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Lundgrin EL, Hatipoglu B. Trending Modalities in Type 2 Diabetes Prevention. J Clin Endocrinol Metab 2025; 110:S187-S192. [PMID: 39998920 DOI: 10.1210/clinem/dgaf040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Indexed: 02/27/2025]
Abstract
CONTEXT Prediabetes now affects a substantial proportion of the population, marking a growing group of individuals at increased risk for the development of type 2 diabetes (T2D). Given the profound effect of T2D on an individual's morbidity and mortality, T2D prevention is of critical importance. EVIDENCE ACQUISITION We searched PubMed and Ovid MEDLINE databases for recent systematic reviews, meta-analyses, and original research articles pertaining to prediabetes and the prevention of T2D. EVIDENCE SYNTHESIS T2D prevention strategies have focused on intensive lifestyle modification as well as numerous medications that ultimately improve insulin resistance. Recently, a better understanding of the gut microbiome's role in diabetes progression has suggested a possible preventive role for fecal transplant. Finally, multiple incretin pharmaceutical agents have been developed that show promise in the prevention and treatment of T2D. CONCLUSION The number of novel ways to prevent T2D is rapidly growing. A thorough understanding of the indications, outcomes, and limitations of these new therapies is critical for all who care for individuals with diabetes.
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Affiliation(s)
- Erika L Lundgrin
- Department of Pediatric Endocrinology, Rainbow Babies and Children's Hospital, Cleveland, OH 44106, USA
- Diabetes and Metabolic Care Center, Division of Endocrinology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
- School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Betul Hatipoglu
- Diabetes and Metabolic Care Center, Division of Endocrinology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
- School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
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Hindle VK, Veasley NM, Holscher HD. Microbiota-Focused Dietary Approaches to Support Health: A Systematic Review. J Nutr 2025; 155:381-401. [PMID: 39486521 PMCID: PMC11867136 DOI: 10.1016/j.tjnut.2024.10.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 10/01/2024] [Accepted: 10/28/2024] [Indexed: 11/04/2024] Open
Abstract
Diet affects the intestinal microbiota. Increasingly, research is linking the intestinal microbiota to various human health outcomes. Consumption of traditional prebiotics (inulin, fructo-oligosaccharides, and galacto-oligosaccharides) confers health benefits through substrate utilization by select intestinal microorganisms, namely Bifidobacterium and Lactobacilli spp. A similar but distinct concept focused on microorganisms to support human health is through direct consumption of certain live microorganisms recognized as probiotics, which classically include Lactobacilli or Bifidobacterium strains. With advances in sequencing technologies and culturing techniques, other novel functional intestinal microorganisms are being increasingly identified and studied to determine how they may underpin human health benefits. These novel microorganisms are targeted for enrichment within the autochthonous intestinal microbiota through dietary approaches and are also gaining interest as next-generation probiotics because of their purported beneficial properties. Thus, characterizing dietary approaches that nourish select microorganisms in situ is necessary to propel biotic-focused research forward. As such, we reviewed the literature to summarize findings on dietary approaches that nourish the human intestinal microbiota and benefit health to help fill the gap in knowledge on the connections between certain microorganisms, the metabolome, and host physiology. The overall objective of this systematic review was to summarize the impact of dietary interventions with the propensity to nourish certain intestinal bacteria, affect microbial metabolite concentrations, and support gastrointestinal, metabolic, and cognitive health in healthy adults. Findings from the 17 randomized controlled studies identified in this systematic review indicated that dietary interventions providing dietary fibers, phytonutrients, or unsaturated fatty acids differentially enriched Akkermansia, Bacteroides, Clostridium, Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus species, with variable effects on microbial metabolites and subsequent associations with physiologic markers of gastrointestinal and metabolic health. These findings have implications for biotic-focused research on candidate prebiotic substrates as well as next-generation probiotics.
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Affiliation(s)
- Veronica K Hindle
- Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL, United States
| | - Nadine M Veasley
- Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, United States
| | - Hannah D Holscher
- Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL, United States; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, United States; Personalized Nutrition Initiative, University of Illinois Urbana-Champaign, Urbana, IL, United States.
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Mazumder MHH, Hussain S. Air-Pollution-Mediated Microbial Dysbiosis in Health and Disease: Lung-Gut Axis and Beyond. J Xenobiot 2024; 14:1595-1612. [PMID: 39449427 PMCID: PMC11503347 DOI: 10.3390/jox14040086] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 10/14/2024] [Accepted: 10/16/2024] [Indexed: 10/26/2024] Open
Abstract
Growing evidence suggests physiological and pathological functions of lung and gut microbiomes in various pathologies. Epidemiological and experimental data associate air pollution exposure with host microbial dysbiosis in the lungs and gut. Air pollution through increased reactive oxygen species generation, the disruption of epithelial barrier integrity, and systemic inflammation modulates microbial imbalance. Microbiome balance is crucial in regulating inflammation and metabolic pathways to maintain health. Microbiome dysbiosis is proposed as a potential mechanism for the air-pollution-induced modulation of pulmonary and systemic disorders. Microbiome-based therapeutic approaches are increasingly gaining attention and could have added value in promoting lung health. This review summarizes and discusses air-pollution-mediated microbiome alterations in the lungs and gut in humans and mice and elaborates on their role in health and disease. We discuss and summarize the current literature, highlight important mechanisms that lead to microbial dysbiosis, and elaborate on pathways that potentially link lung and lung microbiomes in the context of environmental exposures. Finally, we discuss the lung-liver-gut axis and its potential pathophysiological implications in air-pollution-mediated pathologies through microbial dysbiosis.
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Affiliation(s)
- Md Habibul Hasan Mazumder
- Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA;
- Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA
- Department of Pharmaceutical and Pharmacological Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA
| | - Salik Hussain
- Department of Physiology, Pharmacology & Toxicology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA;
- Center for Inhalation Toxicology (iTOX), School of Medicine, West Virginia University, Morgantown, WV 26506, USA
- Department of Microbiology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA
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Yan S, Wang H, Feng B, Ye L, Chen A. Causal relationship between gut microbiota and diabetic nephropathy: a two-sample Mendelian randomization study. Front Immunol 2024; 15:1332757. [PMID: 38533501 PMCID: PMC10964483 DOI: 10.3389/fimmu.2024.1332757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/26/2024] [Indexed: 03/28/2024] Open
Abstract
Objective Emerging evidence has provided compelling evidence linking gut microbiota (GM) and diabetic nephropathy (DN) via the "gut-kidney" axis. But the causal relationship between them hasn't been clarified yet. We perform a Two-Sample Mendelian randomization (MR) analysis to reveal the causal connection with GM and the development of DN, type 1 diabetes nephropathy (T1DN), type 2 diabetes nephropathy (T2DN), type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM). Methods We used summary data from MiBioGen on 211 GM taxa in 18340 participants. Generalized MR analysis methods were conducted to estimate their causality on risk of DN, T1DN, T2DN, T1DM and T2DM from FinnGen. To ensure the reliability of the findings, a comprehensive set of sensitivity analyses were conducted to confirm the resilience and consistency of the results. Results It was showed that Class Verrucomicrobiae [odds ratio (OR) =1.5651, 95%CI:1.1810-2.0742,PFDR=0.0018], Order Verrucomicrobiales (OR=1.5651, 95%CI: 1.1810-2.0742, PFDR=0.0018) and Family Verrucomicrobiaceae (OR=1.3956, 95%CI:1.0336-1.8844, PFDR=0.0296) had significant risk of DN. Our analysis found significant associations between GM and T2DN, including Class Verrucomimicrobiae (OR=1.8227, 95% CI: 1.2414-2.6763, PFDR=0.0139), Order Verrucomimicrobiae (OR=1.5651, 95% CI: 1.8227-2.6764, PFDR=0.0024), Rhodospirillales (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0026), and Family Verrucomicroniaceae (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0083). The Eubacteriumprotogenes (OR=0.4076, 95% CI: 0.2415-0.6882, PFDR=0.0021) exhibited a protection against T1DN. Sensitivity analyses confirmed that there was no significant heterogeneity and pleiotropy. Conclusions At the gene prediction level, we identified the specific GM that is causally linked to DN in both T1DM and T2DM patients. Moreover, we identified distinct microbial changes in T1DN that differed from those seen in T2DN, offering valuable insights into GM signatures associated with subtype of nephropathy.
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Affiliation(s)
- Shuxiang Yan
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Hua Wang
- Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Baiyu Feng
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Lin Ye
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Anqun Chen
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
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Taheriazam A, Entezari M, Firouz ZM, Hajimazdarany S, Hossein Heydargoy M, Amin Moghadassi AH, Moghadaci A, Sadrani A, Motahhary M, Harif Nashtifani A, Zabolian A, Tabari T, Hashemi M, Raesi R, Jiang M, Zhang X, Salimimoghadam S, Ertas YN, Sun D. Eco-friendly chitosan-based nanostructures in diabetes mellitus therapy: Promising bioplatforms with versatile therapeutic perspectives. ENVIRONMENTAL RESEARCH 2023; 228:115912. [PMID: 37068723 DOI: 10.1016/j.envres.2023.115912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/04/2023] [Accepted: 04/13/2023] [Indexed: 05/16/2023]
Abstract
Nature-derived polymers, or biopolymers, are among the most employed materials for the development of nanocarriers. Chitosan (CS) is derived from the acetylation of chitin, and this biopolymer displays features such as biocompatibility, biodegradability, low toxicity, and ease of modification. CS-based nano-scale delivery systems have been demonstrated to be promising carriers for drug and gene delivery, and they can provide site-specific delivery of cargo. Owing to the high biocompatibility of CS-based nanocarriers, they can be used in the future in clinical trials. On the other hand, diabetes mellitus (DM) is a chronic disease that can develop due to a lack of insulin secretion or insulin sensitivity. Recently, CS-based nanocarriers have been extensively applied for DM therapy. Oral delivery of insulin is the most common use of CS nanoparticles in DM therapy, and they improve the pharmacological bioavailability of insulin. Moreover, CS-based nanostructures with mucoadhesive features can improve oral bioavailability of insulin. CS-based hydrogels have been developed for the sustained release of drugs and the treatment of DM complications such as wound healing. Furthermore, CS-based nanoparticles can mediate delivery of phytochemicals and other therapeutic agents in DM therapy, and they are promising compounds for the treatment of DM complications, including nephropathy, neuropathy, and cardiovascular diseases, among others. The surface modification of nanostructures with CS can improve their properties in terms of drug delivery and release, biocompatibility, and others, causing high attention to these nanocarriers in DM therapy.
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Affiliation(s)
- Afshin Taheriazam
- Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Zeinab Mohammadi Firouz
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Shima Hajimazdarany
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Amir Hossein Amin Moghadassi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Amin Sadrani
- Department of Orthopedics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | - Amirhossein Zabolian
- Department of Orthopedics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Teimour Tabari
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Rasoul Raesi
- Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical-Surgical Nursing, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Mengyuan Jiang
- Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, China
| | - Xuebin Zhang
- Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, China
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, Kayseri, Turkey; ERNAM-Nanotechnology Research and Application Center, Erciyes University, Kayseri, Turkey.
| | - Dongdong Sun
- Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, China.
