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Yu S, Huang F, Huang Y, Yan F, Li Y, Xu S, Zhao Y, Zhang X, Chen R, Chen X, Zhang P. Deciphering the influence of gut and oral microbiomes on menopause for healthy aging. J Genet Genomics 2025; 52:601-614. [PMID: 39577767 DOI: 10.1016/j.jgg.2024.11.010] [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: 09/27/2024] [Revised: 11/08/2024] [Accepted: 11/14/2024] [Indexed: 11/24/2024]
Abstract
Menopause is characterized by the cessation of menstruation and a decline in reproductive function, which is an intrinsic component of the aging process. However, it has been a frequently overlooked field of women's health. The oral and gut microbiota, constituting the largest ecosystem within the human body, are important for maintaining human health and notably contribute to the healthy aging of menopausal women. Therefore, a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance. This paper presents the current understanding of the microbiome during menopause, with a particular focus on alterations in the oral and gut microbiota. Our study elucidates the complex interplay between the microbiome and sex hormone levels, explores microbial crosstalk dynamics, and investigates the associations between the microbiome and diseases linked to menopause. Additionally, this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases. Given that menopause can last for approximately 30 years, gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions, which may result in symptomatic relief from menopause and an increase in quality of life in women.
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Affiliation(s)
- Shuting Yu
- Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Feiling Huang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, China
| | - Yixuan Huang
- Beijing ClouDNA Technology Co., Ltd., Beijing 101407, China
| | - Fangxu Yan
- Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yi Li
- Hunan Agriculture University, Changsha, Hunan 410128, China
| | - Shenglong Xu
- Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Yan Zhao
- Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Xinlei Zhang
- Beijing ClouDNA Technology Co., Ltd., Beijing 101407, China
| | - Rong Chen
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, China.
| | - Xingming Chen
- Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
| | - Peng Zhang
- Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Rare Disease Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
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Wu O, Gao J, Zhang X, Liu W, Zhang H, Khederzadeh S, Lu X, Wu Y. TLR5's Role in Obesity-related Hypertension: Updated Evidence and Prospects. Angiology 2025:33197251326384. [PMID: 40079382 DOI: 10.1177/00033197251326384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/15/2025]
Abstract
Toll-like receptor 5 (TLR5), integral to the immune system as a primary sensor for flagellin, is central to the link between innate and adaptive immunity, modulating immune responses and cytokine production essential for defense against flagellated pathogens and immune tolerance. This review consolidates the understanding of TLR5's structural and signaling mechanisms and its interactions with flagellin, shedding light on its dual role in immune responses and its promise as a therapeutic target. It highlights TLR5's intricate role in the pathogenesis of obesity-related hypertension, a growing global health concern that correlates with rising obesity rates and is characterized by a complex interplay of immune responses and metabolic dysregulation. Despite the current understanding, the impact of TLR5 on obesity-related hypertension is marked by conflicting findings, indicating a need for further exploration. The review critically analyzes the existing literature, providing novel insights from rodent models and human studies that underscore TLR5's therapeutic potential, setting the stage for transformative research in managing obesity-related hypertension. It calls for deeper investigation into TLR5's multifaceted role, emphasizing its promise as a target for managing obesity-related hypertension and the necessity for future research to clarify its complexities and to innovate treatment strategies.
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Affiliation(s)
- Ou Wu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, P.R. China
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China
| | - Jin Gao
- Clinical Laboratory, the Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, P.R. China
| | - Xingyu Zhang
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Wei Liu
- JFIntelligent Healthcare Technology Co. Ltd, Nanchang, Jiangxi, P.R. China
| | - Hu Zhang
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital Affiliated with Medical College of Zhejiang University, Hangzhou, Zhejiang, P.R. China
| | - Saber Khederzadeh
- Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, P.R. China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, P.R. China
| | - Xi Lu
- Hangzhou Vocational and Technical College, Hangzhou, Zhejiang, P.R. China
| | - Ya Wu
- Anhui Medical University, Hefei, Anhui, P.R. China
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Islam MM, Islam MM, Rahman MA, Ripon MAR, Hossain MS. Gut microbiota in obesity and related complications: Unveiling the complex interplay. Life Sci 2023; 334:122211. [PMID: 38084672 DOI: 10.1016/j.lfs.2023.122211] [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: 09/12/2023] [Revised: 10/24/2023] [Accepted: 10/24/2023] [Indexed: 12/18/2023]
Abstract
In recent years, the obesity epidemic has escalated into a serious public health catastrophe that is only getting worse. However, research into the pathophysiological pathways behind the obesity development and the illnesses that it is associated with is ongoing. In the last decades, it is now clear that the gut microbiota plays a significant role in the genesis and progression of obesity and obesity-related illnesses, particularly changes in its metabolites and composition as obesity progresses. Here, we provide a summary of the processes by which variations in gut metabolite levels and the composition of gut microbiota affect obesity and associated disorders. The bacteria residing in the gut release several chemicals that influence the appetite control, metabolism, and other systems. Since it can either encourage or restrict the deposition of fat in several different ways, the gut microbiota's role in obesity is debatable. Additionally, we go over potential therapeutic approaches that could be utilized to alter gut microbiota composition and focus on the important metabolic pathways associated with obesity and metabolic disorders linked to obesity.
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Affiliation(s)
- Md Monirul Islam
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Md Mahmodul Islam
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Md Abdur Rahman
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Md Abdur Rahman Ripon
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Mohammad Salim Hossain
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
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Oraphruek P, Chusak C, Ngamukote S, Sawaswong V, Chanchaem P, Payungporn S, Suantawee T, Adisakwattana S. Effect of a Multispecies Synbiotic Supplementation on Body Composition, Antioxidant Status, and Gut Microbiomes in Overweight and Obese Subjects: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients 2023; 15:nu15081863. [PMID: 37111082 PMCID: PMC10141052 DOI: 10.3390/nu15081863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/05/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Studies investigating the effect of multispecies synbiotic supplementation in obesity management are limited. The current study was performed to evaluate the effects of multispecies probiotics mixed with fructooligosaccharides on body composition, antioxidant status, and gut microbiome composition in overweight and obese individuals. We employed a randomized, double-blind, placebo-controlled trial design, in which 63 individuals aged 18-45 years were assigned to receive either a synbiotic supplement or placebo for 12 weeks. The synbiotic group consumed a daily dose of 37 × 109 colony-forming units (CFU) of a unique blend of seven different probiotics, along with 2 g of fructooligosaccharides, while the placebo group consumed 2 g of maltodextrin daily. Assessments were performed at baseline, week 6, and the end of the study. The results of the study indicated that synbiotic supplementation resulted in a significant reduction in waist circumference and body fat percentage compared to the baseline measurements, as observed at 12 weeks. At the end of the study, there were no significant differences observed in body weight, BMI, waist circumference, or percentage of body fat between the synbiotic group and the placebo group. An analysis of plasma antioxidant capacity revealed that synbiotic supplementation caused a significant increase in Trolox equivalent antioxidant capacity (TEAC) and a concomitant decrease in malondialdehyde (MDA) in the test group when compared to the placebo. For the gut microbiota analysis, synbiotic supplementation significantly decreased Firmicutes abundance and the Firmicutes/Bacteroidetes (F/B) ratio at week 12 as compared to the placebo group. Nevertheless, the synbiotic group did not exhibit any substantial alterations in other biochemical blood parameters compared to the placebo group. These findings suggest that multispecies synbiotic supplementation could be a beneficial strategy to improve body composition, antioxidant status, and gut microbiome composition in overweight and obese subjects.
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Affiliation(s)
- Piyarat Oraphruek
- Phytochemical and Functional Food Research Unit for Clinical Nutrition, Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Charoonsri Chusak
- Phytochemical and Functional Food Research Unit for Clinical Nutrition, Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Sathaporn Ngamukote
- Phytochemical and Functional Food Research Unit for Clinical Nutrition, Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Vorthon Sawaswong
- Center of Excellence in Systems Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Prangwalai Chanchaem
- Center of Excellence in Systems Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Sunchai Payungporn
- Center of Excellence in Systems Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Tanyawan Suantawee
- Phytochemical and Functional Food Research Unit for Clinical Nutrition, Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Sirichai Adisakwattana
- Phytochemical and Functional Food Research Unit for Clinical Nutrition, Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Immunogenic Modification of Ligilactobacillus agilis by Specific Amino Acid Substitution of Flagellin. Appl Environ Microbiol 2022; 88:e0127722. [PMID: 36173204 PMCID: PMC9599256 DOI: 10.1128/aem.01277-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Ligilactobacillus agilis is a flagellated motile commensal microbe that resides in the gastrointestinal tract of mammals and birds. Flagellin, the major subunit protein of flagellar filament, from pathogenic bacteria is generally a proinflammatory molecule that stimulates immune cells via Toll-like receptor 5 (TLR5). Interestingly, the flagellins of L. agilis are known to be immunologically attenuated despite the fact that the structure of the proteins, including the TLR5 recognition site, is highly conserved among bacteria. The results of our previous study suggested that this is attributed to the differences in three specific amino acids within the conserved TLR5 recognition site; however, this hypothesis remains to be confirmed. In this study, a series of recombinant L. agilis flagellins, with amino acid substitutions at the TLR5 recognition site, were constructed, and their immunogenic activity was evaluated in vitro. Then, an L. agilis strain with an active immunogenic TLR5 recognition site was generated. In vitro and in vivo immunological studies revealed that the mutant L. agilis strain with the modified flagellin was more immunogenic than the wild-type strain. In conclusion, the specific amino acid residues in L. agilis flagellins likely contribute to the discrimination between pathogens and commensals by the host defense system. Additionally, the immunogenically potent L. agilis mutants may serve as a useful platform for oral vaccine delivery. IMPORTANCE The interactions between gut microbes and immune cells play an important role in the health and disease of hosts. Ligilactobacillus agilis is a flagellated commensal bacterium found in the gut of mammals and birds. However, the flagellin proteins of L. agilis are immunologically attenuated and barely induce TLR5-dependent inflammation, unlike the flagellins of several pathogenic bacteria. This study demonstrated that three specific amino acids in the flagellin protein are responsible for this low immunogenicity in L. agilis. The results obtained herein improve our understanding of the symbiosis between gut microbes and their hosts.
