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Eslami M, Pakmehr A, Pourghazi F, Kami A, Ejtahed HS, Mohajeri-Tehrani M, Hasani-Ranjbar S, Larijani B. The anti-obesity effects of postbiotics: A systematic review of pre-clinical and clinical studies. Clin Nutr ESPEN 2024; 64:370-389. [PMID: 39461594 DOI: 10.1016/j.clnesp.2024.10.153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/30/2024] [Accepted: 10/09/2024] [Indexed: 10/29/2024]
Abstract
BACKGROUND The growing prevalence of obesity has become a major concern worldwide, therefore a great number of studies are conducted every day in the field of obesity. Since postbiotics are a newly introduced term, there is not much systematic evidence about their function and impact on obesity. We designed this study to systematically review the effect of different types of postbiotics on obesity. METHODS A systematic search was conducted using PubMed, SCOPUS, and Web of Science databases up to August 2023. Both human and animal interventional studies that investigated the effects of any type of postbiotic on obesity and obesity-related factors were eligible. Screening, data extraction, and quality assessment were conducted independently by two researchers. The quality of the studies was appraised using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE's) risk of bias tool. RESULTS Of the 19373 retrieved studies, finally, 49 studies were included (9 human studies and 40 animal studies). Short-chain fatty acids and heat-killed (inactivated) bacteria were the most used postbiotics. In human clinical trials, inactivated Lactobacillus amylovorus (CP1563), Bifidobacterium animalis subsp. lactis (CECT 8145) and Pediococcus pentosaceus (LP28) were administered orally as postbiotics which improved body composition and anthropometric indices. Animal studies evaluated other types of postbiotics including muramyl dipeptide, cell-free extracts, urolithin A&B, extracellular Vesicles, exopolysaccharides, and surface Layer Proteins, supporting the anti-obesity effects of postbiotics. CONCLUSION Postbiotics seem to be a safe intervention and the results were in favor of a reduction in adipogenesis as well as an increase in energy expenditure. Further high-quality studies are required in this relatively new topic.
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Affiliation(s)
- Maysa Eslami
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Azin Pakmehr
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzad Pourghazi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Atefe Kami
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohammadreza Mohajeri-Tehrani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shirin Hasani-Ranjbar
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Jeyaraman M, Mariappan T, Jeyaraman N, Muthu S, Ramasubramanian S, Santos GS, da Fonseca LF, Lana JF. Gut microbiome: A revolution in type II diabetes mellitus. World J Diabetes 2024; 15:1874-1888. [PMID: 39280189 PMCID: PMC11372632 DOI: 10.4239/wjd.v15.i9.1874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 06/11/2024] [Accepted: 07/18/2024] [Indexed: 08/27/2024] Open
Abstract
Type II diabetes mellitus (T2DM) has experienced a dramatic increase globally across countries of various income levels over the past three decades. The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors. While numerous pharmaceutical therapies have been developed, there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects. In this context, the exploration of the gut microbiome presents a promising avenue. Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals, suggesting its potential role in the disease's pathogenesis and progression. This emerging field offers diverse applications, particularly in modifying the gut environment through the administration of prebiotics, probiotics, and fecal microbiome transfer. These inter-ventions aim to restore a healthy microbiome balance, which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM. Although current results from clinical trials have not yet shown dramatic effects on diabetes management, the groundwork has been laid for deeper investigation. Ongoing and future clinical trials are critical to advancing our understanding of the microbiome's impact on diabetes. By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism, researchers can develop more targeted interventions. The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM, potentially reducing the disease's burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic, systemic health improvements.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Tejaswin Mariappan
- Department of Community Medicine, Government Stanley Medical College and Hospital, Chennai 600001, Tamil Nadu, India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Government Medical College, Karur 639004, Tamil Nadu, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Gabriel Silva Santos
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
| | - Lucas Furtado da Fonseca
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
| | - José Fábio Lana
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
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Lin Z, Sun L. Research advances in the therapy of metabolic syndrome. Front Pharmacol 2024; 15:1364881. [PMID: 39139641 PMCID: PMC11319131 DOI: 10.3389/fphar.2024.1364881] [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: 01/05/2024] [Accepted: 07/08/2024] [Indexed: 08/15/2024] Open
Abstract
Metabolic syndrome refers to the pathological state of metabolic disorder of protein, fat, carbohydrate, and other substances in the human body. It is a syndrome composed of a group of complex metabolic disorders, whose pathogenesis includes multiple genetic and acquired entities falling under the category of insulin resistance and chronic low-grade inflammationand. It is a risk factor for increased prevalence and mortality from diabetes and cardiovascular disease. Cardiovascular diseases are the predominant cause of morbidity and mortality globally, thus it is imperative to investigate the impact of metabolic syndrome on alleviating this substantial disease burden. Despite the increasing number of scientists dedicating themselves to researching metabolic syndrome in recent decades, numerous aspects of this condition remain incompletely understood, leaving many questions unanswered. In this review, we present an epidemiological analysis of MetS, explore both traditional and novel pathogenesis, examine the pathophysiological repercussions of metabolic syndrome, summarize research advances, and elucidate the mechanisms underlying corresponding treatment approaches.
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Affiliation(s)
- Zitian Lin
- Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom
- Zhejiang University-University of Edinburgh Institute, International Campus, Zhejiang University, Haining, China
| | - Luning Sun
- Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China
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Jiang R, Cong Z, Zheng L, Zhang L, Guan Q, Wang S, Fang J, Chen J, Liu M. Global research trends in regulating gut microbiome to improve type 2 diabetes mellitus: bibliometrics and visual analysis. Front Endocrinol (Lausanne) 2024; 15:1401070. [PMID: 38887274 PMCID: PMC11181692 DOI: 10.3389/fendo.2024.1401070] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/17/2024] [Indexed: 06/20/2024] Open
Abstract
Background Gut microbiome (GM) and type 2 diabetes mellitus (T2DM) have two-way effects. Improving T2DM by modulating GM in various ways, such as diet, exercise, and medication, is gradually becoming popular, and related studies have yielded positive results. However, there is still a lack of high-quality bibliometric analyses of research in this area. This study aims to systematize and comprehensively summarize the knowledge structure, research tropics, and research trends of GM and T2DM through bibliometric analysis. Methods Publications related to GM and T2DM before January 9, 2024, in the Web of Science Core Collection (WOSCC) were searched in this study. Microsoft Excel 2019 was used to analyze publishing trends and CiteSpace (v.6.1.R6 Advanced) was used to analyze institutions, cited journals, references, and keywords.SCImago Graphica (v.1.0.39) was used to analyze countries/regions, institutions' collaborations, cited authors, and published journals. Results We finally included 1004 articles published from 2008 to 2023. The number of published articles showed an upward trend and reached its peak in 2022. China is the country with the largest number of articles, Univ Copenhagen is the institution with the largest number of articles, Fukui, Michiaki, Hamaguchi, Masahide are the scholars with the largest number of articles, and Cani and Patrice D. are the scholars with the largest number of citations. NUTRIENTS(Q1/5.9) published the most publications, while Nature (Q1/64.8; Cited 804 times) is the most frequently cited journal. Gut microbiota, Obesity, and insulin resistance are the most frequently used keywords. This study found that current researches focus on the effects of diet, exercise, and pharmacological modification of GM to improve T2DM and explores specific mechanisms. Future researches will focus on three areas: complications of T2DM and specific physiological processes, methods and measures to regulate GM, and new experimental techniques and assays. Conclusion The current researches confirmed the effects and specific mechanisms of modulating GM to improve T2DM. Further exploration of the effects of modulating GM on T2DM complications and specific physiologic processes is a future trend of research. Exploring specific methods for regulating GM and developing new experimental techniques and assays are important for future research.
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Affiliation(s)
- Rongsheng Jiang
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Zhengri Cong
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Likun Zheng
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Long Zhang
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Qifan Guan
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Sixian Wang
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Jinxu Fang
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
| | - Jiahao Chen
- College of Medical Information, Changchun University of Chinese Medicine, Changchun, China
| | - Mingjun Liu
- College of Acupuncture and Tuina, Changchun University of Chinese Medicine, Changchun, China
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Hasanian-Langroudi F, Ghasemi A, Hedayati M, Siadat SD, Tohidi M. Novel Insight into the Effect of Probiotics in the Regulation of the Most Important Pathways Involved in the Pathogenesis of Type 2 Diabetes Mellitus. Probiotics Antimicrob Proteins 2024; 16:829-844. [PMID: 37162668 DOI: 10.1007/s12602-023-10056-8] [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] [Accepted: 03/02/2023] [Indexed: 05/11/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is considered one of the most common disorders worldwide. Although several treatment modalities have been developed, the existing interventions have not yielded the desired results. Therefore, researchers have focused on finding treatment choices with low toxicity and few adverse effects that could control T2DM efficiently. Various types of research on the role of gut microbiota in developing T2DM and its related complications have led to the growing interest in probiotic supplementation. Several properties make these organisms unique in terms of human health, including their low cost, high reliability, and good safety profile. Emerging evidence has demonstrated that three of the most important signaling pathways, including nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and nuclear factor erythroid 2-related factor 2 (Nrf2), which involved in the pathogenesis of T2DM, play key functions in the effects of probiotics on this disease. Hence, we will focus on the clinical applications of probiotics in the management of T2DM. Then, we will also discuss the roles of the involvement of various probiotics in the regulation of the most important signaling pathways (NF-κB, PI3K/Akt, and Nrf2) involved in the pathogenesis of T2DM.
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Affiliation(s)
- Farzaneh Hasanian-Langroudi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box, Tehran, 19395-4763, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
- Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran.
| | - Maryam Tohidi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box, Tehran, 19395-4763, Iran.
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Othman MB, Takeda R, Sekita M, Okazaki K, Sakamoto K. Amber (Succinite) Extract Enhances Glucose Uptake through the Up-Regulation of ATP and Down-Regulation of ROS in Mouse C2C12 Cells. Pharmaceuticals (Basel) 2024; 17:586. [PMID: 38794156 PMCID: PMC11124190 DOI: 10.3390/ph17050586] [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: 03/25/2024] [Revised: 04/29/2024] [Accepted: 05/01/2024] [Indexed: 05/26/2024] Open
Abstract
Traditionally, amber (Succinite) has been used to alleviate all types of pain, skin allergies, and headaches. However, no studies have been conducted on its antidiabetic and antioxidant effects. In this study, differentiated skeletal muscle C2C12 cells were used to demonstrate the protective effects of amber (AMB) against H2O2-induced cell death. In addition, the effects of AMB on glucose uptake and ATP production were investigated. Our results showed that AMB at 10, 25, and 50 μg/mL suppressed the elevation of ROS production induced by H2O2 in a dose-dependent manner. Moreover, AMB enhanced glucose utilization in C2C12 cells through the improvement of ATP production and an increase in PGC-1α gene expression resulting in an amelioration of mitochondrial activity. On the other hand, AMB significantly increased the gene expression of glucose transporters GLUT4 and GLUT1. Our finding suggests that AMB can be used as a natural supplement for diabetes treatment and for the promotion of skeletal muscle function.
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Affiliation(s)
- Mahmoud Ben Othman
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan;
| | - Reiko Takeda
- Kohaku Bio Technology Co., Ltd., Morioka 020-8551, Japan; (R.T.); (M.S.); (K.O.)
| | - Marie Sekita
- Kohaku Bio Technology Co., Ltd., Morioka 020-8551, Japan; (R.T.); (M.S.); (K.O.)
| | - Kazuma Okazaki
- Kohaku Bio Technology Co., Ltd., Morioka 020-8551, Japan; (R.T.); (M.S.); (K.O.)
| | - Kazuichi Sakamoto
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan;
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Shen W, Chen Q, Lin R, Hu Z, Luo M, Ren Y, Huang K, Wang L, Chen S, Wang L, Ruan Y, Feng L. Imbalance of gut microbiota in gestational diabetes. BMC Pregnancy Childbirth 2024; 24:226. [PMID: 38561737 PMCID: PMC10983739 DOI: 10.1186/s12884-024-06423-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 03/14/2024] [Indexed: 04/04/2024] Open
Abstract
AIM To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients. METHODS A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition. RESULTS (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643). CONCLUSIONS Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients. TRIAL REGISTRATION The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 ).
