1
|
Zhou P, Liu Q, Zhao Y, Wu Y, Shen J, Duan T, Che L, Zhang Y, Yan H. Yeast protein as a fishmeal substitute: impacts on reproductive performance, immune responses, and gut microbiota in two sow hybrids. Front Cell Infect Microbiol 2025; 15:1579950. [PMID: 40330018 PMCID: PMC12052836 DOI: 10.3389/fcimb.2025.1579950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 03/24/2025] [Indexed: 05/08/2025] Open
Abstract
Introduction The persistent African swine fever epidemic has significantly compromised China's swine production. To accelerate production recovery, commercial farms are increasingly adopting retention of two-way backcross sows (Landrace × Yorkshire × Landrace, LLY) for breeding. This study aimed to investigate the effects of yeast protein, an emerging sustainable protein source, on reproductive performance, immune responses, and gut microbiota in two-way crossbred sows (Landrace × Yorkshire, LY) and LLY sows. Methods The experiment employed a 2×2 factorial design evaluating two fixed factors: sow hybrid (LY vs LLY) and yeast protein supplementation (0% vs 2.6%). The four treatment groups were: LY sows without yeast protein supplementation (LY-C), LLY sows without yeast protein supplementation (LLY-C), LY sows with yeast protein supplementation (LY-YP), and LLY sows with yeast protein supplementation (LLY-YP). A total of one hundred healthy sows of 2-6 parities (50 LY sows and 50 LLY sows), were stratified by backfat thickness, body weight, and parity, then randomly allocated to the four treatment groups on day 105 of gestation, with 25 sows in each group. The experimental period lasted from day 106 of gestation to day 18 of lactation. Results and conclusion Yeast protein supplementation showed no significant effects on most reproductive parameters of different sow hybrids, but reduced backfat loss by 30.5% during lactation (P < 0.05) and demonstrated a numerical reduction in mummification rate of fetuses (P = 0.06). Immunological assessments revealed that LLY sows exhibited 26.8% lower serum IgM concentration than LY sows (P < 0.05), while yeast protein supplementation significantly reduced serum IL-1β levels by 45.6% (P < 0.05) on day 18 of lactation. 16S rRNA gene sequencing analysis revealed comparable fecal microbial diversity across treatments (P > 0.05), though differences were observed in certain bacterial genera between LY and LLY sows during late gestation and lactation. Yeast protein supplementation enriched beneficial bacteria including Ruminococcaceae_UCG-002, Rikenellaceae_RC9_gut_group, and Christensenellaceae_R_7_group, while suppressing potentially detrimental bacteria such as Family_XIII_AD3011_group (P < 0.05). These findings demonstrate the practical feasibility of retaining LLY sows for commercial breeding. Yeast protein supplementation, as a substitute for fishmeal during late gestation and lactation, significantly reduced lactational backfat loss, moderately attenuated inflammatory response, and enhanced gut microbiome homeostasis through selective microbial enrichment in sows.
Collapse
Affiliation(s)
- Pan Zhou
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Qi Liu
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Yang Zhao
- Animal Breeding and Genetics Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu, China
| | - Yachao Wu
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Jianbo Shen
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Tao Duan
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Long Che
- College of Animal Science and Technology, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China
| | - Yong Zhang
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| | - Honglin Yan
- School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, China
| |
Collapse
|
2
|
Ruiz de la Bastida A, Langa S, Peirotén Á, Curiel JA, Fernández-González R, Maroto M, Arqués J, Gutiérrez-Adán A, Landete JM. Fermented Lignan-Enriched Soy Beverage Ameliorates the Metabolic Effects of a High-Fat Diet on Female Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:5194-5207. [PMID: 39985458 DOI: 10.1021/acs.jafc.4c06947] [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: 02/24/2025]
Abstract
Fermented vegetable beverages have potential beneficial effects on the health associated with the production of bioactive flavonoids and lignans by selected bacterial strains. Here, we studied the effects of a soy beverage and a soy beverage fermented by Bifidobacterium pseudocatenulatum INIA P815, both supplemented with lignan extracts, in a female mouse model on a high-fat diet followed for 16 weeks. The high-fat diet induced an increase in adipose tissue and plasma cholesterol as well as modified the fecal microbiota. Mice groups receiving any of the beverages showed a reduction in the mean area of ovarian fat tissue adipocytes and exhibited bioactive flavonoids and lignans in plasma and tissues, accompanied by a higher antioxidant activity in plasma. The group of mice subjected to the fermented beverage also demonstrated a lower increase in plasma cholesterol levels, an increase in short-chain fatty acid production, and higher levels of daidzein, genistein, enterolignans, and herbacetin in the plasma and organs. Moreover, the fertility of the mice that received the fermented beverage was also enhanced, resulting in a higher percentage of blastocysts per female mouse. Therefore, the consumption of the beverage fermented by B. pseudocatenulatum INIA P815 could be favoring the health of mice by ameliorating, to some extent, the effects of a high-fat diet.
Collapse
Affiliation(s)
- Ana Ruiz de la Bastida
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - Susana Langa
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - Ángela Peirotén
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - José Antonio Curiel
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - Raúl Fernández-González
- Departamento de Reproducción Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - María Maroto
- Departamento de Reproducción Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - Juan Arqués
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - Alfonso Gutiérrez-Adán
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| | - José María Landete
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (INIA-CSIC), Madrid 28040, Spain
| |
Collapse
|
3
|
Lin R, Chen R. Exploring the causal connection: insights into diabetic nephropathy and gut microbiota from whole-genome sequencing databases. Ren Fail 2024; 46:2385065. [PMID: 39090986 PMCID: PMC11299436 DOI: 10.1080/0886022x.2024.2385065] [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: 04/15/2024] [Revised: 07/03/2024] [Accepted: 07/22/2024] [Indexed: 08/04/2024] Open
Abstract
Over recent years, the prevalence of diabetes has been on the rise, paralleling improvements in living standards. Diabetic nephropathy (DN), a prevalent complication of diabetes, has also exhibited a growing incidence. While some clinical studies and reviews have hinted at a link between diabetic nephropathy and gut microbiota (GM), the nature of this connection, specifically its causative nature, remains uncertain. Investigating the causal relationship between diabetic nephropathy and gut microbiota holds the promise of aiding in disease screening and identifying novel biomarkers. In this study, we employed a two-sample Mendelian randomization analysis. Our dataset encompassed 4,111 DN patients from the GWAS database, juxtaposed with 308,539 members forming a control group. The aim was to pinpoint specific categories within the vast spectrum of the 211 known gut microbiota types that may have a direct causal relationship with diabetic nephropathy. Rigorous measures, including extensive heterogeneity and sensitivity analyses, were implemented to mitigate the influence of confounding variables on our experimental outcomes. Ultimately, our comprehensive analysis revealed 15 distinct categories of gut microbiota that exhibit a causal association with diabetic nephropathy. In summary, the phyla Bacteroidota and Verrucomicrobiae, the families Peptostreptococcaceae and Veillonellaceae, the genus Akkermansia, and the species Catenibacterium, Lachnoclostridium, Parasutterella, along with the orders Bacteroidales and Verrucomicrobiales, and the class Bacteroidetes were identified as correlates of increased risk for DN. Conversely, the family Victivallaceae, the species Eubacterium coprostanoligenes, and the Clostridium sensu stricto 1 group were found to be associated with a protective effect against the development of DN.These findings not only provide valuable insights but also open up novel avenues for clinical research, offering fresh directions for potential treatments.