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Wang S, Cui K, Liu J, Hu J, Yan K, Xiao P, Lu Y, Yang X, Liang X. Mogroside-Rich Extract From Siraitia grosvenorii Fruits Ameliorates High-Fat Diet-Induced Obesity Associated With the Modulation of Gut Microbiota in Mice. Front Nutr 2022; 9:870394. [PMID: 35769373 PMCID: PMC9234556 DOI: 10.3389/fnut.2022.870394] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 05/05/2022] [Indexed: 12/29/2022] Open
Abstract
Siraitia grosvenorii is a kind of medicinal food plant. The mogroside-rich extract (MGE) of its fruits can effectively ameliorate obesity, but the underlying mechanisms remain underexplored. In this study, we aimed to determine whether MGE can ameliorate obesity by protecting against the divergences of gut microbiota. Mice were challenged with a high-fat diet (HFD) and treated with MGE by oral gavage. Then, the characteristics of the gut microbiota were determined by 16S rDNA analysis. Our findings showed that MGE could significantly reduce body weight gain and fat tissue weight of the mice fed with HFD. Moreover, MGE markedly attenuated fatty liver, and improved glucose tolerance and insulin sensitivity. We further found that the gut microbiota structures were disturbed by HFD feeding. In particular, the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased, resulting in an increased proportion of Firmicutes to Bacteroidetes (F/B), which contributes to obesity. Interestingly, the abnormal proportion of F/B of HFD feeding mice was restored to the level of control mice by MGE treatment. Additionally, the abundances of obesogenic microbiota, such as Ruminiclostridium and Oscillibacter were also decreased after MGE treatment. In summary, our findings demonstrate that MGE can modulate gut microbiota in obese mice and shed new light on how it alleviates obesity.
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Affiliation(s)
- Siyuan Wang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Kexin Cui
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Jiahao Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Jiahao Hu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Ke Yan
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Peng Xiao
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Yangqing Lu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
| | - Xiaogan Yang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
- Xiaogan Yang,
| | - Xingwei Liang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, China
- College of Animal Science and Technology, Guangxi University, Nanning, China
- *Correspondence: Xingwei Liang,
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Jian C, Silvestre MP, Middleton D, Korpela K, Jalo E, Broderick D, de Vos WM, Fogelholm M, Taylor MW, Raben A, Poppitt S, Salonen A. Gut microbiota predicts body fat change following a low-energy diet: a PREVIEW intervention study. Genome Med 2022; 14:54. [PMID: 35599315 PMCID: PMC9125896 DOI: 10.1186/s13073-022-01053-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/04/2022] [Indexed: 12/17/2022] Open
Abstract
Background Low-energy diets (LEDs) comprise commercially formulated food products that provide between 800 and 1200 kcal/day (3.3–5 MJ/day) to aid body weight loss. Recent small-scale studies suggest that LEDs are associated with marked changes in the gut microbiota that may modify the effect of the LED on host metabolism and weight loss. We investigated how the gut microbiota changed during 8 weeks of total meal replacement LED and determined their associations with host response in a sub-analysis of 211 overweight adults with pre-diabetes participating in the large multicentre PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) clinical trial. Methods Microbial community composition was analysed by Illumina sequencing of the hypervariable V3-V4 regions of the 16S ribosomal RNA (rRNA) gene. Butyrate production capacity was estimated by qPCR targeting the butyryl-CoA:acetate CoA-transferase gene. Bioinformatics and statistical analyses, such as comparison of alpha and beta diversity measures, correlative and differential abundances analysis, were undertaken on the 16S rRNA gene sequences of 211 paired (pre- and post-LED) samples as well as their integration with the clinical, biomedical and dietary datasets for predictive modelling. Results The overall composition of the gut microbiota changed markedly and consistently from pre- to post-LED (P = 0.001), along with increased richness and diversity (both P < 0.001). Following the intervention, the relative abundance of several genera previously associated with metabolic improvements (e.g., Akkermansia and Christensenellaceae R-7 group) was significantly increased (P < 0.001), while flagellated Pseudobutyrivibrio, acetogenic Blautia and Bifidobacterium spp. were decreased (all P < 0.001). Butyrate production capacity was reduced (P < 0.001). The changes in microbiota composition and predicted functions were significantly associated with body weight loss (P < 0.05). Baseline gut microbiota features were able to explain ~25% of variation in total body fat change (post–pre-LED). Conclusions The gut microbiota and individual taxa were significantly influenced by the LED intervention and correlated with changes in total body fat and body weight in individuals with overweight and pre-diabetes. Despite inter-individual variation, the baseline gut microbiota was a strong predictor of total body fat change during the energy restriction period. Trial registration The PREVIEW trial was prospectively registered at ClinicalTrials.gov (NCT01777893) on January 29, 2013. Supplementary Information The online version contains supplementary material available at 10.1186/s13073-022-01053-7.
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Mousavi SE, Delgado-Saborit JM, Adivi A, Pauwels S, Godderis L. Air pollution and endocrine disruptors induce human microbiome imbalances: A systematic review of recent evidence and possible biological mechanisms. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 816:151654. [PMID: 34785217 DOI: 10.1016/j.scitotenv.2021.151654] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/26/2021] [Accepted: 11/09/2021] [Indexed: 05/25/2023]
Abstract
A rich body of literature indicates that environmental factors interact with the human microbiome and influence its composition and functions contributing to the pathogenesis of diseases in distal sites of the body. This systematic review examines the scientific evidence on the effect of environmental toxicants, air pollutants and endocrine disruptors (EDCs), on compositional and diversity of human microbiota. Articles from PubMed, Embase, WoS and Google Scholar where included if they focused on human populations or the SHIME® model, and assessed the effects of air pollutants and EDCs on human microbiome. Non-human studies, not written in English and not displaying original research were excluded. The Newcastle-Ottawa Scale was used to assess the quality of individual studies. Results were extracted and presented in tables. 31 studies were selected, including 24 related to air pollutants, 5 related to EDCs, and 2 related to EDC using the SHIME® model. 19 studies focussed on the respiratory system (19), gut (8), skin (2), vaginal (1) and mammary (1) microbiomes. No sufficient number of studies are available to observe a consistent trend for most of the microbiota, except for streptococcus and veillionellales for which 9 out of 10, and 3 out of 4 studies suggest an increase of abundance with exposure to air pollution. A limitation of the evidence reviewed is the scarcity of existing studies assessing microbiomes from individual systems. Growing evidence suggests that exposure to environmental contaminants could change the diversity and abundance of resident microbiota, e.g. in the upper and lower respiratory, gastrointestinal, and female reproductive system. Microbial dysbiosis might lead to colonization of pathogens and outgrowth of pathobionts facilitating infectious diseases. It also might prime metabolic dysfunctions disrupting the production of beneficial metabolites. Further studies should elucidate the role of environmental pollutants in the development of dysbiosis and dysregulation of microbiota-related immunological processes.
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Affiliation(s)
- Sayed Esmaeil Mousavi
- Department of Water and Wastewater Treatment, Water and Wastewater Consulting Engineers (Design & Research), Isfahan, Iran
| | - Juana Maria Delgado-Saborit
- Perinatal Epidemiology, Environmental Health and Clinical Research, School of Medicine, Universitat Jaume I, Castellon, Spain; Environmental Research Group, MRC Centre for Environment and Health, Imperial College London, United Kingdom; School of Geography, Earth & Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
| | - Anna Adivi
- Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX 76201, USA
| | - Sara Pauwels
- Department of Public Health and Primary Care, Centre Environment & Health, KU Leuven, Belgium
| | - Lode Godderis
- Department of Public Health and Primary Care, Centre Environment & Health, KU Leuven, Belgium; IDEWE, External Service for Prevention and Protection at work, Interleuvenlaan 58, 3001 Heverlee, Belgium.
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Bezhaeva T, Karper J, Quax PHA, de Vries MR. The Intriguing Role of TLR Accessory Molecules in Cardiovascular Health and Disease. Front Cardiovasc Med 2022; 9:820962. [PMID: 35237675 PMCID: PMC8884272 DOI: 10.3389/fcvm.2022.820962] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/19/2022] [Indexed: 12/12/2022] Open
Abstract
Activation of Toll like receptors (TLR) plays an important role in cardiovascular disease development, progression and outcomes. Complex TLR mediated signaling affects vascular and cardiac function including tissue remodeling and repair. Being central components of both innate and adaptive arms of the immune system, TLRs interact as pattern recognition receptors with a series of exogenous ligands and endogenous molecules or so-called danger associated molecular patterns (DAMPs) that are released upon tissue injury and cellular stress. Besides immune cells, a number of structural cells within the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts and cardiac myocytes express TLRs and are able to release or sense DAMPs. Local activation of TLR-mediated signaling cascade induces cardiovascular tissue repair but in a presence of constant stimuli can overshoot and cause chronic inflammation and tissue damage. TLR accessory molecules are essential in guiding and dampening these responses toward an adequate reaction. Furthermore, accessory molecules assure specific and exclusive TLR-mediated signal transduction for distinct cells and pathways involved in the pathogenesis of cardiovascular diseases. Although much has been learned about TLRs activation in cardiovascular remodeling, the exact role of TLR accessory molecules is not entirely understood. Deeper understanding of the role of TLR accessory molecules in cardiovascular system may open therapeutic avenues aiming at manipulation of inflammatory response in cardiovascular disease. The present review outlines accessory molecules for membrane TLRs that are involved in cardiovascular disease progression. We first summarize the up-to-date knowledge on TLR signaling focusing on membrane TLRs and their ligands that play a key role in cardiovascular system. We then survey the current evidence of the contribution of TLRs accessory molecules in vascular and cardiac remodeling including myocardial infarction, heart failure, stroke, atherosclerosis, vein graft disease and arterio-venous fistula failure.
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Affiliation(s)
- Taisiya Bezhaeva
- Department of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
| | - Jacco Karper
- Department of Cardiology, Wilhelmina Hospital Assen, Assen, Netherlands
| | - Paul H. A. Quax
- Department of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
| | - Margreet R. de Vries
- Department of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
- *Correspondence: Margreet R. de Vries
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Rossella C, Laura F, Grazia MM, Raffaele B, Antonio T, Maria P, Francesco DV, Giovanni G. The crosstalk between gut microbiota, intestinal immunological niche and visceral adipose tissue as a new model for the pathogenesis of metabolic and inflammatory diseases: the paradigm of type 2 diabetes mellitus. Curr Med Chem 2022; 29:3189-3201. [PMID: 34986766 DOI: 10.2174/0929867329666220105121124] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 11/12/2021] [Accepted: 11/21/2021] [Indexed: 11/22/2022]
Abstract
Gut microbiota (GM) comprises more than one thousand microorganisms between bacterial species, viruses, fungi, and protozoa, and represents the main actor of a wide net of molecular interactions, involving, among others, the endocrine system, immune responses, and metabolism. GM influences many endocrine functions such as adrenal steroidogenesis, thyroid function, sexual hormones, IGF-1 pathway and peptides produced in gastrointestinal system. It is fundamental in glycaemic control and obesity, while also exerting an important function in modulating the immune system and associated inflammatory disease. The result of this crosstalk in gut mucosa is the formation of the intestinal immunological niche. Visceral adipose tissue (VAT) produces about 600 different peptides, it is involved in lipid and glucose metabolism and in some immune reactions through several adipokines. GM and VAT interact in a bidirectional fashion: while gut dysbiosis can modify VAT adipokines and hormone secretion, VAT hyperplasia modifies GM composition. Acquired or genetic factors leading to gut dysbiosis or increasing VAT (i.e., Western diet) induce a proinflammatory condition, which plays a pivotal role in the development of dysmetabolic and immunologic conditions, such as diabetes mellitus. Diabetes is clearly associated with specific patterns of GM alterations, with an abundance or reduction of GM species involved in controlling mucosal barrier status, glycaemic levels and exerting a pro- or anti-inflammatory activity. All these factors could explain the higher incidence of several inflammatory conditions in Western countries; furthermore, besides the specific alterations observed in diabetes, this paradigm could represent a common pathway acting in many metabolic conditions and could pave the way to a new, interesting therapeutic approach.
