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Chong S, Lin M, Chong D, Jensen S, Lau NS. A systematic review on gut microbiota in type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2025; 15:1486793. [PMID: 39897957 PMCID: PMC11782031 DOI: 10.3389/fendo.2024.1486793] [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: 08/26/2024] [Accepted: 12/18/2024] [Indexed: 02/04/2025] Open
Abstract
Aims/hypothesis The gut microbiota play crucial roles in the digestion and degradation of nutrients, synthesis of biological agents, development of the immune system, and maintenance of gastrointestinal integrity. Gut dysbiosis is thought to be associated with type 2 diabetes mellitus (T2DM), one of the world's fastest growing diseases. The aim of this systematic review is to identify differences in the composition and diversity of the gut microbiota in individuals with T2DM. Methods A systematic search was conducted to identify studies reporting on the difference in gut microbiota composition between individuals with T2DM and healthy controls. Relevant studies were evaluated, and their characteristics and results were extracted using a standardized data extraction form. The studies were assessed for risk of bias and their findings were reported narratively. Results 58 observational studies published between 2010 and 2024 were included. Beta diversity was commonly reported to be different between individuals with T2DM and healthy individuals. Genera Lactobacillus, Escherichia-Shigella, Enterococcus, Subdoligranulum and Fusobacteria were found to be positively associated; while Akkermansia, Bifidobacterium, Bacteroides, Roseburia, Faecalibacteirum and Prevotella were found to be negatively associated with T2DM. Conclusions This systematic review demonstrates a strong association between T2DM and gut dysbiosis, as evidenced by differential microbial abundances and altered diversity indices. Among these taxa, Escherichia-Shigella is consistently associated with T2DM, whereas Faecalibacterium prausnitzii appears to offer a protective effect against T2DM. However, the heterogeneity and observational nature of these studies preclude the establishment of causative relationships. Future research should incorporate age, diet and medication-matched controls, and include functional analysis of these gut microbes. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42023459937.
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Affiliation(s)
- Serena Chong
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- South West Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Mike Lin
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Garvan Institute of Research, Sydney, NSW, Australia
| | - Deborah Chong
- Animal Health Laboratory, Department of Natural Resources and Environment Tasmania, Tasmania, TAS, Australia
| | - Slade Jensen
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- Infectious Disease and Microbiology, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- School of Medicine Antibiotic Resistance and Mobile Elements Groups, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
| | - Namson S. Lau
- South West Sydney Limb Preservation and Wound Research, Ingham Institute for Applied Medical Research, Sydney, NSW, Australia
- South West Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
- Liverpool Diabetes Collaboration, Ingham Institute of Applied Medical Research, Sydney, NSW, Australia
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Huang Y, Tang Y, Zhao X, Xu M, Chen M. Novel insights into the role of gut microbiota and its metabolites in diabetic chronic wounds. FASEB J 2025; 39:e70316. [PMID: 39785136 DOI: 10.1096/fj.202401478rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 12/14/2024] [Accepted: 01/01/2025] [Indexed: 01/12/2025]
Abstract
Wounds in patients with diabetes present significant physical and economic challenges due to impaired healing and prolonged inflammation, exacerbated by complex interactions between microbes. Especially, the development and healing of diabetic foot ulcers (DFUs) remain an urgent clinical problem. The human gut harbors a vast microbial ecosystem comprising intestinal flora and their metabolic products. Recent advancements in research have illuminated the concept of the "gut-skin axis," revealing intricate relationships between gut microbiota, microbiota-derived metabolites, and various skin diseases, including DFUs. This review aims to unravel the formation and healing process of DFUs in the context of the gut-skin axis. We reviewed the current research progress worldwide regarding to the gut-skin axis, compared and discussed significant changes in the microbiota colonizing the skin and gut in patients with DFUs. The roles of microbiota-derived metabolites such as lipopolysaccharides, short-chain fatty acids, and trimethylamine-N-oxide in the development of DFUs are highlighted. We also reviewed treatment strategies currently employed in clinical practice and identified potential therapeutic targets such as probiotics for treating DFUs. The need for more comprehensive experimental designs to elucidate the intricate relationship between gut microbiota and its metabolites in the context of DFUs are therefore highlighted.
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Affiliation(s)
- Yixuan Huang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Ying Tang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Xiaotong Zhao
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Murong Xu
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Mingwei Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
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Tang L, Ding K, Li M, Chao X, Sun T, Guo Y, Peng X, Jia W, Chen T, Xie G, Feng L. Differences in oral microbiota associated with type 2 diabetes mellitus between the Dai and Han populations. J Oral Microbiol 2024; 17:2442420. [PMID: 39763576 PMCID: PMC11703080 DOI: 10.1080/20002297.2024.2442420] [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: 06/13/2024] [Revised: 12/02/2024] [Accepted: 12/04/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) development is closely linked to microbiota, influenced by geography, ethnicity, gender, and age. While the relationship between oral microbiota and T2DM has been explored, specific microbiota associated with T2DM in the Dai and Han populations remains unclear. This study aims to compare oral microbiota differences and identify keystone species between these populations, both with and without T2DM. METHODS We recruited 28 han participants (6 healthy children, 10 healthy adults, 12 adults with T2DM) and 34 Dai participants (11 healthy children, 10 healthy adults, 13 adults with T2DM). Blood samples were collected for biochemical analysis, and saliva samples underwent DNA extraction and 16S rRNA sequencing. RESULTS Age significantly influenced oral microbiota differences between the Dai and Han populations, overshadowing the effects of diabetes. In the Dai population with T2DM, notable increases in Alistipes putredinis, Lactobacillus spp., Faecalibacterium prausnitzii, and Akkermansia muciniphila were observed compared to the Han population. Keystone genera differed, with Fusibacter central to the Dai population's microbial network, while the Han network was more scattered. CONCLUSION This is the first comparative analysis of oral microbiota in the Dai and Han populations with T2DM, highlighting age and ethnicity's influence on microbial composition.
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Affiliation(s)
- Lingtong Tang
- Department of Clinical Laboratory, The People’s Hospital of Gao County, Yibin, Sichuan, China
- Department of Clinical Laboratory, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Keke Ding
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengci Li
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaowen Chao
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Sun
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhuai Guo
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xufei Peng
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Jia
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
| | - Tianlu Chen
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guoxiang Xie
- Human Metabolomics Institute Inc, Shenzhen, China
| | - Lei Feng
- Department of Clinical Laboratory, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, China
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Wang J, Wei HJ, Mao RF, Chang X. Gut microbiota modulating therapy for diabetes mellitus should be individualized. World J Diabetes 2024; 15:2152-2156. [PMID: 39493555 PMCID: PMC11525721 DOI: 10.4239/wjd.v15.i10.2152] [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: 07/11/2024] [Revised: 09/14/2024] [Accepted: 09/18/2024] [Indexed: 09/26/2024] Open
Abstract
In this editorial, we commented on two articles published online in August and September 2024 in the World Journal of Diabetes, which focused on modifying the gut microbiota (GM) to prevent or delay the progression of diabetes mellitus (DM) and DM-related complications. Numerous studies, many of which are animal studies, have indicated the potential role of GM in the pathogenesis of DM. However, the detailed causality and mechanisms between GM and DM have not been fully clarified. Although there have been some reports of a potential role of modifying the GM in treating DM, most lack long-term observations and are not mechanistic. Additionally, the GM and its role in DM might vary among individuals; therefore, GM-targeted interventions should be individualized to realize their therapeutic potential.
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Affiliation(s)
- Jin Wang
- Department of Ultrasound Medicine, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing 211200, Jiangsu Province, China
| | - Hong-Juan Wei
- Neonatal Intensive Care Unit, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing 211200, Jiangsu Province, China
| | - Rui-Feng Mao
- School of Life Science, Huaiyin Normal University, Huai'an 223300, Jiangsu Province, China
| | - Xin Chang
- Department of Ultrasound Medicine, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing 211200, Jiangsu Province, China
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Talib N, Mohamad NE, Ho CL, Masarudin MJ, Alitheen NB. Modulatory Effects of Isolated Lactobacillus paracasei from Malaysian Water Kefir Grains on the Intestinal Barrier and Gut Microbiota in Diabetic Mice. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10367-4. [PMID: 39313703 DOI: 10.1007/s12602-024-10367-4] [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] [Accepted: 09/13/2024] [Indexed: 09/25/2024]
Abstract
Type 2 diabetes (T2DM) is one of the four major types of non-communicable diseases that have become a global health concern. Water kefir is a product of a brown sugar solution fermented with kefir grains which comprises around 30 microbial species in its grains. Water kefir possesses a wide range of health benefits, including anti-hyperlipidemic effects, and reduces hypertension and blood glucose levels in animal models. Reportedly, consuming water kefir containing probiotics may enhance the intestinal barrier and positively influence the composition of the intestinal microflora. The present study aimed to evaluate the regulatory effects of Lactobacillus paracasei isolated from Malaysian water kefir grains (MWKG) on the alterations of intestinal barrier and gut microbiota in diabetic mice via histopathological analysis of the distal colon and 16S rRNA gene sequencing on fecal microbiome. Results indicated that the administration of isolated Lactobacillus paracasei from MWKG to diabetic mice ameliorated the dominant probiotic phyla in the gut microbiota. Results showed that lower dose (LD) and high dose (HD) treatments of the isolated Lactobacillus paracasei could significantly reduce inflammatory cell infiltration in the distal colon of diabetic mice. The treatments revealed a significant decrease in the relative abundance of Firmicutes in the gut, 0.27 ± 0.06% for LD and 0.34 ± 0.04% for HD, compared to untreated (UN) diabetic mice, 0.40 ± 0.02%. These results suggest that L. paracasei isolated from MWKG could serve as a potential dietary supplement against intestinal inflammation and modify gut microbiota composition in patients with T2DM.
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Affiliation(s)
- Noorshafadzilah Talib
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Nurul Elyani Mohamad
- Biotechnology Research Institute, Universiti Malaysia Sabah, 88400, Kota Kinabalu, Sabah, Malaysia
| | - Chai Ling Ho
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Mas Jaffri Masarudin
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Noorjahan Banu Alitheen
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.
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Kobyliak N, Khomenko M, Falalyeyeva T, Fedchenko A, Savchuk O, Tseyslyer Y, Ostapchenko L. Probiotics for pancreatic β-cell function: from possible mechanism of action to assessment of effectiveness. Crit Rev Microbiol 2024; 50:663-683. [PMID: 37705353 DOI: 10.1080/1040841x.2023.2257776] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 07/27/2023] [Accepted: 09/06/2023] [Indexed: 09/15/2023]
Abstract
Type 2 diabetes (T2D) is a metabolic disease characterized by chronic hyperglycemia because of insulin resistance (IR) and\or pancreatic β-cell dysfunction. Last century research showed that gut microbiota has a direct effect on metabolism and metabolic diseases. New studies into the human microbiome and its connection with the host is making it possible to develop new therapies for a wide variety of diseases. Inflammation is a well-known precursor to metabolic syndrome, which increases the risk of hypertension, visceral obesity, and dyslipidemia, which can lead to T2D through the damage of pancreatic β-cell and reduce insulin secretion. Current understanding for beneficial effects of probiotics in T2D strictly rely on both animal and clinical data, which mostly focused on their impact on IR, anthropometric parameters, glycemic control and markers of chronic systemic inflammation. From the other hand, there is a lack of evidence-based probiotic efficacy on pancreatic β-cell function in terms of T2D and related metabolic disorders. Therefore, current review will focus on the efficacy of probiotics for the protection of β-cells damage and it`s mechanism in patients with T2D.
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Affiliation(s)
- Nazarii Kobyliak
- Endocrinology Department, Bogomolets National Medical University, Kyiv, Ukraine
- Medical Laboratory CSD, Kyiv, Ukraine
| | - Maria Khomenko
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Tetyana Falalyeyeva
- Medical Laboratory CSD, Kyiv, Ukraine
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
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Huang S, Li F, Quan C, Jin D. Intestinal flora: a potential pathogenesis mechanism and treatment strategy for type 1 diabetes mellitus. Gut Microbes 2024; 16:2423024. [PMID: 39520706 PMCID: PMC11552262 DOI: 10.1080/19490976.2024.2423024] [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: 04/23/2024] [Revised: 07/05/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by destruction of pancreatic β-cells, leading to insulin deficiency and hyperglycemia, and its incidence is increasing year by year. The pathogenesis of T1DM is complex, mainly including genetic and environmental factors. Intestinal flora is the largest microbial community in the human body and plays a very important role in human health and disease. In recent years, more and more studies have shown that intestinal flora and its metabolites, as an environmental factor, regulate the development of T1DM through various mechanisms such as altering the intestinal mucosal barrier, influencing insulin secretion and body immune regulation. Intestinal flora transplantation, probiotic supplementation, and other approaches to modulate the intestinal flora appear to be potential therapeutic approaches for T1DM. This article reviews the dysbiosis of the intestinal flora in T1DM, the potential mechanisms by which the intestinal flora affects T1DM, as well as discusses potential approaches to treating T1DM by intervening in the intestinal flora.
