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Liu J, Li F, Yang L, Luo S, Deng Y. Gut microbiota and its metabolites regulate insulin resistance: traditional Chinese medicine insights for T2DM. Front Microbiol 2025; 16:1554189. [PMID: 40177494 PMCID: PMC11963813 DOI: 10.3389/fmicb.2025.1554189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 02/27/2025] [Indexed: 04/05/2025] Open
Abstract
The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and chronic low-grade inflammation. However, despite the widespread use of first-line antidiabetic drugs, IR in diabetes and its complications continue to rise. The gut microbiota and its metabolic products may promote the development of T2DM by exacerbating IR. Therefore, regulating the gut microbiota has become a promising therapeutic strategy, with particular attention given to probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. This review first examines the relationship between gut microbiota and IR in T2DM, summarizing the research progress of microbiota-based therapies in modulating IR. We then delve into how gut microbiota-related metabolic products contribute to IR. Finally, we summarize the research findings on the role of traditional Chinese medicine in regulating the gut microbiota and its metabolic products to improve IR. In conclusion, the gut microbiota and its metabolic products play a crucial role in the pathophysiological process of T2DM by modulating IR, offering new insights into potential therapeutic strategies for T2DM.
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Affiliation(s)
- Jing Liu
- School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Fuxing Li
- Ningxiang Traditional Chinese Medicine Hospital, Changsha, China
| | - Le Yang
- School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Shengping Luo
- School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Yihui Deng
- School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
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Min H, Choi KS, Yun S, Jang S. Live Biotherapeutic Products for Metabolic Diseases: Development Strategies, Challenges, and Future Directions. J Microbiol Biotechnol 2025; 35:e2410054. [PMID: 40081885 PMCID: PMC11925753 DOI: 10.4014/jmb.2410.10054] [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: 10/31/2024] [Revised: 01/11/2025] [Accepted: 01/12/2025] [Indexed: 03/16/2025]
Abstract
Metabolic diseases, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, have emerged as major global health challenges. Recent research has revealed that the gut microbiome is closely associated with the development of these conditions. The Food and Drug Administration has recognized certain probiotic strains with therapeutic potential, classifying them as live biotherapeutic products (LBPs). LBPs, which are derived from naturally occurring microorganisms, may present an effective strategy for treating metabolic diseases by restoring gut microbiota balance and regulating metabolic functions. This review explores the development of LBPs specifically for metabolic disease treatments, covering every phase from strain identification, non-clinical and clinical trials, manufacturing and formulation to regulatory approval. Furthermore, it addresses the challenges involved in the commercialization of these therapies. By offering critical insights into the research and development of LBPs for metabolic disease treatment, this review aims to contribute to the progress of these promising therapies.
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Affiliation(s)
- Heonhae Min
- Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
| | - Kyu-Sung Choi
- Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
| | - Saebom Yun
- Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
| | - Sungho Jang
- Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
- Division of Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
- Research Center for Bio Materials and Process Development, Incheon National University, Incheon 22012, Republic of Korea
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Soliz-Rueda JR, Cuesta-Marti C, O'Mahony SM, Clarke G, Schellekens H, Muguerza B. Gut microbiota and eating behaviour in circadian syndrome. Trends Endocrinol Metab 2025; 36:15-28. [PMID: 39095231 DOI: 10.1016/j.tem.2024.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 07/04/2024] [Accepted: 07/12/2024] [Indexed: 08/04/2024]
Abstract
Eating behaviour and circadian rhythms are closely related. The type, timing, and quantity of food consumed, and host circadian rhythms, directly influence the intestinal microbiota, which in turn impacts host circadian rhythms and regulates food intake beyond homeostatic eating. This Opinion discusses the impact of food intake and circadian disruptions induced by an obesogenic environment on gut-brain axis signalling. We also explore potential mechanisms underlying the effects of altered gut microbiota on food intake behaviour and circadian rhythmicity. Understanding the crosstalk between gut microbiota, circadian rhythms, and unhealthy eating behaviour is crucial to addressing the obesity epidemic, which remains one of the biggest societal challenges of our time.
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Affiliation(s)
- Jorge R Soliz-Rueda
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira I Virgili, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain; Center of Environmental, Food and Toxicological Technology (TecnATox), Tarragona, Spain
| | - Cristina Cuesta-Marti
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Ireland, Cork, Ireland
| | - Siobhain M O'Mahony
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Ireland, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Harriët Schellekens
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Ireland, Cork, Ireland.
| | - Begoña Muguerza
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira I Virgili, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain; Center of Environmental, Food and Toxicological Technology (TecnATox), Tarragona, Spain
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D’Almeida AP, Neta AAI, de Andrade-Lima M, de Albuquerque TL. Plant-based probiotic foods: current state and future trends. Food Sci Biotechnol 2024; 33:3401-3422. [PMID: 39493382 PMCID: PMC11525375 DOI: 10.1007/s10068-024-01674-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 06/23/2024] [Accepted: 07/11/2024] [Indexed: 11/05/2024] Open
Abstract
Abstract Plant-based probiotic foods (PBPFs) have recently become a notable choice for many consumers. While less recognized than dairy products, these foods offer efficient alternatives for individuals with lactose intolerance, vegans, or those aiming for more sustainable dietary practices. Traditional fermented PBPFs, such as kimchi, sauerkraut, and kombucha, are part of cultures from different countries and have gained more significant popularity in recent years globally due to their peculiar flavors and health benefits. However, new plant-based probiotic products have also been studied and made available to consumers of the growing demand in this sector. Therefore, this review discusses trends in plant-based probiotic production, known benefits, and characteristics. Challenges currently faced in manufacturing, distribution, marketing, consumer acceptance, and legislation are also discussed. Graphical abstract
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Affiliation(s)
- Alan Portal D’Almeida
- Department of Chemical Engineering, Technology Center, Federal University of Ceará, Fortaleza, CE 60455-760 Brazil
| | - Aida Aguilera Infante Neta
- Department of Food Engineering, Center for Agricultural Sciences, Federal University of Ceará, Fortaleza, CE 60020-181 Brazil
| | - Micael de Andrade-Lima
- Natural Resources Institute (NRI), University of Greenwich, Medway Campus, Chatham, ME4 4TB UK
| | - Tiago Lima de Albuquerque
- Department of Food Engineering, Center for Agricultural Sciences, Federal University of Ceará, Fortaleza, CE 60020-181 Brazil
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Talib N, Mohamad NE, Yeap SK, Ho CL, Masarudin MJ, Abd-Aziz S, Izham MNM, Kumar MR, Hussin Y, Alitheen NB. Anti-Diabetic Effect of Lactobacillus Paracasei Isolated from Malaysian Water Kefir Grains. Probiotics Antimicrob Proteins 2024; 16:2161-2180. [PMID: 37755545 DOI: 10.1007/s12602-023-10159-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/12/2023] [Indexed: 09/28/2023]
Abstract
The prevalence of type 2 diabetes mellitus (T2DM) is alarming because it is always linked to the increase in chronic diseases, mortality, and socioeconomic burden. Water kefir has a wide range of functional and probiotic characteristics attributed to the microorganisms present in the kefir grains. The present study aims to evaluate the in vivo anti-diabetic potential of the isolated Lactobacillus paracasei from Malaysian water kefir grains (MWKG) which was reported to have excellent probiotic properties and high antioxidant activities as reported previously. High-fat diet/streptozotocin (HFD/STZ) induction was used to obtain a T2DM model followed by treatment with the isolated L. paracasei from MWKG. The levels of glucose, insulin, and in vivo liver antioxidants were quantified after 14 weeks. Gene expression analysis of the liver was also carried out using microarray analysis, and several genes were selected for validation using quantitative real-time PCR. Insulin tolerance test demonstrated that the L. paracasei isolated from the MWKG alleviated T2DM by improving the area under the curve of the insulin tolerance test whereby low-dose and high-dose concentrations treated groups showed 2424.50 ± 437.02 mmol/L·min and 2017.50 ± 347.09 mmol/L·min, respectively, compared to untreated diabetic mice which was 3884.50 ± 39.36 mmol/L·min. Additionally, treatment with the isolated L. paracasei from MWKG regulated the expression of several genes related to glucose homeostasis and lipid metabolism in diabetic mice. These results suggested that the isolated L. paracasei from MWKG could be a potential dietary supplement for T2DM.
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Affiliation(s)
- Noorshafadzilah Talib
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Nurul Elyani Mohamad
- Biotechnology Research Institute, Universiti Malaysia Sabah, 88400, Kota Kinabalu, Sabah, Malaysia
| | - Swee Keong Yeap
- China-ASEAN College of Marine Sciences, Xiamen University Malaysia, 43900, Sepang, Malaysia
| | - Chai Ling Ho
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Mas Jaffri Masarudin
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Suraini Abd-Aziz
- Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Mira Nadiah Mohd Izham
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Muganti Rajah Kumar
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Yazmin Hussin
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia
| | - Noorjahan Banu Alitheen
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia.
- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia.
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6
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Ng CYJ, Zhong L, Ng HS, Goh KS, Zhao Y. Managing Type 2 Diabetes Mellitus via the Regulation of Gut Microbiota: A Chinese Medicine Perspective. Nutrients 2024; 16:3935. [PMID: 39599721 PMCID: PMC11597546 DOI: 10.3390/nu16223935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 11/11/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and inadequate insulin production. Given the increased frequency of T2DM and the health issues it can cause, there is an increasing need to develop alternative T2DM management strategies. One such approach is Chinese Medicine (CM), a complementary therapy widely used in T2DM treatment. Given the emphasis on gut microbiota in current research, studying CM in the treatment of T2DM via gut microbiota modulation could be beneficial. Scope and approach: The use of various CM methods for managing T2DM via gut microbiota modulation is highlighted in this review. Following an introduction of the gut microbiota and its role in T2DM pathogenesis, we will review the potential interactions between gut microbiota and T2DM. Thereafter, we will review various CM treatment modalities that modulate gut microbiota and provide perspectives for future research. Key findings and discussion: In T2DM, Akkermansia, Bifidobacterium, and Firmicutes are examples of gut microbiota commonly imbalanced. Studies have shown that CM therapies can modulate gut microbiota, leading to beneficial effects such as reduced inflammation, improved metabolism, and improved immunity. Among these treatment modalities, Chinese Herbal Medicine and acupuncture are the most well-studied, and several in vivo studies have demonstrated their potential in managing T2DM by modulating gut microbiota. However, the underlying biomolecular mechanisms of actions are not well elucidated, which is a key area for future research. Future studies could also investigate alternate CM therapies such as moxibustion and CM exercises and conduct large-scale clinical trials to validate their effectiveness in treatment.