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Affiliation(s)
- Weiyi Shen
- Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
- Prevention and Treatment Research Center of Senescent Disease, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, China
| | - Qianyi Chen
- Department of Nutriology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
| | - Renbin Lin
- Department of Gastroenterology, Hangzhou Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medicine University, Hangzhou, 310005, Zhejiang Province, China
| | - Zhefang Hu
- Department of Nutriology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
| | - Man Luo
- Department of Nutriology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
| | - Yanwei Ren
- Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
| | - Keren Huang
- Department of Nutriology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
| | - Li Wang
- Department of Nutriology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
| | - Shujie Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
- Prevention and Treatment Research Center of Senescent Disease, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, China
| | - Lan Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
- Prevention and Treatment Research Center of Senescent Disease, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang Province, China
| | - Yu Ruan
- Department of Endocrinology and Metabolism, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China
| | - Lijun Feng
- Department of Nutriology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang Province, China.
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Tian Z, Zhang X, Yao G, Jin J, Zhang T, Sun C, Wang Z, Zhang Q. Intestinal flora and pregnancy complications: Current insights and future prospects. IMETA 2024; 3:e167. [PMID: 38882493 PMCID: PMC11170975 DOI: 10.1002/imt2.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/27/2023] [Accepted: 12/22/2023] [Indexed: 06/18/2024]
Abstract
Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as "sterile womb" versus "in utero colonization." Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut-derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.
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Affiliation(s)
- Zhenyu Tian
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Xinjie Zhang
- Department of Biology University College London London UK
| | - Guixiang Yao
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Jiajia Jin
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Tongxue Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Chunhua Sun
- Department of Health Management Center, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan China
| | - Zhe Wang
- Department of Geriatrics Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China
| | - Qunye Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
- Cardiovascular Disease Research Center of Shandong First Medical University Central Hospital Affiliated to Shandong First Medical University Jinan China
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Ma L, La X, Zhang B, Xu W, Tian C, Fu Q, Wang M, Wu C, Chen Z, Chang H, Li JA. Total Astragalus saponins can reverse type 2 diabetes mellitus-related intestinal dysbiosis and hepatic insulin resistance in vivo. Front Endocrinol (Lausanne) 2023; 14:1190827. [PMID: 38053727 PMCID: PMC10694298 DOI: 10.3389/fendo.2023.1190827] [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: 08/07/2023] [Accepted: 10/31/2023] [Indexed: 12/07/2023] Open
Abstract
Objective Intestinal flora homeostasis in rats with type 2 diabetes mellitus (T2DM) was evaluated to explore the effects of total Astragalus saponins (TAS) on hepatic insulin resistance (IR). Methods Six-week-old male Sprague-Dawley rats were fed high-fat and high-sugar diet for 4 weeks and intraperitoneally injected with streptozotocin to induce T2DM, and they were then randomly divided into control, model, metformin, and TAS groups. Stool, serum, colon, and liver samples were collected after 8 weeks of drug administration for relevant analyses. Results TAS reduced fasting blood glucose, 2-hour postprandial blood glucose, area under the curve of oral glucose tolerance test, glycated serum protein, homeostasis model assessment of insulin resistance, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in T2DM rats but increased insulin, C-peptide, and high-density lipoprotein cholesterol levels. Moreover, TAS improved the morphology and structure of liver and colon tissues and improved the composition of the intestinal microbiome and bacterial community structure at different taxonomic levels. In addition, TAS increased the protein expression of hepatic IRS-1, PI3K, PDK1, and p-AKT and decreased the protein expression of p-GSK-3β. Meanwhile, TAS increased the mRNA expression of liver PDK1, PI3K, and GS and decreased the mRNA expression of GSK-3β. Conclusion TAS can ameliorate T2DM-related abnormal glucose and blood lipid metabolism, intestinal dysbiosis, and IR.
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Affiliation(s)
- Leilei Ma
- School of Public Health, North China University of Science and Technology, Tangshan, China
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Xiaojin La
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Biwei Zhang
- School of Public Health, North China University of Science and Technology, Tangshan, China
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Wenxuan Xu
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Chunyu Tian
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Qianru Fu
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Meng Wang
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Chenxi Wu
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Zhen Chen
- Oriental Herbs Korlatolt felelossegu tarsasag, Budapest, Hungary
| | - Hong Chang
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
| | - Ji-an Li
- School of Public Health, North China University of Science and Technology, Tangshan, China
- He Bei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China
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10
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Tang J, Wei Y, Pi C, Zheng W, Zuo Y, Shi P, Chen J, Xiong L, Chen T, Liu H, Zhao Q, Yin S, Ren W, Cao P, Zeng N, Zhao L. The therapeutic value of bifidobacteria in cardiovascular disease. NPJ Biofilms Microbiomes 2023; 9:82. [PMID: 37903770 PMCID: PMC10616273 DOI: 10.1038/s41522-023-00448-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 10/03/2023] [Indexed: 11/01/2023] Open
Abstract
There has been an increase in cardiovascular morbidity and mortality over the past few decades, making cardiovascular disease (CVD) the leading cause of death worldwide. However, the pathogenesis of CVD is multi-factorial, complex, and not fully understood. The gut microbiome has long been recognized to play a critical role in maintaining the physiological and metabolic health of the host. Recent scientific advances have provided evidence that alterations in the gut microbiome and its metabolites have a profound influence on the development and progression of CVD. Among the trillions of microorganisms in the gut, bifidobacteria, which, interestingly, were found through the literature to play a key role not only in regulating gut microbiota function and metabolism, but also in reducing classical risk factors for CVD (e.g., obesity, hyperlipidemia, diabetes) by suppressing oxidative stress, improving immunomodulation, and correcting lipid, glucose, and cholesterol metabolism. This review explores the direct and indirect effects of bifidobacteria on the development of CVD and highlights its potential therapeutic value in hypertension, atherosclerosis, myocardial infarction, and heart failure. By describing the key role of Bifidobacterium in the link between gut microbiology and CVD, we aim to provide a theoretical basis for improving the subsequent clinical applications of Bifidobacterium and for the development of Bifidobacterium nutritional products.
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Affiliation(s)
- Jia Tang
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Yumeng Wei
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Chao Pi
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Wenwu Zheng
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Ying Zuo
- Department of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Peng Shi
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Jinglin Chen
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Linjin Xiong
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Tao Chen
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Huiyang Liu
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Qianjiao Zhao
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Suyu Yin
- Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, P.R. China
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Wei Ren
- National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China
| | - Peng Cao
- The Affiliated Hospital of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, P.R. China.
| | - Nan Zeng
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China.
| | - Ling Zhao
- Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China.
- Chengdu University of Traditional Chinese Medicine State Key Laboratory of Southwestern Chinese Medicine Resources, 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan, 611137, P.R. China.
- Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China.
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11
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Wang J, Qin Y, Jiang J, Shan H, Zhao C, Li S. The Effect of Theaflavins on the Gut Microbiome and Metabolites in Diabetic Mice. Foods 2023; 12:3865. [PMID: 37893758 PMCID: PMC10606624 DOI: 10.3390/foods12203865] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 10/29/2023] Open
Abstract
With the development of diabetes, the gut microbiome falls into a state of dysbiosis, further affecting its progression. Theaflavins (TFs), a type of tea polyphenol derivative, show anti-diabetic properties, but their effect on the gut microbiome in diabetic mice is unclear. It is unknown whether the improvement of TFs on hyperglycemia and hyperlipidemia in diabetic mice is related to gut microbiota. Therefore, in this study, different concentrations of TFs were intragastrically administered to mice with diabetes induced by a high-fat-diet to investigate their effects on blood glucose, blood lipid, and the gut microbiome in diabetic mice, and the plausible mechanism underlying improvement in diabetes was explored from the perspective of the gut microbiome. The results showed that the TFs intervention significantly improved the hyperglycemia and hyperlipidemia of diabetic mice and affected the structure of the gut microbiome by promoting the growth of bacteria positively related to diabetes and inhibiting those negatively related to diabetes. The changes in short-chain fatty acids in mice with diabetes and functional prediction analysis suggested that TFs may affect carbohydrate metabolism and lipid metabolism by regulating the gut microbiome. These findings emphasize the ability of TFs to shape the diversity and structure of the gut microbiome in mice with diabetes induced by a high-fat diet combined with streptozotocin and have practical implications for the development of functional foods with TFs.
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Affiliation(s)
- Jun Wang
- School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China; (J.W.)
| | - Yixin Qin
- School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China; (J.W.)
| | - Jingjing Jiang
- School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China; (J.W.)
| | - Hongyan Shan
- School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China; (J.W.)
| | - Changyu Zhao
- School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China; (J.W.)
| | - Songnan Li
- Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou 225009, China
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12
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Vallianou NG, Kounatidis D, Tsilingiris D, Panagopoulos F, Christodoulatos GS, Evangelopoulos A, Karampela I, Dalamaga M. The Role of Next-Generation Probiotics in Obesity and Obesity-Associated Disorders: Current Knowledge and Future Perspectives. Int J Mol Sci 2023; 24:ijms24076755. [PMID: 37047729 PMCID: PMC10095285 DOI: 10.3390/ijms24076755] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/31/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023] Open
Abstract
Obesity and obesity-associated disorders pose a major public health issue worldwide. Apart from conventional weight loss drugs, next-generation probiotics (NGPs) seem to be very promising as potential preventive and therapeutic agents against obesity. Candidate NGPs such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Anaerobutyricum hallii, Bacteroides uniformis, Bacteroides coprocola, Parabacteroides distasonis, Parabacteroides goldsteinii, Hafnia alvei, Odoribacter laneus and Christensenella minuta have shown promise in preclinical models of obesity and obesity-associated disorders. Proposed mechanisms include the modulation of gut flora and amelioration of intestinal dysbiosis, improvement of intestinal barrier function, reduction in chronic low-grade inflammation and modulation of gut peptide secretion. Akkermansia muciniphila and Hafnia alvei have already been administered in overweight/obese patients with encouraging results. However, safety issues and strict regulations should be constantly implemented and updated. In this review, we aim to explore (1) current knowledge regarding NGPs; (2) their utility in obesity and obesity-associated disorders; (3) their safety profile; and (4) their therapeutic potential in individuals with overweight/obesity. More large-scale, multicentric and longitudinal studies are mandatory to explore their preventive and therapeutic potential against obesity and its related disorders.