Collapse
Affiliation(s)
- Rui Lin
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Rongping Chen
- Department of Endocrinology, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| |
Collapse
|
4
|
Ashraf A, Hassan MI. Microbial Endocrinology: Host metabolism and appetite hormones interaction with gut microbiome. Mol Cell Endocrinol 2024; 592:112281. [PMID: 38810719 DOI: 10.1016/j.mce.2024.112281] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 05/07/2024] [Accepted: 05/26/2024] [Indexed: 05/31/2024]
Affiliation(s)
- Anam Ashraf
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
| |
Collapse
|
5
|
Datta S, Pasham S, Inavolu S, Boini KM, Koka S. Role of Gut Microbial Metabolites in Cardiovascular Diseases-Current Insights and the Road Ahead. Int J Mol Sci 2024; 25:10208. [PMID: 39337693 PMCID: PMC11432476 DOI: 10.3390/ijms251810208] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of premature morbidity and mortality globally. The identification of novel risk factors contributing to CVD onset and progression has enabled an improved understanding of CVD pathophysiology. In addition to the conventional risk factors like high blood pressure, diabetes, obesity and smoking, the role of gut microbiome and intestinal microbe-derived metabolites in maintaining cardiovascular health has gained recent attention in the field of CVD pathophysiology. The human gastrointestinal tract caters to a highly diverse spectrum of microbes recognized as the gut microbiota, which are central to several physiologically significant cascades such as metabolism, nutrient absorption, and energy balance. The manipulation of the gut microbial subtleties potentially contributes to CVD, inflammation, neurodegeneration, obesity, and diabetic onset. The existing paradigm of studies suggests that the disruption of the gut microbial dynamics contributes towards CVD incidence. However, the exact mechanistic understanding of such a correlation from a signaling perspective remains elusive. This review has focused upon an in-depth characterization of gut microbial metabolites and their role in varied pathophysiological conditions, and highlights the potential molecular and signaling mechanisms governing the gut microbial metabolites in CVDs. In addition, it summarizes the existing courses of therapy in modulating the gut microbiome and its metabolites, limitations and scientific gaps in our current understanding, as well as future directions of studies involving the modulation of the gut microbiome and its metabolites, which can be undertaken to develop CVD-associated treatment options. Clarity in the understanding of the molecular interaction(s) and associations governing the gut microbiome and CVD shall potentially enable the development of novel druggable targets to ameliorate CVD in the years to come.
Collapse
Affiliation(s)
- Sayantap Datta
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
| | - Sindhura Pasham
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| | - Sriram Inavolu
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| | - Krishna M Boini
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
| | - Saisudha Koka
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| |
Collapse
|
6
|
Ma G, Yan H, Tye KD, Tang X, Luo H, Li Z, Xiao X. Effect of probiotic administration during pregnancy on the functional diversity of the gut microbiota in healthy pregnant women. Microbiol Spectr 2024; 12:e0041324. [PMID: 38687069 PMCID: PMC11237737 DOI: 10.1128/spectrum.00413-24] [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: 02/14/2024] [Accepted: 04/15/2024] [Indexed: 05/02/2024] Open
Abstract
Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera Blautia and Ruminococcus, as well as the species Subdoligranulum, showed significantly higher relative abundances compared to the control group (CG) (P < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG (P < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG (P < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism (P < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and Vibrio cholerae pathogenic cycle (P < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women. IMPORTANCE Probiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism. This could potentially open up new avenues for preventing various pregnancy-related complications. This also provides new insights into the effects of probiotic consumption during pregnancy on the gut microbiota and offers a convenient method for exploring the potential mechanisms underlying the impact of probiotics on the gut microbiota of pregnant women.
Collapse
Affiliation(s)
- Guangyu Ma
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Hao Yan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Kian Deng Tye
- Department of Obstetrics and Gynecology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiaomei Tang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Huijuan Luo
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Zhe Li
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiaomin Xiao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| |
Collapse
|
7
|
Chen Y, Xie C, Lei Y, Ye D, Wang L, Xiong F, Wu H, He Q, Zhou H, Li L, Xing J, Wang C, Zheng M. Theabrownin from Qingzhuan tea prevents high-fat diet-induced MASLD via regulating intestinal microbiota. Biomed Pharmacother 2024; 174:116582. [PMID: 38642504 DOI: 10.1016/j.biopha.2024.116582] [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: 11/23/2023] [Revised: 04/05/2024] [Accepted: 04/10/2024] [Indexed: 04/22/2024] Open
Abstract
The aim of this study was to investigate whether the therapeutic effect of theabrownin extracted from Qingzhuan tea (QTB) on metabolic dysfunction-associated steatosis liver disease (MASLD) is related to the regulation of intestinal microbiota and its metabolite short-chain fatty acids (SCFAs). Mice were divided into four groups and received normal diet (ND), high-fat diet (HFD) and HFD+QTB (180, 360 mg/kg) for 8 weeks. The results showed that QTB significantly reduced the body weight of HFD mice, ameliorated liver lipid and dyslipidemia, and increased the level of intestinal SCFAs in HFD mice. The results of 16 S rRNA showed that the relative abundance of Bacteroides, Blautia and Lachnoclostridium and their main metabolites acetate and propionate were significantly increased after QTB intervention. The relative abundance of Colidextribacter, Faecalibaculum and Lactobacillus was significantly reduced. QTB can also significantly up-regulate the expression of ATGL, PPARα, FFAR2 and FFAR3, and inhibit the expression of LXRα, SREBP-1c, FAS and HMGCR genes. This makes it possible to act as a prebiotic to prevent MASLD.
Collapse
Affiliation(s)
- Yong Chen
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Chen Xie
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China; Obstetrics and Gynecology of the Second Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, China
| | - Yining Lei
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Dan Ye
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Le Wang
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Fang Xiong
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Hui Wu
- Xianning Public Inspection Center of Hubei Province, Xianning 437100, China
| | - Qiang He
- Xianning Public Inspection Center of Hubei Province, Xianning 437100, China
| | - Hongfu Zhou
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Ling Li
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Jun Xing
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Cai Wang
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China
| | - Min Zheng
- Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China; Hubei Industrial Technology Research Institute of Intelligent Health, Xianning 437100, China.
| |
Collapse
|
8
|
Martínez-López YE, Neri-Rosario D, Esquivel-Hernández DA, Padron-Manrique C, Vázquez-Jiménez A, Sánchez-Castañeda JP, Girón-Villalobos D, Mendoza-Ortíz C, Reyes-Escogido MDL, Evia-Viscarra ML, Aguilar-Garcia A, Resendis-Antonio O, Guardado-Mendoza R. Effect of metformin and metformin/linagliptin on gut microbiota in patients with prediabetes. Sci Rep 2024; 14:9678. [PMID: 38678119 PMCID: PMC11055900 DOI: 10.1038/s41598-024-60081-y] [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: 09/23/2023] [Accepted: 04/18/2024] [Indexed: 04/29/2024] Open
Abstract
Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic β-cell function (Pβf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes. These treatments increased the abundance of GM SCFA-producing bacteria M (Fusicatenibacter and Blautia) and LM (Roseburia, Bifidobacterium, and [Eubacterium] hallii group). We performed a mediation analysis with structural equation models (SEM). In conclusion, M and LM therapies improve insulin sensitivity and Pβf in prediabetics. GM is partially associated with these improvements since the SEM models suggest a weak association between specific bacterial genera and improvements in IS and Pβf.
Collapse
Affiliation(s)
- Yoscelina Estrella Martínez-López
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
- Programa de Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
- Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato, León, Guanajuato, Mexico
| | - Daniel Neri-Rosario
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
- Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
| | | | - Cristian Padron-Manrique
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
- Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
| | - Aarón Vázquez-Jiménez
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
| | - Jean Paul Sánchez-Castañeda
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
- Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
| | - David Girón-Villalobos
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
- Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
| | - Cristian Mendoza-Ortíz
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico
- Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico
| | | | | | | | - Osbaldo Resendis-Antonio
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico.