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Affiliation(s)
- Cianci Rossella
- Dipartimento di Medicina e Chirurgia Traslazionale Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario A. Gemelli, IRCCS Largo A. Gemelli, 8 00168 Rome, Italy
| | - Franza Laura
- Emergency Medicine, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Massaro Maria Grazia
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Borriello Raffaele
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Tota Antonio
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Pallozzi Maria
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - De Vito Francesco
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Gambassi Giovanni
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
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11
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Jastrząb R, Graczyk D, Siedlecki P. Molecular and Cellular Mechanisms Influenced by Postbiotics. Int J Mol Sci 2021; 22:ijms222413475. [PMID: 34948270 PMCID: PMC8707144 DOI: 10.3390/ijms222413475] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/29/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
In recent years, commensal bacteria colonizing the human body have been recognized as important determinants of health and multiple pathologic conditions. Among the most extensively studied commensal bacteria are the gut microbiota, which perform a plethora of functions, including the synthesis of bioactive products, metabolism of dietary compounds, and immunomodulation, both through attenuation and immunostimulation. An imbalance in the microbiota population, i.e., dysbiosis, has been linked to many human pathologies, including various cancer types and neurodegenerative diseases. Targeting gut microbiota and microbiome-host interactions resulting from probiotics, prebiotics, and postbiotics is a growing opportunity for the effective treatment of various diseases. As more research is being conducted, the microbiome field is shifting from simple descriptive analysis of commensal compositions to more molecular, cellular, and functional studies. Insight into these mechanisms is of paramount importance for understanding and modulating the effects that microbiota, probiotics, and their derivatives exert on host health.
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12
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Tian J, Bai B, Gao Z, Yang Y, Wu H, Wang X, Wang J, Li M, Tong X. Alleviation Effects of GQD, a Traditional Chinese Medicine Formula, on Diabetes Rats Linked to Modulation of the Gut Microbiome. Front Cell Infect Microbiol 2021; 11:740236. [PMID: 34692563 PMCID: PMC8531589 DOI: 10.3389/fcimb.2021.740236] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 09/22/2021] [Indexed: 01/14/2023] Open
Abstract
Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.
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Affiliation(s)
- Jiaxing Tian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Bingbing Bai
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Science, Beijing, China
| | - Zezheng Gao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yingying Yang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haoran Wu
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinmiao Wang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun Wang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Science, Beijing, China
| | - Min Li
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaolin Tong
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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13
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Wei YX, Zheng KY, Wang YG. Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity. World J Gastroenterol 2021; 27:5555-5565. [PMID: 34588751 PMCID: PMC8433617 DOI: 10.3748/wjg.v27.i33.5555] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/24/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut microbiota. An important next step is to elucidate a human-relevant “map’’ of microbiota-host interactions that regulate the metabolic health of the host. An improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat obesity. Intestinal mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions, including cancer, neurodegeneration, and aging. The mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly understood. Understanding the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier breakage. Changes in the composition and function of the gut microbiota, i.e., dysbiosis, are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier dysfunction. Many effects of the microbiota on the host are mediated by microbiota-derived metabolites. In this review, we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic diseases. The design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.
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Affiliation(s)
- Yan-Xia Wei
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Kui-Yang Zheng
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
| | - Yu-Gang Wang
- Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
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14
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Schreurs MPH, de Vos van Steenwijk PJ, Romano A, Dieleman S, Werner HMJ. How the Gut Microbiome Links to Menopause and Obesity, with Possible Implications for Endometrial Cancer Development. J Clin Med 2021; 10:jcm10132916. [PMID: 34209916 PMCID: PMC8268108 DOI: 10.3390/jcm10132916] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/23/2021] [Accepted: 06/25/2021] [Indexed: 12/11/2022] Open
Abstract
Background: Interest is growing in the dynamic role of gut microbiome disturbances in human health and disease. No direct evidence is yet available to link gut microbiome dysbiosis to endometrial cancer. This review aims to understand any association between microbiome dysbiosis and important risk factors of endometrial cancer, high estrogen levels, postmenopause and obesity. Methods: A systematic search was performed with PubMed as primary database. Three separate searches were performed to identify all relevant studies. Results: Fifteen studies were identified as highly relevant and included in the review. Eight articles focused on the relationship with obesity and eight studies focused on the menopausal change or estrogen levels. Due to the heterogeneity in patient populations and outcome measures, no meta-analysis could be performed. Both the menopausal change and obesity were noted to enhance dysbiosis by reducing microbiome diversity and increasing the Firmicutes to Bacteroidetes ratio. Both also incurred estrobolome changes, leading to increased systemic estrogen levels, especially after menopause. Furthermore, microbiome dysbiosis was reported to be related to systemic inflammation through toll-like receptor signaling deficiencies and overexpression of pro-inflammatory cytokines. Conclusions: This review highlights that the female gut microbiome is intrinsically linked to estrogen levels, menopausal state and systemic inflammation, which indicates gut microbiome dysbiosis as a potential hallmark for risk stratification for endometrial cancer. Studies are needed to further define the role the gut microbiome plays in women at risk for endometrial cancer.
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Affiliation(s)
- Malou P. H. Schreurs
- Department of Obstetrics, Gynecology and Gynecologic Oncology, Medisch Spectrum Twente, 7512 KZ Enschede, The Netherlands
- Maastricht University Medical Centre, Department of Obstetrics and Gynecology, GROW—School for Oncology and Development Biology, 6202 AZ Maastricht, The Netherlands; (P.J.d.V.v.S.); (A.R.); (H.M.J.W.)
- Correspondence:
| | - Peggy J. de Vos van Steenwijk
- Maastricht University Medical Centre, Department of Obstetrics and Gynecology, GROW—School for Oncology and Development Biology, 6202 AZ Maastricht, The Netherlands; (P.J.d.V.v.S.); (A.R.); (H.M.J.W.)
| | - Andrea Romano
- Maastricht University Medical Centre, Department of Obstetrics and Gynecology, GROW—School for Oncology and Development Biology, 6202 AZ Maastricht, The Netherlands; (P.J.d.V.v.S.); (A.R.); (H.M.J.W.)
| | - Sabine Dieleman
- Maastricht University Medical Centre, Department of Surgery, GROW—School for Oncology and Developmental Biology, 6202 AZ Maastricht, The Netherlands;
| | - Henrica M. J. Werner
- Maastricht University Medical Centre, Department of Obstetrics and Gynecology, GROW—School for Oncology and Development Biology, 6202 AZ Maastricht, The Netherlands; (P.J.d.V.v.S.); (A.R.); (H.M.J.W.)
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15
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Borella F, Carosso AR, Cosma S, Preti M, Collemi G, Cassoni P, Bertero L, Benedetto C. Gut Microbiota and Gynecological Cancers: A Summary of Pathogenetic Mechanisms and Future Directions. ACS Infect Dis 2021; 7:987-1009. [PMID: 33848139 DOI: 10.1021/acsinfecdis.0c00839] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Over the past 20 years, important relationships between the microbiota and human health have emerged. A link between alterations of microbiota composition (dysbiosis) and cancer development has been recently demonstrated. In particular, the composition and the oncogenic role of intestinal bacterial flora has been extensively investigated in preclinical and clinical studies focusing on gastrointestinal tumors. Overall, the development of gastrointestinal tumors is favored by dysbiosis as it leads to depletion of antitumor substances (e.g., short-chain fatty acids) produced by healthy microbiota. Moreover, dysbiosis leads to alterations of the gut barrier, promotes a chronic inflammatory status through activation of toll-like receptors, and causes metabolic and hormonal dysregulations. However, the effects of these imbalances are not limited to the gastrointestinal tract and they can influence gynecological tumor carcinogenesis as well. The purpose of this Review is to provide a synthetic update about the mechanisms of interaction between gut microbiota and the female reproductive tract favoring the development of neoplasms. Furthermore, novel therapeutic approaches based on the modulation of microbiota and their role in gynecological oncology are discussed.
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Affiliation(s)
- Fulvio Borella
- Obstetrics and Gynecology Unit 1, Sant’ Anna Hospital, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy
| | - Andrea Roberto Carosso
- Obstetrics and Gynecology Unit 1, Sant’ Anna Hospital, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy
| | - Stefano Cosma
- Obstetrics and Gynecology Unit 1, Sant’ Anna Hospital, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy
| | - Mario Preti
- Obstetrics and Gynecology Unit 1, Sant’ Anna Hospital, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy
| | - Giammarco Collemi
- Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | | | - Luca Bertero
- Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Chiara Benedetto
- Obstetrics and Gynecology Unit 1, Sant’ Anna Hospital, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy
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16
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The Effect of LPS and Flagellin on the Process of Lipolysis in Mesenchymal Stromal Cells during Adipogenic Differentiation. Bull Exp Biol Med 2021; 170:571-574. [PMID: 33725252 DOI: 10.1007/s10517-021-05108-4] [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: 06/22/2020] [Indexed: 10/21/2022]
Abstract
We analyzed the effects of bacterial pathogen-associated molecular patterns (LPS and flagellin) and adrenergic agonist isoproterenol on the content of total and phosphorylated (Ser552) hormone-sensitive lipase in mesenchymal stromal cells and cell products of their adipogenic differentiation. The expression of hormone-sensitive lipase and an increase in the content of its activated phosphorylated form were demonstrated by Western blotting in cells of all three lines of adipogenic differentiation. Under the influence of flagellin, the content of total and phosphorylated forms of hormone-sensitive lipase increased in brown adipocytes, while LPS induced a decrease in the content of total hormone-sensitive lipase in white adipocytes. We hypothesize that bacterial pathogen-associated molecular patterns can activate lipolysis under pathological conditions associated with slow remodeling of the adipose tissue.
