|
1
|
Fan X, Zhou Y, Bai W, Li X, Lin L, Lin H, Yang M, Yu X, Wang J, Lin L, Wang W. Intravital imaging of translocated bacteria via fluorogenic labeling of gut microbiota in situ. Proc Natl Acad Sci U S A 2025; 122:e2415845122. [PMID: 40153461 PMCID: PMC12002288 DOI: 10.1073/pnas.2415845122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 02/19/2025] [Indexed: 03/30/2025] Open
Abstract
The translocation of bacteria from intestinal tracts into blood vessels and distal organs plays pivotal roles in the pathogenesis of numerous severe diseases. Intravital monitoring of bacterial translocation, however, is not yet feasible, which greatly hinders us from comprehending this spatially and temporally dynamic process. Here we report an in vivo fluorogenic labeling method, which enables in situ imaging of mouse gut microbiota and real-time tracking of the translocated bacteria. By mimicking the peptidoglycan stem peptide in bacteria, a tetrapeptide probe composed of alternating D- and L-amino acids and separately equipped with a fluorophore and a quencher on the N- and C-terminal amino acid, is designed. Because of its resistance to host proteases, it can be directly used in gavage and achieves fluorogenic labeling of the microbiota in the gut via the functioning of the L,D-transpeptidases of the labeled bacteria. Using intravital two-photon microscopy, we then successfully visualize the translocation of gut bacteria into the bloodstream and liver in obesity mouse models. This technique can help further exploration into the spatiotemporal activities of gut microbiota in vivo, and be valuable in investigating the less understood pathogenicity of bacterial translocation in many severe diseases.
Collapse
Affiliation(s)
- Xinqi Fan
- State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai200032, China
| | - Yingjun Zhou
- State Key Laboratory of Genetic Engineering, Department of Microbiology, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai200438, China
- Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai200127, China
| | - Wenjuan Bai
- Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai200025, China
| | - Xue Li
- State Key Laboratory of Genetic Engineering, Department of Microbiology, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai200438, China
| | - Liyuan Lin
- Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai200127, China
| | - Huibin Lin
- Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai200127, China
| | - Ming Yang
- State Key Laboratory of Genetic Engineering, Department of Microbiology, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai200438, China
| | - Xiaofei Yu
- State Key Laboratory of Genetic Engineering, Department of Microbiology, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai200438, China
| | - Jing Wang
- Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai200025, China
| | - Liang Lin
- State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai200032, China
| | - Wei Wang
- State Key Laboratory of Genetic Engineering, Department of Microbiology, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai200438, China
- Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai200127, China
| |
Collapse
|
|
2
|
Chudzicka-Strugała I, Kubiak A, Banaszewska B, Wysocka E, Zwozdziak B, Siakowska M, Pawelczyk L, Duleba AJ. Six-month randomized, placebo controlled trial of synbiotic supplementation in women with polycystic ovary syndrome undergoing lifestyle modifications. Arch Gynecol Obstet 2025; 311:499-506. [PMID: 39636391 PMCID: PMC11890239 DOI: 10.1007/s00404-024-07833-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 11/08/2024] [Indexed: 12/07/2024]
Abstract
PURPOSE To determine whether long-term administration of synbiotics affects clinical, endocrine and metabolic aspects of polycystic ovary syndrome (PCOS) in overweight and obese subjects undergoing intensive lifestyle modifications. METHODS During six-month trial, all subjects underwent intensive lifestyle modifications (diet and exercise). The subjects were randomized (1:1) to receive synbiotic supplementation (Synbiotic Group) or placebo (Placebo Group). RESULTS Subjects in the Placebo Group and the Synbiotic Group experienced significant reduction of BMI (- 8% and - 11%, respectively; both at P < 0.0001) and body fat percentage (- 11% and - 14%, respectively; both at P < 0.0001). These effects were statistically comparable for both groups. Total testosterone was not significantly changed in the Placebo Group (- 5%, P = 0.41) while it greatly declined in the Synbiotic Group (- 40%; P < 0.0001); the difference between these groups was significant (P = 0.0002). Synbiotic supplementation was superior to placebo in reducing LH (- 21%; P = 0.047), total cholesterol (- 6%; P = 0.002), low-density lipoprotein cholesterol (- 6%; P = 0.044), triglycerides (- 29%; P = 0.049), LPS (- 23%; P = 0.001) and LPS-binding protein (- 21%; P = 0.001). CONCLUSIONS Synbiotic supplementation led to a marked improvement of several key clinical and laboratory aspects of PCOS including an improvement of hyperandrogenism, lipid profile, and markers of endotoxemia. TRIAL REGISTRATION Clinical Trial Registration Number: NCT03325023 (URL, clinicaltrials.gov; date of registration 10/26/2017).
Collapse
Affiliation(s)
| | - Anna Kubiak
- Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, 60-535, Poznan, Poland
| | - Beata Banaszewska
- Department of Laboratory Diagnostics, Poznan University of Medical Sciences, 60-569, Poznan, Poland
| | - Ewa Wysocka
- Department of Laboratory Diagnostics, Poznan University of Medical Sciences, 60-569, Poznan, Poland
| | - Barbara Zwozdziak
- Department of Medical Microbiology, Poznan University of Medical Sciences, 60-535, Poznan, Poland
| | - Martyna Siakowska
- Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, 60-535, Poznan, Poland
| | - Leszek Pawelczyk
- Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, 60-535, Poznan, Poland
| | - Antoni J Duleba
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, 9500 Gilman Drive, 0633, San Diego, CA, 92093-0633, USA.
| |
Collapse
|
|
3
|
Otaru S, Jones LE, Carpenter DO. Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study. Environ Health 2024; 23:58. [PMID: 38926689 PMCID: PMC11210132 DOI: 10.1186/s12940-024-01098-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 06/18/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. METHODS We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. RESULTS In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. CONCLUSIONS We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.
Collapse
Affiliation(s)
- Sarah Otaru
- Department of Environmental Health Sciences, University at Albany, State University of New York, 1 University Place, Rensselaer, NY, USA
- Institute for Health and the Environment (IHE), 5 University Place, Rensselaer, NY, USA
| | - Laura E Jones
- Institute for Health and the Environment (IHE), 5 University Place, Rensselaer, NY, USA.
- Center for Biostatistics, Bassett Research Institute, 1 Atwell Rd., Cooperstown, NY, USA.
- Department of Epidemiology and Biostatistics, School of Public Health, State University of New York, 1 University Place, Rensselaer, NY, USA.
| | - David O Carpenter
- Department of Environmental Health Sciences, University at Albany, State University of New York, 1 University Place, Rensselaer, NY, USA
- Institute for Health and the Environment (IHE), 5 University Place, Rensselaer, NY, USA
| |
Collapse
|
|
4
|
Sheng D, Li P, Xiao Z, Li X, Liu J, Xiao B, Liu W, Zhou L. Identification of bidirectional causal links between gut microbiota and narcolepsy type 1 using Mendelian randomization. Sleep 2024; 47:zsae004. [PMID: 38174762 DOI: 10.1093/sleep/zsae004] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 12/16/2023] [Indexed: 01/05/2024] Open
Abstract
STUDY OBJECTIVES Narcolepsy type 1 (NT1), characterized by cataplexy and orexin deficiency, is a rare and frequently debilitating neurological disorder. It has been noted to have connections with the gut microbiota, yet the exact causal relationships remain unclear. METHODS We conducted a comprehensive bidirectional Mendelian randomization (MR) study to rigorously investigate the causal links between the gut microbiota and NT1, utilizing genetic datasets from the MiBioGen consortium and FinnGen consortium, respectively. The inverse-variance weighted (IVW) method was employed to obtain the primary MR estimates, supplemented by several alternative methods as well as sensitivity analyses including Cochran's Q, MR-Egger, MR pleiotropy residual sum and outlier, leave-one-out, and genetic colocalization. RESULTS Our findings indicated that an increased relative abundance of five genera including Blautia (p = 4.47E-5), Collinsella (p = 0.036), Gordonibacter (p = 0.047), Hungatella (p = 0.015), and Lachnospiraceae UCG010 (p = 0.027) may be associated with a decreased risk of NT1. Conversely, an increased relative abundance of class Betaproteobacteria (p = 0.032), genus Alloprevotella (p = 0.009), and genus Ruminiclostridium6 (p = 0.029) may potentially heighten the risk of NT1. The onset of NT1 may lead to a decrease in the relative abundance of genus Eubacterium eligens group (p = 0.022), while a increase in the family Family XI (p = 0.009), genus Hungatella (p = 0.005), genus Prevotella (p = 0.013), and unknown genus id.2001 (p = 0.019). These findings remained robust under all sensitivity analyses. CONCLUSIONS Our results offer robust evidence for the bidirectional causal links between particular gut microbial taxa and NT1, underscoring the significance of the microbiota-gut-brain axis in the pathological process of NT1.
Collapse
Affiliation(s)
- Dandan Sheng
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Peihong Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zheng Xiao
- Department of Pathology, First Hospital of Changsha, Changsha, Hunan, China
| | - Xinru Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jing Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Bo Xiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Weiping Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Luo Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| |
Collapse
|
|
5
|
Ferrer MD, Reynés C, Jiménez L, Malagraba G, Monserrat-Mesquida M, Bouzas C, Sureda A, Tur JA, Pons A. Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation. Int J Mol Sci 2024; 25:3001. [PMID: 38474248 DOI: 10.3390/ijms25053001] [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: 01/18/2024] [Revised: 02/28/2024] [Accepted: 03/02/2024] [Indexed: 03/14/2024] Open
Abstract
SARS-CoV-2 induces a hyperinflammatory reaction due to the excessive release of cytokines during the immune response. The bacterial endotoxin lipopolysaccharide (LPS) contributes to the low-grade inflammation associated with the metabolic syndrome, enhancing the hyperinflammatory reaction induced by the SARS-CoV-2 infection. The intake of sodium nitrate, a precursor of nitrite and nitric oxide, influences the antioxidant and pro-inflammatory gene expression profile after immune stimulation with LPS in peripheral blood mononuclear cells from metabolic syndrome patients. We aimed to assess the inflammatory and antioxidant responses of immune cells from metabolic syndrome patients to exposure to the SARS-CoV-2 spike protein (S protein) together with LPS and the effect of nitrite in these responses. Whole blood samples obtained from six metabolic syndrome patients were cultured for 16 h at 37 °C with four different media: control medium, control medium plus LPS (100 ng/mL), control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL), and control medium plus LPS (100 ng/mL) plus S protein (10 ng/mL) plus nitrite (5 µM). Immune stimulation with the LPS/S protein enhanced nitrate biosynthesis from nitrite oxidation and probably from additional organic precursors. In vitro incubations with the LPS/S protein enhanced the expression and/or release of pro-inflammatory TNFα, IL-6, IL-1β, and TLR4, as well as the expression of the anti-inflammatory IL-1ra and IL-10 and antioxidant enzymes. Nitrite attenuated the pro- and anti-inflammatory response induced by the S protein without interfering with the activation of TLR4 and antioxidant enzyme expression, raising the possibility that nitrite could have potential as a coadjutant in the treatment of COVID-19.
