1
|
Du W, Zou ZP, Ye BC, Zhou Y. Gut microbiota and associated metabolites: key players in high-fat diet-induced chronic diseases. Gut Microbes 2025; 17:2494703. [PMID: 40260760 PMCID: PMC12026090 DOI: 10.1080/19490976.2025.2494703] [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: 01/03/2025] [Revised: 02/26/2025] [Accepted: 04/11/2025] [Indexed: 04/24/2025] Open
Abstract
Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.
Collapse
Affiliation(s)
- Wei Du
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Zhen-Ping Zou
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Bang-Ce Ye
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Ying Zhou
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| |
Collapse
|
2
|
Xia J, Wang Y, Li X, Liu L, Zhang P, Dai W, Luo P, Wang G, Li Y. The mechanism of perilla oil in regulating lipid metabolism. Food Chem 2025; 476:143318. [PMID: 39977980 DOI: 10.1016/j.foodchem.2025.143318] [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: 09/18/2024] [Revised: 02/05/2025] [Accepted: 02/08/2025] [Indexed: 02/22/2025]
Abstract
Emerging science supports the role of lipid metabolism disorders in the occurrence and development of chronic diseases. Dietary intervention has been shown to be an effective strategy for regulating lipid metabolism. Recent studies showed that perilla is rich in various effective ingredients, including fatty acids, flavonoids, and phenolic acids. These ingredients exhibit a myriad of benefits, notably enhancing intestinal health and helping to manage metabolic diseases. Perilla oil stands out as a promising agent for regulating lipid metabolism, underscoring its potential for various health applications. This review introduces the active ingredients in perilla and provides a systematic overview of the mechanism by which perilla oil regulates lipid metabolism to expand its application value. Further research should focus on exploring the dose effect and absorption efficiency of perilla oil in clinical applications.
Collapse
Affiliation(s)
- Jiawei Xia
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China; Guizhou Rapeseed Institute, Guizhou Province Academy of Agricultural Sciences, No. 270-0061 Baiyun Road, Jinyang District, Guiyang, Guizhou 550008, China
| | - Yi Wang
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Xin Li
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Li Liu
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Pin Zhang
- Guizhou Rapeseed Institute, Guizhou Province Academy of Agricultural Sciences, No. 270-0061 Baiyun Road, Jinyang District, Guiyang, Guizhou 550008, China
| | - Wendong Dai
- Guizhou Rapeseed Institute, Guizhou Province Academy of Agricultural Sciences, No. 270-0061 Baiyun Road, Jinyang District, Guiyang, Guizhou 550008, China
| | - Peng Luo
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China
| | - Guoze Wang
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China.
| | - Yanhong Li
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, School of Public Health, Guizhou Medical University, Guiyang 561113, China.
| |
Collapse
|
3
|
Gopalakrishnan V, Kumar C, Robertsen I, Morehouse C, Sparklin B, Khader S, Henry I, Johnson LK, Hertel JK, Christensen H, Sandbu R, Greasley PJ, Sellman BR, Åsberg A, Andersson S, Löfmark RJ, Hjelmesæth J, Karlsson C, Cohen TS. A multi-omics microbiome signature is associated with the benefits of gastric bypass surgery and is differentiated from diet induced weight loss through 2 years of follow-up. Mucosal Immunol 2025:S1933-0219(25)00040-6. [PMID: 40222615 DOI: 10.1016/j.mucimm.2025.04.002] [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: 10/14/2024] [Revised: 03/04/2025] [Accepted: 04/07/2025] [Indexed: 04/15/2025]
Abstract
Roux-en-Y gastric bypass (GBP) surgery is an effective treatment for reducing body weight and correcting metabolic dysfunction in individuals with severe obesity. Herein, we characterize the differences between very low energy diet (VLED) and GBP induced weight loss by multi-omic analyses of microbiome and host features in a non-randomized, controlled, single-center study. Eighty-eight participants with severe obesity were recruited into two arms - GBP versus VLED with matching weight loss for 6 weeks and 2-years of follow-up. A dramatic shift in the distribution of gut microbial taxa and their functional capacity was seen in the GBP group at Week 2 after surgery and was sustained through 2 years. Multi-omic analyses were performed after 6 weeks of matching weight loss between the GBP and VLED groups, which pointed to microbiome derived metabolites such as indoxyl sulphate as characterizing the GBP group. We also identified an inverse association between Streptococcus parasanguinis (an oral commensal) and plasma levels of tryptophan and tyrosine. These data have important implications, as they reveal a significant robust restructuring of the microbiome away from a baseline dysbiotic state in the GBP group. Furthermore, multi-omics modelling points to potentially novel mechanistic insights at the intersection of the microbiome and host.
Collapse
Affiliation(s)
| | - Chanchal Kumar
- Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
| | - Ida Robertsen
- Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, PO 1068 Blindern, 0316 Oslo, Norway
| | - Christopher Morehouse
- Discovery Microbiome, Early Vaccines and Immune Therapies, Biopharmaceuticals R&D, AstraZeneca, USA
| | - Ben Sparklin
- Discovery Microbiome, Early Vaccines and Immune Therapies, Biopharmaceuticals R&D, AstraZeneca, USA
| | - Shameer Khader
- Data Science and Artificial Intelligence, Biopharmaceuticals R&D, AstraZeneca, USA.
| | - Ian Henry
- Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Line Kristin Johnson
- Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, P.O.Box 2168, 3103 Tønsberg, Norway
| | - Jens K Hertel
- Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, P.O.Box 2168, 3103 Tønsberg, Norway
| | - Hege Christensen
- Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, PO 1068 Blindern, 0316 Oslo, Norway
| | - Rune Sandbu
- Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, P.O.Box 2168, 3103 Tønsberg, Norway
| | - Peter J Greasley
- Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Bret R Sellman
- Discovery Microbiome, Early Vaccines and Immune Therapies, Biopharmaceuticals R&D, AstraZeneca, USA
| | - Anders Åsberg
- Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, PO 1068 Blindern, 0316 Oslo, Norway; Department of Transplantation Medicine, Oslo University Hospital, P.O.Box 4950 Nydalen 0424 Oslo, Norway
| | - Shalini Andersson
- Oligonucleotide Discovery, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Rasmus Jansson Löfmark
- Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Jøran Hjelmesæth
- Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, P.O.Box 2168, 3103 Tønsberg, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, 0318 Oslo, Norway
| | - Cecilia Karlsson
- Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Taylor S Cohen
- Late Vaccines and Immune Therapies, Biopharmaceuticals R&D, AstraZeneca, USA.
| |
Collapse
|
4
|
Saad MJA, Santos A. The Microbiota and Evolution of Obesity. Endocr Rev 2025; 46:300-316. [PMID: 39673174 PMCID: PMC11894537 DOI: 10.1210/endrev/bnae033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 09/03/2024] [Accepted: 12/12/2024] [Indexed: 12/16/2024]
Abstract
Obesity is a major global concern and is generally attributed to a combination of genetic and environmental factors. Several hypotheses have been proposed to explain the evolutionary origins of obesity epidemic, including thrifty and drifty genotypes, and changes in thermogenesis. Here, we put forward the hypothesis of metaflammation, which proposes that due to intense selection pressures exerted by environmental pathogens, specific genes that help develop a robust defense mechanism against infectious diseases have had evolutionary advantages and that this may contribute to obesity in modern times due to connections between the immune and energy storage systems. Indeed, incorporating the genetic variations of gut microbiota into the complex genetic framework of obesity makes it more polygenic than previously believed. Thus, uncovering the evolutionary origins of obesity requires a multifaceted approach that considers the complexity of human history, the unique genetic makeup of different populations, and the influence of gut microbiome on host genetics.
Collapse
Affiliation(s)
- Mario J A Saad
- Department of Internal Medicine, School of Medical Sciences, University of Campinas, CEP 13083-887 Campinas, SP, Brazil
| | - Andrey Santos
- Department of Internal Medicine, School of Medical Sciences, University of Campinas, CEP 13083-887 Campinas, SP, Brazil
| |
Collapse
|
5
|
Wu H, Li Y, Jiang Y, Li X, Wang S, Zhao C, Yang X, Chang B, Yang J, Qiao J. Machine learning prediction of obesity-associated gut microbiota: identifying Bifidobacterium pseudocatenulatum as a potential therapeutic target. Front Microbiol 2025; 15:1488656. [PMID: 39974372 PMCID: PMC11839209 DOI: 10.3389/fmicb.2024.1488656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 12/05/2024] [Indexed: 02/21/2025] Open
Abstract
Background The rising prevalence of obesity and related metabolic disorders highlights the urgent need for innovative research approaches. Utilizing machine learning (ML) algorithms to predict obesity-associated gut microbiota and validating their efficacy with specific bacterial strains could significantly enhance obesity management strategies. Methods We leveraged gut microbiome data from 1,563 healthy individuals and 2,043 overweight patients sourced from the GMrepo database. We assessed the anti-obesity effects of Bifidobacterium pseudocatenulatum through experimentation with Caenorhabditis elegans and C3H10T1/2 cells. Results Our analysis revealed a significant correlation between gut bacterial composition and body weight. The top 40 bacterial species were utilized to develop ML models, with XGBoost demonstrating the highest predictive accuracy. SHAP analysis indicated a negative association between the relative abundance of six bacterial species, including B. pseudocatenulatum, and body mass index (BMI). Furthermore, B. pseudocatenulatum was shown to reduce lipid accumulation in C. elegans and inhibit lipid differentiation in C3H10T1/2 cells. Conclusion Bifidobacterium pseudocatenulatum holds potential as a therapeutic agent for managing diet-induced obesity, underscoring its relevance in microbiome-based obesity research and intervention.
Collapse
Affiliation(s)
- Hao Wu
- Zhejiang Institute of Tianjin University (Shaoxing), Shaoxing, China
| | - Yuan Li
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, China
| | - Yuxuan Jiang
- Yidu Cloud (Beijing) Technology Co., Ltd., Beijing, China
| | - Xinran Li
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, China
| | - Shenglan Wang
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, China
| | - Changle Zhao
- Zhejiang Institute of Tianjin University (Shaoxing), Shaoxing, China
- Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
| | - Ximiao Yang
- Zhejiang Institute of Tianjin University (Shaoxing), Shaoxing, China
| | - Baocheng Chang
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, China
| | - Juhong Yang
- NHC Key Lab of Hormones and Development and Tianjin Key Lab of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin, China
- Guangdong Medical University, Zhanjiang, China
| | - Jianjun Qiao
- Zhejiang Institute of Tianjin University (Shaoxing), Shaoxing, China
- Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
| |
Collapse
|
6
|
Ren Y, Tao M, Wang X, Pu X, Guo G, Chen K, Zhao B, Hou Y, Yang X, Xu Y. Gut microbiota and quantitative traits divergence at different altitude of long-tailed dwarf hamsters, Cricetulus longicaudatus. Front Microbiol 2025; 15:1531629. [PMID: 39925881 PMCID: PMC11804260 DOI: 10.3389/fmicb.2024.1531629] [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: 11/20/2024] [Accepted: 12/23/2024] [Indexed: 02/11/2025] Open
Abstract
To investigate the community structure and diversity of gut microflora and their function in body mass regulation, as well as the effects of various locations on gut microbiota and Cricetulus longicaudatus body mass regulation at various elevations. We examined the diversity, abundance, and community structure of the gut microbiota of long-tailed dwarf hamsters from eight regions in Shanxi province during summer using 16S rDNA sequencing technology and analyzed the relationships between these microbiota and environmental variables as well as morphological indicators. The results revealed Firmicutes and Bacteroidetes as the dominant phyla at the phylum level, with Lactobacillus emerging as the predominant genus. We observed differences of gut microflora between different areas, and this diversity is affected by altitude. The high-altitude areas individuals had lower β diversity of gut microbiota than the low-altitude area. Moreover, the body and skull indexes of long-tailed dwarf hamsters also changed with altitude. The result presented in this study indicated that the body size of long-tailed dwarf hamsters conforms to Bergmann's law. And Providencia had significant correlation with body size. Finally, functional analysis of the gut microbiota showed changes in metabolic function that depended on elevation, and collinear network analysis showed how the gut microbiota interacts with each other. All of these results suggest that long-tailed hamsters are different depending on their altitude, with altitude being the main factor affecting both the structure of microbes and the way their metabolism works. This study shows that altitude has a big effect on the gut microbiota and phenotypic traits of long-tailed hamsters. It also shows how well this species can adapt to changes in altitude.