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Affiliation(s)
- Chester Yan Jie Ng
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
| | - Linda Zhong
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
| | - Han Seong Ng
- Singapore General Hospital, Outram Rd., Singapore 169608, Singapore
- Academy of Chinese Medicine Singapore, 705 Serangoon Road, Singapore 328127, Singapore
| | - Kia Seng Goh
- Academy of Chinese Medicine Singapore, 705 Serangoon Road, Singapore 328127, Singapore
- Singapore College of Traditional Chinese Medicine, 640 Lor 4 Toa Payoh, Singapore 319522, Singapore
| | - Yan Zhao
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
- Academy of Chinese Medicine Singapore, 705 Serangoon Road, Singapore 328127, Singapore
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7
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Santos AA, Duarte R, Duarte M, Arella F, Marques V, Roos S, Rodrigues CMP. Impact of Lactobacillaceae supplementation on the multi-organ axis during MASLD. Life Sci 2024; 354:122948. [PMID: 39117140 DOI: 10.1016/j.lfs.2024.122948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 07/15/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
The gut-liver axis plays a pivotal role in maintaining body homeostasis. Disruption of the gut-liver axis is linked to a multitude of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Probiotic strains from the Lactobacillaceae family are commonly used to mitigate experimental MASLD. Over the years, numerous studies have demonstrated the efficacy of these probiotics, often focusing on the outcome of liver disease. This review aims to further understand MASLD as a systemic metabolic dysfunction and to highlight the effects of probiotics on multi-organ axis, including organs such as the gastrointestinal tract, pancreas, muscle, adipose tissue, and the immune system. We specifically discuss evidence on how supplementation with Lactobacillaceae strains may alleviate MASLD by not only restoring liver health but also by modulating the physiology of other organ systems.
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Affiliation(s)
- André A Santos
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
| | - Raquel Duarte
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Madalena Duarte
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Fabiola Arella
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Vanda Marques
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
| | - Stefan Roos
- Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Sweden
| | - Cecília M P Rodrigues
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal
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8
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Jeyaraman M, Mariappan T, Jeyaraman N, Muthu S, Ramasubramanian S, Santos GS, da Fonseca LF, Lana JF. Gut microbiome: A revolution in type II diabetes mellitus. World J Diabetes 2024; 15:1874-1888. [PMID: 39280189 PMCID: PMC11372632 DOI: 10.4239/wjd.v15.i9.1874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 06/11/2024] [Accepted: 07/18/2024] [Indexed: 08/27/2024] Open
Abstract
Type II diabetes mellitus (T2DM) has experienced a dramatic increase globally across countries of various income levels over the past three decades. The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors. While numerous pharmaceutical therapies have been developed, there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects. In this context, the exploration of the gut microbiome presents a promising avenue. Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals, suggesting its potential role in the disease's pathogenesis and progression. This emerging field offers diverse applications, particularly in modifying the gut environment through the administration of prebiotics, probiotics, and fecal microbiome transfer. These inter-ventions aim to restore a healthy microbiome balance, which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM. Although current results from clinical trials have not yet shown dramatic effects on diabetes management, the groundwork has been laid for deeper investigation. Ongoing and future clinical trials are critical to advancing our understanding of the microbiome's impact on diabetes. By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism, researchers can develop more targeted interventions. The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM, potentially reducing the disease's burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic, systemic health improvements.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
| | - Tejaswin Mariappan
- Department of Community Medicine, Government Stanley Medical College and Hospital, Chennai 600001, Tamil Nadu, India
| | - Naveen Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
| | - Sathish Muthu
- Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Government Medical College, Karur 639004, Tamil Nadu, India
- Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| | - Swaminathan Ramasubramanian
- Department of Orthopaedics, Government Medical College, Omandurar Government Estate, Chennai 600002, Tamil Nadu, India
| | - Gabriel Silva Santos
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
| | - Lucas Furtado da Fonseca
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
| | - José Fábio Lana
- Department of Orthopaedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, São Paulo, Brazil
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Kobyliak N, Khomenko M, Falalyeyeva T, Fedchenko A, Savchuk O, Tseyslyer Y, Ostapchenko L. Probiotics for pancreatic β-cell function: from possible mechanism of action to assessment of effectiveness. Crit Rev Microbiol 2024; 50:663-683. [PMID: 37705353 DOI: 10.1080/1040841x.2023.2257776] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 07/27/2023] [Accepted: 09/06/2023] [Indexed: 09/15/2023]
Abstract
Type 2 diabetes (T2D) is a metabolic disease characterized by chronic hyperglycemia because of insulin resistance (IR) and\or pancreatic β-cell dysfunction. Last century research showed that gut microbiota has a direct effect on metabolism and metabolic diseases. New studies into the human microbiome and its connection with the host is making it possible to develop new therapies for a wide variety of diseases. Inflammation is a well-known precursor to metabolic syndrome, which increases the risk of hypertension, visceral obesity, and dyslipidemia, which can lead to T2D through the damage of pancreatic β-cell and reduce insulin secretion. Current understanding for beneficial effects of probiotics in T2D strictly rely on both animal and clinical data, which mostly focused on their impact on IR, anthropometric parameters, glycemic control and markers of chronic systemic inflammation. From the other hand, there is a lack of evidence-based probiotic efficacy on pancreatic β-cell function in terms of T2D and related metabolic disorders. Therefore, current review will focus on the efficacy of probiotics for the protection of β-cells damage and it`s mechanism in patients with T2D.
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Affiliation(s)
- Nazarii Kobyliak
- Endocrinology Department, Bogomolets National Medical University, Kyiv, Ukraine
- Medical Laboratory CSD, Kyiv, Ukraine
| | - Maria Khomenko
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Tetyana Falalyeyeva
- Medical Laboratory CSD, Kyiv, Ukraine
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
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10
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Li S, Liu Z, Zhang Q, Su D, Wang P, Li Y, Shi W, Zhang Q. The Antidiabetic Potential of Probiotics: A Review. Nutrients 2024; 16:2494. [PMID: 39125375 PMCID: PMC11313988 DOI: 10.3390/nu16152494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/26/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
Diabetes has become one of the most prevalent global epidemics, significantly impacting both the economy and the health of individuals. Diabetes is associated with numerous complications, such as obesity; hyperglycemia; hypercholesterolemia; dyslipidemia; metabolic endotoxemia; intestinal barrier damage; insulin-secretion defects; increased oxidative stress; and low-grade, systemic, and chronic inflammation. Diabetes cannot be completely cured; therefore, current research has focused on developing various methods to control diabetes. A promising strategy is the use of probiotics for diabetes intervention. Probiotics are a class of live, non-toxic microorganisms that can colonize the human intestine and help improve the balance of intestinal microbiota. In this review, we summarize the current clinical studies on using probiotics to control diabetes in humans, along with mechanistic studies conducted in animal models. The primary mechanism by which probiotics regulate diabetes is improved intestinal barrier integrity, alleviated oxidative stress, enhanced immune response, increased short-chain fatty acid production, etc. Therefore, probiotic supplementation holds great potential for the prevention and management of diabetes.
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Affiliation(s)
- Shiming Li
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100193, China
| | - Zichao Liu
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Qi Zhang
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Dan Su
- Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA;
| | - Pengjie Wang
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Yixuan Li
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Wenbiao Shi
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Qian Zhang
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
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11
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Suslov AV, Panas A, Sinelnikov MY, Maslennikov RV, Trishina AS, Zharikova TS, Zharova NV, Kalinin DV, Pontes-Silva A, Zharikov YO. Applied physiology: gut microbiota and antimicrobial therapy. Eur J Appl Physiol 2024; 124:1631-1643. [PMID: 38683402 DOI: 10.1007/s00421-024-05496-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 04/22/2024] [Indexed: 05/01/2024]
Abstract
The gut microbiota plays an important role in maintaining human health and in the pathogenesis of several diseases. Antibiotics are among the most commonly prescribed drugs and have a significant impact on the structure and function of the gut microbiota. The understanding that a healthy gut microbiota prevents the development of many diseases has also led to its consideration as a potential therapeutic target. At the same time, any factor that alters the gut microbiota becomes important in this approach. Exercise and antibacterial therapy have a direct effect on the microbiota. The review reflects the current state of publications on the mechanisms of intestinal bacterial involvement in the pathogenesis of cardiovascular, metabolic, and neurodegenerative diseases. The physiological mechanisms of the influence of physical activity on the composition of the gut microbiota are considered. The mechanisms of the common interface between exercise and antibacterial therapy will be considered using the example of several socially important diseases. The aim of the study is to show the physiological relationship between the effects of exercise and antibiotics on the gut microbiota.
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Affiliation(s)
- Andrey V Suslov
- Russian National Centre of Surgery, Avtsyn Research Institute of Human Morphology, Moscow, 117418, Russia
- Pirogov Russian National Research Medical University (RNRMU), Moscow, 117997, Russia
| | - Alin Panas
- N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), St. Trubetskaya, 8, Bld. 2, Moscow, 119991, Russia
| | - Mikhail Y Sinelnikov
- Department of Oncology, Radiotherapy and Reconstructive Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119048, Russia
| | - Roman V Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119435, Russia
| | - Aleksandra S Trishina
- N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), St. Trubetskaya, 8, Bld. 2, Moscow, 119991, Russia
| | - Tatyana S Zharikova
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 125009, Russia
- Lomonosov Moscow State University, Moscow, 119991, Russia
| | - Nataliya V Zharova
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 125009, Russia
| | - Dmitry V Kalinin
- Pathology Department, A.V. Vishnevsky National Medical Research Center of Surgery, Moscow, 115093, Russia
| | - André Pontes-Silva
- Postgraduate Program in Physical Therapy (PPGFT), Department of Physical Therapy (DFisio), Universidade Federal de São Carlos (UFSCar), São Carlos (SP), Brazil.
| | - Yury O Zharikov
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, 125009, Russia
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12
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Hasanian-Langroudi F, Ghasemi A, Hedayati M, Siadat SD, Tohidi M. Novel Insight into the Effect of Probiotics in the Regulation of the Most Important Pathways Involved in the Pathogenesis of Type 2 Diabetes Mellitus. Probiotics Antimicrob Proteins 2024; 16:829-844. [PMID: 37162668 DOI: 10.1007/s12602-023-10056-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/02/2023] [Indexed: 05/11/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is considered one of the most common disorders worldwide. Although several treatment modalities have been developed, the existing interventions have not yielded the desired results. Therefore, researchers have focused on finding treatment choices with low toxicity and few adverse effects that could control T2DM efficiently. Various types of research on the role of gut microbiota in developing T2DM and its related complications have led to the growing interest in probiotic supplementation. Several properties make these organisms unique in terms of human health, including their low cost, high reliability, and good safety profile. Emerging evidence has demonstrated that three of the most important signaling pathways, including nuclear factor kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and nuclear factor erythroid 2-related factor 2 (Nrf2), which involved in the pathogenesis of T2DM, play key functions in the effects of probiotics on this disease. Hence, we will focus on the clinical applications of probiotics in the management of T2DM. Then, we will also discuss the roles of the involvement of various probiotics in the regulation of the most important signaling pathways (NF-κB, PI3K/Akt, and Nrf2) involved in the pathogenesis of T2DM.
