Clinica Valle Giulia, GeneraLife IVF, Via De Notaris 2B, 00197 Rome, Italy
- Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via Sant’Andrea 34, 61029 Urbino, Italy
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Ibrahim HIM. Epigenetic Regulation of Obesity-Associated Type 2 Diabetes. Medicina (B Aires) 2022; 58:medicina58101366. [PMID: 36295527 PMCID: PMC9607337 DOI: 10.3390/medicina58101366] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 09/22/2022] [Accepted: 09/26/2022] [Indexed: 11/16/2022] Open
Abstract
Obesity is becoming more widespread, and epidemics of this condition are now considered present in all developed countries, leading to public health concerns. The dramatic increases in obesity, type 2 diabetes mellitus (T2DM), and related vascular difficulties are causing a public health crisis. Thus, it is imperative that these trends are curbed. Understanding the molecular underpinnings of these diseases is crucial to aiding in their detection or even management. Thus, understanding the mechanisms underlying the interactions between environment, lifestyle, and genetics is important for developing effective strategies for the management of obesity. The focus is on finding the vital role of epigenetic changes in the etiology of obesity. Genome and epigenome-wide approaches have revealed associations with T2DM. The epigenome indicates that there is a systematic link between genetic variants and environmental factors that put people at risk of obesity. The present review focuses on the epigenetic mechanism linked with obesity-associated T2DM. Although the utilization of epigenetic treatments has been discussed with reference to certain cancers, several challenges remain to be addressed for T2DM.
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Affiliation(s)
- Hairul Islam Mohamed Ibrahim
- Department of Biological Science, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
- Division of Microbiology and Immunology, Pondicherry Centre for Biological Science and Educational Trust, Puducherry 605004, India
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Boros É, Hegedűs Z, Kellermayer Z, Balogh P, Nagy I. Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease. Front Immunol 2022; 13:991346. [PMID: 36177008 PMCID: PMC9513375 DOI: 10.3389/fimmu.2022.991346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that associates with, among others, increased risk of colorectal cancer. There is a growing evidence that miRNAs have important roles in pathological processes, such as inflammation or carcinogenesis. Understanding the molecular mechanisms such as alterations in microRNAome upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of IBD. Hence, we conducted a genome wide microRNAome analysis by applying miRNA-Seq in a rat model of experimental colitis, validated the data by QPCR, examined the expression of a selection of precursor and mature miRNAs, performed in depth biological interpretation using Ingenuity Pathway Analysis and tested the obtained results on samples derived from human patients. We identified specific, interdependent expression pattern of activator/repressor transcription factors, miRNAs and their direct targets in the inflamed colon samples. Particularly, decreased expression of the miR-200 family members (miR-200a/b/c,-141, and -429) and miR-27b correlates with the reduced level of their enhancers (HNF1B, E2F1), elevated expression of their repressors (ZEB2, NFKB1) and increased expression of their target genes (ZEB2, RUNX1). Moreover, the marked upregulation of six miR-27b target genes (IFI16, GCA, CYP1B1, RUNX1, MEF2C and MMP13) in the inflamed colon tissues is a possible direct consequence of the lack of repression due to the downregulated miRNA-27b expression. Our data indicate that changes in microRNAome are associated with the pathophysiology of IBD, consequently, microRNAs offer potential targets for the diagnosis, prognosis and treatment of IBD.