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17
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Crovesy L, El-Bacha T, Rosado EL. Modulation of the gut microbiota by probiotics and symbiotics is associated with changes in serum metabolite profile related to a decrease in inflammation and overall benefits to metabolic health: a double-blind randomized controlled clinical trial in women with obesity. Food Funct 2021; 12:2161-2170. [PMID: 33565558 DOI: 10.1039/d0fo02748k] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Modulation of the gut microbiota may help in treating obesity by improving host metabolic health. We aimed to evaluate the effects of probiotics or symbiotics on body weight and serum metabolite profile in women with obesity. A double-blind, parallel, randomized, controlled clinical trial was conducted with 32 adult women with body mass index ranging from 30 to 34.9 kg m-2. Volunteers followed a low-energy diet and were subjected to 8 weeks intervention: probiotic group (PG - Bifidobacterium lactis UBBLa-70, n = 10), symbiotic group (SG - Bifidobacterium lactis UBBLa-70 and fructooligosaccharide, n = 11), or control group (CG - placebo, n = 11). Analyses of anthropometric variables, gut microbiota and serum metabolites by 1H nuclear magnetic resonance (NMR) were performed at baseline and after the intervention. Multivariate statistics showed that all groups presented a decrease in glycerol and increase in arginine, glutamine and 2-oxoisovalerate. Therefore, a low-energy diet per se promoted changes in the metabolite profile related to decreased inflammation and positive effects on body weight. SG presented unique changes in metabolites (increase in pyruvate and alanine and decrease in citrate and BCAA). Negative correlations between arginine and glutamine with fat mass were observed in the SG. PG presented a decrease in 1H NMR lipid signals and negative correlation between Verrucomicrobia and Firmicutes with (CH2)n lipids. Both probiotics and symbiotics promoted changes in metabolites related to improved metabolic health. Specific metabolite changes following symbiotic intervention might suggest some advantage in providing Bifidobacterium lactis in combination with fructooligosaccharide in a low-energy diet, rather than probiotics or diet alone. Clinical trial: NCT02505854.
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Affiliation(s)
- Louise Crovesy
- Department of Nutrition and Dietetics (DND), Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro - RJ, Brazil.
| | - Tatiana El-Bacha
- Lebiome - Núcleo de estudos com bioativos, Mitocôndria e metabolismo da placenta, Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro - RJ, Brazil
| | - Eliane Lopes Rosado
- Department of Nutrition and Dietetics (DND), Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro - RJ, Brazil.
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18
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Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis. SCI 2021. [DOI: 10.3390/sci3010013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] Open
Abstract
Toll-like receptor 5 ligand, flagellin, and vascular adhesion protein 1 (VAP-1) are involved in non-alcoholic fatty liver disease. This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected into C57BL/6J (WT) and C57BL/6-Aoc3-/- (VAP-1 KO) mice on a high-fat diet twice a week every 2 weeks for 10 weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration, and lipolysis in visceral adipose tissue. Consequently, an increased release of glycerol led to hepatic steatosis in WT, but not in KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT mice, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.
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19
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Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis. SCI 2019. [DOI: 10.3390/sci1030065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.
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20
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Cao SY, Zhao CN, Xu XY, Tang GY, Corke H, Gan RY, Li HB. Dietary plants, gut microbiota, and obesity: Effects and mechanisms. Trends Food Sci Technol 2019. [DOI: 10.1016/j.tifs.2019.08.004] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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21
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Martin CL, Jima D, Sharp GC, McCullough LE, Park SS, Gowdy KM, Skaar D, Cowley M, Maguire RL, Fuemmeler B, Collier D, Relton CL, Murphy SK, Hoyo C. Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study. Epigenetics 2019; 14:325-340. [PMID: 30773972 PMCID: PMC6557549 DOI: 10.1080/15592294.2019.1581594] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 01/25/2019] [Accepted: 01/28/2019] [Indexed: 01/03/2023] Open
Abstract
Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4-5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: -0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: -0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity.
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Affiliation(s)
- Chantel L Martin
- a Department of Epidemiology , Gillings School of Global Public Health, University of North Carolina , Chapel Hill , NC , USA
| | - Dereje Jima
- b Center of Human Health and the Environment , North Carolina State University , Raleigh , USA
- c Bioinformatics Research Center , North Carolina State University , Raleigh , NC , USA
| | - Gemma C Sharp
- d Medical Research Integrative Epidemiology Unit , Bristol Medical School, Population Health Sciences, University of Bristol , Bristol , UK
| | - Lauren E McCullough
- e Department of Epidemiology , Rollins School of Public Health, Emory University , Atlanta , GA , USA
| | - Sarah S Park
- f Department of Biological Sciences , North Carolina State University , Raleigh , NC , USA
| | - Kymberly M Gowdy
- g Department of Pharmacology and Toxicology , Brody School of Medicine, East Carolina University , Greenville , NC , USA
| | - David Skaar
- f Department of Biological Sciences , North Carolina State University , Raleigh , NC , USA
| | - Michael Cowley
- f Department of Biological Sciences , North Carolina State University , Raleigh , NC , USA
| | - Rachel L Maguire
- f Department of Biological Sciences , North Carolina State University , Raleigh , NC , USA
| | - Bernard Fuemmeler
- h Department of Health Behavior and Policy , Virginia Commonwealth University , Richmond , VA , USA
| | - David Collier
- i Department of Pediatrics , Brody School of Medicine, East Carolina University , Greenville , NC , USA
| | - Caroline L Relton
- d Medical Research Integrative Epidemiology Unit , Bristol Medical School, Population Health Sciences, University of Bristol , Bristol , UK
| | - Susan K Murphy
- j Division of Reproductive Sciences, Department of Obstetrics and Gynecology , Duke University School of Medicine , Durham , NC , USA
| | - Cathrine Hoyo
- b Center of Human Health and the Environment , North Carolina State University , Raleigh , USA
- f Department of Biological Sciences , North Carolina State University , Raleigh , NC , USA
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22
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Hibberd AA, Yde CC, Ziegler ML, Honoré AH, Saarinen MT, Lahtinen S, Stahl B, Jensen HM, Stenman LK. Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults. Benef Microbes 2019; 10:121-135. [PMID: 30525950 DOI: 10.3920/bm2018.0028] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The gut microbiota contributes to host energy metabolism, and altered gut microbiota has been associated with obesity-related metabolic disorders. We previously reported that a probiotic alone or together with a prebiotic controls body fat mass in healthy overweight or obese individuals in a randomised, double-blind, placebo controlled clinical study (ClinicalTrials.gov NCT01978691). We now aimed to investigate whether changes in the gut microbiota may be associated with the observed clinical benefits. Faecal and plasma samples were obtained from a protocol compliant subset (n=134) of participants from a larger clinical study where participants were randomised (1:1:1:1) into four groups: (1) placebo, 12 g/d microcrystalline cellulose; (2) Litesse® Ultra™ polydextrose (LU), 12 g/day; (3) Bifidobacterium animalis subsp. lactis 420™ (B420), 1010 cfu/d in 12 g microcrystalline cellulose; (4) LU+B420, 1010 cfu/d of B420 in 12 g/d LU for 6 months of intervention. The faecal microbiota composition and metabolites were assessed as exploratory outcomes at baseline, 2, 4, 6 months, and +1 month post-intervention and correlated to obesity-related clinical outcomes. Lactobacillus and Akkermansia were more abundant with B420 at the end of the intervention. LU+B420 increased Akkermansia, Christensenellaceae and Methanobrevibacter, while Paraprevotella was reduced. Christensenellaceae was consistently increased in the LU and LU+B420 groups across the intervention time points, and correlated negatively to waist-hip ratio and energy intake at baseline, and waist-area body fat mass after 6 months treatment with LU+B420. Functional metagenome predictions indicated alterations in pathways related to cellular processes and metabolism. Plasma bile acids glycocholic acid, glycoursodeoxycholic acid, and taurohyodeoxycholic acid and tauroursodeoxycholic acid were reduced in LU+B420 compared to Placebo. Consumption of B420 and its combination with LU resulted in alterations of the gut microbiota and its metabolism, and may support improved gut barrier function and obesity-related markers.
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Affiliation(s)
- A A Hibberd
- 1 Genomics and Microbiome Science, DuPont Nutrition & Health, 4300 Duncan Avenue, Saint Louis, MO 63110, USA
| | - C C Yde
- 2 DuPont Nutrition Biosciences ApS, Edwin Rahrsvej 38, 8220 Brabrand, Aarhus, Denmark
- 3 Department of Food Science, Aarhus University, Kirstinebjergvej 10, 5792 Aarslev, Denmark
| | - M L Ziegler
- 4 DuPont Nutrition & Health, 3329 Agriculture Drive, Madison, WI 53716, USA
| | - A H Honoré
- 2 DuPont Nutrition Biosciences ApS, Edwin Rahrsvej 38, 8220 Brabrand, Aarhus, Denmark
| | - M T Saarinen
- 5 Global Health and Nutrition Science, DuPont Nutrition & Health, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - S Lahtinen
- 5 Global Health and Nutrition Science, DuPont Nutrition & Health, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - B Stahl
- 4 DuPont Nutrition & Health, 3329 Agriculture Drive, Madison, WI 53716, USA
| | - H M Jensen
- 2 DuPont Nutrition Biosciences ApS, Edwin Rahrsvej 38, 8220 Brabrand, Aarhus, Denmark
| | - L K Stenman
- 5 Global Health and Nutrition Science, DuPont Nutrition & Health, Sokeritehtaantie 20, 02460 Kantvik, Finland
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Duan J, Liang S, Feng L, Yu Y, Sun Z. Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro. Int J Nanomedicine 2018; 13:7303-7318. [PMID: 30519016 PMCID: PMC6233484 DOI: 10.2147/ijn.s185348] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Background As a promising nanocarrier in biomedical fields, silica nanoparticles (SiNPs) could transfer from the circulatory system to multiple organs. Among these, blood–liver molecular exchange is a critical factor in biological response to NPs. However, the potential effect of SiNPs on hepatic lipid metabolism is unclear. In this study, we employed three models to attempt discover whether and how SiNPs disturb hepatic lipid metabolism in vivo and in vitro. Methods Firstly we used ICR mice models to evaulated the effects of SiNPs on the serum and hepatic lipid levels through repeated intravenous administration, meanwhile, the protein expressions of protein markers of lipogenesis (ACC1 and FAS), the key enzyme of fatty acid β-oxidation, CPT1A,and leptin levels in liver were detected by western blot. For verification studies, the model organism zebrafish and cultured hepatic L02 cells were further performed. The TLR5 and adipocytokine-signaling pathway were verified. Results Inflammatory cell infiltration and mild steatosis induced by SiNPs were observed in the liver. Cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were elevated significantly in both blood serum and liver tissue, whereas the ratio of high-density:low-density lipoprotein cholesterol was markedly decreased. Protein markers of lipogenesis (ACC1 and FAS) were elevated significantly in liver tissue, whereas the key enzyme of fatty acid β-oxidation, CPT1A, was decreased significantly. Interestingly, leptin levels in the SiNP-treated group were also elevated markedly. In addition, SiNPs caused hepatic damage and steatosis in zebrafish and enhanced hyperlipemia in high-cholesterol diet zebrafish. Similarly, SiNPs increased the release of inflammatory cytokines (IL1β, IL6, IL8, and TNFα) and activated the TLR5-signaling pathway in hepatic L02 cells. Conclusion In summary, our study found that SiNPs triggered hyperlipemia and hepatic steatosis via the TLR5-signaling pathway. This suggests that regulation of TLR5 could be a novel therapeutic target to reduce side effects of NPs in living organisms.