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Affiliation(s)
- Shengnan Huang
- Immunology Biology Key Laboratory, Yanbian University, Yanji, China
- Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji, China
| | - Fangfang Li
- Immunology Biology Key Laboratory, Yanbian University, Yanji, China
- Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji, China
| | - Chunhua Quan
- Central Laboratory, The Affiliated Hospital of Yanbian University, Yanji, China
| | - Dan Jin
- Immunology Biology Key Laboratory, Yanbian University, Yanji, China
- Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji, China
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Mathrani A, Lu LW, Sequeira-Bisson IR, Silvestre MP, Hoggard M, Barnett D, Fogelholm M, Raben A, Poppitt SD, Taylor MW. Gut microbiota profiles in two New Zealand cohorts with overweight and prediabetes: a Tū Ora/PREVIEW comparative study. Front Microbiol 2023; 14:1244179. [PMID: 38033566 PMCID: PMC10687470 DOI: 10.3389/fmicb.2023.1244179] [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: 06/23/2023] [Accepted: 10/20/2023] [Indexed: 12/02/2023] Open
Abstract
Obesity-related metabolic diseases such as type 2 diabetes (T2D) are major global health issues, affecting hundreds of millions of people worldwide. The underlying factors are both diverse and complex, incorporating biological as well as cultural considerations. A role for ethnicity - a measure of self-perceived cultural affiliation which encompasses diet, lifestyle and genetic components - in susceptibility to metabolic diseases such as T2D is well established. For example, Asian populations may be disproportionally affected by the adverse 'TOFI' (Thin on the Outside, Fat on the Inside) profile, whereby outwardly lean individuals have increased susceptibility due to excess visceral and ectopic organ fat deposition. A potential link between the gut microbiota and metabolic disease has more recently come under consideration, yet our understanding of the interplay between ethnicity, the microbiota and T2D remains incomplete. We present here a 16S rRNA gene-based comparison of the fecal microbiota of European-ancestry and Chinese-ancestry cohorts with overweight and prediabetes, residing in New Zealand. The cohorts were matched for mean fasting plasma glucose (FPG: mean ± SD, European-ancestry: 6.1 ± 0.4; Chinese-ancestry: 6.0 ± 0.4 mmol/L), a consequence of which was a significantly higher mean body mass index in the European group (BMI: European-ancestry: 37.4 ± 6.8; Chinese-ancestry: 27.7 ± 4.0 kg/m2; p < 0.001). Our findings reveal significant microbiota differences between the two ethnicities, though we cannot determine the underpinning factors. In both cohorts Firmicutes was by far the dominant bacterial phylum (European-ancestry: 93.4 ± 5.5%; Chinese-ancestry: 79.6 ± 10.4% of 16S rRNA gene sequences), with Bacteroidetes and Actinobacteria the next most abundant. Among the more abundant (≥1% overall relative sequence abundance) genus-level taxa, four zero-radius operational taxonomic units (zOTUs) were significantly higher in the European-ancestry cohort, namely members of the Subdoligranulum, Blautia, Ruminoclostridium, and Dorea genera. Differential abundance analysis further identified a number of additional zOTUs to be disproportionately overrepresented across the two ethnicities, with the majority of taxa exhibiting a higher abundance in the Chinese-ancestry cohort. Our findings underscore a potential influence of ethnicity on gut microbiota composition in the context of individuals with overweight and prediabetes.
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Affiliation(s)
- Akarsh Mathrani
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Louise W. Lu
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
| | - Ivana R. Sequeira-Bisson
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
| | - Marta P. Silvestre
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
- Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS), NOVA University of Lisbon, Lisbon, Portugal
| | - Michael Hoggard
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
| | - Daniel Barnett
- Department of Statistics, University of Auckland, Auckland, New Zealand
| | - Mikael Fogelholm
- Department of Food and Nutrition, Faculty of Agriculture and Forestry, University of Helsinki, Helsinki, Finland
| | - Anne Raben
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
- Clinical Research, Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Sally D. Poppitt
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Human Nutrition Unit, University of Auckland, Auckland, New Zealand
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Michael W. Taylor
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
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Han CY, Ye XM, Lu JP, Jin HY, Wang P, Xu WW, Zhang M. Effect of Benaglutide on Gut Microbiota and Fecal Metabolites in Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2023; 16:2329-2344. [PMID: 37577040 PMCID: PMC10416789 DOI: 10.2147/dmso.s418757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 07/22/2023] [Indexed: 08/15/2023] Open
Abstract
Objective Benaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has been approved in the treatment of type 2 diabetes mellitus (T2DM). It is known to lead to significant weight loss, and it is hypothesized that changes in gut microbiota may play a significant role in such weight loss. However, it is unclear how gut microbiota and metabolites change as a result of benaglutide treatment. Methods Healthy participants and patients with T2DM were included in this study. They received differentiated treatments, and stool specimens were collected separately. These stool specimens were subjected to 16S ribosomal RNA amplicon and metagenomic sequencing to create fecal metabolomic profiles. The diversity of gut microbiota and metabolic products in the stools of each participant was analyzed. Results The data showed that Faecalibacterium prausnitzii was abundant in the gut microbiota of the control group, which was entirely made up of healthy individuals; however, it showed a statistically significant decrease in patients with T2DM treated with metformin alone, while no significant decrease was observed in patients treated with metformin combined with benaglutide. A metagenomic analysis revealed that benaglutide could improve the fecal microbiota diversity in patients with T2DM. Furthermore, there was a statistically significant correlation between the changes in the metabolites of patients with T2DM and the changes in their gut microbiota (including F. prausnitzii) after treatment with metformin and benaglutide. Conclusion These findings suggest that the weight-reducing effect of benaglutide is attributed to its ability to normalize the gut microbiota of patients with T2DM, particularly by increasing the abundance of F. prausnitzii.
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Affiliation(s)
- Chen-Yu Han
- Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People's Republic of China
| | - Xiao-Mei Ye
- Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People's Republic of China
| | - Jia-Ping Lu
- Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People's Republic of China
| | - Hai-Ying Jin
- Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People's Republic of China
| | - Ping Wang
- Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People's Republic of China
| | - Wei-Wei Xu
- Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People's Republic of China
| | - Min Zhang
- Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People's Republic of China
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Zhao G, Xie L, Wu Y, Wang B, Teng W, Sun Z, Kao Q, Liu W, Pi X, Ma H. Effects of urbanization and lifestyle habits on the intestinal microbiota of adolescents in eastern China. Front Microbiol 2023; 14:989303. [PMID: 37378282 PMCID: PMC10291051 DOI: 10.3389/fmicb.2023.989303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 05/23/2023] [Indexed: 06/29/2023] Open
Abstract
Introduction Owing to urbanization, living habits have changed widely, leading to alterations in the intestinal microbiota of urban residents. However, there are few studies on the characteristics of intestinal microbiota of adolescents living in different urbanized areas in China. Methods A total of 302 fecal samples collected from adolescent students in eastern China were examined. 16S rRNA high-throughput sequencing was used to identify the fecal microbiota. These data were combined with questionnaire survey results to investigate the effect of urbanization on the intestinal microbiota of adolescents in eastern China. Moreover, the role of lifestyle habits in this relationship was also evaluated. Results The results revealed significant differences in the structure of the intestinal microbiota among adolescents living in regions with different levels of urbanization. Adolescents living in urban regions had a significantly higher proportion of Bacteroides (p < 0.001, FDR = 0.004), whereas those living in towns and rural regions had higher proportions of Bifidobacterium (p < 0.001, FDR < 0.001) and Prevotella (p < 0.05, FDR = 0.019). The diversity of the intestinal microbiota was higher in urban residents than in adolescents living in towns and rural regions (p < 0.05). In addition, the differences in intestinal microbiota across individuals living in cities, towns, and rural regions were related to dietary preferences, flavor preferences, and sleep and exercise durations. Adolescents who ate more meat had more Dorea (LDA = 3.622, p = 0.04), while the abundance of Escherichia-Shigella is higher among adolescents who ate more condiments (LDA = 4.285, p = 0.02). The abundance of Dialister was significantly increased in adolescents with longer sleep durations (LDA = 4.066, p = 0.03). Adolescents who exercised for a long duration had more Faecalibacterium than those who exercised for a shorter duration (LDA = 4.303, p = 0.04). Discussion Our research has preliminarily demonstrated that there were differences in the composition of Gut microbiome in stool samples of adolescents living in different urbanized areas, and provide a scientific basis for the maintenance of a healthy intentional microbota in adolescences.
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Affiliation(s)
- Gang Zhao
- Department of Infectious Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Lu Xie
- School of Public Health, Hangzhou Normal University, Hangzhou, China
| | - Yan Wu
- Department of Infectious Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Bing Wang
- Department of Infectious Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Weilin Teng
- Department of Infectious Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Zhou Sun
- Department of Infectious Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Qingjun Kao
- Department of Infectious Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou, China
| | - Wei Liu
- Zhejiang Academy of Agriculture Sciences, Institute of Plant Protection and Microbiology, Hangzhou, China
| | - Xionge Pi
- Zhejiang Academy of Agriculture Sciences, Institute of Plant Protection and Microbiology, Hangzhou, China
| | - Haiyan Ma
- School of Public Health, Hangzhou Normal University, Hangzhou, China
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11
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Siptroth J, Moskalenko O, Krumbiegel C, Ackermann J, Koch I, Pospisil H. Variation of butyrate production in the gut microbiome in type 2 diabetes patients. INTERNATIONAL MICROBIOLOGY : THE OFFICIAL JOURNAL OF THE SPANISH SOCIETY FOR MICROBIOLOGY 2023:10.1007/s10123-023-00324-6. [PMID: 36780038 PMCID: PMC10397123 DOI: 10.1007/s10123-023-00324-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 12/22/2022] [Accepted: 01/04/2023] [Indexed: 02/14/2023]
Abstract
BACKGROUND Diabetes mellitus type 2 is a common disease that poses a challenge to the healthcare system. The disease is very often diagnosed late. A better understanding of the relationship between the gut microbiome and type 2 diabetes can support early detection and form an approach for therapies. Microbiome analysis offers a potential opportunity to find markers for this disease. Next-generation sequencing methods can be used to identify the bacteria present in the stool sample and to generate a microbiome profile through an analysis pipeline. Statistical analysis, e.g., using Student's t-test, allows the identification of significant differences. The investigations are not only focused on single bacteria, but on the determination of a comprehensive profile. Also, the consideration of the functional microbiome is included in the analyses. The dataset is not from a clinical survey, but very extensive. RESULTS By examining 946 microbiome profiles of diabetes mellitus type 2 sufferers (272) and healthy control persons (674), a large number of significant genera (25) are revealed. It is possible to identify a large profile for type 2 diabetes disease. Furthermore, it is shown that the diversity of bacteria per taxonomic level in the group of persons with diabetes mellitus type 2 is significantly reduced compared to a healthy control group. In addition, six pathways are determined to be significant for type 2 diabetes describing the fermentation to butyrate. These parameters tend to have high potential for disease detection. CONCLUSIONS With this investigation of the gut microbiome of persons with diabetes type 2 disease, we present significant bacteria and pathways characteristic of this disease.