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Affiliation(s)
- Natalia G. Vallianou
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Street, 10676 Athens, Greece
| | - Dimitris Kounatidis
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Street, 10676 Athens, Greece
| | - Dimitrios Tsilingiris
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Fotis Panagopoulos
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Street, 10676 Athens, Greece
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece
- Department of Microbiology, Sismanogleio General Hospital, 1 Sismanogleiou Street, 15126 Athens, Greece
| | - Angelos Evangelopoulos
- Roche Hellas Diagnostics S.A., 18-20 Amarousiou-Chalandriou Street, 15125 Athens, Greece
| | - Irene Karampela
- 2nd Department of Critical Care, Medical School, University of Athens, Attikon General University Hospital, 1 Rimini Street, 12462 Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece
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13
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Park SJ, Sharma A, Lee HJ. Postbiotics against Obesity: Perception and Overview Based on Pre-Clinical and Clinical Studies. Int J Mol Sci 2023; 24:6414. [PMID: 37047387 PMCID: PMC10095054 DOI: 10.3390/ijms24076414] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/13/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
Overweight and obesity are significant global public health concerns that are increasing in prevalence at an alarming rate. Numerous studies have demonstrated the benefits of probiotics against obesity. Postbiotics are the next generation of probiotics that include bacteria-free extracts and nonviable microorganisms that may be advantageous to the host and are being increasingly preferred over regular probiotics. However, the impact of postbiotics on obesity has not been thoroughly investigated. Therefore, the goal of this review is to gather in-depth data on the ability of postbiotics to combat obesity. Postbiotics have been reported to have significant potential in alleviating obesity. This review comprehensively discusses the anti-obesity effects of postbiotics in cellular, animal, and clinical studies. Postbiotics exert anti-obesity effects via multiple mechanisms, with the major mechanisms including increased energy expenditure, reduced adipogenesis and adipocyte differentiation, suppression of food intake, inhibition of lipid absorption, regulation of lipid metabolism, and regulation of gut dysbiosis. Future research should include further in-depth studies on strain identification, scale-up of postbiotics, identification of underlying mechanisms, and well-defined clinical studies. Postbiotics could be a promising dietary intervention for the prevention and management of obesity.
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Affiliation(s)
- Seon-Joo Park
- Department of Food and Nutrition, College of Bionanotechnology, Gachon University, Seongnam-si 13120, Republic of Korea;
- Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam-si 13120, Republic of Korea
| | - Anshul Sharma
- Department of Food and Nutrition, College of Bionanotechnology, Gachon University, Seongnam-si 13120, Republic of Korea;
| | - Hae-Jeung Lee
- Department of Food and Nutrition, College of Bionanotechnology, Gachon University, Seongnam-si 13120, Republic of Korea;
- Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam-si 13120, Republic of Korea
- Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea
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14
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Hendricks SA, Vella CA, New DD, Aunjum A, Antush M, Geidl R, Andrews KR, Balemba OB. High-Resolution Taxonomic Characterization Reveals Novel Human Microbial Strains with Potential as Risk Factors and Probiotics for Prediabetes and Type 2 Diabetes. Microorganisms 2023; 11:758. [PMID: 36985331 PMCID: PMC10051885 DOI: 10.3390/microorganisms11030758] [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: 02/03/2023] [Revised: 02/27/2023] [Accepted: 03/11/2023] [Indexed: 03/18/2023] Open
Abstract
Alterations in the composition of the gut microbiota is thought to play a key role in causing type 2 diabetes, yet is not fully understood, especially at the strain level. Here, we used long-read DNA sequencing technology of 16S-ITS-23S rRNA genes for high-resolution characterization of gut microbiota in the development of type 2 diabetes. Gut microbiota composition was characterized from fecal DNA from 47 participants divided into 4 cohorts based on glycemic control: normal glycemic control (healthy; n = 21), reversed prediabetes (prediabetes/healthy; n = 8), prediabetes (n = 8), or type 2 diabetes (n = 10). A total of 46 taxa were found to be possibly related to progression from healthy state to type 2 diabetes. Bacteroides coprophilus DSM 18228, Bifidobacterium pseudocatenulatum DSM 20438, and Bifidobacterium adolescentis ATCC 15703 could confer resistance to glucose intolerance. On the other hand, Odoribacter laneus YIT 12061 may be pathogenic as it was found to be more abundant in type 2 diabetes participants than other cohorts. This research increases our understanding of the structural modulation of gut microbiota in the pathogenesis of type 2 diabetes and highlights gut microbiota strains, with the potential for targeted opportunistic pathogen control or consideration for probiotic prophylaxis and treatment.
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Affiliation(s)
- Sarah A. Hendricks
- Institute for Interdisciplinary Data Sciences, University of Idaho, Moscow, ID 83843, USA
| | - Chantal A. Vella
- Department of Movement Sciences, University of Idaho, Moscow, ID 83843, USA
- WWAMI Medical Education Program, University of Idaho, Moscow, ID 83843, USA
| | - Daniel D. New
- Institute for Interdisciplinary Data Sciences, University of Idaho, Moscow, ID 83843, USA
| | - Afiya Aunjum
- Department of Movement Sciences, University of Idaho, Moscow, ID 83843, USA
| | - Maximilian Antush
- Department of Movement Sciences, University of Idaho, Moscow, ID 83843, USA
| | - Rayme Geidl
- WWAMI Medical Education Program, University of Idaho, Moscow, ID 83843, USA
| | - Kimberly R. Andrews
- Institute for Interdisciplinary Data Sciences, University of Idaho, Moscow, ID 83843, USA
| | - Onesmo B. Balemba
- WWAMI Medical Education Program, University of Idaho, Moscow, ID 83843, USA
- Department of Biological Sciences, University of Idaho, Moscow, ID 83843, USA
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15
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Das S, Gnanasambandan R. Intestinal microbiome diversity of diabetic and non-diabetic kidney disease: Current status and future perspective. Life Sci 2023; 316:121414. [PMID: 36682521 DOI: 10.1016/j.lfs.2023.121414] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/09/2023] [Accepted: 01/17/2023] [Indexed: 01/21/2023]
Abstract
A significant portion of the health burden of diabetic kidney disease (DKD) is caused by both type 1 and type 2 diabetes which leads to morbidity and mortality globally. It is one of the most common diabetic complications characterized by loss of renal function with high prevalence, often leading to acute kidney disease (AKD). Inflammation triggered by gut microbiota is commonly associated with the development of DKD. Interactions between the gut microbiota and the host are correlated in maintaining metabolic and inflammatory homeostasis. However, the fundamental processes through which the gut microbiota affects the onset and progression of DKD are mainly unknown. In this narrative review, we summarised the potential role of the gut microbiome, their pathogenicity between diabetic and non-diabetic kidney disease (NDKD), and their impact on host immunity. A well-established association has already been seen between gut microbiota, diabetes and kidney disease. The gut-kidney interrelationship is confirmed by mounting evidence linking gut dysbiosis to DKD, however, it is still unclear what is the real cause of gut dysbiosis, the development of DKD, and its progression. In addition, we also try to distinguish novel biomarkers for early detection of DKD and the possible therapies that can be used to regulate the gut microbiota and improve the host immune response. This early detection and new therapies will help clinicians for better management of the disease and help improve patient outcomes.
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Affiliation(s)
- Soumik Das
- School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India
| | - Ramanathan Gnanasambandan
- School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
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16
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Singh V, Lee G, Son H, Amani S, Baunthiyal M, Shin JH. Anti-diabetic prospects of dietary bio-actives of millets and the significance of the gut microbiota: A case of finger millet. Front Nutr 2022; 9:1056445. [PMID: 36618686 PMCID: PMC9815516 DOI: 10.3389/fnut.2022.1056445] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
Finger millet (Eleusine coracana) is a staple food in several parts of the world because of its high nutritional value. In addition to its high nutrient content, finger millet contains numerous bioactive compounds, including polyphenol (10.2 mg/g TAE), flavonoid (5.54 mg/g CE), phytic acid (0.48%), and dietary fiber (15-20%). Polyphenols are known for their anti-oxidant and anti-diabetic role. Phytic acid, previously considered an anti-nutritive substance, is now regarded as a nutraceutical as it reduces carbohydrate digestibility and thus controls post-prandial glucose levels and obesity. Thus, finger millet is an attractive diet for patients with diabetes. Recent findings have revealed that the anti-oxidant activity and bio-accessibility of finger millet polyphenols increased significantly (P < 0.05) in the colon, confirming the role of the gut microbiota. The prebiotic content of finger millet was also utilized by the gut microbiota, such as Faecalibacterium, Eubacterium, and Roseburia, to generate colonic short-chain fatty acids (SCFAs), and probiotic Bifidobacterium and Lactobacillus, which are known to be anti-diabetic in nature. Notably, finger millet-induced mucus-degrading Akkermansia muciniphila can also help in alleviate diabetes by releasing propionate and Amuc_1100 protein. Various millet bio-actives effectively controlled pathogenic gut microbiota, such as Shigella and Clostridium histolyticum, to lower gut inflammation and, thus, the risk of diabetes in the host. In the current review, we have meticulously examined the role of gut microbiota in the bio-accessibility of millet compounds and their impact on diabetes.
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Affiliation(s)
- Vineet Singh
- Department of Applied Biosciences, Kyungpook National University, Daegu, Republic of Korea
| | - GyuDae Lee
- Department of Applied Biosciences, Kyungpook National University, Daegu, Republic of Korea
| | - HyunWoo Son
- Department of Applied Biosciences, Kyungpook National University, Daegu, Republic of Korea
| | - Sliti Amani
- Department of Applied Biosciences, Kyungpook National University, Daegu, Republic of Korea
| | - Mamta Baunthiyal
- Department of Biotechnology, Govind Ballabh Pant Institute of Engineering and Technology, Ghurdauri, India,*Correspondence: Mamta Baunthiyal,
| | - Jae-Ho Shin
- Department of Applied Biosciences, Kyungpook National University, Daegu, Republic of Korea,Jae-Ho Shin,
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17
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Hu R, Zou L, Wang L, Xu C, Qi M, Yang Z, Jiang G, Ji L. Probiotics alleviate maternal metabolic disorders and offspring-islet abnormalities in gestational diabetic mice. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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18
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Pan Z, Mao B, Zhang Q, Tang X, Yang B, Zhao J, Cui S, Zhang H. Postbiotics Prepared Using Lactobacillus paracasei CCFM1224 Prevent Nonalcoholic Fatty Liver Disease by Modulating the Gut Microbiota and Liver Metabolism. Int J Mol Sci 2022; 23:ijms232113522. [PMID: 36362307 PMCID: PMC9653709 DOI: 10.3390/ijms232113522] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 11/06/2022] Open
Abstract
Postbiotics are rich in a variety of bioactive components, which may have beneficial effects in inhibiting hepatic lipid accumulation. In this study, we investigated the preventive effects of postbiotics (POST) prepared from Lactobacillus paracasei on non-alcoholic fatty liver disease (NAFLD). Our results showed that when mice ingested a high-fat diet (HFD) and POST simultaneously, weight gain was slowed, epididymal white fat hypertrophy and insulin resistance were suppressed, serum biochemical indicators related to blood lipid metabolism were improved, and hepatic steatosis and liver inflammation decreased. Bacterial sequencing showed that POST modulated the gut microbiota in HFD mice, increasing the relative abundance of Akkermansia and reducing the relative abundance of Lachnospiraceae NK4A136 group, Ruminiclostridium and Bilophila. Spearman’s correlation analysis revealed significant correlations between lipid metabolism parameters and gut microbes. Functional prediction results showed that the regulation of gut microbiota was associated with the improvement of metabolic status. The metabolomic analysis of the liver revealed that POST-regulated liver metabolic pathways, such as glycerophospholipid and ether lipid metabolism, pantothenate and CoA biosynthesis, some parts of amino acid metabolism, and other metabolic pathways. In addition, POST regulated the gene expression in hepatocytes at the mRNA level, thereby regulating lipid metabolism. These findings suggest that POST plays a protective role against NAFLD and may exert its efficacy by modulating the gut microbiota and liver metabolism, and these findings may be applied to related functional foods.