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Affiliation(s)
- Farzaneh Hasanian-Langroudi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box, Tehran, 19395-4763, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
- Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran.
| | - Maryam Tohidi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box, Tehran, 19395-4763, Iran.
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13
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Shi B, Li H, He X. Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation. Gut Microbes 2024; 16:2323237. [PMID: 38411391 PMCID: PMC10900281 DOI: 10.1080/19490976.2024.2323237] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 02/21/2024] [Indexed: 02/28/2024] Open
Abstract
The gut microbiome is known as the tenth system of the human body that plays a vital role in the intersection between health and disease. The considerable inter-individual variability in gut microbiota poses both challenges and great prospects in promoting precision medicine in cardiovascular diseases (CVDs). In this review, based on the development, evolution, and influencing factors of gut microbiota in a full life circle, we summarized the recent advances on the characteristic alteration in gut microbiota in CVDs throughout different life stages, and depicted their pathological links in mechanism, as well as the highlight achievements of targeting gut microbiota in CVDs prevention, diagnosis and treatment. Personalized strategies could be tailored according to gut microbiota characteristics in different life stages, including gut microbiota-blood metabolites combined prediction and diagnosis, dietary interventions, lifestyle improvements, probiotic or prebiotic supplements. However, to fulfill the promise of a lifelong cardiovascular health, more mechanism studies should progress from correlation to causality and decipher novel mechanisms linking specific microbes and CVDs. It is also promising to use the burgeoning artificial intelligence and machine learning to target gut microbiota for developing diagnosis system and screening for new therapeutic interventions.
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Affiliation(s)
- Bozhong Shi
- Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haoyu Li
- Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaomin He
- Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children’s Medical Center, National Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
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14
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Qu Q, He P, Zhang Y, Yang S, Zeng P. The Intervention of Probiotics on Type 2 Diabetes Mellitus in Animal Models. Mol Nutr Food Res 2024; 68:e2200815. [PMID: 37967330 DOI: 10.1002/mnfr.202200815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 07/18/2023] [Indexed: 11/17/2023]
Abstract
Type 2 diabetes accounts for more than 90% of diabetes patients with the incidence and prevalence continuously rising globally. As a prospective therapy strategy for type 2 diabetes, probiotics have shown beneficial effects both in animal experiments and human clinical trials. This review summarizes the commonly used animal models in probiotic intervention research and presents the evidence and mechanism of diabetes intervention with probiotics in these animal models. Probiotics can help maintain glucose homeostasis, improve lipid metabolism, promote the production of short-chain fatty acids, and reduce inflammatory reactions in animal models. However, the clinical translation of benefits from probiotics is still challenged by intrinsic differences between experimental animal models and humans, and the application of humanized non-rodent diabetic animal models may contribute to the clinical translation of probiotics in the future.
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Affiliation(s)
- Qianyu Qu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 61000, China
| | - Penggang He
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 61000, China
| | - Yuqi Zhang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 61000, China
| | - Shujuan Yang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 61000, China
| | - Peibin Zeng
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 61000, China
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15
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Rathod P, Yadav RP. Gut microbiome as therapeutic target for diabesity management: opportunity for nanonutraceuticals and associated challenges. Drug Deliv Transl Res 2024; 14:17-29. [PMID: 37552394 DOI: 10.1007/s13346-023-01404-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2023] [Indexed: 08/09/2023]
Abstract
Diabesity is showing rising prevalence. Current treatment modalities include pharmacological and non-pharmacological approaches, yet associated with various drawbacks. Recently, gut microbial dysbiosis is documented as a crucial factor in the pathogenesis of diabesity. Targeting gut microbiome using modulators shows promising therapeutic strategy for diabesity management. In this line, nanonutraceuticals represent new class of gut microbial modulators. The present article explores the potential of nanonutraceuticals including nanoprobiotics, nanoprebiotics, and plant-derived nanovesicles that are fabricated on the ecofriendly food based scaffold with gut microbial modulatory potential for diabesity management. A number of compelling evidences from different studies support Bifidobacterium, Enterococcus, and Bacteroides genera and Lactobacillus plantarum and Akkermansia muciniphila species significant in diabesity management. The probable mechanisms reported for gut microbial dysbiosis-induced diabesity are mentioned. The review findings suggest gut microbiome as significant therapeutic target for diabesity management. Moreover, ecofriendly nanonutraceuticals developed using natural products including food-grade materials are efficient modulators of gut microbiome and indicate next-generation diabesity therapeutics. Clinical studies are imperative as further exploration may provide new dimensions to the future research.
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Affiliation(s)
- Priyanka Rathod
- MGMIHS OMICS Research Center, MGM Central Research Laboratory, MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India
- Department of Medical Biotechnology, MGM School of Biomedical Sciences, MGM Institute of Health Sciences, Kamothe-410209, Navi Mumbai, Maharashtra, India
| | - Raman P Yadav
- MGMIHS OMICS Research Center, MGM Central Research Laboratory, MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India.
- Department of Medical Biotechnology, MGM School of Biomedical Sciences, MGM Institute of Health Sciences, Kamothe-410209, Navi Mumbai, Maharashtra, India.
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16
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Song H, Xue H, Zhang Z, Wang J, Li A, Zhang J, Luo P, Zhan M, Zhou X, Chen L, Fang Y. Amelioration of Type 2 Diabetes Using Four Strains of Lactobacillus Probiotics: Effects on Gut Microbiota Reconstitution-Mediated Regulation of Glucose Homeostasis, Inflammation, and Oxidative Stress in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:20801-20814. [PMID: 37991826 DOI: 10.1021/acs.jafc.3c04665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2023]
Abstract
This study aims to explore the preventive effects and underlying mechanisms of Lactobacillus fermentum CKCC1858 (CKCC1), L. fermentum CKCC1369 (CKCC2), Lactobacillus plantarum CKCC1312 (CKCC3), and Lactobacillus gasseri CKCC1913 (CKCC4) on high-fat diet combined with streptozotocin (HFD/STZ)-stimulated type 2 diabetes (T2D) in mice. Generally, the results indicated that most of the four probiotics reduced weight loss and liver and pancreas damage, significantly (p < 0.05) improved glucose metabolism by regulating glucagon-like peptide-1 (GLP-1), fasting glucose and insulin levels, and increasing expression of glucose transporters. Probiotics improved hyperlipemia, inflammation, and oxidative stress by reducing the secretion of blood lipids and proinflammatory cytokines, increasing antioxidant enzymes. Metagenomic results revealed that probiotics restored gut microbiota via enhancing (reducing) the relative abundance of beneficial bacteria (harmful bacteria) and altered specific metabolic pathways in T2D mice. CKCC1, CKCC3, and CKCC4 showed excellent effects compared to CKCC2. These results indicated that probiotics potentially prevented T2D, which is strain-specific.
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Affiliation(s)
- Hainan Song
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China
| | - Hui Xue
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China
| | - Zeng Zhang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China
| | - Jun Wang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China
| | - Ao Li
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China
| | - Jiachao Zhang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China
| | - Pengfei Luo
- ClassyKiss Dairy (Shenzhen) Co., Ltd., Shenzhen 518000, China
| | - Meng Zhan
- ClassyKiss Dairy (Shenzhen) Co., Ltd., Shenzhen 518000, China
| | - Xiaoli Zhou
- ClassyKiss Dairy (Shenzhen) Co., Ltd., Shenzhen 518000, China
| | - Lihao Chen
- ClassyKiss Dairy (Shenzhen) Co., Ltd., Shenzhen 518000, China
| | - Yajing Fang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou 570228, China
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17
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Zikou E, Dovrolis N, Dimosthenopoulos C, Gazouli M, Makrilakis K. The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece-A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients 2023; 15:4663. [PMID: 37960315 PMCID: PMC10647535 DOI: 10.3390/nu15214663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/16/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
The role of probiotic supplementation in type 2 diabetes (T2D) treatment is controversial. The present study aimed to assess the effects of a multi-strain probiotic supplement (LactoLevureR (containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii)) over 6 months, primarily on glycemic control as well as on lipid levels and alterations in the gut microbiome, among individuals with T2D residing in Greece. A total of 91 adults with T2D (mean age [±SD] 65.12 ± 10.92 years, 62.6% males) were randomized to receive the probiotic supplement or a matching placebo capsule, once daily, for 6 months. Blood chemistries and anthropometric parameters were conducted every 3 months, and stool samples were collected at baseline and at 6 months. Significant reductions in HbA1c, fasting blood glucose, and total cholesterol were observed in participants treated with the probiotic supplement (n = 46) compared to the controls (n = 45), even after adjustment for a greater decrease in adiposity (waist circumference). Although there were no statistically significant differences in the diversity of the gut microbiome (α and β diversity), the administration of probiotics did influence several genera, metabolites, and key enzymes associated with diabetes. Overall, the administration of the multi-strain probiotic LactoLevureR over a 6-month period in individuals with T2D was well-tolerated and had a positive impact on metabolic parameters, alongside improvements in indices of adiposity.
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Affiliation(s)
- Eva Zikou
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, 11527 Athens, Greece; (E.Z.); (C.D.)
| | - Nikolas Dovrolis
- Department of Basic Medical Sciences, Laboratory of Biology, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece; (N.D.); (M.G.)
| | - Charilaos Dimosthenopoulos
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, 11527 Athens, Greece; (E.Z.); (C.D.)
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece; (N.D.); (M.G.)
| | - Konstantinos Makrilakis
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, 11527 Athens, Greece; (E.Z.); (C.D.)