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Affiliation(s)
- Julienne Siptroth
- High Performance Computing in Life Sciences, Technical University of Applied Sciences Wildau, Wildau, Germany.
| | - Olga Moskalenko
- BIOMES NGS GmbH, Schwartzkopffstraße 1, 15745, Wildau, Germany
| | | | - Jörg Ackermann
- Department of Molecular Bioinformatics, Institute of Computer Science, Goethe University Frankfurt, 60325, Frankfurt am Main, Germany
| | - Ina Koch
- Department of Molecular Bioinformatics, Institute of Computer Science, Goethe University Frankfurt, 60325, Frankfurt am Main, Germany
| | - Heike Pospisil
- High Performance Computing in Life Sciences, Technical University of Applied Sciences Wildau, Wildau, Germany
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12
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Ahmed LA, Al-Massri KF. Gut Microbiota Modulation for Therapeutic Management of Various Diseases: A New Perspective Using Stem Cell Therapy. Curr Mol Pharmacol 2023; 16:43-59. [PMID: 35196976 DOI: 10.2174/1874467215666220222105004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 11/08/2021] [Accepted: 12/16/2021] [Indexed: 11/22/2022]
Abstract
Dysbiosis has been linked to various diseases ranging from cardiovascular, neurologic, gastrointestinal, respiratory, and metabolic illnesses to cancer. Restoring of gut microbiota balance represents an outstanding clinical target for the management of various multidrug-resistant diseases. Preservation of gut microbial diversity and composition could also improve stem cell therapy which now has diverse clinical applications in the field of regenerative medicine. Gut microbiota modulation and stem cell therapy may be considered a highly promising field that could add up towards the improvement of different diseases, increasing the outcome and efficacy of each other through mutual interplay or interaction between both therapies. Importantly, more investigations are required to reveal the cross-talk between microbiota modulation and stem cell therapy to pave the way for the development of new therapies with enhanced therapeutic outcomes. This review provides an overview of dysbiosis in various diseases and their management. It also discusses microbiota modulation via antibiotics, probiotics, prebiotics, and fecal microbiota transplant to introduce the concept of dysbiosis correction for the management of various diseases. Furthermore, we demonstrate the beneficial interactions between microbiota modulation and stem cell therapy as a way for the development of new therapies in addition to limitations and future challenges regarding the applications of these therapies.
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Affiliation(s)
- Lamiaa A Ahmed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Khaled F Al-Massri
- Department of Pharmacy and Biotechnology, Faculty of Medicine and Health Sciences, University of Palestine, Gaza, Palestine
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13
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Gradisteanu Pircalabioru G, Chifiriuc MC, Picu A, Petcu LM, Trandafir M, Savu O. Snapshot into the Type-2-Diabetes-Associated Microbiome of a Romanian Cohort. Int J Mol Sci 2022; 23:ijms232315023. [PMID: 36499348 PMCID: PMC9741184 DOI: 10.3390/ijms232315023] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/19/2022] [Accepted: 11/27/2022] [Indexed: 12/02/2022] Open
Abstract
The prevalence of type 2 diabetes mellitus (T2D) is alarmingly increasing worldwide, urgently calling for a better understanding of the underlying mechanisms in order to step up prevention and improve therapeutic approaches. It is becoming evident that the gut microbiota seem to have an endless capacity to impact T2D. In this study, we profile the gut microbiome patterns in T2D patients from Romania, by using quantitative Real-Time PCR and next generation sequencing. We enrolled a total of 150 individuals (105 T2D patients, 50 of them without metformin treatment and 45 healthy volunteers). The levels of potentially beneficial butyrate-producing bacteria were significantly reduced, while potentially pathogenic microorganisms such as Enterobacteriaceae and Fusobacterium were enriched in T2D patients. We evaluated the correlation between clinical parameters and gut microbiota and identified the genera Bacteroides, Alistipes, Dialister, Bilophila and Sutterella as possible detrimental factors in T2D. Our findings suggest that the gut microbiota may be a potential target in novel approaches to halt the development of T2D-associated complications.
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Affiliation(s)
- Gratiela Gradisteanu Pircalabioru
- Research Institute of University of Bucharest (ICUB), 050095 Bucharest, Romania;
- Academy of Romanian Scientists, 050045 Bucharest, Romania
- Correspondence:
| | - Mariana-Carmen Chifiriuc
- Research Institute of University of Bucharest (ICUB), 050095 Bucharest, Romania;
- Academy of Romanian Scientists, 050045 Bucharest, Romania
- Romanian Academy, 010071 Bucharest, Romania
- Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
| | - Ariana Picu
- “N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 020042 Bucharest, Romania; (A.P.); (L.M.P.); (O.S.)
| | - Laura Madalina Petcu
- “N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 020042 Bucharest, Romania; (A.P.); (L.M.P.); (O.S.)
| | - Maria Trandafir
- Department of Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 5th District, 050474 Bucharest, Romania;
| | - Octavian Savu
- “N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 020042 Bucharest, Romania; (A.P.); (L.M.P.); (O.S.)
- Department of Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 5th District, 050474 Bucharest, Romania;
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Salamon D, Zapała B, Krawczyk A, Potasiewicz A, Nikiforuk A, Stój A, Gosiewski T. Comparison of iSeq and MiSeq as the two platforms for 16S rRNA sequencing in the study of the gut of rat microbiome. Appl Microbiol Biotechnol 2022; 106:7671-7681. [PMID: 36322250 PMCID: PMC9628524 DOI: 10.1007/s00253-022-12251-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 10/11/2022] [Accepted: 10/15/2022] [Indexed: 11/17/2022]
Abstract
Abstract Amplicon-based next-generation sequencing (NGS) of the 16S ribosomal RNA (16S) regions is a culture-free method used to identify and analyze Procaryota occurring within a given sample. The prokaryotic 16S rRNA gene contains conserved regions and nine variable regions (V1-V9) frequently used for phylogenetic classification of genus or species in diverse microbial populations. This work compares the accuracy and efficacy of two platforms, iSeq and MiSeq from Illumina, used in sequencing 16S rRNA. The most important similarities and differences of 16S microbiome sequencing in 20 fecal rat samples were described. Genetic libraries were prepared according to 16S Metagenomic Sequencing Library Preparation (Illumina) for the V3 and V4 regions of the 16S. The species richness obtained using iSeq technology was lower compared to MiSeq. At the second taxonomy level (L2), the abundance of taxa was comparable for both platforms. At the L7, the taxa abundance was significantly different, and the number of taxa was higher for the MiSeq. The alpha diversity was lower for iSeq than for MiSeq, starting from the order to the species level. The beta diversity estimation revealed statistically significant differences in microbiota diversity starting from the class level to the species level in samples sequenced on two investigated platforms. This work disclosed that the iSeq platform could be used to evaluate the bacterial profile of the samples to characterize the overall profile. The MiSeq System seems to be better for a detailed analysis of the differences in the microbiota composition. Key points • iSeq platform allows to shorten the sequencing time three times compared to the MiSeq. • iSeq can only be used for an initial and quick microbiome assessment. • MiSeq is better for a detailed analysis of the differences in the microbiota composition. Supplementary information The online version contains supplementary material available at 10.1007/s00253-022-12251-z.
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Affiliation(s)
- Dominika Salamon
- grid.5522.00000 0001 2162 9631Department of Molecular Medical Microbiology, Jagiellonian University Medical College, Krakow, Poland
| | - Barbara Zapała
- grid.5522.00000 0001 2162 9631Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
| | - Agnieszka Krawczyk
- grid.5522.00000 0001 2162 9631Department of Molecular Medical Microbiology, Jagiellonian University Medical College, Krakow, Poland
| | - Agnieszka Potasiewicz
- grid.418903.70000 0001 2227 8271Department of Behavioural Neuroscience and Drug Development, Polish Academy of Sciences, Maj Institute of Pharmacology, Krakow, Poland
| | - Agnieszka Nikiforuk
- grid.418903.70000 0001 2227 8271Department of Behavioural Neuroscience and Drug Development, Polish Academy of Sciences, Maj Institute of Pharmacology, Krakow, Poland
| | - Anastazja Stój
- grid.412700.00000 0001 1216 0093Department of Hematology Diagnostics and Genetics, University Hospital, Krakow, Poland
| | - Tomasz Gosiewski
- grid.5522.00000 0001 2162 9631Department of Molecular Medical Microbiology, Jagiellonian University Medical College, Krakow, Poland
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15
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Ionescu RF, Enache RM, Cretoiu SM, Gaspar BS. Gut Microbiome Changes in Gestational Diabetes. Int J Mol Sci 2022; 23:12839. [PMID: 36361626 PMCID: PMC9654708 DOI: 10.3390/ijms232112839] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 10/20/2022] [Accepted: 10/21/2022] [Indexed: 08/27/2023] Open
Abstract
Gestational diabetes mellitus (GDM), one of the most common endocrine pathologies during pregnancy, is defined as any degree of glucose intolerance with onset or first discovery in the perinatal period. Physiological changes that occur in pregnant women can lead to inflammation, which promotes insulin resistance. In the general context of worldwide increasing obesity in young females of reproductive age, GDM follows the same ascending trend. Changes in the intestinal microbiome play a decisive role in obesity and the development of insulin resistance and chronic inflammation, especially in patients with type 2 diabetes mellitus (T2D). To date, various studies have also associated intestinal dysbiosis with metabolic changes in women with GDM. Although host metabolism in women with GDM has not been fully elucidated, it is of particular importance to analyze the available data and to discuss the actual knowledge regarding microbiome changes with potential impact on the health of pregnant women and newborns. We analyzed peer-reviewed journal articles available in online databases in order to summarize the most recent findings regarding how variations in diet and metabolic status of GDM patients can contribute to alteration of the gut microbiome, in the same way that changes of the gut microbiota can lead to GDM. The most frequently observed alteration in the microbiome of patients with GDM was either an increase of the Firmicutes phylum, respectively, or a decrease of the Bacteroidetes and Actinobacteria phyla. Gut dysbiosis was still present postpartum and can impact the development of the newborn, as shown in several studies. In the evolution of GDM, probiotic supplementation and regular physical activity have the strongest evidence of proper blood glucose control, favoring fetal development and a healthy outcome for the postpartum period. The current review aims to summarize and discuss the most recent findings regarding the correlation between GDM and dysbiosis, and current and future methods for prevention and treatment (lifestyle changes, pre- and probiotics administration). To conclude, by highlighting the role of the gut microbiota, one can change perspectives about the development and progression of GDM and open up new avenues for the development of innovative therapeutic targets in this disease.
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Affiliation(s)
- Ruxandra Florentina Ionescu
- Department of Cardiology I, Central Military Emergency Hospital “Dr Carol Davila”, 030167 Bucharest, Romania
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Robert Mihai Enache
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Sanda Maria Cretoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Bogdan Severus Gaspar
- Surgery Department, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Surgery Clinic, Bucharest Emergency Clinical Hospital, 014461 Bucharest, Romania
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16
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Mousa WK, Chehadeh F, Husband S. Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front Immunol 2022; 13:906258. [PMID: 36341463 PMCID: PMC9632986 DOI: 10.3389/fimmu.2022.906258] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 09/20/2022] [Indexed: 09/29/2023] Open
Abstract
Trillions of microbes survive and thrive inside the human body. These tiny creatures are crucial to the development and maturation of our immune system and to maintain gut immune homeostasis. Microbial dysbiosis is the main driver of local inflammatory and autoimmune diseases such as colitis and inflammatory bowel diseases. Dysbiosis in the gut can also drive systemic autoimmune diseases such as type 1 diabetes, rheumatic arthritis, and multiple sclerosis. Gut microbes directly interact with the immune system by multiple mechanisms including modulation of the host microRNAs affecting gene expression at the post-transcriptional level or production of microbial metabolites that interact with cellular receptors such as TLRs and GPCRs. This interaction modulates crucial immune functions such as differentiation of lymphocytes, production of interleukins, or controlling the leakage of inflammatory molecules from the gut to the systemic circulation. In this review, we compile and analyze data to gain insights into the underpinning mechanisms mediating systemic autoimmune diseases. Understanding how gut microbes can trigger or protect from systemic autoimmune diseases is crucial to (1) tackle these diseases through diet or lifestyle modification, (2) develop new microbiome-based therapeutics such as prebiotics or probiotics, (3) identify diagnostic biomarkers to predict disease risk, and (4) observe and intervene with microbial population change with the flare-up of autoimmune responses. Considering the microbiome signature as a crucial player in systemic autoimmune diseases might hold a promise to turn these untreatable diseases into manageable or preventable ones.