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Affiliation(s)
- Zhenghao Pan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Bingyong Mao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Qiuxiang Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xin Tang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Bo Yang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Shumao Cui
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Correspondence: ; Tel.: +86-0510-85912155
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
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19
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Alka Ahuja, Saraswathy Mp, Nandakumar S, Prakash F A, Kn G, Um D. Role of the Gut Microbiome in Diabetes and Cardiovascular Diseases Including Restoration and Targeting Approaches- A Review. DRUG METABOLISM AND BIOANALYSIS LETTERS 2022; 15:133-149. [PMID: 36508273 DOI: 10.2174/2949681015666220615120300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 03/15/2022] [Accepted: 03/18/2022] [Indexed: 12/15/2022]
Abstract
Metabolic diseases, including cardiovascular diseases (CVD) and diabetes, have become the leading cause of morbidity and mortality worldwide. Gut microbiota appears to play a vital role in human disease and health, according to recent scientific reports. The gut microbiota plays an important role in sustaining host physiology and homeostasis by creating a cross-talk between the host and microbiome via metabolites obtained from the host's diet. Drug developers and clinicians rely heavily on therapies that target the microbiota in the management of metabolic diseases, and the gut microbiota is considered the biggest immune organ in the human body. They are highly associated with intestinal immunity and systemic metabolic disorders like CVD and diabetes and are reflected as potential therapeutic targets for the management of metabolic diseases. This review discusses the mechanism and interrelation between the gut microbiome and metabolic disorders. It also highlights the role of the gut microbiome and microbially derived metabolites in the pathophysiological effects related to CVD and diabetes. It also spotlights the reasons that lead to alterations of microbiota composition and the prominence of gut microbiota restoration and targeting approaches as effective treatment strategies in diabetes and CVD. Future research should focus onunderstanding the functional level of some specific microbial pathways that help maintain physiological homeostasis, multi-omics, and develop novel therapeutic strategies that intervene with the gut microbiome for the prevention of CVD and diabetes that contribute to a patient's well-being.
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Affiliation(s)
- Alka Ahuja
- College of Pharmacy, National University of Science and Technology, PC130, Muscat, Sultanate of Oman
| | - Saraswathy Mp
- Department of Microbiology, ESIC Medical College and PGIMSR, Chennai-600078, India
| | - Nandakumar S
- Department of Biotechnology, Pondicherry University, Kalapet, Puducherry-605014, India
| | - Arul Prakash F
- Centre of Molecular Medicine and Diagnostics (COMMAND), Saveetha Dental College and Hospital, Saveetha Institute of Medical & Technical Sciences, Chennai- 600077, India
| | - Gurpreet Kn
- College of Pharmacy, National University of Science and Technology, PC130, Muscat, Sultanate of Oman
| | - Dhanalekshmi Um
- College of Pharmacy, National University of Science and Technology, PC130, Muscat, Sultanate of Oman
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20
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Li Y, Chen M, Ma Y, Yang Y, Cheng Y, Ma H, Ren D, Chen P. Regulation of viable/inactivated/lysed probiotic Lactobacillus plantarum H6 on intestinal microbiota and metabolites in hypercholesterolemic mice. NPJ Sci Food 2022; 6:50. [PMID: 36316361 PMCID: PMC9622822 DOI: 10.1038/s41538-022-00167-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 10/11/2022] [Indexed: 01/24/2023] Open
Abstract
Evidence suggests that probiotic interventions reduce non-communicable diseases (NCDs) risk. However, its therapeutic effect and mechanism are still unclear. To evaluate the hypocholesterolemic effect of Lactobacillus plantarum H6 (L.p H6), a new commercial patent strain capable of preventing hypercholesterolemia, and its mechanism in depth, three states of the strain were prepared, namely, viable (vH6), heat-inactivated (iH6), and ultrasonically-lysed (uH6) bacteria cells. The results showed that v/i/uH6 cells could lower serum and liver blood lipid levels, alleviate liver damage and improve glucose tolerance test (GTT) and insulin tolerance test (ITT) indexes. v/i/uH6 cells improved the gut microbial composition and significantly reduced the Firmicutes to Bacteroidetes ratio (F/B ratio) in feces. In particular, Muribaculaceae may be a potential biomarker for effective cholesterol reduction. Also, the recovery of these biochemical indices and gut microbiome was found following fecal microbiota transplantation (FMT) using stool from vH6 treated mice. The v/i/uH6 cells increased the intestinal flora metabolism of vitamins-cofactors, as well as amino acids, while decreasing the relative content of primary bile acids. The Pearson correlation analysis showed that norank_f__Muribaculaceae and Lactobacillus had a negative correlation with blood lipid levels. Overall, v/i/uH6 cells were effective in improving hypercholesterolemia in mice, and this effect was attributed partly to the regulation of intestinal microbiota and metabolites related to lipid metabolism. Our findings provided a theoretical basis for the industrial development of probiotics and postbiotics and the treatment of cholesterol diseases.
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Affiliation(s)
- Yue Li
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
| | - Mengling Chen
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
| | - Yuxuan Ma
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
| | - Yue Yang
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
| | - Ying Cheng
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
| | - Huijing Ma
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
| | - Dayong Ren
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
| | - Ping Chen
- grid.464353.30000 0000 9888 756XCollege of Food Science and Engineering, Jilin Agricultural University, 130118 Changchun, China
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21
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Thakur PS, Aggarwal D, Takkar B, Shivaji S, Das T. Evidence Suggesting the Role of Gut Dysbiosis in Diabetic Retinopathy. Invest Ophthalmol Vis Sci 2022; 63:21. [PMID: 35877085 PMCID: PMC9339698 DOI: 10.1167/iovs.63.8.21] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Purpose Gut dysbiosis has been identified and tested in human trials for its role in diabetes mellitus (DM). The gut-retina axis could be a potential target for retardation of diabetic retinopathy (DR), a known complication of DM. This study reviews the evidence suggesting gut dysbiosis in DR. Methods The published literature in the past 5 years was reviewed using predetermined keywords and articles. The review intended to determine changes in gut microbiome in DR, the hypothesized mechanisms linking to the gut-retina axis, its predictive potential for progression of DR, and the possible therapeutic targets. Results The gut microbiota of people with DM differ from those without it, and the gut microbiota of people with DR differ from those without it. The difference is more significant in the former (DM versus no DM) and less significant in the latter (DM without DR versus DM with DR). Early research has suggested mechanisms of the gut-retina axis, but these are not different from known changes in the gut microbiome of people with DM. The current evidence on the predictive value of the gut microbiome in the occurrence and progression of DR is low. Therapeutic avenues targeting the gut-retina axis include lifestyle changes, pharmacologic inhibitors, probiotics, and fecal microbiota transplantation. Conclusions Investigating the therapeutic utility of the gut ecosystem for DM and its complications like DR is an emerging area of research. The gut-retina axis could be a target for retardation of DR but needs longitudinal regional studies adjusting for dietary habits.
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Affiliation(s)
- Pratima Singh Thakur
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
| | - David Aggarwal
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
| | - Brijesh Takkar
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India.,Indian Health Outcomes, Public Health, and Economics Research (IHOPE) Centre, L V Prasad Eye Institute, Hyderabad, India.,https://orcid.org/0000-0001-5779-7645
| | - Sisinthy Shivaji
- Prof. Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India.,https://orcid.org/0000-0003-0376-4658
| | - Taraprasad Das
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India.,https://orcid.org/0000-0002-1295-4528
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22
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Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther 2022; 7:216. [PMID: 35794109 PMCID: PMC9259665 DOI: 10.1038/s41392-022-01073-0] [Citation(s) in RCA: 327] [Impact Index Per Article: 109.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/15/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into a medically manageable chronic condition. Insulin is a key peptide hormone and mediates the systemic glucose metabolism in different tissues. Insulin resistance (IR) is a disordered biological response for insulin stimulation through the disruption of different molecular pathways in target tissues. Acquired conditions and genetic factors have been implicated in IR. Recent genetic and biochemical studies suggest that the dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids and toxic lipid metabolites promote IR in other tissues. IR is associated with several groups of abnormal syndromes that include obesity, diabetes, metabolic dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), and other abnormalities. Although no medication is specifically approved to treat IR, we summarized the lifestyle changes and pharmacological medications that have been used as efficient intervention to improve insulin sensitivity. Ultimately, the systematic discussion of complex mechanism will help to identify potential new targets and treat the closely associated metabolic syndrome of IR.
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Affiliation(s)
- Mengwei Li
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | - Xiaowei Chi
- Development Center for Medical Science & Technology National Health Commission of the People's Republic of China, 100044, Beijing, China
| | - Ying Wang
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | | | - Wenwei Xie
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | - Hanmei Xu
- The Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation of Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, China.
- State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China.
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23
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Shen Y, Sun Y, Wang X, Xiao Y, Ma L, Lyu W, Zheng Z, Wang W, Li J. Liver Transcriptome and Gut Microbiome Analysis Reveals the Effects of High Fructose Corn Syrup in Mice. Front Nutr 2022; 9:921758. [PMID: 35845805 PMCID: PMC9280673 DOI: 10.3389/fnut.2022.921758] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 06/01/2022] [Indexed: 11/13/2022] Open
Abstract
High fructose corn syrup (HFCS) is a viscous mixture of glucose and fructose that is used primarily as a food additive. This article explored the effect of HFCS on lipid metabolism-expressed genes and the mouse gut microbiome. In total, ten 3-week-old male C57BL/6J mice were randomly divided into two groups, including the control group, given purified water (Group C) and 30% HFCS in water (Group H) for 16 weeks. Liver and colonic content were collected for transcriptome sequencing and 16S rRNA gene sequencing, respectively. HFCS significantly increased body weight, epididymal, perirenal fat weight in mice (p < 0.05), and the proportion of lipid droplets in liver tissue. The expression of the ELOVL fatty acid elongase 3 (Elovl3) gene was reduced, while Stearoyl-Coenzyme A desaturase 1 (Scd1), peroxisome proliferator activated receptor gamma (Pparg), fatty acid desaturase 2 (Fads2), acyl-CoA thioesterase 2 (Acot2), acyl-CoA thioesterase 2 (Acot3), acyl-CoA thioesterase 4 (Acot4), and fatty acid binding protein 2 (Fabp2) was increased in Group H. Compared with Group C, the abundance of Firmicutes was decreased in Group H, while the abundance of Bacteroidetes was increased, and the ratio of Firmicutes/Bacteroidetes was obviously decreased. At the genus level, the relative abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Erysipelatoclostridium, and Parasutterella was increased in Group H, whereas that of Staphylococcus, Peptococcus, Parabacteroides, Donghicola, and Turicibacter was reduced in Group H. Pparg, Acot2, Acot3, and Scd1 were positively correlated with Erysipelatoclostridium and negatively correlated with Parabacteroides, Staphylococcus, and Turicibacter. Bifidobacterium was negatively correlated with Elovl3. Overall, HFCS affects body lipid metabolism by affecting the expression of lipid metabolism genes in the liver through the gut microbiome.
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Affiliation(s)
- Yu Shen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China
- Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Yangying Sun
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China
| | - Xiaoli Wang
- Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Yingping Xiao
- Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Lingyan Ma
- Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Wentao Lyu
- Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Zibin Zheng
- Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Wen Wang
- Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Jinjun Li
- Institute of Food Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
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24
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Lopez-Tello J, Schofield Z, Kiu R, Dalby MJ, van Sinderen D, Le Gall G, Sferruzzi-Perri AN, Hall LJ. Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice. Cell Mol Life Sci 2022; 79:386. [PMID: 35760917 PMCID: PMC9236968 DOI: 10.1007/s00018-022-04379-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 05/09/2022] [Accepted: 05/14/2022] [Indexed: 12/22/2022]
Abstract
The gut microbiota plays a central role in regulating host metabolism. While substantial progress has been made in discerning how the microbiota influences host functions post birth and beyond, little is known about how key members of the maternal gut microbiota can influence feto-placental growth. Notably, in pregnant women, Bifidobacterium represents a key beneficial microbiota genus, with levels observed to increase across pregnancy. Here, using germ-free and specific-pathogen-free mice, we demonstrate that the bacterium Bifidobacterium breve UCC2003 modulates maternal body adaptations, placental structure and nutrient transporter capacity, with implications for fetal metabolism and growth. Maternal and placental metabolome were affected by maternal gut microbiota (i.e. acetate, formate and carnitine). Histological analysis of the placenta confirmed that Bifidobacterium modifies placental structure via changes in Igf2P0, Dlk1, Mapk1 and Mapk14 expression. Additionally, B. breve UCC2003, acting through Slc2a1 and Fatp1-4 transporters, was shown to restore fetal glycaemia and fetal growth in association with changes in the fetal hepatic transcriptome. Our work emphasizes the importance of the maternal gut microbiota on feto-placental development and sets a foundation for future research towards the use of probiotics during pregnancy.