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Affiliation(s)
- Junchao Duan
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China, ; .,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China, ;
| | - Shuang Liang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China, ; .,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China, ;
| | - Lin Feng
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China, ; .,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China, ;
| | - Yang Yu
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China, ; .,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China, ;
| | - Zhiwei Sun
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, PR China, ; .,Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, PR China, ;
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24
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Arias-Jayo N, Abecia L, Alonso-Sáez L, Ramirez-Garcia A, Rodriguez A, Pardo MA. High-Fat Diet Consumption Induces Microbiota Dysbiosis and Intestinal Inflammation in Zebrafish. MICROBIAL ECOLOGY 2018; 76:1089-1101. [PMID: 29736898 DOI: 10.1007/s00248-018-1198-9] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 04/27/2018] [Indexed: 05/26/2023]
Abstract
Energy-dense foods and overnutrition represent major starting points altering lipid metabolism, systemic inflammation and gut microbiota. The aim of this work was to investigate the effects of a high-fat diet (HFD) over a period of 25 days on intestinal microbiota and inflammation in zebrafish. Microbial composition of HFD-fed animals was analysed and compared to controls by 16S rRNA sequencing and quantitative PCR. The expression level on several genes related to inflammation was tested. Furthermore, microscopic assessment of the intestine was performed in both conditions. The consumption of the HFD resulted in microbial dysbiosis, characterised by an increase in the relative abundance of the phylum Bacteroidetes. Moreover, an emerging intestinal inflammation via NF-κβ activation was confirmed by the overexpression of several genes related to signalling receptors, antimicrobial metabolism and the inflammatory cascade. The intestinal barrier was also damaged, with an increase of goblet cell mucin production. This is the first study performed in zebrafish which suggests that the consumption of a diet enriched with 10% fat changes the intestinal microbial community composition, which was correlated with low-grade inflammation.
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Affiliation(s)
- Nerea Arias-Jayo
- Food research, Azti, Parque tecnológico de Bizkaia, Astondo Bidea 609, 48160, Derio, Spain.
| | - Leticia Abecia
- CIC bioGUNE, Parque Tecnológico de Bizkaia, Edificio 801A, 48160, Derio, Spain
| | - Laura Alonso-Sáez
- Marine research, Azti, Txatxarramendi ugartea z/g, 48395, Txatxarramendi, Spain
| | - Andoni Ramirez-Garcia
- Departmento de Immunología, Microbiología y Parasitología, Facultad de Ciencia y Tecnología, Universidad del País Vasco (UPV/EHU), 48940, Leioa, Spain
| | - Alfonso Rodriguez
- St Luke's General Hospital, Freshford Road, Friarsinch, Kilkenny, R95 FY71, Ireland
| | - Miguel A Pardo
- Food research, Azti, Parque tecnológico de Bizkaia, Astondo Bidea 609, 48160, Derio, Spain
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25
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Laing B, Barnett MPG, Marlow G, Nasef NA, Ferguson LR. An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets. Expert Rev Gastroenterol Hepatol 2018; 12:969-983. [PMID: 30052094 DOI: 10.1080/17474124.2018.1505497] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.
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Affiliation(s)
- Bobbi Laing
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,b School of Nursing, Faculty of Medical and Health Sciences , The University of Auckland , Auckland , New Zealand
| | - Matthew P G Barnett
- c Food Nutrition & Health Team, Food & Bio-Based Products Group , AgResearch Limited , Palmerston North , New Zealand.,d Liggins Institute , The High-Value Nutrition National Science Challenge , Auckland , New Zealand.,e Riddet Institute , Massey University , Palmerston North , New Zealand
| | - Gareth Marlow
- f Institute of Medical Genetics , Cardiff University , Cardiff , Wales , UK
| | - Noha Ahmed Nasef
- e Riddet Institute , Massey University , Palmerston North , New Zealand.,g College of Health, Massey Institute of Food Science and Technology , Palmerston North , New Zealand
| | - Lynnette R Ferguson
- a Discipline of Nutrition and Dietetics, Faculty of Medical Health Sciences , The University of Auckland , Auckland , New Zealand.,h Auckland Cancer Research Society, Faculty of Medical and Health Sciences, Grafton Campus , The University of Auckland , Auckland , New Zealand
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26
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Galla S, Chakraborty S, Cheng X, Yeo J, Mell B, Zhang H, Mathew AV, Vijay-Kumar M, Joe B. Disparate effects of antibiotics on hypertension. Physiol Genomics 2018; 50:837-845. [PMID: 30095376 DOI: 10.1152/physiolgenomics.00073.2018] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Gut microbiota are associated with a variety of complex polygenic diseases. The usage of broad-spectrum antibiotics by patients affected by such diseases is an important environmental factor to consider, because antibiotics, which are widely prescribed to curb pathological bacterial infections, also indiscriminately eliminate gut commensal microbiota. However, the extent to which antibiotics reshape gut microbiota and per se contribute to these complex diseases is understudied. Because genetics play an important role in predisposing individuals to these modern diseases, we hypothesize that the extent to which antibiotics influence complex diseases depends on the host genome and metagenome. The current study tests this hypothesis in the context of hypertension, which is a serious risk factor for cardiovascular diseases. A 3 × 2 factorial design was used to test the blood pressure (BP) and microbiotal effects of three different antibiotics, neomycin, minocycline, and vancomycin, on two well-known, preclinical, genetic models of hypertension, the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), both of which develop hypertension, but for different genetic reasons. Regardless of the class, oral administration of antibiotics increased systolic blood pressure of the S rat, while minocycline and vancomycin, but not neomycin, lowered systolic blood pressure in the SHR. These disparate BP effects were accompanied by significant alterations in gut microbiota. Our study highlights the need to consider an individualized approach for the usage of antibiotics among hypertensives, as their BP could be affected differentially based on their individual genetic and microbiotal communities.
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Affiliation(s)
- S Galla
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
| | - S Chakraborty
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
| | - X Cheng
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
| | - J Yeo
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
| | - B Mell
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
| | - H Zhang
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
| | - A V Mathew
- Department of Internal Medicine-Nephrology, University of Michigan , Ann Arbor, Michigan
| | - M Vijay-Kumar
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
| | - B Joe
- Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio
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Abstract
In recent years, the gut microbiota (the microorganisms that live in our digestive tract) has become an area of great interest. Indeed, this intestinal microbial community performs essential functions in maintaining our health, and has been proven to influence host physiology and metabolism. Thereby, dysregulation of this gut microbiota may be implicated in the development of various diseases, including obesity. However, studies rarely assess causality, which requires the use of germ-free animals and microbiota transplant. Using these strategies, some gut microbiota were shown to confer obesity and associated metabolic disorders to mice, suggesting a causative link between gut bacteria and metabolic diseases.
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Singh SP, Huck O, Abraham NG, Amar S. Kavain Reduces Porphyromonas gingivalis-Induced Adipocyte Inflammation: Role of PGC-1α Signaling. THE JOURNAL OF IMMUNOLOGY 2018; 201:1491-1499. [PMID: 30037847 DOI: 10.4049/jimmunol.1800321] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 06/28/2018] [Indexed: 12/11/2022]
Abstract
A link between obesity and periodontitis has been suggested because of compromised immune response and chronic inflammation in obese patients. In this study, we evaluated the anti-inflammatory properties of Kavain, an extract from Piper methysticum, on Porphyromonas gingivalis-induced inflammation in adipocytes with special focus on peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) and related pathways. The 3T3-L1 mouse preadipocytes and primary adipocytes harvested from mouse adipose tissue were infected with P. gingivalis, and inflammation (TNF-α; adiponectin/adipokines), oxidative stress, and adipogenic marker (FAS, CEBPα, and PPAR-γ) expression were measured. Furthermore, effect of PGC-1α knockdown on Kavain action was evaluated. Results showed that P. gingivalis worsens adipocyte dysfunction through increase of TNF-α, IL-6, and iNOS and decrease of PGC-1α and adiponectin. Interestingly, although Kavain obliterated P. gingivalis-induced proinflammatory effects in wild-type cells, Kavain did not affect PGC-1α-deficient cells, strongly advocating for Kavain effects being mediated by PGC-1α. In vivo adipocytes challenged with i.p. injection of P. gingivalis alone or P. gingivalis and Kavain displayed the same phenotype as in vitro adipocytes. Altogether, our findings established anti-inflammatory and antioxidant effects of Kavain on adipocytes and emphasized protective action against P. gingivalis-induced adipogenesis. The use of compounds such as Kavain offer a portal to potential therapeutic approaches to counter chronic inflammation in obesity-related diseases.