Collapse
Affiliation(s)
- Yue Ren
- College of Plant Protection, Shanxi Agricultural University, Taiyuan, China
| | - Mengfan Tao
- College of Plant Protection, Shanxi Agricultural University, Taiyuan, China
| | | | - Xinsheng Pu
- College of Plant Protection, Shanxi Agricultural University, Taiyuan, China
| | - Guangtong Guo
- College of Plant Protection, Shanxi Agricultural University, Taiyuan, China
| | - Kuiyou Chen
- College of Plant Protection, Shanxi Agricultural University, Taiyuan, China
| | - Bingyu Zhao
- College of Plant Protection, Shanxi Agricultural University, Taiyuan, China
| | - Yu Hou
- College of Plant Protection, Shanxi Agricultural University, Taiyuan, China
| | - Xin'gen Yang
- Shanxi Key Laboratory of Integrated Pest Management in Agriculture, College of Plant Protection, Shanxi Agricultural University, Taiyuan, Shanxi, China
| | - Yumei Xu
- Shanxi Key Laboratory of Integrated Pest Management in Agriculture, College of Plant Protection, Shanxi Agricultural University, Taiyuan, Shanxi, China
| |
Collapse
|
7
|
Hong J, Fu T, Liu W, Yu M, Lin Y, Min C, Lin D. Gut microbiota dynamics in KK-Ay mice: restoration following antibiotic treatment. Folia Microbiol (Praha) 2024; 69:1159-1173. [PMID: 38536641 DOI: 10.1007/s12223-024-01157-0] [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: 10/18/2023] [Accepted: 03/11/2024] [Indexed: 09/07/2024]
Abstract
The primary aim of this study was to investigate the alterations in the microbial community of KK-Ay mice following antibiotic treatment. A comparative analysis of the gut microbiota was conducted between KK-Ay mice treated with antibiotics and those without treatment. The microbial community dynamics in antibiotic-treated KK-Ay mice were meticulously assessed over an eight-week period using 16S rDNA sequencing analysis. Simultaneously, dynamic renal function measurements were performed. The results demonstrated a marked decrease in bacterial DNA abundance following antibiotic intervention, coupled with a substantial reduction in bacterial diversity and a profound alteration in microbial composition. These observed microbiota changes persisted in the KK-Ay mice throughout the eight-week post-antibiotic treatment period. Particularly noteworthy was the reemergence of bacterial populations after two weeks or more, resulting in a microbiota composition resembling that of untreated KK-Ay mice. This transition was characterized by a significant increase in the abundance of clostridia at the class level, Lachnospirales and Oscillospirales at the order level, and Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Concurrently, there was a notable decrease in Clostridia_UCG-014. The observed alterations in the gut microbiota of antibiotic-treated KK-Ay mice suggest a dynamic response to antibiotic intervention and subsequent restoration towards the original untreated state.
Collapse
Affiliation(s)
- Jinni Hong
- Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China
- Guangdong Provincial Institute of Geriatric, Guangzhou, People's Republic of China
| | - Tingting Fu
- Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China
- Guangdong Provincial Institute of Geriatric, Guangzhou, People's Republic of China
| | - Weizhen Liu
- Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China
- Guangdong Provincial Institute of Geriatric, Guangzhou, People's Republic of China
| | - Miao Yu
- Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China
- Guangdong Provincial Institute of Geriatric, Guangzhou, People's Republic of China
| | - Yanshan Lin
- Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China
- Guangdong Provincial Institute of Geriatric, Guangzhou, People's Republic of China
| | - Cunyun Min
- Department of Traditional Chinese Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China
- Guangdong Provincial Institute of Geriatric, Guangzhou, People's Republic of China
| | - Datao Lin
- Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
| |
Collapse
|
8
|
Thabet E, Dief AE, Arafa SAF, Yakout D, Ali MA. Antibiotic-induced gut microbe dysbiosis alters neurobehavior in mice through modulation of BDNF and gut integrity. Physiol Behav 2024; 283:114621. [PMID: 38925433 DOI: 10.1016/j.physbeh.2024.114621] [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: 01/07/2024] [Revised: 05/11/2024] [Accepted: 06/24/2024] [Indexed: 06/28/2024]
Abstract
Gut microbiota is essential for intestinal integrity and brain functions. Herein we aimed to investigate the effects of alteration of gut microbiome using broad-spectrum antibiotics on CD 1 male mice (germ-modified group (GM). Moreover, we co-administrated probiotics with or without antibiotics for four weeks and evaluated if probiotics could reverse these behavioral and intestinal effects. GM, co-administered antibiotics and probiotics, and probiotics-only groups were compared to control mice of the same sex, age, and weight that did not receive either drug (n=12 in all groups). Cultivation of aerobic and anaerobic bacteria was evaluated by fecal culture of all groups. We tested exploratory behavior, anxiety, memory, depression-like behavior, and hippocampal and frontal lobe BDNF protein level alterations in response to antibiotics and its downstream effect on the PI3K/Akt1/Bcl2 pathway. Intestinal integrity was evaluated using gene expression analysis of ZO-1, claudin, and occludin genes. Additionally, the inflammatory TLR4 and p-p38 MAPK pathways in the intestines were investigated. Twice-daily administration of oral antibiotics for four weeks significantly reduced total bacterial count and upregulated TLR4 and p-p38.GM mice showed a significant reduction in BDNF(P =0.04), impaired spatial memory, and long-term memory as evidenced by decreased T maze correct alternation trails and shortened retention time in the passive avoidance test in GM(P =0.01). Passive avoidance showed significantly increased latency after probiotics intake. Depressive-like behavior was more pronounced in GM mice as assessed by the tail suspension test (P =0.01). GM showed significant upregulation(p<0.001) of the TLR4 and p-p38 MAPK pathway. Co-administration of probiotics with antibiotics showed an increase in BDNF levels, and upregulation of the cell survival PI3K/Akt1/Bcl2 pathway, significantly higher relative abundance in the firmucutes members, a significant decrease in the Firmicutes/Bacteroidetes ratio and downregulation of TLR4 and p-p38 MAPK. The tight junction proteins ZO-1, claudin and occludin were downregulated by antibiotic administration for four weeks and restored by probiotics. Collectively, the data suggest that long-term use of antibiotics appears to disrupt the intestinal epithelial barrier and alter neurobehavioral qualities specifically, long-term memory and exploratory drive, possibly through the reduction of BDNF, and probiotics partially reverse these effects. Our study emphasizes the effect of prolonged intake of antibiotics on production of dysbiosis as well as the impact of the antibiotic induced intestinal inflammation on neurobehavioral aspects in mice as the memory and anxiety-like behavior. We also reveal that co-administration of probiotics can reverse these changes.
Collapse
Affiliation(s)
- Eman Thabet
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
| | - Abeer E Dief
- Department of Medical Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Shams A-F Arafa
- Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Dalia Yakout
- Department of Clinical Pharmacology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Mennatallah A Ali
- Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt
| |
Collapse
|
9
|
Liu F, Ye F, Yang Y, Kang Z, Liu Y, Chen W, Wang S, Kou H, Kang L, Sun J. Gut bacteria are essential for development of an invasive bark beetle by regulating glucose transport. Proc Natl Acad Sci U S A 2024; 121:e2410889121. [PMID: 39110737 PMCID: PMC11331112 DOI: 10.1073/pnas.2410889121] [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: 05/31/2024] [Accepted: 07/09/2024] [Indexed: 08/21/2024] Open
Abstract
Insects and their gut bacteria form a tight and beneficial relationship, especially in utilization of host nutrients. The red turpentine beetle (RTB), a destructive and invasive pine pest, employs mutualistic microbes to facilitate its invasion success. However, the molecular mechanism underlying the utilization of nutrients remains unknown. In this study, we found that gut bacteria are crucial for the utilization of D-glucose, a main carbon source for RTB development. Downstream assays revealed that gut bacteria-induced gut hypoxia and the secretion of riboflavin are responsible for RTB development by regulating D-glucose transport via the activation of a hypoxia-induced transcription factor 1 (Hif-1α). Further functional investigations confirmed that Hif-1α mediates glucose transport by direct upregulation of two glucose transporters (ST10 and ST27), thereby promoting RTB development. Our findings reveal how gut bacteria regulate the development of RTB, and promote our understanding of the mutualistic relationship of animals and their gut bacteria.
Collapse
Affiliation(s)
- Fanghua Liu
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Fangyuan Ye
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| | - Yunwen Yang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Zhiwei Kang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Yang Liu
- State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, Haidian District100193, China
| | - Wei Chen
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Saige Wang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Hongru Kou
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| | - Le Kang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| | - Jianghua Sun
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| |
Collapse
|
10
|
Vliex LMM, Penders J, Nauta A, Zoetendal EG, Blaak EE. The individual response to antibiotics and diet - insights into gut microbial resilience and host metabolism. Nat Rev Endocrinol 2024; 20:387-398. [PMID: 38486011 DOI: 10.1038/s41574-024-00966-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2024] [Indexed: 06/16/2024]
Abstract
Antibiotic use disrupts microbial composition and activity in humans, but whether this disruption in turn affects host metabolic health is unclear. Cohort studies show associations between antibiotic use and an increased risk of developing obesity and type 2 diabetes mellitus. Here, we review available clinical trials and show the disruptive effect of antibiotic use on the gut microbiome in humans, as well as its impact on bile acid metabolism and microbial metabolites such as short-chain fatty acids. Placebo-controlled human studies do not show a consistent effect of antibiotic use on body weight and insulin sensitivity at a population level, but rather an individual-specific or subgroup-specific response. This response to antibiotic use is affected by the resistance and resilience of the gut microbiome, factors that determine the extent of disruption and the speed of recovery afterwards. Nutritional strategies to improve the composition and functionality of the gut microbiome, as well as its recovery after antibiotic use (for instance, with prebiotics), require a personalized approach to increase their efficacy. Improved insights into key factors that influence the individual-specific response to antibiotics and dietary intervention may lead to better efficacy in reversing or preventing antibiotic-induced microbial dysbiosis as well as strategies for preventing cardiometabolic diseases.
Collapse
Affiliation(s)
- Lars M M Vliex
- Department of Human Biology, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - John Penders
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Arjen Nauta
- FrieslandCampina, Amersfoort, The Netherlands
| | - Erwin G Zoetendal
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Ellen E Blaak
- Department of Human Biology, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands.
| |
Collapse
|
11
|
Miao S, Yin J, Liu S, Zhu Q, Liao C, Jiang G. Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58:8117-8134. [PMID: 38701366 DOI: 10.1021/acs.est.4c02018] [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: 05/05/2024]
Abstract
Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.
Collapse
Affiliation(s)
- Shiyu Miao
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jia Yin
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- School of Environment, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shuang Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qingqing Zhu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chunyang Liao
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- School of Environment, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guibin Jiang
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
- School of Environment, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
- Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan 430056, China
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China
| |
Collapse
|
12
|
Shi Y, Chen J, Qu D, Sun Q, Yu Y, Zhang H, Liu Z, Sha J, Sun Y. Ginsenoside Rg 5 Activates the LKB1/AMPK/mTOR Signaling Pathway and Modifies the Gut Microbiota to Alleviate Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet. Nutrients 2024; 16:842. [PMID: 38542753 PMCID: PMC10974897 DOI: 10.3390/nu16060842] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/05/2024] [Accepted: 03/09/2024] [Indexed: 01/05/2025] Open
Abstract
The primary objective of this investigation was to elucidate the manner in which ginsenoside Rg5 (Rg5) ameliorates nonalcoholic fatty liver disease (NAFLD) via the modulation of the gut microbiota milieu. We administered either a standard diet (ND) or a high-fat diet (HFD), coupled with 12-week treatment employing two distinct doses of Rg5 (50 and 100 mg/kg/d), to male C57BL/6J mice. In comparison to the HFD cohort, the Rg5-treated group demonstrated significant enhancements in biochemical parameters, exemplified by a substantial decrease in lipid concentrations, as well as the reduced expression of markers indicative of oxidative stress and liver injury. This signifies a mitigation of hepatic dysfunction induced by an HFD. Simultaneously, Rg5 demonstrates the capacity to activate the LKB1/AMPK/mTOR signaling pathway, instigating energy metabolism and consequently hindering the progression of NAFLD. Furthermore, we underscored the role of Rg5 in the treatment of NAFLD within the gut-microbiota-liver axis. Analysis via 16S rRNA sequencing unveiled that Rg5 intervention induced alterations in gut microbiota composition, fostering an increase in beneficial bacteria, such as Bacteroides and Akkermansia, while concurrently reducing the relative abundance of detrimental bacteria, exemplified by Olsenella. Furthermore, employing fecal microbiota transplantation (FMT) experiments, we observed analogous outcomes in mice subjected to fecal bacterial transplants, providing additional verification of the capacity of Rg5 to mitigate NAFLD in mice by actively participating in the restoration of gut microbiota via FMT. Drawing from these data, the regulation of the gut microbiota is recognized as an innovative strategy for treating or preventing NAFLD and metabolic syndrome. Consequently, these research findings suggest that Rg5 holds promise as a potential therapeutic agent for NAFLD management.
Collapse
Affiliation(s)
- Yingying Shi
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (Y.S.); (Q.S.); (H.Z.)
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Jianbo Chen
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Di Qu
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Qiang Sun
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (Y.S.); (Q.S.); (H.Z.)
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Yang Yu
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Hao Zhang
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (Y.S.); (Q.S.); (H.Z.)
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Zhengbo Liu
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Jiyue Sha
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| | - Yinshi Sun
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; (Y.S.); (Q.S.); (H.Z.)