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Affiliation(s)
- Walaa K. Mousa
- Biology Department, Whitman College, Walla Walla, WA, United States
- College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates
- College of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Fadia Chehadeh
- Biology Department, Whitman College, Walla Walla, WA, United States
| | - Shannon Husband
- Biology Department, Whitman College, Walla Walla, WA, United States
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17
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Rustanti N, Murdiati A, Juffrie M, Rahayu ES. Effect of Probiotic Lactobacillus plantarum Dad-13 on Metabolic Profiles and Gut Microbiota in Type 2 Diabetic Women: A Randomized Double-Blind Controlled Trial. Microorganisms 2022; 10:microorganisms10091806. [PMID: 36144408 PMCID: PMC9502685 DOI: 10.3390/microorganisms10091806] [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] [Received: 08/21/2022] [Revised: 09/05/2022] [Accepted: 09/06/2022] [Indexed: 11/30/2022] Open
Abstract
Several pathways link type 2 diabetes (T2D) mellitus to the gut microbiome. By modifying the gut microbiota (GM), probiotics may be useful in the treatment of T2D. Lactobacillus plantarum Dad-13 is an indigenous Indonesian probiotic strain that has colonized the digestive tracts of healthy Indonesian adults. Furthermore, the GM of Indonesians is dominated by L. plantarum. The probiotic L. plantarum Dad-13 is likely suitable for Indonesians. This study aimed to assess the effect of the probiotic L. plantarum Dad-13 on metabolic profiles and GM of women with T2D in Yogyakarta, Indonesia. Twenty women from each group of forty T2D patients received either a probiotic or a placebo. The probiotic group consumed 1 g skim milk powder containing 1010 CFU/g L. plantarum daily for 11 weeks. The placebo group received 1 g skim milk powder only daily for 11 weeks. At the start and end of the experiment, anthropometric measures, dietary intake surveys, blood samples, and fecal samples were obtained. The GM analysis of all samples was performed using polymerase chain reaction, and Illumina Novaseq was applied to the selected samples from each group at the beginning and end of the trial. Short-chain fatty acids (SCFAs) were analyzed with gas chromatography. The level of HbA1c in the probiotic group (n:10) significantly decreased from 9.34 ± 2.79% to 8.32 ± 2.04%. However, in comparison with the placebo (n:8), L. plantarum Dad-13 supplementation did not significantly decrease the HbA1c level. No significant change was observed in the fasting blood sugar and total cholesterol levels in either group. The GM analysis showed that L. plantarum Dad-13 supplementation resulted in a considerable increase in the L. plantarum number. No significant changes were observed in the Bifidobacterium and Prevotella populations. In addition, no significant change was observed in the fecal pH and SCFA (e.g., acetic acid, propionate, butyrate, and total SCFA) after supplementation with L. plantarum Dad-13.
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Affiliation(s)
- Ninik Rustanti
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Jl. Flora No 1 Bulaksumur, Yogyakarta 55281, Indonesia
- Department of Nutrition Science, Faculty of Medicine, Universitas Diponegoro, Jl. Prof Soedarto, Tembalang Semarang 50275, Indonesia
| | - Agnes Murdiati
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Jl. Flora No 1 Bulaksumur, Yogyakarta 55281, Indonesia
| | - Mohammad Juffrie
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Jl. Farmako Sekip Utara, Yogyakarta 55281, Indonesia
| | - Endang Sutriswati Rahayu
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Jl. Flora No 1 Bulaksumur, Yogyakarta 55281, Indonesia
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Jl. Teknika Utara Barek, Yogyakarta 55281, Indonesia
- Center of Excellence for Probiotics, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
- Correspondence:
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18
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Bai J, Wan Z, Zhang Y, Wang T, Xue Y, Peng Q. Composition and diversity of gut microbiota in diabetic retinopathy. Front Microbiol 2022; 13:926926. [PMID: 36081798 PMCID: PMC9445585 DOI: 10.3389/fmicb.2022.926926] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 08/05/2022] [Indexed: 11/13/2022] Open
Abstract
ObjectiveDiabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of gut microbiota in DR patients and explores the correlation between gut microbiota and clinical characteristics of DR.MethodsA total of 50 stool samples were collected from 50 participants, including 25 DR patients and 25 healthy controls (HCs). 16S ribosomal RNA gene sequencing was used to analyze the gut microbial composition in these two groups. DNA was extracted from the fecal samples using the MiSeq platform.ResultsThe microbial structure and composition of DR patients were different from that of HCs. The microbial richness of gut microbiota in DR was higher than that of normal individuals. The alterations of microbiome of DR patients were associated with disrupted Firmicutes, Bacteroidetes, Synergistota, and Desulfobacterota phyla. In addition, increased levels of Bacteroides, Megamonas, Ruminococcus_torques_group, Lachnoclostridium, and Alistipes, and decreased levels of Blautia, Eubacterium_ hallii_group, Collinsella, Dorea, Romboutsia, Anaerostipes, and Fusicatenibacter genera were observed in the DR groups. Additionally, a stochastic forest model was developed to identify a set of biomarkers with seven bacterial genera that can differentiate patients with DR from those HC. The microbial communities exhibited varied functions in these two groups because of the alterations of the above-mentioned bacterial genera.ConclusionThe altered composition and function of gut microbiota in DR patients indicated that gut microbiome could be used as non-invasive biomarkers, improve clinical diagnostic methods, and identify putative therapeutic targets for DR.
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Elsherbiny NM, Ramadan M, Abu Faddan NH, Hassan EA, Ali ME, Abd El-Rehim ASED, Abbas WA, Abozaid MAA, Hassanin E, Mohamed GA, Hetta HF, Salah M. Impact of Geographical Location on the Gut Microbiota Profile in Egyptian Children with Type 1 Diabetes Mellitus: A Pilot Study. Int J Gen Med 2022; 15:6173-6187. [PMID: 35864993 PMCID: PMC9296103 DOI: 10.2147/ijgm.s361169] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 06/10/2022] [Indexed: 12/11/2022] Open
Abstract
Purpose To investigate the compositional and functional characteristics of T1DM-associated gut microbiota in two Egyptian cities and to study the geographical locality effects. Patients and Methods This case-control study included 32 children with controlled T1DM and 16 controls, selected from two different regions of Egypt. The gut microbiota of both diabetic and control children was analyzed through 16S rRNA gene sequencing; this was done using the Illumina MiSeq platform. Results Consistent findings among the diabetic children included significantly lower alpha diversity than the control children, as well as a lower mean Firmicutes/Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and the genera Prevotella and Ruminococcus. In the diabetic children, there were also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and the genera Lactobacilli, Bacteroides, and Faecalibacterium. When comparing the two diabetic groups, the Ismailia group (IsDM) was found to have a significantly higher F/B ratio and diversity indices, with resultant differences at the functional level. Conclusion There are a number of consistent changes in the microbiota profile characterizing the diabetic groups irrespective of the geographical location including significantly lower alpha diversity, mean Firmicutes/ Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and genera Prevotella and Ruminococcus. There are also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and genera Lactobacilli, Bacteroides, and Faecalibacterium pointing to the greater driving power of the disease.
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Affiliation(s)
- Nahla M Elsherbiny
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohammed Ramadan
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | - Nagla H Abu Faddan
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Elham Ahmed Hassan
- Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohamed E Ali
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | | | - Wael A Abbas
- Department of Internal Medicine, Gastroenterology and Hepatology Unit, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohamed A A Abozaid
- Department of Internal Medicine, Gastroenterology and Hepatology Unit, Faculty of Medicine, Assiut University, Assiut, Egypt
| | | | - Ghada A Mohamed
- Department of Internal Medicine, Endocrine Unit, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Helal F Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohammed Salah
- Department of Microbiology and Immunology, Faculty of pharmacy, Port Said University, Port Said, Egypt
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Chen F, He L, Li J, Yang S, Zhang B, Zhu D, Wu Z, Zhang S, Hou D, Ouyang C, Yi J, Xiao C, Hou K. Polyethylene Glycol Loxenatide Injection (GLP-1) Protects Vascular Endothelial Cell Function in Middle-Aged and Elderly Patients With Type 2 Diabetes by Regulating Gut Microbiota. Front Mol Biosci 2022; 9:879294. [PMID: 35782875 PMCID: PMC9240776 DOI: 10.3389/fmolb.2022.879294] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 04/19/2022] [Indexed: 02/05/2023] Open
Abstract
Objective: To evaluate the protective effect of Polyethylene Glycol Loxenatide Injection (Glucagon-like peptide-1, GLP-1) on endothelial cells from middle-aged and elderly patients with newly diagnosed or poorly controlled type 2 diabetes mellitus (T2DM). GLP-1 weekly formulation was analyzed for cardiovascular disease protection and correlated with intestinal flora. Design: Stool samples were collected from middle-aged and elderly patients with new-onset or poorly controlled type 2 diabetes in Longhu People's Hospital and Shantou Central Hospital from June 2019 to November 2019. Samples were collected at week 0, 4, and 8 of treatment with GLP-1 weekly formulations. Samples were analyzed for metagenomic sequencing. Analysis was performed to compare the characteristics of the gut microbiota at week 0, 4, and 8 of GLP-1 treatment and to correlate different microbiota with characteristic clinical parameters. Results: Statistical differences were found in blood glucose lowering, cardiovascular endothelial, and inflammation-related indices between week 0 and W4 and in blood glucose lowering and cardiovascular endothelial indices from week 0 to 8 in the newly diagnosed or poorly controlled type 2 diabetic patients treated with GLP-1. Changes in gut microbiota at week 0, 4, and 8 after using GLP-1 were not statistically different, but had an overall trend of rising and then falling, and with different bacteria, that were correlated with different clinical indicators. Conclusion: GLP-1 improves endothelial cell function indicators in middle-aged and elderly diabetic patients, which may be related to its alteration of the population numbers of gut microbiota such as Acinetobacter, Eubacterium ramulus ATCC 29099, and Bacteroides_faecis. This study provides a guidance for the treatment of type 2 diabetic patients.
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Affiliation(s)
- Fengwu Chen
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Department of Endocrine and Metabolic Diseases, Longhu People’s Hospital, Shantou, China
| | - Lina He
- Key Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province, Yichun University, Yichun, China
| | - Jilin Li
- Department of Cardiology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Shuhui Yang
- Department of Endocrine and Metabolic Diseases, Shantou Central Hospital, Shantou, China
| | - Bangzhou Zhang
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- School of Basic Medical Science, Central South University, Changsha, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu People’s Hospital, Shantou, China
| | - Zezhen Wu
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Department of Endocrine and Metabolic Diseases, Longhu People’s Hospital, Shantou, China
| | - Shuo Zhang
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Department of Endocrine and Metabolic Diseases, Longhu People’s Hospital, Shantou, China
| | - Ducheng Hou
- Department of Endocrine and Metabolic Diseases, Longhu People’s Hospital, Shantou, China
| | - Cong Ouyang
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Jianfeng Yi
- Key Laboratory for Research on Active Ingredients in Natural Medicine of Jiangxi Province, Yichun University, Yichun, China
| | - Chuanxing Xiao
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- School of Basic Medical Science, Central South University, Changsha, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Kaijian Hou
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Department of Endocrine and Metabolic Diseases, Longhu People’s Hospital, Shantou, China
- School of Basic Medical Science, Central South University, Changsha, China
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21
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Du Y, Neng Q, Li Y, Kang Y, Guo L, Huang X, Chen M, Yang F, Hong J, Zhou S, Zhao J, Yu F, Su H, Kong X. Gastrointestinal Autonomic Neuropathy Exacerbates Gut Microbiota Dysbiosis in Adult Patients With Type 2 Diabetes Mellitus. Front Cell Infect Microbiol 2022; 11:804733. [PMID: 35211420 PMCID: PMC8861497 DOI: 10.3389/fcimb.2021.804733] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 12/17/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE The diabetic autonomic neuropathy is one of the most common complications in type 2 diabetes mellitus (T2DM), especially gastrointestinal autonomic neuropathy (GAN), which occurs in up to 75% of patients. The study aimed to investigate the gut microbiota composition, structure, and function in T2DM patients with GAN (T2DM_GAN) and set up a link between gut microbiota and clinical characteristics of patients. METHODS DNA was extracted from fecal samples of three groups using the kit method: healthy volunteers (n = 19), the patients with T2DM (n = 76), and T2DM_GAN (n = 27). Sequencing of 16S ribosomal DNA was performed using the MiSeq platform. RESULTS According to the clinical data, higher age, lower triglyceride, and lower body mass index were the main features of patients with T2DM_GAN. The gut microbiota analysis showed that Bacteroidetes, Firmicutes, and Proteobacteria constituted the three dominant phyla in healthy individuals. In addition, the gut microbiota structure and function of T2DM_GAN patients were clearly different from that of T2DM patients. T2DM patients were characterized by Fusobacteria, Fusobacteriia, Fusobacteriales, Fusobacteriaceae, Fusobacterium, Lachnoclostridium, and Fusobacterium_mortiferum. Those gut microbiota may be involved in carotenoid and flavonoid biosyntheses. Relatively, the Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Escherichia-Shigella, Megasphaera, Escherichia_coli, and Megasphaera_elsdenii were characteristic in the T2DM_GAN patients. Those may be involved in bacterial invasion of epithelial cells and pathogenic Escherichia coli infection. CONCLUSIONS GAN exacerbated gut microbiota dysbiosis in adult patients with T2DM. The findings indicated that phyla Fusobacteria and class Gammaproteobacteria were closely related to the occurrence of T2DM. Especially the latter may promote T2DM_GAN.