Collapse
Affiliation(s)
- Miguel D Ferrer
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Clara Reynés
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
| | - Laura Jiménez
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
| | - Gianluca Malagraba
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
| | - Margalida Monserrat-Mesquida
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Cristina Bouzas
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Josep A Tur
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Antoni Pons
- Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands-IUNICS, 07122 Palma, Spain
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| |
Collapse
|
|
6
|
Gui L, Wang S, Wang J, Liao W, Chen Z, Pan D, Xia H, Sun G, Tian S. Effects of forsythin extract in
Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet. FOOD SCIENCE AND HUMAN WELLNESS 2024; 13:659-667. [DOI: 10.26599/fshw.2022.9250055] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/31/2024]
|
|
7
|
Simonyan RM, Feschyan SM, Madoyan RA, Simonyan GM, Sargsyan HH, Babayan MA, Yekmalyan HH, Melkonyan MM, Simonyan MA, Manukyan AL. Superoxide-producing associates from gastrointestinal bacteria: stimulation of its growth by exogenous superoxide-producing complex from raspberries. Free Radic Res 2024; 58:145-155. [PMID: 38426488 DOI: 10.1080/10715762.2024.2325940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 02/19/2024] [Indexed: 03/02/2024]
Abstract
Aerobic organisms including the gut microbiota have an essential antioxidant status, as a result of which these bacteria protect organisms from various pathologies and diseases. The goal of the given investigation is (1) the isolation and purification of the isoforms of endogenous О2--producing associate from gastrointestinal bacteria (Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium bifidum); (2) determination of the effective concentrations of exogenous О2- produced by a complex of NADPH-containing protein component and Fe(III) (NPC-Fe(III)) from raspberries on the growth of the gastrointestinal bacteria in a nutrient medium in vitro. Ion-exchange chromatography on cellulose DE-52 and gel filtration on Sephadex G-100 at the pH of 9.5 was used to isolate and purify the NLP-Nox isoforms. Specific maximal optical absorption spectra of the Nox isoforms were observed in a weakly opalescent aqueous solution of the NLP-Nox isoforms. The specific contents of these NLP-Nox isoforms, as well as their composition, the stationary concentration of produced О2-, and the mechanism of О2- production were determined. The stimulating effect on the growth of these gastrointestinal bacteria in the nutrient medium of MRS broth and MRS agar in vitro under the influence of О2-, as a product of a new thermostable and acid-stable complex NPC-Fe(III) was determined. The NPC-Fe(III) complex, from raspberries was determined as well. Thus, for the first time, the isolation and purification of О2-- producing thermostable NADPH-containing lipoprotein-NADPH oxidase (NLP-Nox) associate from gastrointestinal bacteria membranes (continuously producing О2- under the aerobic conditions), and the stimulation of these bacteria growth by О2- formed by the complex from raspberries were demonstrated.
Collapse
Affiliation(s)
- Ruzan M Simonyan
- H. Buniatyan Institute of Biochemistry NAS RA, Laboratory of "Metabolism of Reactive Oxygen", Yerevan, Armenia
| | - Sona M Feschyan
- Department of Biology, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia
| | - Roza A Madoyan
- H.Buniatyan Institute of Biochemistry NAS RA, Laboratory of "Analytical Chromatography and mass spectral research", Yerevan, Armenia
| | - Gegham M Simonyan
- H. Buniatyan Institute of Biochemistry NAS RA, Laboratory of "Metabolism of Reactive Oxygen", Yerevan, Armenia
| | - Hasmik H Sargsyan
- H.Buniatyan Institute of Biochemistry NAS RA, Laboratory of "Analytical Chromatography and mass spectral research", Yerevan, Armenia
| | - Madlena A Babayan
- H. Buniatyan Institute of Biochemistry NAS RA, Laboratory of "Metabolism of Reactive Oxygen", Yerevan, Armenia
| | - Hasmik H Yekmalyan
- H. Buniatyan Institute of Biochemistry NAS RA, Laboratory of "Metabolism of Reactive Oxygen", Yerevan, Armenia
| | - Magdalina M Melkonyan
- Department of Medical Chemistry, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia
- Cobrain Center, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia
| | - Maxim A Simonyan
- H. Buniatyan Institute of Biochemistry NAS RA, Laboratory of "Metabolism of Reactive Oxygen", Yerevan, Armenia
| | - Ashkhen L Manukyan
- Department of Medical Chemistry, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia
- Cobrain Center, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia
| |
Collapse
|
|
8
|
Ding H, Liu J, Chen Z, Huang S, Yan C, Kwek E, He Z, Zhu H, Chen ZY. Protocatechuic acid alleviates TMAO-aggravated atherosclerosis via mitigating inflammation, regulating lipid metabolism, and reshaping gut microbiota. Food Funct 2024; 15:881-893. [PMID: 38165856 DOI: 10.1039/d3fo04396g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
Trimethylamine-N-oxide (TMAO) is a risk factor for atherosclerosis. As a natural phenolic acid, protocatechuic acid (PCA) is abundant in various plant foods. The present study investigated the effect of PCA on TMAO-aggravated atherosclerosis in ApoE-/- mice. The mice were randomly divided into five groups and fed one of the following five diets for 12 weeks: namely a low-fat diet (LFD), a western diet (WD), a WD + 0.2% TMAO diet (WDT), a WDT + 0.5% PCA diet (WDT + LPCA), and a WDT + 1.0% PCA diet (WDT + HPCA). Results demonstrated that dietary TMAO exacerbated the development of atherosclerosis by eliciting inflammation and disturbing lipid metabolism. The diet with PCA at 1% reduced TMAO-induced aortic plaque by 30% and decreased the levels of plasma pro-inflammatory cytokines. PCA also improved lipid metabolism by up-regulating the hepatic gene expression of peroxisome proliferator-activated receptor alpha (PPARα). In addition, PCA supplementation enhanced fecal excretion of fatty acids and decreased hepatic fat accumulation. PCA supplementation favorably modulated gut microbiota by increasing the α-diversity with an increase in the abundance of beneficial genera (Rikenella, Turicibacter, Clostridium_sensu_stricto and Bifidobacterium) and a decrease in the abundance of the harmful Helicobacter genus. In summary, PCA could alleviate the TMAO-exacerbated atherosclerosis and inflammation, improve the lipid metabolism, and modulate gut microbiota.
Collapse
Affiliation(s)
- Huafang Ding
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Jianhui Liu
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Jiangsu Province Engineering Research Center of Edible Fungus Preservation and Intensive Processing, Nanjing 210023, China
| | - Zixing Chen
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Shouhe Huang
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Chi Yan
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Erika Kwek
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Zouyan He
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Hanyue Zhu
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Zhen-Yu Chen
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| |
Collapse
|
|
9
|
Li SX, Guo Y. Gut microbiome: New perspectives for type 2 diabetes prevention and treatment. World J Clin Cases 2023; 11:7508-7520. [DOI: 10.12998/wjcc.v11.i31.7508] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/19/2023] [Accepted: 10/23/2023] [Indexed: 11/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.
Collapse
Affiliation(s)
- Shu-Xiao Li
- School of Clinical Medicine, Changchun University of Traditional Chinese Medicine, Changchun 130000, Jilin Province, China
| | - Yan Guo
- School of Clinical Medicine, Changchun University of Traditional Chinese Medicine, Changchun 130000, Jilin Province, China
| |
Collapse
|
|
10
|
Zhao J, Zhao F, Yuan J, Liu H, Wang Y. Gut microbiota metabolites, redox status, and the related regulatory effects of probiotics. Heliyon 2023; 9:e21431. [PMID: 38027795 PMCID: PMC10643359 DOI: 10.1016/j.heliyon.2023.e21431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 09/29/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
Oxidative stress is a state of imbalance between oxidation and antioxidation. It is caused by excess levels of free radicals and leads to the damage of DNA, proteins, and lipids. The crucial role of gut microbiota in regulating oxidative stress has been widely demonstrated. Studies have suggested that the redox regulatory effects of gut microbiota are related to gut microbiota metabolites, including fatty acids, lipopolysaccharides, tryptophan metabolites, trimethylamine-N-oxide and polyphenolic metabolites. In recent years, the potential benefits of probiotics have been gaining increasing scientific interest owing to their ability to modulate gut microbiota and oxidative stress. In this review, we summarise the adverse health effects of oxidative stress and discuss the role of the gut microbiota and its metabolites in redox regulation. Based on the influence of gut microbiota metabolites, the roles of probiotics in preventing oxidative stress are highlighted.
Collapse
Affiliation(s)
| | | | - Junmeng Yuan
- College of Animal Science and Technology, Qingdao Agricultural University, 266109, Qingdao, China
| | - Huawei Liu
- College of Animal Science and Technology, Qingdao Agricultural University, 266109, Qingdao, China
| | - Yang Wang
- College of Animal Science and Technology, Qingdao Agricultural University, 266109, Qingdao, China
| |
Collapse
|
|
11
|
Song W, Wang T, Cui X, Li L, Chen B, Li Y, Yue T. Lactobacillus coryniformis subsp. torquens T3 alleviates non-alcoholic fatty liver disease via reconstruction of the gut microbiota and redox system. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:6814-6825. [PMID: 37300818 DOI: 10.1002/jsfa.12774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 05/26/2023] [Accepted: 06/02/2023] [Indexed: 06/12/2023]
Abstract
BACKGROUND A high-fat diet (HFD) that induces obesity has become the most common type of diet worldwide, leading to serious global health issues. Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Probiotic supplements have been shown to help alleviate obesity. The present study aimed to investigate the mechanism by which Lactobacillus coryniformis supsp. torquens T3 (T3L) alleviated NAFLD induced by HFD via reconstruction of the gut microbiota and redox system. RESULTS The results showed that, compared with the HFD group, T3L inhibited obesity and relieved fat accumulation in the liver of mice with NAFLD. In addition, T3L inhibited liver inflammation and oxidative stress injury in NAFLD mice by regulating the lipopolysaccharide (LPS) inflammatory pathway in the liver. Furthermore, T3L changed the composition of the intestinal flora, reduced the abundance of harmful bacteria in the intestinal tract, enhanced the mechanical function of the intestinal barrier, and increased the short-chain fatty acid contents, thus inhibiting the secondary metabolite LPS, which directly causes liver damage through the portal vein. CONCLUSION In summary, T3L ameliorated NAFLD induced by obesity through the liver-gut axis pathway, thus reducing oxidative stress and liver injury. © 2023 Society of Chemical Industry.
Collapse
Affiliation(s)
- Wei Song
- College of Food Science and Technology, Northwest University, Xi'an, China
- Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Xi'an, china
- Research Center of Food Safety Risk Assessment and Control, Xi'an, China
| | - Tianyi Wang
- Department of Food Science and Engineering, Harbin Institute of Technology, Harbin, China
| | - Xiaole Cui
- College of Food Science and Technology, Northwest University, Xi'an, China
- Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Xi'an, china
- Research Center of Food Safety Risk Assessment and Control, Xi'an, China
| | - Lingling Li
- College of Food Science and Technology, Northwest University, Xi'an, China
- Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Xi'an, china
- Research Center of Food Safety Risk Assessment and Control, Xi'an, China
| | - Bing Chen
- College of Food Science and Technology, Northwest University, Xi'an, China
- Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Xi'an, china
- Research Center of Food Safety Risk Assessment and Control, Xi'an, China
| | - Yanjie Li
- Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences and Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Tianli Yue
- College of Food Science and Technology, Northwest University, Xi'an, China
- Laboratory of Nutritional and Healthy Food-Individuation Manufacturing Engineering, Xi'an, china
- Research Center of Food Safety Risk Assessment and Control, Xi'an, China
| |
Collapse
|
|
12
|
Widjaja F, Rietjens IMCM. From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes. Biomedicines 2023; 11:2658. [PMID: 37893032 PMCID: PMC10603957 DOI: 10.3390/biomedicines11102658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/22/2023] [Accepted: 09/24/2023] [Indexed: 10/29/2023] Open
Abstract
The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine-feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either -20 °C for up to a few months or -80 °C for a longer period-up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.
Collapse
Affiliation(s)
- Frances Widjaja
- Division of Toxicology, Wageningen University & Research, 6708 WE Wageningen, The Netherlands;
| | | |
Collapse
|
|
13
|
Ecklu-Mensah G, Choo-Kang C, Maseng MG, Donato S, Bovet P, Viswanathan B, Bedu-Addo K, Plange-Rhule J, Oti Boateng P, Forrester TE, Williams M, Lambert EV, Rae D, Sinyanya N, Luke A, Layden BT, O'Keefe S, Gilbert JA, Dugas LR. Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study. Nat Commun 2023; 14:5160. [PMID: 37620311 PMCID: PMC10449869 DOI: 10.1038/s41467-023-40874-x] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 08/11/2023] [Indexed: 08/26/2023] Open
Abstract
The relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.