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Affiliation(s)
- Shailendra P Singh
- Department of Pharmacology, New York Medical College, Valhalla, NY 10595
| | - Olivier Huck
- INSERM, UMR 1260, Regenerative Nanomedicine (Fédération de Médicine Translationalle de Strasbourg), 67000 Strasbourg, France; and.,Periodontology, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France
| | - Nader G Abraham
- Department of Pharmacology, New York Medical College, Valhalla, NY 10595
| | - Salomon Amar
- Department of Pharmacology, New York Medical College, Valhalla, NY 10595;
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29
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Keskitalo A, Munukka E, Toivonen R, Hollmén M, Kainulainen H, Huovinen P, Jalkanen S, Pekkala S. Enterobacter cloacae administration induces hepatic damage and subcutaneous fat accumulation in high-fat diet fed mice. PLoS One 2018; 13:e0198262. [PMID: 29847581 PMCID: PMC5976205 DOI: 10.1371/journal.pone.0198262] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 05/16/2018] [Indexed: 12/14/2022] Open
Abstract
Accumulating evidence indicates that gut microbiota plays a significant role in obesity, insulin resistance and associated liver disorders. Family Enterobacteriaceae and especially Enterobacter cloacae strain B29 have been previously linked to obesity and hepatic damage. The underlying mechanisms, however, remain unclear. Therefore, we comprehensively examined the effects of E. cloacae subsp. cloacae (ATCC® 13047™) administration on host metabolism of mice fed with high-fat diet (HFD). C57BL/6N mice were randomly divided into HFD control, chow control, and E. cloacae treatment groups. The E. cloacae treatment group received live bacterial cells in PBS intragastrically twice a week, every other week for 13 weeks. Both control groups received PBS intragastrically. After the 13-week treatment period, the mice were sacrificed for gene and protein expression and functional analyses. Our results show that E. cloacae administration increased subcutaneous fat mass and the relative proportion of hypertrophic adipocytes. Both subcutaneous and visceral fat had signs of decreased insulin signaling and elevated lipolysis that was reflected in higher serum glycerol levels. In addition, E. cloacae -treated mice had significantly higher hepatic AST and AST/ALT ratio, and their liver histology indicated fibrosis, demonstrating that E. cloacae subsp. cloacae administration promotes hepatic damage in HFD fed mice.
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Affiliation(s)
- Anniina Keskitalo
- Institute of Biomedicine, University of Turku, Turku, Finland
- Department of Clinical Microbiology, Turku University Hospital, Turku, Finland
| | - Eveliina Munukka
- Department of Clinical Microbiology, Turku University Hospital, Turku, Finland
| | - Raine Toivonen
- Institute of Biomedicine, University of Turku, Turku, Finland
| | - Maija Hollmén
- Institute of Biomedicine, University of Turku, Turku, Finland
- Medicity Research Laboratory, University of Turku, Turku, Finland
| | - Heikki Kainulainen
- Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Pentti Huovinen
- Institute of Biomedicine, University of Turku, Turku, Finland
| | - Sirpa Jalkanen
- Institute of Biomedicine, University of Turku, Turku, Finland
- Medicity Research Laboratory, University of Turku, Turku, Finland
| | - Satu Pekkala
- Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
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30
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Alderete TL, Jones RB, Chen Z, Kim JS, Habre R, Lurmann F, Gilliland FD, Goran MI. Exposure to traffic-related air pollution and the composition of the gut microbiota in overweight and obese adolescents. ENVIRONMENTAL RESEARCH 2018; 161:472-478. [PMID: 29220800 PMCID: PMC5747978 DOI: 10.1016/j.envres.2017.11.046] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 11/23/2017] [Accepted: 11/27/2017] [Indexed: 05/05/2023]
Abstract
BACKGROUND Traffic-related air pollution (TRAP) exposure has been linked to type 2 diabetes and metabolic dysfunction in humans. Animal studies suggest that air pollutants may alter the composition of the gut microbiota, which may negatively impact metabolic health through changes in the composition and/or function of the gut microbiome. OBJECTIVES The primary aim of this study was to determine whether elevated TRAP exposure was correlated with gut bacterial taxa in overweight and obese adolescents from the Meta-AIR (Metabolic and Asthma Incidence Research) study. The secondary aim was to examine whether gut microbial taxa correlated with TRAP were also correlated with risk factors for type 2 diabetes (e.g., fasting glucose levels). We additionally explored whether correlations between TRAP and these metabolic risk factors could be explained by the relative abundance of these taxa. METHODS Participants (17-19 years; n=43) were enrolled between 2014 and 2016 from Southern California. The CALINE4 line dispersion model was used to model prior year residential concentrations of nitrogen oxides (NOx) as a marker of traffic emissions. The relative abundance of fecal microbiota was characterized by 16S rRNA sequencing and spearman partial correlations were examined after adjusting for body fat percent. RESULTS Freeway TRAP was correlated with decreased Bacteroidaceae (r=-0.48; p=0.001) and increased Coriobacteriaceae (r=0.48; p<0.001). These same taxa were correlated with fasting glucose levels, including Bacteroidaceae (r=-0.34; p=0.04) and Coriobacteriaceae (r=0.41; p<0.01). Further, freeway TRAP was positively correlated fasting glucose (r=0.45; p=0.004) and Bacteroidaceae and Coriobacteriaceae explained 24% and 29% of the correlation between TRAP and fasting glucose levels. CONCLUSIONS Increased TRAP exposure was correlated with gut microbial taxa and fasting glucose levels. Gut microbial taxa that were correlated with TRAP partially explained the correlation between TRAP and fasting glucose levels. These results suggest that exposure to air pollutants may negatively impact metabolic health via alterations in the gut microbiota.
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Affiliation(s)
- Tanya L Alderete
- Department of Preventive Medicine, Division of Environmental Health, University of Southern California, Los Angeles, CA, USA.
| | - Roshonda B Jones
- Department of Preventive Medicine, Diabetes and Obesity Research Institute, University of Southern California, Los Angeles, CA, USA
| | - Zhanghua Chen
- Department of Preventive Medicine, Division of Environmental Health, University of Southern California, Los Angeles, CA, USA
| | - Jeniffer S Kim
- Department of Preventive Medicine, Division of Environmental Health, University of Southern California, Los Angeles, CA, USA
| | - Rima Habre
- Department of Preventive Medicine, Division of Environmental Health, University of Southern California, Los Angeles, CA, USA
| | | | - Frank D Gilliland
- Department of Preventive Medicine, Division of Environmental Health, University of Southern California, Los Angeles, CA, USA
| | - Michael I Goran
- Department of Preventive Medicine, Diabetes and Obesity Research Institute, University of Southern California, Los Angeles, CA, USA; Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA, USA
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31
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Janket SJ, Nunn ME, Salih E, Baird AE. Evidence-Based Approach in Translational Dental Research. TRANSLATIONAL ORAL HEALTH RESEARCH 2018:81-101. [DOI: 10.1007/978-3-319-78205-8_8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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32
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Su A, Yang W, Zhao L, Pei F, Yuan B, Zhong L, Ma G, Hu Q. Flammulina velutipes polysaccharides improve scopolamine-induced learning and memory impairment in mice by modulating gut microbiota composition. Food Funct 2018; 9:1424-1432. [DOI: 10.1039/c7fo01991b] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Flammulina velutipes polysaccharides (FVP) and the FVP-induced microbiota have been proved to be effective in improving learning and memory impairment in mice.
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Affiliation(s)
- Anxiang Su
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
| | - Wenjian Yang
- College of Food Science and Engineering
- Nanjing University of Finance and Economics
- Nanjing 210023
- People's Republic of China
| | - Liyan Zhao
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
| | - Fei Pei
- College of Food Science and Engineering
- Nanjing University of Finance and Economics
- Nanjing 210023
- People's Republic of China
| | - Biao Yuan
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
| | - Lei Zhong
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
| | - Gaoxing Ma
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
| | - Qiuhui Hu
- College of Food Science and Technology
- Nanjing Agricultural University
- Nanjing 210095
- People's Republic of China
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33
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Yang J, Yan H. TLR5: beyond the recognition of flagellin. Cell Mol Immunol 2017; 14:1017-1019. [PMID: 29151579 DOI: 10.1038/cmi.2017.122] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Accepted: 10/08/2017] [Indexed: 12/20/2022] Open
Affiliation(s)
- Jingyi Yang
- Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
| | - Huimin Yan
- Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
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34
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Romano KA, Martinez-Del Campo A, Kasahara K, Chittim CL, Vivas EI, Amador-Noguez D, Balskus EP, Rey FE. Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption. Cell Host Microbe 2017; 22:279-290.e7. [PMID: 28844887 DOI: 10.1016/j.chom.2017.07.021] [Citation(s) in RCA: 142] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 06/13/2017] [Accepted: 07/31/2017] [Indexed: 01/05/2023]
Abstract
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.
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Affiliation(s)
- Kymberleigh A Romano
- Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA
| | - Ana Martinez-Del Campo
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
| | - Kazuyuki Kasahara
- Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA
| | - Carina L Chittim
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
| | - Eugenio I Vivas
- Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA
| | - Daniel Amador-Noguez
- Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA
| | - Emily P Balskus
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
| | - Federico E Rey
- Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
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35
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Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice. ISME JOURNAL 2017; 11:1667-1679. [PMID: 28375212 DOI: 10.1038/ismej.2017.24] [Citation(s) in RCA: 168] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 11/10/2016] [Accepted: 01/27/2017] [Indexed: 02/06/2023]
Abstract
Faecalibacterium prausnitzii is considered as one of the most important bacterial indicators of a healthy gut. We studied the effects of oral F. prausnitzii treatment on high-fat fed mice. Compared to the high-fat control mice, F. prausnitzii-treated mice had lower hepatic fat content, aspartate aminotransferase and alanine aminotransferase, and increased fatty acid oxidation and adiponectin signaling in liver. Hepatic lipidomic analyses revealed decreases in several species of triacylglycerols, phospholipids and cholesteryl esters. Adiponectin expression was increased in the visceral adipose tissue, and the subcutaneous and visceral adipose tissues were more insulin sensitive and less inflamed in F. prausnitzii-treated mice. Further, F. prausnitzii treatment increased muscle mass that may be linked to enhanced mitochondrial respiration, modified gut microbiota composition and improved intestinal integrity. Our findings show that F. prausnitzii treatment improves hepatic health, and decreases adipose tissue inflammation in mice and warrant the need for further studies to discover its therapeutic potential.
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Rintala A, Pietilä S, Munukka E, Eerola E, Pursiheimo JP, Laiho A, Pekkala S, Huovinen P. Gut Microbiota Analysis Results Are Highly Dependent on the 16S rRNA Gene Target Region, Whereas the Impact of DNA Extraction Is Minor. J Biomol Tech 2017; 28:19-30. [PMID: 28260999 DOI: 10.7171/jbt.17-2801-003] [Citation(s) in RCA: 107] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Next-generation sequencing (NGS) is currently the method of choice for analyzing gut microbiota composition. As gut microbiota composition is a potential future target for clinical diagnostics, it is of utmost importance to enhance and optimize the NGS analysis procedures. Here, we have analyzed the impact of DNA extraction and selected 16S rDNA primers on the gut microbiota NGS results. Bacterial DNA from frozen stool specimens was extracted with 5 commercially available DNA extraction kits. Special attention was paid to the semiautomated DNA extraction methods that could expedite the analysis procedure, thus being especially suitable for clinical settings. The microbial composition was analyzed with 2 distinct protocols: 1 targeting the V3-V4 and the other targeting the V4-V5 area of the bacterial 16S rRNA gene. The overall effect of DNA extraction on the gut microbiota 16S rDNA profile was relatively small, whereas the 16S rRNA gene target region had an immense impact on the results. Furthermore, semiautomated DNA extraction methods clearly appeared suitable for NGS procedures, proposing that application of these methods could importantly reduce hands-on time and human errors without compromising the validity of results.