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Affiliation(s)
- Jorge Lopez-Tello
- Department of Physiology, Development, and Neuroscience, Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
| | - Zoe Schofield
- Gut Microbes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Raymond Kiu
- Gut Microbes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Matthew J Dalby
- Gut Microbes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | | | - Gwénaëlle Le Gall
- Norwich Medical School, University of East Anglia, Bob Champion Research and Education Building, James Watson Road, Norwich Research Park, Norwich, UK
| | - Amanda N Sferruzzi-Perri
- Department of Physiology, Development, and Neuroscience, Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
| | - Lindsay J Hall
- Gut Microbes and Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.
- Norwich Medical School, University of East Anglia, Bob Champion Research and Education Building, James Watson Road, Norwich Research Park, Norwich, UK.
- Chair of Intestinal Microbiome, School of Life Sciences, ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany.
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25
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Lotus seed resistant starch ameliorates high-fat diet induced hyperlipidemia by fatty acid degradation and glycerolipid metabolism pathways in mouse liver. Int J Biol Macromol 2022; 215:79-91. [PMID: 35718147 DOI: 10.1016/j.ijbiomac.2022.06.077] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/02/2022] [Accepted: 06/11/2022] [Indexed: 11/23/2022]
Abstract
We investigated the potential efficacy and underlying mechanisms of Lotus seed Resistant Starch (LRS) for regulating hyperlipidemia in mice fed a High-fat Diet (HFD). Mouse were fed a normal diet (Normal Control group, NC group), HFD alone (MC group), HFD plus lovastatin (PC group), or HFD with low/medium/high LRS (LLRS, MLRS, and HLRS groups, respectively) for 4 weeks. LRS supplementation significantly decreased body weight and significantly reduced serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipopro-tein cholesterol compared with the MC group. LRS also significantly alleviated hepatic steatosis, especially in the MLRS group, which also showed a significantly reduced visceral fat index. LLRS supplementation significantly regulated genes associated with glycerolipid metabolism and steroid hormone biosynthesis (Lpin1 and Ugt2b38), MLRS significantly regulated genes related to fatty acid degradation, fatty acid elongation, and glycerolipid metabolism (Lpin1, Hadha, Aldh3a2, and Acox1), whereas HLRS significantly regulated genes related to fatty acid elongation and glycerolipid metabolism (Lpin1, Elovl3, Elovol5, and Agpat3). The fatty acid-degradation pathway regulated by MLRS thus exerts better control of serum lipid levels, body weight, visceral fat index, and liver steatosis in mice compared with LLRS- and HLRS-regulated pathways.
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26
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Singh V, Park YJ, Lee G, Unno T, Shin JH. Dietary regulations for microbiota dysbiosis among post-menopausal women with type 2 diabetes. Crit Rev Food Sci Nutr 2022; 63:9961-9976. [PMID: 35635755 DOI: 10.1080/10408398.2022.2076651] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Type 2 diabetes (T2D) and T2D-associated comorbidities, such as obesity, are serious universally prevalent health issues among post-menopausal women. Menopause is an unavoidable condition characterized by the depletion of estrogen, a gonadotropic hormone responsible for secondary sexual characteristics in women. In addition to sexual dimorphism, estrogen also participates in glucose-lipid homeostasis, and estrogen depletion is associated with insulin resistance in the female body. Estrogen level in the gut also regulates the microbiota composition, and even conjugated estrogen is actively metabolized by the estrobolome to maintain insulin levels. Moreover, post-menopausal gut microbiota is different from the pre-menopausal gut microbiota, as it is less diverse and lacks the mucolytic Akkermansia and short-chain fatty acid (SCFA) producers such as Faecalibacterium and Roseburia. Through various metabolites (SCFAs, secondary bile acid, and serotonin), the gut microbiota plays a significant role in regulating glucose homeostasis, oxidative stress, and T2D-associated pro-inflammatory cytokines (IL-1, IL-6). While gut dysbiosis is common among post-menopausal women, dietary interventions such as probiotics, prebiotics, and synbiotics can ease post-menopausal gut dysbiosis. The objective of this review is to understand the relationship between post-menopausal gut dysbiosis and T2D-associated factors. Additionally, the study also provided dietary recommendations to avoid T2D progression among post-menopausal women.
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Affiliation(s)
- Vineet Singh
- Department of Applied Biosciences, Kyungpook National University, Daegu, South Korea
| | - Yeong-Jun Park
- Department of Applied Biosciences, Kyungpook National University, Daegu, South Korea
| | - GyuDae Lee
- Department of Applied Biosciences, Kyungpook National University, Daegu, South Korea
| | - Tatsuya Unno
- Department of Biotechnology, Jeju National University, Jeju, South Korea
| | - Jae-Ho Shin
- Department of Applied Biosciences, Kyungpook National University, Daegu, South Korea
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27
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Paul P, Kaul R, Abdellatif B, Arabi M, Upadhyay R, Saliba R, Sebah M, Chaari A. The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review. Front Nutr 2022; 9:906243. [PMID: 35711547 PMCID: PMC9197462 DOI: 10.3389/fnut.2022.906243] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 04/08/2022] [Indexed: 12/12/2022] Open
Abstract
Background One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients. Methods Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022. Results From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects. Conclusion Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.
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Affiliation(s)
- Pradipta Paul
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Ridhima Kaul
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Basma Abdellatif
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Maryam Arabi
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Rohit Upadhyay
- Department of Medicine—Nephrology and Hypertension, Tulane University, School of Medicine, New Orleans, LA, United States
| | - Reya Saliba
- Distributed eLibrary, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Majda Sebah
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Ali Chaari
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
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28
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Yeo E, Brubaker PL, Sloboda DM. The intestine and the microbiota in maternal glucose homeostasis during pregnancy. J Endocrinol 2022; 253:R1-R19. [PMID: 35099411 PMCID: PMC8942339 DOI: 10.1530/joe-21-0354] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 01/31/2022] [Indexed: 11/23/2022]
Abstract
It is now well established that, beyond its role in nutrient processing and absorption, the intestine and its accompanying gut microbiome constitute a major site of immunological and endocrine regulation that mediates whole-body metabolism. Despite the growing field of host-microbe research, few studies explore what mechanisms govern this relationship in the context of pregnancy. During pregnancy, significant maternal metabolic adaptations are made to accommodate the additional energy demands of the developing fetus and to prevent adverse pregnancy outcomes. Recent data suggest that the maternal gut microbiota may play a role in these adaptations, but changes to maternal gut physiology and the underlying intestinal mechanisms remain unclear. In this review, we discuss selective aspects of intestinal physiology including the role of the incretin hormone, glucagon-like peptide 1 (GLP-1), and the role of the maternal gut microbiome in the maternal metabolic adaptations to pregnancy. Specifically, we discuss how bacterial components and metabolites could mediate the effects of the microbiota on host physiology, including nutrient absorption and GLP-1 secretion and action, and whether these mechanisms may change maternal insulin sensitivity and secretion during pregnancy. Finally, we discuss how these pathways could be altered in disease states during pregnancy including maternal obesity and diabetes.
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Affiliation(s)
- Erica Yeo
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Patricia L Brubaker
- Department of Physiology, University of Toronto, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Deborah M Sloboda
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
- Department of Obstetrics, Gynecology and Pediatrics, McMaster University, Hamilton, ON, Canada
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Petakh P, Kamyshna I, Nykyforuk A, Yao R, Imbery JF, Oksenych V, Korda M, Kamyshnyi A. Immunoregulatory Intestinal Microbiota and COVID-19 in Patients with Type Two Diabetes: A Double-Edged Sword. Viruses 2022; 14:477. [PMID: 35336884 PMCID: PMC8955861 DOI: 10.3390/v14030477] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 02/06/2022] [Accepted: 02/24/2022] [Indexed: 01/09/2023] Open
Abstract
Coronavirus disease 2019, or COVID-19, is a major challenge facing scientists worldwide. Alongside the lungs, the system of organs comprising the GI tract is commonly targeted by COVID-19. The dysbiotic modulations in the intestine influence the disease severity, potentially due to the ability of the intestinal microbiota to modulate T lymphocyte functions, i.e., to suppress or activate T cell subpopulations. The interplay between the lungs and intestinal microbiota is named the gut-lung axis. One of the most usual comorbidities in COVID-19 patients is type 2 diabetes, which induces changes in intestinal microbiota, resulting in a pro-inflammatory immune response, and consequently, a more severe course of COVID-19. However, changes in the microbiota in this comorbid pathology remain unclear. Metformin is used as a medication to treat type 2 diabetes. The use of the type 2 diabetes drug metformin is a promising treatment for this comorbidity because, in addition to its hypoglycemic action, it can increase amount of intestinal bacteria that induce regulatory T cell response. This dual activity of metformin can reduce lung damage and improve the course of the COVID-19 disease.
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Affiliation(s)
- Pavlo Petakh
- Department of Biochemistry and Pharmacology, Uzhhorod National University, 88000 Uzhhorod, Ukraine; (P.P.); (A.N.)
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Iryna Kamyshna
- Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, Majdan Voli 1, 46001 Ternopil, Ukraine;
| | - Andriy Nykyforuk
- Department of Biochemistry and Pharmacology, Uzhhorod National University, 88000 Uzhhorod, Ukraine; (P.P.); (A.N.)
| | - Rouan Yao
- Center of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway;
| | - John F. Imbery
- Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway;
| | - Valentyn Oksenych
- Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway;
| | - Mykhaylo Korda
- Department of Medical Biochemistry, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine;
| | - Aleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
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Bielka W, Przezak A, Pawlik A. The Role of the Gut Microbiota in the Pathogenesis of Diabetes. Int J Mol Sci 2022; 23:ijms23010480. [PMID: 35008906 PMCID: PMC8745411 DOI: 10.3390/ijms23010480] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/26/2021] [Accepted: 12/29/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus is a significant clinical and therapeutic problem because it can lead to serious long-term complications. Its pathogenesis is not fully understood, but there are indications that dysbiosis can play a role in the development of diabetes, or that it appears during the course of the disease. Changes in microbiota composition are observed in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. These modifications are associated with pro-inflammation, increased intestinal permeability, endotoxemia, impaired β-cell function and development of insulin resistance. This review summarizes the role of the gut microbiota in healthy individuals and the changes in bacterial composition that can be associated with T1D or T2D. It also presents new developments in diabetes therapy based on influencing the gut microbiota as a promising method to alter the course of diabetes. Moreover, it highlights the lacking data and suggests future directions needed to prove the causal relationship between dysbiosis and diabetes, both T1D and T2D.