- Coordinación de la Investigación Científica - Red de Apoyo a la Investigación - Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico.
| | - Rodolfo Guardado-Mendoza
- Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato, León, Guanajuato, Mexico.
| |
Collapse
|
9
|
Tayyib HMU, Ali A, Jabeen S, Habib-Ur-Rehman, Kamran H, Bajaber MA, Usman M, Zhang X. Restoration of gut dysbiosis through Clostridium butyricum and magnesium possibly balance blood glucose levels: an experimental study. BMC Microbiol 2024; 24:105. [PMID: 38561662 PMCID: PMC10983686 DOI: 10.1186/s12866-024-03218-3] [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: 09/09/2023] [Accepted: 02/07/2024] [Indexed: 04/04/2024] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by an elevated level of blood glucose due to the absence of insulin secretion, ineffectiveness, or lack of uptake of secreted insulin in the body. The improperly diagnosed and poorly managed DM can cause severe damage to organs in the body like the nerves, eyes, heart, and kidneys. This study was aimed at investigating the effect of Clostridium butyricum (probiotic) with magnesium supplementation to evaluate the effect on gut microbial dysbiosis and blood glucose levels. In the laboratory, 6-8 weeks old 24 male albino rats weighing 200-250 g were given free access to water and food. Diabetes was induced using streptozotocin (60 mg/kg) in overnight fasted rats. Diabetic rats were randomly divided into four groups (n = 6, 6 replicates in each group). Metformin (100 mg/kg/day) with a standard basal diet was provided to control group (G0), Clostridium butyricum (1.5 × 105 CFU/day) with standard basal diet was provided to treatment group (G1), magnesium (500 mg/kg/day) was provided to group (G2). Clostridium butyricum (1.5 × 105 CFU/day) and magnesium (300 mg/kg/day) in combination with a standard basal diet was provided to group (G3). Blood Glucose, Magnesium blood test and microbial assay were done. Random blood glucose levels were monitored twice a week for 21 days and were represented as mean of each week. The results conclude that Clostridium butyricum (1.5 × 105 CFU) is very effective in balancing random blood glucose levels from 206.6 ± 67.7 to 85.1 ± 3.8 (p = 0.006) compared to other groups (p > 0.005). The results of stool analysis showed that Clostridium butyricum as probiotic restores microbial dysbiosis as evident by the 105 CFU Clostridium butyricum load in G1, which was higher than G0, G2 and G3 which were 103 and 104 CFU respectively. The findings of this study conclude that Clostridium butyricum supplementation improved blood glucose levels and intestinal bacterial load in type II diabetes mellitus.
Collapse
Affiliation(s)
- Hafiz Muhammad Ubaid Tayyib
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, P. R. China
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Amjed Ali
- University Institute of Physical therapy, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Shaista Jabeen
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Habib-Ur-Rehman
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Hafsa Kamran
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, Pakistan
| | - Majed A Bajaber
- Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia
| | - Muhammad Usman
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, P. R. China.
| | - Xiao Zhang
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, P. R. China.
- Yantai Longch Technologies. CO., LTD, Yantai, P. R. China.
| |
Collapse
|
10
|
Zeng Y, Wu Y, Zhang Q, Xiao X. Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio 2024; 15:e0203223. [PMID: 38055342 PMCID: PMC10790698 DOI: 10.1128/mbio.02032-23] [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] [Indexed: 12/08/2023] Open
Abstract
Gut microbiota exert influence on gastrointestinal mucosal permeability, bile acid metabolism, short-chain fatty acid synthesis, dietary fiber fermentation, and farnesoid X receptor/Takeda G protein-coupled receptor 5 (TGR5) signal transduction. The incretin glucagon-like peptide 1 (GLP-1) is mainly produced by L cells in the gut and regulates postprandial blood glucose. Changes in gut microbiota composition and function have been observed in obesity and type 2 diabetes (T2D). Meanwhile, the function and rhythm of GLP-1 have also been affected in subjects with obesity or T2D. Therefore, it is necessary to discuss the link between the gut microbiome and GLP-1. In this review, we describe the interaction between GLP-1 and the gut microbiota in metabolic diseases. On the one hand, gut microbiota metabolites stimulate GLP-1 secretion, and gut microbiota affect GLP-1 function and rhythm. On the other hand, the mechanism of action of GLP-1 on gut microbiota involves the inflammatory response. Additionally, we discuss the effects and mechanism of various interventions, such as prebiotics, probiotics, antidiabetic drugs, and bariatric surgery, on the crosstalk between gut microbiota and GLP-1. Finally, we stress that gut microbiota can be used as a target for metabolic diseases, and the clinical application of GLP-1 receptor agonists should be individualized.
Collapse
Grants
- 81870545, 81870579, 82170854, 81570715, 81170736 MOST | National Natural Science Foundation of China (NSFC)
- 7202163 Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)
- Z201100005520011 Beijing Municipal Science and Technology Commission, Adminitrative Commission of Zhongguancun Science Park
- 2017YFC1309603, 2021YFC2501700, 2016YFA0101002, 2018YFC2001100 MOST | National Key Research and Development Program of China (NKPs)
- 2019DCT-M-05 Beijing Municipal Human Resources and Social Security Bureau (BMHRSSB)
- 2017PT31036, 2018PT31021 Chinese Academy of Medical Sciences (CAMS)
- 2017PT32020, 2018PT32001 Chinese Academy of Medical Sciences (CAMS)
- CIFMS2017-I2M-1-008, CIFMS2021-I2M-1-002 Chinese Academy of Medical Sciences (CAMS)
- 2022-PUMCH- C-019, 2022-PUMCH-B-121 National High Level Hospital Clinical Research Funding
Collapse
Affiliation(s)
- Yuan Zeng
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yifan Wu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Qian Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xinhua Xiao
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| |
Collapse
|
11
|
Du C, Zuo F, Cao Y, Zang Y. Anti-diabetic effects of natural and modified 'Ganzhou' navel orange peel pectin on type 2 diabetic mice via gut microbiota. Food Funct 2023; 14:10977-10990. [PMID: 38014521 DOI: 10.1039/d3fo04118b] [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: 11/29/2023]
Abstract
Pectin, a kind of dietary fiber, has attracted much attention owing to its beneficial effect on human health in recent years. In this study, the effects of both 'Ganzhou' navel orange peel pectin (GOP) and modified GOP (MGOP) on type 2 diabetes (T2DM) were investigated. The results indicated that GOP and MGOP intervention had positive effects on T2DM in C57BL/6 mice. After modification, pectin can be changed into low methoxy pectin (LMP) and the content of GalA can increase, which endow MGOP with significant effects on improving lipid metabolism (TC, TG, and LDL-C decreased by 30.46%, 50%, and 37.56%, respectively, and HDL-C increased by 56%) and OGTT, further reducing insulin resistance (insulin decreased by 74.35%). In addition, MGOP was superior to GOP in improving oxidative stress (GSH and GSH-Px increased by 52.05% and 29.08% respectively, and MDA decreased by 84.02%), inhibiting inflammation and promoting SCFA synthesis. 16S rRNA analysis showed that MGOP changed the composition of intestinal microbiota in diabetic mice, decreased the abundance of Alistipes, Helicobacter and Oscillibacter, and increased the relative abundance of Dubosiella, Akkermansiaceae, and Atopobiaceae. The phenotypes of the gut microbiome also changed accordingly, which showed that MGOP significantly inhibited the growth of Gram-negative bacteria and potential pathogenic bacteria and reversed the related complications. Taken together, our findings revealed that MGOP intake regulated lipid metabolism and oxidative stress and improved the gut health of mice, with promising effects against T2DM and related complications.
Collapse
Affiliation(s)
- Chao Du
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China
- National Coarse Cereals Engineering Research Center, Daqing, Heilongjiang, China.
| | - Feng Zuo
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China
- National Coarse Cereals Engineering Research Center, Daqing, Heilongjiang, China.
| | - Yang Cao
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China
- National Coarse Cereals Engineering Research Center, Daqing, Heilongjiang, China.
| | - Yanqing Zang
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China
- National Coarse Cereals Engineering Research Center, Daqing, Heilongjiang, China.
| |
Collapse
|
12
|
Lagunas-Rangel FA, Liao S, Williams MJ, Trukhan V, Fredriksson R, Schiöth HB. Drosophila as a Rapid Screening Model to Evaluate the Hypoglycemic Effects of Dipeptidyl Peptidase 4 (DPP4) Inhibitors: High Evolutionary Conservation of DPP4. Biomedicines 2023; 11:3032. [PMID: 38002032 PMCID: PMC10669173 DOI: 10.3390/biomedicines11113032] [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: 10/11/2023] [Revised: 11/09/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, have been an integral part of the treatment of type 2 diabetes mellitus (T2DM) for several years. Despite their remarkable efficacy in lowering glucose levels and their compatibility with other hypoglycemic drugs, recent studies have revealed adverse effects, prompting the search for improved drugs within this category, which has required the use of animal models to verify the hypoglycemic effects of these compounds. Currently, in many countries the use of mammals is being significantly restricted, as well as cost prohibitive, and alternative in vivo approaches have been encouraged. In this sense, Drosophila has emerged as a promising alternative for several compelling reasons: it is cost-effective, offers high experimental throughput, is genetically manipulable, and allows the assessment of multigenerational effects, among other advantages. In this study, we present evidence that diprotin A, a DPP4 inhibitor, effectively reduces glucose levels in Drosophila hemolymph. This discovery underscores the potential of Drosophila as an initial screening tool for novel compounds directed against DPP4 enzymatic activity.