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun 130112, China; (J.C.); (D.Q.); (Y.Y.); (Z.L.)
| |
Collapse
|
13
|
Zhu M, Cheng Y, Tang Y, Li S, Rao P, Zhang G, Xiao L, Liu J. Nanoparticles alleviate non-alcoholic steatohepatitis via ER stress sensor-mediated intestinal barrier damage and gut dysbiosis. Front Microbiol 2024; 14:1271835. [PMID: 38516345 PMCID: PMC10956414 DOI: 10.3389/fmicb.2023.1271835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 10/11/2023] [Indexed: 03/23/2024] Open
Abstract
Introduction The gut microbiota plays an important role in the development of non-alcoholic steatohepatitis (NASH), but the underlying mechanism is unclear. It has been found that the transcription factor XBP1s plays an important role in regulating inflammation and lipid metabolism and maintaining the integrity of intestinal barrier. However, whether XBP1s modulates the development of NASH by regulating the integrity of the intestinal barrier and altering the composition of the gut microbiota remains unknown. Methods Mice fed with a fat-, fructose-, cholesterol-rich (FFC) diet for 24 weeks successfully established the NASH model, as demonstrated by significant hepatic steatosis, inflammation, hepatocyte injury and fibrosis. The profile of gut microbiota dynamically changed with the different stages of NAFLD via 16S rDNA sequencing the feces from mice fed with FFC diet for 0, 12, or 24 weeks or NASH mice treated with siRNA-loaded folic acid-modified TPGS (hereafter named FT@XBP1). Results NASH mice had significantly higher abundance of Firmicutes, Blautia and Bacteroides, and lower abundance of Bifidobacterium and GCA-900066575. FT@XBP1 supplementation had a significantly attenuated effect on FFC diet-induced weight gain, hepatic fat accumulation, dyslipidemia, inflammatory cytokines, ER stress and fibrosis. In particularly, FT@XBP1 modulates the composition of the intestinal flora; for example, NASH mice demonstrated higher abundance of Blautia and Bacteroides, and lower abundance of Actinobacteriota, Muribaculaceae and Bifidobacterium, which were partially restored by FT@XBP1 treatment. Mechanistically, FT@XBP1 increased the expression of ZO-1 in the intestine and had the potential to restore intestinal barrier integrity and improve antimicrobial defense to alleviate enterogenic endotoxemia and activation of inflammatory signaling pathways. Discussion Regulation of the key transcription factor XBP1s can partially restore the intestinal microbiota structure, maintain the integrity of intestinal mucosal barrier, and prevent the progression of NASH, providing new evidence for treating NASH.
Collapse
Affiliation(s)
- Manman Zhu
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yong Cheng
- School of Pharmacy, Anhui Medical University, Hefei, Anhui, China
| | - Yue Tang
- School of Pharmacy, Anhui Medical University, Hefei, Anhui, China
| | - Shuojiao Li
- Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Peng Rao
- School of Pharmacy, Anhui Medical University, Hefei, Anhui, China
| | - Guiyang Zhang
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
| | - Lei Xiao
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jiatao Liu
- Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| |
Collapse
|
14
|
Soleimani RA, Milani PG, Rad AH. The role of gut microbiota on obesity management: a review of the evidence. GASTROINTESTINAL NURSING 2024; 22:26-32. [DOI: 10.12968/gasn.2024.22.1.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
In the last 40 years, there has been a significant increase in the number of people who are overweight, obese and experience combined metabolic disorders. Gut microbiota has been shown to influence energy metabolism and is therefore a significant factor in the development of obesity. A person's diet, in particular, the nutritional value of that diet, is a crucial connection between gut microbiota composition and metabolism. This review explores the role of normal colonic microbiota and the gut environment. These mechanisms connect microbiota with obesity, the presence of gut microbiota in obese individuals and the impact of bioactive compounds in dairy products on gut microbiota. Research shows that gut microbiota play a crucial role in regulating energy metabolism and influencing the development of obesity. Changes in diet can alter the composition and levels of gut microbiota, and consuming bioactive components can help reshape the metabolic profile of obese individuals.
Collapse
Affiliation(s)
- Roya Abedi Soleimani
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Payam Gonbari Milani
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aziz Homayouni Rad
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
15
|
Adarthaiya S, Sehgal A. Moringa oleifera Lam. as a potential plant for alleviation of the metabolic syndrome-A narrative review based on in vivo and clinical studies. Phytother Res 2024; 38:755-775. [PMID: 38015048 DOI: 10.1002/ptr.8079] [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: 04/27/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 11/29/2023]
Abstract
The metabolic syndrome (MetS) refers to the co-occurrence of risk factors, including hyperglycaemia, increased body weight, hypertension and dyslipidemia, which eventually lead to diabetes and cardiovascular disease, a common health problem worldwide. Recently, there has been an increasing interest in the use of plant-based products for the management of MetS, because of their less detrimental and more beneficial effects. Moringa oleifera (Moringaceae), commonly known as drumstick, is cultivated worldwide for its nutritional and medicinal properties. This review focuses on the in vivo and human studies concerning the potential of M. oleifera in the alleviation of MetS and its comorbidities. The search for relevant articles was carried out in PubMed and Google Scholar databases. Randomised controlled and clinical trials from the PubMed database were included in this review. The results suggested that the administration of M. oleifera, in vivo, shows clear signs of improvement in MetS indices. Despite fewer human studies, the existing data documented convincing results that uphold the potential of M. oleifera against MetS. Therefore, future research discussing the probable mechanism of action is much needed which could further assure the usage of M. oleifera in the treatment regimen of MetS.
Collapse
Affiliation(s)
- Saikrupa Adarthaiya
- Department of Zoology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, India
| | - Amit Sehgal
- Department of Zoology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, India
| |
Collapse
|
16
|
Meng Q, Li Y, Xu Y, Wang Y. Acetobacter and lactobacillus alleviate the symptom of insulin resistance by blocking the JNK-JAK/STAT pathway in Drosophila melanogaster. Biochim Biophys Acta Mol Basis Dis 2024; 1870:166901. [PMID: 37774935 DOI: 10.1016/j.bbadis.2023.166901] [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: 09/15/2023] [Accepted: 09/26/2023] [Indexed: 10/01/2023]
Abstract
The dysregulation of intestinal microbiota is well-known to be one of the main causes of insulin resistance in both vertebrates and invertebrates. Specially, the acetobacter and lactobacillus have been identified as potentially capable of alleviating insulin resistance. However, the molecular mechanism underlying this effect requires further elucidation. In this study, we employed Drosophila melanogaster (fruit fly) as a model organism to delineate how intestinal microbiota disrupts the host intestinal signaling pathway, contributing to insulin resistance. Our findings demonstrate that a long-term high-sugar diet lead to a reduction in the general diversity of intestinal microbiota in flies, as well as a marked decrease in the abundances of acetobacter and lactobacillus. Furthermore, we observed that symptoms of insulin resistance were alleviated by feeding flies with acetobacter or lactobacillus, indicating that these microorganisms play an essential role in maintaining blood sugar homeostasis in flies. Conversely, when all intestinal microbiota was removed, flies show severe symptoms of insulin resistance, confirming that the critical role of intestinal microbiota in maintaining host blood sugar homeostasis. Our studies suggested that the intestinal but not fat body JNK pathway mediates the communication of intestinal microbiota and host insulin pathway. In flies, downregulation of JNK activity alleviates symptoms of insulin resistance by decreasing the activity of the JAK/STAT pathway. However, this offsets the therapeutic effects of supplying flies with acetobacter or lactobacillus, suggesting that the therapeutic function of these microorganisms is based on their interaction with JNK-JAK/STAT axis. Taken together, our study reveals that acetobacter and lactobacillus alleviate insulin resistance symptoms in a JNK-JAK/STAT pathway-dependent manner, indicating the therapeutic potential of probiotic supplementation and regulation of the activities of JNK-JAK/STAT pathway for diabetes control.
Collapse
Affiliation(s)
- Qinghao Meng
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Ying Li
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Yidong Xu
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Yiwen Wang
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
| |
Collapse
|
17
|
Fei N, Xie B, Long TJ, StGeorge M, Tan A, Manzoor S, Sidebottom AM, Spedale M, Theriault BR, Sulakhe D, Chang EB. The Host-specific Microbiota is Required for Diet-Specific Metabolic Homeostasis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.11.05.565654. [PMID: 37986759 PMCID: PMC10659342 DOI: 10.1101/2023.11.05.565654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
In complex mammals, the importance and host-specificity of microbial communities have been demonstrated through their positive effects on host immune fitness or performance. However, whether host metabolic physiology homeostasis depends on a specific bacterial community exclusive to the host remains unclear. Here, we show that the coevolved host-specific microbiota is required to maintain diet-specific flexible and sufficient metabolic homeostasis through a high colonization rate, modulating gut metabolites, and related targets. Using germ-free (GF) mice, we tested whether the fitness benefiting the host metabolic phenotype of microbiota was host-specific. We demonstrated that GF mice associated with exogenous microbiota (human microbiota (HM)), which exhibited different and reduced gut microbial species diversity, significantly elevated metabolic rate, and exhibited metabolic insufficiency, all characteristics of GF mice. Strikingly, the absence of the host-specific microbiome attenuated high-fat diet-specific metabolism features. Different diets caused different metabolic changes in only host-specific microbiota-associated mice, not the host-microbiota mismatched mice. While RNA sequencing revealed subtle changes in the expression of genes in the liver, GF mice and HM mice showed considerably altered expression of genes associated with metabolic physiology compared to GF mice associated with host-specific microbiota. The effect of diet outweighed microbiota in the liver transcriptome. These changes occurred in the setting of decreased luminal short-chain fatty acids (SCFAs) and the secondary bile acid (BAs) pool and downstream gut signaling targets in HM and GF mice, which affects whole-body metabolism. These data indicate that a foreign microbial community provides little metabolic benefit to the host when compared to a host-specific microbiome, due to the colonization selection pressure and microbiota-derived metabolites dysfunction. Overall, microbiome fitness effects on the host metabolic phenotype were host-specific. Understanding the impact of the host-specificity of the microbiome on metabolic homeostasis may provide important insights for building a better probiotic. Highlights Microbiome fitness effects on the host metabolic phenotype were host-specific in mammals.Human microbiota-associated mice exhibited lower host metabolic fitness or performance, and similar functional costs in GF mice.Different diets cause different metabolic changes only in host-specific microbiota-associated mice, not the host-microbiota mismatched mice.The defective gut microbiota in host-specific microbiota, microbial metabolites and related targets likely drive the metabolic homeostasis.
Collapse
|
18
|
Sheykhsaran E, Abbasi A, Ebrahimzadeh Leylabadlo H, Sadeghi J, Mehri S, Naeimi Mazraeh F, Feizi H, Bannazadeh Baghi H. Gut microbiota and obesity: an overview of microbiota to microbial-based therapies. Postgrad Med J 2023; 99:384-402. [PMID: 35140178 DOI: 10.1136/postgradmedj-2021-141311] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/15/2022] [Indexed: 12/14/2022]
Abstract
The increasing prevalence of obesity and overweight is a significant public concern throughout the world. Obesity is a complex disorder involving an excessive amount of body fat. It is not just a cosmetic concern. It is a medical challenge that increases the risk of other diseases and health circumstances, such as diabetes, heart disease, high blood pressure and certain cancers. Environmental and genetic factors are involved in obesity as a significant metabolic disorder along with diabetes. Gut microbiota (GM) has a high potential for energy harvesting from the diet. In the current review, we aim to consider the role of GM, gut dysbiosis and significant therapies to treat obesity. Dietary modifications, probiotics, prebiotics, synbiotics compounds, using faecal microbiota transplant, and other microbial-based therapies are the strategies to intervene in obesity reducing improvement. Each of these factors serves through various mechanisms including a variety of receptors and compounds to control body weight. Trial and animal investigations have indicated that GM can affect both sides of the energy-balancing equation; first, as an influencing factor for energy utilisation from the diet and also as an influencing factor that regulates the host genes and energy storage and expenditure. All the investigated articles declare the clear and inevitable role of GM in obesity. Overall, obesity and obesity-relevant metabolic disorders are characterised by specific modifications in the human microbiota's composition and functions. The emerging therapeutic methods display positive and promising effects; however, further research must be done to update and complete existing knowledge.