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18
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Patra D, Banerjee D, Ramprasad P, Roy S, Pal D, Dasgupta S. Recent insights of obesity-induced gut and adipose tissue dysbiosis in type 2 diabetes. Front Mol Biosci 2023; 10:1224982. [PMID: 37842639 PMCID: PMC10575740 DOI: 10.3389/fmolb.2023.1224982] [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: 05/18/2023] [Accepted: 09/14/2023] [Indexed: 10/17/2023] Open
Abstract
An imbalance in microbial homeostasis, referred to as dysbiosis, is critically associated with the progression of obesity-induced metabolic disorders including type 2 diabetes (T2D). Alteration in gut microbial diversity and the abundance of pathogenic bacteria disrupt metabolic homeostasis and potentiate chronic inflammation, due to intestinal leakage or release of a diverse range of microbial metabolites. The obesity-associated shifts in gut microbial diversity worsen the triglyceride and cholesterol level that regulates adipogenesis, lipolysis, and fatty acid oxidation. Moreover, an intricate interaction of the gut-brain axis coupled with the altered microbiome profile and microbiome-derived metabolites disrupt bidirectional communication for instigating insulin resistance. Furthermore, a distinct microbial community within visceral adipose tissue is associated with its dysfunction in obese T2D individuals. The specific bacterial signature was found in the mesenteric adipose tissue of T2D patients. Recently, it has been shown that in Crohn's disease, the gut-derived bacterium Clostridium innocuum translocated to the mesenteric adipose tissue and modulates its function by inducing M2 macrophage polarization, increasing adipogenesis, and promoting microbial surveillance. Considering these facts, modulation of microbiota in the gut and adipose tissue could serve as one of the contemporary approaches to manage T2D by using prebiotics, probiotics, or faecal microbial transplantation. Altogether, this review consolidates the current knowledge on gut and adipose tissue dysbiosis and its role in the development and progression of obesity-induced T2D. It emphasizes the significance of the gut microbiota and its metabolites as well as the alteration of adipose tissue microbiome profile for promoting adipose tissue dysfunction, and identifying novel therapeutic strategies, providing valuable insights and directions for future research and potential clinical interventions.
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Affiliation(s)
- Debarun Patra
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Dipanjan Banerjee
- Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Assam, India
| | - Palla Ramprasad
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Soumyajit Roy
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Durba Pal
- Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, Punjab, India
| | - Suman Dasgupta
- Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Assam, India
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19
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Modulatory effects of Lactiplantibacillus plantarum on chronic metabolic diseases. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2022.10.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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20
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Kumari V B C, Huligere SS, Alotaibi G, Al Mouslem AK, Bahauddin AA, Shivanandappa TB, Ramu R. Antidiabetic Activity of Potential Probiotics Limosilactobacillus spp., Levilactobacillus spp., and Lacticaseibacillus spp. Isolated from Fermented Sugarcane Juice: A Comprehensive In Vitro and In Silico Study. Nutrients 2023; 15:nu15081882. [PMID: 37111101 PMCID: PMC10144524 DOI: 10.3390/nu15081882] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/10/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Probiotics are regarded as a potential source of functional foods for improving the microbiota in human gut. When consumed, these bacteria can control the metabolism of biomolecules, which has numerous positive effects on health. Our objective was to identify a probiotic putative Lactobacillus spp. from fermented sugarcane juice that can prevent α-glucosidase and α-amylase from hydrolyzing carbohydrates. Isolates from fermented sugarcane juice were subjected to biochemical, molecular characterization (16S rRNA) and assessed for probiotic traits. Cell-free supernatant (CS) and extract (CE) and also intact cells (IC) were examined for the inhibitory effect on α-glucosidase and α-amylase. CS of the strain showed the highest inhibition and was subjected to a liquid chromatography-mass spectrometry (LCMS) analysis to determine the organic acid profile. The in silico approach was employed to assess organic acid stability and comprehend enzyme inhibitors' impact. Nine isolates were retained for further investigation based on the preliminary biochemical evaluation. Limosilactobacillus spp., Levilactobacillus spp., and Lacticaseibacillus spp. were identified based on similarity > 95% in homology search (NCBI database). The strains had a higher survival rate (>98%) than gastric and intestinal fluids, also a high capacity for adhesion (hydrophobicity > 56%; aggregation > 80%; HT-29 cells > 54%; buccal epithelial cells > 54%). The hemolytic assay indicated that the isolates could be considered safe. The isolates' derivatives inhibited enzymes to varying degrees, with α-glucosidase inhibition ranging from 21 to 85% and α-amylase inhibition from 18 to 75%, respectively. The CS of RAMULAB54 was profiled for organic acid that showed the abundance of hydroxycitric acid, citric acid, and lactic acid indicating their role in the observed inhibitory effects. The in silico approach has led us to understand that hydroxycitric acid has the ability to inhibit both the enzymes (α-glucosidase and α-amylase) effectively. Inhibiting these enzymes helps moderate postprandial hyperglycemia and regulates blood glucose levels. Due to their promising antidiabetic potential, these isolates can be used to enhance intestinal health.
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Affiliation(s)
- Chandana Kumari V B
- Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
| | - Sujay S Huligere
- Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
| | - Ghallab Alotaibi
- Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, Shaqra 11961, Saudi Arabia
| | - Abdulaziz K Al Mouslem
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al Ahsa 31982, Saudi Arabia
| | - Ammar Abdulraheem Bahauddin
- Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah 42535, Saudi Arabia
| | | | - Ramith Ramu
- Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
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21
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Guo Y, Liu M, Liu X, Zheng M, Xu X, Liu X, Gong J, Liu H, Liu J. Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity. Foods 2023; 12:foods12081578. [PMID: 37107373 PMCID: PMC10137368 DOI: 10.3390/foods12081578] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/01/2023] [Accepted: 04/05/2023] [Indexed: 04/29/2023] Open
Abstract
Gut microbiota plays an important role in the pathophysiology of obesity. Fungal polysaccharide can improve obesity, but the potential mechanism needs further study. This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. At the genus level, the abundance of Lactobacillus increased and that of Bacteroides decreased. At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. The untargeted metabolomics indicated that 36 metabolites were related to the anti-obesity effect of SRP. Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity.
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Affiliation(s)
- Yunlong Guo
- National Engineering Research Center for Wheat and Corn Deep Processing, College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Meihong Liu
- National Engineering Research Center for Wheat and Corn Deep Processing, College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
| | - Xin Liu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Mingzhu Zheng
- National Engineering Research Center for Wheat and Corn Deep Processing, College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
| | - Xiuying Xu
- National Engineering Research Center for Wheat and Corn Deep Processing, College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
| | - Xiaokang Liu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Jiyu Gong
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
| | - Huimin Liu
- National Engineering Research Center for Wheat and Corn Deep Processing, College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
| | - Jingsheng Liu
- National Engineering Research Center for Wheat and Corn Deep Processing, College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
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22
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Jia L, Huang S, Sun B, Shang Y, Zhu C. Pharmacomicrobiomics and type 2 diabetes mellitus: A novel perspective towards possible treatment. Front Endocrinol (Lausanne) 2023; 14:1149256. [PMID: 37033254 PMCID: PMC10076675 DOI: 10.3389/fendo.2023.1149256] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/14/2023] [Indexed: 04/11/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM), a major driver of mortality worldwide, is more likely to develop other cardiometabolic risk factors, ultimately leading to diabetes-related mortality. Although a set of measures including lifestyle intervention and antidiabetic drugs have been proposed to manage T2DM, problems associated with potential side-effects and drug resistance are still unresolved. Pharmacomicrobiomics is an emerging field that investigates the interactions between the gut microbiome and drug response variability or drug toxicity. In recent years, increasing evidence supports that the gut microbiome, as the second genome, can serve as an attractive target for improving drug efficacy and safety by manipulating its composition. In this review, we outline the different composition of gut microbiome in T2DM and highlight how these microbiomes actually play a vital role in its development. Furthermore, we also investigate current state-of-the-art knowledge on pharmacomicrobiomics and microbiome's role in modulating the response to antidiabetic drugs, as well as provide innovative potential personalized treatments, including approaches for predicting response to treatment and for modulating the microbiome to improve drug efficacy or reduce drug toxicity.
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Affiliation(s)
- Liyang Jia
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shiqiong Huang
- Department of Pharmacy, The First Hospital of Changsha, Changsha, China
| | - Boyu Sun
- Department of Pharmacy, The Third People’s Hospital of Qingdao, Qingdao, China
| | - Yongguang Shang
- Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Yongguang Shang, ; Chunsheng Zhu,
| | - Chunsheng Zhu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Yongguang Shang, ; Chunsheng Zhu,
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Meng X, Liu S, Liu Q, Zhang Y, Jing L, Huang X, Sun J, Ye L. Anti-oxidative stress properties by Lactiplantibacillus plantarum SCS3 in streptozotocin-induced diabetic mice. CYTA - JOURNAL OF FOOD 2022. [DOI: 10.1080/19476337.2022.2136759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Affiliation(s)
- Xiao Meng
- College of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Shukun Liu
- College of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qiuyan Liu
- College of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Ying Zhang
- College of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Lin Jing
- College of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xinyi Huang
- College of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Jiayi Sun
- Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Lu Ye
- Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan, China
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Lactobacillus-fermented yogurt exerts hypoglycemic, hypocholesterolemic, and anti-inflammatory activities in STZ-induced diabetic Wistar rats. Nutr Res 2022; 108:22-32. [PMID: 36395709 DOI: 10.1016/j.nutres.2022.10.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 10/06/2022] [Accepted: 10/09/2022] [Indexed: 11/07/2022]
Abstract
Hyperglycemia is a symptom of type 2 diabetes mellitus, a chronic metabolic disease characterized by elevated blood glucose concentrations. Antidiabetic drugs are common treatments for this metabolic disorder; however, they may have unpleasant side effects. This study hypothesized that probiotic fermented products could preserve nutritional value, maintain metabolic homeostasis, and attenuate the inflammatory response associated with diabetes while reducing side effects. Lactobacillus plantarum KU985438 and Lactobacillus rhamnosus KU985439 showed the lowest alfa-amylase enzyme (α-amylase) activity among 8 lactobacilli tested. These 2 strains were used to develop functional fermented milk products, and their antidiabetic efficacy was tested in induced diabetic Wistar rats. The treatment of diabetic rats with L. plantarum KU985438 or L. rhamnosus KU985439 fermented yogurt resulted in a considerable reduction in blood glucose concentrations (136.79% and 145.17%, respectively) and α-amylase concentrations (56.84% and 56.84%, respectively) compared with conventional treatments. Diabetes relief began after 4 days of yogurt consumption compared with drug-based treatment. Significant improvements in both liver and kidney enzyme concentrations were also observed, in addition to a significant increase in high-density lipoprotein cholesterol concentrations and improved lipid profiles. Inhibition in nuclear factor κB and an increase in Bcl-2 concentrations were also detected. Histopathological examination of both hepatic and pancreatic cells revealed the positive effects of the studied treatment compared with standard treatment. Therefore, the selected Lactobacilli, which has hypoglycemic potential, could be used to produce functional nutraceutical antidiabetic supplements.