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Affiliation(s)
- Yuhui Du
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
- Endocrinology Branch, The First People’s Hospital of Yunnan Province, Kunming, China
- School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Qiongli Neng
- Endocrinology Branch, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Yu Li
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
- School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Yongbo Kang
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Liqiong Guo
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Xinwei Huang
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Minghui Chen
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
| | - Fan Yang
- Nutrition Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Jingan Hong
- Nutrition Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Shuai Zhou
- Neurosurgery Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Jianhua Zhao
- Neurosurgery Department, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Fubing Yu
- Digestive System Department, Affiliated Hospital of Yunnan University, Kunming, China
| | - Heng Su
- Endocrinology Branch, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Xiangyang Kong
- Medical Faculty, Kunming University of Science and Technology, Kunming, China
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22
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Xu Q, Ni JJ, Han BX, Yan SS, Wei XT, Feng GJ, Zhang H, Zhang L, Li B, Pei YF. Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study. Front Immunol 2022; 12:746998. [PMID: 35140703 PMCID: PMC8819003 DOI: 10.3389/fimmu.2021.746998] [Citation(s) in RCA: 164] [Impact Index Per Article: 54.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 12/20/2021] [Indexed: 12/12/2022] Open
Abstract
Background Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship. Objective To reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis. Materials and Methods We assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation. Results Combining the results from the discovery and replication stages, we identified one causal bacterial genus, Bifidobacterium. A higher relative abundance of the Bifidobacterium genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339-1.922; PFDR = 4.19 × 10-7] and CeD (OR: 1.401; 95% CI, 1.139-1.722; PFDR = 2.03 × 10-3), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the Bifidobacterium genus. Conclusion This study implied a causal relationship between the Bifidobacterium genus and T1D and CeD, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs.
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Affiliation(s)
- Qian Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Jing-Jing Ni
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Bai-Xue Han
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Shan-Shan Yan
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Xin-Tong Wei
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Gui-Juan Feng
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Hong Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Lei Zhang
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
- Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Bin Li
- Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Affiliated Wujiang Hospital of Nantong University, Suzhou, China
| | - Yu-Fang Pei
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
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23
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Tanaka K, Harata G, Miyazawa K, He F, Tanigaki S, Kobayashi Y. The gut microbiota of non-obese Japanese pregnant women with gestational diabetes mellitus. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2022; 41:4-11. [PMID: 35036248 PMCID: PMC8727054 DOI: 10.12938/bmfh.2021-025] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 07/26/2021] [Indexed: 01/08/2023]
Abstract
Recent evidence has shown that gut microbiota dysbiosis is associated with development of gestational diabetes mellitus (GDM). However, the gut microbiota composition of non-obese women with GDM, which accounts for a relatively large percentage of Asian GDM, is unknown. We investigated the characteristics of gut microbiota of Japanese pregnant women with GDM. Fecal samples from Japanese pregnant women with GDM (n=20) and normal glucose tolerance (NGT, n=16) were collected at the time of GDM diagnosis (T1), at 35-37 weeks of gestation (T2), and at 4 weeks postpartum (T3). Gut microbiota composition was characterized from fecal DNA by sequencing of 16S rRNA genes. Serum samples were collected late in the third trimester, and the circulating levels of adiponectin and IL-6 were measured by ELISA. At the genus level, Peptostreptococcaceae Romboutsia was enriched in GDM women at T1 (p=0.008) and T2 (p=0.047). The women with lower serum adiponectin tended to have more Romboutsia. The Shannon index was significantly lower in the GDM women at T3 than in the NGT women (p=0.008), and that of the GDM women decreased significantly from T2 to T3 (p=0.02). No significant difference in bacterial community structure was found in a beta diversity analysis. The non-obese GDM women (body mass index <25.0 kg/m2) showed a lower abundance of Coriobacteriaceae Collinsella at T1 (p=0.03) and higher abundance of Akkermansia at T2 (p=0.04) than the normal control. The non-obese GDM women had the distinctive gut microbiota profiles. Analysis of gut microbiota is potentially useful for risk assessment of GDM in non-obese pregnant women.
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Affiliation(s)
- Kei Tanaka
- Department of Obstetrics and Gynecology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan
| | - Gaku Harata
- Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama 241-0023, Japan
| | - Kenji Miyazawa
- Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama 241-0023, Japan
| | - Fang He
- Technical Research Laboratory, Takanashi Milk Products Co., Ltd., Yokohama 241-0023, Japan
| | - Shinji Tanigaki
- Department of Obstetrics and Gynecology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan
| | - Yoichi Kobayashi
- Department of Obstetrics and Gynecology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan
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24
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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: 71] [Impact Index Per Article: 23.7] [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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25
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Ballan R, Saad SMI. Characteristics of the Gut Microbiota and Potential Effects of Probiotic Supplements in Individuals with Type 2 Diabetes mellitus. Foods 2021; 10:foods10112528. [PMID: 34828808 PMCID: PMC8622611 DOI: 10.3390/foods10112528] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/13/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022] Open
Abstract
The increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide has become a burden to healthcare systems. In 2019, around 463 million adults were living with diabetes mellitus, and T2DM accounted for 90 to 95% of cases. The relationship between the gut microbiota and T2DM has been explored with the advent of metagenomic techniques. Genome-wide association studies evaluating the microbiota of these individuals have pointed to taxonomic, functional, and microbial metabolite imbalances and represent a potential intervention in T2DM management. Several microbial metabolites and components, such as imidazole propionate, trimethylamine, and lipopolysaccharides, appear to impair insulin signaling, while short-chain fatty acids, secondary bile acids, and tryptophan metabolites may improve it. In addition, the use of probiotics with the aim of transiently restoring the microbial balance or reducing the effects of microbial metabolites that impair insulin sensitivity has been explored. Herein, we critically review the available literature on the changes in the gut microbiota in T2DM together with potential adjuvant therapies that may improve the health status of this population.
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Affiliation(s)
- Rafael Ballan
- Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil;
- Food Research Center, University of São Paulo, São Paulo 05508-080, SP, Brazil
| | - Susana Marta Isay Saad
- Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil;
- Food Research Center, University of São Paulo, São Paulo 05508-080, SP, Brazil
- Correspondence: ; Tel.: +55-11-3091-2378
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26
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Bezrodny SL, Mardanly SG, Zatevalov AM, Tereshina EV, Mironov AY, Pomazanov VV. Assessment of the state of intestinal microbiocenosis based on bacterial endotoxin and plasmalogen in elderly persons with type 2 diabetes mellitus pathology. Klin Lab Diagn 2021; 66:565-570. [PMID: 34543536 DOI: 10.51620/0869-2084-2021-66-9-565-570] [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: 06/13/2023]
Abstract
The concentration of bacterial plasmalogen 18a and endotoxin in the blood of elderly people 45-90 years old with the pathology of type 2 diabetes mellitus (DM 2) - the main group and without diabetes mellitus - the comparison group was investigated. The concentration of both plasmalogen 18a and endotoxin in the blood of individuals with DM 2 pathology is statistically significantly higher than in the blood of individuals without DM 2 pathology. To assess the state of microbiocenosis and predict type 2 diabetes mellitus, decisive rules have been determined in the form of threshold values of plasma concentrations 18a and endotoxin in the blood of elderly people with a suspected or established diagnosis of type 2 diabetes. Using ROC analysis, it was found that values above 20.66 μg / ml for plasmalogen 18a, and 0.48 nmol / ml for endotoxin, determine the presence of type 2 diabetes mellitus pathology in the 45-90 age group.
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Affiliation(s)
- S L Bezrodny
- CJSC «Ecolab»
- G.N. Gabrichevskii Moscow research institute of epidemiology and microbiology of Rospotrebnadzor
| | - S G Mardanly
- CJSC «Ecolab»
- The «State Humanitarian and Technological University»
- FGAOU VO «First MGMU named after I.M. Sechenov» Ministry of Health of Russia
| | - A M Zatevalov
- G.N. Gabrichevskii Moscow research institute of epidemiology and microbiology of Rospotrebnadzor
| | | | - A Yu Mironov
- G.N. Gabrichevskii Moscow research institute of epidemiology and microbiology of Rospotrebnadzor
- Federal research and clinical center of specialized medical care and medical technologies FMBA of Russia
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27
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Que Y, Cao M, He J, Zhang Q, Chen Q, Yan C, Lin A, Yang L, Wu Z, Zhu D, Chen F, Chen Z, Xiao C, Hou K, Zhang B. Gut Bacterial Characteristics of Patients With Type 2 Diabetes Mellitus and the Application Potential. Front Immunol 2021; 12:722206. [PMID: 34484230 PMCID: PMC8415158 DOI: 10.3389/fimmu.2021.722206] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 07/26/2021] [Indexed: 12/13/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a complex disorder comprehensively influenced by genetic and environmental risk, and research increasingly has indicated the role of microbial dysbiosis in T2DM pathogenesis. However, studies comparing the microbiome characteristics between T2DM and healthy controls have reported inconsistent results. To further identify and describe the characteristics of the intestinal flora of T2DM patients, we performed a systematic review and meta-analysis of stool microbial profiles to discern and describe microbial dysbiosis in T2DM and to explore heterogeneity among 7 studies (600 T2DM cases, 543 controls, 1143 samples in total). Using a random effects model and a fixed effects model, we observed significant differences in beta diversity, but not alpha diversity, between individuals with T2DM and controls. We identified various operational taxonomic unit (OTUs) and bacterial genera with significant odds ratios for T2DM. The T2DM signatures derived from a single study by stepwise feature selection could be applied in other studies. By training on multiple studies, we improved the detection accuracy and disease specificity for T2DM. We also discuss the relationship between T2DM-enriched or T2DM-depleted genera and probiotics and provide new ideas for diabetes prevention and improvement.
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Affiliation(s)
- Yanyan Que
- Department of Endocrinology, Zhongshan Hospital Xiamen University, Xiamen, China
| | - Man Cao
- Department of Mathematics and Numerical Simulation and High-Performance Computing Laboratory, School of Sciences, Nanchang University, Nanchang, China
| | - Jianquan He
- Department of Rehabilitation, Zhongshan Hospital Xiamen University, Xiamen, China.,School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Qiang Zhang
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Qiongyun Chen
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Changsheng Yan
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Aiqiang Lin
- Department of Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Luxi Yang
- School of Medicine, Xiamen University, Xiamen, China
| | - Zezhen Wu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, China.,Graduate School, Medical College of Shantou University, Shantou, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, China
| | - Fengwu Chen
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, China
| | - Zhangran Chen
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Chuanxing Xiao
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.,School of Medicine, Xiamen University, Xiamen, China
| | - Kaijian Hou
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, China
| | - Bangzhou Zhang
- Department of Gastroenterology, Zhongshan Hospital Xiamen University, Xiamen, China.,School of Medicine, Xiamen University, Xiamen, China
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28
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Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications. Mediators Inflamm 2021; 2021:5110276. [PMID: 34447287 PMCID: PMC8384524 DOI: 10.1155/2021/5110276] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 07/26/2021] [Indexed: 02/07/2023] Open
Abstract
Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.
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29
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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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30
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Ghorbani Y, Schwenger KJP, Allard JP. Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes. Eur J Nutr 2021; 60:2361-2379. [PMID: 33651137 DOI: 10.1007/s00394-021-02520-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 02/16/2021] [Indexed: 12/11/2022]
Abstract
PURPOSE Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions. RESULTS This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D. CONCLUSION There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.
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Affiliation(s)
- Yasaman Ghorbani
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Toronto General Hospital, University Health Network, Toronto, Canada
| | | | - Johane P Allard
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
- Toronto General Hospital, University Health Network, Toronto, Canada.
- Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
- Department of Medicine, University of Toronto, Toronto, Canada.
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, 585 University Avenue, 9N-973, Toronto, ON, M5G 2N2, Canada.