Collapse
Affiliation(s)
- Elham Sheykhsaran
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Abbasi
- Student Research Committee, Department of Food Sciences and Technology Research Institute, Faculty of Nutrition Sciences and food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Javid Sadeghi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samaneh Mehri
- Department of Biochemistry and structural Biology, University of Alabama, Birmingham, Alabama, USA
| | - Fariba Naeimi Mazraeh
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Feizi
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
19
|
Xia Y, Yang HC, Zhang K, Tian JJ, Li ZF, Yu EM, Li HY, Gong WB, Xie WP, Wang GJ, Xie J. Berberine regulates glucose metabolism in largemouth bass by modulating intestinal microbiota. Front Physiol 2023; 14:1147001. [PMID: 36969581 PMCID: PMC10033662 DOI: 10.3389/fphys.2023.1147001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 02/24/2023] [Indexed: 03/11/2023] Open
Abstract
This study examined the role of intestinal microbiota in berberine (BBR)-mediated glucose (GLU) metabolism regulation in largemouth bass. Four groups of largemouth bass (133.7 ± 1.43 g) were fed with control diet, BBR (1 g/kg feed) supplemented diet, antibiotic (ATB, 0.9 g/kg feed) supplemented diet and BBR + ATB (1g/kg feed +0.9 g/kg feed) supplemented diet for 50 days. BBR improved growth, decreased the hepatosomatic and visceral weight indices, significantly downregulated the serum total cholesterol and GLU levels, and significantly upregulated the serum total bile acid (TBA) levels. The hepatic hexokinase, pyruvate kinase, GLU-6-phosphatase and glutamic oxalacetic transaminase activities in the largemouth bass were significantly upregulated when compared with those in the control group. The ATB group exhibited significantly decreased final bodyweight, weight gain, specific growth rates and serum TBA levels, and significantly increased hepatosomatic and viscera weight indices, hepatic phosphoenolpyruvate carboxykinase, phosphofructokinase, and pyruvate carboxylase activities, and serum GLU levels. Meanwhile, the BBR + ATB group exhibited significantly decreased final weight, weight gain and specific growth rates, and TBA levels and significantly increased hepatosomatic and viscera weight indices and GLU levels. High-throughput sequencing revealed that compared with those in the control group, the Chao one index and Bacteroidota contents were significantly upregulated and the Firmicutes contents were downregulated in the BBR group. Additionally, the Shannon and Simpson indices and Bacteroidota levels were significantly downregulated, whereas the Firmicutes levels were significantly upregulated in ATB and BBR + ATB groups. The results of in-vitro culture of intestinal microbiota revealed that BBR significantly increased the number of culturable bacteria. The characteristic bacterium in the BBR group was Enterobacter cloacae. Biochemical identification analysis revealed that E. cloacae metabolizes carbohydrates. The size and degree of vacuolation of the hepatocytes in the control, ATB, and ATB + BBR groups were higher than those in the BBR group. Additionally, BBR decreased the number of nuclei at the edges and the distribution of lipids in the liver tissue. Collectively, BBR reduced the blood GLU level and improved GLU metabolism in largemouth bass. Comparative analysis of experiments with ATB and BBR supplementation revealed that BBR regulated GLU metabolism in largemouth bass by modulating intestinal microbiota.
Collapse
Affiliation(s)
- Yun Xia
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Hui-Ci Yang
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Kai Zhang
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Jing-Jing Tian
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Zhi-Fei Li
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Er-Meng Yu
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Hong-Yan Li
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Wang-Bao Gong
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Wen-Ping Xie
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
| | - Guang-Jun Wang
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
- *Correspondence: Guang-Jun Wang, ; Jun Xie,
| | - Jun Xie
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
- Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya, China
- *Correspondence: Guang-Jun Wang, ; Jun Xie,
| |
Collapse
|
20
|
Xu T, Wang X, Chen Y, Li H, Zhao L, Ding X, Zhang C. Microbiome Features Differentiating Unsupervised-Stratification-Based Clusters of Patients with Abnormal Glycometabolism. mBio 2023; 14:e0348722. [PMID: 36651735 PMCID: PMC9973283 DOI: 10.1128/mbio.03487-22] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 12/23/2022] [Indexed: 01/19/2023] Open
Abstract
The alteration of gut microbiota structure plays a pivotal role in the pathogenesis of abnormal glycometabolism. However, the microbiome features identified in patient groups stratified solely based on glucose levels remain controversial among different studies. In this study, we stratified 258 participants (discovery cohort) into three clusters according to an unsupervised method based on 16 clinical parameters involving the levels of blood glucose, insulin, and lipid. We found 67 cluster-specific microbiome features (i.e., amplicon sequence variants [ASVs]) based on 16S rRNA gene V3-V4 region sequencing. Specifically, ASVs belonging to Barnesville and Alistipes were enriched in cluster 1, in which participants had the lowest blood glucose levels, high insulin sensitivity, and a high-fecal short-chain fatty acid concentration. ASVs belonging to Prevotella copri and Ruminococcus gnavus were enriched in cluster 2, which was characterized by a moderate level of blood glucose, serious insulin resistance, and high levels of cholesterol and triglyceride. Cluster 3 was characterized by a high level of blood glucose and insulin deficiency, enriched with ASVs in P. copri and Bacteroides vulgatus. In addition, machine learning classifiers using the 67 cluster-specific ASVs were used to distinguish individuals in one cluster from those in the other two clusters both in discovery and testing cohorts (n = 83). Therefore, microbiome features identified based on the unsupervised stratification of patients with more inclusive clinical parameters may better reflect microbiota alterations associated with the progression of abnormal glycometabolism. IMPORTANCE The gut microbiota is altered in patients with type 2 diabetes (T2D) and prediabetes. The association of particular bacteria with T2D, however, varied among studies, which has made it challenging to develop precision medicine approaches for the prevention and alleviation of T2D. Blood glucose level is the only parameter in clustering patients when identifying the T2D-related bacteria in previous studies. This stratification ignores the fact that patients within the same blood glucose range differ in their insulin resistance and dyslipidemia, which also may be related to disordered gut microbiota. In addition to parameters of blood glucose levels, we also used additional parameters involving insulin and lipid levels to stratify participants into three clusters and further identified cluster-specific microbiome features. We further validated the association between these microbiome features and glycometabolism with an independent cohort. This study highlights the importance of stratification of patients with blood glucose, insulin, and lipid levels when identifying the microbiome features associated with the progression of abnormal glycometabolism.
Collapse
Affiliation(s)
- Ting Xu
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Xuejiao Wang
- Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Chen
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Li
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Liping Zhao
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
- Department of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition and Health, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, New Jersey, USA
| | - Xiaoying Ding
- Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chenhong Zhang
- State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
21
|
Qureshi N, Desousa J, Siddiqui AZ, Drees BM, Morrison DC, Qureshi AA. Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus. Int J Mol Sci 2023; 24:2732. [PMID: 36769056 PMCID: PMC9916932 DOI: 10.3390/ijms24032732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/17/2023] [Accepted: 01/19/2023] [Indexed: 02/04/2023] Open
Abstract
Diabetes is currently the fifth leading cause of death by disease in the USA. The underlying mechanisms for type 2 Diabetes Mellitus (DM2) and the enhanced susceptibility of such patients to inflammatory disorders and infections remain to be fully defined. We have recently shown that peripheral blood mononuclear cells (PBMCs) from non-diabetic people upregulate expression of inflammatory genes in response to proteasome modulators, such as bacterial lipopolysaccharide (LPS) and soybean lectin (LEC); in contrast, resveratrol (RES) downregulates this response. We hypothesized that LPS and LEC will also elicit a similar upregulation of gene expression of key signaling mediators in (PBMCs) from people with type 2 diabetes (PwD2, with chronic inflammation) ex vivo. Unexpectedly, using next generation sequencing (NGS), we show for the first time, that PBMCs from PwD2 failed to elicit a robust LPS- and LEC-induced gene expression of proteasome subunit LMP7 (PSMB8) and mediators of T cell signaling that were observed in non-diabetic controls. These repressed genes included: PSMB8, PSMB9, interferon-γ, interferon-λ, signal-transducer-and-activator-of-transcription-1 (STAT1), human leukocyte antigen (HLA DQB1, HLA DQA1) molecules, interleukin 12A, tumor necrosis factor-α, transporter associated with antigen processing 1 (TAP1), and several others, which showed a markedly weak upregulation with toxins in PBMCs from PwD2, as compared to those from non-diabetics. Resveratrol (proteasome inhibitor) further downregulated the gene expression of these inflammatory mediators in PBMCs from PwD2. These results might explain why PwD2 may be susceptible to infectious disease. LPS and toxins may be leading to inflammation, insulin resistance, and thus, metabolic changes in the host cells.
Collapse
Affiliation(s)
- Nilofer Qureshi
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
- Department of Pharmacology/Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA
| | - Julia Desousa
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
- Department of Pharmacology/Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA
| | - Adeela Z. Siddiqui
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - Betty M. Drees
- Internal Medicine, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - David C. Morrison
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
| | - Asaf A. Qureshi
- Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
| |
Collapse
|
22
|
Van Hul M, Cani PD. The gut microbiota in obesity and weight management: microbes as friends or foe? Nat Rev Endocrinol 2023; 19:258-271. [PMID: 36650295 DOI: 10.1038/s41574-022-00794-0] [Citation(s) in RCA: 123] [Impact Index Per Article: 61.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/12/2022] [Indexed: 01/18/2023]
Abstract
Obesity is caused by a long-term difference between energy intake and expenditure - an imbalance that is seemingly easily restored by increasing exercise and reducing caloric consumption. However, as simple as this solution appears, for many people, losing excess weight is difficult to achieve and even more difficult to maintain. The reason for this difficulty is that energy intake and expenditure, and by extension body weight, are regulated through complex hormonal, neural and metabolic mechanisms that are under the influence of many environmental factors and internal responses. Adding to this complexity, the microorganisms (microbes) that comprise the gut microbiota exert direct effects on the digestion, absorption and metabolism of food. Furthermore, the gut microbiota exerts a miscellany of protective, structural and metabolic effects both on the intestinal milieu and peripheral tissues, thus affecting body weight by modulating metabolism, appetite, bile acid metabolism, and the hormonal and immune systems. In this Review, we outline historical and recent advances in understanding how the gut microbiota is involved in regulating body weight homeostasis. We also discuss the opportunities, limitations and challenges of using gut microbiota-related approaches as a means to achieve and maintain a healthy body weight.
Collapse
Affiliation(s)
- Matthias Van Hul
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain (Université catholique de Louvain), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO Department, WEL Research Institute, Wavre, Belgium
| | - Patrice D Cani
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain (Université catholique de Louvain), Brussels, Belgium.
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO Department, WEL Research Institute, Wavre, Belgium.
| |
Collapse
|
23
|
Drewes AM, Brock C, Drewes AM. Autonomic Visceral Neuropathy and Gastrointestinal Disorders. THE DIABETES TEXTBOOK 2023:967-978. [DOI: 10.1007/978-3-031-25519-9_58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
24
|
Wang M, Yan LY, Qiao CY, Zheng CC, Niu CG, Huang ZW, Pan YH. Ecological shifts of salivary microbiota associated with metabolic-associated fatty liver disease. Front Cell Infect Microbiol 2023; 13:1131255. [PMID: 36864882 PMCID: PMC9971218 DOI: 10.3389/fcimb.2023.1131255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Accepted: 01/30/2023] [Indexed: 02/16/2023] Open
Abstract
Introduction Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease related to metabolic syndrome. However, ecological shifts in the saliva microbiome in patients with MAFLD remain unknown. This study aimed to investigate the changes to the salivary microbial community in patients with MAFLD and explore the potential function of microbiota. Methods Salivary microbiomes from ten MAFLD patients and ten healthy participants were analyzed by 16S rRNA amplicon sequencing and bioinformatics analysis. Body composition, plasma enzymes, hormones, and blood lipid profiles were assessed with physical examinations and laboratory tests. Results The salivary microbiome of MAFLD patients was characterized by increased α-diversity and distinct β-diversity clustering compared with control subjects. Linear discriminant analysis effect size analysis showed a total of 44 taxa significantly differed between the two groups. Genera Neisseria, Filifactor, and Capnocytophaga were identified as differentially enriched genera for comparison of the two groups. Co-occurrence networks suggested that the salivary microbiota from MAFLD patients exhibited more intricate and robust interrelationships. The diagnostic model based on the salivary microbiome achieved a good diagnostic power with an area under the curve of 0.82(95% CI: 0.61-1). Redundancy analysis and spearman correlation analysis revealed that clinical variables related to insulin resistance and obesity were strongly associated with the microbial community. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to metabolism were more prevalent in the two groups. Conclusions Patients with MAFLD manifested ecological shifts in the salivary microbiome, and the saliva microbiome-based diagnostic model provides a promising approach for auxiliary MAFLD diagnosis.
Collapse
Affiliation(s)
- Min Wang
- Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
- Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Li-Ya Yan
- Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Cai-Yun Qiao
- Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Chu-Chu Zheng
- Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Chen-Guang Niu
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
| | - Zheng-Wei Huang
- Department of Endodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- *Correspondence: Zheng-Wei Huang, ; Yi-Huai Pan,
| | - Yi-Huai Pan
- Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
- Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
- *Correspondence: Zheng-Wei Huang, ; Yi-Huai Pan,
| |
Collapse
|
25
|
Luo S, Zhang H, Jiang X, Xia Y, Tang S, Duan X, Sun W, Gao M, Chen C, Zou Z, Zhou L, Qiu J. Antibiotics administration alleviates the high fat diet-induced obesity through altering the lipid metabolism in young mice. Lipids 2023; 58:19-32. [PMID: 36253942 DOI: 10.1002/lipd.12361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 08/24/2022] [Accepted: 09/19/2022] [Indexed: 02/04/2023]
Abstract
Currently, there is a global trend of rapid increase in obesity, especially among adolescents. The antibiotics cocktails (ABX) therapy is commonly used as an adjunctive treatment for gut microbiota related diseases, including obesity. However, the effects of broad-spectrum antibiotics alone on young obese hosts have rarely been reported. In the present study, the 3-week-old C57BL/6J male mice fed a high-fat diet (HFD) were intragastric administration with ampicillin, vancomycin, metronidazole or neomycin for 30 days. The lipid metabolites in plasma were assessed by biochemical assay kits, and genes related to lipid metabolite in the white adipose were assessed by qPCR. To further analyze the underlying mechanisms, the expression of genes related to lipid metabolism, inflammatory reactions and oxidative stress in the liver were determined by qPCR assay. In addition, the expression of oxidative damage-associated proteins in the liver were detected by western blot. The results showed that oral antibiotics exposure could reduce body weight and fat index in HFD-fed mice, concurrent with the increase of white adipose lipolysis genes and the decrease of hepatic lipogenic genes. Furthermore, antibiotics treatment could clearly reverse the HFD-induced elevation of oxidative damage-related proteins in the liver. Together, these findings will provide valuable clues into the effects of antibiotics on obesity.