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Varga A, Makszin L, Bufa A, Sipos D, Kása P, Pál S, Rosenstiel P, Sommer F, Kocsis B, Péterfi Z. Efficacy of lyophilised bacteria-rich faecal sediment and supernatant with reduced bacterial count for treating patients with Clostridioides difficile Infection - A novel method for capsule faecal microbiota transfer. Front Cell Infect Microbiol 2023; 13:1041384. [PMID: 36756616 PMCID: PMC9899802 DOI: 10.3389/fcimb.2023.1041384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 01/03/2023] [Indexed: 01/24/2023] Open
Abstract
Background and aims Faecal microbiota transfer (FMT) has managed to earn its place in the Clostridioides difficile infection (CDI) guidelines by having comparable efficacy and recurrence rate of fidaxomicin. After more than 100 successful FMT administration through nasogastric tube, we started using hard gelatine capsules filled with lyophilised faecal sediment and supernatant. Our main question was whether uncoated capsules (containing faecal sediment or supernatant) are comparable to the widely used nasogastric tubes in CDI. We also investigated the effect of storage and time on the survival rate of bacteria in the samples. Methods We compared the efficacy of our capsules to other treatment options of CDI at the Department of Infectology at the University of Pécs (Hungary). For our study, stool was collected from a single donor. We treated 10 patients with relapsing CDI, 5 of them received supernatant, 5 received sediment. Donor samples were stored on 4 different temperatures and tested to determine the survival rates of bacteria. As pilot projects, we also assessed the changes of bacterial taxa, protein- and lipid compositions. Moreover, we selected 4 patients to compare their samples prior and after FMT by using microbiome (16S amplicon sequencing), protein, and lipid analyses. Results 4 out of the 5 patients who received supernatant became symptomless within 2 days after FMT. In the sediment group 3 out of 5 patients were cured from CDI. Comparing the supernatant to the sediment, we found significantly lower number of colony-forming units in the supernatant. We found that -80°C is the most suitable temperature to store the samples. The stool lipid profiles of recipients showed a more diverse composition after FMT, and changes in the stool protein profiles were observed as well. In the microbiome analysis, we observed an increase in the alpha diversity after FMT. Conclusions Our study of 10 patients showed good efficacy of lyophilised faecal supernatant using capsules. The single donor approach proved to be effective in our investigation. A significantly lower CFU number was sufficient for the effect, the separation can be achieved by widely available instruments. For storage temperature, -20°C was sufficient in our clinical practice.
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Affiliation(s)
- Adorján Varga
- 1stDepartment of Internal Medicine - Department of Infectology, University of Pécs, Medical School, Pécs, Hungary.,Department of Medical Microbiology and Immunology, University of Pécs, Medical School, Pécs, Hungary
| | - Lilla Makszin
- Institute of Bioanalysis, Medical School, and Szentágothai Research Center, University of Pécs, Pécs, Hungary
| | - Anita Bufa
- Institute of Bioanalysis, Medical School, and Szentágothai Research Center, University of Pécs, Pécs, Hungary
| | - Dávid Sipos
- 1stDepartment of Internal Medicine - Department of Infectology, University of Pécs, Medical School, Pécs, Hungary
| | - Péter Kása
- Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Faculty of Pharmacy, Pécs, Hungary
| | - Szilárd Pál
- Institute of Pharmaceutical Technology and Biopharmacy, University of Pécs, Faculty of Pharmacy, Pécs, Hungary
| | - Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Kiel, Germany
| | - Felix Sommer
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Kiel, Germany
| | - Béla Kocsis
- Department of Medical Microbiology and Immunology, University of Pécs, Medical School, Pécs, Hungary
| | - Zoltán Péterfi
- 1stDepartment of Internal Medicine - Department of Infectology, University of Pécs, Medical School, Pécs, Hungary
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Liu B, Zhang L, Yang H, Zheng H, Liao X. Microbiota: A potential orchestrator of antidiabetic therapy. Front Endocrinol (Lausanne) 2023; 14:973624. [PMID: 36777348 PMCID: PMC9911464 DOI: 10.3389/fendo.2023.973624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 01/17/2023] [Indexed: 01/28/2023] Open
Abstract
The gut microbiota, as a 'new organ' of humans, has been identified to affect many biological processes, including immunity, inflammatory response, gut-brain neural circuits, and energy metabolism. Profound dysbiosis of the gut microbiome could change the metabolic pattern, aggravate systemic inflammation and insulin resistance, and exacerbate metabolic disturbance and the progression of type 2 diabetes (T2D). The aim of this review is to focus on the potential roles and functional mechanisms of gut microbiota in the antidiabetic therapy. In general, antidiabetic drugs (α-glucosidase inhibitor, biguanides, incretin-based agents, and traditional Chinese medicine) induce the alteration of microbial diversity and composition, and the levels of bacterial component and derived metabolites, such as lipopolysaccharide (LPS), short chain fatty acids (SCFAs), bile acids and indoles. The altered microbial metabolites are involved in the regulation of gut barrier, inflammation response, insulin resistance and glucose homeostasis. Furthermore, we summarize the new strategies for antidiabetic treatment based on microbial regulation, such as pro/prebiotics administration and fecal microbiota transplantation, and discuss the need for more basic and clinical researches to evaluate the feasibility and efficacy of the new therapies for diabetes.
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Affiliation(s)
| | | | | | - Hongting Zheng
- Department of Endocrinology, Chongqing Education Commission Key Laboratory of Diabetic Translational Research, the Second Affiliated Hospital of Army Medical University, Chongqing, China
| | - Xiaoyu Liao
- Department of Endocrinology, Chongqing Education Commission Key Laboratory of Diabetic Translational Research, the Second Affiliated Hospital of Army Medical University, Chongqing, China
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Fenneman AC, Bruinstroop E, Nieuwdorp M, van der Spek AH, Boelen A. A Comprehensive Review of Thyroid Hormone Metabolism in the Gut and Its Clinical Implications. Thyroid 2023; 33:32-44. [PMID: 36322786 DOI: 10.1089/thy.2022.0491] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Background: The gut is a target organ of thyroid hormone (TH) that exerts its action via the nuclear thyroid hormone receptor α1 (TRα1) expressed in intestinal epithelial cells. THs are partially metabolized via hepatic sulfation and glucuronidation, resulting in the production of conjugated iodothyronines. Gut microbiota play an important role in peripheral TH metabolism as they produce and secrete enzymes with deconjugation activity (β-glucuronidase and sulfatase), via which TH can re-enter the enterohepatic circulation. Summary: Intestinal epithelium homeostasis (the finely tuned balance between cell proliferation and differentiation) is controlled by the crosstalk between triiodothyronine and TRα1 and the presence of specific TH transporters and TH-activating and -inactivating enzymes. Patients and experimental murine models with a dominant-negative mutation in the TRα exhibit gross abnormalities in the morphology of the intestinal epithelium and suffer from severe symptoms of a dysfunctional gastrointestinal tract. Over the past decade, gut microbiota has been identified as an essential factor in health and disease, depending on its compositional and functional profile. This has led to a renewed interest in the so-called gut-thyroid axis. Disruption of gut microbial homeostasis (dysbiosis) is associated with autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis, Graves' disease, and Graves' orbitopathy. These studies reviewed here provide new insights into the gut microbiota roles in thyroid disease pathogenesis and may be an initial step toward microbiota-based therapies in AITD. However, it should be noted that cause-effect mechanisms remain to be proven, for which prospective cohort studies, randomized clinical trials, and experimental studies are needed. Conclusion: This review aims at providing a comprehensive insight into the interplay between TH metabolism and gut homeostasis.
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Affiliation(s)
- Aline C Fenneman
- Department of Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Eveline Bruinstroop
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Anne H van der Spek
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Anita Boelen
- Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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Aljutaily T, Rehan M, Moustafa MMA, Barakat H. Effect of Intermittent Fasting, Probiotic-Fermented Camel Milk, and Probiotic-Fermented Camel Milk Incorporating Sukkari Date on Diet-Induced Obesity in Rats. FERMENTATION-BASEL 2022; 8:619. [DOI: 10.3390/fermentation8110619] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Obesity causes metabolic syndrome disorders that are detrimental to health. The current study examined the effects of intermittent fasting (IF), fermented camel milk (FCM), and fermented camel milk incorporating 10% Sukkari date (FCM-D) on weight loss, blood profile, and antioxidant status in obese rats for 6 weeks. Subsequently, leptin and adiponectin levels and histopathological examination of adipose tissue were carried out. Results showed that IF with FCM or FCM-D decreased body weight by 0.92 and −5.45%, respectively. IF alone lowered non-fasting blood glucose (NFBG) and fasting blood glucose FBG after 6 weeks, whereas adding FCM or FCM-D reduced NFBG after 4 weeks. Intermittently fasting obese rats given FCM or FCM-D had the lowest blood glucose levels (BGL). The hypolipidemic effects of IF, FCM, and FCM-D on obese rats reduced triglycerides (TG), cholesterols (CHO), and their derivatives. FCM-D with IF presented a superior effect on lipid profile. A reduction rate of 40, 37, 66, and 40% for TG, CHO, low-density lipoprotein (LDL-c), and very low-density lipoprotein (VLDL-c), respectively, and an increase in HDL-C by 34% were noticed. Reductions of 40, 37, 66, and 40% for TG, CHO, LDL-c, and VLDL-c, respectively, and a 34% rise in high-density lipoprotein (HDL-C) were noted. Combining IF with FCM or FCM-D lowered the atherogenic index (AI) by 42% and 59%, respectively. Remarkably, treating rats with FCM+IF or FCM-D+IF effectively attenuated leptin and adiponectin levels. Malondialdehyde (MDA) was significantly decreased in a type-dependent manner. Implementing FCM-D or FCM with IF significantly attenuated reduced glutathione (GSH), superoxide dismutase (SOD), MDA, and catalase (CAT) levels. The most efficient treatment was giving FCM-D with IF. Histopathologically, adipocyte lipolysis increases free fatty acids (FFAs) and promotes inflammation. Only IF+FCM-D indicated no histopathological alteration except for a few focal areas of a few inflammatory cell infiltrations in the parenchyma. In conclusion, combining IF and Probiotic-FCM or Probiotic-FCM-D effectively accelerated weight loss, attenuated metabolic markers, and reversed histopathological alterations. Thus, IF combined with Probiotic-FCM or Probiotic-FCM-D is highly recommended for weight loss, strengthening antioxidative status, and preventing health disorders.
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Affiliation(s)
- Thamer Aljutaily
- Department of Food Science and Human Nutrition, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia
| | - Medhat Rehan
- Department of Plant Production and Protection, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia
- Department of Genetics, Faculty of Agriculture, Kafrelsheikh University, Kafr El-Sheikh 33516, Egypt
| | | | - Hassan Barakat
- Department of Food Science and Human Nutrition, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah 51452, Saudi Arabia
- Department of Food Technology, Faculty of Agriculture, Benha University, Moshtohor 13736, Egypt
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Thakur PS, Aggarwal D, Takkar B, Shivaji S, Das T. Evidence Suggesting the Role of Gut Dysbiosis in Diabetic Retinopathy. Invest Ophthalmol Vis Sci 2022; 63:21. [PMID: 35877085 PMCID: PMC9339698 DOI: 10.1167/iovs.63.8.21] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Purpose Gut dysbiosis has been identified and tested in human trials for its role in diabetes mellitus (DM). The gut-retina axis could be a potential target for retardation of diabetic retinopathy (DR), a known complication of DM. This study reviews the evidence suggesting gut dysbiosis in DR. Methods The published literature in the past 5 years was reviewed using predetermined keywords and articles. The review intended to determine changes in gut microbiome in DR, the hypothesized mechanisms linking to the gut-retina axis, its predictive potential for progression of DR, and the possible therapeutic targets. Results The gut microbiota of people with DM differ from those without it, and the gut microbiota of people with DR differ from those without it. The difference is more significant in the former (DM versus no DM) and less significant in the latter (DM without DR versus DM with DR). Early research has suggested mechanisms of the gut-retina axis, but these are not different from known changes in the gut microbiome of people with DM. The current evidence on the predictive value of the gut microbiome in the occurrence and progression of DR is low. Therapeutic avenues targeting the gut-retina axis include lifestyle changes, pharmacologic inhibitors, probiotics, and fecal microbiota transplantation. Conclusions Investigating the therapeutic utility of the gut ecosystem for DM and its complications like DR is an emerging area of research. The gut-retina axis could be a target for retardation of DR but needs longitudinal regional studies adjusting for dietary habits.