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Affiliation(s)
- Éva Boros
- Seqomics Biotechnology Ltd., Mórahalom, Hungary
- Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary
| | - Zoltán Hegedűs
- Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary
- Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Pécs, Hungary
| | - Zoltán Kellermayer
- Department of Immunology and Biotechnology, University of Pécs, Pécs, Hungary
- Lymphoid Organogenesis Research Group, Szentágothai János Research Center, University of Pécs, Pécs, Hungary
| | - Péter Balogh
- Department of Immunology and Biotechnology, University of Pécs, Pécs, Hungary
- Lymphoid Organogenesis Research Group, Szentágothai János Research Center, University of Pécs, Pécs, Hungary
| | - István Nagy
- Seqomics Biotechnology Ltd., Mórahalom, Hungary
- Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary
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The mediating role of the gut microbiome in the association between ambient air pollution and autistic traits. Int J Hyg Environ Health 2022; 246:114047. [DOI: 10.1016/j.ijheh.2022.114047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/29/2022] [Accepted: 09/30/2022] [Indexed: 11/05/2022]
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ROLE OF GUT MICROBIOTA IN DEPRESSION: UNDERSTANDING MOLECULAR PATHWAYS, RECENT RESEARCH, AND FUTURE DIRECTION. Behav Brain Res 2022; 436:114081. [PMID: 36037843 DOI: 10.1016/j.bbr.2022.114081] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 08/20/2022] [Accepted: 08/24/2022] [Indexed: 11/21/2022]
Abstract
Gut microbiota, also known as the "second brain" in humans because of the regulatory role it has on the central nervous system via neuronal, chemical and immune pathways. It has been proven that there exists a bidirectional communication between the gut and the brain. Increasing evidence supports that this crosstalk is linked to the etiology and treatment of depression. Reports suggest that the gut microbiota control the host epigenetic machinery in depression and gut dysbiosis causes negative epigenetic modifications via mechanisms like histone acetylation, DNA methylation and non-coding RNA mediated gene inhibition. The gut microbiome can be a promising approach for the management of depression. The diet and dietary metabolites like kynurenine, tryptophan, and propionic acid also greatly influence the microbiome composition and thereby, the physiological activities. This review gives a bird-eye view on the pathological updates and currently used treatment approaches targeting the gut microbiota in depression.
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Chen L, Xu X, Wu X, Cao H, Li X, Hou Z, Wang B, Liu J, Ji X, Zhang P, Li H. A comparison of the composition and functions of the oral and gut microbiotas in Alzheimer’s patients. Front Cell Infect Microbiol 2022; 12:942460. [PMID: 36093178 PMCID: PMC9448892 DOI: 10.3389/fcimb.2022.942460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/05/2022] [Indexed: 11/13/2022] Open
Abstract
Objective Alterations in the oral or gut microbiotas have been reported in patients with subjective and mild cognitive impairment or AD dementia. However, whether these microbiotas change with the severity of the AD spectrum (mild, moderate, and severe AD) remains unknown. Thus, we compared alterations in the composition and gene functions of the oral and gut microbiota between different phases of AD. Methods We recruited 172 individuals and classified these into three groups: healthy controls (n = 40), a mild AD group (n = 43) and a moderate AD group (n = 89). Subgingival plaques and fecal samples were collected from all individuals. Then, we conducted 16S ribosomal RNA. sequencing to analyze the microbiotas. Results In order of the severity of cognition impairment (from normal to mild and to moderate AD), the oral abundances of the phyla Firmicutes and Fusobacteria showed a gradual upwards trend, while the abundance of the Proteobacteria phylum gradually decreased. In contrast, the abundance of the Firmicutes and Bacteroidetes phyla in the gut decreased progressively, while that of the Proteobacteria, Verrucomicrobia and Actinobacteria phyla increased gradually. Key differences were identified in the microbiomes when compared between the mild AD and moderate AD groups when applying the linear discriminant analysis effect size (LEfSe) algorithm. LEfSe analysis revealed alterations that were similar to those described above; furthermore, different bacterial taxa were associated with MMSE scores and age. KEGG analysis showed that the functional pathways associated with the oral microbiota were mainly involved in membrane transport and carbohydrate metabolism, while the gene functions of the fecal microbiota related to metabolism of amino acids, energy, cofactors and vitamins; identified significant differences among the three groups. Venn diagram analysis revealed that the number of genera that were present in both the oral and gut microbiota increased progressively from NC to mild AD and then to moderate AD. Conclusions This study is the first to report a comparative analysis of the oral and fecal microbiota of patients with mild and moderate AD. The compositions and functions of the oral and gut microbiotas differed when compared between different stages of AD.