Collapse
Affiliation(s)
- Shiyue Luo
- Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Hongyang Zhang
- Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Xuejun Jiang
- Center of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, People's Republic of China.,Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Yinyin Xia
- Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China.,Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Shixin Tang
- Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Xinhao Duan
- Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Wei Sun
- Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Min Gao
- Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Chengzhi Chen
- Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China.,Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Zhen Zou
- Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China.,Institute of Life Sciences, Chongqing Medical University, Chongqing, People's Republic of China
| | - Lixiao Zhou
- Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China.,Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| | - Jingfu Qiu
- Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China.,Research Center for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China
| |
Collapse
|
26
|
Zhou Z, Pan X, Li L. Crosstalk between liver macrophages and gut microbiota: An important component of inflammation-associated liver diseases. Front Cell Dev Biol 2022; 10:1070208. [PMID: 36483677 PMCID: PMC9723159 DOI: 10.3389/fcell.2022.1070208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 11/10/2022] [Indexed: 08/30/2023] Open
Abstract
Hepatic macrophages have been recognized as primary sensors and responders in liver inflammation. By processing host or exogenous biochemical signals, including microbial components and metabolites, through the gut-liver axis, hepatic macrophages can both trigger or regulate inflammatory responses. Crosstalk between hepatic macrophages and gut microbiota is an important component of liver inflammation and related liver diseases, such as acute liver injury (ALI), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). This review summarizes recent advances in knowledge related to the crosstalk between hepatic macrophages and gut microbiota, including the therapeutic potential of targeting hepatic macrophages as a component of gut microecology in inflammation-associated liver diseases.
Collapse
Affiliation(s)
| | | | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
27
|
Ruiz-González R, Lajud N, Tejeda-Martínez AR, Flores-Soto ME, Valdez-Alarcón JJ, Tellez LA, Roque A. Antibiotic-induced microbiota depletion in normally-reared adult rats mimics the neuroendocrine effects of early life stress. Brain Res 2022; 1793:148055. [PMID: 35985361 DOI: 10.1016/j.brainres.2022.148055] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/09/2022] [Accepted: 08/11/2022] [Indexed: 01/06/2023]
Abstract
Early life stress induced by maternal separation (MS) causes neuroendocrine, behavioral, and metabolic alterations that are related to gut dysbiosis. MS also increases microglial activation and decreases neurogenesis. Whether these long-term alterations are maintained or worsened in the absence of gut microbiota remains unknown. Hence, this study evaluated the effect of MS symptomatology after antibiotic-induced microbiota depletion (AIMD) in adult rats. Control and maternally separated (3 h per day from postnatal day one to 14, MS180) rats were subjected to AIMD for one month, then assessed for behavioral, metabolic, and neuroendocrine responses. Effects of MS180 and AIMD on gut microbiota were confirmed by qPCR. The data indicate that MS180 caused a passive coping strategy in the forced swimming test and decreased hippocampal neurogenesis. In addition, fasting glucose, cholesterol, and corticosterone levels increased, which correlated with a decrease in Lactobacillus spp counts in the caecum. AIMD also increased immobility in the forced swimming test, decreased hippocampal neurogenesis, and augmented corticosterone levels. However, it had no effects on glucose homeostasis or plasma lipid levels. Furthermore, the MS180-induced long-term effects on behavior and neurogenesis were not affected by microbiota depletion. Meanwhile, the metabolic imbalance was partially reversed in MS180 + AIMD rats. These results show that AIMD mimics the behavioral consequences of MS180 but may prevent metabolic imbalance, suggesting that gut dysbiosis could be part of the mechanisms involved in the maintenance of the long-term consequences of early life stress.
Collapse
Affiliation(s)
- Roberto Ruiz-González
- Laboratorio de Neurobiología del Desarrollo, División de Neurociencias, Centro de Investigación Biomédica de Michoacán (CIBIMI), Instituto Mexicano del Seguro Social, Morelia, Michoacán, Mexico
| | - Naima Lajud
- Laboratorio de Neurobiología del Desarrollo, División de Neurociencias, Centro de Investigación Biomédica de Michoacán (CIBIMI), Instituto Mexicano del Seguro Social, Morelia, Michoacán, Mexico.
| | - Aldo Rafael Tejeda-Martínez
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Guadalajara, Mexico
| | - Mario Eduardo Flores-Soto
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Guadalajara, Mexico
| | - Juan José Valdez-Alarcón
- Centro Multidisciplinario de Estudios Biotecnología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico
| | - Luis A Tellez
- Laboratorio de Neurobiología de la Conducta Motivada, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Mexico
| | - Angélica Roque
- Laboratorio de Neurobiología del Desarrollo, División de Neurociencias, Centro de Investigación Biomédica de Michoacán (CIBIMI), Instituto Mexicano del Seguro Social, Morelia, Michoacán, Mexico
| |
Collapse
|
28
|
An J, Wang L, Song S, Tian L, Liu Q, Mei M, Li W, Liu S. Electroacupuncture reduces blood glucose by regulating intestinal flora in type 2 diabetic mice. J Diabetes 2022; 14:695-710. [PMID: 36195536 PMCID: PMC9574722 DOI: 10.1111/1753-0407.13323] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 08/13/2022] [Accepted: 09/15/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND The development of diabetes is closely related to the gut microbiota in recent studies, which can be influenced by intestinal motility. A few studies report that electroacupuncture (EA) can lower blood glucose. EA can promote colonic motility and influence gut microbes. In this study, we explored the effect of the EA on blood glucose level in mice with type 2 diabetes (T2D) and its mechanism. METHODS The T2D mice model, fecal microbiota transplantation mice model, and KitW/Wv mice model (Point mutation of mouse W locus encoding kit gene)were used to investigate the effect of EA on blood glucose as well as the mechanism; The blood glucose and insulin resistance level and the intestinal flora were evaluated. The level of intestinal junction protein, inflammatory cytokines in the serum, interstitial cells of Cajal content, and colonic motility were detected. Lastly, the IKKβ/NF-κB-JNK-IRS-1-AKT pathway was explored. RESULTS EA lowered the blood glucose level, altered the gut microbiota, and promoted colonic motility in T2D mice. EA-altered microbiota decreased the blood glucose level and insulin resistance in the antibiotics-treated diabetic mice. EA increased tight junction protein, lowered inflammatory factors, and regulated the IKKβ/NF-κB-JNK-IRS-1-AKT pathway in the liver and muscles. EA could not reduce the blood glucose and regulated gut microbiota in the KitW/Wv mice model. CONCLUSIONS EA promoted intestinal motility to regulate the intestinal flora, thereby reducing the level of systemic inflammation, and ultimately lowering the blood glucose by the IKKβ/NF-κB-JNK-IRS-1-AKT signal pathway.
Collapse
Affiliation(s)
- Jing An
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Lingli Wang
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Shuangning Song
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Lugao Tian
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Qingqing Liu
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Minhui Mei
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Wenhua Li
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Shi Liu
- Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| |
Collapse
|
29
|
Chen HJ, Bischoff A, Galley JD, Peck L, Bailey MT, Gur TL. Discrete role for maternal stress and gut microbes in shaping maternal and offspring immunity. Neurobiol Stress 2022; 21:100480. [PMID: 36532381 PMCID: PMC9755033 DOI: 10.1016/j.ynstr.2022.100480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 07/28/2022] [Accepted: 08/18/2022] [Indexed: 01/11/2023] Open
Abstract
Psychosocial stress is prevalent during pregnancy, and is associated with immune dysfunction, both for the mother and the child. The gut microbiome has been implicated as a potential mechanism by which stress during pregnancy can impact both maternal and offspring immune function; however, the complex interplay between the gut microbiome and the immune system is not well-understood. Here, we leverage a model of antimicrobial-mediated gut microbiome reduction, in combination with a well-established model of maternal restraint stress, to investigate the independent effects of and interaction between maternal stress and the gut microbiome in shaping maternal and offspring immunity. First, we confirmed that the antimicrobial treatment reduced maternal gut bacterial load and altered fecal alpha and beta diversity, with a reduction in commensal microbes and an increase in the relative abundance of rare taxa. Prenatal stress also disrupted the gut microbiome, according to measures of both alpha and beta diversity. Furthermore, prenatal stress and antimicrobials independently induced systemic and gastrointestinal immune suppression in the dam with a concomitant increase in circulating corticosterone. While stress increased neutrophils in the maternal circulation, lymphoid cells and monocytes were not impacted by either stress or antimicrobial treatment. Although the fetal immune compartment was largely spared, stress increased circulating neutrophils and CD8 T cells, and antibiotics increased neutrophils and reduced T cells in the adult offspring. Altogether, these data indicate similar, but discrete, roles for maternal stress and gut microbes in influencing maternal and offspring immune function.
Collapse
Affiliation(s)
- Helen J. Chen
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Medical Scientist Training Program, The Ohio State University, Columbus, OH, USA
| | - Allison Bischoff
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jeffrey D. Galley
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Lauren Peck
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,The Ohio State University College of Medicine, Columbus, OH, USA
| | - Michael T. Bailey
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Center for Microbial Pathogenesis, The Research Institute, Nationwide Children's Hospital, Columbus, OH, USA,Biosciences Division, College of Dentistry, The Ohio State University, Columbus, OH, USA
| | - Tamar L. Gur
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Medical Scientist Training Program, The Ohio State University, Columbus, OH, USA,Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Obstetrics & Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Corresponding author. 120A Institute for Behavioral Medicine Research Building, 460 Medical Center Drive, Columbus, OH, 43210, USA.
| |
Collapse
|
30
|
Abstract
We are host to an assembly of microorganisms that vary in structure and function along the length of the gut and from the lumen to the mucosa. This ecosystem is collectively known as the gut microbiota and significant efforts have been spent during the past 2 decades to catalog and functionally describe the normal gut microbiota and how it varies during a wide spectrum of disease states. The gut microbiota is altered in several cardiometabolic diseases and recent work has established microbial signatures that may advance disease. However, most research has focused on identifying associations between the gut microbiota and human diseases states and to investigate causality and potential mechanisms using cells and animals. Since the gut microbiota functions on the intersection between diet and host metabolism, and can contribute to inflammation, several microbially produced metabolites and molecules may modulate cardiometabolic diseases. Here we discuss how the gut bacterial composition is altered in, and can contribute to, cardiometabolic disease, as well as how the gut bacteria can be targeted to treat and prevent metabolic diseases.
Collapse
Affiliation(s)
- Louise E Olofsson
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden
| | - Fredrik Bäckhed
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden.,Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Denmark.,Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden
| |
Collapse
|
31
|
Gimenes GM, Santana GO, Scervino MVM, Curi R, Pereira JNB. A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine. Braz J Med Biol Res 2022; 55:e11910. [PMID: 36000611 PMCID: PMC9394691 DOI: 10.1590/1414-431x2022e11910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes
mellitus (T2DM) that allows researchers to monitor diabetes-induced changes
without jeopardizing the effects of obesity. This rat strain exhibits notable
gastrointestinal features associated with T2DM, such as marked alterations in
intestinal morphology, reduced intestinal motility, slow transit, and modified
microbiota compared to Wistar rats. The primary treatments for diabetic patients
include administration of hypoglycemic agents and insulin, and lifestyle
changes. Emerging procedures, including alternative therapies, metabolic
surgeries, and modulation of the intestinal microbiota composition, have been
shown to improve the diabetic state of GK rats. This review describes the
morpho-physiological diabetic-associated features of the gastrointestinal tract
(GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery
and modulation of gut microbiota composition, used to target the GIT of this
animal model to improve the diabetic state.