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Affiliation(s)
- Pratima Singh Thakur
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
| | - David Aggarwal
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
| | - Brijesh Takkar
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India.,Indian Health Outcomes, Public Health, and Economics Research (IHOPE) Centre, L V Prasad Eye Institute, Hyderabad, India.,https://orcid.org/0000-0001-5779-7645
| | - Sisinthy Shivaji
- Prof. Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India.,https://orcid.org/0000-0003-0376-4658
| | - Taraprasad Das
- Anant Bajaj Retina Institute-Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India.,https://orcid.org/0000-0002-1295-4528
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11
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Takáčová M, Bomba A, Tóthová C, Micháľová A, Turňa H. Any Future for Faecal Microbiota Transplantation as a Novel Strategy for Gut Microbiota Modulation in Human and Veterinary Medicine? Life (Basel) 2022; 12:723. [PMID: 35629390 PMCID: PMC9146664 DOI: 10.3390/life12050723] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/28/2022] [Accepted: 05/10/2022] [Indexed: 11/16/2022] Open
Abstract
Alterations in the composition of the intestinal microbiome, also known as dysbiosis, are the result of many factors such as diet, antibiotics, stress, diseases, etc. There are currently several ways to modulate intestinal microbiome such as dietary modulation, the use of antimicrobials, prebiotics, probiotics, postbiotics, and synbiotics. Faecal microbiota transplantation (FMT) represents one new method of gut microbiota modulation in humans with the aim of reconstructing the intestinal microbiome of the recipient. In human medicine, this form of bacteriotherapy is successfully used in cases of recurrent Clostridium difficile infection (CDI). FMT has been known in large animal medicine for several years. In small animal medicine, the use of FMT is not part of normal practice.
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Affiliation(s)
- Martina Takáčová
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
| | - Alojz Bomba
- Prebiotix s.r.o., 024 01 Kysucké Nové Mesto, Slovakia
| | - Csilla Tóthová
- Clinic of Ruminants, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
| | - Alena Micháľová
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
| | - Hana Turňa
- Small Animal Clinic, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
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12
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Wei N, Lu J, Lin Z, Wang X, Cai M, Jiang S, Chen X, Zhu S, Zhang D, Cui L. Systemic Evaluation of the Effect of Diabetes Mellitus on Breast Cancer in a Mouse Model. Front Oncol 2022; 12:829798. [PMID: 35578660 PMCID: PMC9106558 DOI: 10.3389/fonc.2022.829798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 03/31/2022] [Indexed: 12/01/2022] Open
Abstract
Breast cancer complicated with diabetes mellitus (DM) is a common disease. To evaluate the effect of preexisting DM on breast cancer progression without drug interference, we used a streptozotocin (STZ)-induced type 2 diabetes mellitus BALB/c mouse model. We found that 4T1 breast cancer complicated with DM decreased the mouse survival time compared with 4T1-bearing mice. The diversity of gut microbiome was affected by DM. The infiltration of mucosal-associated invariant T cell (MAIT), CD8+ T cell, and CD4+ T cell in the tumor was significantly decreased in the DM-4T1 group compared with the 4T1 group. The transcriptome data of tumor tissues indicated that the expressions of inflammatory C–C chemokine- and metabolism-related genes were greatly changed. The abnormal expression of these genes may be related with the decreased T-cell infiltration in DM-4T1. In conclusion, the gut microbiome and tumor microenvironment of diabetic breast cancer patients have unique features. The effect of diabetes on breast cancer should be considered in the treatment for diabetic breast cancer patients.
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Affiliation(s)
- Nana Wei
- Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, China
| | - Jinmiao Lu
- Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
| | - Zhibing Lin
- Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoyu Wang
- Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Mengmeng Cai
- Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
| | - Shengyao Jiang
- Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaoyu Chen
- Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
| | - Shilan Zhu
- Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
| | - Dong Zhang
- Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Li Cui
- Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Li Cui,
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13
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Boussamet L, Rajoka MSR, Berthelot L. Microbiota, IgA and Multiple Sclerosis. Microorganisms 2022; 10:microorganisms10030617. [PMID: 35336190 PMCID: PMC8954136 DOI: 10.3390/microorganisms10030617] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 12/16/2022] Open
Abstract
Multiple sclerosis (MS) is a neuroinflammatory disease characterized by immune cell infiltration in the central nervous system and destruction of myelin sheaths. Alterations of gut bacteria abundances are present in MS patients. In mouse models of neuroinflammation, depletion of microbiota results in amelioration of symptoms, and gavage with MS patient microbiota exacerbates the disease and inflammation via Th17 cells. On the other hand, depletion of B cells using anti-CD20 is an efficient therapy in MS, and growing evidence shows an important deleterious role of B cells in MS pathology. However, the failure of TACI-Ig treatment in MS highlighted the potential regulatory role of plasma cells. The mechanism was recently demonstrated involving IgA+ plasma cells, specific for gut microbiota and producing IL-10. IgA-coated bacteria in MS patient gut exhibit also modifications. We will focus our review on IgA interactions with gut microbiota and IgA+ B cells in MS. These recent data emphasize new pathways of neuroinflammation regulation in MS.
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Affiliation(s)
- Léo Boussamet
- Centre for Research in Transplantation and Translation Immunology, Nantes Université, Inserm, CR2TI UMR, 1064 Nantes, France;
| | - Muhammad Shahid Riaz Rajoka
- Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan;
| | - Laureline Berthelot
- Centre for Research in Transplantation and Translation Immunology, Nantes Université, Inserm, CR2TI UMR, 1064 Nantes, France;
- Correspondence:
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14
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Zhai L, Wu J, Lam YY, Kwan HY, Bian ZX, Wong HLX. Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes. Int J Mol Sci 2021; 22:ijms222312846. [PMID: 34884651 PMCID: PMC8658018 DOI: 10.3390/ijms222312846] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 11/19/2021] [Accepted: 11/24/2021] [Indexed: 12/18/2022] Open
Abstract
Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.
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Affiliation(s)
- Lixiang Zhai
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (L.Z.); (J.W.); (H.Y.K.)
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, New Territories, Hong Kong, China;
| | - Jiayan Wu
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (L.Z.); (J.W.); (H.Y.K.)
| | - Yan Y. Lam
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, New Territories, Hong Kong, China;
| | - Hiu Yee Kwan
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (L.Z.); (J.W.); (H.Y.K.)
| | - Zhao-Xiang Bian
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (L.Z.); (J.W.); (H.Y.K.)
- Centre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, New Territories, Hong Kong, China;
- Correspondence: (Z.-X.B.); (H.L.X.W.)
| | - Hoi Leong Xavier Wong
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (L.Z.); (J.W.); (H.Y.K.)
- Correspondence: (Z.-X.B.); (H.L.X.W.)
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15
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Kunasegaran T, Balasubramaniam VRMT, Arasoo VJT, Palanisamy UD, Ramadas A. The Modulation of Gut Microbiota Composition in the Pathophysiology of Gestational Diabetes Mellitus: A Systematic Review. BIOLOGY 2021; 10:biology10101027. [PMID: 34681126 PMCID: PMC8533096 DOI: 10.3390/biology10101027] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 10/08/2021] [Accepted: 10/08/2021] [Indexed: 02/08/2023]
Abstract
Simple Summary Recent studies have placed a great deal of emphasis on the importance of the microbiome, especially the link between the alteration of gut microbiota and multiple associated diseases. Gut microbiota changes in pregnancy have a significant impact on metabolic function and may contribute to gestational diabetes mellitus (GDM). Although GDM carries long-term health risks that affect women, there are also significant short- and severe long-term consequences for the offspring. Regardless, there is a notable lack of research focusing on the impact of prominent microorganisms involved in the development of GDM. A comprehensive review was conducted to gather relevant data on the types of microorganisms that have been associated with GDM. The review found that certain microorganisms impact the onset and progression of GDM during pregnancy. Several bacterial strains associated with GDM are influenced by a diet high in fat and low in fiber. Therefore, integrating the idea of a microbiome-based individualized dietary intervention into gestational diabetes management may be incredibly beneficial. Abstract General gut microbial dysbiosis in diabetes mellitus, including gestational diabetes mellitus (GDM), has been reported in a large body of literature. However, evidence investigating the association between specific taxonomic classes and GDM is lacking. Thus, we performed a systematic review of peer-reviewed observational studies and trials conducted among women with GDM within the last ten years using standard methodology. The National Institutes of Health (NIH) quality assessment tools were used to assess the quality of the included studies. Fourteen studies investigating microbial interactions with GDM were found to be relevant and included in this review. The synthesis of literature findings demonstrates that Bacteroidetes, Proteobacteria, Firmicutes, and Actinobacteria phyla, such as Desulfovibrio, Ruminococcaceae, P. distasonis, Enterobacteriaceae, Collinsella, and Prevotella, were positively associated with GDM. In contrast, Bifidobacterium and Faecalibacterium, which produce butyrate, are negatively associated with GDM. These bacteria were associated with inflammation, adiposity, and glucose intolerance in women with GDM. Lack of good diet management demonstrated the alteration of gut microbiota and its impact on GDM glucose homeostasis. The majority of the studies were of good quality. Therefore, there is great potential to incorporate personalized medicine targeting microbiome modulation through dietary intervention in the management of GDM.
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16
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Zaky A, Glastras SJ, Wong MYW, Pollock CA, Saad S. The Role of the Gut Microbiome in Diabetes and Obesity-Related Kidney Disease. Int J Mol Sci 2021; 22:9641. [PMID: 34502562 PMCID: PMC8431784 DOI: 10.3390/ijms22179641] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetic kidney disease (DKD) is a progressive disorder, which is increasing globally in prevalence due to the increased incidence of obesity and diabetes mellitus. Despite optimal clinical management, a significant number of patients with diabetes develop DKD. Hence, hitherto unrecognized factors are likely to be involved in the initiation and progression of DKD. An extensive number of studies have demonstrated the role of microbiota in health and disease. Dysregulation in the microbiota resulting in a deficiency of short chain fatty acids (SCFAs) such as propionate, acetate, and butyrate, by-products of healthy gut microbiota metabolism, have been demonstrated in obesity, type 1 and type 2 diabetes. However, it is not clear to date whether such changes in the microbiota are causative or merely associated with the diseases. It is also not clear which microbiota have protective effects on humans. Few studies have investigated the centrality of reduced SCFA in DKD development and progression or the potential therapeutic effects of supplemental SCFAs on insulin resistance, inflammation, and metabolic changes. SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. In this review, we will summarize the complex relationship between the gut microbiota and the kidney, examine the evidence for the role of gut dysbiosis in diabetes and obesity-related kidney disease, and explore the mechanisms involved. In addition, we will describe the role of potential therapies that modulate the gut microbiota to prevent or reduce kidney disease progression.