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Hassan NE, El-Masry SA, Nageeb A, El Hussieny MS, Khalil A, Aly MM, Soliman MAT, Ismail A, El-Saeed G, Hashish A, Selim M. Correlation between Gut Microbiota, its Metabolic Products, and their Association with Liver Enzymes among Sample of Egyptian Females. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2022.7909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background and Aim: The gut microbiota appears to play a critical role in the pathogenesis of obesity, liver metabolism and the associated diseases. The present study aimed to identify the existing gut microbiota enterotypes and its metabolic products profiles among a sample of normal weight and obese Egyptian females, and to investigate the correlation between gut microbiota; body mass index andliver enzymes among them.Methods: A case-control cross-sectional study, included 112 Egyptian females; 82obese and30 normal weight; with age ranged from 25 up to 60 years. For each participant, anthropometric measurements (weight, height and BMI), laboratory investigations (AST, ALT, SCFA, CRP) and microbiota analysis were done. Results: The obese females had higher significant values of CRP,AST, ALTand SCFA. In addition, obese females had insignificant higher values of log Bacteroidetes, log firmicutes, log firmicutes/ Bacteroidetes ratio, and log lactobacillus, and insignificant lower values of log bifidobacteria; than normal weight group.Among normal weight group, Lactobacillus shad significant positive correlations with SCFA, Bifidobacteria and Firmicutes, and significant negative correlations with AST, ALTand CRP. Bifidobacteria had significant negative correlations with Ht and ALT. Bacteroidetes bacteria had significant positive correlations with SCFA, and significant negative correlations with age and height. Firmicutes bacteria had significant negative correlations with AST and ALT. Firmicutes / Bacteroidetes Ratio had significant negative correlations with AST, ALTand SCFA. Among obese group, Lactobacillus and Bifidobacteria had significant negative correlations with Firmicutes / Bacteroidetes Ratio however; these correlations were insignificant among normal weight group. Moreover, there were insignificant correlations between any type of studied microbiota and any of the anthropometric or laboratory parameters; except Firmicutes bacteria had significant negative correlations with ALT.Conclusion: The beneficial Lactobacillus and bifidobacteria have its good impact in improving obesity status, liver function in form of ALT.
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Bakir-Gungor B, Bulut O, Jabeer A, Nalbantoglu OU, Yousef M. Discovering Potential Taxonomic Biomarkers of Type 2 Diabetes From Human Gut Microbiota via Different Feature Selection Methods. Front Microbiol 2021; 12:628426. [PMID: 34512559 PMCID: PMC8424122 DOI: 10.3389/fmicb.2021.628426] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 05/03/2021] [Indexed: 12/24/2022] Open
Abstract
Human gut microbiota is a complex community of organisms including trillions of bacteria. While these microorganisms are considered as essential regulators of our immune system, some of them can cause several diseases. In recent years, next-generation sequencing technologies accelerated the discovery of human gut microbiota. In this respect, the use of machine learning techniques became popular to analyze disease-associated metagenomics datasets. Type 2 diabetes (T2D) is a chronic disease and affects millions of people around the world. Since the early diagnosis in T2D is important for effective treatment, there is an utmost need to develop a classification technique that can accelerate T2D diagnosis. In this study, using T2D-associated metagenomics data, we aim to develop a classification model to facilitate T2D diagnosis and to discover T2D-associated biomarkers. The sequencing data of T2D patients and healthy individuals were taken from a metagenome-wide association study and categorized into disease states. The sequencing reads were assigned to taxa, and the identified species are used to train and test our model. To deal with the high dimensionality of features, we applied robust feature selection algorithms such as Conditional Mutual Information Maximization, Maximum Relevance and Minimum Redundancy, Correlation Based Feature Selection, and select K best approach. To test the performance of the classification based on the features that are selected by different methods, we used random forest classifier with 100-fold Monte Carlo cross-validation. In our experiments, we observed that 15 commonly selected features have a considerable effect in terms of minimizing the microbiota used for the diagnosis of T2D and thus reducing the time and cost. When we perform biological validation of these identified species, we found that some of them are known as related to T2D development mechanisms and we identified additional species as potential biomarkers. Additionally, we attempted to find the subgroups of T2D patients using k-means clustering. In summary, this study utilizes several supervised and unsupervised machine learning algorithms to increase the diagnostic accuracy of T2D, investigates potential biomarkers of T2D, and finds out which subset of microbiota is more informative than other taxa by applying state-of-the art feature selection methods.
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Affiliation(s)
- Burcu Bakir-Gungor
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gül University, Kayseri, Turkey
| | - Osman Bulut
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gül University, Kayseri, Turkey
| | - Amhar Jabeer
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gül University, Kayseri, Turkey
| | - O. Ufuk Nalbantoglu
- Department of Computer Engineering, Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey
| | - Malik Yousef
- Department of Information Systems, Zefat Academic College, Zefat, Israel
- Galilee Digital Health Research Center, Zefat Academic College, Zefat, Israel
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Khalil NA, Eltahan NR, Elaktash HM, Aly S, Sarbini SR. Prospective evaluation of probiotic and prebiotic supplementation on diabetic health associated with gut microbiota. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2021.101149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Tang C, Kong L, Shan M, Lu Z, Lu Y. Protective and ameliorating effects of probiotics against diet-induced obesity: A review. Food Res Int 2021; 147:110490. [PMID: 34399486 DOI: 10.1016/j.foodres.2021.110490] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 05/05/2021] [Accepted: 05/23/2021] [Indexed: 02/07/2023]
Abstract
Diet-induced obesity is one of the major public health concerns all over the world, and obesity also contributes to the development of other chronic diseases such as non-alcoholic fatty acid liver disease, type 2 diabetes mellitus and cardiovascular diseases. Evidence shows that the pathogenesis of obesity and obesity-associated chronic diseases are closely related to dysregulation of lipid metabolism, glucose metabolism and cholesterol metabolism, and oxidative stress, endoplasmic reticulum stress, abnormal gut microbiome and chronic low-grade inflammation. Recently, in view of potential effects on lipid metabolism, glucose metabolism, cholesterol metabolism and intestinal microbiome, as well as anti-oxidative and anti-inflammatory activities, natural probiotics, including live and dead probiotics, and probiotic components and metabolites, have attracted increasing attention and are considered as novel strategies for preventing and ameliorating obesity and obesity-related chronic diseases. Specifically, this review is presented on the anti-obesity effects of probiotics and underlying molecular mechanisms, which will provide a theoretical basis of anti-obesity probiotics for the development of functional foods.
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Affiliation(s)
- Chao Tang
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Liangyu Kong
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Mengyuan Shan
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Zhaoxin Lu
- College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China.
| | - Yingjian Lu
- College of Food Science & Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China.
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35
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Al-Jameel SS. Association of diabetes and microbiota: An update. Saudi J Biol Sci 2021; 28:4446-4454. [PMID: 34354429 PMCID: PMC8324937 DOI: 10.1016/j.sjbs.2021.04.041] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/15/2021] [Accepted: 04/17/2021] [Indexed: 12/19/2022] Open
Abstract
Diabetes is an emerging health condition globally and is suggested to have a direct connection with the gut microbiota that determine our metabolic outcomes. Sensitivity to insulin and glucose metabolism is normal in healthy people as compared to those people who cannot maintain their glucose metabolism. One of the reasons of the differences is that healthy people have different microbiome that leads to achieve more short chain fatty acids and make up more branched amino acids, while the gut microbiota of the other group of people are more likely to produce compounds that affects glucose metabolism. Herein, this review will present the research related to the impact of gut microbes on diabetes carried out in the past decade. The review focus on the relation between gut microbiota and Type-1 Diabetes (T1D), Type-2 Diabetes (T2D), and how gut microbiota could be an alternative therapy for treatment of diabetes.
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Affiliation(s)
- Suhailah S Al-Jameel
- Department of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
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Corb Aron RA, Abid A, Vesa CM, Nechifor AC, Behl T, Ghitea TC, Munteanu MA, Fratila O, Andronie-Cioara FL, Toma MM, Bungau S. Recognizing the Benefits of Pre-/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium. Microorganisms 2021; 9:microorganisms9030618. [PMID: 33802777 PMCID: PMC8002498 DOI: 10.3390/microorganisms9030618] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 03/09/2021] [Accepted: 03/15/2021] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are diseases that can be influenced by the structure of gut microbiota, whose improvement is often neglected in metabolic pathology. This review highlights the following main aspects: the relationship between probiotics/gut microbes with the pathogenesis of MetS, the particular positive roles of Akkermansia muciniphila supplementation in the onset of MetS, and the interaction between dietary polyphenols (prebiotics) with gut microbiota. Therefore, an extensive and in-depth analysis of the often-neglected correlation between gut microbiota and chronic metabolic diseases was conducted, considering that this topic continues to fascinate and stimulate researchers through the discovery of novel strains and their beneficial properties.
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Affiliation(s)
- Raluca Anca Corb Aron
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (R.A.C.A.); (C.M.V.)
| | - Areha Abid
- Department of Food Science, Faculty of Agricultural and Food Sciences, University of Debrecen, 4032 Debrecen, Hungary;
| | - Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (R.A.C.A.); (C.M.V.)
| | - Aurelia Cristina Nechifor
- Department of Analytical Chemistry, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 011061 Bucharest, Romania;
| | - Tapan Behl
- Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India;
| | - Timea Claudia Ghitea
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (T.C.G.); (M.M.T.)
| | - Mihai Alexandru Munteanu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.A.M.); (O.F.)
| | - Ovidiu Fratila
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (M.A.M.); (O.F.)
| | - Felicia Liana Andronie-Cioara
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
| | - Mirela Marioara Toma
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (T.C.G.); (M.M.T.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (T.C.G.); (M.M.T.)
- Correspondence: ; Tel.: +40-726-776-588
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Wang L, Yu X, Xu X, Ming J, Wang Z, Gao B, Xing Y, Zhou J, Fu J, Liu T, Liu X, Garstka MA, Wang X, Ji Q. The Fecal Microbiota Is Already Altered in Normoglycemic Individuals Who Go on to Have Type 2 Diabetes. Front Cell Infect Microbiol 2021; 11:598672. [PMID: 33680988 PMCID: PMC7930378 DOI: 10.3389/fcimb.2021.598672] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 01/04/2021] [Indexed: 12/19/2022] Open
Abstract
Objective Mounting evidence has suggested a link between gut microbiome characteristics and type 2 diabetes (T2D). To determine whether these alterations occur before the impairment of glucose regulation, we characterize gut microbiota in normoglycemic individuals who go on to develop T2D. Methods We designed a nested case-control study, and enrolled individuals with a similar living environment. A total of 341 normoglycemic individuals were followed for 4 years, including 30 who developed T2D, 33 who developed prediabetes, and their matched controls. Fecal samples (developed T2D, developed prediabetes and controls: n=30, 33, and 63, respectively) collected at baseline underwent metagenomics sequencing. Results Compared with matched controls, individuals who went on to develop T2D had lower abundances of Bifidobacterium longum, Coprobacillus unclassified, and Veillonella dispar and higher abundances of Roseburia hominis, Porphyromonas bennonis, and Paraprevotella unclassified. The abundance of Bifidobacterium longum was negatively correlated with follow-up blood glucose levels. Moreover, the microbial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of carbohydrate metabolism, methane metabolism, amino acid metabolism, fatty acid metabolism, and membrane transport were changed between the two groups. Conclusions We found that fecal microbiota of healthy individuals who go on to develop T2D had already changed when they still were normoglycemic. These alterations of fecal microbiota might provide insights into the development of T2D and a new perspective for identifying individuals at risk of developing T2D.