Collapse
Affiliation(s)
- G M Gimenes
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - G O Santana
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - M V M Scervino
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - R Curi
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil.,Centro Bioindustrial, Instituto Butantan, São Paulo, SP, Brasil
| | - J N B Pereira
- Laboratório Estratégico de Diagnóstico Molecular, Instituto Butantan, São Paulo, SP, Brasil
| |
Collapse
|
32
|
Al-Qadami G, Verma G, Van Sebille Y, Le H, Hewson I, Bateman E, Wardill H, Bowen J. Antibiotic-Induced Gut Microbiota Depletion Accelerates the Recovery of Radiation-Induced Oral Mucositis in Rats. Int J Radiat Oncol Biol Phys 2022; 113:845-858. [PMID: 35398457 DOI: 10.1016/j.ijrobp.2022.03.036] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 03/06/2022] [Accepted: 03/30/2022] [Indexed: 11/16/2022]
Abstract
PURPOSE Due to its pivotal role in the modulation of immune and inflammatory responses, the gut microbiota has emerged as a key modulator of cancer treatment-induced gastrointestinal mucositis. However, it is not clear yet how it affects radiation therapy-induced oral mucositis (OM). As such, this study aimed to explore the gut microbiota's role in the pathogenesis of radiation-induced OM in rats. METHODS AND MATERIALS Male Sprague Dawley rats were treated with 20 Gy x-ray radiation (Rx) delivered to the snout, with or without antibiotic-induced microbiota depletion (AIMD). OM severity was assessed, and tongue tissues were collected on day 9 and 15 postradiation for tissue injury and inflammatory markers assessment. RESULTS AIMD+Rx had a significantly shorter duration of severe OM compared with Rx alone group. Macroscopically, the tongue ulcer-like area was smaller in AIMD+Rx compared with the Rx group. Microscopically, a smaller percentage of the mucosal ulcer was observed in the dorsal tongue of AIMD+Rx compared with the Rx group. AIMD+Rx also had significantly lower levels of interleukin 6, interleukin 1 beta, and toll like receptor 4 in the tongue tissues than the Rx group. CONCLUSIONS The gut microbiota plays a role in OM pathogenesis, mainly in the recovery phase, through the modulation of proinflammatory pathways. Future microbiota-targeted interventions may improve OM in clinical settings.
Collapse
Affiliation(s)
| | - Gunjan Verma
- Adelaide Dental School, University of Adelaide, Adelaide
| | | | - Hien Le
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide
| | | | - Emma Bateman
- School of Biomedicine, University of Adelaide, Adelaide
| | - Hannah Wardill
- School of Biomedicine, University of Adelaide, Adelaide; Precision Medicine Theme (Cancer), South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Joanne Bowen
- School of Biomedicine, University of Adelaide, Adelaide
| |
Collapse
|
33
|
Chen RA, Wu WK, Panyod S, Liu PY, Chuang HL, Chen YH, Lyu Q, Hsu HC, Lin TL, Shen TCD, Yang YT, Zou HB, Huang HS, Lin YE, Chen CC, Ho CT, Lai HC, Wu MS, Hsu CC, Sheen LY. Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition. mSystems 2022; 7:e0017222. [PMID: 35670534 PMCID: PMC9239188 DOI: 10.1128/msystems.00172-22] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 04/22/2022] [Indexed: 12/30/2022] Open
Abstract
Antibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have indicated that exposure to these antibiotic residues in food may be associated with childhood obesity. Herein, the effect of exposure to a residual dose of tylosin-an antibiotic growth promoter-on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of tylosin were found to facilitate high-fat-diet-induced obesity, induce insulin resistance, and perturb gut microbiota composition in mice. The obesity-related phenotypes were transferrable to germfree recipient mice, indicating that the effects of a TMDI dose of tylosin on obesity and insulin resistance occurred mainly via alteration of the gut microbiota. Tylosin TMDI exposure restricted to early life, the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to tylosin TMDI doses was sufficient to modify the ratio of primary to secondary bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low doses of antibiotic residues, whether continuously or in early life, could exert long-lasting effects on host metabolism by altering the gut microbiota and its metabolites. IMPORTANCE This study demonstrates that even with limited exposure in early life, a residual dose of tylosin might cause long-lasting metabolic disturbances by altering the gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.
Collapse
Affiliation(s)
- Rou-An Chen
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Wei-Kai Wu
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Suraphan Panyod
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Po-Yu Liu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsiao-Li Chuang
- National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan
| | - Yi-Hsun Chen
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Qiang Lyu
- Department of Chemistry, National Taiwan University, Taipei, Taiwan
| | - Hsiu-Ching Hsu
- The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan
| | - Tzu-Lung Lin
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ting-Chin David Shen
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Yu-Tang Yang
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsin-Bai Zou
- Department of Chemistry, National Taiwan University, Taipei, Taiwan
| | - Huai-Syuan Huang
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Yu-En Lin
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA
| | - Hsin-Chih Lai
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Chih Hsu
- Department of Chemistry, National Taiwan University, Taipei, Taiwan
| | - Lee-Yan Sheen
- Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan
- Center for Food and Biomolecules, National Taiwan University, Taipei, Taiwan
- National Center for Food Safety Education and Research, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
34
|
Babenko AY. Metformin in prediabetes: key mechanisms for the prevention of diabetes and cardiometabolic risks. MEDITSINSKIY SOVET = MEDICAL COUNCIL 2022:96-103. [DOI: 10.21518/2079-701x-2022-16-10-96-103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Today, prediabetes is regarded by the world medical community as early diabetes mellitus. The accumulated research evidence shows that prediabetes is characterized by a spectrum of complications that are similar to those of diabetes mellitus, which means that the deterioration of cardiovascular prognosis starts already at the stage of prediabetes. In the current timeframe, metformin is actually the only drug that is widely prescribed for the treatment of prediabetes to prevent type 2 diabetes mellitus and cardiovascular diseases associated with insulin resistance and hyperinsulinemia. Meanwhile, metabolically unhealthy obesity characterized by hyperinsulinemia and insulin resistance is associated with a significantly unfavourable course of prediabetes, as well as the highest risk of developing both type 2 diabetes mellitus and cardiovascular diseases, development/ progression of chronic kidney disease. The theme of this review is the priority of metformin for the management of the most prognostically unfavourable phenotypes of prediabetes. The review is also devoted to the description of the most significant mechanisms that provide effects of metformin underlying the management of key disorders that determine the unfavourable prognosis of prediabetes. In particular, it sets forth the role of unhealthy nutrition, its effects on the development of imbalance of the composition of gut microbiota, which, in turn, entails a cascade of metabolic disorders underlying the development of metabolic ill health. The review sets forth the key role of metformin as a drug that protects against the development of these disorders. The information presented in this review will be useful to personalize the choice of both the scope and nature of interventions in patients with different phenotypic characteristics.
Collapse
|
35
|
Thomas MS, Blesso CN, Calle MC, Chun OK, Puglisi M, Fernandez ML. Dietary Influences on Gut Microbiota with a Focus on Metabolic Syndrome. Metab Syndr Relat Disord 2022; 20:429-439. [PMID: 35704900 DOI: 10.1089/met.2021.0131] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
There is a clear correlation between gut microbiota, diet, and metabolic outcomes. A diet high in fiber has been shown to decrease inflammation, increase insulin sensitivity, and reduce dyslipidemias whereas a diet high in fat and sugar leads to dyslipidemia, insulin resistance, and low-grade inflammation. There is recent evidence suggesting that the human gut microbiota has a significant role in the development or the resolution of metabolic syndrome (MetS) and associated conditions. Leading a stressful, sedentary lifestyle with limited or no physical activity and consuming an unhealthy diet high in saturated fat, simple carbohydrates, and sodium and low in dietary fiber and in high-quality protein are some of the contributing factors. Unhealthy diets have been shown to induce alterations in the gut microbiota and contribute to the pathogenesis of MetS by altering microbiota composition and disrupting the intestinal barrier, which leads to low-grade systemic inflammation. In contrast, healthy diets can lead to changes in microbiota that increase gut barrier function and increase the production of anti-inflammatory biomarkers. This review aims at providing a more in-depth discussion of diet-induced dysbiosis of the gut microbiota and its effect on MetS. Here, we discuss the possible mechanisms involved in the development of the metabolic biomarkers that define MetS, with an emphasis on the role of sugar and dietary fiber in microbiome-mediated changes in low-grade systemic inflammation and metabolic dysfunction.
Collapse
Affiliation(s)
- Minu S Thomas
- Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA
| | - Christopher N Blesso
- Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA
| | - Mariana C Calle
- Health Sciences Department ST 110-M, Worcester University, Worcester, Massachusetts, USA
| | - Ock K Chun
- Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA
| | - Michael Puglisi
- Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA
| | - Maria Luz Fernandez
- Department of Nutritional Sciences, University of Connecticut, Storrs, Connecticut, USA
| |
Collapse
|
36
|
Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, Zhu D, Koya JB, Wei L, Li J, Chen ZS. Microbiota in health and diseases. Signal Transduct Target Ther 2022; 7:135. [PMID: 35461318 PMCID: PMC9034083 DOI: 10.1038/s41392-022-00974-4] [Citation(s) in RCA: 1211] [Impact Index Per Article: 403.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 02/07/2023] Open
Abstract
The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.
Collapse
Affiliation(s)
- Kaijian Hou
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Zhuo-Xun Wu
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Xuan-Yu Chen
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Jing-Quan Wang
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Dongya Zhang
- Microbiome Research Center, Moon (Guangzhou) Biotech Ltd, Guangzhou, 510535, China
| | - Chuanxing Xiao
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Jagadish B Koya
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Liuya Wei
- School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, China
| | - Jilin Li
- Department of Cardiovascular, The Second Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| |
Collapse
|
37
|
Environmental Factors and the Risk of Developing Type 1 Diabetes-Old Disease and New Data. BIOLOGY 2022; 11:biology11040608. [PMID: 35453807 PMCID: PMC9027552 DOI: 10.3390/biology11040608] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/10/2022] [Accepted: 04/14/2022] [Indexed: 12/16/2022]
Abstract
Simple Summary Despite many studies, the risk factors of type 1 diabetes (T1DM) in children and adolescents are still not fully understood and remain a big challenge. Therefore, an extensive online search for scientific research on factors related to diabetes has been performed for the identification of new factors of unexplained etiology. A better understanding of the role of viral, bacterial, and yeast-like fungi infections related to the risk of T1DM in children and adolescents and the identification of new risk factors, especially those spread by the droplet route, is of great importance for people and families with diabetes. Abstract The incidence of type 1 diabetes (T1D) is increasing worldwide. The onset of T1D usually occurs in childhood and is caused by the selective destruction of insulin-producing pancreatic islet cells (β-cells) by autoreactive T cells, leading to insulin deficiency. Despite advanced research and enormous progress in medicine, the causes of T1D are still not fully understood. Therefore, an extensive online search for scientific research on environmental factors associated with diabetes and the identification of new factors of unexplained etiology has been carried out using the PubMed, Cochrane, and Embase databases. The search results were limited to the past 11 years of research and discovered 143 manuscripts published between 2011 and 2022. Additionally, 21 manuscripts from between 2000 and 2010 and 3 manuscripts from 1974 to 2000 were referenced for historical reference as the first studies showcasing a certain phenomenon or mechanism. More and more scientists are inclined to believe that environmental factors are responsible for the increased incidence of diabetes. Research results show that higher T1D incidence is associated with vitamin D deficiency, a colder climate, and pollution of the environment, as well as the influence of viral, bacterial, and yeast-like fungi infections. The key viral infections affecting the risk of developing T1DM are rubella virus, mumps virus, Coxsackie virus, cytomegalovirus, and enterovirus. Since 2020, i.e., from the beginning of the COVID-19 pandemic, more and more studies have been looking for a link between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and diabetes development. A better understanding of the role of viral, bacterial, and yeast-like fungi infections related to the risk of T1DM in children and adolescents and the identification of new risk factors, especially those spread by the droplet route, is of great importance for people and families with diabetes.
Collapse
|
38
|
Dong Z, Lv W, Zhang C, Chen S. Correlation Analysis of Gut Microbiota and Serum Metabolome With Porphyromonas gingivalis-Induced Metabolic Disorders. Front Cell Infect Microbiol 2022; 12:858902. [PMID: 35463645 PMCID: PMC9022097 DOI: 10.3389/fcimb.2022.858902] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/16/2022] [Indexed: 12/12/2022] Open
Abstract
Periodontitis has been demonstrated to increase the risk of metabolic syndrome (MetS), but the underlying mechanism remains unclear. Recent studies have indicated periodontopathic bacteria such as Porphyromonas gingivalis could induce gut microbiota (GM) dysbiosis and aggravate metabolic disorders. However, the effects of microbial metabolites have barely been evaluated. Here, we investigated the alteration of serum metabolome with P. gingivalis-induced metabolic disorders, and explored the correlations of GM and serum metabolites. In this study, we orally administered P. gingivalis ATCC33277 to C57BL/6 mice and performed metagenomic sequencing and untargeted metabolomics with fecal samples and serum collection. In vivo experiments showed a higher proportion of fat mass and worse glucose tolerance in P. gingivalis-administered mice, accompanied with an increase of adipose inflammation and gut permeability, which was similar to HFD-induced obese mice. Metagenomic sequencing indicated a compositional and functional alteration of GM. Untargeted metabolomics revealed an alteration of metabolites in P. gingivalis-administered mice, and most of them were engaged in metabolic pathways, such as tryptophan metabolism and choline metabolism. Correlation analysis between GM and serum metabolome indicated strong relativity with P. gingivalis administration. These results demonstrated some specific microbiota-derived metabolites in the pathogenesis of P. gingivalis-induced metabolic disorders, providing promising targets for the development of novel treatment strategies for MetS.