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Affiliation(s)
- Amgad Zaky
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
| | - Sarah J. Glastras
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
- Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
| | - May Y. W. Wong
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
- Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
| | - Carol A. Pollock
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
- Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
| | - Sonia Saad
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
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17
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Wang Y, Ye X, Ding D, Lu Y. Characteristics of the intestinal flora in patients with peripheral neuropathy associated with type 2 diabetes. J Int Med Res 2021; 48:300060520936806. [PMID: 32938282 PMCID: PMC7503028 DOI: 10.1177/0300060520936806] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To study the characteristics of the intestinal flora in patients with diabetic peripheral neuropathy (DPN) and analyze the association between the intestinal flora and clinical indicators. METHODS We classified 80 subjects into three groups: patients with DPN (n = 45), patients type 2 diabetes without DPN (n = 21), and healthy controls (n = 14). The intestinal flora composition was compared among the three groups, and the correlation between the intestinal flora and clinical indicators was analyzed. RESULTS At the phylum level, the richness of Firmicutes and Actinobacteria was elevated in the DN group, and that of Bacteroidetes was decreased. At the genus level, the richness of Bacteroides and Faecalibacterium was significantly decreased in the DPN group, whereas that of Escherichia-Shigella, Lachnoclostridium, Blautia, Megasphaera, and Ruminococcus torques group was increased. The homeostasis model assessment insulin resistance index was positively correlated with Megasphaera richness. Glycine ursodeoxycholic acid was positively correlated with Ruminococcus gnavus group and Phascolarctobacterium richness. Tauroursodeoxycholic acid was positively correlated with Ruminococcus gnavus group and Parabacteroides richness. CONCLUSION There was obvious intestinal microbiota disorder in patients with DPN, which may be related to insulin resistance. These changes may have important roles in the development of DPN.
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Affiliation(s)
- Yayun Wang
- Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaolong Ye
- Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dafa Ding
- Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yibing Lu
- Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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18
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Abstract
Cardiovascular disease (CVD) is currently the leading cause of death worldwide. Although many well-known conditions cause CVD, recent research has suggested that alterations to the gut microbiome may also promote CVD. The gastrointestinal tract houses trillions of bacteria, some of which in large numbers are considered to be part of a healthy gut microbiome profile. These "good" bacteria have the ability to process and digest complex carbohydrates into short-chain fatty acids (SFCA). These SCFA serve as signaling molecules, immune-modulating molecules, and sources of energy. However, with gut dysbiosis, there is an overgrowth of certain bacteria and these bacteria overly produce phosphatidylcholine, choline, and carnitine into the waste product trimethylamine-N-oxide (TMAO). Elevated TMAO levels are associated with an increased risk of atherosclerosis, myocardial infarction, thrombosis, and stroke. Therefore, introducing therapeutic interventions that alter a dysbiotic gut profile back to a healthy gut microbiome may be the key to reducing the incidence of cardiovascular disease in some conditions. The purpose of this review is to critically examine and consolidate the relevant information bearing on this concept. Our goal is to provide the informational framework for the possible use of microbiome modification as an optional therapeutic modality.
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Affiliation(s)
- Andrea A Astudillo
- Osteopathic Medicine, Nova Southeastern University, Dr. Kiran C. Patel College of Osteopathic Medicine, Davie, USA
| | - Harvey N Mayrovitz
- Medical Education, Nova Southeastern University, Dr. Kiran C. Patel College of Allopathic Medicine, Davie, USA
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19
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Huang Y, Wang Z, Ma H, Ji S, Chen Z, Cui Z, Chen J, Tang S. Dysbiosis and Implication of the Gut Microbiota in Diabetic Retinopathy. Front Cell Infect Microbiol 2021; 11:646348. [PMID: 33816351 PMCID: PMC8017229 DOI: 10.3389/fcimb.2021.646348] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 03/02/2021] [Indexed: 12/16/2022] Open
Abstract
The pathogenesis of type 2 diabetes mellitus (T2DM) is commonly associated with altered gut bacteria. However, whether the microbial dysbiosis that exists in human diabetic patients with or without retinopathy is different remains largely unknown. Here, we collected clinical information and fecal samples from 75 participants, including 25 diabetic patients without retinopathy (DM), 25 diabetic patients with retinopathy (DR), and 25 healthy controls (HC). The gut microbial composition in the three groups was analyzed using 16S ribosomal RNA (rRNA) gene sequencing. Microbial structure and composition differed in the three groups. The α and β diversities in both the DM and DR groups were reduced compared with those in the HC group. Blautia was the most abundant genus, especially in the DM group. In addition, increased levels of Bifidobacterium and Lactobacillus and decreased levels of Escherichia-Shigella, Faecalibacterium, Eubacterium_hallii_group and Clostridium genera were observed in the DM and DR groups compared with the HC group. Furthermore, a biomarker set of 25 bacterial families, which could distinguish patients in the DR group from those in the DM and HC groups was identified, with the area under the curve values ranging from 0.69 to 0.85. Of note, Pasteurellaceae, which was increased in DM and decreased in DR compared with HC, generated a high AUC (0.74) as an individual predictive biomarker. Moreover, 14 family biomarkers were associated with fasting blood glucose levels or diabetes, with most of them being negatively correlated. In summary, our study establishes compositional alterations of gut microbiota in DM and DR, suggesting the potential use of gut microbiota as a non-invasive biomarker for clinical and differential diagnosis, as well as identifying potential therapeutic targets of diabetic retinopathy.
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Affiliation(s)
- Yinhua Huang
- Aier School of Ophthalmology, Central South University, Changsha, China.,Aier Eye Institute, Changsha, China
| | - Zhijie Wang
- Aier School of Ophthalmology, Central South University, Changsha, China.,Aier Eye Institute, Changsha, China
| | | | | | | | | | - Jiansu Chen
- Aier School of Ophthalmology, Central South University, Changsha, China.,Aier Eye Institute, Changsha, China.,Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.,Institute of Ophthalmology, Medical College, Jinan University, Guangzhou, China
| | - Shibo Tang
- Aier School of Ophthalmology, Central South University, Changsha, China.,Aier Eye Institute, Changsha, China.,CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
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20
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Gradisteanu Pircalabioru G, Corcionivoschi N, Gundogdu O, Chifiriuc MC, Marutescu LG, Ispas B, Savu O. Dysbiosis in the Development of Type I Diabetes and Associated Complications: From Mechanisms to Targeted Gut Microbes Manipulation Therapies. Int J Mol Sci 2021; 22:2763. [PMID: 33803255 PMCID: PMC7967220 DOI: 10.3390/ijms22052763] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/06/2021] [Accepted: 03/08/2021] [Indexed: 12/12/2022] Open
Abstract
Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host-microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approaches.
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Affiliation(s)
| | - Nicolae Corcionivoschi
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT9 5PX, UK;
| | - Ozan Gundogdu
- Faculty of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK;
| | - Mariana-Carmen Chifiriuc
- Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania; (G.G.P.); (L.G.M.); (B.I.)
- Academy of Romanian Scientists, 050045 Bucharest, Romania
| | | | - Bogdan Ispas
- Research Institute of University of Bucharest (ICUB), 300645 Bucharest, Romania; (G.G.P.); (L.G.M.); (B.I.)
| | - Octavian Savu
- “N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 2nd District, 020042 Bucharest, Romania;
- Department of Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 5th District, 050474 Bucharest, Romania
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21
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Zha H, Liu F, Ling Z, Chang K, Yang J, Li L. Multiple bacteria associated with the more dysbiotic genitourinary microbiomes in patients with type 2 diabetes mellitus. Sci Rep 2021; 11:1824. [PMID: 33469094 PMCID: PMC7815922 DOI: 10.1038/s41598-021-81507-x] [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: 06/09/2020] [Accepted: 01/07/2021] [Indexed: 02/08/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) influences the human health and can cause significant illnesses. The genitourinary microbiome profiles in the T2DM patients remain poorly understood. In the current study, a series of bioinformatic and statistical analyses were carried out to determine the multiple bacteria associated with the more dysbiotic genitourinary microbiomes (i.e., those with lower dysbiosis ratio) in T2DM patients, which were sequenced by Illumina-based 16S rRNA gene amplicon sequencing. All the genitourinary microbiomes from 70 patients with T2DM were clustered into three clusters of microbiome profiles, i.e., Cluster_1_T2DM, Cluster_2_T2DM and Cluster_3_T2DM, with Cluster_3_T2DM at the most dysbiotic genitourinary microbial status. The three clustered T2DM microbiomes were determined with different levels of alpha diversity indices, and driven by distinct urinalysis variables. OTU12_Clostridiales and OTU28_Oscillospira were likely to drive the T2DM microbiomes to more dysbiotic status, while OTU34_Finegoldia could play a vital role in maintaining the least dysbiotic T2DM microbiome (i.e., Cluster_1_T2DM). The functional metabolites K08300_ribonuclease E, K01223_6-phospho-beta-glucosidase and K00029_malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) were most associated with Cluster_1_T2DM, Cluster_2_T2DM and Cluster_3_T2DM, respectively. The characteristics and multiple bacteria associated with the more dysbiotic genitourinary microbiomes in T2DM patients may help with the better diagnosis and management of genitourinary dysbiosis in T2DM patients.
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Affiliation(s)
- Hua Zha
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
- School of Biological Sciences, The University of Auckland, Auckland, New Zealand
- Institute of Marine Science, The University of Auckland, Auckland, New Zealand
| | - Fengping Liu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
- School of Medicine, Jiangnan University, Wuxi, China
| | - Zongxin Ling
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
| | - Kevin Chang
- Department of Statistics, The University of Auckland, Auckland, New Zealand
| | - Jiezuan Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310000, China.
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Abstract
Nutritional content and timing are increasingly appreciated to constitute important human variables collectively impacting all aspects of human physiology and disease. However, person-specific mechanisms driving nutritional impacts on the human host remain incompletely understood, while current dietary recommendations remain empirical and nonpersonalized. Precision nutrition aims to harness individualized bodies of data, including the human gut microbiome, in predicting person-specific physiological responses (such as glycemic responses) to food. With these advances notwithstanding, many unknowns remain, including the long-term efficacy of such interventions in delaying or reversing human metabolic disease, mechanisms driving these dietary effects, and the extent of the contribution of the gut microbiome to these processes. We summarize these conceptual advances, while highlighting challenges and means of addressing them in the next decade of study of precision medicine, toward generation of insights that may help to evolve precision nutrition as an effective future tool in a variety of "multifactorial" human disorders.
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Li H, Fang Q, Nie Q, Hu J, Yang C, Huang T, Li H, Nie S. Hypoglycemic and Hypolipidemic Mechanism of Tea Polysaccharides on Type 2 Diabetic Rats via Gut Microbiota and Metabolism Alteration. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:10015-10028. [PMID: 32811143 DOI: 10.1021/acs.jafc.0c01968] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Diabetes mellitus is a serious threat to human health. Tea is cultivated around the world, and its polysaccharide components are reported to be an effective approach for managing type 2 diabetes with fewer adverse effects than medication. To examine the therapeutic effect of tea polysaccharides on diabetes, a type 2 diabetic rat model was generated. We showed that tea polysaccharides remarkably decreased fasting blood glucose and the levels of total cholesterol, total triglyceride, low-density lipoprotein cholesterol, and free fatty acid of type 2 diabetic rats. 16S rRNA sequencing and metabolomics were used to investigate the variation of gut microbiota and the metabolites profiles of diabetic rats after intervention of tea polysaccharides. We found that tea polysaccharides maintained the diversity of gut microbiota and restored the relative abundance of some bacterial genera (Lachnospira, Victivallis, Roseburia, and Fluviicola) which was reduced by diabetes. According to metabolomics analysis, we found that amino acid and other related metabolites was influenced by tea polysaccharides intervention. Correlation analysis among metabolites, gut microbiota, and parameters of hypoglycemic indicated that tea polysaccharides had hypoglycemic and hypolipidemic effect on type 2 diabetes via the modulation of gut microbiota and the improvement of host metabolism.