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Affiliation(s)
- Lili Chen
- The School of Nursing, Fujian Medical University, Fuzhou, China
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Nursing Department, Fujian Provincial Hospital, Fuzhou, China
| | - Xinhua Xu
- The School of Nursing, Fujian Medical University, Fuzhou, China
| | - Xiaoqi Wu
- College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Huizhen Cao
- The School of Nursing, Fujian Medical University, Fuzhou, China
- Nursing Department, Fujian Provincial Hospital South Branch, Fuzhou, China
| | - Xiuli Li
- The School of Nursing, Fujian Medical University, Fuzhou, China
| | - Zhaoyi Hou
- The School of Nursing, Fujian Medical University, Fuzhou, China
| | - Bixia Wang
- The School of Nursing, Fujian Medical University, Fuzhou, China
| | - Jinxiu Liu
- The School of Nursing, Fujian Medical University, Fuzhou, China
| | - Xinli Ji
- The School of Nursing, Fujian Medical University, Fuzhou, China
| | - Ping Zhang
- The School of Nursing, Fujian Medical University, Fuzhou, China
| | - Hong Li
- The School of Nursing, Fujian Medical University, Fuzhou, China
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Nursing Department, Fujian Provincial Hospital, Fuzhou, China
- *Correspondence: Hong Li,
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Wang L, Zhang W, Wu X, Liang X, Cao L, Zhai J, Yang Y, Chen Q, Liu H, Zhang J, Ding Y, Zhu F, Tang J. MIAOME: Human Microbiome Affect The Host Epigenome. Comput Struct Biotechnol J 2022; 20:2455-2463. [PMID: 35664224 PMCID: PMC9136154 DOI: 10.1016/j.csbj.2022.05.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/11/2022] [Accepted: 05/12/2022] [Indexed: 01/10/2023] Open
Abstract
Besides the genetic factors having tremendous influences on the regulations of the epigenome, the microenvironmental factors have recently gained extensive attention for their roles in affecting the host epigenome. There are three major types of microenvironmental factors: microbiota-derived metabolites (MDM), microbiota-derived components (MDC) and microbiota-secreted proteins (MSP). These factors can regulate host physiology by modifying host gene expression through the three highly interconnected epigenetic mechanisms (e.g. histone modifications, DNA modifications, and non-coding RNAs). However, no database was available to provide the comprehensive factors of these types. Herein, a database entitled 'Human Microbiome Affect The Host Epigenome (MIAOME)' was constructed. Based on the types of epigenetic modifications confirmed in the literature review, the MIAOME database captures 1068 (63 genus, 281 species, 707 strains, etc.) human microbes, 91 unique microbiota-derived metabolites & components (16 fatty acids, 10 bile acids, 10 phenolic compounds, 10 vitamins, 9 tryptophan metabolites, etc.) derived from 967 microbes; 50 microbes that secreted 40 proteins; 98 microbes that directly influence the host epigenetic modification, and provides 3 classifications of the epigenome, including (1) 4 types of DNA modifications, (2) 20 histone modifications and (3) 490 ncRNAs regulations, involved in 160 human diseases. All in all, MIAOME has compiled the information on the microenvironmental factors influence host epigenome through the scientific literature and biochemical databases, and allows the collective considerations among the different types of factors. It can be freely assessed without login requirement by all users at: http://miaome.idrblab.net/ttd/
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Affiliation(s)
- Lidan Wang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Wei Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xianglu Wu
- Joint International Research Laboratory of Reproductive and Development, Department of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Xiao Liang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Lijie Cao
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Jincheng Zhai
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Yiyang Yang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Qiuxiao Chen
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Hongqing Liu
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Jun Zhang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Yubin Ding
- Joint International Research Laboratory of Reproductive and Development, Department of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China
- Corresponding authors at: School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China (J. Tang).
| | - Feng Zhu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Corresponding authors at: School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China (J. Tang).
| | - Jing Tang
- School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
- Joint International Research Laboratory of Reproductive and Development, Department of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China
- Corresponding authors at: School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China (J. Tang).