Collapse
Affiliation(s)
- ZhengJie Dong
- Department of Implantology, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China
| | - WanQi Lv
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China
| | - ChenYang Zhang
- Department of Implantology, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China
- *Correspondence: ChenYang Zhang, ; Si Chen,
| | - Si Chen
- Department of Implantology, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China
- State Key Laboratory of Molecular Engineering of Ploymers, Fudan University, Shanghai, China
- *Correspondence: ChenYang Zhang, ; Si Chen,
| |
Collapse
|
39
|
Yang Q, Zhang J, Zhu Y. Potential Roles of the Gut Microbiota in Pancreatic Carcinogenesis and Therapeutics. Front Cell Infect Microbiol 2022; 12:872019. [PMID: 35463649 PMCID: PMC9019584 DOI: 10.3389/fcimb.2022.872019] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/14/2022] [Indexed: 11/28/2022] Open
Abstract
The intestinal microenvironment is composed of normal gut microbiota and the environment in which it lives. The largest microecosystem in the human body is the gut microbiota, which is closely related to various diseases of the human body. Pancreatic cancer (PC) is a common malignancy of the digestive system worldwide, and it has a 5-year survival rate of only 5%. Early diagnosis of pancreatic cancer is difficult, so most patients have missed their best opportunity for surgery at the time of diagnosis. However, the etiology is not entirely clear, but there are certain associations between PC and diet, lifestyle, obesity, diabetes and chronic pancreatitis. Many studies have shown that the translocation of the gut microbiota, microbiota dysbiosis, imbalance of the oral microbiota, the interference of normal metabolism function and toxic metabolite products are closely associated with the incidence of PC and influence its prognosis. Therefore, understanding the correlation between the gut microbiota and PC could aid the diagnosis and treatment of PC. Here, we review the correlation between the gut microbiota and PC and the research progresses for the gut microbiota in the diagnosis and treatment of PC.
Collapse
Affiliation(s)
- Qiaoyu Yang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
- Queen Mary College, Nanchang University, Nanchang, China
| | - Jihang Zhang
- Institute of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
| |
Collapse
|
40
|
Oral antibiotics reduce voluntary exercise behavior in athletic mice. Behav Processes 2022; 199:104650. [PMID: 35504410 DOI: 10.1016/j.beproc.2022.104650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 04/20/2022] [Accepted: 04/27/2022] [Indexed: 11/17/2022]
|
41
|
Erinle TJ, MacIsaac J, Yang C, Adewole DI. Effect of red osier dogwood extract on growth performance, blood biochemical parameters, and gut functionality of broiler chickens challenged or unchallenged intraperitoneally with Salmonella Enteritidis lipopolysaccharide. Poult Sci 2022; 101:101861. [PMID: 35544959 PMCID: PMC9118149 DOI: 10.1016/j.psj.2022.101861] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 03/04/2022] [Accepted: 03/08/2022] [Indexed: 02/02/2023] Open
Abstract
As we advance in the search for antibiotic-alternatives, harnessing plant materials with high total polyphenol concentration (TPC) would be quintessential. Given the high TPC in red osier dogwood (ROD) extract, the current study aimed to determine its efficacy on the growth performance, intestinal health, blood biochemistry, and antioxidant capacity of broiler chickens. A 21-day 4x2 factorial feeding trial was conducted based on two main factors namely, dietary treatments and Salmonella Enteritidis Lipopolysaccharides SE-LPS) challenge. A total of 384 one-day-old mixed-sex Cobb-500 broiler chicks were randomly allotted to four dietary treatments - Negative control (NC), NC + 0.05% bacitracin methylene disalicylate (BMD), NC + 0.3%ROD, and NC+0.5% ROD. Each treatment was assigned to eight replicates with six birds/replicate. On d 13 and 20, half of the birds were intraperitoneally injected with 1mL phosphate-buffered-saline /kg BW of birds (Unchallenged-group) and the remaining half with 1mg SE-LPS /kg BW of birds (Challenged-group). Average weight gain (AWG), average feed intake (AFI), feed conversion ratio (FCR), and mortality were determined weekly. On d 21, ten chickens/treatment were euthanized for measuring blood biochemical parameters, immune organ weights, caecal SCFA, and caeca microbiota. The SE-LPS decreased (P < 0.05) AWG and FCR on d 14 and 21, respectively. On d 14, 21, and overall basis, both ROD extract levels marginally improved (P < 0.05) the AWG of unchallenged birds compared to other treatments in the unchallenged-group. Challenged and unchallenged birds fed ROD extract had deeper (P < 0.05) crypt depth (CD) and higher villus height:CD, respectively, in the ileum. Globulin (GLB) and albumin:GLB were increased and reduced (P < 0.05), respectively, among birds fed 0.3%ROD compared to other treatments. There was no treatment effect on caeca SCFA, relative weight of immune organs, and serum antioxidants. Birds fed ROD extract had a higher (P < 0.05) relative abundance of caecal Lactobacillus and Streptococcus genera compared to the antibiotic treatment. Conclusively, incorporating 0.3% and 0.5%ROD extract into broiler chickens' nutrition improved growth performance and ileal morphology, and modified caecal microbiota of broiler chickens, regardless of the intraperitoneal SE-LPS challenge.
Collapse
Affiliation(s)
- Taiwo J Erinle
- Department of Animal Science and Aquaculture, Faculty of Agriculture, Dalhousie University, Truro NS B2N 5E3, Canada
| | - Janice MacIsaac
- Department of Animal Science and Aquaculture, Faculty of Agriculture, Dalhousie University, Truro NS B2N 5E3, Canada
| | - Chengbo Yang
- Department of Animal Science, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg MB R3T 2N2, Canada
| | - Deborah I Adewole
- Department of Animal Science and Aquaculture, Faculty of Agriculture, Dalhousie University, Truro NS B2N 5E3, Canada.
| |
Collapse
|
42
|
Zhang WX, Zeng XX, Chen Q, Yu K, Zheng H, Yu XG, Zhang YJ, Zhang J, Huang HY, Huang LS. Prenatal environmental antibiotics and fetal and postnatal growth: A biomonitoring-based prospective study in Eastern China. CHEMOSPHERE 2022; 288:132657. [PMID: 34699881 DOI: 10.1016/j.chemosphere.2021.132657] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 10/19/2021] [Accepted: 10/22/2021] [Indexed: 06/13/2023]
Abstract
Thus far, the effect of environmental antibiotics exposure to offspring's growth remains unclear. Here we aimed to evaluate whether and to what extent environmental antibiotics exposure is associated with fetal and postnatal growth. A total of 735 pregnant women and their full-term offspring from the Shanghai Obesity Birth Cohort were involved in the study. Maternal urine specimen was collected during the third trimester, and urinary concentration of fifteen environmental antibiotics was measured by liquid chromatography-tandem mass spectrometry and enzymatic method. Children were followed at birth, 12, 24 and 60 months, and growth parameters of the weight and height of children were recorded. Linear regression model was applied, and it was found that maternal veterinary antibiotic (VA) concentration was negatively associated with birth weight and ponderal index [per natural-logarithm (ln)-unit: adjusted β (95% confidence interval, CI) = - 42.1 (- 74.0, - 10.3) for birth weight, -0.11 (- 0.19, - 0.02) for birth weight z-score, and - 0.03 (- 0.05, - 0.002) for ponderal index]. Regarding specific VA, each ln-unit increment of florfenicol concentrations was likely to be associate with 39.7 g (95%CI: - 69.3, - 10.1) reduced birth weight, 0.10 (95%CI: - 0.18, - 0.02) reduced birth weight z-score, and 0.02 g/cm3 (95%CI: - 0.04, - 0.00) reduced ponderal index. Ciprofloxacin, a preferred-as-veterinary antibiotic, showed a similar dose-response relationship with neonatal anthropometric parameters to florfenicol. However, these adverse effects diminished as children grew up to 12-, 24- and 60-month-old. Larger prospective cohort studies and animal experiments are warranted to verify the hypothesis that environmental antibiotics exposure in early life, even at low doses, may cause fetal growth restriction.
Collapse
Affiliation(s)
- Wei-Xi Zhang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xin-Xin Zeng
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Infectious Diseases, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qian Chen
- MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kan Yu
- Department of Infectious Diseases, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hang Zheng
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Infectious Diseases, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiao-Gang Yu
- MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yong-Jun Zhang
- Department of Neonatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Zhang
- MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - He-Yu Huang
- Department of Infectious Diseases, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Li-Su Huang
- Department of Infectious Diseases, Xinhua Children's Hospital, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| |
Collapse
|
43
|
Martínez-Montoro JI, Kuchay MS, Balaguer-Román A, Martínez-Sánchez MA, Frutos MD, Fernández-García JC, Ramos-Molina B. Gut microbiota and related metabolites in the pathogenesis of nonalcoholic steatohepatitis and its resolution after bariatric surgery. Obes Rev 2022; 23:e13367. [PMID: 34729904 DOI: 10.1111/obr.13367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/06/2021] [Accepted: 09/06/2021] [Indexed: 12/17/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasing in parallel with the rising prevalence of obesity, leading to major health and socioeconomic consequences. To date, the most effective therapeutic approach for NAFLD is weight loss. Accordingly, bariatric surgery (BS), which produces marked reductions in body weight, is associated with significant histopathological improvements in advanced stages of NAFLD, such as nonalcoholic steatohepatitis (NASH) and liver fibrosis. BS is also associated with substantial taxonomical and functional alterations in gut microbiota, which are believed to play a significant role in metabolic improvement after BS. Interestingly, gut microbiota and related metabolites may be implicated in the pathogenesis of NAFLD through diverse mechanisms, including specific microbiome signatures, short chain fatty acid production or the modulation of one-carbon metabolism. Moreover, emerging evidence highlights the potential association between gut microbiota changes after BS and NASH resolution. In this review, we summarize the current knowledge on the relationship between NAFLD severity and gut microbiota, as well as the role of the gut microbiome and related metabolites in NAFLD improvement after BS.
Collapse
Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain
| | - Mohammad Shafi Kuchay
- Division of Endocrinology and Diabetes, Medanta - The Medicity Hospital, Gurugram, Haryana, India
| | - Andrés Balaguer-Román
- Department of General and Digestive System Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain.,Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain
| | | | - María Dolores Frutos
- Department of General and Digestive System Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - José Carlos Fernández-García
- Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain
| | - Bruno Ramos-Molina
- Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain
| |
Collapse
|
44
|
Aggarwal H, Pathak P, Singh V, Kumar Y, Shankar M, Das B, Jagavelu K, Dikshit M. Vancomycin-Induced Modulation of Gram-Positive Gut Bacteria and Metabolites Remediates Insulin Resistance in iNOS Knockout Mice. Front Cell Infect Microbiol 2022; 11:795333. [PMID: 35127558 PMCID: PMC8807491 DOI: 10.3389/fcimb.2021.795333] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 12/23/2021] [Indexed: 12/27/2022] Open
Abstract
The role of oxidative and nitrosative stress has been implied in both physiology and pathophysiology of metabolic disorders. Inducible nitric oxide synthase (iNOS) has emerged as a crucial regulator of host metabolism and gut microbiota activity. The present study examines the role of the gut microbiome in determining host metabolic functions in the absence of iNOS. Insulin-resistant and dyslipidemic iNOS-/- mice displayed reduced microbial diversity, with a higher relative abundance of Allobaculum and Bifidobacterium, gram-positive bacteria, and altered serum metabolites along with metabolic dysregulation. Vancomycin, which largely depletes gram-positive bacteria, reversed the insulin resistance (IR), dyslipidemia, and related metabolic anomalies in iNOS-/- mice. Such improvements in metabolic markers were accompanied by alterations in the expression of genes involved in fatty acid synthesis in the liver and adipose tissue, lipid uptake in adipose tissue, and lipid efflux in the liver and intestine tissue. The rescue of IR in vancomycin-treated iNOS-/- mice was accompanied with the changes in select serum metabolites such as 10-hydroxydecanoate, indole-3-ethanol, allantoin, hippurate, sebacic acid, aminoadipate, and ophthalmate, along with improvement in phosphatidylethanolamine to phosphatidylcholine (PE/PC) ratio. In the present study, we demonstrate that vancomycin-mediated depletion of gram-positive bacteria in iNOS-/- mice reversed the metabolic perturbations, dyslipidemia, and insulin resistance.