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Affiliation(s)
- Haishan Li
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Qingying Fang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Qixing Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Jielun Hu
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Chao Yang
- Department of Urology and Surgery, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, United States
| | - Tao Huang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Hu Li
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
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Mandrah K, Jain V, Ansari JA, Roy SK. Metabolomic perturbation precedes glycolytic dysfunction and procreates hyperglycemia in a rat model due to bisphenol S exposure. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2020; 77:103372. [PMID: 32203925 DOI: 10.1016/j.etap.2020.103372] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 02/25/2020] [Accepted: 03/10/2020] [Indexed: 05/27/2023]
Abstract
Previous studies highlighted bisphenol S (BPS), an industrial chemical responsible for harmful effects comparable to its congener substance bisphenol A (BPA). Accounted for various adversities to biological functions, it could alter the expression of endogenous metabolites in many metabolic processes. The study was aimed to investigate the altered metabolites in hyperglycemic condition triggered by sub-chronic exposure of BPS in serum and urine samples of Wistar rats. Invaded effects of hyperglycemia due to BPS exposure on Wistar rats were investigated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Metabolomic profiling of serum and urinary metabolites was done by gas chromatography-mass spectrometry (GC-MS) analysis. The metabolomics data were represented by one way ANOVA, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) along with the mapping of perturbed metabolic pathways. The OGTT and ITT showed increased levels of glucose in treated animals with median and high doses, indicating the manifestation of hyperglycemia. The metabolomic profiling of serum and urine revealed BPS could cause consequential metabolomic perturbation mainly of amino acids, sugars, and organic acids. Furthermore, the extrapolation of Kyoto Encyclopedia of Genes and Genomes (KEGG) based systematic analysis helped to monitor the altered pathways, including amino acids, glycolysis, pyruvate metabolism, etc., which were provoked due to BPS exposure. The overview of the perturbed metabolite profiling in rats promisingly showed early diagnostic markers of hyperglycemic condition triggered due to the BPS exposure. Findings from this study will be helpful towards the exploration of mechanistic insights of several disturbed pathways.
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Affiliation(s)
- Kapil Mandrah
- Analytical Chemistry Laboratory, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Veena Jain
- Analytical Chemistry Laboratory, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Jamal Ahmad Ansari
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; Immunotoxicology Laboratory, Food Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, 226001, India
| | - Somendu Kumar Roy
- Analytical Chemistry Laboratory, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
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Nyavor Y, Brands CR, May G, Kuther S, Nicholson J, Tiger K, Tesnohlidek A, Yasuda A, Starks K, Litvinenko D, Linden DR, Bhattarai Y, Kashyap PC, Forney LJ, Balemba OB. High-fat diet-induced alterations to gut microbiota and gut-derived lipoteichoic acid contributes to the development of enteric neuropathy. Neurogastroenterol Motil 2020; 32:e13838. [PMID: 32168415 PMCID: PMC7319907 DOI: 10.1111/nmo.13838] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 01/28/2020] [Accepted: 02/21/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND High-fat diet, microbial alterations and lipopolysaccharide (LPS) are thought to cause enteric diabetic neuropathy and intestinal dysmotility. However, the role of the gut microbiota, lipoteichoic acid (LTA) from Gram-positive bacteria and short-chain fatty acids (SCFAs) in the development of diabetic enteric neuropathy and intestinal dysmotility is not well understood. Our aim was to examine the role of the gut microbiota, LTA and SCFAs in the development of diabetic enteric neuropathy and intestinal dysmotility. METHODS We fed germ-free (GF) and conventionally raised (CR) mice either a high-fat (HFD) or standard chow diet (SCD) for 8 weeks. We analyzed the microbial community composition in CR mice using 16S rRNA sequencing and damage to myenteric neurons using immunohistochemistry. We also studied the effects of LPS, LTA, and SCFAs on duodenal muscularis externa contractions and myenteric neurons using cultured preparations. KEY RESULTS High-fat diet ingestion reduced the total number and the number of nitrergic myenteric neurons per ganglion in the duodenum of CR but not in GF-HFD mice. GF mice had fewer neurons per ganglion compared with CR mice. CR mice fed a HFD had increased abundance of Gram-positive bacteria. LTA and LPS did not affect the frequency of duodenal muscularis contractions after 24 hours of cultured but reduced the density of nitrergic myenteric neurons and increased oxidative stress and TNFα production in myenteric ganglia. SCFAs did not affect muscularis contractions or injure myenteric neurons. CONCLUSIONS & INFERENCES Gut microbial alterations induced increase in Gram-positive bacterial LTA may contribute to enteric neuropathy.
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Affiliation(s)
- Yvonne Nyavor
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
| | | | - George May
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
| | - Sydney Kuther
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
| | | | - Kathryn Tiger
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
| | | | - Allysha Yasuda
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
| | - Kiefer Starks
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
| | - Diana Litvinenko
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
| | - David R. Linden
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - Yogesh Bhattarai
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Purna C. Kashyap
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA,Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - Larry J. Forney
- University of Idaho, 875 Perimeter Drive, LSS 252 Moscow, ID 83844
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Gestational Diabetes Mellitus Is Associated with Reduced Dynamics of Gut Microbiota during the First Half of Pregnancy. mSystems 2020; 5:5/2/e00109-20. [PMID: 32209715 PMCID: PMC7093821 DOI: 10.1128/msystems.00109-20] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
GDM is one of the most common metabolic disorders during pregnancy and is associated with adverse short-term and long-term maternal and fetal outcomes. The aim of this study was to examine the connection between dynamic variations in gut microbiota and development of GDM. Whereas shifts in gut microbiota composition and function have been previously reported to be associated with GDM, very little is known regarding the early microbial changes that occur before the diagnosis of GDM. This study demonstrated that the dynamics in gut microbiota during the first half of pregnancy differed significantly between GDM and normoglycemic women. Our findings suggested that gut microbiota may potentially serve as an early biomarker for GDM. Women with gestational diabetes mellitus (GDM) have different gut microbiota in late pregnancy compared to women without GDM. It remains unclear whether alterations of gut microbiota can be identified prior to the diagnosis of GDM. This study characterized dynamic changes of gut microbiota from the first trimester (T1) to the second trimester (T2) and evaluated their relationship with later development of GDM. Compared with the control group (n = 103), the GDM group (n = 31) exhibited distinct dynamics of gut microbiota, evidenced by taxonomic, functional, and structural shifts from T1 to T2. Linear discriminant analysis (LDA) revealed that there were 10 taxa in T1 and 7 in T2 that differed in relative abundance between the GDM and control groups, including a consistent decrease in the levels of Coprococcus and Streptococcus in the GDM group. While the normoglycemic women exhibited substantial variations of gut microbiota from T1 to T2, their GDM-developing counterparts exhibited clearly reduced inter-time point shifts, as corroborated by the results of Wilcoxon signed-rank test and balance tree analysis. Moreover, cooccurrence network analysis revealed that the interbacterial interactions in the GDM group were minimal compared with those in the control group. In conclusion, lower numbers of dynamic changes in gut microbiota in the first half of pregnancy are associated with the development of GDM. IMPORTANCE GDM is one of the most common metabolic disorders during pregnancy and is associated with adverse short-term and long-term maternal and fetal outcomes. The aim of this study was to examine the connection between dynamic variations in gut microbiota and development of GDM. Whereas shifts in gut microbiota composition and function have been previously reported to be associated with GDM, very little is known regarding the early microbial changes that occur before the diagnosis of GDM. This study demonstrated that the dynamics in gut microbiota during the first half of pregnancy differed significantly between GDM and normoglycemic women. Our findings suggested that gut microbiota may potentially serve as an early biomarker for GDM.
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Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic β-Cell Growth and Insulin Secretion. Int J Mol Sci 2020; 21:ijms21030910. [PMID: 32019155 PMCID: PMC7037182 DOI: 10.3390/ijms21030910] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/22/2020] [Accepted: 01/26/2020] [Indexed: 02/06/2023] Open
Abstract
In the past 15 years, gut microbiota emerged as a crucial player in health and disease. Enormous progress was made in the analysis of its composition, even in the discovery of novel species. It is time to go beyond mere microbiota-disease associations and, instead, provide more causal analyses. A key mechanism of metabolic regulation by the gut microbiota is through the production of short-chain fatty acids (SCFAs). Acting as supplemental nutrients and specific ligands of two G-protein-coupled receptors (GPCRs), they target the intestines, brain, liver, and adipose tissue, and they regulate appetite, energy expenditure, adiposity, and glucose production. With accumulating but sometimes conflicting research results, key questions emerged. Do SCFAs regulate pancreatic islets directly? What is the effect of β-cell-specific receptor deletions? What are the mechanisms used by SCFAs to regulate β-cell proliferation, survival, and secretion? The receptors FFA2/3 are normally expressed on pancreatic β-cells. Deficiency in FFA2 may have caused glucose intolerance and β-cell deficiency in mice. However, this was contrasted by a double-receptor knockout. Even more controversial are the effects of SCFAs on insulin secretion; there might be no direct effect at all. Unable to draw clear conclusions, this review reveals some of the recent controversies.
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Wieërs G, Belkhir L, Enaud R, Leclercq S, Philippart de Foy JM, Dequenne I, de Timary P, Cani PD. How Probiotics Affect the Microbiota. Front Cell Infect Microbiol 2020; 9:454. [PMID: 32010640 PMCID: PMC6974441 DOI: 10.3389/fcimb.2019.00454] [Citation(s) in RCA: 305] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Accepted: 12/13/2019] [Indexed: 12/15/2022] Open
Abstract
Probiotics have been used to treat a variety of diseases for decades; however, what is the rationale for their application? Such a treatment was first proposed in the early nineteenth century based on observations of decreased bifidobacterial populations in children suffering from diarrhea, suggesting that oral intake of bifidobacteria could replete this subpopulation of the microbiota and improve health. Since then, studies have shown modifications in the gut or skin microbiota in the course of a variety of diseases and suggested positive effects of certain probiotics. Most studies failed to report any impact on the microbiota. The impact of probiotics as well as of bacteria colonizing food does not reside in their ability to graft in the microbiota but rather in sharing genes and metabolites, supporting challenged microbiota, and directly influencing epithelial and immune cells. Such observations argue that probiotics could be associated with conventional drugs for insulin resistance, infectious diseases, inflammatory diseases, and psychiatric disorders and could also interfere with drug metabolism. Nevertheless, in the context of a plethora of probiotic strains and associations produced in conditions that do not allow direct comparisons, it remains difficult to know whether a patient would benefit from taking a particular probiotic. In other words, although several mechanisms are observed when studying a single probiotic strain, not all individual strains are expected to share the same effects. To clarify the role of probiotics in the clinic, we explored the relation between probiotics and the gut and skin microbiota.