Collapse
Affiliation(s)
- Gertrude Ecklu-Mensah
- Department of Pediatrics, Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Candice Choo-Kang
- Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA
| | - Maria Gjerstad Maseng
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Dep. of Gastroenterology, Oslo University Hospital, Oslo, Norway
- Bio-Me, Oslo, Norway
| | - Sonya Donato
- Department of Pediatrics, Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Pascal Bovet
- University Center for Primary Care and Public Health (Unisanté), Lausanne University Hospital, Lausanne, Switzerland
- Ministry of Health, Victoria, Republic of Seychelles
| | | | - Kweku Bedu-Addo
- Department of Physiology, SMS, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Jacob Plange-Rhule
- Department of Physiology, SMS, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Prince Oti Boateng
- Department of Physiology, SMS, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Terrence E Forrester
- Solutions for Developing Countries, University of the West Indies, Mona, Kingston, Jamaica
| | - Marie Williams
- Solutions for Developing Countries, University of the West Indies, Mona, Kingston, Jamaica
| | - Estelle V Lambert
- Research Unit for Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South Africa
| | - Dale Rae
- Research Unit for Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South Africa
| | - Nandipha Sinyanya
- Research Unit for Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South Africa
| | - Amy Luke
- Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA
| | - Brian T Layden
- Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
- Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA
| | - Stephen O'Keefe
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jack A Gilbert
- Department of Pediatrics, Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
| | - Lara R Dugas
- Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA.
- Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
| |
Collapse
|
|
14
|
Ecklu-Mensah G, Choo-Kang C, Gjerstad Maseng M, Donato S, Bovet P, Bedu-Addo K, Plange-Rhule J, Forrester TE, Lambert EV, Rae D, Luke A, Layden BT, O’Keefe S, Gilbert JA, Dugas LR. Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: The METS-Microbiome Study. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.03.21.533195. [PMID: 36993742 PMCID: PMC10055249 DOI: 10.1101/2023.03.21.533195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
Abstract
The relationship between the gut microbiota, short chain fatty acid (SCFA) metabolism, and obesity remains unclear due to conflicting reports from studies with limited statistical power. Additionally, this association has rarely been explored in large scale diverse populations. Here, we investigated associations between fecal microbial composition, predicted metabolic potential, SCFA concentrations, and obesity in a large ( N = 1,934) adult cohort of African-origin spanning the epidemiologic transition, from Ghana, South Africa, Jamaica, Seychelles, and the United States (US). The greatest gut microbiota diversity and total fecal SCFA concentration was found in the Ghanaian population, while the lowest levels were found in the US population, respectively representing the lowest and the highest end of the epidemiologic transition spectrum. Country-specific bacterial taxa and predicted-functional pathways were observed, including an increased prevalence of Prevotella , Butyrivibrio , Weisella and Romboutsia in Ghana and South Africa, while Bacteroides and Parabacteroides were enriched in Jamaican and the US populations. Importantly, 'VANISH' taxa, including Butyricicoccus and Succinivibrio , were significantly enriched in the Ghanaian cohort, reflecting the participants' traditional lifestyles. Obesity was significantly associated with lower SCFA concentrations, a decrease in microbial richness, and dissimilarities in community composition, and reduction in the proportion of SCFA synthesizing bacteria including Oscillospira , Christensenella , Eubacterium , Alistipes , Clostridium and Odoribacter . Further, the predicted proportions of genes in the lipopolysaccharide (LPS) synthesis pathway were enriched in obese individuals, while genes associated with butyrate synthesis via the dominant pyruvate pathway were significantly reduced in obese individuals. Using machine learning, we identified features predictive of metabolic state and country of origin. Country of origin could accurately be predicted by the fecal microbiota (AUC = 0.97), whereas obesity could not be predicted as accurately (AUC = 0.65). Participant sex (AUC = 0.75), diabetes status (AUC = 0.63), hypertensive status (AUC = 0.65), and glucose status (AUC = 0.66) could all be predicted with different success. Interestingly, within country, the predictive accuracy of the microbiota for obesity was inversely correlated to the epidemiological transition, being greatest in Ghana (AUC = 0.57). Collectively, our findings reveal profound variation in the gut microbiota, inferred functional pathways, and SCFA synthesis as a function of country of origin. While obesity could be predicted accurately from the microbiota, the variation in accuracy in parallel with the epidemiological transition suggests that differences in the microbiota between obesity and non-obesity may be larger in low-to-middle countries compared to high-income countries. Further examination of independent study populations using multi-omic approaches will be necessary to determine the factors that drive this association.
Collapse
Affiliation(s)
| | - Candice Choo-Kang
- Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA
| | - Maria Gjerstad Maseng
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Dep. of Gastroenterology, Oslo University Hospital, Oslo, Norway
- Bio-Me, Oslo, Norway
| | - Sonya Donato
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Pascal Bovet
- University Center for Primary Care and Public Health (Unisanté), Lausanne, Switzerland& Ministry of Health, Republic of Seychelles Department of Physiology, SMS
| | - Kweku Bedu-Addo
- Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | - Terrence E. Forrester
- Solutions for Developing Countries, University of the West Indies, Mona, Kingston, Jamaica
| | - Estelle V. Lambert
- Research Unit for Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South Africa
| | - Dale Rae
- Research Unit for Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South Africa
| | - Amy Luke
- Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA
| | - Brian T. Layden
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
- Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA
| | | | - Jack A. Gilbert
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Lara R. Dugas
- Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA
- Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| |
Collapse
|
|
15
|
Schirò G, Iacono S, Balistreri CR. The Role of Human Microbiota in Myasthenia Gravis: A Narrative Review. Neurol Int 2023; 15:392-404. [PMID: 36976669 PMCID: PMC10053295 DOI: 10.3390/neurolint15010026] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/05/2023] [Accepted: 03/07/2023] [Indexed: 03/15/2023] Open
Abstract
Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by fluctuating weakness of the skeletal muscles. Although antibodies against the neuromuscular junction components are recognized, the MG pathogenesis remains unclear, even if with a well-known multifactorial character. However, the perturbations of human microbiota have been recently suggested to contribute to MG pathogenesis and clinical course. Accordingly, some products derived from commensal flora have been demonstrated to have anti-inflammatory effects, while other have been shown to possess pro-inflammatory properties. In addition, patients with MG when compared with age-matched controls showed a distinctive composition in the oral and gut microbiota, with a typical increase in Streptococcus and Bacteroides and a reduction in Clostridia as well as short-chain fatty acid reduction. Moreover, restoring the gut microbiota perturbation has been evidenced after the administration of probiotics followed by an improvement of symptoms in MG cases. To highlight the role of the oral and gut microbiota in MG pathogenesis and clinical course, here, the current evidence has been summarized and reviewed.
Collapse
Affiliation(s)
- Giuseppe Schirò
- Neurology Unit, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| | - Salvatore Iacono
- Neurology Unit, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
- Correspondence:
| | - Carmela Rita Balistreri
- Cellular and Molecular Laboratory, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| |
Collapse
|
|
16
|
Abdullah B, Idorus MY, Daud S, Aazmi S, Pillai TK, Zain ZM. Gut Microbiota Composition in the First and Third Trimester of Pregnancy among Malay Women is Associated with Body Mass Index: A Pilot Study. Malays J Med Sci 2023; 30:116-128. [PMID: 36875193 PMCID: PMC9984101 DOI: 10.21315/mjms2023.30.1.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 06/11/2022] [Indexed: 03/05/2023] Open
Abstract
Background This study has analysed the pattern of gut microbiota during the first and third trimesters among pregnant Malay women. Methods This was a pilot prospective observational study involving 12 pregnant Malay women without any endocrine disorders and on neither antibiotics nor probiotics. Demographic details and anthropometric measurements were obtained, and the faecal 16S ribosomal ribonucleic acid (rRNA) metagenome microbiota of the first and third trimesters (T1 and T3) were analysed. Univariate and multivariate statistics, partial least squares discriminant analysis (PLSDA) and Kendall rank correlation testing were used to identify key genera and associations with pregnancy trimester and body mass index (BMI). Results The most abundant phyla were Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria, with significant differences in composition at the genus level demonstrated between T1 and T3. Sequencing showed a statistically significant difference in beta diversity between normal and abnormal BMI at all taxonomic ranks (R 2 = 0.60; Q 2 = 0.23) and genus levels (R 2 = 0.57; Q 2 = 0.37). The relative abundances of Akkermansia (P < 0.05; false discovery rate [FDR] < 0.05), Olsenella (P < 0.05; FDR < 0.05) and Oscillospira (P < 0.05; FDR < 0.05) were found to be significantly higher in normal BMI cases by 2.4, 3.4 and 3.1 times, respectively. Conclusion Three genera (Akkermansia, Olsenella and Oscillospira) were correlated with normal BMI during pregnancy. All three could be promising biotherapeutic targets in body weight regulation during pregnancy, subsequently reducing complications associated with higher BMI.
Collapse
Affiliation(s)
- Bahiyah Abdullah
- Maternofetal and Embryo (MatE) Research Group, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.,Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
| | - Mohd Yusri Idorus
- Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
| | - Suzanna Daud
- Maternofetal and Embryo (MatE) Research Group, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.,Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
| | - Shafiq Aazmi
- School of Biology, Faculty of Applied Science, Universiti Teknologi MARA, Selangor, Malaysia.,Microbiome Health and Environment (MiHeaRT), Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia
| | - Thanikasalam Kathiresan Pillai
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
| | - Zaini Mohd Zain
- Department of Medical Microbiology and Parasitology, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
| |
Collapse
|
|
17
|
Bubnov R, Spivak M. Pathophysiology-Based Individualized Use of Probiotics and Prebiotics for Metabolic Syndrome: Implementing Predictive, Preventive, and Personalized Medical Approach. ADVANCES IN PREDICTIVE, PREVENTIVE AND PERSONALISED MEDICINE 2023:133-196. [DOI: 10.1007/978-3-031-19564-8_6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
18
|
Loskutov SI, Proshin SN, Ryabukhin DS. Evolutionary aspects of gastrointestinal tract microbiome-host interaction underlying gastrointestinal barrier integrity. RUSSIAN JOURNAL OF INFECTION AND IMMUNITY 2022. [DOI: 10.15789/2220-7619-eao-1633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
In the host sustenance and homeostasis, the microbiome is a key component in the functional system. Throughout ontogenetic development, microbiome including that of the gastrointestinal tract (GIT) is the vital factor that ensures not only host functioning, but also its interaction with environment. To uncover the mechanisms underlying GIT microbiome showing a decisive influence on host organism, a systematic approach is needed, because diverse microorganisms are predominantly localized in different parts of the GIT. Recently, a new interdisciplinary direction of science, nanobioinformatics that has been extensively developed considers gene networks as the major object of study representing a coordinated group of genes that functionally account for formation and phenotypic disclosure of various host traits. Here, an important place should be provided to the genetically determined level of the gastrointestinal tract microbiome, its interaction at the level of the host food systems. There have been increasing evidence indicating that the microbiome is directly involved in the pathogenesis of host diseases showing a multi-layered interaction with host metabolic and immune systems. At the same time, the microbial community is unevenly distributed throughout the gastrointestinal tract, and its different portions are variously active while interacting with the host immune system. The architecture of interaction between the microbiome and host cells is extremely complex, and the interaction of individual cells, at the same time, varies greatly. Bacteria colonizing the crypts of the small intestine regulate enterocyte proliferation by affecting DNA replication and gene expression, while bacteria at the tip of the intestinal villi mediate gene expression responsible for metabolism and immune response. Enterocytes and Paneth cells, in turn, regulate the vital activity of the community of microorganisms through the production of polysaccharides (carbohydrates) and antibacterial factors on their surface. Thus, the integrity of the gastrointestinal barrier (GIB) is maintained, which protects the body from infections and inflammation, while violation of its integrity leads to a number of diseases. It has been shown that depending on the dominance of certain types of bacteria the microbiome can maintain or disrupt GIB integrity. The structural and functional GIB integrity is important for body homeostasis. To date, at least 50 proteins have been characterized as being involved in the structural and functional integrability of tight junctions between gastrointestinal tract epithelial cells. The current review comprehensively discusses such issues and presents original research carried out at various facilities of translational biomedicine.