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Awasthi A, Corrie L, Vishwas S, Gulati M, Kumar B, Chellappan DK, Gupta G, Eri RD, Dua K, Singh SK. Gut Dysbiosis and Diabetic Foot Ulcer: Role of Probiotics. Pharmaceutics 2022; 14:pharmaceutics14112543. [PMID: 36432734 PMCID: PMC9699533 DOI: 10.3390/pharmaceutics14112543] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/07/2022] [Accepted: 11/19/2022] [Indexed: 11/23/2022] Open
Abstract
Diabetic foot ulcer (DFU) is a multifactorial disease and one of the complications of diabetes. The global burden of DFU in the health sector is increasing at a tremendous rate due to its cost management related to hospitalization, medical costs and foot amputation. Hence, to manage DFU/DWs, various attempts have been made, including treating wounds systematically/topically using synthetic drugs, herbal drugs, or tissue engineering based surgical dressings. However, less attention has been paid to the intrinsic factors that are also the leading cause of diabetes mellitus (DM) and its complications. One such factor is gut dysbiosis, which is one of the major causes of enhancing the counts of Gram-negative bacteria. These bacteria produce lipopolysaccharides, which are a major contributing factor toward insulin resistance and inflammation due to the generation of oxidative stress and immunopathy. These all lead to DM and DFU. Probiotics are the commercial form of beneficial gut microbes that are taken as nutraceuticals by people of all ages to improve gut immunity and prevent gut dysbiosis. However, the role of probiotics has been less explored in the management of DFU. Hence, the therapeutic potential of probiotics in managing DFU is fully described in the current review. This report covers the linkage between gut dysbiosis and DFU, sources of probiotics, the mechanisms of probiotics in DW healing, and the impact of probiotic supplementation in treating DFU. In addition, techniques for the stabilization of probiotics, market status, and patents related to probiotics have been also covered. The relevant data were gathered from PubMed, Scopus, Taylor and Francis, Science Direct, and Google Scholar. Our systematic review discusses the utilization of probiotic supplementation as a nutraceutical for the management of DFU.
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Affiliation(s)
- Ankit Awasthi
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Leander Corrie
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Sukriti Vishwas
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Bimlesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jaipur 302017, India
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 602105, India
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, India
| | - Rajaraman D. Eri
- School of Health Sciences, The University of Tasmania, Launceston, TAS 7248, Australia
- Correspondence: (R.D.E.); or (S.K.S.); Tel.: +61-363245467 (R.D.E.); +91-9888720835 (S.K.S.)
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Correspondence: (R.D.E.); or (S.K.S.); Tel.: +61-363245467 (R.D.E.); +91-9888720835 (S.K.S.)
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Theofilis P, Sagris M, Oikonomou E, Antonopoulos AS, Siasos G, Tsioufis K, Tousoulis D. The Anti-Inflammatory Effect of Novel Antidiabetic Agents. Life (Basel) 2022; 12:1829. [PMID: 36362984 PMCID: PMC9696750 DOI: 10.3390/life12111829] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/28/2022] [Accepted: 11/05/2022] [Indexed: 08/10/2023] Open
Abstract
The incidence of type 2 diabetes (T2DM) has been increasing worldwide and remains one of the leading causes of atherosclerotic disease. Several antidiabetic agents have been introduced in trying to regulate glucose control levels with different mechanisms of action. These agents, and sodium-glucose cotransporter-2 inhibitors in particular, have been endorsed by contemporary guidelines in patients with or without T2DM. Their widespread usage during the last three decades has raised awareness in the scientific community concerning their pleiotropic mechanisms of action, including their putative anti-inflammatory effect. In this review, we delve into the anti-inflammatory role and mechanism of the existing antidiabetic agents in the cardiovascular system and their potential use in other chronic sterile inflammatory conditions.
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Affiliation(s)
- Panagiotis Theofilis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Marios Sagris
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Evangelos Oikonomou
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Alexios S. Antonopoulos
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Gerasimos Siasos
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
- 3rd Cardiology Department, Thoracic Diseases Hospital “Sotiria”, University of Athens Medical School, 11527 Athens, Greece
| | - Kostas Tsioufis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
| | - Dimitris Tousoulis
- 1st Cardiology Department, “Hippokration” General Hospital, University of Athens Medical School, 11527 Athens, Greece
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Zemanova N, Omelka R, Mondockova V, Kovacova V, Martiniakova M. Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases. BIOLOGY 2022; 11:1402. [PMID: 36290306 PMCID: PMC9598716 DOI: 10.3390/biology11101402] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/14/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022]
Abstract
The extended microbial genome-the gut microbiome (GM)-plays a significant role in host health and disease. It is able to influence a number of physiological functions. During dysbiosis, GM is associated with the development of various chronic diseases with impaired bone quality. In general, GM is important for bone homeostasis and can affect it via several mechanisms. This review describes the roles of GM in bone homeostasis through influencing the immune and endocrine functions, short-chain fatty acids production, calcium absorption and the gut-brain axis. The relationship between GM composition and several bone-related diseases, specifically osteoporosis, osteoarthritis, rheumatoid arthritis, diabetes mellitus, obesity and bone cancer, is also highlighted and summarized. GM manipulation may become a future adjuvant therapy in the prevention of many chronic diseases. Therefore, the beneficial effects of probiotic therapy to improve the health status of individuals with aforementioned diseases are provided, but further studies are needed to clearly confirm its effectiveness. Recent evidence suggests that GM is responsible for direct and indirect effects on drug efficacy. Accordingly, various GM alterations and interactions related to the treatment of bone-related diseases are mentioned as well.
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Affiliation(s)
- Nina Zemanova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Radoslav Omelka
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Vladimira Mondockova
- Department of Botany and Genetics, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Veronika Kovacova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
| | - Monika Martiniakova
- Department of Zoology and Anthropology, Faculty of Natural Sciences and Informatics, Constantine the Philosopher University in Nitra, 949 74 Nitra, Slovakia
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Xu Z, Zhang J, Wu J, Yang S, Li Y, Wu Y, Li S, Zhang X, Zuo W, Lian X, Lin J, Jiang Y, Xie L, Liu Y, Wang P. Lactobacillus plantarum ST-III culture supernatant ameliorates alcohol-induced cognitive dysfunction by reducing endoplasmic reticulum stress and oxidative stress. Front Neurosci 2022; 16:976358. [PMID: 36188464 PMCID: PMC9515438 DOI: 10.3389/fnins.2022.976358] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 08/15/2022] [Indexed: 11/28/2022] Open
Abstract
Background Long-term alcohol exposure is associated with oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation, which may impair cognitive function. Probiotics supplements can significantly improve cognitive function in neurodegenerative diseases such as Alzheimer’s disease. Nevertheless, the effect of Lactobacillus plantarum ST-III culture supernatant (LP-cs) on alcohol-induced cognitive dysfunction remains unclear. Methods A mouse model of cognitive dysfunction was established by intraperitoneal injection of alcohol (2 g/kg body weight) for 28 days. Mice were pre-treated with LP-cs, and cognitive function was evaluated using the Morris water maze test. Hippocampal tissues were collected for biochemical and molecular analysis. Results LP-cs significantly ameliorated alcohol-induced decline in learning and memory function and hippocampal morphology changes, neuronal apoptosis, and synaptic dysfunction. A mechanistic study showed that alcohol activated protein kinase R-like endoplasmic reticulum kinase (PERK) signaling and suppressed brain derived neurotrophic factor (BDNF) levels via ER stress in the hippocampus, which LP-cs reversed. Alcohol activated oxidative stress and inflammation responses in the hippocampus, which LP-cs reversed. Conclusion LP-cs significantly ameliorated alcohol-induced cognitive dysfunction and cellular stress. LP-cs might serve as an effective treatment for alcohol-induced cognitive dysfunction.
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Affiliation(s)
- Zeping Xu
- Department of Pharmacy, Ningbo Medical Center Li Huili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, China
| | - Jinjing Zhang
- Department of Pharmacy, Affiliated Cixi Hospital, Wenzhou Medical University, Wenzhou, China
| | - Junnan Wu
- School of Mental Health, Wenzhou Medical University, Wenzhou, China
- The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, China
| | - Shizhuo Yang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yuying Li
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yuyu Wu
- School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - Siyuan Li
- School of Mental Health, Wenzhou Medical University, Wenzhou, China
| | - Xie Zhang
- Department of Pharmacy, Ningbo Medical Center Li Huili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, China
| | - Wei Zuo
- The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, China
| | - Xiang Lian
- The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, China
| | - Jianjun Lin
- The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, China
| | - Yongsheng Jiang
- The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, China
| | - Longteng Xie
- The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, China
- Longteng Xie,
| | - Yanlong Liu
- School of Mental Health, Wenzhou Medical University, Wenzhou, China
- The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, China
- *Correspondence: Yanlong Liu,
| | - Ping Wang
- The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, China
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
- Ping Wang,
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Yan J, Li J, Xue Q, Xie S, Jiang J, Li P, Du B. Bacillus sp. DU-106 ameliorates type 2 diabetes by modulating gut microbiota in high-fat-fed and streptozotocin-induced mice. J Appl Microbiol 2022; 133:3126-3138. [PMID: 35951725 DOI: 10.1111/jam.15773] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/09/2022] [Indexed: 11/30/2022]
Abstract
AIMS Type 2 diabetes mellitus (T2D) is a chronic disease that manifests as endocrine and metabolic disorders that seriously threatening public health. This study aimed to investigate the effects of Bacillus sp. DU-106 on anti-diabetic effects and gut microbiota in C57BL/6J mice fed a high-fat diet and streptozotocin-induced T2D. METHODS AND RESULTS Bacillus sp. DU-106 was administered to model mice for eight consecutive weeks. Oral administration of Bacillus sp. DU-106 decreased food and water intake and alleviated body weight loss. Moreover, Bacillus sp. DU-106 imparted several health benefits to mice, including balanced blood glucose, alleviation of insulin resistance in T2D mice, and an improvement in lipid metabolism. Furthermore, Bacillus sp. DU-106 protected against liver and pancreatic impairment. Additionally, Bacillus sp. DU-106 treatment reshaped intestinal flora by enhancing gut microbial diversity and enriching the abundance of certain functional bacteria. CONCLUSION Collectively, these findings suggest that Bacillus sp. DU-106 can ameliorate T2D by regulating the gut microbiota. SIGNIFICANCE AND IMPACT OF STUDY Therefore, a novel probiotic, Bacillus sp. DU-106 may be a promising therapeutic agent for improving and alleviating T2D in mice.