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Affiliation(s)
- Grégoire Wieërs
- Service de Médecine Interne Générale, Clinique Saint Pierre, Ottignies, Belgium
| | - Leila Belkhir
- Service de Médecine Interne et Maladies Infectieuses, Cliniques Universitaires Saint Luc, UCLouvain, Université Catholique de Louvain, Brussels, Belgium
| | - Raphaël Enaud
- CHU Bordeaux, CRCM Pédiatrique, CIC 1401, Université de Bordeaux, INSERM, CRCTB, U1045, CHU Bordeaux, Bordeaux, France
| | - Sophie Leclercq
- Institute of Neuroscience and Louvain Drug Research Institute, UCLouvain, Université Catholique de Louvain, Brussels, Belgium
| | | | | | - Philippe de Timary
- Service de Psychiatrie, Cliniques Universitaires Saint Luc, UCLouvain, Université Catholique de Louvain, Brussels, Belgium
| | - Patrice D. Cani
- Walloon Excellence in Life Sciences and BIOtechnology, Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université Catholique de Louvain, Brussels, Belgium
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Han X, Song C, Feng X, Wang Y, Meng T, Li S, Bai Y, Du B, Sun Q. Isolation and hypoglycemic effects of water extracts from mulberry leaves in Northeast China. Food Funct 2020; 11:3112-3125. [DOI: 10.1039/d0fo00012d] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Diabetes is the main chronic disease that greatly affects human life.
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Affiliation(s)
- Xiaoyun Han
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
| | - Chunyue Song
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
| | - Xiaoxin Feng
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
| | - Yanan Wang
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
| | - Tingting Meng
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
| | - Shichao Li
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
| | - Yunlong Bai
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
| | | | - Qingshen Sun
- Engineering Research Center of Agricultural Microbiology Technology
- Ministry of Education
- Heilongjiang University
- Harbin 150500
- China
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Fang Q, Hu J, Nie Q, Nie S. Effects of polysaccharides on glycometabolism based on gut microbiota alteration. Trends Food Sci Technol 2019. [DOI: 10.1016/j.tifs.2019.08.015] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Lock AM, Bonetti DL, Campbell ADK. The psychological and physiological health effects of fatigue. Occup Med (Lond) 2019; 68:502-511. [PMID: 30445654 DOI: 10.1093/occmed/kqy109] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background The issue of employee fatigue is becoming increasingly prominent, particularly in safety-critical industries. Aims To produce an in-depth review collating the known psychological and physiological health and work effects of fatigue to guide mitigation strategies in safety-critical industries. Methods Literature searches were conducted via scientific databases using appropriate filters and keywords. The available results were collated into a review and commentary. Results Decreased sleep duration and chronodisruption have been shown to cause both significant morbidity and mortality. There is a large body of evidence showing strong associations between fatigue, reduced cognition and occupational accidents, as well as increased metabolic and reproductive health sequelae, some forms of cancer and mortality. Additional evidence links fatigue with mental, gastrointestinal, neurological and chronic pain sequelae. Conclusions Fatigue risk mitigation strategies should be implemented, not only to reduce these short- and long-term health risks in employees of safety-critical industries, but also to create more efficient, productive and effective workplace personnel with longer and more fulfilling careers. This requires improved acute fatigue mitigation, as well as the prevention of cumulative fatigue build-up and the formation of acute-on-chronic fatigue. The health recommendations for fatigue mitigation outlined in this paper are pertinent to all professions where employees have high rates of both acute and chronic fatigue.
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Affiliation(s)
- A M Lock
- Aviation Medicine Unit, RNZAF Base Auckland, Whenuapai, Auckland, New Zealand
| | - D L Bonetti
- Aviation Medicine Unit, RNZAF Base Auckland, Whenuapai, Auckland, New Zealand
| | - A D K Campbell
- Aviation Medicine Unit, RNZAF Base Auckland, Whenuapai, Auckland, New Zealand
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Li K, Zhang L, Xue J, Yang X, Dong X, Sha L, Lei H, Zhang X, Zhu L, Wang Z, Li X, Wang H, Liu P, Dong Y, He L. Dietary inulin alleviates diverse stages of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in db/db mice. Food Funct 2019; 10:1915-1927. [PMID: 30869673 DOI: 10.1039/c8fo02265h] [Citation(s) in RCA: 146] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is closely correlated with chronic low-grade inflammation and gut dysbiosis. Prebiotic inulin (INU) is conducive to modulate gut dysbiosis. However, the impact of dietary inulin on the diverse stages of T2DM remains largely unknown. In the present study, according to the fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT), mice were randomly divided into six groups (15 mice per group): pre-diabetic group (PDM group); inulin-treated pre-diabetic group (INU/PDM group); early diabetic group (EDM group); inulin-treated early diabetic group (INU/EDM group); diabetic group (DM group); inulin-treated diabetic group (INU/DM group). All animal experiments were approved by the Ethics Committee of the General Hospital of Ningxia Medical University (No. 2016-232). After 6 weeks of inulin intervention, the mice were euthanized and the associated indicators were investigated. Dietary inulin significantly reduced FBG, body weights (BWs), glycated hemoglobin (GHb), blood lipid, plasma lipopolysaccharide (LPS), interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-17A in the three inulin-treated groups compared to the untreated groups. But for IL-17A, there remained no significant difference between the PDM group and the INU/PDM group. Moreover, the anti-inflammatory IL-10 showed significant alteration in the INU/PDM and INU/EDM groups, but no significant alteration in the INU/DM group. Sequencing analysis of the gut microbiota showed an elevation in the relative abundance of Cyanobacteria and Bacteroides and a reduction in the relative abundance of Ruminiclostridium_6 in three inulin-treated different stages of T2DM groups, as well as a reduction in the relative abundance of Deferribacteres and Tenericutes in the INU/DM group. A reduction in the relative abundance of Mucispirillum was detected in the INU/PDM and INU/EDM groups. Correlation analysis revealed that Cyanobacteria and Bacteroides abundance were positively correlated with IL-10; Deferribacteres, Tenericutes, Mucispirillum and Ruminiclostridium_6 abundance were closely related to IL-6, TNF-α or IL-17A respectively. Additionally, Mucispirillum and Ruminiclostridium_6 abundance were positively correlated with LPS. Taken together, dietary inulin alleviated the diverse stages of T2DM via suppressing inflammation and modulating gut microbiota.
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Affiliation(s)
- Ke Li
- Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
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Hasan N, Yang H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ 2019; 7:e7502. [PMID: 31440436 PMCID: PMC6699480 DOI: 10.7717/peerj.7502] [Citation(s) in RCA: 431] [Impact Index Per Article: 71.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 07/17/2019] [Indexed: 12/13/2022] Open
Abstract
Gut microbiota have important functions in the body, and imbalances in the composition and diversity of those microbiota can cause several diseases. The host fosters favorable microbiota by releasing specific factors, such as microRNAs, and nonspecific factors, such as antimicrobial peptides, mucus and immunoglobulin A that encourage the growth of specific types of bacteria and inhibit the growth of others. Diet, antibiotics, and age can change gut microbiota, and many studies have shown the relationship between disorders of the microbiota and several diseases and reported some ways to modulate that balance. In this review, we highlight how the host shapes its gut microbiota via specific and nonspecific factors, how environmental and nutritional factors affect it, and how to modulate it using prebiotics, probiotics, and fecal microbiota transplantation.
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Affiliation(s)
- Nihal Hasan
- Department of Microbiology, Northeast Forestry University, Harbin, Heilongjiang, China.,Faculty of Health Science, Al-Baath University, Homs, Syria
| | - Hongyi Yang
- Department of Microbiology, Northeast Forestry University, Harbin, Heilongjiang, China
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Wan Y, Wang F, Yuan J, Li J, Jiang D, Zhang J, Li H, Wang R, Tang J, Huang T, Zheng J, Sinclair AJ, Mann J, Li D. Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial. Gut 2019; 68:1417-1429. [PMID: 30782617 DOI: 10.1136/gutjnl-2018-317609] [Citation(s) in RCA: 411] [Impact Index Per Article: 68.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 12/03/2018] [Accepted: 12/08/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. METHODS In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18-35 years; body mass index <28 kg/m2; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. RESULTS The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p<0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. CONCLUSION Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes. TRIAL REGISTRATION NUMBER NCT02355795; Results.
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Affiliation(s)
- Yi Wan
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
| | - Fenglei Wang
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.,Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, USA
| | - Jihong Yuan
- No. 1 Department of Nutrition, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jie Li
- No. 1 Department of Nutrition, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Dandan Jiang
- No. 1 Department of Nutrition, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jingjing Zhang
- Department of Gastroenterology, School of Medicine, Zhejiang University, Hangzhou, China
| | - Hao Li
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
| | - Ruoyi Wang
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.,Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, USA
| | - Jun Tang
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China
| | - Tao Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Jusheng Zheng
- Institute of Basic Medical Science, Westlake University, Hangzhou, China
| | - Andrew J Sinclair
- Department of Nutrition, Dietetics and Food, Monash University, Melbourne, Australia
| | - Jim Mann
- Department of Human Nutrition and Medicine, University of Otago, Otago, New Zealand
| | - Duo Li
- Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.,Institute of Nutrition and Health, Qingdao University, Qingdao, China
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Correlation between Jejunal Microbial Diversity and Muscle Fatty Acids Deposition in Broilers Reared at Different Ambient Temperatures. Sci Rep 2019; 9:11022. [PMID: 31363155 PMCID: PMC6667446 DOI: 10.1038/s41598-019-47323-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 07/12/2019] [Indexed: 12/14/2022] Open
Abstract
Temperature, which is an important environmental factor in broiler farming, can significantly influence the deposition of fatty acids in muscle. 300 one-day-old broiler chicks were randomly divided into three groups and reared at high, medium and low temperatures (HJ, MJ and LJ), respectively. Breast muscle and jejunal chyme samples were collected and subjected to analyses of fatty acid composition and 16S rRNA gene sequencing. Through spearman’s rank correlation coefficient, the data were used to characterize the correlation between jejunal microbial diversity and muscle fatty acid deposition in the broilers. The results showed that Achromobacter, Stenotrophomonas, Pandoraea, Brevundimonas, Petrobacter and Variovorax were significantly enriched in the MJ group, and all of them were positively correlated with the fatty acid profiling of muscle and multiple lipid metabolism signaling pathways. Lactobacillus was significantly enriched in the HJ group and exhibited a positive correlation with fatty acid deposition. Pyramidobacter, Dialister, Bacteroides and Selenomonas were significantly enriched in the LJ group and displayed negative correlation with fatty acid deposition. Taken together, this study demonstrated that the jejunal microflora manifested considerable changes at high and low ambient temperatures and that jejunal microbiota changes were correlated with fatty acid deposition of muscle in broilers.
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Cui HX, Zhang LS, Luo Y, Yuan K, Huang ZY, Guo Y. A Purified Anthraquinone-Glycoside Preparation From Rhubarb Ameliorates Type 2 Diabetes Mellitus by Modulating the Gut Microbiota and Reducing Inflammation. Front Microbiol 2019; 10:1423. [PMID: 31293553 PMCID: PMC6603233 DOI: 10.3389/fmicb.2019.01423] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 06/05/2019] [Indexed: 12/18/2022] Open
Abstract
Rheum palmatum L. is widely used in traditional Chinese medicine for the treatment of constipation. Here, the therapeutic effects and underlying mechanisms of purified anthraquinone-glycoside preparation from rhubarb (RAGP) on the type 2 diabetes mellitus (T2DM) rats were investigated. After 6 weeks of metformin and RAGP treatment, the weight returned to normal. Fasting blood glucose (FBG), glycated serum protein (GSP), insulin concentration and HOMA-IR index had significantly decreased, and glucagon-like peptide-1 (GLP-1) concentrations had increased. Histological abnormalities in the pancreas and ileum had improved. These effects were associated with enhanced intestinal integrity, thereby reducing the absorption of lipopolysaccharide (LPS) and inflammation. To investigate whether RAGP ameliorated insulin resistance via effects on the gut microbiota, we performed 16s rDNA sequencing of ileal gut contents. This showed an amelioration of gut dysbiosis, with greater abundance of probiotic Lactobacillus and short-chain fatty acid-producing bacteria, and lower abundance of the Lachnospiraceae NK4A136 group and LPS-producing Desulfovibrio. The mechanism of the hypoglycemic effect of RAGP involves regulation of the gut microbiota, activation of the GLP-1/cAMP pathway to ameliorate insulin resistance. Thus, this study provides a theoretical basis for the use of RAGP to treat T2DM, and it may be a novel approach to restore the gut microbiota.