Collapse
|
|
19
|
Naik SS, Ramphall S, Rijal S, Prakash V, Ekladios H, Mulayamkuzhiyil Saju J, Mandal N, Kham NI, Shahid R, Venugopal S. Association of Gut Microbial Dysbiosis and Hypertension: A Systematic Review. Cureus 2022; 14:e29927. [PMID: 36381851 PMCID: PMC9642844 DOI: 10.7759/cureus.29927] [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] [Received: 07/16/2022] [Accepted: 10/04/2022] [Indexed: 01/25/2023] Open
Abstract
Hypertension (HTN) is one of the most prevalent and dangerous cardiovascular diseases worldwide. Recently, its direct or indirect association with gut dysbiosis has been an interest of study for many. It also includes the metabolomic and functional gene changes in hypertensives compared with healthy individuals. This systematic review aims to study quantitative and qualitative interactions between the two and re-defining the heart-gut axis. We have strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 2020, guidelines. We conducted an in-depth search of databases such as PubMed, PubMed Central (PMC), Medline, and ScienceDirect to find relevant studies for our topic of interest. After the final quality check, we included eight articles in the systematic review. A significant difference in richness and diversity in gut microbiota was observed in hypertensive patients compared with healthy controls. There was an increased abundance of many bacteria such as Catabacter, Robinsoleilla, Serratia, Enterobacteriaceae, Ruminococcus torques, Parasutterella, Escherichia, Shigella, and Klebsiella, while a decreased abundance of Sporobacter, Roseburia hominis, Romboutsia spp., and Roseburia. Alteration of the composition also varied based on diet, age, ethnicity, and severity of HTN. Short-chain fatty acids (SCFAs)-producing bacteria are found to be on the lower side in hypertensives owing to the protective property of SCFAs against inflammation, especially butyric acid. From the perspective of metabolomic changes, harmful metabolites for cardiovascular health such as intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPSs), zonulin, sphingomyelins, acylcarnitines, and trimethylamine N-oxide (TMAO) were found to be increased in hypertensives. Changes in these biomarkers further establish the relation between gut epithelial health and high blood pressure (BP). Participants affected by diseases have an overall lower rate of acquiring new genes, which results in a low richness of genes in them compared with healthy individuals. There is increased expression of the choline utilization (cutC) gene and reduced expression of genes associated with biosynthesis and transport of amino acids in high-BP participants. The unique changes in the composition of the microbiota, functional changes in genes, and metabolome collectively help for a better understanding of the pathogenesis of HTN and also suggest the gut as a promising new therapeutic target for HTN. To establish a further causal relationship between the two, more research is required.
Collapse
Affiliation(s)
- Shaili S Naik
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Surat Municipal Institute of Medical Education and Research (SMIMER) Hospital and Medical College, Surat, IND
| | - Shivana Ramphall
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Research, American University of Antigua, Osbourn, ATG
| | - Swarnima Rijal
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Vishakh Prakash
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Government Medical College Kozhikode, Kozhikode, IND
| | - Heba Ekladios
- Department of Psychiatry, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Jiya Mulayamkuzhiyil Saju
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Sree Narayana Institute of Medical Sciences, Ernakulam, IND
- General Surgery, Government Medical College, Thiruvananthapuram, Trivandrum, IND
| | - Naishal Mandal
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Surat Municipal Institute of Medical Education and Research (SMIMER) Hospital and Medical College, Surat, IND
| | - Nang I Kham
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Rabia Shahid
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sathish Venugopal
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| |
Collapse
|
|
20
|
Liu Z, Ding S, Jiang H, Fang J. Egg Protein Transferrin-Derived Peptides Irw (Lle-Arg-Trp) and Iqw (Lle-Gln-Trp) Prevent Obesity Mouse Model Induced by a High-Fat Diet via Reducing Lipid Deposition and Reprogramming Gut Microbiota. Int J Mol Sci 2022; 23:ijms231911227. [PMID: 36232527 PMCID: PMC9569728 DOI: 10.3390/ijms231911227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/19/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Egg-derived peptides play important roles in insulin secretion and sensitivity, oxidative stress, and inflammation, suggesting their possible involvement in obesity management. Hence, the aim of this study is to explore the alleviating effects of IRW (lle-Arg-Trp) and IQW (lle-Gln-Trp) on obesity via the mouse model induced by a high-fat diet. The entire experimental period lasted eight weeks. The results demonstrated that IQW prevented weight gain (6.52%), decreased the glucose, low-density lipoprotein (LDL), malonaldehyde, triglycerides, total cholesterol (TC), and leptin levels, and increased the concentration of adiponectin (p < 0.05, n = 8). Although IRW failed to prevent weight gain, it reduced the concentration of glucose, high-density lipoprotein (HDL), LDL, and leptin, and increased the concentration of adiponectin (p < 0.05, n = 8). Moreover, IRW and IQW increased glucose tolerance and insulin resistance based on the results of the intraperitoneal glucose test and insulin tolerance test (p < 0.05, n = 8). The quantitative polymerase chain reaction results revealed that IRW and IQW downregulated the mRNA expression of DGAT1 (Diacylglycerol O-Acyltransferase 1), DGAT2 (Diacylglycerol O-Acyltransferase 2), TNF-α, IL-6, and IL-1β of liver tissue (p < 0.05, n = 8). The results of the 16S ribosomal RNA amplicon sequencing showed that IQW and IRW tended to reduce the relative abundance of Firmicutes and Parabacteroides, and that IRW enhanced the abundance of Bacteroides (p < 0.05, n = 8). Collectively, IRW and IQW supplementation could alleviate the progression of obesity due to the fact that the supplementation reduced lipid deposition, maintained energy balance, and reprogrammed gut microbiota.
Collapse
Affiliation(s)
- Zhuangzhuang Liu
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
| | - Sujuan Ding
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha 410125, China
| | - Hongmei Jiang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
| | - Jun Fang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
- Correspondence: ; Tel.: +86-731-8461-3600
| |
Collapse
|
|
21
|
Trujillo SM, McKenney EA, Hilderbrand GV, Mangipane LS, Rogers MC, Joly K, Gustine DD, Erlenbach JA, Mangipane BA, Lafferty DJR. Correlating gut microbial membership to brown bear health metrics. Sci Rep 2022; 12:15415. [PMID: 36138067 PMCID: PMC9499961 DOI: 10.1038/s41598-022-19527-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 08/30/2022] [Indexed: 12/02/2022] Open
Abstract
The internal mechanisms responsible for modulating physiological condition, particularly those performed by the gut microbiome (GMB), remain under-explored in wildlife. However, as latitudinal and seasonal shifts in resource availability occur, the myriad micro-ecosystem services facilitated by the GMB may be especially important to wildlife health and resilience. Here, we use brown bears (Ursus arctos) as an ecological model to quantify the relationship between wildlife body condition metrics that are commonly used to assess individual and population-level health and GMB community composition and structure. To achieve these aims, we subsampled brown bear fecal samples collected during United States National Park Service research activities at three National Parks and Preserves (Katmai, Lake Clark, and Gates of the Arctic) and extracted microbial DNA for 16S rRNA amplicon sequencing and microbial taxonomic classification. We analyzed GMB communities using alpha diversity indices, subsequently using Spearman’s correlation analysis to examine relationships between alpha diversity and brown bear health metrics. We found no differences in GMB composition among bears with differing body conditions, nor any correlations between alpha diversity and body condition. Our results indicate that GMB composition reflects diverse foraging strategies while allowing brown bears to achieve similar body condition outcomes.
Collapse
Affiliation(s)
- Sarah M Trujillo
- Wildlife Ecology and Conservation Science Lab, Department of Biology, Northern Michigan University, Marquette, MI, 49855, USA.
| | - Erin A McKenney
- Department of Applied Ecology, North Carolina State University, Raleigh, NC, 27607, USA
| | | | - Lindsey S Mangipane
- Marine Mammals Management, U.S. Fish and Wildlife Service, Anchorage, AK, 99503, USA
| | - Matthew C Rogers
- National Oceanic and Atmospheric Administration, National Marine Fisheries Service, Juneau, AK, 99801, USA
| | - Kyle Joly
- Gates of the Arctic National Park and Preserve, National Park Service, Fairbanks, AK, 99709, USA
| | - David D Gustine
- Marine Mammals Management, U.S. Fish and Wildlife Service, Anchorage, AK, 99503, USA
| | - Joy A Erlenbach
- Kodiak National Wildlife Refuge, U.S. Fish and Wildlife Service, Kodiak, AK, 99615, USA
| | - Buck A Mangipane
- Lake Clark National Park and Preserve, National Park Service, Anchorage, AK, 99501, USA
| | - Diana J R Lafferty
- Wildlife Ecology and Conservation Science Lab, Department of Biology, Northern Michigan University, Marquette, MI, 49855, USA
| |
Collapse
|
|
22
|
Wang H, Zhang H, Gao Z, Zhang Q, Gu C. The mechanism of berberine alleviating metabolic disorder based on gut microbiome. Front Cell Infect Microbiol 2022; 12:854885. [PMID: 36093200 PMCID: PMC9452888 DOI: 10.3389/fcimb.2022.854885] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
With socioeconomic advances and improved living standards, metabolic syndrome has increasingly come into the attention. In recent decades, a growing number of studies have shown that the gut microbiome and its metabolites are closely related to the occurrence and development of many metabolic diseases, and play an important role that cannot be ignored, for instance, obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease and others. The correlation between gut microbiota and metabolic disorder has been widely recognized. Metabolic disorder could cause imbalance in gut microbiota, and disturbance of gut microbiota could aggravate metabolic disorder as well. Berberine (BBR), as a natural ingredient, plays an important role in the treatment of metabolic disorder. Studies have shown that BBR can alleviate the pathological conditions of metabolic disorders, and the mechanism is related to the regulation of gut microbiota: gut microbiota could regulate the absorption and utilization of berberine in the body; meanwhile, the structure and function of gut microbiota also changed after intervention by berberine. Therefore, we summarize relevant mechanism research, including the expressions of nitroreductases-producing bacteria to promote the absorption and utilization of berberine, strengthening intestinal barrier function, ameliorating inflammation regulating bile acid signal pathway and axis of bacteria-gut-brain. The aim of our study is to clarify the therapeutic characteristics of berberine further and provide the theoretical basis for the regulation of metabolic disorder from the perspective of gut microbiota.
Collapse
Affiliation(s)
- Han Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haiyu Zhang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zezheng Gao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiqi Zhang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chengjuan Gu
- Shenzhen Hospital (Futian), Guangzhou University of Chinese Medicine, Shenzhen, China
- *Correspondence: Chengjuan Gu,
| |
Collapse
|
|
23
|
Winek K, Tzur Y, Soreq H. Biological underpinnings of sex differences in neurological disorders. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 164:27-67. [PMID: 36038206 DOI: 10.1016/bs.irn.2022.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The importance of sex differences in neurological disorders has been increasingly acknowledged in recent clinical and basic research studies, but the complex biology and genetics underlying sex-linked biological heterogeneity and its brain-to-body impact remained incompletely understood. Men and women differ substantially in their susceptibility to certain neurological diseases, in the severity of symptoms, prognosis as well as the nature and efficacy of their response to treatments. The detailed mechanisms underlying these differences, especially at the molecular level, are being addressed in many studies but leave a lot to be further revealed. Here, we provide an overview of recent advances in our understanding of how sex differences in the brain and brain-body signaling contribute to neurological disorders and further present some future prospects entailed in terms of diagnostics and therapeutics.
Collapse
Affiliation(s)
- Katarzyna Winek
- The Edmond & Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel; The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Yonat Tzur
- The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Hermona Soreq
- The Edmond & Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel; The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
| |
Collapse
|
|
24
|
Abstract
Systemic Lupus Erythematosus is a complex autoimmune disease and its etiology remains unknown. Increased gut permeability has been reported in lupus patients, yet whether it promotes or results from lupus progression is unclear. Recent studies indicate that an impaired intestinal barrier allows the translocation of bacteria and bacterial components into systemic organs, increasing immune cell activation and autoantibody generation. Indeed, induced gut leakage in a mouse model of lupus enhanced disease characteristics, including the production of anti-dsDNA antibody, serum IL-6 as well as cell apoptosis. Gut microbiota dysbiosis has been suggested to be one of the factors that decreases gut barrier integrity by outgrowing harmful bacteria and their products, or by perturbation of gut immune homeostasis, which in turn affects gut barrier integrity. The restoration of microbial balance eliminates gut leakage in mice, further confirming the role of microbiota in maintaining gut barrier integrity. In this review, we discuss recent advances on the association between microbiota dysbiosis and leaky gut, as well as their influences on the progression of lupus. The modifications on host microbiota and gut integrity may offer insights into the development of new lupus treatment.