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Affiliation(s)
- Li Wang
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xinwen Yu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiaoqiang Xu
- Department of Bioinformatics, Aimigene Institute, Shenzhen, China
| | - Jie Ming
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhifeng Wang
- Department of Bioinformatics, Aimigene Institute, Shenzhen, China
| | - Bin Gao
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ying Xing
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jie Zhou
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jianfang Fu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Tao Liu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiangyang Liu
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Malgorzata A Garstka
- Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaokai Wang
- Department of Bioinformatics, Aimigene Institute, Shenzhen, China
| | - Qiuhe Ji
- Endocrinology Research Center, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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Mohammad S, Thiemermann C. Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions. Front Immunol 2021; 11:594150. [PMID: 33505393 PMCID: PMC7829348 DOI: 10.3389/fimmu.2020.594150] [Citation(s) in RCA: 250] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 11/23/2020] [Indexed: 12/12/2022] Open
Abstract
Diet-induced metabolic endotoxemia is an important factor in the development of many chronic diseases in animals and man. The gut epithelium is an efficient barrier that prevents the absorption of liposaccharide (LPS). Structural changes to the intestinal epithelium in response to dietary alterations allow LPS to enter the bloodstream, resulting in an increase in the plasma levels of LPS (termed metabolic endotoxemia). LPS activates Toll-like receptor-4 (TLR4) leading to the production of numerous pro-inflammatory cytokines and, hence, low-grade systemic inflammation. Thus, metabolic endotoxemia can lead to several chronic inflammatory conditions. Obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) can also cause an increase in gut permeability and potential pharmacological and dietary interventions could be used to reduce the chronic low-grade inflammation associated with endotoxemia.
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Affiliation(s)
- Shireen Mohammad
- William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
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Ghaemi F, Fateh A, Sepahy AA, Zangeneh M, Ghanei M, Siadat SD. Blood microbiota composition in Iranian pre-diabetic and type 2 diabetic patients. Hum Antibodies 2021; 29:243-248. [PMID: 34151785 DOI: 10.3233/hab-210450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Type 2 diabetes as the most prevalent metabolic disorder, is one of the major causes of morbidity and mortality worldwide. Recent studies suggest that body microbiota may play a role in developing metabolic disorders including type 2 diabetes. The objective of the present study was to investigate the blood microbiota composition in Iranian pre-diabetic and type 2 diabetic patients compared to healthy individuals. METHODS Blood samples were taken after 12-h fasting from 90 participants, 30 healthy individuals, 30 type 2 diabetes patients and 30 pre-diabetic participants. The buffy coat layer separated by centrifugation at 800 and DNA was extracted using a column-based method. Composition and load of blood microbiota was evaluated by real-time PCR method using genus specific 16S rRNA primers. RESULTS The load of Akkermansia, and Faecalibacterium was higher in normal volunteers compared to pre-diabetic and type 2 diabetes group (p< 0.05).The load of Bifidobacterium was higher in normal volunteers compared to type 2 diabetes patients (p= 0.02). In contrast, the load of Lactobacillus and Escherichia coli was higher in pre-diabetics and type 2 diabetes patients compared to normal volunteers (p< 0.05).The load of Bacteroides fragilis was not statistically different between studied groups but it was higher in males compared to female group (p= 0.04). the load of other bacteria was not significantly different between male and female participants. CONCLUSION There is difference between microbiota composition in white blood cells of pre-diabetic and type 2 diabetes patients compared to healthy people. Determination of blood microbiota pattern may have a role in diagnosis and preventive of type 2 diabetes in a certain population. For more clarification about correlation between blood microbiota and type 2 diabetes, larger studies with more participants in different ethnical populations is suggested.
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Affiliation(s)
- Farahnaz Ghaemi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Abolfazl Fateh
- Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Abbas Akhavan Sepahy
- Department of Microbiology, Tehran North Branch, Islamic Azad University, Tehran, Iran
| | - Mehrangiz Zangeneh
- Department of Infectious Diseases, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Mostafa Ghanei
- Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran
- Endocrinology & Metabolism Research Center, Endocrinology & Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Salles BIM, Cioffi D, Ferreira SRG. Probiotics supplementation and insulin resistance: a systematic review. Diabetol Metab Syndr 2020; 12:98. [PMID: 33292434 PMCID: PMC7656736 DOI: 10.1186/s13098-020-00603-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 10/20/2020] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Research on intestinal microbiota has grown considerably, as well as the interest on probiotics' supplementation effects on metabolism. Considering high prevalence rates of metabolic diseases linked by insulin resistance, we performed a systematic review of existing literature which addressed the role of probiotics in modulating insulin sensitivity in animals and humans. METHODS This systematic review was based on PRISMA guidelines. Searches for original articles published in English from 1990 to January 2020 were made in the electronic database of PubMed from the National Library of Medicine, using Medical Subject Headings to identify longitudinal studies conducted in animals and humans which reported effects of probiotics in a variety of insulin resistance parameters. RESULTS Overall, results from 27 probiotic interventions (Lactobacillus, Bifidobacterium, Clostridium and Akkermansia) indicated significant beneficial changes in insulin resistance measures in animal studies. Additionally, they improved lipid profile, inflammatory and oxidative markers, short-chain fatty acids production and microbiota composition. In seven clinical trials, samples and designs were heterogeneous. Five showed benefits in insulin resistance parameters and in two others no effect was detected. CONCLUSION Available data regarding the effects of certain probiotics do not guarantee sustained amelioration of insulin resistance in humans. Consistent beneficial results for intestinal barrier function, immune system and metabolism were reported in animals may encourage long-term randomized clinical trials in people with obesity and cardiometabolic risk. Whether supplementation with probiotics in combination with medications and/or prebiotics, associated with a healthy lifestyle, will prove useful to attenuate insulin resistance requires further investigation.
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Affiliation(s)
- Bárbara Izabel Moraes Salles
- Departamento de Epidemiologia, Faculdade de Saúde Pública, School of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715, São Paulo, SP, CEP 01246-904, Brazil
| | - Débora Cioffi
- Departamento de Epidemiologia, Faculdade de Saúde Pública, School of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715, São Paulo, SP, CEP 01246-904, Brazil
| | - Sandra Roberta G Ferreira
- Departamento de Epidemiologia, Faculdade de Saúde Pública, School of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715, São Paulo, SP, CEP 01246-904, Brazil.
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Ding QY, Tian JX, Li M, Lian FM, Zhao LH, Wei XX, Han L, Zheng YJ, Gao ZZ, Yang HY, Fang XY, Tong XL. Interactions Between Therapeutics for Metabolic Disease, Cardiovascular Risk Factors, and Gut Microbiota. Front Cell Infect Microbiol 2020; 10:530160. [PMID: 33194785 PMCID: PMC7644821 DOI: 10.3389/fcimb.2020.530160] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 09/16/2020] [Indexed: 12/11/2022] Open
Abstract
With improved standards of living, the incidence of multiple metabolic disorders has increased year by year, especially major risk factors for cardiovascular disease such as hyperglycemia and hyperlipidemia, continues to increase. Emerging epidemiological data and clinical trials have shown the additional protective effects of some metabolic therapy drugs against cardiovascular diseases. A series of studies have found that these drugs may work by modulating the composition of gut microbiota. In this review, we provide a brief overview of the contribution of the gut microbiota to both metabolic disorders and cardiovascular diseases, as well as the response of gut microbiota to metabolic therapy drugs with cardiovascular benefits. In this manner, we link the recent advances in microbiome studies on metabolic treatment drugs with their cardiovascular protective effects, suggesting that intestinal microorganisms may play a potential role in reducing cardiovascular risk factors. We also discuss the potential of microorganism-targeted therapeutics as treatment strategies for preventing and/or treating cardiovascular disease and highlight the need to establish causal links between therapeutics for metabolic diseases, gut microbiota modulation, and cardiovascular protection.
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Affiliation(s)
- Qi-You Ding
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Jia-Xing Tian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Min Li
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Feng-Mei Lian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Lin-Hua Zhao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiu-Xiu Wei
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Lin Han
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yu-Jiao Zheng
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Ze-Zheng Gao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Hao-Yu Yang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Xin-Yi Fang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Xiao-Lin Tong
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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42
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He YJ, You CG. The Potential Role of Gut Microbiota in the Prevention and Treatment of Lipid Metabolism Disorders. Int J Endocrinol 2020; 2020:8601796. [PMID: 33005189 PMCID: PMC7509545 DOI: 10.1155/2020/8601796] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 08/24/2020] [Accepted: 09/03/2020] [Indexed: 12/17/2022] Open
Abstract
Due to changes in lifestyle, diet structure, and aging worldwide, the incidence of metabolic syndromes such as hyperlipidemia, hypertension, diabetes, and obesity is increasing. Metabolic syndrome is considered to be closely related to cardiovascular disease and severely affects human health. In recent years, researchers have revealed that the gut microbiota, through its own or interacting metabolites, has a positive role in regulating metabolic syndrome. Therefore, the gut microbiota has been a new "organ" for the treatment of metabolic syndrome. The role has not been clarified, and more research is necessary to prove the specific role of specific strains. Probiotics are also believed to regulate metabolic syndromes by regulating the gut microbiota and are expected to become a new preparation for treating metabolic syndromes. This review focuses on the regulation of lipid metabolism disorders by the gut microbiota through the effects of bile acids (BA), short-chain fatty acids (SCFAs), bile salt hydrolase (BSH), and genes such as ABCG5 and ABCG8, FXR, NPC1L, and LDL-R.
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Affiliation(s)
- Yan-Jun He
- Laboratory Medicine Center, Lanzhou University Second Hospital, No. 82 Cuiyingmen Lanzhou, Lanzhou 730030, Gansu, China
| | - Chong-Ge You
- Laboratory Medicine Center, Lanzhou University Second Hospital, No. 82 Cuiyingmen Lanzhou, Lanzhou 730030, Gansu, China
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43
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Elias-Oliveira J, Leite JA, Pereira ÍS, Guimarães JB, Manso GMDC, Silva JS, Tostes RC, Carlos D. NLR and Intestinal Dysbiosis-Associated Inflammatory Illness: Drivers or Dampers? Front Immunol 2020; 11:1810. [PMID: 32903730 PMCID: PMC7438795 DOI: 10.3389/fimmu.2020.01810] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 07/07/2020] [Indexed: 12/12/2022] Open
Abstract
The intestinal microbiome maintains a close relationship with the host immunity. This connection fosters a health state by direct and indirect mechanisms. Direct influences occur mainly through the production of short-chain fatty acids (SCFAs), gastrointestinal hormones and precursors of bioactive molecules. Indirect mechanisms comprise the crosstalk between bacterial products and the host's innate immune system. Conversely, intestinal dysbiosis is a condition found in a large number of chronic intestinal inflammatory diseases, such as ulcerative colitis and Crohn's disease, as well as in diseases associated with low-grade inflammation, such as obesity, type 1 and 2 diabetes mellitus and cardiovascular diseases. NOD-Like receptors (NLRs) are cytoplasmic receptors expressed by adaptive and innate immune cells that form a multiprotein complex, termed the inflammasome, responsible for the release of mature interleukin (IL)-1β and IL-18. NLRs are also involved in the recognition of bacterial components and production of antimicrobial molecules that shape the gut microbiota and maintain the intestinal homeostasis. Recent novel findings show that NLRs may act as positive or negative regulators of inflammation by modulating NF-κB activation. This mini-review presents current and updated evidence on the interplay between NLRs and gut microbiota and their dual role, contributing to progression or conferring protection, in diabetes and other inflammatory diseases.