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Affiliation(s)
- Hong-Xin Cui
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China
- Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Zhengzhou, China
| | - Ling-Shuai Zhang
- College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yang Luo
- Jiyang College of Zhejiang Agriculture and Forestry University, Zhuji, China
| | - Ke Yuan
- Jiyang College of Zhejiang Agriculture and Forestry University, Zhuji, China
| | | | - Ying Guo
- Zhejiang Chinese Medical University, Hangzhou, China
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Nie P, Li Z, Wang Y, Zhang Y, Zhao M, Luo J, Du S, Deng Z, Chen J, Wang Y, Chen S, Wang L. Gut microbiome interventions in human health and diseases. Med Res Rev 2019; 39:2286-2313. [PMID: 30994937 DOI: 10.1002/med.21584] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 02/27/2019] [Accepted: 03/24/2019] [Indexed: 02/06/2023]
Abstract
Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.
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Affiliation(s)
- Pengqing Nie
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.,Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.,Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Zhiqiang Li
- Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Yimeng Wang
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.,Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Yubing Zhang
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.,Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Mengna Zhao
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.,Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Jie Luo
- Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Shiming Du
- Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Zixin Deng
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China
| | - Jincao Chen
- Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Yunfu Wang
- Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Shi Chen
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.,Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.,Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Lianrong Wang
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.,Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.,Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
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Aguayo-Mazzucato C, Diaque P, Hernandez S, Rosas S, Kostic A, Caballero AE. Understanding the growing epidemic of type 2 diabetes in the Hispanic population living in the United States. Diabetes Metab Res Rev 2019; 35:e3097. [PMID: 30445663 PMCID: PMC6953173 DOI: 10.1002/dmrr.3097] [Citation(s) in RCA: 149] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 11/12/2018] [Accepted: 11/13/2018] [Indexed: 12/15/2022]
Abstract
The prevalence and incidence of type 2 diabetes (T2D) among the Hispanic population in the United States are higher than the national average. This is partly due to sociocultural factors, such as lower income and decreased access to education and health care, as well as a genetic susceptibility to obesity and higher insulin resistance. This review focuses on understanding the Hispanic population living in the United States from a multidisciplinary approach and underlines the importance of cultural, social, and biological factors in determining the increased risk of T2D in this population. An overview of the acute and chronic complications of T2D upon this population is included, which is of paramount importance to understand the toll that diabetes has upon this population, the health system, and society as a whole. Specific interventions directed to the Hispanic populations are needed to prevent and alleviate some of the burdens of T2D. Different prevention strategies based on medications, lifestyle modifications, and educational programmes are discussed herein. Diabetes self-management education (DSME) is a critical element of care of all people with diabetes and is considered necessary to improve patient outcomes. To be more effective, programmes should take into consideration cultural factors that influence the development and progression of diabetes. These interventions aim to enhance long-term effects by reducing the incidence, morbidity, and mortality of T2D in the Hispanic population of the United States.
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Affiliation(s)
| | - Paula Diaque
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Sonia Hernandez
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
- Surgery Department, University of Chicago, Chicago, Illinois, USA
| | - Silvia Rosas
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Aleksandar Kostic
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
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Okazaki F, Zang L, Nakayama H, Chen Z, Gao ZJ, Chiba H, Hui SP, Aoki T, Nishimura N, Shimada Y. Microbiome Alteration in Type 2 Diabetes Mellitus Model of Zebrafish. Sci Rep 2019; 9:867. [PMID: 30696861 PMCID: PMC6351536 DOI: 10.1038/s41598-018-37242-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2018] [Accepted: 11/28/2018] [Indexed: 12/21/2022] Open
Abstract
Understanding the gut microbiota in metabolic disorders, including type 2 diabetes mellitus (T2DM), is now gaining importance due to its potential role in disease risk and progression. We previously established a zebrafish model of T2DM, which shows glucose intolerance with insulin resistance and responds to anti-diabetic drugs. In this study, we analysed the gut microbiota of T2DM zebrafish by deep sequencing the 16S rRNA V3-V4 hypervariable regions, and imputed a functional profile using predictive metagenomic tools. While control and T2DM zebrafish were fed with the same kind of feed, the gut microbiota in T2DM group was less diverse than that of the control. Predictive metagenomics profiling using PICRUSt revealed functional alternation of the KEGG pathways in T2DM zebrafish. Several amino acid metabolism pathways (arginine, proline, and phenylalanine) were downregulated in the T2DM group, similar to what has been previously reported in humans. In summary, we profiled the gut microbiome in T2DM zebrafish, which revealed functional similarities in gut bacterial environments between these zebrafish and T2DM affected humans. T2DM zebrafish can become an alternative model organism to study host-bacterial interactions in human obesity and related diseases.
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Affiliation(s)
- Fumiyoshi Okazaki
- Department of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, Japan.,Department of Bioinformatics, Mie University Advanced Science Research Promotion Center, Tsu, Mie, Japan.,Mie University Zebrafish Drug Screening Center, Tsu, Mie, Japan
| | - Liqing Zang
- Mie University Zebrafish Drug Screening Center, Tsu, Mie, Japan.,Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie, Japan
| | - Hiroko Nakayama
- Mie University Zebrafish Drug Screening Center, Tsu, Mie, Japan.,Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie, Japan
| | - Zhen Chen
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, 060-0812, Japan
| | - Zi-Jun Gao
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, 060-0812, Japan
| | - Hitoshi Chiba
- Department of Nutrition, Sapporo University of Health Sciences, Nakanuma Nishi-4-2-1-15, Higashi-ku, Sapporo, 007-0894, Japan
| | - Shu-Ping Hui
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, 060-0812, Japan
| | - Takahiko Aoki
- Department of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, Japan
| | - Norihiro Nishimura
- Mie University Zebrafish Drug Screening Center, Tsu, Mie, Japan.,Graduate School of Regional Innovation Studies, Mie University, Tsu, Mie, Japan
| | - Yasuhito Shimada
- Department of Bioinformatics, Mie University Advanced Science Research Promotion Center, Tsu, Mie, Japan. .,Mie University Zebrafish Drug Screening Center, Tsu, Mie, Japan. .,Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
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Laferrère B, Pattou F. Weight-Independent Mechanisms of Glucose Control After Roux-en-Y Gastric Bypass. Front Endocrinol (Lausanne) 2018; 9:530. [PMID: 30250454 PMCID: PMC6140402 DOI: 10.3389/fendo.2018.00530] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 08/22/2018] [Indexed: 12/14/2022] Open
Abstract
Roux-en-Y gastric bypass results in large and sustained weight loss and resolution of type 2 diabetes in 60% of cases at 1-2 years. In addition to calorie restriction and weight loss, various gastro-intestinal mediated mechanisms, independent of weight loss, also contribute to glucose control. The anatomical re-arrangement of the small intestine after gastric bypass results in accelerated nutrient transit, enhances the release of post-prandial gut hormones incretins and of insulin, alters the metabolism and the entero-hepatic cycle of bile acids, modifies intestinal glucose uptake and metabolism, and alters the composition and function of the microbiome. The amelioration of beta cell function after gastric bypass in individuals with type 2 diabetes requires enteric stimulation. However, beta cell function in response to intravenous glucose stimulus remains severely impaired, even in individuals in full clinical diabetes remission. The permanent impairment of the beta cell may explain diabetes relapse years after surgery.
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Affiliation(s)
- Blandine Laferrère
- Division of Endocrinology, New York Obesity Nutrition Research Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, United States
| | - François Pattou
- Translational Research on Diabetes, UMR 1190, Inserm, Université Lille, Lille, France
- Endocrine and Metabolic Surgery, CHU Lille, Lille, France
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41
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Xu YH, Gao CL, Guo HL, Zhang WQ, Huang W, Tang SS, Gan WJ, Xu Y, Zhou H, Zhu Q. Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice. J Endocrinol 2018; 238:231-244. [PMID: 29941502 DOI: 10.1530/joe-18-0137] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 06/25/2018] [Indexed: 12/12/2022]
Abstract
Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo and in vitro experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both in vivo and in vitro Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines' secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity.
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Affiliation(s)
- You-Hua Xu
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
| | - Chen-Lin Gao
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- Department of EndocrinologyAffiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Heng-Li Guo
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
| | - Wen-Qian Zhang
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
| | - Wei Huang
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- Department of EndocrinologyAffiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Shan-Shan Tang
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
| | - Wen-Jun Gan
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
| | - Yong Xu
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- Department of EndocrinologyAffiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Hua Zhou
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
| | - Quan Zhu
- Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
- State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
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42
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Li F, Sun G, Wang Z, Wu W, Guo H, Peng L, Wu L, Guo X, Yang Y. Characteristics of fecal microbiota in non-alcoholic fatty liver disease patients. SCIENCE CHINA-LIFE SCIENCES 2018; 61:770-778. [PMID: 29948900 DOI: 10.1007/s11427-017-9303-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 05/01/2018] [Indexed: 12/16/2022]
Abstract
This study was designed to investigate the gut microbiota of patients with non-alcoholic fatty liver disease. The inclusive and exclusive criteria for NAFLD patients and healthy subjects were formulated, and detailed clinical data were collected. The genomic DNA of stool samples were extracted for 16S rDNA sequencing, and the amplified V4-region was sequenced on the Illumina Miseq platform. Metastats analysis was performed to identify the differential taxa between the groups. Redundancy analysis was used to evaluate the association between gut microbial structure and clinical variables. Thirty NAFLD patients and 37 healthy controls were involved. The 16S rDNA sequencing showed that there was a dramatic variability of the fecal microbiota among all the individuals. Metastats analysis identified eight families and 12 genera with significant differences between the two groups. When some clinical parameters, such as waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR), were enrolled in Redundancy analysis, the distribution of the two group of samples was obviously changed. The compositional shifts in fecal bacterial communities of NAFLD patients from the healthy controls were mainly at family or genus levels. According to our Redundancy analysis, insulin resistance and obesity might be closely related to both NAFLD phenotype and intestinal microecology.
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Affiliation(s)
- Fan Li
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
- Department of Liver Disease, PLA Army General Hospital, Beijing, 100700, China
| | - Gang Sun
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Zikai Wang
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Wenming Wu
- Department of Gastroenterology, General Hospital of Jinan Military Region, Jinan, 250012, China
| | - He Guo
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Lili Wu
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Xu Guo
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, 100853, China.