Collapse
Affiliation(s)
| | - Laurence Morel
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| |
Collapse
|
|
25
|
Pisoni S, Marrachelli VG, Morales JM, Maestrini S, Di Blasio AM, Monleón D. Sex Dimorphism in the Metabolome of Metabolic Syndrome in Morbidly Obese Individuals. Metabolites 2022; 12:metabo12050419. [PMID: 35629923 PMCID: PMC9147578 DOI: 10.3390/metabo12050419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 04/30/2022] [Accepted: 05/03/2022] [Indexed: 12/10/2022] Open
Abstract
Adult morbid obesity is defined as abnormal or excessive fat accumulation, mostly resulting from a long-term unhealthy lifestyle. Between 10% and 30% of people with obesity exhibit low cardiometabolic risk. The metabolic syndrome has been suggested as an indicator of obesity-related metabolic dysregulation. Although the prevalence of obesity does not seem to be sex-related and metabolic syndrome occurs at all ages, in the last few years, sex-specific differences in the pathophysiology, diagnosis, and treatment of metabolic syndrome have received attention. The aim of this study was to determine the prevalence of metabolic syndrome and its components in different sex and age groups in people with metabolic unhealthy obesity and to compare them with people with metabolic healthy obesity. We analyzed the metabolome in 1350 well-phenotyped morbidly obese individuals and showed that there is a strong sex-dependent association of metabolic syndrome with circulating metabolites. Importantly, we demonstrated that metabolic dysregulation in women and men with severe obesity and metabolic syndrome is age-dependent. The metabolic profiles from our study showed age-dependent sex differences in the impact of MetS which are consistent with the cardiometabolic characterization. Although there is common ground for MetS in the metabolome of severe obesity, men older than 54 are affected in a more extensive and intensive manner. These findings strongly argue for more studies aimed at unraveling the mechanisms that underlie this sex-specific metabolic dysregulation in severe obesity. Moreover, these findings suggest that women and men might benefit from differential sex and age specific interventions to prevent the adverse cardiometabolic effects of severe obesity.
Collapse
Affiliation(s)
- Serena Pisoni
- Department of Pathology, Medicine and Odontology Faculty, University of Valencia, 46010 Valencia, Spain; (S.P.); (J.M.M.)
| | - Vannina G. Marrachelli
- Department of Physiology, Medicine and Odontology Faculty, University of Valencia, 46010 Valencia, Spain;
- Clinical Hospital Research Foundation-INCLIVA and CIBERFES, 46010 Valencia, Spain
| | - Jose M. Morales
- Department of Pathology, Medicine and Odontology Faculty, University of Valencia, 46010 Valencia, Spain; (S.P.); (J.M.M.)
- Clinical Hospital Research Foundation-INCLIVA and CIBERFES, 46010 Valencia, Spain
| | - Sabrina Maestrini
- Laboratory of Molecular Genetics, Istituto Auxologico Italiano IRCCS, 20145 Milano, Italy; (S.M.); (A.M.D.B.)
| | - Anna M. Di Blasio
- Laboratory of Molecular Genetics, Istituto Auxologico Italiano IRCCS, 20145 Milano, Italy; (S.M.); (A.M.D.B.)
| | - Daniel Monleón
- Department of Pathology, Medicine and Odontology Faculty, University of Valencia, 46010 Valencia, Spain; (S.P.); (J.M.M.)
- Clinical Hospital Research Foundation-INCLIVA and CIBERFES, 46010 Valencia, Spain
- Correspondence:
| |
Collapse
|
|
26
|
Whole-Genome Shotgun Metagenomic Sequencing Reveals Distinct Gut Microbiome Signatures of Obese Cats. Microbiol Spectr 2022; 10:e0083722. [PMID: 35467389 PMCID: PMC9241680 DOI: 10.1128/spectrum.00837-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Overweight and obesity are growing health problems in domestic cats, increasing the risks of insulin resistance, lipid dyscrasias, neoplasia, cardiovascular disease, and decreasing longevity. The signature of obesity in the feline gut microbiota has not been studied at the whole-genome metagenomic level. We performed whole-genome shotgun metagenomic sequencing in the fecal samples of eight overweight/obese and eight normal cats housed in the same research environment. We obtained 271 Gbp of sequences and generated a 961-Mbp de novo reference contig assembly, with 1.14 million annotated microbial genes. In the obese cat microbiome, we discovered a significant reduction in microbial diversity (P < 0.01) and Firmicutes abundance (P = 0.005), as well as decreased Firmicutes/Bacteroidetes ratios (P = 0.02), which is the inverse of obese human/mouse microbiota. Linear discriminant analysis and quantitative PCR (qPCR) validation revealed significant increases of Bifidobacterium sp., Olsenella provencensis, Dialister sp.CAG:486, and Campylobacter upsaliensis as the hallmark of obese microbiota among 400 enriched species, whereas 1,525 bacterial species have decreased abundance in the obese microbiome. Phascolarctobacterium succinatutens and an uncharacterized Erysipelotrichaceae bacterium are highly abundant (>0.05%) in the normal gut with over 400-fold depletion in the obese microbiome. Fatty acid synthesis-related pathways are significantly overrepresented in the obese compared with the normal cat microbiome. In conclusion, we discovered dramatically decreased microbial diversity in obese cat gut microbiota, suggesting potential dysbiosis. A panel of seven significantly altered, highly abundant species can serve as a microbiome indicator of obesity. Our findings in the obese cat microbiome composition, abundance, and functional capacities provide new insights into feline obesity. IMPORTANCE Obesity affects around 45% of domestic cats, and licensed drugs for treating feline obesity are lacking. Physical exercise and calorie restrictions are commonly used for weight loss but with limited efficacy. Through comprehensive analyses of normal and obese cat gut bacteria flora, we identified dramatic shifts in the obese gut microbiome, including four bacterial species significantly enriched and two species depleted in the obese cats. The key bacterial community and functional capacity alterations discovered from this study will inform new weight management strategies for obese cats, such as evaluations of specific diet formulas that alter the microbiome composition, and the development of prebiotics and probiotics that promote the increase of beneficial species and the depletion of obesity-associated species. Interestingly, these bacteria identified in our study were also reported to affect the weight loss success in human patients, suggesting translational potential in human obesity.
Collapse
|
|
27
|
Exploring the Gut Microbiome in Myasthenia Gravis. Nutrients 2022; 14:nu14081647. [PMID: 35458209 PMCID: PMC9027283 DOI: 10.3390/nu14081647] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/10/2022] [Accepted: 04/12/2022] [Indexed: 12/13/2022] Open
Abstract
The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host’s antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota’s relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG’s clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.
Collapse
|
|
28
|
Cao S, Shaw EL, Quarles WR, Sasaki GY, Dey P, Hodges JK, Pokala A, Zeng M, Bruno RS. Daily Inclusion of Resistant Starch-Containing Potatoes in a Dietary Guidelines for Americans Dietary Pattern Does Not Adversely Affect Cardiometabolic Risk or Intestinal Permeability in Adults with Metabolic Syndrome: A Randomized Controlled Trial. Nutrients 2022; 14:1545. [PMID: 35458108 PMCID: PMC9026745 DOI: 10.3390/nu14081545] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/30/2022] [Accepted: 04/05/2022] [Indexed: 11/16/2022] Open
Abstract
Poor diet quality influences cardiometabolic risk. Although potatoes are suggested to adversely affect cardiometabolic health, controlled trials that can establish causality are limited. Consistent with potatoes being rich in micronutrients and resistant starch, we hypothesized that their inclusion in a Dietary Guidelines for Americans (DGA)-based dietary pattern would improve cardiometabolic and gut health in metabolic syndrome (MetS) persons. In a randomized cross-over trial, MetS persons (n = 27; 32.5 ± 1.3 year) consumed a DGA-based diet for 2 weeks containing potatoes (DGA + POTATO; 17.5 g/day resistant starch) or bagels (DGA + BAGEL; 0 g/day resistant starch) prior to completing oral glucose and gut permeability tests. Blood pressure, fasting glucose and insulin, and insulin resistance decreased (p < 0.05) from baseline regardless of treatment without any change in body mass. Oral glucose-induced changes in brachial artery flow-mediated dilation, nitric oxide homeostasis, and lipid peroxidation did not differ between treatment arms. Serum endotoxin AUC0−120 min and urinary lactulose/mannitol, but not urinary sucralose/erythritol, were lower in DGA + POTATO. Fecal microbiome showed limited between-treatment differences, but the proportion of acetate was higher in DGA + POTATO. Thus, short-term consumption of a DGA-based diet decreases cardiometabolic risk, and the incorporation of resistant starch-containing potatoes into a healthy diet reduces small intestinal permeability and postprandial endotoxemia.
Collapse
Affiliation(s)
- Sisi Cao
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| | - Emily L. Shaw
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| | - William R. Quarles
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| | - Geoffrey Y. Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| | - Priyankar Dey
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, Punjab, India
| | - Joanna K. Hodges
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| | - Avinash Pokala
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| | - Min Zeng
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| | - Richard S. Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH 43210, USA; (S.C.); (E.L.S.); (W.R.Q.); (G.Y.S.); (P.D.); (J.K.H.); (A.P.); (M.Z.)
| |
Collapse
|
|
29
|
Abdullah B, Daud S, Aazmi MS, Idorus MY, Mahamooth MIJ. Gut microbiota in pregnant Malaysian women: a comparison between trimesters, body mass index and gestational diabetes status. BMC Pregnancy Childbirth 2022; 22:152. [PMID: 35209853 PMCID: PMC8876553 DOI: 10.1186/s12884-022-04472-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 02/14/2022] [Indexed: 11/10/2022] Open
Abstract
Background The primary purpose of the study is to determine the variation of gut microbiota composition between first (T1) and third trimester (T3); gestational diabetes mellitus (GDM) and non-gestational diabetes mellitus (NGDM); and also within a different category of Body Mass Index (BMI) of selected pregnant Malaysian women. Methods A prospective observational study on selected 38 pregnant Malaysian women attending a tertiary medical centre was carried out. Those with preexisting diabetes, metabolic syndrome or any other endocrine disorders were excluded. GDM was determined using oral glucose tolerance test (OGTT) while BMI was stratified as underweight, normal, pre-obese and obese. Fecal samples were then collected during the first trimester (T1) and the third trimester (T3). The V3-V4 region of 16S rRNA gene amplicon libraries were sequenced and analyzed using QIIME (version 1.9.1) and METAGENassist. Results Twelve women (31.6%) were diagnosed as GDM. A trend of lower α-diversity indices in GDM, pre-obese and obese pregnant women were observed. Partial Least Squares Discriminant Analysis (PLS-DA) shows a clustering of gut microbiota according to GDM status and BMI, but not by trimester. Genera Acidaminococcus, Clostridium, Megasphaera and Allisonella were higher, and Barnesiella and Blautia were lower in GDM group (P < 0.005). Obese patients had gut microbiota that was enriched with bacteria of Negativicutes and Proteobacteria class such as Megamonas, Succinatimonas and Dialister (P < 0.005). The normal and mild underweight profiles on the other hand had a higher bacteria from the class of Clostridia (Papillibacter, Oscillibacter, Oscillospira, Blautia, Dorea) and Bacteroidia (Alistipes, Prevotella, Paraprevotella) (P < 0.005). Conclusion The prevalence and variation of several key bacteria from classes of Negativicutes, Clostridia and Proteobacteria has potential metabolic links with GDM and body weight during pregnancy which require further functional validation. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-04472-x.
Collapse
Affiliation(s)
- Bahiyah Abdullah
- Maternofetal and Embryo (MatE) Research Group, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia. .,Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.
| | - Suzanna Daud
- Maternofetal and Embryo (MatE) Research Group, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia.,Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia
| | - Mohd Shafiq Aazmi
- School of Biology, Faculty of Applied Science, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor Darul Ehsan, Malaysia
| | - Mohd Yusri Idorus
- Faculty of Medicine, Institute of Medical Molecular Biotechnology, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia
| | - Mas Irfan Jaya Mahamooth
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia
| |
Collapse
|
|
30
|
Bakker GJ, Meijnikman AS, Scheithauer TP, Davids M, Aydin Ö, Boerlage TCC, de Brauw LM, van de Laar AW, Gerdes VE, Groen AK, van Raalte DH, Herrema H, Nieuwdorp M. Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity. Obes Sci Pract 2022; 8:56-65. [PMID: 35127122 PMCID: PMC8804924 DOI: 10.1002/osp4.545] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/07/2021] [Accepted: 06/22/2021] [Indexed: 12/15/2022] Open
Abstract
AIMS Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. MATERIAL AND METHODS Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. RESULTS Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. CONCLUSIONS Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.