Collapse
Affiliation(s)
- Francisco Alejandro Lagunas-Rangel
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
| | - Sifang Liao
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
| | - Michael J. Williams
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
| | | | - Robert Fredriksson
- Department of Pharmaceutical Biosciences, Uppsala University, 751 24 Uppsala, Sweden;
| | - Helgi B. Schiöth
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, 751 24 Uppsala, Sweden; (F.A.L.-R.); (S.L.); (M.J.W.)
| |
Collapse
|
13
|
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
|
14
|
Zhao Q, Chen Y, Huang W, Zhou H, Zhang W. Drug-microbiota interactions: an emerging priority for precision medicine. Signal Transduct Target Ther 2023; 8:386. [PMID: 37806986 PMCID: PMC10560686 DOI: 10.1038/s41392-023-01619-w] [Citation(s) in RCA: 80] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 07/20/2023] [Accepted: 08/24/2023] [Indexed: 10/10/2023] Open
Abstract
Individual variability in drug response (IVDR) can be a major cause of adverse drug reactions (ADRs) and prolonged therapy, resulting in a substantial health and economic burden. Despite extensive research in pharmacogenomics regarding the impact of individual genetic background on pharmacokinetics (PK) and pharmacodynamics (PD), genetic diversity explains only a limited proportion of IVDR. The role of gut microbiota, also known as the second genome, and its metabolites in modulating therapeutic outcomes in human diseases have been highlighted by recent studies. Consequently, the burgeoning field of pharmacomicrobiomics aims to explore the correlation between microbiota variation and IVDR or ADRs. This review presents an up-to-date overview of the intricate interactions between gut microbiota and classical therapeutic agents for human systemic diseases, including cancer, cardiovascular diseases (CVDs), endocrine diseases, and others. We summarise how microbiota, directly and indirectly, modify the absorption, distribution, metabolism, and excretion (ADME) of drugs. Conversely, drugs can also modulate the composition and function of gut microbiota, leading to changes in microbial metabolism and immune response. We also discuss the practical challenges, strategies, and opportunities in this field, emphasizing the critical need to develop an innovative approach to multi-omics, integrate various data types, including human and microbiota genomic data, as well as translate lab data into clinical practice. To sum up, pharmacomicrobiomics represents a promising avenue to address IVDR and improve patient outcomes, and further research in this field is imperative to unlock its full potential for precision medicine.
Collapse
Affiliation(s)
- Qing Zhao
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Yao Chen
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Weihua Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Honghao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, Changsha, 410078, PR China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha, 410078, PR China
- National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, 410008, PR China
| | - Wei Zhang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, PR China.
- The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, PR China.
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, PR China.
- Central Laboratory of Hunan Cancer Hospital, Central South University, 283 Tongzipo Road, Changsha, 410013, PR China.
| |
Collapse
|
15
|
Paripati N, Nesi L, Sterrett JD, Dawud LM, Kessler LR, Lowry CA, Perez LJ, DeSipio J, Phadtare S. Gut Microbiome and Lipidome Signatures in Irritable Bowel Syndrome Patients from a Low-Income, Food-Desert Area: A Pilot Study. Microorganisms 2023; 11:2503. [PMID: 37894161 PMCID: PMC10609137 DOI: 10.3390/microorganisms11102503] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 09/29/2023] [Accepted: 10/02/2023] [Indexed: 10/29/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastroenterological disorder with triggers such as fructose. We showed that our IBS patients suffering from socioeconomic challenges have a significantly high consumption of high-fructose corn syrup (HFCS). Here, we characterize gut microbial dysbiosis and fatty acid changes, with respect to IBS, HFCS consumption, and socioeconomic factors. Fecal samples from IBS patients and healthy controls were subjected to microbiome and lipidome analyses. We assessed phylogenetic diversity and community composition of the microbiomes, and used linear discriminant analysis effect size (LEfSe), analysis of compositions of microbiomes (ANCOM) on highly co-occurring subcommunities (modules), least absolute shrinkage and selection operator (LASSO) on phylogenetic isometric log-ratio transformed (PhILR) taxon abundances to identify differentially abundant taxa. Based on a Procrustes randomization test, the microbiome and lipidome datasets correlated significantly (p = 0.002). Alpha diversity correlated with economic factors (p < 0.001). Multiple subsets of the phylogenetic tree were associated with HFCS consumption (p < 0.001). In IBS patients, relative abundances of potentially beneficial bacteria such as Monoglobaceae, Lachnospiraceae, and Ruminococcaceae were lower (p = 0.007), and Eisenbergiella, associated with inflammatory disorders, was higher. In IBS patients, certain saturated fatty acids were higher and unsaturated fatty acids were lower (p < 0.05). Our study aims first to underscore the influence of HFCS consumption and socioeconomic factors on IBS pathophysiology, and provides new insights that inform patient care.
Collapse
Affiliation(s)
- Nikita Paripati
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
- Department of Emergency Medicine, Penn Medicine, Pittsburgh, PA 15261, USA
| | - Lauren Nesi
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
- Department of Urology, Detroit Medical Center, Detroit, MI 4820, USA
| | - John D Sterrett
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Lamya'a M Dawud
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Lyanna R Kessler
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Christopher A Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA
| | - Lark J Perez
- Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA
| | - Joshua DeSipio
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
- Department of Gastroenterology, Cooper University Hospital, Camden, NJ 08103, USA
| | - Sangita Phadtare
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| |
Collapse
|
16
|
Tian E, Wang F, Zhao L, Sun Y, Yang J. The pathogenic role of intestinal flora metabolites in diabetic nephropathy. Front Physiol 2023; 14:1231621. [PMID: 37469558 PMCID: PMC10352811 DOI: 10.3389/fphys.2023.1231621] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 06/26/2023] [Indexed: 07/21/2023] Open
Abstract
With the increasing incidence of diabetes, diabetic kidney disease has become a major cause of chronic kidney disease. The role of the gut microbiota in diabetes and its related complications have been extensively investigated; the modulatory effect of the gut microbiota on the host depends on several gut microbial metabolites, particularly short-chain fatty acids, secondary bile acids, and trimethylamine N-oxide. In this review, we focused on the evidence related to the pathogenic role of each of the gut microbial metabolites in diabetic nephropathy. The main novel therapies targeting the gut microbiota include probiotics, dietary prebiotics, synbiotic supplements, and faecal microbiota transplants, although there is no standard treatment principle. Further research is therefore needed to elucidate the link between gut microbes and diabetic nephropathy, and more therapeutic targets should be explored to treat diabetic nephropathy with dysbiosis of the gut microbes.
Collapse
Affiliation(s)
- En Tian
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Feng Wang
- Beibei Traditional Chinese Medicine Hospital, Chongqing, China
| | - Lei Zhao
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Sun
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jurong Yang
- The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
17
|
Bai Y, Zhang Y, Wang Z, Pi Y, Zhao J, Wang S, Han D, Wang J. Amylopectin Partially Substituted by Cellulose in the Hindgut Was Beneficial to Short-Chain Fatty Acid Production and Probiotic Colonization. Microbiol Spectr 2023; 11:e0381522. [PMID: 37036363 PMCID: PMC10269567 DOI: 10.1128/spectrum.03815-22] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 03/20/2023] [Indexed: 04/11/2023] Open
Abstract
Undigested amylopectin fermentation in the hindguts of humans and pigs with low digestive capacity has been proven to be a low-efficiency method of energy supply. In this study, we researched the effects and mechanisms of amylopectin fermentation on hindgut microbiota and metabolite production using an in vitro fermentation trial and ileal infusion pigs model. In addition, we also researched the effects of interaction between amylopectin and cellulose during hindgut fermentation in this study. Our results showed that amylopectin had higher short-chain fatty acid (SCFA) production and dry matter digestibility (DMD) than cellulose but was not significantly different from a mixture of amylopectin and cellulose (Amycel vitro) during in vitro fermentation. The Amycel vitro group even had the highest reducing sugar content and amylase activity among all groups. The ileal infusion trial produced similar results to vitro fermentation trial: the mixture of amylopectin and cellulose infusion (Amycel vivo) significantly increased the levels of reducing sugar, acetate, and butyrate in the hindgut compared with the amylopectin infusion (Amy vivo). The mixture of amylopectin and cellulose infusion also resulted in increased Shannon index and probiotic colonization in the hindgut. The relative abundance of Romboutsia in the Amycel vivo group, which was considered a noxious bacteria in the Amycel vivo group, was also significantly lower than that in the Amy vivo group. In summary, the high level of amylopectin fermentation in the hindgut was harmful to intestinal microbiota, but amylopectin partially substituted with cellulose was beneficial to SCFA production and probiotic colonization. IMPORTANCE A high-starch (mainly amylopectin) diet is usually accompanied by the fermentation of undigested amylopectin in the hindgut of humans and pigs with low digestive capacity and might be detrimental to the intestinal microbiota. In this research, we investigated the fermentation characteristics of amylopectin through an in vitro fermentation method and used an ileal infusion pig model to verify the fermentation trial results and explore the microbiota regulatory effect. The interaction effects between amylopectin and cellulose during hindgut fermentation were also researched in this study. Our research revealed that the large amount of amylopectin fermentation in the hindgut was detrimental to the intestinal microbiota. Amylopectin partially substituted by cellulose was not only beneficial to antioxidant ability and fermentation efficiency, but also promoted SCFA production and probiotic colonization in the hindgut. These findings provide new strategies to prevent intestinal microbiota dysbiosis caused by amylopectin fermentation.