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Li S, Shao Y, Li K, HuangFu C, Wang W, Liu Z, Cai Z, Zhao B. Vascular Cognitive Impairment and the Gut Microbiota. J Alzheimers Dis 2018; 63:1209-1222. [PMID: 29689727 DOI: 10.3233/jad-171103] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Sinian Li
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Yiming Shao
- The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Kanglan Li
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Changmei HuangFu
- Department of Gerontology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Wenjie Wang
- Department of Neurosurgery, The Central Hospital of Longhua District, Shenzhen, China
| | - Zhou Liu
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Zhiyou Cai
- Department of Neurology, Chongqing General Hospital, Chongqing, China
| | - Bin Zhao
- Department of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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44
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Riaz Rajoka MS, Jin M, Haobin Z, Li Q, Shao D, Huang Q, Shi J. Impact of dietary compounds on cancer-related gut microbiota and microRNA. Appl Microbiol Biotechnol 2018; 102:4291-4303. [PMID: 29589094 DOI: 10.1007/s00253-018-8935-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 03/12/2018] [Accepted: 03/13/2018] [Indexed: 02/07/2023]
Abstract
Cancer is one of the most common causes of death worldwide. Extensive research has been conducted on cancer; regardless, the link between cancer and diet remains undetermined. Recent studies have emphasized the importance of miRNAs in cancer-associated pathways from the perspective of dietary modulation. We highlighted the recent data on dietary modulation of gut microbiota and miRNAs related to cancer on the basis of recently published results. The targets of miRNAs are oncogenes or tumor suppressors that mediate the progression and initiation of carcinogenesis. Different miRNAs display complex expression profiles in response to dietary manipulation. Various dietary components, such as fatty acids, resveratrol, isothiocyanate, and curcumin, have been effectively used in cancer prevention and treatment. This potency is attributed to the capability of these components to alter miRNA expression, thereby modulating the vital pathways involved in metastasis, invasion, apoptosis, tumor growth, and cell proliferation.
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Affiliation(s)
- Muhammad Shahid Riaz Rajoka
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China.
| | - Mingliang Jin
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Zhao Haobin
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Qi Li
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Dongyan Shao
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Qingsheng Huang
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Junling Shi
- Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China.
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Harsch IA, Konturek PC. The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into "Old" Diseases. Med Sci (Basel) 2018; 6:E32. [PMID: 29673211 PMCID: PMC6024804 DOI: 10.3390/medsci6020032] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 04/09/2018] [Accepted: 04/10/2018] [Indexed: 12/12/2022] Open
Abstract
The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.
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Affiliation(s)
- Igor Alexander Harsch
- Division of Endocrinology and Metabolism, Thuringia Clinic Saalfeld "Georgius Agricola", Department of Internal Medicine II, Teaching Hospital of the University of Jena, Rainweg 68, D-07318 Saalfeld/Saale, Germany.
| | - Peter Christopher Konturek
- Division of Gastroenterology, Thuringia Clinic Saalfeld "Georgius Agricola", Department of Internal Medicine II, Teaching Hospital of the University of Jena, Rainweg 68, D-07318 Saalfeld/Saale, Germany.
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Shimada R, Fujita M, Yuasa M, Sawamura H, Watanabe T, Nakashima A, Suzuki K. Oral administration of green algae, Euglena gracilis, inhibits hyperglycemia in OLETF rats, a model of spontaneous type 2 diabetes. Food Funct 2018; 7:4655-4659. [PMID: 27775129 DOI: 10.1039/c6fo00606j] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In the present study, the effects of Euglena and paramylon on hyperglycemia were examined in Otsuka Long-Evans Tokushima fatty (OLETF; type 2 diabetes mellitus model) rats. OLETF rats were fed an AIN-93 M diet containing cellulose, Euglena, or paramylon for 10 weeks. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. An oral glucose-tolerance test (OGTT) was performed at 0 and 10 weeks. OLETF control rats were obese because of bulimia and showed abdominal fat accumulation and hyperglycemia. Euglena supplementation improved hyperglycemia and decreased food intake, body weight gain, and abdominal fat. However, there were no changes in the paramylon-supplemented group compared to the OLETF control group. Triglyceride concentrations in the serum and liver were lower in Euglena-supplemented rats than in OLETF control rats. There was a correlation between hepatic triglyceride concentration and the area under the curve (AUC) of OGTT at 10 weeks. This suggests that the improvement in glycemic control in the Euglena-supplemented group may depend on substances other than paramylon present in Euglena.
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Affiliation(s)
- Ryoko Shimada
- Department of Dietary Environment Analysis, School of Human Science and Environment, University of Hyogo, 1-1-12 Sinzaike Honcho, Himeji 670-0092, Japan. and Department of Health and Nutrition, Faculty of Health Science, Osaka Aoyama University, 2-11-1 Niina, Minoh, Osaka 562-8580, Japan
| | - Miho Fujita
- Department of Dietary Environment Analysis, School of Human Science and Environment, University of Hyogo, 1-1-12 Sinzaike Honcho, Himeji 670-0092, Japan.
| | - Masahiro Yuasa
- Department of Dietary Environment Analysis, School of Human Science and Environment, University of Hyogo, 1-1-12 Sinzaike Honcho, Himeji 670-0092, Japan. and Department of Nutrition Science, Faculty of Nursing and Nutrition, University of Nagasaki, 1-1-1 Manabino, Nagayo-cho, Nishi-Sonogi-gun, Nagasaki 851-2195, Japan
| | - Hiromi Sawamura
- Department of Molecular Nutrition, School of Human Science and Environment, University of Hyogo, 1-1-12 Sinzaike Honcho, Himeji 670-0092, Japan
| | - Toshiaki Watanabe
- Department of Dietary Environment Analysis, School of Human Science and Environment, University of Hyogo, 1-1-12 Sinzaike Honcho, Himeji 670-0092, Japan. and Department of Health and Nutrition, Faculty of Health Science, Osaka Aoyama University, 2-11-1 Niina, Minoh, Osaka 562-8580, Japan
| | - Ayaka Nakashima
- Euglena Co., Ltd., 5-33-1 Shiba, Minato-ku, Tokyo 108-0014, Japan
| | - Kengo Suzuki
- Euglena Co., Ltd., 5-33-1 Shiba, Minato-ku, Tokyo 108-0014, Japan
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47
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Microbes in the Treatment of Diabetes and Its Complications. Microb Biotechnol 2018. [DOI: 10.1007/978-981-10-7140-9_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Santoro A, Ostan R, Candela M, Biagi E, Brigidi P, Capri M, Franceschi C. Gut microbiota changes in the extreme decades of human life: a focus on centenarians. Cell Mol Life Sci 2018; 75:129-148. [PMID: 29032502 PMCID: PMC5752746 DOI: 10.1007/s00018-017-2674-y] [Citation(s) in RCA: 160] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 09/29/2017] [Indexed: 12/20/2022]
Abstract
The gut microbiota (GM) is a complex, evolutionarily molded ecological system, which contributes to a variety of physiological functions. The GM is highly dynamic, being sensitive to environmental stimuli, and its composition changes over the host's entire lifespan. However, the basic question of how much these changes may be ascribed to variables such as population, diet, genetics and gender, and/or to the aging process per se is still largely unanswered. We argue that comparison among studies on centenarians-the best model of healthy aging and longevity-recruited from different geographical areas/populations (different genetics and dietary habits) can help to disentangle the contribution of aging and non-aging-related variables to GM remodeling with age. The current review focuses on the role of population, gender and host genetics as possible drivers of GM modification along the human aging process. The feedback impact of age-associated GM variation on the GM-brain axis and GM metabolomics is also discussed. We likewise address the role of GM in neurodegenerative diseases such as Parkinson's and Alzheimer's, and its possible therapeutic use, taking advantage of the fact that centenarians are characterized by an extreme (healthy) phenotype versus patients suffering from age-related pathologies. Finally, it is argued that longitudinal studies combining metagenomics sequencing and in-depth phylogenetic analysis with a comprehensive phenotypic characterization of centenarians and patients using up-to-date omics (metabolomics, transcriptomics and meta-transcriptomics) are urgently needed.
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Affiliation(s)
- Aurelia Santoro
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum-University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy.
- Interdepartmental Centre "L. Galvani" (CIG) Alma Mater Studiorum-University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy.
| | - Rita Ostan
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum-University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy
- Interdepartmental Centre "L. Galvani" (CIG) Alma Mater Studiorum-University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy
| | - Marco Candela
- Department of Pharmacy and Biotechnology (FABIT), Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy
| | - Elena Biagi
- Department of Pharmacy and Biotechnology (FABIT), Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy
| | - Patrizia Brigidi
- Department of Pharmacy and Biotechnology (FABIT), Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy
| | - Miriam Capri
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum-University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy
- Interdepartmental Centre "L. Galvani" (CIG) Alma Mater Studiorum-University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy
| | - Claudio Franceschi
- Institute of Neurological Sciences (IRCCS), Via Altura 3, 40139, Bologna, Italy
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Abstract
Gut microbiota and its metabolites play pivotal roles in host physiology and pathology. Short-chain fatty acids (SCFAs), as a group of metabolites, exert positive regulatory effects on energy metabolism, hormone secretion, immune inflammation, hypertension, and cancer. The functions of SCFAs are related to their activation of transmembrane G protein-coupled receptors and their inhibition of histone acetylation. Though controversial, growing evidence suggests that SCFAs, which regulate inflammation, oxidative stress, and fibrosis, have been involved in kidney disease through the activation of the gut–kidney axis; however, the molecular relationship among gut microbiota–derived metabolites, signaling pathways, and kidney disease remains to be elucidated. This review will provide an overview of the physiology and functions of SCFAs in kidney disease.
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Affiliation(s)
- Lingzhi Li
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Liang Ma
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Ping Fu
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China
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50
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Jia L, Li D, Feng N, Shamoon M, Sun Z, Ding L, Zhang H, Chen W, Sun J, Chen YQ. Anti-diabetic Effects of Clostridium butyricum CGMCC0313.1 through Promoting the Growth of Gut Butyrate-producing Bacteria in Type 2 Diabetic Mice. Sci Rep 2017; 7:7046. [PMID: 28765642 PMCID: PMC5539151 DOI: 10.1038/s41598-017-07335-0] [Citation(s) in RCA: 117] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 06/28/2017] [Indexed: 12/11/2022] Open
Abstract
Patients with type 2 diabetes (T2D) have decreased butyrate-producing bacteria. We hypothesized that supplementation with butyrate-producing bacteria may exert beneficial effects on T2D. The current study investigated the effects of well-characterized butyrate-producing bacteria Clostridium butyricum CGMCC0313.1 (CB0313.1) on hyperglycemia and associated metabolic dysfunction in two diabetic mouse models. CB0313.1 was administered daily by oral gavage to leptindb/db mice for 5 weeks starting from 3 weeks of age, and to HF diabetic mice induced by high fat diet (HFD) plus streptozotocin (STZ) in C57BL/6J mice for 13 weeks starting from 4 weeks of age. CB0313.1 improved diabetic markers (fasting glucose, glucose tolerance, insulin tolerance, GLP-1 and insulin secretion), and decreased blood lipids and inflammatory tone. Furthermore, CB0313.1 reversed hypohepatias and reduced glucose output. We also found that CB0313.1 modulated gut microbiota composition, characterized by a decreased ratio of Firmicutes to Bacteroidetes, reduced Allobaculum bacteria that were abundant in HF diabetic mice and increased butyrate-producing bacteria. Changes in gut microbiota following CB0313.1 treatment were associated with enhanced peroxisome proliferator–activated receptor-γ (PPARγ), insulin signaling molecules and mitochondrial function markers. Together, our study suggests that CB0313.1 may act as a beneficial probiotic for the prevention and treatment of hyperglycemia and associated metabolic dysfunction.
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Affiliation(s)
- Lingling Jia
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China.,Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, P. R. China
| | - Dongyao Li
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Ninghan Feng
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, P. R. China.,Wuxi No. 2 Hospital, Jiangsu, P. R. China
| | - Muhammad Shamoon
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Zhenghua Sun
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Lei Ding
- Department of Biology and Chemistry, University Bremen. Leobener Str., NW 2, 28359, Bremen, Germany
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China
| | - Jia Sun
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China. .,Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, P. R. China.
| | - Yong Q Chen
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P. R. China. .,Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, P. R. China. .,Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
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