Collapse
Affiliation(s)
- Guido J. Bakker
- Department of Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
| | - Abraham S. Meijnikman
- Department of Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
| | - Torsten P. Scheithauer
- Department of Experimental Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
- Department of Internal MedicineDiabetes CenterAmsterdam UMC, Location VUMC AmsterdamAmsterdamThe Netherlands
| | - Mark Davids
- Department of Experimental Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
| | - Ömrüm Aydin
- Department of Bariatric SurgerySpaarne GasthuisHaarlemThe Netherlands
| | | | | | | | - Victor E. Gerdes
- Department of Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
- Department of Bariatric SurgerySpaarne GasthuisHaarlemThe Netherlands
| | - Albert K. Groen
- Department of Experimental Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
| | - Daniël H. van Raalte
- Department of Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
- Department of Experimental Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
- Department of Internal MedicineDiabetes CenterAmsterdam UMC, Location VUMC AmsterdamAmsterdamThe Netherlands
| | - Hilde Herrema
- Department of Experimental Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
| | - Max Nieuwdorp
- Department of Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
- Department of Experimental Vascular MedicineAmsterdam UMC, Location AMC at University of AmsterdamAmsterdamThe Netherlands
- Department of Internal MedicineDiabetes CenterAmsterdam UMC, Location VUMC AmsterdamAmsterdamThe Netherlands
- Department of Molecular and Clinical MedicineSahlgrenska Academy, University of Gothenburg, Wallenberg LaboratoryGothenburgSweden
| |
Collapse
|
|
31
|
|
|
32
|
Safety Evaluation and In vivo Strain-Specific Functionality of Bacillus Strains Isolated from Korean Traditional Fermented Foods. Probiotics Antimicrob Proteins 2021; 13:60-71. [PMID: 32607730 DOI: 10.1007/s12602-020-09672-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Unveiling and understanding differences in physiological features below the species level may serve as an essential fast-screening tool for selecting strains that can promote a specific probiotic effect. To study the intra-species diversity of Bacillus, a genus with a wide range of enzyme activities and specificity, 190 Bacillus strains were isolated from traditional Korean fermented food products. Altogether, in the preliminary safety screening, 8 of these strains were found negative for lecithinase and hemolysis activity and were selected for further investigations. On the basis of different levels of enzyme functionalities (high or low proteolytic, amylolytic, and lipolytic (PAL) activities), two Bacillus subtilis strains were selected for an in vivo study. Each of the two strains was separately administered at a level of 1 × 108 CFU per day to C57BL/6 mice that were fed 60% high-fat diet ad libitum for 8 weeks, while Xenical, an anti-obesity drug, was used as a positive control in the experimental setup. B. subtilis M34 and B. subtilis GS40a with low and high amylolytic activities, respectively, induced significantly different and contrasting physiological effects. The production of short-chain fatty acids appeared to be closely associated with a shift in the gut microbiota.
Collapse
|
|
33
|
Kim JH, Kim K, Kim W. Gut microbiota restoration through fecal microbiota transplantation: a new atopic dermatitis therapy. Exp Mol Med 2021; 53:907-916. [PMID: 34017060 PMCID: PMC8178377 DOI: 10.1038/s12276-021-00627-6] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 03/16/2021] [Accepted: 03/17/2021] [Indexed: 02/07/2023] Open
Abstract
The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.
Collapse
Affiliation(s)
- Jong-Hwa Kim
- Department of Microbiology, Chung-Ang University College of Medicine, Seoul, South Korea
| | - Kiyoung Kim
- Department of Microbiology, Chung-Ang University College of Medicine, Seoul, South Korea
| | - Wonyong Kim
- Department of Microbiology, Chung-Ang University College of Medicine, Seoul, South Korea.
| |
Collapse
|
|
34
|
Robert C, Buisson C, Laugerette F, Abrous H, Rainteau D, Humbert L, Vande Weghe J, Meugnier E, Loizon E, Caillet F, Van Dorsselaer B, Urdaci M, Vaysse C, Michalski MC. Impact of Rapeseed and Soy Lecithin on Postprandial Lipid Metabolism, Bile Acid Profile, and Gut Bacteria in Mice. Mol Nutr Food Res 2021; 65:e2001068. [PMID: 33742729 DOI: 10.1002/mnfr.202001068] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 02/16/2021] [Indexed: 01/01/2023]
Abstract
SCOPE Synthetic emulsifiers have recently been shown to promote metabolic syndrome and considerably alter gut microbiota. Yet, data are lacking regarding the effects of natural emulsifiers, such as plant lecithins rich in essential α-linolenic acid (ALA), on gut and metabolic health. METHODS AND RESULTS For 5 days, male Swiss mice are fed diets containing similar amounts of ALA and 0, 1, 3, or 10% rapeseed lecithin (RL) or 10% soy lecithin (SL). Following an overnight fast, they are force-fed the same oil mixture and euthanized after 90 minutes. The consumption of lecithin significantly increased fecal levels of the Clostridium leptum group (p = 0.0004), regardless of origin or dose, without altering hepatic or intestinal expression of genes of lipid metabolism. 10%-RL increased ALA abundance in plasma triacylglycerols at 90 minutes, reduced cecal bile acid hydrophobicity, and increased their sulfatation, as demonstrated by the increased hepatic RNA expression of Sult2a1 (p = 0.037) and cecal cholic acid-7 sulfate (CA-7S) concentration (p = 0.05) versus 0%-lecithin. CONCLUSION After only 5 days, nutritional doses of RL and SL modified gut bacteria in mice, by specifically increasing C. leptum group. RL also increased postprandial ALA abundance and induced beneficial modifications of the bile acid profile. ALA-rich lecithins, especially RL, may then appear as promising natural emulsifiers.
Collapse
Affiliation(s)
- Chloé Robert
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
- ITERG, Equipe Nutrition, Santé et Biochimie des Lipides, Canéjan, FR-33610, France
| | - Charline Buisson
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
| | - Fabienne Laugerette
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
| | - Hélène Abrous
- ITERG, Equipe Nutrition, Santé et Biochimie des Lipides, Canéjan, FR-33610, France
| | - Dominique Rainteau
- Sorbonne Universités, UPMC Univ. Paris 6, ENS, PSL Research University, CNRS, INSERM, APHP, Laboratory of BioMolecules (LBM), Paris, FR-75005, France
| | - Lydie Humbert
- Sorbonne Universités, UPMC Univ. Paris 6, ENS, PSL Research University, CNRS, INSERM, APHP, Laboratory of BioMolecules (LBM), Paris, FR-75005, France
| | - Justine Vande Weghe
- UMR5248, Laboratory of Microbiology and Applied Biochemistry, Bordeaux Sciences Agro, Gradignan, FR-33170, France
| | - Emmanuelle Meugnier
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
| | - Emmanuelle Loizon
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
| | - François Caillet
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
| | - Benjamin Van Dorsselaer
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
| | - Maria Urdaci
- UMR5248, Laboratory of Microbiology and Applied Biochemistry, Bordeaux Sciences Agro, Gradignan, FR-33170, France
| | - Carole Vaysse
- ITERG, Equipe Nutrition, Santé et Biochimie des Lipides, Canéjan, FR-33610, France
| | - Marie-Caroline Michalski
- CarMeN laboratory, INRAE, UMR1397, INSERM, U1060, INSA-Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, FR-69310, France
| |
Collapse
|
|
35
|
Ilias I, Goulas S, Zabuliene L. Polycystic ovary syndrome: Pathways and mechanisms for possible increased susceptibility to COVID-19. World J Clin Cases 2021; 9:2711-2720. [PMID: 33969054 PMCID: PMC8058679 DOI: 10.12998/wjcc.v9.i12.2711] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/16/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023] Open
Abstract
In 75% of women with polycystic ovary syndrome (PCOS), insulin action is impaired. In obesity, visceral adipose tissue becomes dysfunctional: Chronic inflammation is favored over storage, contributing to the development of metabolic complications. PCOS, metabolic syndrome (MetSy) and non-alcoholic fatty liver disease (NAFLD) apparently share common pathogenic factors; these include abdominal adiposity, excess body weight and insulin resistance. Alterations in the gut microbiome have been noted in women with PCOS compared to controls; these may lead to deterioration of the intestinal barrier, increased gut mucosal permeability and immune system activation, hyperinsulinemia and glucose intolerance, which hamper normal ovarian function and follicular development (all being hallmarks of PCOS). It has been proposed that PCOS may entail higher susceptibility to coronavirus disease 2019 (COVID-19) via its associated comorbidities (NAFLD, obesity, MetSy and alterations in the gut microbiome). Studies have found an association between acute respiratory distress syndrome (seen in severe cases of COVID-19) and the intestinal microbiome. Furthermore, apparently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can gain entry to the gastrointestinal tract via locally-expressed angiotensin converting enzyme type 2 receptors. Excess body weight is associated with more severe COVID-19 and increased mortality. Although robust links between SARS-CoV-2 infection and PCOS/NAFLD/gut microbiome/metabolic consequences are yet to be confirmed, it seems that strategies for adapting the intestinal microbiome could help reduce the severity of COVID-19 in women with PCOS with or without NAFLD, MetSy or obesity.
Collapse
Affiliation(s)
- Ioannis Ilias
- Department of Endocrinology, Elena Venizelou Hospital, Athens GR-11521, Greece
| | - Spyridon Goulas
- Department of Gastroenterology Unit, Elena Venizelou Hospital, Athens GR-11521, Greece
| | - Lina Zabuliene
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius LT-03101, Lithuania
| |
Collapse
|
|
36
|
Croci S, D’Apolito LI, Gasperi V, Catani MV, Savini I. Dietary Strategies for Management of Metabolic Syndrome: Role of Gut Microbiota Metabolites. Nutrients 2021; 13:nu13051389. [PMID: 33919016 PMCID: PMC8142993 DOI: 10.3390/nu13051389] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 04/15/2021] [Accepted: 04/16/2021] [Indexed: 12/21/2022] Open
Abstract
Metabolic syndrome (MetS) is a complex pathophysiological state with incidence similar to that of a global epidemic and represents a risk factor for the onset of chronic non-communicable degenerative diseases (NCDDs), including cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and some types of cancer. A plethora of literature data suggest the potential role of gut microbiota in interfering with the host metabolism, thus influencing several MetS risk factors. Perturbation of the gut microbiota’s composition and activity, a condition known as dysbiosis, is involved in the etiopathogenesis of multiple chronic diseases. Recent studies have shown that some micro-organism-derived metabolites (including trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS) of Gram-negative bacteria, indoxyl sulfate and p-cresol sulfate) induce subclinical inflammatory processes involved in MetS. Gut microbiota’s taxonomic species or abundance are modified by many factors, including diet, lifestyle and medications. The main purpose of this review is to highlight the correlation between different dietary strategies and changes in gut microbiota metabolites. We mainly focus on the validity/inadequacy of specific dietary patterns to reduce inflammatory processes, including leaky gut and subsequent endotoxemia. We also describe the chance of probiotic supplementation to interact with the immune system and limit negative consequences associated with MetS.