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Hernandez AR, Kemp KM, Burke SN, Buford TW, Carter CS. Influence of Aging, Macronutrient Composition and Time-Restricted Feeding on the Fischer344 x Brown Norway Rat Gut Microbiota. Nutrients 2022; 14:nu14091758. [PMID: 35565725 PMCID: PMC9105022 DOI: 10.3390/nu14091758] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 02/01/2023] Open
Abstract
Both ketogenic diets (KD) and time-restricted feeding (TRF) regimens have the ability to influence several parameters of physical health, including gut microbiome composition and circulating cytokine concentration. Moreover, both of these dietary interventions prevent common impairments associated with the aging process. However, significantly altering macronutrient intake, which is required for a KD, may be unappealing to individuals and decrease compliance to dietary treatments. In contrast to a KD, TRF allows individuals to continue eating the foods they are used to, and only requires a change in the time of day at which they eat. Therefore, we investigated both a KD and a diet with a more Western-like macronutrient profile in the context of TRF, and compared both diets to animals allowed access to standard chow ad libitum in young adult and aged rats. While limited effects on cytokine levels were observed, both methods of microbiome analysis (16S sequencing and metagenomics) indicate that TRF and KDs significantly altered the gut microbiome in aged rats. These changes were largely dependent on changes to feeding paradigm (TRF vs. ad libitum) alone regardless of macronutrient content for many gut microbiota, but there were also macronutrient-specific changes. Specifically, functional analysis indicates significant differences in several pathways, including those involved in the tricarboxylic acid (TCA) cycle, carbohydrate metabolism and neurodegenerative disease. These data indicate that age- and disease-related gut dysbiosis may be ameliorated through the use of TRF with both standard diets and KDs.
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Affiliation(s)
- Abbi R. Hernandez
- Division of Gerontology, Geriatrics and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (T.W.B.); (C.S.C.)
- UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Nathan Shock Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Correspondence:
| | - Keri M. Kemp
- CardioRenal Physiology and Medicine Section, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Sara N. Burke
- Center for Cognitive Aging and Memory, Department of Neuroscience and McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32611, USA;
| | - Thomas W. Buford
- Division of Gerontology, Geriatrics and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (T.W.B.); (C.S.C.)
- UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Nathan Shock Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Integrative Center for Aging Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Geriatric Research Education and Clinical Center, Birmingham VA Medical Center, Birmingham, AL 35294, USA
| | - Christy S. Carter
- Division of Gerontology, Geriatrics and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (T.W.B.); (C.S.C.)
- UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Nathan Shock Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Integrative Center for Aging Research, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Yang F, Yang Y, Chen L, Zhang Z, Liu L, Zhang C, Mai Q, Chen Y, Chen Z, Lin T, Chen L, Guo H, Zhou L, Shen H, Chen X, Liu L, Zhang G, Liao H, Zeng L, Zeng G. The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA. Gut Microbes 2022; 14:2029997. [PMID: 35343370 PMCID: PMC8966992 DOI: 10.1080/19490976.2022.2029997] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut microbiota may impact TB outcomes are not fully understood. Here, we found that broad-spectrum antibiotics treatment increased susceptibility to Mycobacterium tuberculosis (M. tuberculosis) infection and modulated pulmonary inflammatory responses in mouse M. tuberculosis infection model. We then identified a commensal gut bacteria-regulated lncRNA, termed lncRNA-CGB, which was down-regulated by dysbiosis of gut microbiota during TB infection. Furthermore, we found that Bacteroides fragilis (B. fragilis) was a direct regulator of lncRNA-CGB, and oral administration of B. fragilis enhanced expression of lncRNA-CGB and promoted anti-TB immunity. Genomic knock-out of lncRNA-CGB led to reduced IFN-γ expression and impaired anti-TB immunity, therefore leading to detrimental effects on M. tuberculosis infection. Mechanistically, lncRNA-CGB interacted with EZH2 and negatively regulated H3K27 tri-methylation (H3K27Me3) epigenetic programming, leading to enhanced IFN-γ expression. Thus, this work not only uncovered previously unrecognized importance of gut bacteria-lncRNA-EZH2-H3K27Me3 axis in conferring immune protection against TB but also identified a potential new paradigm to develop a microbiota-based treatment against TB and potentially other diseases.