Collapse
Affiliation(s)
- Yu Bai
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
- State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Yaowen Zhang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhenyu Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Yu Pi
- Key Laboratory of Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Jinbiao Zhao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shujun Wang
- State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Dandan Han
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Junjun Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| |
Collapse
|
18
|
Wu L, Liu X, Zhang A, Chen H, Zhao R, Jia Y. Chronic corticosterone exposure disrupts hepatic and intestinal bile acid metabolism in chicken. Front Vet Sci 2023; 10:1147024. [PMID: 37266385 PMCID: PMC10229839 DOI: 10.3389/fvets.2023.1147024] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 03/27/2023] [Indexed: 06/03/2023] Open
Abstract
Objective Chronic stress leads to a high circulating level of glucocorticoids, which disrupts lipid metabolism and causes non-alcoholic fatty liver disease in mice and humans. Meanwhile, bile acid (BA), a class of metabolites initially synthesized in the liver and further metabolized by gut microbiota, plays a vital role in lipid metabolism. This study aimed to investigate the effects of glucocorticoids on BA metabolism and gut microbiota in chickens. Methods In this study, 35-day-old chickens were injected with 4 mg/kg/day corticosterone (Cort) for 14 days to simulate chronic stress. Results Cort treatment significantly increased the triglyceride contents in the plasma and the liver. HE and oil-red staining showed that Cort treatment induced fatty liver in chickens. Meanwhile, Cort exposure downregulated total bile acid (TBA) content in the liver while increasing the TBA in feces. UPLC-HRMS results showed that Cort exposure significantly decreased the hepatic levels of CDCA, T-alpha-MCA, and T-beta-MCA. Moreover, Cort exposure significantly reduced the expression of genes related to BA synthesis (CYP8B1 and CYP27A1), conjugation (BACS), and regulation (KLβ and FGFR4). 16s sequencing results showed that Cort treatment significantly decreased the amount of Lachnospiraceae, Eisenbergiella, Blautia, and Eubacterium and increased the abundance of Barnesiella, Lactobacillus, and Helicobacter. Spearman correlation analysis showed a significant positive correlation between fecal TBA and the abundance of Lactobacillales, Lactobacillus, and Barnesiella. In comparison, TBA in the liver was positively correlated with Eubacterium, and negatively correlated with Helicobacter. Conclusion In summary, chronic Cort exposure disrupts hepatic and intestinal bile acid metabolism inducing gut microbiome dysbiosis, which might associate with the development of fatty liver in chickens.
Collapse
Affiliation(s)
- Lei Wu
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
| | - Xinyi Liu
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
| | - Aijia Zhang
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
| | - Huimin Chen
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
| | - Ruqian Zhao
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
| | - Yimin Jia
- Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
- Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing, China
| |
Collapse
|
19
|
Loo YT, Howell K, Suleria H, Zhang P, Liu S, Ng K. Fibre fermentation and pig faecal microbiota composition are affected by the interaction between sugarcane fibre and (poly)phenols in vitro. Int J Food Sci Nutr 2023; 74:219-233. [PMID: 36915255 DOI: 10.1080/09637486.2023.2187329] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
We investigated the effects of (poly)phenol-rich sugarcane extract (PRSE), sugarcane fibre (SCFiber), and the combination of them (PRSE + SCFiber) on the gut microbiota and short-chain fatty acids (SCFA) production using in vitro digestion and pig faecal fermentation. Measuring total phenolic content and antioxidant activity through the in vitro digestion stages showed that PRSE + SCFiber increased the delivery of (poly)phenols to the in vitro colonic fermentation stage compared to PRSE alone. The PRSE + SCFiber modulated the faecal microbiota profile by enhancing the relative abundances of Prevotella, Lactobacillus, and Blautia, and reducing the relative abundance of Streptococcus. PRSE + SCFiber also mitigated the inhibitory effects of PRSE on SCFA production. These results suggest that the inclusion of sugarcane fibre with PRSE could increase the availability of phenolic compounds in the colon and modulate the gut microbiota towards a more favourable profile.
Collapse
Affiliation(s)
- Yit Tao Loo
- School of Agriculture, Ecosystem, Food & Forest Science, Faculty of Science, The University of Melbourne, Victoria, Australia
| | - Kate Howell
- School of Agriculture, Ecosystem, Food & Forest Science, Faculty of Science, The University of Melbourne, Victoria, Australia
| | - Hafiz Suleria
- School of Agriculture, Ecosystem, Food & Forest Science, Faculty of Science, The University of Melbourne, Victoria, Australia
| | - Pangzhen Zhang
- School of Agriculture, Ecosystem, Food & Forest Science, Faculty of Science, The University of Melbourne, Victoria, Australia
| | - Siyao Liu
- School of Agriculture, Ecosystem, Food & Forest Science, Faculty of Science, The University of Melbourne, Victoria, Australia
| | - Ken Ng
- School of Agriculture, Ecosystem, Food & Forest Science, Faculty of Science, The University of Melbourne, Victoria, Australia
| |
Collapse
|
20
|
Xia Y, Lee G, Takei N, Takahashi H, Kuda T. Detection of typical indigenous gut bacteria related to turmeric (Curcuma longa) powder in mouse caecum and human faecal cultures. Mol Biol Rep 2023; 50:2963-2974. [PMID: 36648695 DOI: 10.1007/s11033-022-08237-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 12/22/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND Turmeric (Curcuma longa; TM) is widely used as a spice and possesses anti-inflammatory, antioxidant, and antibacterial properties. The relationship between TM functions and gut microbiota is still unclear. METHODS AND RESULTS To investigate the effect of TM on gut microbiota and to identify indigenous gut bacteria that are responsive to TM, we fed Institute of Cancer Research mice a diet containing either no fibre (NF, n = 6) or 5% (w/w) TM (n = 6) for 14 days. Moreover, we obtained human stool samples from four healthy volunteers and incubated the samples without (control) or with 2% (w/v) TM at 37 °C for 24 h. Subsequently, microbiota analysis in murine caecal samples and human faecal cultures was performed using 16S rRNA (V4) amplicon sequencing. Higher faecal weights (p < 0.01) and lower plasma triacylglycerol levels (p < 0.05) were measured in the TM-fed mice than in the NF-fed mice. Furthermore, TM feeding increased the abundance of butyrate-producing and other short-chain fatty acid (SCFA)-producing bacteria in mice as well as in human faecal cultures, and Roseburia bacteria were detected as TM-responsive indigenous gut bacteria (TM-RIB) both in mice and in human faecal cultures. Lastly, in the case of human faecal cultures, SCFA contents and antioxidant properties were higher in TM cultures than in control cultures (p < 0.05). CONCLUSION TM appears to hold the potential to positively affect the host by altering the gut microbiota. Further studies are required to clarify the synergistic effects of TM and TM-RIB.