Collapse
Affiliation(s)
| | | | - Valeria Gasperi
- Correspondence: (V.G.); (M.V.C.); Tel.: +39-06-72596465 (V.G. & M.V.C.)
| | | | | |
Collapse
|
|
37
|
Li A, Wang N, Li N, Li B, Yan F, Song Y, Hou J, Huo G. Modulation effect of chenpi extract on gut microbiota in high-fat diet-induced obese C57BL/6 mice. J Food Biochem 2021; 45:e13541. [PMID: 33570789 DOI: 10.1111/jfbc.13541] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 09/06/2020] [Accepted: 10/02/2020] [Indexed: 01/11/2023]
Abstract
The current study employed high-fat diet (HFD) induced murine model to assess the relationship between the lipid-lowering effect of aged citrus peel (chenpi) extract and the alterations of gut microbiota. The results showed that intake of chenpi extract for 12 week dose-dependently suppressed HFD-induced body weight, food intake, Lee's index, together with decreased the level of fasting blood glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol. Moreover, chenpi extract administration up-regulated the abundance and diversity of fecal microbiota and down-regulated the ratio of Firmicutes-to-Bacteroidetes, which was characterized by the lower family of Lachnospiraceae, Helicobacteraceae, and Desulfovibrionaceae, and higher family of Bacteroidales_S24-7, Bacteroidaceae, Rikenellaceae, and Ruminococcaceae. Consistently, at the genus levels, chenpi extract treatment reversed the expansions of Helicobacter, Lachnospiraceae_UCG-006, and Desulfovibrio, while increased the abundance of Bacteroides, Rikenellaceae_RC9_gut_group, and Alistipes (belonging to Rikenellaceae family), Anaerotruncus and Odoribacter (belonging to Ruminococcaceae family), which were significantly negatively correlated with the levels of the serum lipid parameters. In conclusion, our findings indicated that anti-obesity ability of chenpi extract might be related to the improvement of gut microbiota imbalance. PRACTICAL APPLICATIONS: With the improvement of living standards, the incidence of metabolic diseases such as obesity, hypertension, and diabetes has increased significantly, and it has become a public health problem that seriously affects the health of the people. Chenpi contains a large amount of active ingredients, flavonoids, and other compounds, which can promote the absorption of the digestive system and have good effects on diseases such as the cardiovascular system. Our previous study has confirmed that the chenpi extract effectively regulated the glucose and lipid metabolism disorder induced by high-fat diet. However, it is not clear whether the effect is closely related to the improvement of gut microbiota. Accordingly, our result would provide a theoretical basis for future research on the relationship between obesity, chenpi extract, and gut microbiota, and support additional understanding of its potential anti-obesity effects.
Collapse
Affiliation(s)
- Aili Li
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Nana Wang
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Na Li
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Bailiang Li
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Fenfen Yan
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Yue Song
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Juncai Hou
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Guicheng Huo
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| |
Collapse
|
|
38
|
Abstract
Our understanding of the pathogenesis of acne vulgaris is still evolving. It is known that multiple factors impact acne pathophysiology, including genetic, hormonal, inflammatory, and environmental influences. Because of its implications in many of these factors, diet has been a part of the acne discussion for decades. Several studies have evaluated the significance of the glycemic index of various foods and glycemic load in patients with acne, demonstrating individuals with acne who consume diets with a low glycemic load have reduced acne lesions compared with individuals on high glycemic load diets. Dairy has also been a focus of study regarding dietary influences on acne; whey proteins responsible for the insulinotropic effects of milk may contribute more to acne development than the actual fat or dairy content. Other studies have examined the effects of omega-3 fatty acid and γ-linoleic acid consumption in individuals with acne, showing individuals with acne benefit from diets consisting of fish and healthy oils, thereby increasing omega-3 and omega-6 fatty acid intake. Recent research into the effects of probiotic administration in individuals with acne present promising results; further study of the effects of probiotics on acne is needed to support the findings of these early studies. In this review, we discuss the current evidence regarding the diets of US patients with acne and how they may impact acne and acne treatment.
Collapse
Affiliation(s)
- Hilary Baldwin
- The Acne Treatment and Research Center, 142 Joralemon Street, suite 8A, Brooklyn, NY, 11201, USA.
- Rutgers Robert Wood Johnson Medical Center, New Brunswick, NJ, USA.
| | - Jerry Tan
- Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
- Windsor Clinical Research Inc., Windsor, ON, Canada
| |
Collapse
|
|
39
|
Jameson JK, Mathiesen G, Pope PB, Westereng B, La Rosa SL. Biochemical characterization of two cellobiose 2-epimerases and application for efficient production of lactulose and epilactose. CURRENT RESEARCH IN BIOTECHNOLOGY 2021. [DOI: 10.1016/j.crbiot.2021.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
|
|
40
|
Le Magueresse-Battistoni B. Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17249403. [PMID: 33333918 PMCID: PMC7765367 DOI: 10.3390/ijerph17249403] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/10/2020] [Accepted: 12/14/2020] [Indexed: 12/21/2022]
Abstract
Obesity and metabolic-related diseases, among which diabetes, are prominent public health challenges of the 21st century. It is now well acknowledged that pollutants are a part of the equation, especially endocrine-disrupting chemicals (EDCs) that interfere with the hormonal aspect. The aim of the review is to focus on adipose tissue, a central regulator of energy balance and metabolic homeostasis, and to highlight the significant differences in the endocrine and metabolic aspects of adipose tissue between males and females which likely underlie the differences of the response to exposure to EDCs between the sexes. Moreover, the study also presents an overview of several mechanisms of action by which pollutants could cause adipose tissue dysfunction. Indeed, a better understanding of the mechanism by which environmental chemicals target adipose tissue and cause metabolic disturbances, and how these mechanisms interact and sex specificities are essential for developing mitigating and sex-specific strategies against metabolic diseases of chemical origin. In particular, considering that a scenario without pollutant exposure is not a realistic option in our current societies, attenuating the deleterious effects of exposure to pollutants by acting on the gut-adipose tissue axis may constitute a new direction of research.
Collapse
Affiliation(s)
- Brigitte Le Magueresse-Battistoni
- Univ-Lyon, CarMeN Laboratory, INSERM U1060, INRAé U1397, Université Claude Bernard Lyon1, F-69310 Pierre-Bénite, France; ; Tel.: +33-(0)-426235919; Fax: +33-(0)-426235916
- CarMeN Laboratory, INSERM U1060, Hopital Lyon-Sud, Bâtiment CENS ELI-2D, 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite, France
| |
Collapse
|
|
41
|
Pham MT, Yang JJ, Balasubramaniam A, Rahim AR, Adi P, Do TTM, Herr DR, Huang CM. Leuconostoc mesenteroides mediates an electrogenic pathway to attenuate the accumulation of abdominal fat mass induced by high fat diet. Sci Rep 2020; 10:21916. [PMID: 33318546 PMCID: PMC7736347 DOI: 10.1038/s41598-020-78835-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 11/27/2020] [Indexed: 11/26/2022] Open
Abstract
Although several electrogenic bacteria have been identified, the physiological effect of electricity generated by bacteria on host health remains elusive. We found that probiotic Leuconostoc mesenteroides (L. mesenteroides) can metabolize linoleic acid to yield electricity via an intracellular cyclophilin A-dependent pathway. Inhibition of cyclophilin A significantly abolished bacterial electricity and lowered the adhesion of L. mesenteroides to the human gut epithelial cell line. Butyrate from L. mesenteroides in the presence of linoleic acid were detectable and mediated free fatty acid receptor 2 (Ffar2) to reduce the lipid contents in differentiating 3T3-L1 adipocytes. Oral administration of L. mesenteroides plus linoleic acid remarkably reduced high-fat-diet (HFD)-induced formation of 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species (ROS) biomarker, and decreased abdominal fat mass in mice. The reduction of 4-HNE and abdominal fat mass was reversed when cyclophilin A inhibitor-pretreated bacteria were administered to mice. Our studies present a novel mechanism of reducing abdominal fat mass by electrogenic L. mesenteroides which may yield electrons to enhance colonization and sustain high amounts of butyrate to limit ROS during adipocyte differentiation.
Collapse
Affiliation(s)
- Minh Tan Pham
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, 32001, Taiwan
| | - John Jackson Yang
- Department of Life Sciences, National Central University, Taoyuan, Taiwan
| | - Arun Balasubramaniam
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, 32001, Taiwan
| | - Adelia Riezka Rahim
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, 32001, Taiwan
| | - Prakoso Adi
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, 32001, Taiwan
| | - Thi Tra My Do
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, 32001, Taiwan
| | - Deron Raymond Herr
- Department of Pharmacology, National University of Singapore, Singapore, Singapore
| | - Chun-Ming Huang
- Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, 32001, Taiwan.
| |
Collapse
|
|
42
|
Saarinen MT, Kärkkäinen O, Hanhineva K, Tiihonen K, Hibberd A, Mäkelä KA, Raza GS, Herzig KH, Anglenius H. Metabolomics analysis of plasma and adipose tissue samples from mice orally administered with polydextrose and correlations with cecal microbiota. Sci Rep 2020; 10:21577. [PMID: 33299048 PMCID: PMC7726573 DOI: 10.1038/s41598-020-78484-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 11/20/2020] [Indexed: 01/07/2023] Open
Abstract
Polydextrose (PDX) is a branched glucose polymer, utilized as a soluble dietary fiber. Recently, PDX was found to have hypolipidemic effects and effects on the gut microbiota. To investigate these findings more closely, a non-targeted metabolomics approach, was exploited to determine metabolic alterations in blood and epididymal adipose tissue samples that were collected from C57BL/6 mice fed with a Western diet, with or without oral administration of PDX. Metabolomic analyses revealed significant differences between PDX- and control mice, which could be due to differences in diet or due to altered microbial metabolism in the gut. Some metabolites were found in both plasma and adipose tissue, such as the bile acid derivative deoxycholic acid and the microbiome-derived tryptophan metabolite indoxyl sulfate, both of which increased by PDX. Additionally, PDX increased the levels of glycine betaine and L-carnitine in plasma samples, which correlated negatively with plasma TG and positively correlated with bacterial genera enriched in PDX mice. The results demonstrated that PDX caused differential metabolite patterns in blood and adipose tissues and that one-carbon metabolism, associated with glycine betaine and L-carnitine, and bile acid and tryptophan metabolism are associated with the hypolipidemic effects observed in mice that were given PDX.
Collapse
Affiliation(s)
| | - Olli Kärkkäinen
- Afekta Technologies Ltd., Kuopio, Finland
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Kati Hanhineva
- Afekta Technologies Ltd., Kuopio, Finland
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Kirsti Tiihonen
- DuPont Nutrition & Biosciences, Global Health & Nutrition Science, Kantvik, Finland
| | - Ashley Hibberd
- DuPont Nutrition & Biosciences, Genomics & Microbiome Science, St. Louis, MO, USA
| | - Kari Antero Mäkelä
- Institute of Biomedicine, Medical Research Center (MRC), University of Oulu, and University Hospital, Oulu, Finland
| | - Ghulam Shere Raza
- Institute of Biomedicine, Medical Research Center (MRC), University of Oulu, and University Hospital, Oulu, Finland
| | - Karl-Heinz Herzig
- Institute of Biomedicine, Medical Research Center (MRC), University of Oulu, and University Hospital, Oulu, Finland
- Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland
| | - Heli Anglenius
- DuPont Nutrition & Biosciences, Global Health & Nutrition Science, Kantvik, Finland
| |
Collapse
|
|
43
|
Gut mycobiomes are altered in people with type 2 Diabetes Mellitus and Diabetic Retinopathy. PLoS One 2020; 15:e0243077. [PMID: 33259537 PMCID: PMC7707496 DOI: 10.1371/journal.pone.0243077] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 11/14/2020] [Indexed: 01/14/2023] Open
Abstract
Studies have documented dysbiosis in the gut mycobiome in people with Type 2 diabetes mellitus (T2DM). However, it is not known whether dysbiosis in the gut mycobiome of T2DM patients would be reflected in people with diabetic retinopathy (DR) and if so, is the observed mycobiome dysbiosis similar in people with T2DM and DR. Gut mycobiomes were generated from healthy controls (HC), people with T2DM and people with DR through Illumina sequencing of ITS2 region. Data were analysed using QIIME and R software. Dysbiotic changes were observed in people with T2DM and DR compared to HC at the phyla and genera level. Mycobiomes of HC, T2DM and DR could be discriminated by heat map analysis, Beta diversity analysis and LEfSE analysis. Spearman correlation of fungal genera indicated more negative correlation in HC compared to T2DM and DR mycobiomes. This study demonstrates dysbiosis in the gut mycobiomes in people with T2DM and DR compared to HC. These differences were significant both at the phyla and genera level between people with T2DM and DR as well. Such studies on mycobiomes may provide new insights and directions to identification of specific fungi associated with T2DM and DR and help developing novel therapies for Diabetes Mellitus and DR.