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Affiliation(s)
- Fang Yang
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Yi Yang
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Lingming Chen
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Zhiyi Zhang
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Linna Liu
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina,Linna Liu Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China
| | - Chunmin Zhang
- Drepartment of Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Picu, GuangzhouChina
| | - Qiongdan Mai
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Yiwei Chen
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Zixu Chen
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Tao Lin
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina
| | - Liang Chen
- Guangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, GuangzhouChina
| | - Huixin Guo
- Guangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, GuangzhouChina
| | - Lin Zhou
- Guangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, GuangzhouChina
| | - Hongbo Shen
- Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Institute for Advanced Study, Tongji University School of Medicine, Shanghai, China
| | - Xinchun Chen
- Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, GuangdongChina
| | - Lei Liu
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, National Clinical Research Center for Tuberculosis, Southern University of Science and Technology, National Clinical Research Center for Tuberculosis, Shenzhen, China
| | - Guoliang Zhang
- Institute for Hepatology, National Clinical Research Center for Infectious Disease, Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, National Clinical Research Center for Tuberculosis, Southern University of Science and Technology, National Clinical Research Center for Tuberculosis, Shenzhen, China
| | - Hongying Liao
- De
partment of Thoracic Surgery, Thoracic Cancer Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China,Hongying Liao Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lingchan Zeng
- Clinical Research Center, Department of Medical Records Management, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China,Lingchan Zeng Clinical Research Center, Department of Medical Records Management, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Gucheng Zeng
- Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, GuangzhouChina,CONTACT Gucheng Zeng Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education
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Sheng C, Yang K, He B, Du W, Cai Y, Han Y. Combination of gut microbiota and plasma amyloid-β as a potential index for identifying preclinical Alzheimer's disease: a cross-sectional analysis from the SILCODE study. Alzheimers Res Ther 2022; 14:35. [PMID: 35164860 PMCID: PMC8843023 DOI: 10.1186/s13195-022-00977-x] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 02/06/2022] [Indexed: 12/15/2022]
Abstract
Background Plasma amyloid-β (Aβ) may facilitate identification of individuals with brain amyloidosis. Gut microbial dysbiosis in Alzheimer’s disease (AD) is increasingly being recognized. However, knowledge about alterations of gut microbiota in preclinical AD, as well as whether the combination of plasma Aβ and gut microbiota could identify preclinical AD, remains largely unknown. Methods This study recruited 34 Aβ-negative cognitively normal (CN−) participants, 32 Aβ-positive cognitively normal (CN+) participants, and 22 patients with cognitive impairment (CI), including 11 patients with mild cognitive impairment (MCI) and 11 AD dementia patients. All participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Meso Scale Discovery (MSD) kits were used to quantify the plasma Aβ40, Aβ42, and Aβ42/Aβ40 in CN− and CN+ participants. Using Spearman’s correlation analysis, the associations of global standard uptake value rate (SUVR) with altered gut microbiota and plasma Aβ markers were separately evaluated. Furthermore, the discriminative power of the combination of gut microbiota and plasma Aβ markers for identifying CN+ individuals was investigated. Results Compared with the CN− group, the CN+ group showed significantly reduced plasma Aβ42 (p = 0.011) and Aβ42/Aβ40 (p = 0.003). The relative abundance of phylum Bacteroidetes was significantly enriched, whereas phylum Firmicutes and class Deltaproteobacteria were significantly decreased in CN+ individuals in comparison with that in CN− individuals. Particularly, the relative abundance of phylum Firmicutes and its corresponding SCFA-producing bacteria exhibited a progressive decline tendency from CN− to CN+ and CI. Besides, the global brain Aβ burden was negatively associated with the plasma Aβ42/Aβ40 (r = −0.298, p = 0.015), family Desulfovibrionaceae (r = −0.331, p = 0.007), genus Bilophila (r = −0.247, p = 0.046), and genus Faecalibacterium (r = −0.291, p = 0.018) for all CN participants. Finally, the combination of plasma Aβ markers, altered gut microbiota, and cognitive performance reached a relatively good discriminative power in identifying individuals with CN+ from CN− (AUC = 0.869, 95% CI 0.782 ~ 0.955). Conclusions This study provided the evidence that the gut microbial composition was altered in preclinical AD. The combination of plasma Aβ and gut microbiota may serve as a non-invasive, cost-effective diagnostic tool for early AD screening. Targeting the gut microbiota may be a novel therapeutic strategy for AD. Trial registration This study has been registered in ClinicalTrials.gov (NCT03370744, https://www.clinicaltrials.gov) in November 15, 2017. Supplementary Information The online version contains supplementary material available at 10.1186/s13195-022-00977-x.
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Affiliation(s)
- Can Sheng
- Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
| | - Kun Yang
- Evidence-Based Medicine Center, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.,Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Beiqi He
- Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, 570228, China
| | - Wenying Du
- Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
| | - Yanning Cai
- Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.,Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100053, China.,Department of Biobank, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
| | - Ying Han
- Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China. .,Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, 570228, China. .,Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, 100053, China. .,National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China.