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Affiliation(s)
- Jefferson Elias-Oliveira
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Jefferson Antônio Leite
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Ítalo Sousa Pereira
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Jhefferson Barbosa Guimarães
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Gabriel Martins da Costa Manso
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - João Santana Silva
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Rita Cássia Tostes
- Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Daniela Carlos
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
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44
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Kobyliak N, Falalyeyeva T, Tsyryuk O, Eslami M, Kyriienko D, Beregova T, Ostapchenko L. New insights on strain-specific impacts of probiotics on insulin resistance: evidence from animal study. J Diabetes Metab Disord 2020; 19:289-296. [PMID: 32550178 PMCID: PMC7270447 DOI: 10.1007/s40200-020-00506-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 02/05/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS сomparative animal study of effectiveness of intermittent administration of lyophilized single-, three- and alive multistrain probiotic in short courses on insulin resistance (IR) in rats with experimental obesity. METHODS 70 rats were divided into 7 groups (n = 10 in each). Rats of group I were left intact. Newborn rats in groups II-VII were administered monosodium glutamate (MSG) (4 mg/g) by injection. Rats in group II (MSG-obesity group) were left untreated. The rats in groups III-V received lyophilized mono-probiotics B.animalis VKL, B.animalis VKB, L.casei IMVB-7280 respectively. The rats in group VI received all three of these probiotic strains mixed together. Group VII was treated with multi-probiotic "Symbiter", containing 14 different live probiotic strains (Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter genera). RESULTS Treatment of newborn rats with MSG lead to the development of obesity in all MSG-obesity rats and up to 20-70% after probiotic administration. Additions to probiotic composition, with preference to alive strains (group VII), led to significantly lower rates of obesity, decrease in HOMA-IR (p < 0.001), proinflammatory cytokines levels - IL-1β (p = 0.003), IL-12Bp40 (p < 0.001) and elevation of adiponectin (p = 0.003), TGF-β (p = 0.010) in comparison with MSG-obesity group. Analysis of results in groups treated with single-strain probiotics (groups III-V) shows significant decrease in HOMA-IR, but changes were less pronounced as compared to mixture groups and did not achieve intact rats level. Other metabolic parameters were not affected significantly by single strains. CONCLUSION Our findings provide major clues for how to design and use probiotics with more efficient compositions in obesity and IR management and may bring new insights into how host-microbe interactions contribute to such protective effects.
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Affiliation(s)
- Nazarii Kobyliak
- Department Endocrinology, Bogomolets National Medical University, T. Shevchenko boulevard, 13, Kyiv, 01601 Ukraine
| | - Tetyana Falalyeyeva
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
| | - Olena Tsyryuk
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
| | - Majid Eslami
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | | | - Tetyana Beregova
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
| | - Liudmila Ostapchenko
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
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45
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Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, Shulzhenko N. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine 2020; 51:102590. [PMID: 31901868 PMCID: PMC6948163 DOI: 10.1016/j.ebiom.2019.11.051] [Citation(s) in RCA: 1049] [Impact Index Per Article: 209.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 11/14/2019] [Accepted: 11/29/2019] [Indexed: 12/12/2022] Open
Abstract
A substantial body of literature has provided evidence for the role of gut microbiota in metabolic diseases including type 2 diabetes. However, reports vary regarding the association of particular taxonomic groups with disease. In this systematic review, we focused on the potential role of different bacterial taxa affecting diabetes. We have summarized evidence from 42 human studies reporting microbial associations with disease, and have identified supporting preclinical studies or clinical trials using treatments with probiotics. Among the commonly reported findings, the genera of Bifidobacterium, Bacteroides, Faecalibacterium, Akkermansia and Roseburia were negatively associated with T2D, while the genera of Ruminococcus, Fusobacterium, and Blautia were positively associated with T2D. We also discussed potential molecular mechanisms of microbiota effects in the onset and progression of T2D.
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Affiliation(s)
- Manoj Gurung
- Colleges of Veterinary Medicine, Oregon State University, 700 SW 30th street, Corvallis, OR, 97331, USA
| | - Zhipeng Li
- Colleges of Veterinary Medicine, Oregon State University, 700 SW 30th street, Corvallis, OR, 97331, USA
| | - Hannah You
- Colleges of Veterinary Medicine, Oregon State University, 700 SW 30th street, Corvallis, OR, 97331, USA
| | - Richard Rodrigues
- Colleges of Pharmacy, Oregon State University, 160 SW 26th street, Corvallis, OR 97331, USA
| | - Donald B Jump
- Colleges of Public Health, Oregon State University, 160 SW 26th street, Corvallis, OR 97331, USA
| | - Andrey Morgun
- Colleges of Pharmacy, Oregon State University, 160 SW 26th street, Corvallis, OR 97331, USA.
| | - Natalia Shulzhenko
- Colleges of Veterinary Medicine, Oregon State University, 700 SW 30th street, Corvallis, OR, 97331, USA.
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46
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Ben Othman M, Sakamoto K. Effect of inactivated Bifidobacterium longum intake on obese diabetes model mice (TSOD). Food Res Int 2019; 129:108792. [PMID: 32036897 DOI: 10.1016/j.foodres.2019.108792] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 10/28/2019] [Accepted: 10/30/2019] [Indexed: 02/06/2023]
Abstract
Obesity and diabetes have been increasing at an alarming rate worldwide. Studies have shown the futility of chemical drugs in the treatment of obesity and diabetes. Bifidobacterium longum (BL), a common member of the gut microbiota throughout the human lifespan, has been widely reported to play a role in host health and disease. Here, we evaluated the effects of inactivated cells of BL (IBL) on obesity and blood glucose levels in TSOD mice by administering IBL orally for 5 weeks. The treated mice showed a significant decrease of body weight gain, adipose tissue mass and blood glucose levels, as well as a significant reduction in blood glucose during an oral glucose tolerance test. The treatment also resulted in reduced levels of cholesterol, triglycerides, and NEFA. Moreover, serum and urine analysis showed low creatinine levels in IBL-treated mice. These data demonstrate that IBL may have the potential to prevent obesity and diabetes.
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Affiliation(s)
- Mahmoud Ben Othman
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
| | - Kazuichi Sakamoto
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
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47
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Su Z, Nie Y, Huang X, Zhu Y, Feng B, Tang L, Zheng G. Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns. Front Pharmacol 2019; 10:1193. [PMID: 31649547 PMCID: PMC6795753 DOI: 10.3389/fphar.2019.01193] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 09/17/2019] [Indexed: 12/23/2022] Open
Abstract
Metabolic syndrome, characterized by central obesity, hypertension, and hyperlipidemia, increases the morbidity and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that hepatic fatty acid accumulation can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria are the major sites of fatty acid β-oxidation, which is the major degradation mechanism of fatty acids. Mitochondrial dysfunction has been shown to be involved in the development of hepatic fatty acid–induced hepatic insulin resistance. Mitochondrial autophagy (mitophagy), a catabolic process, selectively degrades damaged mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial dynamics and function. Therefore, mitophagy can promote mitochondrial fatty acid oxidation to inhibit hepatic fatty acid accumulation and improve hepatic insulin resistance. Here, we review advances in our understanding of the relationship between mitophagy and hepatic insulin resistance. Additionally, we also highlight the potential value of mitophagy in the treatment of hepatic insulin resistance and metabolic syndrome.
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Affiliation(s)
- Zuqing Su
- Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yutong Nie
- Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiufang Huang
- Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.,The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ying Zhu
- Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bing Feng
- Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lipeng Tang
- Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Guangjuan Zheng
- Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
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48
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Regulation of Gut Microbiota and Metabolic Endotoxemia with Dietary Factors. Nutrients 2019; 11:nu11102277. [PMID: 31547555 PMCID: PMC6835897 DOI: 10.3390/nu11102277] [Citation(s) in RCA: 171] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 09/13/2019] [Accepted: 09/18/2019] [Indexed: 02/08/2023] Open
Abstract
Metabolic endotoxemia is a condition in which blood lipopolysaccharide (LPS) levels are elevated, regardless of the presence of obvious infection. It has been suggested to lead to chronic inflammation-related diseases such as obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease (NAFLD), pancreatitis, amyotrophic lateral sclerosis, and Alzheimer’s disease. In addition, it has attracted attention as a target for the prevention and treatment of these chronic diseases. As metabolic endotoxemia was first reported in mice that were fed a high-fat diet, research regarding its relationship with diets has been actively conducted in humans and animals. In this review, we summarize the relationship between fat intake and induction of metabolic endotoxemia, focusing on gut dysbiosis and the influx, kinetics, and metabolism of LPS. We also summarize the recent findings about dietary factors that attenuate metabolic endotoxemia, focusing on the regulation of gut microbiota. We hope that in the future, control of metabolic endotoxemia using dietary factors will help maintain human health.
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49
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Tsukahara T, Kawase T, Yoshida H, Bukawa W, Kan T, Toyoda A. Preliminary investigation of the effect of oral supplementation of Lactobacillus plantarum strain SNK12 on mRNA levels of neurotrophic factors and GABA receptors in the hippocampus of mice under stress-free and sub-chronic mild social defeat-stressing conditions. Biosci Biotechnol Biochem 2019; 83:2345-2354. [PMID: 31524073 DOI: 10.1080/09168451.2019.1659717] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The effect of Lactobacillus plantarum SNK12 (CPLP) supplementation on mRNA levels of hippocampal neurotrophic factors and gamma aminobutyric acid receptors (GABAR) was tested. In Experiment 1, stress-free, unsupplemented and CPLP (4 × 108 cells/head)-supplemented male C57BL/6J (B6) mice were the experimental animals. In Experiment 2, intruder (male, B6) mice [negative control; unsupplemented, sub-chronic mild social defeat stress (sCSDS)-induced; and CPLP-supplemented, sCSDS-induced] were exposed to aggressor mice (adult male Slc:ICR). mRNA levels of neurotrophic factors and GABAR in hippocampal samples of these mice were analyzed. In CPLP-supplemented mice of both experiments, mRNA levels of bdnf, nt-3, and GABAR were upregulated. Moreover, a tendency toward the improvement of habituation ability (Experiment 1) and behavior (Experiment 2) was observed in mice, which may be associated with upregulated neurotrophic factors and GABAR. We demonstrated that oral supplementation of CPLP to stress-free and stress-induced mice upregulated mRNA levels of hippocampal neurotrophic factors and GABAR.
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Affiliation(s)
| | | | | | - Wakoto Bukawa
- Non-Profit Organization, The Japanese Association of Clinical Research on Supplements, Saitama, Japan
| | | | - Atsushi Toyoda
- College of Agriculture, Ibaraki University, Ibaraki, Japan.,United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo, Japan
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50
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Wang Y, Zhao W, Shi J, Wang J, Hao J, Pang X, Huang X, Chen X, Li Y, Jin R, Ge Q. Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model. FASEB J 2019; 33:10140-10151. [DOI: 10.1096/fj.201900238rr] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Yifan Wang
- Department of ImmunologySchool of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking University Beijing China
| | - Weijia Zhao
- Department of ImmunologySchool of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking University Beijing China
| | - Junxiu Shi
- Department of Developmental Cell BiologyKey Laboratory of Cell BiologyMinistry of Public HealthKey Laboratory of Medical Cell BiologyMinistry of EducationChina Medical University Shenyang China
| | - Jiachi Wang
- Department of Developmental Cell BiologyKey Laboratory of Cell BiologyMinistry of Public HealthKey Laboratory of Medical Cell BiologyMinistry of EducationChina Medical University Shenyang China
| | - Jie Hao
- Department of ImmunologySchool of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking University Beijing China
| | - Xuewen Pang
- Department of ImmunologySchool of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking University Beijing China
| | - Xiaojun Huang
- Beijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking University People's HospitalInstitute of Hematology Beijing China
| | - Xiaoping Chen
- State Key Laboratory of Space Medicine Fundamentals and ApplicationChinese Astronaut Research and Training Center Beijing China
| | - Yongzhi Li
- State Key Laboratory of Space Medicine Fundamentals and ApplicationChinese Astronaut Research and Training Center Beijing China
| | - Rong Jin
- Department of ImmunologySchool of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking University Beijing China
| | - Qing Ge
- Department of ImmunologySchool of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking University Beijing China
- Department of Integration of Chinese and Western MedicineSchool of Basic Medical SciencesPeking University Beijing China
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