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Lyu Y, Lin L, Xie Y, Li D, Xiao M, Zhang Y, Cheung SCK, Shaw PC, Yang X, Chan PKS, Kong APS, Zuo Z. Blood-Glucose-Lowering Effect of Coptidis Rhizoma Extracts From Different Origins via Gut Microbiota Modulation in db/db Mice. Front Pharmacol 2021; 12:684358. [PMID: 34211397 PMCID: PMC8239385 DOI: 10.3389/fphar.2021.684358] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 05/27/2021] [Indexed: 01/14/2023] Open
Abstract
Background:Coptidis rhizoma extracts (CREs) have been used widely for their anti-diabetic and anti-microbial activities, and berberine/jatrorrhizine/coptisine/palmatine are the primary bioactive components. Although guidelines have adopted content analyses of these components as a quality control method for CREs, it is difficult to differentiate the CREs from different sources using this method because of the lack of indications for their related pharmacological activities. Purpose: To explore the effect of CREs (CREA/CREB/CREC) with different compositions of major components on the gut microbiota and blood glucose levels in db/db mice. Methods: Degradation of berberine/jatrorrhizine/coptisine/palmatine from CREA/CREB/CREC in rat/mouse intestinal contents and their impact on nine common gastrointestinal bacteria were investigated. In addition, the effects of oral administration of CREA/CREB/CREC for 2 weeks on the gut microbiota and blood glucose levels in db/db mice were monitored via insulin/glucose tolerance test (ITT/GTT), insulin concentration, homeostatic model assessment of insulin resistance and fecal 16S rRNA sequencing. Results and Conclusion: The total amount of berberine/jatrorrhizine/coptisine/palmatine was highest in CREA. Clostridium perfringens was strongly inhibited by all three CREs, with CREA demonstrating the most significant inhibitory effects on minimum inhibitory concentration, time-kill kinetics, and ATP production. In db/db mice, CREA resulted in the most significant decrease in ITT/GTT and depicted different changes in the microbiota from CREB/CREC. Thus, CREs with different compositions of berberine/jatrorrhizine/coptisine/palmatine differed in terms of time-kill kinetics and ATP production assays on C. perfringens. CREA revealed the potent bacterial inhibitory effects and glucose-lowering activity.
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Affiliation(s)
- Yuanfeng Lyu
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Lin Lin
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Yuning Xie
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Dan Li
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Min Xiao
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Yufeng Zhang
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Stanley Chun Kai Cheung
- School of Life Sciences and Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Pang Chui Shaw
- School of Life Sciences and Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Xiao Yang
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Paul Kay Sheung Chan
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Alice Pik Shan Kong
- Division of Endocrinology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
| | - Zhong Zuo
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China
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Sathkumara HD, Eaton JL, Field MA, Govan BL, Ketheesan N, Kupz A. A murine model of tuberculosis/type 2 diabetes comorbidity for investigating the microbiome, metabolome and associated immune parameters. Animal Model Exp Med 2021; 4:181-188. [PMID: 34179725 PMCID: PMC8212822 DOI: 10.1002/ame2.12159] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 02/01/2021] [Indexed: 01/02/2023] Open
Abstract
Tuberculosis (TB) is one of the deadliest infectious diseases in the world. The metabolic disease type 2 diabetes (T2D) significantly increases the risk of developing active TB. Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication. Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection, injury and neoplastic changes. Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients. In this study, using a diet-induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility, we investigated how the intestinal microbiota may impact the development of T2D, and how the gut microbial composition changes following a very low-dose aerosol infection with Mycobacterium tuberculosis (Mtb). Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non-diabetic animals. The observed differences were comparable to previous clinical reports in TB patients, in which it was shown that Mtb infection causes rapid loss of microbial diversity. Furthermore, diversity index and principle component analyses demonstrated distinct clustering of Mtb-infected non-diabetic mice vs. Mtb-infected T2D mice. Our findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters, microbiota and the immune-metabolome of TB/T2D comorbidity. This model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut microbiota and the gut-lung axis.
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Affiliation(s)
- Harindra D. Sathkumara
- Centre for Molecular TherapeuticsAustralian Institute of Tropical Health and MedicineJames Cook UniversityCairns & TownsvilleQLDAustralia
| | - Janet L. Eaton
- College of Public Health, Medical and Veterinary SciencesJames Cook UniversityTownsvilleQLDAustralia
| | - Matt A. Field
- Centre for Molecular TherapeuticsAustralian Institute of Tropical Health and MedicineJames Cook UniversityCairns & TownsvilleQLDAustralia
- Centre for Tropical Bioinformatics and Molecular BiologyJames Cook UniversityCairnsQLDAustralia
- John Curtin School of Medical ResearchAustralian National UniversityCanberraACTAustralia
| | - Brenda L. Govan
- Centre for Molecular TherapeuticsAustralian Institute of Tropical Health and MedicineJames Cook UniversityCairns & TownsvilleQLDAustralia
- College of Public Health, Medical and Veterinary SciencesJames Cook UniversityTownsvilleQLDAustralia
| | | | - Andreas Kupz
- Centre for Molecular TherapeuticsAustralian Institute of Tropical Health and MedicineJames Cook UniversityCairns & TownsvilleQLDAustralia
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Abstract
PURPOSE OF REVIEW An increasing body of evidence suggests that the gut microbiome influences the pathogenesis of insulin resistance and type 2 diabetes (T2D). In this review, we will discuss the latest findings regarding the mechanisms linking the gut microbiome and microbial metabolites with T2D and therapeutic approaches based on the gut microbiota for the prevention and treatment of T2D. RECENT FINDINGS Alterations in the gut microbial composition are associated with the risk of T2D. The gut microbiota can metabolize dietary- and host-derived factors to produce numerous microbial metabolites, which are involved in metabolic processes modulating nutrition and energy harvest, gut barrier function, systemic inflammation, and glucose metabolism. Microbial metabolites are important mediators of microbial-host crosstalk impacting host glucose metabolism. Furthermore, microbiome-based interventions may have beneficial effects on glycemic control. Future research is required to develop personalized T2D therapy based on microbial composition and/or metabolites.
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Xiao Y, Niu Y, Mao M, Lin H, Wang B, Wu E, Zhao H, Li S. [Correlation analysis between type 2 diabetes and core gut microbiota]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:358-369. [PMID: 33849826 DOI: 10.12122/j.issn.1673-4254.2021.03.07] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To analyze the species, abundance and structure differences of intestinal flora between patients with type 2 diabetes mellitus (T2D) and healthy individuals and explore the correlation between intestinal flora changes and T2D. OBJECTIVE We collected a total of 133 clinical fecal samples from 78 healthy individuals and 55 patients with T2D. Hiseq2500 was used for high-throughput sequencing of the V3+V4 regions of the 16S rRNA gene. Usearch and QIIME were used for data splicing and filtering, classification and species annotation. The Alpha diversity index and Beta diversity index of the samples were analyzed using R language data packets to compare the richness and diversity of the sample flora. The flora differences were compared between the two groups and the disease marker flora was screened after correction of the relevant factors. PICRUST software was used to predict the function of different flora. OBJECTIVE There was significant difference in the intestinal flora diversity between the two groups. Cluster analysis showed that Fimicutes and Bacteroidetes were the dominant species at the phylum level. LefSe analysis showed that significant differences in the relative abundance between the two groups in 2 phyla, 3 classes, 3 orders, 4 families and 10 genera. After correction for the influence of related factors, the markers of T2Drelated bacteria groups were identified, including Bifidobacterium, Bifidobacteriales, Bifidobacteriaceae, Actinobacteria, Bacilli, Lactobacillales, Lactobacillaceae and Lactobacillus. On this basis, analysis of KEGG metabolic pathways of the differential flora revealed significant differences in 36 KEGG metabolic pathways between the two groups, and the citric acid cycle, lipopolysaccharide biosynthesis and other metabolic pathways were all up-regulated in T2D group. OBJECTIVE The composition and abundance of intestinal flora were different between T2D group and the normal group, and T2D group showed the characteristics of ecological imbalance.
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Affiliation(s)
- Y Xiao
- School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine, Ministry of Education, Beijing 100081, China
| | - Y Niu
- School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine, Ministry of Education, Beijing 100081, China
| | - M Mao
- School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine, Ministry of Education, Beijing 100081, China
| | - H Lin
- School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine, Ministry of Education, Beijing 100081, China
| | - B Wang
- School Hospital, Minzu University of China, Beijing 100081, China
| | - E Wu
- School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine, Ministry of Education, Beijing 100081, China
| | - H Zhao
- School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine, Ministry of Education, Beijing 100081, China
| | - S Li
- School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine, Ministry of Education, Beijing 100081, China
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Huda MN, Kim M, Bennett BJ. Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes. Front Endocrinol (Lausanne) 2021; 12:632335. [PMID: 33897618 PMCID: PMC8060771 DOI: 10.3389/fendo.2021.632335] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 02/04/2021] [Indexed: 12/20/2022] Open
Abstract
Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.
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Affiliation(s)
- M. Nazmul Huda
- Department of Nutrition, University of California Davis, Davis, CA, United States
- Obesity and Metabolism Research Unit, United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Davis, CA, United States
| | - Myungsuk Kim
- Department of Nutrition, University of California Davis, Davis, CA, United States
- Obesity and Metabolism Research Unit, United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Davis, CA, United States
| | - Brian J. Bennett
- Department of Nutrition, University of California Davis, Davis, CA, United States
- Obesity and Metabolism Research Unit, United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Davis, CA, United States
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Shang J, Liu F, Zhang B, Dong K, Lu M, Jiang R, Xu Y, Diao L, Zhao J, Tang H. Liraglutide-induced structural modulation of the gut microbiota in patients with type 2 diabetes mellitus. PeerJ 2021; 9:e11128. [PMID: 33850659 PMCID: PMC8019531 DOI: 10.7717/peerj.11128] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 02/26/2021] [Indexed: 12/12/2022] Open
Abstract
Accumulating evidence has suggested the importance of gut microbiota in the development of type 2 diabetes mellitus (T2DM). In the present study, 40 patients with T2DM were treated with liraglutide for 4 months. Feces samples and clinical characteristics were collected from these 40 T2DM patients before and after the liraglutide treatment. The diversity and composition of gut microbiota in the two groups were determined by sequencing the V4 region of bacterial 16S rRNA genes. Meanwhile, blood glucose, insulin, hemoglobin A1c (HbA1c), and lipid metabolism were also measured in the pre- and post-liraglutide-treatment groups. We find that Baseline HbA1c was associated with liraglutide treatment response (R2 = 0.527, β = − 0.726, p < 0.0001). After adjusted for baseline HbA1c, blood urea nitrogen was associated with liraglutide treatment response. Besides, our results showed reduced gut microbial alpha diversity, different community structure distribution and altered microbial interaction network in patients treated with liraglutide. The liner discriminant analysis (LDA) effect size (LEfSe) analysis showed that 21 species of bacteria were abundant in the pre-liraglutide-treatment group and 15 species were abundant in the post-liraglutide-treatment group. In addition, we also find that Megamonas were significantly correlated with older age, diabetes duration and diabetic retinopathy, Clostridum were significantly correlated with family history of diabetes and Oscillospira were significantly correlated with both diabetic retinopathy and diabetic peripheral neuropathy. Functional analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and cluster of orthologous groups (COG) annotations enriched three KEGG metabolic pathways and six functional COG categories in the post-liraglutide-treatment group. In conclusion, our research suggests that baseline HbA1c, blood urea nitrogen and gut microbiota are associated with the liraglutide treatment applied on patients with T2DM. These findings may contribute to the beneficial effects of liraglutide against diabetes.
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Affiliation(s)
- Junjie Shang
- Nanyang Second General Hospital, Nanyang, Henan Province, China
| | - Fang Liu
- Kaifeng Central Hospital, Kaifeng, Henan Province, China
| | - Bing Zhang
- Nanyang Second General Hospital, Nanyang, Henan Province, China
| | - Kunlun Dong
- Nanyang Second General Hospital, Nanyang, Henan Province, China
| | - Man Lu
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Rongfeng Jiang
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Yue Xu
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Le Diao
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Jiangman Zhao
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
| | - Hui Tang
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
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Analysis of the Gut Mycobiome in Adult Patients with Type 1 and Type 2 Diabetes Using Next-Generation Sequencing (NGS) with Increased Sensitivity-Pilot Study. Nutrients 2021; 13:nu13041066. [PMID: 33806027 PMCID: PMC8064496 DOI: 10.3390/nu13041066] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/19/2021] [Accepted: 03/22/2021] [Indexed: 01/23/2023] Open
Abstract
The studies on microbiome in the human digestive tract indicate that fungi could also be one of the external factors affecting development of diabetes. The aim of this study was to evaluate the quantitative and qualitative mycobiome composition in the colon of the adults with type 1 (T1D), n = 26 and type 2 (T2D) diabetes, n = 24 compared to the control group, n = 26. The gut mycobiome was characterized in the stool samples using the analysis of the whole internal transcribed spacer (ITS) region of the fungal rDNA gene cluster by next-generation sequencing (NGS) with increased sensitivity. At the L2 (phylum) level, Basidiomycota fungi were predominant in all 3 study groups. Group T1D presented significantly lower number of Ascomycota compared to the T2D group, and at the L6 (genus) level, the T1D group presented significantly lower number of Saccharomyces genus compared to control and T2D groups. In the T1D group, a significant positive correlation between total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and fungi of the genus Saccharomyces, and in the T2D group, a negative correlation between the total cholesterol level and Malassezia genus was found. The obtained results seem to be a good foundation to extend the analysis of the relationship between individual genera and species of fungi and the parameters determining the metabolism of carbohydrates and lipids in the human body.