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Mora-Janiszewska O, Faryniak-Zuzak A, Darmochwał-Kolarz D. Epigenetic Links between Microbiota and Gestational Diabetes. Int J Mol Sci 2022; 23:1831. [PMID: 35163753 PMCID: PMC8837149 DOI: 10.3390/ijms23031831] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/29/2022] [Accepted: 02/03/2022] [Indexed: 02/01/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is considered a significant and increasing worldwide problem. The growing body of evidence on this topic has allowed us to point out that a hostile intrauterine environment in mothers with GDM via epigenetic mechanisms induces "diabetogenic" and "obesogenic" changes in an offspring's DNA. This sets a vicious intergenerational cycle of metabolic diseases in motion, gradually deteriorating the health of the human population. One of the most important participants of this process seems to be altered microbiota. There is a chance that the identification of specific epigenetic marks may provide a key for future diagnostic, prognostic and therapeutic solutions in the field of personalised medicine. Given the reversibility of most epigenetic changes, there is an opportunity to improve the long-term health of the human population. In this manuscript, we aim to summarise available data on epigenetic changes among women suffering from GDM and their progeny, in association with alterations in the microbiome.
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Moya-Alvarez V, Sansonetti PJ. Understanding the pathways leading to gut dysbiosis and enteric environmental dysfunction in infants: the influence of maternal dysbiosis and other microbiota determinants during early life. FEMS Microbiol Rev 2022; 46:6516326. [PMID: 35088084 DOI: 10.1093/femsre/fuac004] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 12/10/2021] [Accepted: 01/25/2022] [Indexed: 11/13/2022] Open
Abstract
Maternal environmental enteric dysfunction (EED) encompasses undernutrition with an inflammatory gut profile, a variable degree of dysbiosis and increased translocation of pathogens in the gut mucosa. Even though recent research findings have shed light on the pathological pathways underlying the establishment of the infant gut dysbiosis, evidence on how maternal EED influences the development of gut dysbiosis and EED in the offspring remains elusive. This review summarizes the current knowledge on the effect of maternal dysbiosis and EED on infant health, and explores recent progress in unraveling the mechanisms of acquisition of a dysbiotic gut microbiota in the offspring. In Western communities, maternal inoculum, delivery mode, perinatal antibiotics, feeding practices, and infections are the major drivers of the infant gut microbiota during the first two years of life. In other latitudes, the infectious burden and maternal malnutrition might introduce further risk factors for infant gut dysbiosis. Novel tools, such as transcriptomics and metabolomics, have become indispensable to analyze the metabolic environment of the infant in utero and post-partum. Human-milk oligosaccharides have essential prebiotic, antimicrobial, and anti-biofilm properties that might offer additional therapeutic opportunities.
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Affiliation(s)
- Violeta Moya-Alvarez
- Molecular Microbial Pathogenesis - INSERM U1202, Department of Cell Biology and Infection, 28 rue du Dr. Roux, Institut Pasteur, 75015 Paris, France.,Epidemiology of Emergent Diseases Unit, Global Health Department, 25 rue du Dr. Roux, Institut Pasteur, 75015 Paris, France
| | - Philippe J Sansonetti
- Molecular Microbial Pathogenesis - INSERM U1202, Department of Cell Biology and Infection, 28 rue du Dr. Roux, Institut Pasteur, 75015 Paris, France.,Chaire de Microbiologie et Maladies Infectieuses, Collège de France, Paris, France.,The Center for Microbes, Development and Health, Institut Pasteur de Shanghai, China
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van der Vossen EWJ, Bastos D, Stols-Gonçalves D, de Goffau MC, Davids M, Pereira JPB, Li Yim AYF, Henneman P, Netea MG, de Vos WM, de Jonge W, Groen AK, Nieuwdorp M, Levin E. Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome. Gut Microbes 2022; 13:1993513. [PMID: 34747338 PMCID: PMC8583152 DOI: 10.1080/19490976.2021.1993513] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.