Collapse
|
|
44
|
Lee Y, Lee HY. Revisiting the Bacterial Phylum Composition in Metabolic Diseases Focused on Host Energy Metabolism. Diabetes Metab J 2020; 44:658-667. [PMID: 32662252 PMCID: PMC7643595 DOI: 10.4093/dmj.2019.0220] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 02/05/2020] [Indexed: 12/13/2022] Open
Abstract
Over a hundred billion bacteria are found in human intestines. This has emerged as an environmental factor in metabolic diseases, such as obesity and related diseases. The majority of these bacteria belong to two dominant phyla, Bacteroidetes and Firmicutes. Since the ratio of Firmicutes to Bacteroidetes increases in people with obesity and in various animal models, it has been assumed that phylum composition causes the increase in occurrence of metabolic diseases over the past decade. However, this assumption has been challenged by recent studies that have found even an opposite association of phylum composition within metabolic diseases. Moreover, the gut microbiota affects host energy metabolism in various ways including production of metabolites and interaction with host intestinal cells to regulate signaling pathways that affect energy metabolism. However, the direct effect of gut bacteria on host energy intake, such as energy consumption by the bacteria itself and its effects on intestinal energy absorption, has been underestimated. This review aims to discuss whether increased ratio of Firmicutes to Bacteroidetes is associated with the development of metabolic diseases, and whether energy competition between the bacteria and host is a missing part of the mechanism linking gut microbiota to metabolic diseases.
Collapse
Affiliation(s)
- Yeonmi Lee
- Laboratory of Mitochondrial and Metabolic Diseases, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea
| | - Hui-Young Lee
- Laboratory of Mitochondrial and Metabolic Diseases, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea
- Division of Molecular Medicine, Department of Medicine, Gachon University College of Medicine, Incheon, Korea
| |
Collapse
|
|
45
|
Quarles WR, Pokala A, Shaw EL, Ortega-Anaya J, Hillmann L, Jimenez-Flores R, Bruno RS. Alleviation of Metabolic Endotoxemia by Milk Fat Globule Membrane: Rationale, Design, and Methods of a Double-Blind, Randomized, Controlled, Crossover Dietary Intervention in Adults with Metabolic Syndrome. Curr Dev Nutr 2020; 4:nzaa130. [PMID: 32885133 PMCID: PMC7456308 DOI: 10.1093/cdn/nzaa130] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/20/2020] [Accepted: 07/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Milk fat globule membrane (MFGM) is a phospholipid-rich component of dairy fat that might explain the benefits of full-fat dairy products on cardiometabolic risk. Preclinical studies support that MFGM decreases gut permeability, which could attenuate gut-derived endotoxin translocation and consequent inflammatory responses that impair cardiometabolic health. OBJECTIVES To describe the rationale, study design, and planned outcomes that will evaluate the efficacy of MFGM-enriched milk compared with a comparator beverage on health-promoting gut barrier functions in persons with metabolic syndrome (MetS). METHODS We plan a double-blind, randomized, crossover trial in which people with MetS will receive a rigorously controlled eucaloric diet for 2 wk that contains 3 daily servings of an MFGM-enriched bovine milk beverage or a comparator beverage that is formulated with nonfat dairy powder, coconut and palm oils, and soy phospholipids. Compliance will be monitored by assessing urinary para-aminobenzoic acid that is added to all test beverages. After the intervention, participants will ingest a high-fat/high-carbohydrate meal challenge to assess metabolic excursions at 30-min intervals for 3 h. Nondigestible sugar probes also will be ingested prior to collecting 24-h urine to assess region-specific gut permeability. Intervention efficacy will be determined based on circulating endotoxin (primary outcome) and glycemia (secondary outcome). Tertiary outcomes include: gut and systemic inflammatory responses, microbiota composition and SCFAs, gut permeability, and circulating insulin and incretins. EXPECTED RESULTS MFGM is expected to decrease circulating endotoxin and glycemia without altering body mass. These improvements are anticipated to be accompanied by decreased gut permeability, decreased intestinal and circulating biomarkers of inflammation, increased circulating incretins, and beneficial antimicrobial and prebiotic effects in the gut microbiome. CONCLUSIONS Demonstration of improvements in gut barrier functions that limit endotoxemia and glycemia could help to establish direct evidence that full-fat dairy lowers cardiometabolic risk, especially in people with MetS.The clinical trial associated with this article has been registered at clinicaltrials.gov (NCT03860584).
Collapse
Affiliation(s)
- William R Quarles
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Avi Pokala
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Emily L Shaw
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Joana Ortega-Anaya
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, USA
| | - Lisa Hillmann
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| | - Rafael Jimenez-Flores
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, USA
| |
Collapse
|
|
46
|
Sunwoo J, Ji SC, Kim AH, Yu K, Cho J, Jang I, Lee S. Impact of Vancomycin-Induced Changes in the Intestinal Microbiota on the Pharmacokinetics of Simvastatin. Clin Transl Sci 2020; 13:752-760. [PMID: 32058642 PMCID: PMC7359932 DOI: 10.1111/cts.12761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 12/19/2019] [Indexed: 12/22/2022] Open
Abstract
The pharmacokinetic (PK) properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the PKs of simvastatin. An open-label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for PK analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of microbiota considerably decreased, and the composition was altered. In particular, the relative abundance of Bacteroidetes decreased, whereas that of proteobacteria increased. In addition, changes in fecal metabolites, including D-glucuronic acid, were observed. However, systemic exposure of simvastatin was not changed whereas that of hydroxysimvastatin showed a tendency to increase. The relationship between the change of PKs of simvastatin and the change of gut microbiota and fecal metabolites were not clearly observed.
Collapse
Affiliation(s)
- Jung Sunwoo
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Sang Chun Ji
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Andrew HyoungJin Kim
- Department of MedicineDivision of Infectious DiseasesWashington University School of MedicineSt. LouisMissouriUSA
| | - Kyung‐Sang Yu
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - Joo‐Youn Cho
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - In‐Jin Jang
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| | - SeungHwan Lee
- Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulKorea
| |
Collapse
|
|
47
|
Wang J, Chen WD, Wang YD. The Relationship Between Gut Microbiota and Inflammatory Diseases: The Role of Macrophages. Front Microbiol 2020; 11:1065. [PMID: 32582063 PMCID: PMC7296120 DOI: 10.3389/fmicb.2020.01065] [Citation(s) in RCA: 165] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 04/29/2020] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota, an integral part of the human body, comprise bacteria, fungi, archaea, and protozoa. There is consensus that the disruption of the gut microbiota (termed “gut dysbiosis”) is influenced by host genetics, diet, antibiotics, and inflammation, and it is closely linked to the pathogenesis of inflammatory diseases, such as obesity and inflammatory bowel disease (IBD). Macrophages are the key players in the maintenance of tissue homeostasis by eliminating invading pathogens and exhibit extreme plasticity of their phenotypes, such as M1 or M2, which have been demonstrated to exert pro- and anti-inflammatory functions. Microbiota-derived metabolites, short-chain fatty acids (SCFAs) and Gram-negative bacterial lipopolysaccharides (LPS), exert anti-inflammatory or pro-inflammatory effects by acting on macrophages. Understanding the role of macrophages in gut microbiota-inflammation interactions might provide us a novel method for preventing and treating inflammatory diseases. In this review, we summarize the recent research on the relationship between gut microbiota and inflammation and discuss the important role of macrophages in this context.
Collapse
Affiliation(s)
- Ji Wang
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Wei-Dong Chen
- Key Laboratory of Molecular Pathology, School of Basic Medical Science, Inner Mongolia Medical University, Hohhot, China.,Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, Hebi People's Hospital, School of Medicine, Henan University, Kaifeng, China
| | - Yan-Dong Wang
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| |
Collapse
|
|
48
|
Cai H, Wen Z, Li X, Meng K, Yang P. Lactobacillus plantarum FRT10 alleviated high-fat diet-induced obesity in mice through regulating the PPARα signal pathway and gut microbiota. Appl Microbiol Biotechnol 2020; 104:5959-5972. [PMID: 32409945 DOI: 10.1007/s00253-020-10620-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 03/31/2020] [Accepted: 04/09/2020] [Indexed: 12/20/2022]
Abstract
Previous studies showed that probiotics supplementation contributed to alleviate obesity. This work was to assess the efficacy of Lactobacillus plantarum FRT10 from sour dough in alleviating obesity in mice fed with a high-fat diet (HFD), and the underlying mechanisms focusing on modulation of the gut microbiota profile. Kunming mice were fed with a regular diet (CT), a high-fat diet (HFD), and two HFDs containing low and high doses of L. plantarum FRT10 for 8 weeks. The physiological and biochemical modulations in liver were analyzed. Cecal contents were analyzed by high-throughput 16S ribosomal RNA sequencing. FRT10 supplementation significantly reduced body weight gain, fat weight, and liver triacylglycerols (TGs) and alanine aminotransferase (ALT) concentrations (P < 0.05). FRT10 significantly ameliorated the HFD-induced gut dysbiosis, as evidenced by increased abundance of microbes, including Butyricicoccus, Butyricimonas, Intestinimonas, Odoribacter, and Alistipes, and decreased abundance of Desulfovibrionaceae, Roseburia, and Lachnoclostridium. Lactobacillus, Bifidobacterium, and Akkermansia were markedly increased after FRT10 intervention. In addition, real-time quantitative PCR revealed that FRT10 upregulated the mRNA expression levels of peroxisome proliferator-activated receptor-α (PPARα) and carnitine palmitoyltransferase-1α (CPT1α), and downregulated the mRNA expression levels of sterol regulatory element-binding protein 1 (SREBP-1) and TG-synthesizing enzyme diacylglycerol acyltransferase 1 (DGAT1) in liver. These findings suggested that FRT10 had anti-obesity effects in obese mice partly related to the activation of PPARα/CPT1α pathway. FRT10 can be considered a single probiotic agent for preventing HFD-induced obesity in humans and animals.
Collapse
Affiliation(s)
- Hongying Cai
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.,National Engineering Research Center of Biological Feed, Beijing, 100081, China
| | - Zhiguo Wen
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Xiumei Li
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Kun Meng
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Peilong Yang
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China. .,National Engineering Research Center of Biological Feed, Beijing, 100081, China.
| |
Collapse
|
|
49
|
Cassani L, Gomez-Zavaglia A, Simal-Gandara J. Technological strategies ensuring the safe arrival of beneficial microorganisms to the gut: From food processing and storage to their passage through the gastrointestinal tract. Food Res Int 2020; 129:108852. [DOI: 10.1016/j.foodres.2019.108852] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 11/18/2019] [Accepted: 11/20/2019] [Indexed: 02/08/2023]
|
|
50
|
Park JE, Oh SH, Cha YS. Lactobacillus Brevis OPK-3 from Kimchi Prevents Obesity and Modulates the Expression of Adipogenic and Pro-Inflammatory Genes in Adipose Tissue of Diet-Induced Obese Mice. Nutrients 2020; 12:nu12030604. [PMID: 32110872 PMCID: PMC7146405 DOI: 10.3390/nu12030604] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 02/20/2020] [Accepted: 02/24/2020] [Indexed: 12/15/2022] Open
Abstract
Our previous study reported that lactic acid bacteria (L. brevis OPK-3) isolated from kimchi ameliorated intracellular lipid accumulation in 3T3-L1 adipocyte. The current study explored potential roles of L. brevis OPK-3 (KLAB) on preventing body weight gain and its effect on the inflammatory response of adipose tissue. Male C57BL/6 mice (n = 10) were divided into four groups: normal diet with distilled water (NDC), high-fat diet with distilled water (HDC), high-fat diet with L-ornithine (OTC) or high-fat diet with KLAB. The KLAB supplement resulted in significantly lower body weight, lower epididymal fat tissue mass, and lower serum and hepatic TG levels than the HDC. KLAB supplementation improved serum cytokines, and real-time polymerase chain reaction (PCR) analysis showed significantly lower inflammatory cytokine mRNA levels in epididymal adipose tissue. These results suggest that the administration of KLAB inhibits the induction of inflammation in adipose tissue along with the inhibition of weight gain. Therefore, this study demonstrates the therapeutic and beneficial value of this strain produced during the fermentation of kimchi.
Collapse
Affiliation(s)
- Jung Eun Park
- Department of Food Science and Human Nutrition, Jeonbuk National University and Obesity Research Center, Jeonju, 54896 Jeonbuk, Korea;
| | - Suk-Heung Oh
- Department of Food and Biotechnology, Woosuk University, Samnye-eup, Wanju-gun 55338, Jeonbuk, Korea;
| | - Youn-Soo Cha
- Department of Food Science and Human Nutrition, Jeonbuk National University and Obesity Research Center, Jeonju, 54896 Jeonbuk, Korea;
- Correspondence: ; Tel.: +82-63-270-4258
| |
Collapse
|