Collapse
Affiliation(s)
- Yumeng Xia
- Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan.
| | - Gayang Lee
- Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Natsumi Takei
- Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Hajime Takahashi
- Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan
| | - Takashi Kuda
- Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan
| |
Collapse
|
21
|
Effects of Initial Combinations of Gemigliptin Plus Metformin Compared with Glimepiride Plus Metformin on Gut Microbiota and Glucose Regulation in Obese Patients with Type 2 Diabetes: The INTESTINE Study. Nutrients 2023; 15:nu15010248. [PMID: 36615904 PMCID: PMC9824054 DOI: 10.3390/nu15010248] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/02/2022] [Accepted: 12/06/2022] [Indexed: 01/06/2023] Open
Abstract
The efficacy and safety of medications can be affected by alterations in gut microbiota in human beings. Among antidiabetic medications, incretin-based therapy such as dipeptidyl peptidase 4 inhibitors might affect gut microbiomes, which are related to glucose metabolism. This was a randomized, controlled, active-competitor study that aimed to compare the effects of combinations of gemigliptin−metformin vs. glimepiride−metformin as initial therapies on gut microbiota and glucose homeostasis in drug-naïve patients with type 2 diabetes. Seventy drug-naïve patients with type 2 diabetes (mean age, 52.2 years) with a glycated hemoglobin (HbA1c) level ≥7.5% were assigned to either gemigliptin−metformin or glimepiride−metformin combination therapies for 24 weeks. Changes in gut microbiota, biomarkers linked to glucose regulation, body composition, and amino acid blood levels were investigated. Although both treatments decreased the HbA1c levels significantly, the gemigliptin−metformin group achieved HbA1c ≤ 7.0% without hypoglycemia or weight gain more effectively than did the glimepiride−metformin group (59% vs. 24%; p < 0.05). At the phylum level, the Firmicutes/Bacteroidetes ratio tended to decrease after gemigliptin−metformin therapy (p = 0.065), with a notable depletion of taxa belonging to Firmicutes, including Lactobacillus, Ruminococcus torques, and Streptococcus (all p < 0.05). However, regardless of the treatment modality, a distinct difference in the overall gut microbiome composition was noted between patients who reached the HbA1c target goal and those who did not (p < 0.001). Treatment with gemigliptin−metformin resulted in a higher achievement of the glycemic target without hypoglycemia or weight gain, better than with glimepiride−metformin; these improvements might be related to beneficial changes in gut microbiota.
Collapse
|
22
|
Jia L, Huang S, Sun B, Shang Y, Zhu C. Pharmacomicrobiomics and type 2 diabetes mellitus: A novel perspective towards possible treatment. Front Endocrinol (Lausanne) 2023; 14:1149256. [PMID: 37033254 PMCID: PMC10076675 DOI: 10.3389/fendo.2023.1149256] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/14/2023] [Indexed: 04/11/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM), a major driver of mortality worldwide, is more likely to develop other cardiometabolic risk factors, ultimately leading to diabetes-related mortality. Although a set of measures including lifestyle intervention and antidiabetic drugs have been proposed to manage T2DM, problems associated with potential side-effects and drug resistance are still unresolved. Pharmacomicrobiomics is an emerging field that investigates the interactions between the gut microbiome and drug response variability or drug toxicity. In recent years, increasing evidence supports that the gut microbiome, as the second genome, can serve as an attractive target for improving drug efficacy and safety by manipulating its composition. In this review, we outline the different composition of gut microbiome in T2DM and highlight how these microbiomes actually play a vital role in its development. Furthermore, we also investigate current state-of-the-art knowledge on pharmacomicrobiomics and microbiome's role in modulating the response to antidiabetic drugs, as well as provide innovative potential personalized treatments, including approaches for predicting response to treatment and for modulating the microbiome to improve drug efficacy or reduce drug toxicity.
Collapse
Affiliation(s)
- Liyang Jia
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shiqiong Huang
- Department of Pharmacy, The First Hospital of Changsha, Changsha, China
| | - Boyu Sun
- Department of Pharmacy, The Third People’s Hospital of Qingdao, Qingdao, China
| | - Yongguang Shang
- Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Yongguang Shang, ; Chunsheng Zhu,
| | - Chunsheng Zhu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Yongguang Shang, ; Chunsheng Zhu,
| |
Collapse
|
23
|
Wu X, Zhao L, Zhang Y, Li K, Yang J. The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease. Front Physiol 2023; 14:1166685. [PMID: 37153213 PMCID: PMC10160444 DOI: 10.3389/fphys.2023.1166685] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/12/2023] [Indexed: 05/09/2023] Open
Abstract
Diabetic kidney disease (DKD) is a common complication in patients with diabetes mellitus (DM). Increasing evidence suggested that the gut microbiota participates in the progression of DKD, which is involved in insulin resistance, renin-angiotensin system (RAS) activation, oxidative stress, inflammation and immunity. Gut microbiota-targeted therapies including dietary fiber, supplementation with probiotics or prebiotics, fecal microbiota transplantation and diabetic agents that modulate the gut microbiota, such as metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors. In this review, we summarize the most important findings about the role of the gut microbiota in the pathogenesis of DKD and the application of gut microbiota-targeted therapies.
Collapse
Affiliation(s)
- Xiaofang Wu
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lei Zhao
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yujiang Zhang
- Department of Nephrology, Chongqing Jiangjin Second People’s Hospital, Chongqing, China
| | - Kailong Li
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jurong Yang
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
- *Correspondence: Jurong Yang,
| |
Collapse
|
24
|
Su S, Wang L, Fu S, Zhao J, He X, Chen Q, Belobrajdic DP, Yu C, Liu H, Wu H, Han P, Yang B, Huang Y, Liu Y, He J. Effects of oat ( Avena sativa L.) hay diet supplementation on the intestinal microbiome and metabolome of Small-tail Han sheep. Front Microbiol 2022; 13:1032622. [PMID: 36590432 PMCID: PMC9801518 DOI: 10.3389/fmicb.2022.1032622] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 11/24/2022] [Indexed: 12/23/2022] Open
Abstract
Supplementation of the sheep diet with oats (Avena sativa L.) improves animal growth and meat quality, however effects on intestinal microbes and their metabolites was not clear. This study aimed to establish the effect of dietary oat supplementation on rumen and colonic microbial abundance and explore the relationship with subsequent changes in digesta metabolites. Twenty Small-tail Han sheep were randomly assigned to a diet containing 30 g/100 g of maize straw (Control) or oat hay (Oat). After 90-days on experimental diets, rumen and colon digesta were collected and microbial diversity was determined by 16S rRNA gene Illumina NovaSeq sequencing and metabolomics was conducted using Ultra-high performance liquid chromatography Q-Exactive mass spectrometry (UHPLC-QE-MS). Compared to Control group, oat hay increased the abundance of Bacteroidetes and Fibrobacteres as well as known short-chain fatty acid (SCFA) producers Prevotellaceae, Ruminococcaceae and Fibrobacteraceae in rumen (p < 0.05). In rumen digesta, the Oat group showed had higher levels of (3Z,6Z)-3,6-nonadienal, Limonene-1,2-epoxide, P-tolualdehyde, and Salicylaldehyde compared to Control (p < 0.05) and these metabolites were positively correlated with the abundance of cecal Prevotellaceae NK3B31. In conclusion, supplementation of the sheep diet with oat hay improved desirable microbes and metabolites in the rumen, providing insight into mechanisms whereby meat quality can be improved by oat hay supplementation.