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Affiliation(s)
- Anniina Rintala
- Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland;; Department of Clinical Microbiology and Immunology, Turku University Hospital, Turku, Finland
| | | | - Eveliina Munukka
- Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland;; Department of Clinical Microbiology and Immunology, Turku University Hospital, Turku, Finland
| | - Erkki Eerola
- Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland;; Department of Clinical Microbiology and Immunology, Turku University Hospital, Turku, Finland
| | | | - Asta Laiho
- Turku Centre for Biotechnology, Turku, Finland
| | - Satu Pekkala
- Unit of Health Sciences, Faculty of Sports, University of Jyväskylä, Jyväskylä, Finland
| | - Pentti Huovinen
- Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
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Aguirre M, Venema K. Challenges in simulating the human gut for understanding the role of the microbiota in obesity. Benef Microbes 2016; 8:31-53. [PMID: 27903093 DOI: 10.3920/bm2016.0113] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
There is an elevated incidence of cases of obesity worldwide. Therefore, the development of strategies to tackle this condition is of vital importance. This review focuses on the necessity of optimising in vitro systems to model human colonic fermentation in obese subjects. This may allow to increase the resolution and the physiological relevance of the information obtained from this type of studies when evaluating the potential role that the human gut microbiota plays in obesity. In light of the parameters that are currently used for the in vitro simulation of the human gut (which are mostly based on information derived from healthy subjects) and the possible difference with an obese condition, we propose to revise and improve specific standard operating procedures.
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Affiliation(s)
- M Aguirre
- 1 Top Institute of Food and Nutrition, P.O. Box 557, 6700 AA Wageningen, the Netherlands.,2 Department of Human Biology, Faculty of Health, Medicine and Life Sciences, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.,3 The Netherlands Organization for Applied Scientific Research (TNO), P.O. Box 360, 3700 AJ Zeist, the Netherlands
| | - K Venema
- 1 Top Institute of Food and Nutrition, P.O. Box 557, 6700 AA Wageningen, the Netherlands.,2 Department of Human Biology, Faculty of Health, Medicine and Life Sciences, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands.,4 Beneficial Microbes Consultancy, Johan Karschstraat 3, 6709 TN Wageningen, the Netherlands
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Fialho A, Fialho A, Thota P, McCullough A, Shen B. Higher visceral to subcutaneous fat ratio is associated with small intestinal bacterial overgrowth. Nutr Metab Cardiovasc Dis 2016; 26:773-777. [PMID: 27282099 DOI: 10.1016/j.numecd.2016.04.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Revised: 04/06/2016] [Accepted: 04/09/2016] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND AIMS There is a lack of studies evaluating the association between small intestinal bacterial overgrowth (SIBO) and abdominal fat. The aim of this study was to evaluate whether visceral fat area (VFA), subcutaneous fat area (SFA) or visceral to subcutaneous fat ratio (VFA/SFA ratio) were associated with SIBO. METHODS AND RESULTS In this case-control study, 152 eligible patients submitted to glucose hydrogen/methane breath test who also had computed tomography (CT) of the abdomen performed were included. Clinical and demographic information was obtained. VFA and SFA were measured using Image J software at lumbar 3 level on CT cross-sectional image of the 152 patients included in this study, 68 patients (44.7%) tested positive for SIBO. In the univariate analysis, the presence of SIBO was associated with older age (65.2 ± 1.5 vs. 59.3 ± 1.5, p = 0.007); type 2 diabetes mellitus (33.8% vs. 17.9%; p = 0.019); hypertension (63.2% vs. 39.3%; p = 0.003); metabolic syndrome (85.3% vs. 64.3%; p = 0.003); and higher VFA/SFA ratio (1.0 ± 0.1 vs. 0.7 ± 0.1; p < 0.001). In multivariate analysis, metabolic syndrome (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p = 0.035) and higher VFA/SFA ratio (OR: 3.3; 95% CI: 1.6-7.2; p = 0.002) remained independently associated with SIBO. CONCLUSION The presence of SIBO was found to be associated with high VFA/SFA ratio measured from cross-sectional CT image.
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Affiliation(s)
- A Fialho
- Department of Internal Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA.
| | - A Fialho
- Department of Internal Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - P Thota
- Department of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - A McCullough
- Department of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - B Shen
- Department of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA
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Harakeh SM, Khan I, Kumosani T, Barbour E, Almasaudi SB, Bahijri SM, Alfadul SM, Ajabnoor GMA, Azhar EI. Gut Microbiota: A Contributing Factor to Obesity. Front Cell Infect Microbiol 2016; 6:95. [PMID: 27625997 PMCID: PMC5003832 DOI: 10.3389/fcimb.2016.00095] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Accepted: 08/17/2016] [Indexed: 12/25/2022] Open
Abstract
Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 10(14) microorganisms reside within the lower human intestine and many of these 10(14) microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity.
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Affiliation(s)
- Steve M Harakeh
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University Jeddah, Saudi Arabia
| | - Imran Khan
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz UniversityJeddah, Saudi Arabia; Department of Biochemistry, Faculty of Science, King Abdulaziz UniversityJeddah, Saudi Arabia
| | - Taha Kumosani
- Department of Biochemistry, Faculty of Science, King Abdulaziz UniversityJeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz UniversityJeddah, Saudi Arabia
| | - Elie Barbour
- Department of Animal and Veterinary Sciences, Faculty of Agricultural and Food Sciences, American University of BeirutBeirut, Lebanon; Department of Biochemistry, Faculty of Science, King Abdulaziz UniversityJeddah, Saudi Arabia
| | - Saad B Almasaudi
- Biology Department, Faculty of Science, King Abdulaziz University Jeddah, Saudi Arabia
| | - Suhad M Bahijri
- Clinical Biochemistry Department, College of Medicine, Nutrition Unit-King Fahd Medical Research Center, King Abdulaziz University Jeddah, Saudi Arabia
| | | | - Ghada M A Ajabnoor
- Clinical Biochemistry Department, College of Medicine, Nutrition Unit-King Fahd Medical Research Center, King Abdulaziz University Jeddah, Saudi Arabia
| | - Esam I Azhar
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz UniversityJeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Science, King Abdulaziz UniversityJeddah, Saudi Arabia
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Gu BX, Wang X, Yin BL, Guo HB, Zhang HL, Zhang SD, Zhang CL. Abnormal expression of TLRs may play a role in lower embryo quality of women with polycystic ovary syndrome. Syst Biol Reprod Med 2016; 62:353-8. [PMID: 27367829 DOI: 10.1080/19396368.2016.1187683] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
UNLABELLED Toll-like receptors (TLRs) localize in mammalian ovary, including granulosa cells, cumulus cells, and theca cells. Previous studies demonstrated that TLRs may be important for the cumulus-oocyte complex expansion and fertilization. There is no evidence to indicate that the deletion of TLRs will induce infertility; however, the abnormal expression of TLRs may decrease oocyte quality and fertility rate. In the present study, we investigated the effects of polycystic ovary syndrome (PCOS) on the expression of TLRs in cumulus cells by using western-blot and quantitative real-time PCR (qRT-PCR) analyses. We found that the expression of TLR4 and 9 in cumulus cells was influenced significantly by PCOS. We also observed that overweight/obesity changed the expression of TLR2 and 5 in cumulus cells of PCOS subjects. In addition, we found that the rate of available embryos of women with PCOS was slightly lower. These results indicate that the abnormal expression of TLRs in cumulus may be a reason for the lower embryo quality of women with PCOS. ABBREVIATIONS ART: assisted reproductive technology BMI: body mass index COC: cumulus-cell-oocyte complex PCOS: polycystic ovary syndrome q RT-PCR quantitative real-time PCR TLRs: Toll-like receptors.
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Affiliation(s)
- Bao-Xia Gu
- a Reproductive Medicine Center , Henan Provincial People's Hospital & People's Hospital of Zhengzhou University , Zhengzhou , Henan , P.R. China
| | - Xue Wang
- a Reproductive Medicine Center , Henan Provincial People's Hospital & People's Hospital of Zhengzhou University , Zhengzhou , Henan , P.R. China
| | - Bao-Li Yin
- a Reproductive Medicine Center , Henan Provincial People's Hospital & People's Hospital of Zhengzhou University , Zhengzhou , Henan , P.R. China
| | - Hai-Bin Guo
- a Reproductive Medicine Center , Henan Provincial People's Hospital & People's Hospital of Zhengzhou University , Zhengzhou , Henan , P.R. China
| | - He-Long Zhang
- a Reproductive Medicine Center , Henan Provincial People's Hospital & People's Hospital of Zhengzhou University , Zhengzhou , Henan , P.R. China
| | - Shao-Di Zhang
- a Reproductive Medicine Center , Henan Provincial People's Hospital & People's Hospital of Zhengzhou University , Zhengzhou , Henan , P.R. China
| | - Cui-Lian Zhang
- a Reproductive Medicine Center , Henan Provincial People's Hospital & People's Hospital of Zhengzhou University , Zhengzhou , Henan , P.R. China
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Wasielewski H, Alcock J, Aktipis A. Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health. Ann N Y Acad Sci 2016; 1372:20-8. [DOI: 10.1111/nyas.13118] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Revised: 05/05/2016] [Accepted: 05/06/2016] [Indexed: 12/21/2022]
Affiliation(s)
| | - Joe Alcock
- Department of Emergency Medicine University of New Mexico Albuquerque New Mexico
| | - Athena Aktipis
- Department of Psychology Arizona State University Tempe Arizona
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42
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Impact of gut microbiota on diabetes mellitus. DIABETES & METABOLISM 2016; 42:303-315. [PMID: 27179626 DOI: 10.1016/j.diabet.2016.04.004] [Citation(s) in RCA: 165] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 04/04/2016] [Accepted: 04/07/2016] [Indexed: 02/07/2023]
Abstract
Various functions of the gut are regulated by sophisticated interactions among its functional elements, including the gut microbiota. These microorganisms play a crucial role in gastrointestinal mucosa permeability. They control the fermentation and absorption of dietary polysaccharides to produce short-chain fatty acids, which may explain their importance in the regulation of fat accumulation and the subsequent development of obesity-related diseases, suggesting that they are a crucial mediator of obesity and its consequences. In addition, gut bacteria play a crucial role in the host immune system, modulation of inflammatory processes, extraction of energy from the host diet and alterations of human gene expression. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of diabetes in susceptible individuals. The main objective of this review is to address the pathogenic association between gut microbiota and diabetes, and to explore any novel related therapeutic targets. New insights into the role of the gut microbiota in diabetes could lead to the development of integrated strategies using probiotics to prevent and treat these metabolic disorders.