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Affiliation(s)
- Eduard W. J. van der Vossen
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Diogo Bastos
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands,Horaizon BV, Delft, The Netherlands
| | - Daniela Stols-Gonçalves
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Marcus C. de Goffau
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands,Wellcome Sanger Institute, Cambridge, UK
| | - Mark Davids
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Joao P. B. Pereira
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands,Horaizon BV, Delft, The Netherlands
| | - Andrew Y. F. Li Yim
- Department of Genome Diagnostics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Peter Henneman
- Department of Genome Diagnostics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Mihai G. Netea
- Department of Experimental Internal Medicine, Radboud University, Nijmegen, The Netherlands,Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (Limes), University of Bonn, Bonn, Germany
| | - Willem M. de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands,Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Wouter de Jonge
- Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Albert K. Groen
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands,CONTACT Max Nieuwdorp
| | - Evgeni Levin
- Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands,Horaizon BV, Delft, The Netherlands,Evgeni Levin Department of Vascular Medicine, Amsterdam University Medical Center, Meibergdreef 9, Room G1-143, Amsterdam1105 AZ, The Netherlands
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Hung CC, Chang CC, Huang CW, Nouchi R, Cheng CH. Gut microbiota in patients with Alzheimer's disease spectrum: a systematic review and meta-analysis. Aging (Albany NY) 2022; 14:477-496. [PMID: 35027502 PMCID: PMC8791218 DOI: 10.18632/aging.203826] [Citation(s) in RCA: 110] [Impact Index Per Article: 36.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 12/20/2021] [Indexed: 11/25/2022]
Abstract
CONTEXT Gut dysbiosis has been proposed as one of pathologies in patients with Alzheimer's disease (AD) spectrum. Despite such enthusiasm, the relevant results remain substantially controversial. OBJECTIVE A systematic review and meta-analysis were performed to investigate the differences of gut microbiota (GM) between patients with AD spectrum (including mild cognitive impairment [MCI] and AD) and healthy controls (HC). DATA SOURCES PubMed, MEDLINE, Scopus, and Cochrane Library from January 2000 to August 2021. Eligibility criteria for study selection: Observational trials and pre-intervention data of intervention trials that investigated the abundance of GM in patients with AD spectrum and HC. DATA EXTRACTION AND SYNTHESIS Two reviewers independently identified articles, extracted data, and evaluated the risk of bias. The effect sizes were performed by a random-effect, inverse-variance weighted model. The effects of different countries and of clinical stages on GM abundance were also examined. RESULTS 11 studies consisting of 378 HC and 427 patients with AD spectrum were included in the meta-analysis. Patients with AD, but not MCI, showed significantly reduced GM diversity as compared to HC. We also found more abundance of Proteobacteria, Bifidobacterium and Phascolarctobacterium, but less abundance of Firmicutes, Clostridiaceae, Lachnospiraceae and Rikenellaceae in patients with AD spectrum as compared with HC. The profiles of abundance of Alistipes and Bacteroides in HC and AD spectrum were differentially affected by countries. Finally, when considering clinical stage as a moderator, the comparisons of abundance in Clostridiaceae and Phascolarctobacterium showed large effect sizes, with gradient changes from MCI to AD stage. LIMITATIONS The inclusion of studies originating only from China and the U.S. was a possible limitation. CONCLUSIONS Patients with AD spectrum demonstrated altered GM abundance, which was differentially mediated by countries and clinical stages.
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Affiliation(s)
- Chun-Che Hung
- Department of Occupational Therapy and Graduate Institute of Behavioral Sciences, Chang Gung University, Taoyuan, Taiwan.,Laboratory of Brain Imaging and Neural Dynamics (BIND Lab), Chang Gung University, Taoyuan, Taiwan
| | - Chiung-Chih Chang
- Department of Neurology and Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chi-Wei Huang
- Department of Neurology and Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Rui Nouchi
- Department of Cognitive Health Science, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan.,Smart Aging Research Center (S.A.R.C), Tohoku University, Sendai, Japan
| | - Chia-Hsiung Cheng
- Department of Occupational Therapy and Graduate Institute of Behavioral Sciences, Chang Gung University, Taoyuan, Taiwan.,Laboratory of Brain Imaging and Neural Dynamics (BIND Lab), Chang Gung University, Taoyuan, Taiwan.,Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.,Department of Psychiatry, Chang Gung Memorial Hospital, Linkou, Taiwan
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