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Alvarez-Vieites E, López-Santamarina A, Miranda JM, Del Carmen Mondragón A, Lamas A, Cardelle-Cobas A, Nebot C, Franco CM, Cepeda A. Influence of the Intestinal Microbiota on Diabetes Management. Curr Pharm Biotechnol 2021; 21:1603-1615. [PMID: 32410561 DOI: 10.2174/1389201021666200514220950] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 03/01/2020] [Accepted: 03/10/2020] [Indexed: 11/22/2022]
Abstract
In recent decades, there has been a very rapid increase in the prevalence of diabetes globally, with serious health and economic implications. Although today there are several therapeutic treatments for this disease, these do not address the causes of the disease and have serious side effects, so it is necessary to seek new treatments to replace or complement the existing ones. Among these complementary treatments, a strong link between the intestinal microbiota and diabetes has been demonstrated, which has focused attention on the use of biotherapy to regulate the function of the intestinal microbiota and, thus, treat diabetes. In this way, the main objective of this work is to provide a review of the latest scientific evidence on diabetes, gathering information about new trends in its management, and especially, the influence of the intestinal microbiota and microbiome on this pathology. It is possible to conclude that the relationship between the intestinal microbiota and diabetes is carried out through alterations in energy metabolism, the immune system, changes in intestinal permeability, and a state of low-intensity systemic inflammation. Although, currently, most of the experimental work, using probiotics for diabetes management, has been done on experimental animals, the results obtained are promising. Thus, the modification of the microbiota through biotherapy has shown to improve the symptoms and severity of diabetes through various mechanisms related to these alterations.
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Affiliation(s)
- Eva Alvarez-Vieites
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - Arora López-Santamarina
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - José M Miranda
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - Alicia Del Carmen Mondragón
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - Alexandre Lamas
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - Alejandra Cardelle-Cobas
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - Carolina Nebot
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - Carlos M Franco
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
| | - Alberto Cepeda
- Laboratorio de Higiene Inspeccion y Control de Alimentos, Departamento de Quimica Analitica, Nutricion y Bromatologia, Universidad de Santiago de Compostela, 27002-Lugo, Spain
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Yehualashet AS, Yikna BB. Microbial Ecosystem in Diabetes Mellitus: Consideration of the Gastrointestinal System. Diabetes Metab Syndr Obes 2021; 14:1841-1854. [PMID: 33953584 PMCID: PMC8089103 DOI: 10.2147/dmso.s304497] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 03/31/2021] [Indexed: 12/12/2022] Open
Abstract
Intestinal microbiota is established to be a crucial element in the control of human health, and keeping the symbiotic relationship between the human body and intestinal microbes will have paramount importance. A number of investigations illustrated that many chronic diseases are associated with intestinal micro-ecological disorders implying intestinal floras as an important component among the environmental factors, and perturbations in their composition are correlated with metabolic disorders, including obesity and diabetes mellitus (DM). Increased evidence suggests that alterations in the gut microbial ecosystem have been involved in part in the pathogenesis of both type 1 and type 2 DM. Short chain fatty acids (SCFAs), derived from microbiota, have been studied for their potential action in modulating CNS, gut barrier axis, and the immune system as a promising mechanism for the observed protective effects on diabetes pathogenesis. Besides, the role of bile acid (BA) stimulated receptors to have a significant role in liver metabolism, and pathophysiology of liver-based metabolic diseases has also been investigated. In the current review, we will try to summarize the correlation between intestinal microbiota and diabetes considering the existing current evidence revealing the role of gut microbiota in onset and disease progression.
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Affiliation(s)
- Awgichew Shewasinad Yehualashet
- Pharmacology and Toxicology Unit, Department of Pharmacy, College of Health Sciences, Debre Berhan University, Debre Berhan, Ethiopia
- Correspondence: Awgichew Shewasinad Yehualashet Pharmacology and Toxicology Unit, Department of Pharmacy, College of Health Sciences, Debre Berhan University, PO Box 445, Debre Berhan, EthiopiaTel +251 935450290 Email
| | - Berhan Begashaw Yikna
- Pharmacology and Toxicology Unit, Department of Pharmacy, College of Health Sciences, Debre Berhan University, Debre Berhan, Ethiopia
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40
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Yuan X, Chen R, Zhang Y, Lin X, Yang X, McCormick KL. Gut Microbiota of Chinese Obese Children and Adolescents With and Without Insulin Resistance. Front Endocrinol (Lausanne) 2021; 12:636272. [PMID: 33815293 PMCID: PMC8018175 DOI: 10.3389/fendo.2021.636272] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 02/08/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum cytokines related to glucose metabolism, adropin and angiopoietin-like 4 (ANGPTL4). METHODS Clinical data, fecal bacterial composition, glucose-related hormones, and serum adipokines (adropin and ANGPTL4) were analyzed in 65 Chinese children with exogenous obesity. The composition of the gut microbiota was determined by 16S rRNA-based metagenomics and IR was calculated using the homeostasis model assessment (HOMA). RESULTS The 65 obese subjects were divided into two groups: insulin sensitive (IS) (n=40, 57.5% males) or IR (n=25, 60% males). Principal coordinates analysis revealed that the gut microbiota samples from the IS group clustered together and separated partly from the IR group (p=0.008). By Mann-Whitney U-test, at a phylum level, a reduction of Firmicutes and an increase of Bacteroidetes in the IR subjects was observed. LEfSe analysis revealed that IS subject, when compared to their IR counterparts, harbored members of the order Coriobacteriales, Turicibacterales, Pasteurellales and family Turicibacteraceae, that were significantly more abundant. In contrast, the IR subjects had members of family Peptococcaceae that were significantly more prevalent than the IS subjects (all p<0.05). Spearman's correlation analysis revealed that serum ANGPTL4 was positively associated with genus Bacteroides, Butyricimonas, and Alistipes, and adropin was positively associated with genus Anaerostipes and Alistipes, and negatively associated with genus Blautia (all p<0.05). CONCLUSION In obese children, the gut microbiome in IR subjects was significantly discordant from the IS subjects, and the abundance of some metabolism-related bacteria correlated with the serum concentrations of adropin and ANGPTL4. These observations infer that the gut microbiota may be involved in the regulation of glucose metabolism in obesity.
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Affiliation(s)
- Xin Yuan
- Department of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical University, Fuzhou, China
| | - Ruimin Chen
- Department of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical University, Fuzhou, China
- *Correspondence: Ruimin Chen,
| | - Ying Zhang
- Department of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical University, Fuzhou, China
| | - Xiangquan Lin
- Department of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical University, Fuzhou, China
| | - Xiaohong Yang
- Department of Endocrinology, Genetics and Metabolism, Fuzhou Children’s Hospital of Fujian Medical University, Fuzhou, China
| | - Kenneth L. McCormick
- Division of Pediatric Endocrinology and Diabetes, University of Alabama at Birmingham, Birmingham, AL, United States
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41
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Impact of Diabetes on the Gut and Salivary IgA Microbiomes. Infect Immun 2020; 88:IAI.00301-20. [PMID: 32900816 DOI: 10.1128/iai.00301-20] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/24/2020] [Indexed: 12/14/2022] Open
Abstract
Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but also homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted onto mucosal surfaces and, via the process of immune exclusion, shapes the architecture of these microbiomes. Not all microorganisms at mucosal surfaces are targeted by SIgA; therefore, a better understanding of the SIgA-coated fraction may identify the microbial constituents that stimulate host immune responses in the context of health and disease. Chronic diseases like type 2 diabetes are associated with altered microbial communities (dysbiosis) that in turn affect immune-mediated homeostasis. 16S rRNA gene sequencing of SIgA-coated/uncoated bacteria (IgA-Biome) was conducted on stool and saliva samples of normoglycemic participants and individuals with prediabetes or diabetes (n = 8/group). These analyses demonstrated shifts in relative abundance in the IgA-Biome profiles between normoglycemic, prediabetic, or diabetic samples distinct from that of the overall microbiome. Differences in IgA-Biome alpha diversity were apparent for both stool and saliva, while overarching bacterial community differences (beta diversity) were also observed in saliva. These data suggest that IgA-Biome analyses can be used to identify novel microbial signatures associated with diabetes and support the need for further studies exploring these communities. Ultimately, an understanding of the IgA-Biome may promote the development of novel strategies to restructure the microbiome as a means of preventing or treating diseases associated with dysbiosis at mucosal surfaces.
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Unger AL, Eckstrom K, Jetton TL, Kraft J. Facility-dependent metabolic phenotype and gut bacterial composition in CD-1 mice from a single vendor: A brief report. PLoS One 2020; 15:e0238893. [PMID: 32956361 PMCID: PMC7505418 DOI: 10.1371/journal.pone.0238893] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 08/25/2020] [Indexed: 12/16/2022] Open
Abstract
Utilization of murine models remains a valuable tool in biomedical research, yet, disease phenotype of mice across studies can vary considerably. With advances in next generation sequencing, it is increasingly recognized that inconsistencies in host phenotype can be attributed, at least in part, to differences in gut bacterial composition. Research with inbred murine strains demonstrates that housing conditions play a significant role in variations of gut bacterial composition, however, few studies have assessed whether observed variation influences host phenotype in response to an intervention. Our study initially sought to examine the effects of a long-term (9-months) dietary intervention (i.e., diets with distinct fatty acid compositions) on the metabolic health, in particular glucose homeostasis, of genetically-outbred male and female CD-1 mice. Yet, mice were shipped from two different husbandry facilities of the same commercial vendor (Cohort A and B, respectively), and we observed throughout the study that diet, sex, and aging differentially influenced the metabolic phenotype of mice depending on their husbandry facility of origin. Examination of the colonic bacteria of mice revealed distinct bacterial compositions, including 23 differentially abundant genera and an enhanced alpha diversity in mice of Cohort B compared to Cohort A. We also observed that a distinct metabolic phenotype was linked with these differentially abundant bacteria and indices of alpha diversity. Our findings support that metabolic phenotypic variation of mice of the same strain but shipped from different husbandry facilities may be influenced by their colonic bacterial community structure. Our work is an important precautionary note for future research of metabolic diseases via mouse models, particularly those that seek to examine factors such diet, sex, and aging.
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Affiliation(s)
- Allison L. Unger
- Department of Animal and Veterinary Sciences, The University of Vermont, Burlington, Vermont, United States of America
| | - Korin Eckstrom
- Department of Microbiology and Molecular Genetics, The University of Vermont, Burlington, Vermont, United States of America
| | - Thomas L. Jetton
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, The University of Vermont, Colchester, Vermont, United States of America
| | - Jana Kraft
- Department of Animal and Veterinary Sciences, The University of Vermont, Burlington, Vermont, United States of America
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, The University of Vermont, Colchester, Vermont, United States of America
- * E-mail:
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Radwan S, Gilfillan D, Eklund B, Radwan HM, El Menofy NG, Lee J, Kapuscinski M, Abdo Z. A comparative study of the gut microbiome in Egyptian patients with Type I and Type II diabetes. PLoS One 2020; 15:e0238764. [PMID: 32903276 PMCID: PMC7480833 DOI: 10.1371/journal.pone.0238764] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 08/24/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Diabetes remains a growing public health concern in Egypt, as prevalence of Type II diabetes (TIID) has nearly tripled there in the last two decades. Egypt was ranked ninth worldwide in number of diabetes cases, with prevalence of 15.56% among adults. Recent studies have proposed that disturbance of gut microbiota could influence TIID development and indicated associations between a reduced diversity in microbiomes and Type I diabetes (TID). In the present study, we investigated the composition and abundance of the bacterial microbiome in disease state (TID and TIID) of Egyptian patients. Our goal in this study was to characterize features of the gut microbiota and possible differences associated with TID and TIID in this population. METHODS DNA was extracted from fecal samples taken from 22 TID and 18 TIID outpatients of Al-Hussein hospital, Cairo, Egypt. 16S rRNA amplicon sequencing was used to characterize the bacterial taxa and these reads were processed using the software mothur with analysis utilizing packages vegan, phyloseq and metagenomSeq in R. RESULTS AND CONCLUSIONS Our results highlighted a significant increase in abundance of Gram negative, potentially opportunistic pathogenic taxa (Pseudomonas, Prevotella) in all diabetic groups, compared to the control. Lipopolysccharide (LPS), a component of the gram-negative bacterial wall, can activate local immune response and may result in low-grade systemic inflammation contributing to insulin resistance. The gram-positive Gemella, which is associated with increased risk to diabetes, also had a significant increase in abundance in all diabetic groups, compared to the control. In contrast, the commensal bacterial taxa Turicibacter, Terrisporobacter and Clostridium were found to be more abundant in the control group than in TID. Further studies are needed to understand the role of these taxa in health and disease. Lower Richness and low Shannon diversity, though not statistically significant, were observed for TID subjects with no glucose control and with onset of liver disease or hypertension compared to other subjects. In addition, large variation in alpha diversity within the control group could also be observed. Future studies will include larger samples sizes to further elucidate these findings, as well as possible metagenomic studies to examine the intriguing function of significant microbes.