Collapse
Affiliation(s)
- Shaofeng Su
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Liwei Wang
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China,State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, China
| | - Shaoyin Fu
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Jie Zhao
- Center of Reproductive Medicine, The Affiliated Hospital of Inner Mongolia Medical Hospital, Hohhot, China
| | - Xiaolong He
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Qiuju Chen
- Bayannur Institute of Agriculture and Animal Husbandry Science, Bayannur, China
| | | | - Chuanzong Yu
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Hongkui Liu
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Haiqing Wu
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Pingan Han
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Bin Yang
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Yao Huang
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China
| | - Yongbin Liu
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, China,*Correspondence: Yongbin Liu,
| | - Jiangfeng He
- Inner Mongolia Academy of Agriculture and Husbandry Science, Hohhot, China,State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, China,Jiangfeng He,
| |
Collapse
|
25
|
Wang L, Wang S, Zhang Q, He C, Fu C, Wei Q. The role of the gut microbiota in health and cardiovascular diseases. MOLECULAR BIOMEDICINE 2022; 3:30. [PMID: 36219347 PMCID: PMC9554112 DOI: 10.1186/s43556-022-00091-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 08/05/2022] [Indexed: 11/17/2022] Open
Abstract
The gut microbiota is critical to human health, such as digesting nutrients, forming the intestinal epithelial barrier, regulating immune function, producing vitamins and hormones, and producing metabolites to interact with the host. Meanwhile, increasing evidence indicates that the gut microbiota has a strong correlation with the occurrence, progression and treatment of cardiovascular diseases (CVDs). In patients with CVDs and corresponding risk factors, the composition and ratio of gut microbiota have significant differences compared with their healthy counterparts. Therefore, gut microbiota dysbiosis, gut microbiota-generated metabolites, and the related signaling pathway may serve as explanations for some of the mechanisms about the occurrence and development of CVDs. Several studies have also demonstrated that many traditional and latest therapeutic treatments of CVDs are associated with the gut microbiota and its generated metabolites and related signaling pathways. Given that information, we summarized the latest advances in the current research regarding the effect of gut microbiota on health, the main cardiovascular risk factors, and CVDs, highlighted the roles and mechanisms of several metabolites, and introduced corresponding promising treatments for CVDs regarding the gut microbiota. Therefore, this review mainly focuses on exploring the role of gut microbiota related metabolites and their therapeutic potential in CVDs, which may eventually provide better solutions in the development of therapeutic treatment as well as the prevention of CVDs.
Collapse
Affiliation(s)
- Lu Wang
- grid.412901.f0000 0004 1770 1022Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China ,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, People’s Republic of China
| | - Shiqi Wang
- grid.412901.f0000 0004 1770 1022Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China ,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, People’s Republic of China
| | - Qing Zhang
- grid.412901.f0000 0004 1770 1022Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China ,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, People’s Republic of China
| | - Chengqi He
- grid.412901.f0000 0004 1770 1022Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China ,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, People’s Republic of China
| | - Chenying Fu
- grid.412901.f0000 0004 1770 1022National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China ,grid.412901.f0000 0004 1770 1022Aging and Geriatric Mechanism Laboratory, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Quan Wei
- grid.412901.f0000 0004 1770 1022Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China ,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, People’s Republic of China
| |
Collapse
|
26
|
Zhang X, Ren H, Zhao C, Shi Z, Qiu L, Yang F, Zhou X, Han X, Wu K, Zhong H, Li Y, Li J, Ji L. Metagenomic analysis reveals crosstalk between gut microbiota and glucose-lowering drugs targeting the gastrointestinal tract in Chinese patients with type 2 diabetes: a 6 month, two-arm randomised trial. Diabetologia 2022; 65:1613-1626. [PMID: 35930018 PMCID: PMC9477956 DOI: 10.1007/s00125-022-05768-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 06/06/2022] [Indexed: 11/30/2022]
Abstract
AIMS/HYPOTHESIS The use of oral glucose-lowering drugs, particularly those designed to target the gut ecosystem, is often observed in association with altered gut microbial composition or functional capacity in individuals with type 2 diabetes. The gut microbiota, in turn, plays crucial roles in the modulation of drug efficacy. We aimed to assess the impacts of acarbose and vildagliptin on human gut microbiota and the relationships between pre-treatment gut microbiota and therapeutic responses. METHODS This was a randomised, open-labelled, two-arm trial in treatment-naive type 2 diabetes patients conducted in Beijing between December 2016 and December 2017. One hundred participants with overweight/obesity and newly diagnosed type 2 diabetes were recruited from the Pinggu Hospital and randomly assigned to the acarbose (n=50) or vildagliptin (n=50) group using sealed envelopes. The treatment period was 6 months. Blood, faecal samples and visceral fat data from computed tomography images were collected before and after treatments to measure therapeutic outcomes and gut microbiota. Metagenomic datasets from a previous type 2 diabetes cohort receiving acarbose or glipizide for 3 months were downloaded and processed. Statistical analyses were applied to identify the treatment-related changes in clinical variables, gut microbiota and associations. RESULTS Ninety-two participants were analysed. After 6 months of acarbose (n=44) or vildagliptin (n=48) monotherapy, both groups achieved significant reductions in HbA1c (from 60 to 46 mmol/mol [from 7.65% to 6.40%] in the acarbose group and from 59 to 44 mmol/mol [from 7.55% to 6.20%] in the vildagliptin group) and visceral fat areas (all adjusted p values for pre-post comparisons <0.05). Both arms showed drug-specific and shared changes in relative abundances of multiple gut microbial species and pathways, especially the common reductions in Bacteroidetes species. Three months and 6 months of acarbose-induced changes in microbial composition were highly similar in type 2 diabetes patients from the two independent studies. Vildagliptin treatment significantly enhanced fasting active glucagon-like peptide-1 (GLP-1) levels. Baseline gut microbiota, rather than baseline GLP-1 levels, were strongly associated with GLP-1 response to vildagliptin, and to a lesser extent with GLP-1 response to acarbose. CONCLUSIONS/INTERPRETATION This study reveals common microbial responses in type 2 diabetes patients treated with two glucose-lowering drugs targeting the gut differently and acceptable performance of baseline gut microbiota in classifying individuals with different GLP-1 responses to vildagliptin. Our findings highlight bidirectional interactions between gut microbiota and glucose-lowering drugs. TRIAL REGISTRATION ClinicalTrials.gov NCT02999841 FUNDING: National Key Research and Development Project: 2016YFC1304901.
Collapse
Affiliation(s)
- Xiuying Zhang
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Centre, Beijing, China
| | - Huahui Ren
- BGI-Shenzhen, Shenzhen, China
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Cuiling Zhao
- Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Capital Medical University, Beijing, China
| | | | - Li Qiu
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Centre, Beijing, China
| | | | - Xianghai Zhou
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Centre, Beijing, China
| | - Xueyao Han
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Centre, Beijing, China
| | - Kui Wu
- BGI-Shenzhen, Shenzhen, China
- Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI-Shenzhen, Shenzhen, China
| | | | - Yufeng Li
- Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Capital Medical University, Beijing, China.
| | - Junhua Li
- BGI-Shenzhen, Shenzhen, China.
- Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, China.
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Centre, Beijing, China.
| |
Collapse
|
27
|
Martínez-López YE, Esquivel-Hernández DA, Sánchez-Castañeda JP, Neri-Rosario D, Guardado-Mendoza R, Resendis-Antonio O. Type 2 diabetes, gut microbiome, and systems biology: A novel perspective for a new era. Gut Microbes 2022; 14:2111952. [PMID: 36004400 PMCID: PMC9423831 DOI: 10.1080/19490976.2022.2111952] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The association between the physio-pathological variables of type 2 diabetes (T2D) and gut microbiota composition suggests a new avenue to track the disease and improve the outcomes of pharmacological and non-pharmacological treatments. This enterprise requires new strategies to elucidate the metabolic disturbances occurring in the gut microbiome as the disease progresses. To this end, physiological knowledge and systems biology pave the way for characterizing microbiota and identifying strategies in a move toward healthy compositions. Here, we dissect the recent associations between gut microbiota and T2D. In addition, we discuss recent advances in how drugs, diet, and exercise modulate the microbiome to favor healthy stages. Finally, we present computational approaches for disentangling the metabolic activity underlying host-microbiota codependence. Altogether, we envision that the combination of physiology and computational modeling of microbiota metabolism will drive us to optimize the diagnosis and treatment of T2D patients in a personalized way.