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Affiliation(s)
- Jing Yan
- College of Food Science, South China Agricultural University, 510640, Guangzhou, Guangdong, China
| | - Junjian Li
- College of Food Science, South China Agricultural University, 510640, Guangzhou, Guangdong, China
| | - Qiuyan Xue
- College of Food Science, South China Agricultural University, 510640, Guangzhou, Guangdong, China
| | - Shiqing Xie
- College of Food Science, South China Agricultural University, 510640, Guangzhou, Guangdong, China
| | - Jinjin Jiang
- Guangzhou City Polytechnic, 510405, Guangzhou, Guangdong, China
| | - Pan Li
- College of Food Science, South China Agricultural University, 510640, Guangzhou, Guangdong, China
| | - Bing Du
- College of Food Science, South China Agricultural University, 510640, Guangzhou, Guangdong, China
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Pintarič M, Langerholc T. Probiotic Mechanisms Affecting Glucose Homeostasis: A Scoping Review. Life (Basel) 2022; 12:1187. [PMID: 36013366 PMCID: PMC9409775 DOI: 10.3390/life12081187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 02/08/2023] Open
Abstract
The maintenance of a healthy status depends on the coexistence between the host organism and the microbiota. Early studies have already focused on the nutritional properties of probiotics, which may also contribute to the structural changes in the gut microbiota, thereby affecting host metabolism and homeostasis. Maintaining homeostasis in the body is therefore crucial and is reflected at all levels, including that of glucose, a simple sugar molecule that is an essential fuel for normal cellular function. Despite numerous clinical studies that have shown the effect of various probiotics on glucose and its homeostasis, knowledge about the exact function of their mechanism is still scarce. The aim of our review was to select in vivo and in vitro studies in English published in the last eleven years dealing with the effects of probiotics on glucose metabolism and its homeostasis. In this context, diverse probiotic effects at different organ levels were highlighted, summarizing their potential mechanisms to influence glucose metabolism and its homeostasis. Variations in results due to different methodological approaches were discussed, as well as limitations, especially in in vivo studies. Further studies on the interactions between probiotics, host microorganisms and their immunity are needed.
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Affiliation(s)
- Maša Pintarič
- Department of Microbiology, Biochemistry, Molecular Biology and Biotechnology, Faculty of Agriculture and Life Sciences, University of Maribor, Pivola 10, 2311 Hoče, Slovenia;
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31
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Beneficial effects of probiotic supplementation on glucose and triglycerides in a mouse model of metabolic syndrome. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Ermolenko E, Simanenkova A, Voropaeva L, Lavrenova N, Kotyleva M, Minasian S, Chernikova A, Timkina N, Gladyshev N, Dmitriev A, Suvorov A, Galagudza M, Karonova T. Metformin Influence on the Intestinal Microbiota and Organism of Rats with Metabolic Syndrome. Int J Mol Sci 2022; 23:6837. [PMID: 35743280 PMCID: PMC9224185 DOI: 10.3390/ijms23126837] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/12/2022] [Accepted: 06/13/2022] [Indexed: 01/27/2023] Open
Abstract
Metformin is a first-line drug for DM2 treatment and prevention, but its complex effect on impaired glucose tolerance (IGT), including its influence on myocardial resistance to ischemia-reperfusion injury, is not completely studied. We aimed to evaluate the influence of metformin on the intestinal microbiota (IM), metabolism, and functional and morphological characteristics of myocardium in rats with IGT. IGT was modelled in SPF Wistar rats with a high-fat diet and streptozotocin and nicotinamide injection. Rats were divided into three groups: IGT (without treatment), IGT MET (metformin therapy), and CRL (without IGT induction and treatment). IGT group was characterized by: higher body weight, increased serum glucose and total cholesterol levels, atherogenic coefficient, impairment in the functional parameters of the isolated heart during perfusion, and larger myocardium infarction (MI) size in comparison with the CRL group. IM of IGT rats differed from that of CRL: an increase of Bacteroides, Acinetobacter, Akkermansia, Roseburia, and a decrease of Lactobacillus genera representation. Metformin therapy led to the diminishing of metabolic syndrome (MS) symptoms, which correlated with IM restoration, especially with the growth of Akkermansia spp. and decline of Roseburia populations and their influence on other members of IM. The obtained results allow us to consider from a new point of view the expediency of probiotic A. muciniphila use for MS treatment.
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Affiliation(s)
- Elena Ermolenko
- Federal State Budgetary Institution “Institute of Experimental Medicine”, 197376 Saint Petersburg, Russia; (L.V.); (N.L.); (M.K.); (N.G.); (A.D.); or (A.S.)
| | - Anna Simanenkova
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia; (A.S.); (S.M.); (A.C.); (N.T.); (M.G.); (T.K.)
| | - Lyubov Voropaeva
- Federal State Budgetary Institution “Institute of Experimental Medicine”, 197376 Saint Petersburg, Russia; (L.V.); (N.L.); (M.K.); (N.G.); (A.D.); or (A.S.)
| | - Nadezhda Lavrenova
- Federal State Budgetary Institution “Institute of Experimental Medicine”, 197376 Saint Petersburg, Russia; (L.V.); (N.L.); (M.K.); (N.G.); (A.D.); or (A.S.)
| | - Maryna Kotyleva
- Federal State Budgetary Institution “Institute of Experimental Medicine”, 197376 Saint Petersburg, Russia; (L.V.); (N.L.); (M.K.); (N.G.); (A.D.); or (A.S.)
| | - Sarkis Minasian
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia; (A.S.); (S.M.); (A.C.); (N.T.); (M.G.); (T.K.)
| | - Alena Chernikova
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia; (A.S.); (S.M.); (A.C.); (N.T.); (M.G.); (T.K.)
| | - Natalya Timkina
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia; (A.S.); (S.M.); (A.C.); (N.T.); (M.G.); (T.K.)
| | - Nikita Gladyshev
- Federal State Budgetary Institution “Institute of Experimental Medicine”, 197376 Saint Petersburg, Russia; (L.V.); (N.L.); (M.K.); (N.G.); (A.D.); or (A.S.)
| | - Alexander Dmitriev
- Federal State Budgetary Institution “Institute of Experimental Medicine”, 197376 Saint Petersburg, Russia; (L.V.); (N.L.); (M.K.); (N.G.); (A.D.); or (A.S.)
| | - Alexander Suvorov
- Federal State Budgetary Institution “Institute of Experimental Medicine”, 197376 Saint Petersburg, Russia; (L.V.); (N.L.); (M.K.); (N.G.); (A.D.); or (A.S.)
| | - Michael Galagudza
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia; (A.S.); (S.M.); (A.C.); (N.T.); (M.G.); (T.K.)
| | - Tatiana Karonova
- Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia; (A.S.); (S.M.); (A.C.); (N.T.); (M.G.); (T.K.)
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Kumari VBC, Huligere SS, Ramu R, Naik Bajpe S, Sreenivasa MY, Silina E, Stupin V, Achar RR. Evaluation of Probiotic and Antidiabetic Attributes of Lactobacillus Strains Isolated From Fermented Beetroot. Front Microbiol 2022; 13:911243. [PMID: 35774469 PMCID: PMC9237538 DOI: 10.3389/fmicb.2022.911243] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 05/09/2022] [Indexed: 12/16/2022] Open
Abstract
Fermented foods are sources of functionally salient microbes. These microbes when ingested can regulate biomolecule metabolism which has a plethora of health benefits. Lactic acid bacteria species (LABs) isolated from fermented beetroot were biochemically characterized and validated using 16s rRNA sequence. Also, an in vitro assay was conducted to confirm the probiotic activity of the isolates. The cell-free supernatant (CS), cell-free extract (CE), and intact cell (IC) were evaluated for α-glucosidase and α-amylase inhibition. The six isolates RAMULAB01–06 were categorized to be Lactobacillus spp. by observing phenotypic and biochemical characters. Molecular validation using 16S rDNA sequencing, followed by homology search in NCBI database, suggested that the isolates are >95% similar to L. paracasei and L. casei. Also, isolates exhibited probiotic potential with a high survival rate (>96%) in the gastrointestinal condition, and adherence capability (>53%), colonization (>86%), antibacterial, and antibiotic activity. The safety assessments expressed that the isolates are safe. The α-glucosidase and α-amylase inhibition by CS, CE, and IC ranged from 3.97 ± 1.42% to 53.91 ± 3.11% and 5.1 ± 0.08% to 57.15 ± 0.56%, respectively. Hence, these species have exceptional antidiabetic potential which could be explicated to its use as a functional food and health-related food products.
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Affiliation(s)
- V. B. Chandana Kumari
- Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysore, India
| | - Sujay S. Huligere
- Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysore, India
| | - Ramith Ramu
- Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysore, India
- *Correspondence: Ramith Ramu ; orcid.org/0000-0003-2776-5815
| | - Shrisha Naik Bajpe
- Department of Biotechnology, Sri Dharmasthala Manjunatheshwara College (Autonomous), Ujire, India
| | - M. Y. Sreenivasa
- Department of Studies in Microbiology, University of Mysore, Mysore, India
| | - Ekaterina Silina
- Department of Human Pathology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Institute of Biodesign and Modeling of Complex Systems, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Victor Stupin
- Department of Hospital Surgery 1, N.I. Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia
| | - Raghu Ram Achar
- Division of Biochemistry, School of Life Sciences, JSS Academy of Higher Education and Research, Mysore, India
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Kumari V. B. C, Huligere SS, Shbeer AM, Ageel M, M. K. J, S. JC, Ramu R. Probiotic Potential Lacticaseibacillus casei and Limosilactobacillus fermentum Strains Isolated from Dosa Batter Inhibit α-Glucosidase and α-Amylase Enzymes. Microorganisms 2022; 10:1195. [PMID: 35744713 PMCID: PMC9228708 DOI: 10.3390/microorganisms10061195] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 02/04/2023] Open
Abstract
Fermented food plays a major role in gastrointestinal health, as well as possesses other health benefits, such as beneficiary effects in the management of diabetes. Probiotics are thought to be viable sources for enhancing the microbiome of the human gut. In the present study, using biochemical, physiological, and molecular approaches, the isolated Lactobacillus spp. from dosa batter were identified. The cell-free supernatant (CS), cell-free extract (CE), and intact cells (IC) were evaluated for their inhibitory potential against the carbohydrate hydrolyzing enzymes α-glucosidase and α-amylase. Then, 16S rDNA amplification and sequencing were used to identify the species. A homology search in NCBI database was performed that suggests the isolates are >95% similar to Limosilactobacillus fermentum and Lacticaseibacillus casei. Different standard parameters were used to evaluate the probiotic potential of strains RAMULAB07, RAMULAB08, RAMULAB09, RAMULAB10, RAMULAB11, and RAMULAB12. The strains expressed a significant tolerance to the gastric and intestinal juices with a higher survival rate (>98%). A high adhesion capability was observed by the isolates exhibited through hydrophobicity (>65%), aggregation assays (>75%), and adherence assay on HT-29 cells (>82%) and buccal epithelial cells. In addition, the isolates expressed antibacterial and antibiotic properties. Safety assessments (DNase and hemolytic assay) revealed that the isolates could be classified as safe. α-glucosidase and α-amylase inhibition of the isolates for CS, CE, and IC ranged from 7.50% to 65.01% and 20.21% to 56.91%, respectively. The results suggest that these species have exceptional antidiabetic potential, which may be explained by their use as foods that can have health-enhancing effects beyond basic nutrition.