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43
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Kobyliak N, Virchenko O, Falalyeyeva T. Pathophysiological role of host microbiota in the development of obesity. Nutr J 2016; 15:43. [PMID: 27105827 PMCID: PMC4841968 DOI: 10.1186/s12937-016-0166-9] [Citation(s) in RCA: 99] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Accepted: 04/21/2016] [Indexed: 12/16/2022] Open
Abstract
Overweight and obesity increase the risk for a number of diseases, namely, cardiovascular diseases, type 2 diabetes, dyslipidemia, premature death, non-alcoholic fatty liver disease as well as different types of cancer. Approximately 1.7 billion people in the world suffer from being overweight, most notably in developed countries. Current research efforts have focused on host and environmental factors that may affect energy balance. It was hypothesized that a microbiota profile specific to an obese host with increased energy-yielding behavior may exist. Consequently, the gut microbiota is becoming of significant research interest in relation to obesity in an attempt to better understand the aetiology of obesity and to develop new methods of its prevention and treatment. Alteration of microbiota composition may stimulate development of obesity and other metabolic diseases via several mechanisms: increasing gut permeability with subsequent metabolic inflammation; increasing energy harvest from the diet; impairing short-chain fatty acids synthesis; and altering bile acids metabolism and FXR/TGR5 signaling. Prebiotics and probiotics have physiologic functions that contribute to the health of gut microbiota, maintenance of a healthy body weight and control of factors associated with obesity through their effects on mechanisms that control food intake, body weight, gut microbiota and inflammatory processes.
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Affiliation(s)
- Nazarii Kobyliak
- Bogomolets National Medical University, T. Shevchenko Boulevard, 13, Kyiv, 01601, Ukraine.
| | - Oleksandr Virchenko
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601, Ukraine
| | - Tetyana Falalyeyeva
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601, Ukraine
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Munukka E, Wiklund P, Partanen T, Välimäki S, Laakkonen EK, Lehti M, Fischer-Posovzsky P, Wabitsch M, Cheng S, Huovinen P, Pekkala S. Adipocytes as a Link Between Gut Microbiota-Derived Flagellin and Hepatocyte Fat Accumulation. PLoS One 2016; 11:e0152786. [PMID: 27035341 PMCID: PMC4817958 DOI: 10.1371/journal.pone.0152786] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 03/18/2016] [Indexed: 01/22/2023] Open
Abstract
While the role of both elevated levels of circulating bacterial cell wall components and adipose tissue in hepatic fat accumulation has been recognized, it has not been considered that the bacterial components-recognizing adipose tissue receptors contribute to the hepatic fat content. In this study we found that the expression of adipose tissue bacterial flagellin (FLG)-recognizing Toll-like receptor (TLR) 5 associated with liver fat content (r = 0.699, p = 0.003) and insulin sensitivity (r = -0.529, p = 0.016) in humans (n = 23). No such associations were found for lipopolysaccharides (LPS)-recognizing TLR4. To study the underlying molecular mechanisms of these associations, human HepG2 hepatoma cells were exposed in vitro to the conditioned culture media derived from FLG or LPS-challenged human adipocytes. The adipocyte-mediated effects were also compared to the effects of direct HepG2 exposure to FLG and LPS. We found that the media derived from FLG-treated adipocytes stimulated fat accumulation in HepG2 cells, whereas either media derived from LPS-treated adipocytes or direct FLG or LPS exposure did not. This is likely due to that FLG-treatment of adipocytes increased lipolysis and secretion of glycerol, which is known to serve a substrate for triglyceride synthesis in hepatocytes. Similarly, only FLG-media significantly decreased insulin signaling-related Akt phosphorylation, IRS1 expression and mitochondrial respiratory chain ATP5A. In conclusion, our results suggest that the FLG-induced TLR5 activation in adipocytes increases glycerol secretion from adipocytes and decreases insulin signaling and mitochondrial functions, and increases fat accumulation in hepatocytes. These mechanisms could, at least partly, explain the adipose tissue TLR5 expression associated with liver fat content in humans.
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Affiliation(s)
- Eveliina Munukka
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
- Department of Clinical Microbiology and Immunology, University of Turku, Turku, Finland
| | - Petri Wiklund
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Tiina Partanen
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Sakari Välimäki
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Eija K. Laakkonen
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Maarit Lehti
- LIKES Research Center for Sport and Health Sciences, Jyväskylä, Finland
| | | | - Martin Wabitsch
- Division of Pediatric Endocrinology and Diabetes, University Medical Center Ulm, Ulm, Germany
| | - Sulin Cheng
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
- Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
| | - Pentti Huovinen
- Department of Clinical Microbiology and Immunology, University of Turku, Turku, Finland
| | - Satu Pekkala
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
- Department of Clinical Microbiology and Immunology, University of Turku, Turku, Finland
- * E-mail:
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Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation. Clin Sci (Lond) 2015; 129:1083-96. [PMID: 26464517 DOI: 10.1042/cs20150431] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.
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46
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Yan L, Liang J, Yao C, Wu P, Zeng X, Cheng K, Yin H. Pyrimidine Triazole Thioether Derivatives as Toll-Like Receptor 5 (TLR5)/Flagellin Complex Inhibitors. ChemMedChem 2015; 11:822-6. [DOI: 10.1002/cmdc.201500471] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Indexed: 12/11/2022]
Affiliation(s)
- Lei Yan
- Center of Basic Molecular Science, Department of Chemistry; Tsinghua University; Beijing 100082 China
| | - Jiaqi Liang
- Center of Basic Molecular Science, Department of Chemistry; Tsinghua University; Beijing 100082 China
| | - Chengbo Yao
- Center of Basic Molecular Science, Department of Chemistry; Tsinghua University; Beijing 100082 China
| | - Peiyao Wu
- Center of Basic Molecular Science, Department of Chemistry; Tsinghua University; Beijing 100082 China
| | - Xianfeng Zeng
- Center of Basic Molecular Science, Department of Chemistry; Tsinghua University; Beijing 100082 China
| | - Kui Cheng
- Center of Basic Molecular Science, Department of Chemistry; Tsinghua University; Beijing 100082 China
| | - Hang Yin
- Center of Basic Molecular Science, Department of Chemistry; Tsinghua University; Beijing 100082 China
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Cavalcante-Silva LHA, Galvão JGFM, da Silva JSDF, de Sales-Neto JM, Rodrigues-Mascarenhas S. Obesity-Driven Gut Microbiota Inflammatory Pathways to Metabolic Syndrome. Front Physiol 2015; 6:341. [PMID: 26635627 PMCID: PMC4652019 DOI: 10.3389/fphys.2015.00341] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Accepted: 11/03/2015] [Indexed: 12/28/2022] Open
Abstract
The intimate interplay between immune system, metabolism, and gut microbiota plays an important role in controlling metabolic homeostasis and possible obesity development. Obesity involves impairment of immune response affecting both innate and adaptive immunity. The main factors involved in the relationship of obesity with inflammation have not been completely elucidated. On the other hand, gut microbiota, via innate immune receptors, has emerged as one of the key factors regulating events triggering acute inflammation associated with obesity and metabolic syndrome. Inflammatory disorders lead to several signaling transduction pathways activation, inflammatory cytokine, chemokine production and cell migration, which in turn cause metabolic dysfunction. Inflamed adipose tissue, with increased macrophages infiltration, is associated with impaired preadipocyte development and differentiation to mature adipose cells, leading to ectopic lipid accumulation and insulin resistance. This review focuses on the relationship between obesity and inflammation, which is essential to understand the pathological mechanisms governing metabolic syndrome.
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Affiliation(s)
- Luiz H A Cavalcante-Silva
- Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas, Laboratório de Imunofarmacologia, Centro de Biotecnologia, Universidade Federal da Paraíba João Pessoa, Brasil
| | - José G F M Galvão
- Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas, Laboratório de Imunofarmacologia, Centro de Biotecnologia, Universidade Federal da Paraíba João Pessoa, Brasil
| | - Juliane Santos de França da Silva
- Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, Laboratório de Imunofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba João Pessoa, Brasil
| | - José M de Sales-Neto
- Programa de Pós-Graduação em Biotecnologia, Laboratório de Imunofarmacologia, Centro de Biotecnologia, Universidade Federal da Paraíba João Pessoa, Brasil
| | - Sandra Rodrigues-Mascarenhas
- Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas, Laboratório de Imunofarmacologia, Centro de Biotecnologia, Universidade Federal da Paraíba João Pessoa, Brasil ; Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, Laboratório de Imunofarmacologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba João Pessoa, Brasil ; Programa de Pós-Graduação em Biotecnologia, Laboratório de Imunofarmacologia, Centro de Biotecnologia, Universidade Federal da Paraíba João Pessoa, Brasil
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48
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Abstract
The innate immune system includes several classes of pattern recognition receptors (PRRs), including membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). These receptors detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the extracellular and intracellular space. Intracellular NLRs constitute inflammasomes, which activate and release caspase-1, IL-1β, and IL-18 thereby initiating an inflammatory response. Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the development and progression of diabetes mellitus and diabetic nephropathy. TLR2, TLR4, and the NLRP3 inflammasome can induce the production of various proinflammatory cytokines and are critically involved in inflammatory responses in pancreatic islets, and in adipose, liver and kidney tissues. This Review describes how innate immune system-driven inflammatory processes can lead to apoptosis, tissue fibrosis, and organ dysfunction resulting in insulin resistance, impaired insulin secretion, and renal failure. We propose that careful targeting of TLR2, TLR4, and NLRP3 signalling pathways could be beneficial for the treatment of diabetes mellitus and diabetic nephropathy.
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49
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Qian LL, Li HT, Zhang L, Fang QC, Jia WP. Effect of the Gut Microbiota on Obesity and Its Underlying Mechanisms: an Update. BIOMEDICAL AND ENVIRONMENTAL SCIENCES : BES 2015; 28:839-847. [PMID: 26695364 DOI: 10.1016/s0895-3988(15)30116-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Accepted: 10/27/2015] [Indexed: 01/05/2025]
Affiliation(s)
- Ling Ling Qian
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200025, China; Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Hua Ting Li
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200025, China
| | - Lei Zhang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200025, China; Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Qi Chen Fang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200025, China
| | - Wei Ping Jia
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200025, China; Department of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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