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Affiliation(s)
- Sahar Radwan
- Microbiology and Immunology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Darby Gilfillan
- Department of Microbiology Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America
| | - Bridget Eklund
- Department of Microbiology Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America
| | - Hend M. Radwan
- Microbiology and Immunology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Nagwan G. El Menofy
- Microbiology and Immunology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
| | - Justin Lee
- Department of Microbiology Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America
| | - Marylee Kapuscinski
- Department of Microbiology Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America
| | - Zaid Abdo
- Department of Microbiology Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America
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Gut Microbiota Profile in Patients with Type 1 Diabetes Based on 16S rRNA Gene Sequencing: A Systematic Review. DISEASE MARKERS 2020; 2020:3936247. [PMID: 32908614 PMCID: PMC7474751 DOI: 10.1155/2020/3936247] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 08/07/2020] [Accepted: 08/20/2020] [Indexed: 02/07/2023]
Abstract
The gut microbiota has been presumed to have a role in the pathogenesis of type 1 diabetes (T1D). Significant changes in the microbial composition of T1D patients have been reported in several case-control studies. This study is aimed at systematically reviewing the existing literature, which has investigated the alterations of the intestinal microbiome in T1D patients compared with healthy controls (HCs) using 16S ribosomal RNA-targeted sequencing. The databases of MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched until April 2019 for case-control studies comparing the composition of the intestinal microbiome in T1D patients and HCs based on 16S rRNA gene sequencing techniques. The Newcastle-Ottawa Scale was used to assess the methodological quality. Ten articles involving 260 patients with T1D and 276 HCs were included in this systematic review. The quality scores of all included studies were 6–8 points. In summary, a decreased microbiota diversity and a significantly distinct pattern of clustering with regard to β-diversity were observed in T1D patients when compared with HCs. At the phylum level, T1D was characterised by a reduced ratio of Firmicutes/Bacteroidetes in the structure of the gut community, although no consistent conclusion was reached. At the genus or species level, T1D patients had a reduced abundance of Clostridium and Prevotella compared with HCs, whereas Bacteroides and Ruminococcus were found to be more enriched in T1D patients. This systematic review identified that there is a close association between the gut microbiota and development of T1D. Moreover, gut dysbiosis might be involved in the pathogenesis of T1D, although the causative role of gut microbiota remains to be established. Further well-controlled prospective studies are needed to better understand the role of the intestinal microbiome in the pathogenesis of T1D, which may help explore novel microbiota-based strategies to prevent and treat T1D.
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Mucosal delivery of ESX-1-expressing BCG strains provides superior immunity against tuberculosis in murine type 2 diabetes. Proc Natl Acad Sci U S A 2020; 117:20848-20859. [PMID: 32778586 DOI: 10.1073/pnas.2003235117] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Tuberculosis (TB) claims 1.5 million lives per year. This situation is largely due to the low efficacy of the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG) against pulmonary TB. The metabolic disease type 2 diabetes (T2D) is a risk factor for TB and the mechanisms underlying increased TB susceptibility in T2D are not well understood. Furthermore, it is unknown if new TB vaccines will provide protection in the context of T2D. Here we used a diet-induced murine model of T2D to investigate the underlying mechanisms of TB/T2D comorbidity and to evaluate the protective capacity of two experimental TB vaccines in comparison to conventional BCG. Our data reveal a distinct immune dysfunction that is associated with diminished recognition of mycobacterial antigens in T2D. More importantly, we provide compelling evidence that mucosal delivery of recombinant BCG strains expressing the Mycobacterium tuberculosis (Mtb) ESX-1 secretion system (BCG::RD1 and BCG::RD1 ESAT-6 ∆92-95) are safe and confer superior immunity against aerosol Mtb infection in the context of T2D. Our findings suggest that the remarkable anti-TB immunity by these recombinant BCG strains is achieved via augmenting the numbers and functional capacity of antigen presenting cells in the lungs of diabetic mice.
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Gut microbiota and metabolites in the pathogenesis of endocrine disease. Biochem Soc Trans 2020; 48:915-931. [DOI: 10.1042/bst20190686] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 04/18/2020] [Accepted: 04/28/2020] [Indexed: 02/07/2023]
Abstract
Type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT) are the two most common autoimmune endocrine diseases that have rising global incidence. These diseases are caused by the immune-mediated destruction of hormone-producing endocrine cells, pancreatic beta cells and thyroid follicular cells, respectively. Both genetic predisposition and environmental factors govern the onset of T1D and HT. Recent evidence strongly suggests that the intestinal microbiota plays a role in accelerating or preventing disease progression depending on the compositional and functional profile of the gut bacterial communities. Accumulating evidence points towards the interplay between the disruption of gut microbial homeostasis (dysbiosis) and the breakdown of host immune tolerance at the onset of both diseases. In this review, we will summarize the major recent findings about the microbiome alterations associated with T1D and HT, and the connection of these changes to disease states. Furthermore, we will discuss the potential mechanisms by which gut microbial dysbiosis modulates the course of the disease, including disruption of intestinal barrier integrity and microbial production of immunomodulatory metabolites. The aim of this review is to provide broad insight into the role of gut microbiome in the pathophysiology of these diseases.
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Gao B, Zhong M, Shen Q, Wu Y, Cao M, Ju S, Chen L. Gut microbiota in early pregnancy among women with Hyperglycaemia vs. Normal blood glucose. BMC Pregnancy Childbirth 2020; 20:284. [PMID: 32393255 PMCID: PMC7216510 DOI: 10.1186/s12884-020-02961-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 04/21/2020] [Indexed: 02/07/2023] Open
Abstract
Background Recent studies suggest that there is a link between the gut microbiota and glucose metabolism. This study aimed to compare the gut microbiota during early pregnancy of women with hyperglycymia to those with normal blood glucose. Methods Gut microbial composition was analysed in 22 women with hyperglycaemia and 28 age-matched healthy controls during their first prenatal visits (< 20 weeks) using high throughput sequencing of the V3-V4 region of the 16S ribosomal RNA gene. Hyperglycemia was diagnosed based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups in 2010. Results Women with hyperglycemia in pregnancy (HIP) had significantly lower microbial richness and diversity compared with healthy pregnant women. The proportions of the Firmicutes and Bacteroidetes phyla and the ratio of Firmicutes:Bacteroidetes were not different between the two groups. We observed that individuals with HIP had an increased abundance of Nocardiaceae, Fusobacteriaceae, etc., whereas healthy controls had significantly higher levels of Christensenellaceae, Clostridiales_vadinBB60_group, Coriobacteriaceae, etc. Similarly, levels of the members of the Ruminococcaceae family, including Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-003, and Ruminococcaceae_UCG-002, were significantly reduced in the HIP group and were negatively correlated with HbA1c. HbA1c levels were positively correlated with Bacteroidaceae and Enterobacteriaceae and negatively correlated with Christensenellaceae, etc. CRP was positively correlated with the Bacteroidaceae and Fusobacteriaceae families and the Fusobacterium genus. Conclusions Our study revealed that individuals with HIP have gut microbial dysbiosis and that certain bacterial groups are associated with glucose metabolism during pregnancy. Further study is needed to provide new ideas to control glucose by modifying the gut microbiota.
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Affiliation(s)
- Beibei Gao
- Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China
| | - Mengdan Zhong
- Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China
| | - Qiong Shen
- Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China
| | - Ying Wu
- Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China
| | - Mengdie Cao
- Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China
| | - Songwen Ju
- Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China
| | - Lei Chen
- Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, China.
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Metagenomic Analysis of Duodenal Microbiota Reveals a Potential Biomarker of Dysbiosis in the Course of Obesity and Type 2 Diabetes: A Pilot Study. J Clin Med 2020; 9:jcm9020369. [PMID: 32013181 PMCID: PMC7074165 DOI: 10.3390/jcm9020369] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 01/19/2020] [Accepted: 01/27/2020] [Indexed: 12/20/2022] Open
Abstract
Numerous scientific studies confirm that, apart from environmental and genetic factors, a significant role is played by gastrointestinal microbiota in the aetiology of type 2 diabetes and obesity. Currently, scientists mainly focus on the distal intestinal microbiota, while the equally important proximal parts of the intestine are overlooked. The aim of the study was a qualitative analysis of the structure of the duodenal mucosa microbiota in groups of patients with obesity and with type 2 diabetes and where obesity qualified for bariatric surgery: sleeve gastrectomy. The microbiological results obtained were compared with some clinical parameters. As a result, it was possible to determine the microbiological core that the treatment and control groups had in common, including phyla: Firmicutes, Proteobacteria, and Actinobacteria. The patients with obesity and with type 2 diabetes and obesity presented a significantly lower number of genus Bifidobacterium compared to healthy subjects. Furthermore, the numbers of Bifidobacterium were positively correlated with the high density lipoprotein (HDL) concentration in the groups under study. The obtained results indicate that bacteria of the genus Bifidobacterium should be considered in the future in the context of a potential biomarker in the progress of type 2 diabetes and obesity.
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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: 1034] [Impact Index Per Article: 206.8] [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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Almugadam BS, Liu Y, Chen SM, Wang CH, Shao CY, Ren BW, Tang L. Alterations of Gut Microbiota in Type 2 Diabetes Individuals and the Confounding Effect of Antidiabetic Agents. J Diabetes Res 2020; 2020:7253978. [PMID: 33062716 PMCID: PMC7539102 DOI: 10.1155/2020/7253978] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 04/07/2020] [Accepted: 04/15/2020] [Indexed: 12/19/2022] Open
Abstract
Type 2 diabetes is a leading cause of morbidity and a common risk of several disorders. Identifying the microbial ecology changes is essential for disease prediction, therapy, and prevention. Thus, our study is aimed at investigating the intestinal microbiota among healthy and type 2 diabetes individuals and exploring the effect of antidiabetic agents on gut bacterial flora. 24 type 2 diabetes (metformin, glimepiride, and nontherapeutic subgroups; N = 8) and 24 healthy control subjects were enrolled in this study, and intestinal bacterial microbiota was investigated by analyzing V3-V4 regions of 16S rRNA gene sequence. Numerous alterations were observed in the gut microbial community of diabetic individuals. These changes were characterized by a significant lowered abundance of Faecalibacterium, Fusobacterium, Dialister, and Elusimicrobium in the nontherapeutic subgroup compared to the healthy control group. Likewise, correlation analysis showed a substantial decline in gut microbiota richness and diversity with the duration of illness. Furthermore, antidiabetic agents restored to some extent the richness and diversity of gut microbiota and improved the abundance of many beneficial bacteria with a significant increase of Methanobrevibacter in the metformin subcategory compared to the nontherapeutic subgroup. In return, they decreased the abundance of some opportunistic pathogens. The findings of this study have added a novel understanding about the pathogenesis of the disease and the mechanisms underlying antidiabetic therapy, which are of potential interest for therapeutic lines and further studies.
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Affiliation(s)
- Babiker Saad Almugadam
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
- Department of Microbiology, Faculty of Medical Laboratory Sciences, University of El Imam El Mahdi, Kosti, White Nile State, Sudan
| | - Yinhui Liu
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
| | - Shen-min Chen
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
| | - Chun-hao Wang
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
| | - Chen-yi Shao
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
| | - Bao-wei Ren
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
| | - Li Tang
- Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China
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