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Affiliation(s)
- Chandana Kumari V. B.
- Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India; (C.K.V.B.); (S.S.H.)
| | - Sujay S. Huligere
- Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India; (C.K.V.B.); (S.S.H.)
| | - Abdullah M. Shbeer
- Department of Surgery, Faculty of Medicine, Jazan University, Jazan 45142, Saudi Arabia; (A.M.S.); (M.A.)
| | - Mohammed Ageel
- Department of Surgery, Faculty of Medicine, Jazan University, Jazan 45142, Saudi Arabia; (A.M.S.); (M.A.)
| | - Jayanthi M. K.
- Department of Pharmacology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India;
| | - Jagadeep Chandra S.
- Department of Microbiology, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India;
| | - Ramith Ramu
- Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India; (C.K.V.B.); (S.S.H.)
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Sumlu E, Bostancı A, Sadi G, Alçığır ME, Akar F. Lactobacillus plantarum improves lipogenesis and IRS-1/AKT/eNOS signalling pathway in the liver of high-fructose-fed rats. Arch Physiol Biochem 2022; 128:786-794. [PMID: 32067511 DOI: 10.1080/13813455.2020.1727527] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
In the present study, we investigated the influence of Lactobacillus plantarum and Lactobacillus helveticus supplementation on lipogenesis, insulin signalling and glucose transporters in liver of high-fructose-fed rats. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Lactobacillus plantarum and L. helveticus supplementations were performed by gastric gavage once a day during final 6 weeks. Dietary high-fructose increased hepatic weight, lipid accumulation and FASN expression as well as caused a significant reduction in IRS-1 expression, pAKT/total AKT and peNOS/total eNOS ratios, but an elevation in GLUT2 and GLUT5 mRNAs in the liver. Lactobacillus plantarum supplementation decreased hepatic weight, triglyceride content and FASN expression as well as improved IRS-1/AKT/eNOS pathway and GLUT2 expression in the liver of high-fructose-fed rats. However, L. helveticus supplementation exerted a restoring effect on lipid accumulation by decreasing FASN expression, and regulating effect on IRS-1 and GLUT2 expressions.
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Affiliation(s)
- Esra Sumlu
- Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
| | - Aykut Bostancı
- Department of Biology, K.Ö. Science Faculty, Karamanoglu Mehmetbey University, Karaman, Turkey
| | - Gökhan Sadi
- Department of Biology, K.Ö. Science Faculty, Karamanoglu Mehmetbey University, Karaman, Turkey
| | - Mehmet Eray Alçığır
- Department of Pathology, Faculty of Veterinary Medicine, Kırıkkale University, Kırıkkale, Turkey
| | - Fatma Akar
- Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
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Wang X, Wang Y, Han M, Liang J, Zhang M, Bai X, Yue T, Gao Z. Evaluating the changes in phytochemical composition, hypoglycemic effect, and influence on mice intestinal microbiota of fermented apple juice. Food Res Int 2022; 155:110998. [DOI: 10.1016/j.foodres.2022.110998] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 01/07/2022] [Accepted: 01/17/2022] [Indexed: 01/11/2023]
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Acrylamide induced glucose metabolism disorder in rats involves gut microbiota dysbiosis and changed bile acids metabolism. Food Res Int 2022; 157:111405. [DOI: 10.1016/j.foodres.2022.111405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 05/05/2022] [Accepted: 05/21/2022] [Indexed: 11/18/2022]
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Liu Y, Zheng S, Cui J, Guo T, Zhang J. Lactiplantibacillus plantarum Y15 alleviate type 2 diabetes in mice via modulating gut microbiota and regulating NF-κB and insulin signaling pathway. Braz J Microbiol 2022; 53:935-945. [PMID: 35150432 PMCID: PMC8853432 DOI: 10.1007/s42770-022-00686-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 01/26/2022] [Indexed: 12/12/2022] Open
Abstract
Probiotics have been used for the treatment of chronic metabolic diseases, including type 2 diabetes (T2D). However, the mechanisms of antidiabetic effects are not well understood. The object of this study is to assess the antidiabetic effect of Lactiplantibacillus plantarum Y15 isolated from Chinese traditional dairy products in vivo. Results revealed that L. plantarum Y15 administration improved the biochemical indexes related to diabetes, reduced pro-inflammatory cytokines, L. plantarum Y15 administration reshaped the structure of gut microbiota, decreased the abundance of LPS-producing, and increased short-chain fatty acids (SCFAs)-producing bacteria, which subsequently reduce the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines. L. plantarum Y15 administration also regulated the expressions of the inflammation and insulin signaling pathway-related genes. These results suggest that L. plantarum Y15 may serve as a potential probiotic for developing food products to ameliorate T2D.
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Affiliation(s)
- Yin Liu
- School of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou, 450002, Henan, China.
| | - Shujuan Zheng
- School of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou, 450002, Henan, China
| | - Jiale Cui
- School of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou, 450002, Henan, China
| | - Tingting Guo
- School of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou, 450002, Henan, China
| | - Jingtao Zhang
- School of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou, 450002, Henan, China
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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: 38] [Impact Index Per Article: 9.5] [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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Ghorbani Y, Schwenger KJP, Allard JP. Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes. Eur J Nutr 2021; 60:2361-2379. [PMID: 33651137 DOI: 10.1007/s00394-021-02520-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 02/16/2021] [Indexed: 12/11/2022]
Abstract
PURPOSE Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions. RESULTS This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D. CONCLUSION There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.
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Affiliation(s)
- Yasaman Ghorbani
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Toronto General Hospital, University Health Network, Toronto, Canada
| | | | - Johane P Allard
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
- Toronto General Hospital, University Health Network, Toronto, Canada.
- Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
- Department of Medicine, University of Toronto, Toronto, Canada.
- Department of Medicine, Division of Gastroenterology, Toronto General Hospital, 585 University Avenue, 9N-973, Toronto, ON, M5G 2N2, Canada.
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Lactobacillus plantarum Reduces Low-Grade Inflammation and Glucose Levels in a Mouse Model of Chronic Stress and Diabetes. Infect Immun 2021; 89:e0061520. [PMID: 34001561 DOI: 10.1128/iai.00615-20] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
This study aimed to examine the effects of Lactobacillus plantarum, a lactic acid bacteria strain isolated from kimchi, on the development of low-grade inflammation and type 2 diabetes mellitus (T2DM) exacerbated by chronic stress. C57BL/6 mice were fed either a high-fat diet (HFD) and randomized into an HFD group or a group that was fed an HFD and subjected to chronic cold exposure-related stress (HFDS), or mice were fed a normal diet (ND) and randomized into an ND group or a group that was fed an ND and subjected to chronic cold exposure-related stress (NDS). Lactobacillus plantarum LRCC5310 (108, 1010 CFU) and LRCC5314 (108, 1010 CFU) as well as L. gasseri BNR17 (108 CFU), as a positive control, were administered orally twice every day to all the mice for 12 weeks. The expression of Glut4 and adiponectin, main glucose transporter-related genes, was upregulated in the LRCC5310- and LRCC5314-treated groups. Levels of serum proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]) and of mRNAs of proinflammatory genes (Tnf-α, Il-6, Ccl2, leptin) were elevated in HFDS mice. The expression of proinflammatory genes was downregulated in LRCC5310- and LRCC5314-treated groups; this was not the case for Tnf-α expression in HFDS mice. Levels of serum corticosterone and mRNA levels of stress-related genes (Npy, Y2r) were decreased in lactic acid bacteria (LAB)-fed groups, with only LRCC5314 downregulating Npy expression in HFDS mice. These results suggest that the LAB strains can normalize the expression of metabolic genes, inhibit inflammatory responses, and suppress stress in HFDS mice.
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Role of Postbiotics in Diabetes Mellitus: Current Knowledge and Future Perspectives. Foods 2021; 10:foods10071590. [PMID: 34359462 PMCID: PMC8306164 DOI: 10.3390/foods10071590] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/29/2021] [Accepted: 07/06/2021] [Indexed: 12/12/2022] Open
Abstract
In the last decade, the gastrointestinal microbiota has been recognised as being essential for health. Indeed, several publications have documented the suitability of probiotics, prebiotics, and symbiotics in the management of different diseases such as diabetes mellitus (DM). Advances in laboratory techniques have allowed the identification and characterisation of new biologically active molecules, referred to as “postbiotics”. Postbiotics are defined as functional bioactive compounds obtained from food-grade microorganisms that confer health benefits when administered in adequate amounts. They include cell structures, secreted molecules or metabolic by-products, and inanimate microorganisms. This heterogeneous group of molecules presents a broad range of mechanisms and may exhibit some advantages over traditional “biotics” such as probiotics and prebiotics. Owing to the growing incidence of DM worldwide and the implications of the microbiota in the disease progression, postbiotics appear to be good candidates as novel therapeutic targets. In the present review, we summarise the current knowledge about postbiotic compounds and their potential application in diabetes management. Additionally, we envision future perspectives on this topic. In summary, the results indicate that postbiotics hold promise as a potential novel therapeutic strategy for DM.
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Zheng F, Wang Z, Stanton C, Ross RP, Zhao J, Zhang H, Yang B, Chen W. Lactobacillus rhamnosus FJSYC4-1 and Lactobacillus reuteri FGSZY33L6 alleviate metabolic syndrome via gut microbiota regulation. Food Funct 2021; 12:3919-3930. [PMID: 33977963 DOI: 10.1039/d0fo02879g] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Metabolic syndrome, which includes a series of metabolic disorders such as hyperglycemia, hyperlipidemia, insulin resistance and obesity, has become a catastrophic disease worldwide. Accordingly, probiotic intervention is a new strategy to alleviate metabolic syndrome, which can adjust the gut microbiota to a certain extent. The aim of the current work was to explore the alleviation of metabolic syndrome by Lactobacillus reuteri and L. rhamnosus. Two L. reuteri and two L. rhamnosus strains were administered to mice with a high-fat diet for 12 weeks. All Lactobacillus strains tested significantly slowed weight gain in the mice. Among four strains, L. reuteri FGSZY33L6 and L. rhamnosus FJSYC4-1 showed the strongest ability to relieve blood glucose disorders, blood lipid disorders, tissue damage, and particularly gut microbiota disorders. Thus, our findings indicate that these strains can regulate the gut microbiota and produce short-chain fatty acids (SCFAs), which can induce satiety hormones, inhibit food intake and increase satiety, and thus improve metabolic syndrome.