Collapse
Affiliation(s)
- Hobby Aggarwal
- Pharmacology Division, Council of Scientific and Industrial Research (CSIR)-Central Drug Research Institute, Lucknow, India
| | - Priya Pathak
- Pharmacology Division, Council of Scientific and Industrial Research (CSIR)-Central Drug Research Institute, Lucknow, India
| | - Vishal Singh
- Department of Nutritional Sciences, The Pennsylvania State University, State College, PA, United States
| | - Yashwant Kumar
- Non-Communicable Diseases Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Manoharan Shankar
- Microbial Physiology Laboratory, Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, India
| | - Bhabatosh Das
- Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, Faridabad, India
| | - Kumaravelu Jagavelu
- Pharmacology Division, Council of Scientific and Industrial Research (CSIR)-Central Drug Research Institute, Lucknow, India
| | - Madhu Dikshit
- Pharmacology Division, Council of Scientific and Industrial Research (CSIR)-Central Drug Research Institute, Lucknow, India
- Non-Communicable Diseases Division, Translational Health Science and Technology Institute, Faridabad, India
| |
Collapse
|
45
|
Abbas MM, Soto P, Ramalingam L, El-Manzalawy Y, Bensmail H, Moustaid-Moussa N. Sex Differences in Fish Oil and Olanzapine Effects on Gut Microbiota in Diet-Induced Obese Mice. Nutrients 2022; 14:349. [PMID: 35057526 PMCID: PMC8780445 DOI: 10.3390/nu14020349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/30/2021] [Accepted: 01/06/2022] [Indexed: 02/05/2023] Open
Abstract
Children are prescribed second-generation antipsychotic (SGA) medications, such as olanzapine (OLZ) for FDA-approved and "off-label" indications. The long-term impact of early-life SGA medication exposure is unclear. Olanzapine and other SGA medications are known to cause excessive weight gain in young and adult patients, suggesting the possibility of long-term complications associated with the use of these drugs, such as obesity, diabetes, and heart disease. Further, the weight gain effects of OLZ have previously been shown to depend on the presence of gut bacteria and treatment with OLZ, which shifts gut bacteria toward an "obesogenic" profile. The purpose of the current study was to evaluate changes in gut bacteria in adult mice following early life treatment with OLZ and being fed either a high-fat diet or a high-fat diet supplemented with fish oil, which has previously been shown to counteract gut dysbiosis, weight gain, and inflammation produced by a high-fat diet. Female and male C57Bl/6J mice were fed a high fat diet without (HF) or with the supplementation of fish oil (HF-FO) and treated with OLZ from postnatal day (PND) 37-65 resulting in four groups of mice: mice fed a HF diet and treated with OLZ (HF-OLZ), mice fed a HF diet and treated with vehicle (HF), mice fed a HF-FO diet and treated with OLZ (HF-FO-OLZ), and mice fed a HF-FO diet and treated with vehicle (HF-FO). Following euthanasia at approximately 164 days of age, we determined changes in gut bacteria populations and serum LPS binding protein, an established marker of gut inflammation and dysbiosis. Our results showed that male HF-FO and HF-FO-OLZ mice had lower body weights, at sacrifice, compared to the HF group, with a comparable body weight across groups in female mice. HF-FO and HF-FO-OLZ male groups also exhibited lower serum LPS binding protein levels compared to the HF group, with no differences across groups in female mice. Gut microbiota profiles were also different among the four groups; the Bacteroidetes-to-Firmicutes (B/F) ratio had the lowest value of 0.51 in the HF group compared to 0.6 in HF-OLZ, 0.9 in HF-FO, and 1.1 in HF-FO-OLZ, with no differences in female mice. In conclusion, FO reduced dietary obesity and its associated inflammation and increased the B/F ratio in male mice but did not benefit the female mice. Although the weight lowering effects of OLZ were unexpected, FO effects persisted in the presence of olanzapine, demonstrating its potential protective effects in male subjects using antipsychotic drugs.
Collapse
Affiliation(s)
- Mostafa M. Abbas
- Department of Translational Data Science and Informatics, Geisinger, Danville, PA 17822, USA; (M.M.A.); (Y.E.-M.)
- Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha 5825, Qatar
| | - Paul Soto
- Department of Nutritional Sciences, Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA; (P.S.); (L.R.)
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70803, USA
- Department of Psychology, Louisiana State University, Baton Rouge, LA 70803, USA
| | - Latha Ramalingam
- Department of Nutritional Sciences, Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA; (P.S.); (L.R.)
- Department of Nutrition and Food Studies, Syracuse University, Syracuse, NY 13210, USA
| | - Yasser El-Manzalawy
- Department of Translational Data Science and Informatics, Geisinger, Danville, PA 17822, USA; (M.M.A.); (Y.E.-M.)
| | - Halima Bensmail
- Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha 5825, Qatar
| | - Naima Moustaid-Moussa
- Department of Nutritional Sciences, Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA; (P.S.); (L.R.)
| |
Collapse
|
46
|
Khushboo, Dubey KK. Microbial metabolites beneficial in regulation of obesity. CURRENT DEVELOPMENTS IN BIOTECHNOLOGY AND BIOENGINEERING 2022:355-375. [DOI: 10.1016/b978-0-12-823506-5.00006-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
47
|
Wang D, Liu J, Zhou L, Zhang Q, Li M, Xiao X. Effects of Oral Glucose-Lowering Agents on Gut Microbiota and Microbial Metabolites. Front Endocrinol (Lausanne) 2022; 13:905171. [PMID: 35909556 PMCID: PMC9326154 DOI: 10.3389/fendo.2022.905171] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 06/14/2022] [Indexed: 11/30/2022] Open
Abstract
The current research and existing facts indicate that type 2 diabetes mellitus (T2DM) is characterized by gut microbiota dysbiosis and disturbed microbial metabolites. Oral glucose-lowering drugs are reported with pleiotropic beneficial effects, including not only a decrease in glucose level but also weight loss, antihypertension, anti-inflammation, and cardiovascular protection, but the underlying mechanisms are still not clear. Evidence can be found showing that oral glucose-lowering drugs might modify the gut microbiome and thereby alter gastrointestinal metabolites to improve host health. Although the connections among gut microbial communities, microbial metabolites, and T2DM are complex, figuring out how antidiabetic agents shape the gut microbiome is vital for optimizing the treatment, meaningful for the instruction for probiotic therapy and gut microbiota transplantation in T2DM. In this review, we focused on the literatures in gut microbiota and its metabolite profile alterations beneficial from oral antidiabetic drugs, trying to provide implications for future study in the developing field of these drugs, such as combination therapies, pre- and probiotics intervention in T2DM, and subjects with pregestational diabetes and gestational diabetes mellitus.
Collapse
Affiliation(s)
- Dongmei Wang
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Jieying Liu
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
- Department of Medical Research Center, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Liyuan Zhou
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Qian Zhang
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Ming Li
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Xinhua Xiao
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
- *Correspondence: Xinhua Xiao,
| |
Collapse
|
48
|
Aggarwal H, Pathak P, Kumar Y, Jagavelu K, Dikshit M. Modulation of Insulin Resistance, Dyslipidemia and Serum Metabolome in iNOS Knockout Mice following Treatment with Nitrite, Metformin, Pioglitazone, and a Combination of Ampicillin and Neomycin. Int J Mol Sci 2021; 23:195. [PMID: 35008623 PMCID: PMC8745663 DOI: 10.3390/ijms23010195] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/28/2021] [Accepted: 12/01/2021] [Indexed: 12/27/2022] Open
Abstract
Oxidative and nitrosative stress plays a pivotal role in the incidence of metabolic disorders. Studies from this lab and others in iNOS-/- mice have demonstrated occurrence of insulin resistance (IR), hyperglycemia and dyslipidemia highlighting the importance of optimal redox balance. The present study evaluates role of nitrite, L-arginine, antidiabetics (metformin, pioglitazone) and antibiotics (ampicillin-neomycin combination, metronidazole) on metabolic perturbations observed in iNOS-/- mice. The animals were monitored for glucose tolerance (IPGTT), IR (insulin, HOMA-IR, QUICKI), circulating lipids and serum metabolomics (LC-MS). Hyperglycemia, hyperinsulinemia and IR were rescued by nitrite, antidiabetics, and antibiotics treatments in iNOS-/- mice. Glucose intolerance was improved with nitrite, metformin and pioglitazone treatment, while ampicillin-neomycin combination normalised the glucose utilization in iNOS-/- mice. Increased serum phosphatidylethanolamine lipids in iNOS-/- mice were reversed by metformin, pioglitazone and ampicillin-neomycin; dyslipidemia was however marginally improved by nitrite treatment. The metabolic improvements were associated with changes in selected serum metabolites-purines, ceramide, 10-hydroxydecanoate, glucosaminate, diosmetin, sebacic acid, 3-nitrotyrosine and cysteamine. Bacterial metabolites-hippurate, indole-3-ethanol; IR marker-aminoadipate and oxidative stress marker-ophthalmate were reduced by pioglitazone and ampicillin-neomycin, but not by nitrite and metformin treatment. Results obtained in the present study suggest a crucial role of gut microbiota in the metabolic perturbations observed in iNOS-/- mice.
Collapse
Affiliation(s)
- Hobby Aggarwal
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; (H.A.); (P.P.); (K.J.)
| | - Priya Pathak
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; (H.A.); (P.P.); (K.J.)
| | - Yashwant Kumar
- Non-Communicable Diseases Division, Translational Health Science and Technology Institute, Faridabad 121001, India;
| | - Kumaravelu Jagavelu
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; (H.A.); (P.P.); (K.J.)
| | - Madhu Dikshit
- Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; (H.A.); (P.P.); (K.J.)
- Non-Communicable Diseases Division, Translational Health Science and Technology Institute, Faridabad 121001, India;
| |
Collapse
|
49
|
Zhuang T, Li W, Yang L, Wang Z, Ding L, Zhou M. Gut Microbiota: Novel Therapeutic Target of Ginsenosides for the Treatment of Obesity and Its Complications. Front Pharmacol 2021; 12:731288. [PMID: 34512356 PMCID: PMC8429618 DOI: 10.3389/fphar.2021.731288] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
Obesity, generally characterized by excessive lipid accumulation, is a metabolic threat worldwide due to its rapid growth in global prevalence. Ginsenosides are crucial components derived from natural plants that can confer metabolic benefits for obese patients. Considering the low bioavailability and degradable properties of ginsenosides in vivo, it should be admitted that the mechanism of ginsenosides on anti-obesity contribution is still obscure. Recently, studies have indicated that ginsenoside intervention has beneficial metabolic effects on obesity and its complications because it allows for the correction of gut microbiota dysbiosis and regulates the secretion of related endogenous metabolites. In this review, we summarize the role of gut microbiota in the pathogenetic process of obesity, and explore the mechanism of ginsenosides for ameliorating obesity, which can modulate the composition of gut microbiota by improving the metabolism of intestinal endogenous substances and alleviating the level of inflammation. Ginsenosides are expected to become a promising anti-obesity medical intervention in the foreseeable clinical settings.
Collapse
Affiliation(s)
- Tongxi Zhuang
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wei Li
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, China
| | - Li Yang
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, China
| | - Zhengtao Wang
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, China
| | - Lili Ding
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, China
| | - Mingmei Zhou
- Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| |
Collapse
|
50
|
Simas AM, Kramer CD, Weinberg EO, Genco CA. Oral infection with a periodontal pathogen alters oral and gut microbiomes. Anaerobe 2021; 71:102399. [PMID: 34090994 DOI: 10.1016/j.anaerobe.2021.102399] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 04/27/2021] [Accepted: 05/25/2021] [Indexed: 01/04/2023]
Abstract
Periodontal disease, an inflammatory bone disease of the oral cavity, affects more than 50% of the United States population over the age of 30. The Gram-negative, anaerobic bacterium Porphyromonas gingivalis, the etiological agent of periodontal disease, is known to induce dysbiosis of the oral microbiome while promoting inflammatory bone loss. We have recently reported that P. gingivalis can also alter the gut microbiota of mice prone to develop inflammatory atherosclerosis. However, it is still unknown whether P. gingivalis induces similar changes to the gut microbiome as it does to oral microbiome. In this study, we demonstrate that P. gingivalis infection increases the diversity of the oral microbiome, allowing for colonization of potentially opportunistic species in the oral microbiome and overgrowth of commensal species in both the oral and gut microbiomes. Since periodontal disease treatment in humans typically involves antibiotic treatment, we also examined the combined effect of P. gingivalis infection on mice pretreated with oral antibiotics. By correlating the oral and cecal microbiota of P. gingivalis-infected mice fed a normal chow diet, we identified blooms of the Gram-negative genera Barnesiella and Bacteroides and imbalances of mucin-degrading bacteria. These disrupted community structures were predicted to have increased detrimental functional capacities including increased flavonoid degradation and l-histidine fermentation. Though antibiotic pretreatment (without P. gingivlais) had a dominant impact on the cecal microbiome, P. gingivalis infection of mice with or without antibiotic pretreatment increased the abundance of the phylum Firmicutes and the Porphyromonadaceae family in the cecum. Collectively, our study demonstrates that P. gingivalis oral infection disrupted the oral and cecal microbiomes of otherwise unperturbed mice, altering their community membership and functional potential.
Collapse
Affiliation(s)
- Alexandra M Simas
- Graduate Program in Biochemical and Molecular Nutrition, Gerald J. and Dorothy R. Friedman School of Nutrition and Science Policy, Tufts University, Boston, MA, 02111, USA; Department of Immunology, Tufts University School of Medicine, 136 Harrison Ave, M & V 701, Boston, MA, 02111, USA.
| | - Carolyn D Kramer
- Department of Immunology, Tufts University School of Medicine, 136 Harrison Ave, M & V 701, Boston, MA, 02111, USA.
| | - Ellen O Weinberg
- Department of Immunology, Tufts University School of Medicine, 136 Harrison Ave, M & V 701, Boston, MA, 02111, USA.
| | - Caroline A Genco
- Department of Immunology, Tufts University School of Medicine, 136 Harrison Ave, M & V 701, Boston, MA, 02111, USA; Graduate Program in Immunology and Molecular Microbiology, School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Ave, M & V 701, Boston, MA, 02111, USA; Molecular Microbiology, School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Ave, M & V 701, Boston, MA, 02111, USA.
| |
Collapse
|