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Affiliation(s)
- Fuli Zheng
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. and School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Zhi Wang
- Department of Cardiopulmonary Rehabilitation, Wuxi Tongren Rehabilitation Hospital, Wuxi, China.
| | - Catherine Stanton
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China and APC Microbiome Ireland, University College Cork, Cork, Ireland and Teagasc Food Research Centre, Moorepark, Co. Cork, Ireland
| | - R Paul Ross
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China and APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. and School of Food Science and Technology, Jiangnan University, Wuxi, China and International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. and School of Food Science and Technology, Jiangnan University, Wuxi, China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China and Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi, China
| | - Bo Yang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. and School of Food Science and Technology, Jiangnan University, Wuxi, China and International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. and School of Food Science and Technology, Jiangnan University, Wuxi, China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China and Beijing Innovation Center of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, China
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Won G, Choi SI, Kang CH, Kim GH. Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 Ameliorates Insulin Resistance in Palmitic Acid-Induced HepG2 Cells and High Fat Diet-Induced Mice. Microorganisms 2021; 9:1139. [PMID: 34070604 PMCID: PMC8228052 DOI: 10.3390/microorganisms9061139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/21/2021] [Accepted: 05/21/2021] [Indexed: 12/30/2022] Open
Abstract
The purpose of this study was to evaluate the capacity of Lactiplantibacillus plantarum MG4296 (MG4296) and Lacticaseibacillus paracasei MG5012 (MG5012) on insulin resistance (IR) and diabetes-related metabolic changes in palmitic acid (PA)-induced HepG2 cells and high-fat diet-induced mice. In vitro, cell-free extracts of MG4296 and MG5012 alleviated IR by increasing glucose uptake and glycogen content in PA-induced insulin-resistant HepG2 cells. In vivo, MG4296 and MG5012 supplementation markedly decreased body weight and glucose tolerance. Administration of both strains also improved serum glucose, glycated hemoglobin, insulin, triglyceride, LDL/HDL ratio, and homeostatic model assessment of IR (HOMA-IR). Histopathological analysis of liver tissue demonstrated a significant reduction in lipid accumulation and glycogen content. Moreover, MG4296 and MG5012 treatment enhanced phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) expression in the liver. Overall, MG4296 and MG5012 could prevent HFD-induced glucose tolerance and hyperglycemia by improving IR. Therefore, L. plantarum MG4296 and L. paracasei MG5012 could be useful as new probiotics candidates to improve T2DM.
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Affiliation(s)
- Gayeong Won
- Department of Health Functional New Materials, Duksung Women’s University, Seoul 01369, Korea;
| | - Soo-Im Choi
- Department of Health Functional New Materials, Duksung Women’s University, Seoul 01369, Korea;
| | | | - Gun-Hee Kim
- Department of Food and Nutrition, Duksung Women’s University, Seoul 01369, Korea
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Edem EE, Nathaniel BU, Nebo KE, Obisesan AO, Olabiyi AA, Akinluyi ET, Ishola AO. Lactobacillus plantarum mitigates sexual-reproductive deficits by modulating insulin receptor expression in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice. Drug Metab Pers Ther 2021; 36:321-336. [PMID: 34002580 DOI: 10.1515/dmpt-2021-1000195] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 04/05/2021] [Indexed: 01/15/2023]
Abstract
OBJECTIVES Hyperinsulinemia increases the risk factor of diabetes and infertility at a manifold. Lactobacillus plantarum has several medical significances with limited reports. Hence, this study assessed the effect of L. plantarum on sexual-reproductive functions and distribution of insulin receptors in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice. METHODS Forty male adult mice were divided into five groups as follows: control, high-fat diet (HFD) + streptozotocin (STZ), therapeutic, co-administration group type 1 (CO-AD) and probiotics. They were either simultaneously exposed to an HFD and L. plantarum treatment for 28 days with a dose of STZ injection to induce hyperinsulinemia on day 28 or treated with L. plantarum for 14 days, and following induction of hyperinsulinemia. Mice were subjected to a sexual behavioural test and thereafter sacrificed under euthanasia condition. Blood, brain and testes were collected for biochemical and immunohistochemical assays. RESULTS Treatment with L. plantarum ameliorated reproductive hormones activity disruption, sexual behavioural defects, antioxidant imbalance, insulin dysregulation and lipid metabolism dysfunction following exposure to HFD + STZ when compared to the hyperinsulinemic untreated mice. CONCLUSIONS Taken together, data from this study reveal that L. plantarum abrogated hyperinsulinemia-induced male sexual and reproductive deficits by modulating antioxidant status, lipid metabolism and insulin signalling in the hypothalamic-pituitary-testicular axis of mice.
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Affiliation(s)
- Edem Ekpenyong Edem
- Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
| | - Blessing Uyo Nathaniel
- Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
| | - Kate Eberechukwu Nebo
- Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
| | - Abiola Oluwatosin Obisesan
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
| | - Ayodeji Augustine Olabiyi
- Department of Medical Biochemistry, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
| | - Elizabeth Toyin Akinluyi
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
| | - Azeez Olakunle Ishola
- Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria
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Guan Y, Sun H, Chen H, Li P, Shan Y, Li X. Physicochemical characterization and the hypoglycemia effects of polysaccharide isolated from Passiflora edulis Sims peel. Food Funct 2021; 12:4221-4230. [PMID: 33876796 DOI: 10.1039/d0fo02965c] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
One polysaccharide, designated as WPEP-A, was isolated from Passiflora edulis Sims peel and its hypoglycemic effects on diabetic db/db mice were evaluated. Physicochemical characterization showed that WPEP-A was composed of galactose, glucose, xylose, rhamnose, galacturonic acid and glucuronic acid with a molecular weight of 9.51 × 104 Da. We observed an inhibition in weight gain and blood glucose levels. Glucose tolerance and insulin tolerance improved after the administration of WPEP-A. In addition, our data showed increased antioxidant enzyme activities. Furthermore, the levels of serum insulin and triglyceride decreased with the recovery of liver damage. Meanwhile, positive changes in short chain fatty acid content were observed, and the mRNA levels of glucagon-like peptide 1 receptor, glucagon and prohormone convertase 3 were up-regulated in the intestinal tract. In summary, our results showed that WPEP-A had hypoglycemic activity and improved intestinal function in diabetic mice, which may contribute to the attenuation of the hypoglycemia effects.
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Affiliation(s)
- Yuan Guan
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Hefei Sun
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Huiying Chen
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Peijun Li
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Yang Shan
- Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China
| | - Xia Li
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
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Huda MN, Kim M, Bennett BJ. Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes. Front Endocrinol (Lausanne) 2021; 12:632335. [PMID: 33897618 PMCID: PMC8060771 DOI: 10.3389/fendo.2021.632335] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 02/04/2021] [Indexed: 12/20/2022] Open
Abstract
Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.
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Affiliation(s)
- M. Nazmul Huda
- Department of Nutrition, University of California Davis, Davis, CA, United States
- Obesity and Metabolism Research Unit, United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Davis, CA, United States
| | - Myungsuk Kim
- Department of Nutrition, University of California Davis, Davis, CA, United States
- Obesity and Metabolism Research Unit, United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Davis, CA, United States
| | - Brian J. Bennett
- Department of Nutrition, University of California Davis, Davis, CA, United States
- Obesity and Metabolism Research Unit, United States Department of Agriculture (USDA), Agricultural Research Service (ARS), Western Human Nutrition Research Center, Davis, CA, United States
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Lee CB, Chae SU, Jo SJ, Jerng UM, Bae SK. The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus. Int J Mol Sci 2021; 22:ijms22073566. [PMID: 33808194 PMCID: PMC8037857 DOI: 10.3390/ijms22073566] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/22/2021] [Accepted: 03/27/2021] [Indexed: 02/08/2023] Open
Abstract
Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.
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Affiliation(s)
- Chae Bin Lee
- College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Korea; (C.B.L.); (S.U.C.); (S.J.J.)
| | - Soon Uk Chae
- College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Korea; (C.B.L.); (S.U.C.); (S.J.J.)
| | - Seong Jun Jo
- College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Korea; (C.B.L.); (S.U.C.); (S.J.J.)
| | - Ui Min Jerng
- Department of Internal Medicine, College of Korean Medicine, Sangji University, Wonju 26339, Korea;
| | - Soo Kyung Bae
- College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Korea; (C.B.L.); (S.U.C.); (S.J.J.)
- Correspondence: ; Tel.: +82-2-2164-4054
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Screening of novel potential antidiabetic Lactobacillus plantarum strains based on in vitro and in vivo investigations. Lebensm Wiss Technol 2021. [DOI: 10.1016/j.lwt.2020.110526] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Archer AC, Muthukumar SP, Halami PM. Lactobacillus fermentum MCC2759 and MCC2760 Alleviate Inflammation and Intestinal Function in High-Fat Diet-Fed and Streptozotocin-Induced Diabetic Rats. Probiotics Antimicrob Proteins 2021; 13:1068-1080. [PMID: 33575913 PMCID: PMC8342349 DOI: 10.1007/s12602-021-09744-0] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2021] [Indexed: 12/12/2022]
Abstract
The growing incidence of type 2 diabetes and obesity has become a worldwide crisis with increased socio-economic burden. Changes in lifestyle and food habits resulting in dysbiosis of the gut microbiota and low-grade inflammation are linked to the rising incidence. The aim of this study was to investigate the effects of potential probiotic Lactobacillus fermentum MCC2759 and MCC2760 on intestinal markers of inflammation using a high-fat diet (HFD)-fed model and a streptozotocin (STZ)-induced diabetic model. Lact. fermentum administration showed improved oral glucose tolerance compared with the model controls of HFD (AUC 1518) and STZ (628.8). Plasma insulin levels improved in the Lact. fermentum treated groups of HFD + MCC2759 (129 ± 4.24 pmol/L) and HFD + MCC2760 (151.5 ± 9.19 pmol/L) in HFD study, while in STZ diabetic study, the insulin levels were normalized with Lact. fermentum administration, for D + MCC2759 (120.5 ± 7.77) and D + MCC2760 (138 ± 5.65 pmol/L) groups. The results showed reduction in inflammatory tone in liver, muscle, and adipose tissues of rats in both models with stimulation of anti-inflammatory IL-10 by real-time quantitative polymerase chain reaction. Additionally, the potential probiotic cultures also displayed normalization of markers related to intestinal barrier integrity (ZO-1), TLR-4 receptor, and insulin sensitivity (GLUT-4, GLP-1, adiponectin). Thus, the results suggest that Lact. fermentum could act as potential probiotic for lifestyle-related disorders such as obesity, diabetes, and metabolic syndrome as both prophylactic and adjunct therapies.
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Affiliation(s)
| | - Serva Peddha Muthukumar
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, 570020, Mysuru, India
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