Collapse
Affiliation(s)
- Yoscelina Estrella Martínez-López
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Programa de Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México,Metabolic Research Laboratory, Department of Medicine and Nutrition. University of Guanajuato. León, Guanajuato, México
| | | | - Jean Paul Sánchez-Castañeda
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México
| | - Daniel Neri-Rosario
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México
| | - Rodolfo Guardado-Mendoza
- Metabolic Research Laboratory, Department of Medicine and Nutrition. University of Guanajuato. León, Guanajuato, México,Research Department, Hospital Regional de Alta Especialidad del Bajío. León, Guanajuato, México,Rodolfo Guardado-Mendoza Metabolic Research Laboratory, Department of Medicine and Nutrition. University of Guanajuato. León, Guanajuato, México
| | - Osbaldo Resendis-Antonio
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Coordinación de la Investigación Científica – Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México,CONTACT Osbaldo Resendis-Antonio Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México (UNAM), Periferico Sur 4809, Arenal Tepepan, Tlalpan, 14610 Ciudad de México, CDMX
| |
Collapse
|
28
|
Burakova I, Smirnova Y, Gryaznova M, Syromyatnikov M, Chizhkov P, Popov E, Popov V. The Effect of Short-Term Consumption of Lactic Acid Bacteria on the Gut Microbiota in Obese People. Nutrients 2022; 14:3384. [PMID: 36014890 PMCID: PMC9415828 DOI: 10.3390/nu14163384] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/12/2022] [Accepted: 08/16/2022] [Indexed: 02/07/2023] Open
Abstract
Obesity is a problem of modern health care that causes the occurrence of many concomitant diseases: arterial hypertension, diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular diseases. New strategies for the treatment and prevention of obesity are being developed that are based on using probiotics for modulation of the gut microbiota. Our study aimed to evaluate the bacterial composition of the gut of obese patients before and after two weeks of lactic acid bacteria (Lactobacillus acidophilus, Lactiplantibacillus plantarum, Limosilactobacillus fermentum, and Lactobacillus delbrueckii) intake. The results obtained showed an increase in the number of members of the phylum Actinobacteriota in the group taking nutritional supplements, while the number of phylum Bacteroidota decreased in comparison with the control group. There has also been an increase in potentially beneficial groups: Bifidobacterium, Blautia, Eubacterium, Anaerostipes, Lactococcus, Lachnospiraceae ND3007, Streptococcus, Escherichia-Shigella, and Lachnoclostridium. Along with this, a decrease in the genera was demonstrated: Faecalibacterium, Pseudobutyrivibrio, Subdoligranulum, Faecalibacterium, Clostridium sensu stricto 1 and 2, Catenibacterium, Megasphaera, Phascolarctobacterium, and the Oscillospiraceae NK4A214 group, which contribute to the development of various metabolic disorders. Modulation of the gut microbiota by lactic acid bacteria may be one of the ways to treat obesity.
Collapse
Affiliation(s)
- Inna Burakova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia
| | - Yuliya Smirnova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia
| | - Mariya Gryaznova
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia
| | - Mikhail Syromyatnikov
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia
| | - Pavel Chizhkov
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia
| | - Evgeny Popov
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia
| | - Vasily Popov
- Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia
| |
Collapse
|
29
|
Lactobacillus plantarum ZY08 relieves chronic alcohol-induced hepatic steatosis and liver injury in mice via restoring intestinal flora homeostasis. Food Res Int 2022; 157:111259. [DOI: 10.1016/j.foodres.2022.111259] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/12/2022] [Accepted: 04/14/2022] [Indexed: 12/12/2022]
|
30
|
Wang T, Guan K, Su Q, Wang X, Yan Z, Kuang K, Wang Y, Zhang Q, Zhou X, Liu B. Change of Gut Microbiota in PRRSV-Resistant Pigs and PRRSV-Susceptible Pigs from Tongcheng Pigs and Large White Pigs Crossed Population upon PRRSV Infection. Animals (Basel) 2022; 12:ani12121504. [PMID: 35739841 PMCID: PMC9219425 DOI: 10.3390/ani12121504] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/28/2022] [Accepted: 06/02/2022] [Indexed: 12/05/2022] Open
Abstract
Simple Summary The gut microbiota could directly induce immune responses and affect the health of the host. In this study, we assessed changes in the gut microbiota of resistant segregated phenotypic pigs under Porcine Reproductive and Respiratory Syndrome Virus exposure. The results showed that the resistance of pigs was related to the composition of gut microbiota. The quantity and relative abundance of probiotics in resistant individuals positively affected host immunity and growth performance, whereas high levels of pathogenic bacteria in susceptible individuals were associated with poorer clinical outcomes. The results of this study suggest that gut microbiota may serve as an effective probiotic resource to provide new methods for PRRS prevention and treatment. Abstract Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the serious infectious diseases that threatens the swine industry. Increasing evidence shows that gut microbiota plays an important role in regulating host immune responses to PRRS virus (PRRSV). The aim of this study was to investigate gut microbiota difference between PRRSV-resistant pigs and PRRSV-suspectable pigs derived from a Tongcheng pigs and Large White pigs crossed population. PRRSV infection induces an increase in the abundance and diversity of gut microbiota. Correlation analysis showed that 36 genera were correlated with viral loads or weight gain after PRRSV infection. Prevotellaceae-NK3B31-group, Christensenellaceae-R7-group, and Parabacteroides were highly correlated with both viral load and weight gain. Notably, the diversity and abundance of beneficial bacteria such as Prevotellaceae-NK3B31-group was high in resistant pigs, and the diversity and abundance of pathogenic bacteria such as Campylobacter and Desulfovibrio were high in susceptible pigs. Gut microbiota were significantly associated with immune function and growth performance, suggesting that these genera might be related to viremia, clinical symptoms, and disease resistance. Altogether, this study revealed the correlation of gut microbiota with PRRSV infection and gut microbiota interventions may provide an effective prevention against PRRSV infection.
Collapse
Affiliation(s)
- Tengfei Wang
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
| | - Kaifeng Guan
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
| | - Qiuju Su
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
| | - Xiaotong Wang
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
| | - Zengqiang Yan
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
| | - Kailin Kuang
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
| | - Yuan Wang
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
| | - Qingde Zhang
- Laboratory Animal Centre, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China;
| | - Xiang Zhou
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
- The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China
- The Engineering Technology Research Center of Hubei Province Local Pig Breed Improvement, Wuhan 430070, China
- Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China
- Correspondence: (X.Z.); (B.L.)
| | - Bang Liu
- Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; (T.W.); (K.G.); (Q.S.); (X.W.); (Z.Y.); (K.K.); (Y.W.)
- The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China
- The Engineering Technology Research Center of Hubei Province Local Pig Breed Improvement, Wuhan 430070, China
- Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China
- Correspondence: (X.Z.); (B.L.)
| |
Collapse
|
31
|
Liu W, Luo Z, Zhou J, Sun B. Gut Microbiota and Antidiabetic Drugs: Perspectives of Personalized Treatment in Type 2 Diabetes Mellitus. Front Cell Infect Microbiol 2022; 12:853771. [PMID: 35711668 PMCID: PMC9194476 DOI: 10.3389/fcimb.2022.853771] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/04/2022] [Indexed: 12/23/2022] Open
Abstract
Alterations in the composition and function of the gut microbiota have been reported in patients with type 2 diabetes mellitus (T2DM). Emerging studies show that prescribed antidiabetic drugs distort the gut microbiota signature associated with T2DM. Even more importantly, accumulated evidence provides support for the notion that gut microbiota, in turn, mediates the efficacy and safety of antidiabetic drugs. In this review, we highlight the current state-of-the-art knowledge on the crosstalk and interactions between gut microbiota and antidiabetic drugs, including metformin, α-glucosidase inhibitors, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter 2 inhibitors, traditional Chinese medicines and other antidiabetic drugs, as well as address corresponding microbial-based therapeutics, aiming to provide novel preventative strategies and personalized therapeutic targets in T2DM.
Collapse
Affiliation(s)
- Wenhui Liu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Zhiying Luo
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Jiecan Zhou
- Institute of Clinical Medicine, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Bao Sun
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacy, Central South University, Changsha, China
- *Correspondence: Bao Sun,
| |
Collapse
|
32
|
Zhang X, Xu B, Hou Z, Xie C, Niu Y, Dai Q, Yan X, Wu D. Dietary ε-Polylysine Affects on Gut Microbiota and Plasma Metabolites Profiling in Mice. Front Nutr 2022; 9:842686. [PMID: 35571901 PMCID: PMC9097516 DOI: 10.3389/fnut.2022.842686] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 03/08/2022] [Indexed: 12/14/2022] Open
Abstract
Given the antibacterial effects of ε-polylysine acting on cell membranes, and that glycerol phospholipids are important components of the cell membrane, we hypothesized that ε-polylysine may regulate glycerophospholipid metabolism by modifying the gut microbiota. To test this hypothesis, we treated post-weaning C57 mice with different levels of ε-polylysine (0, 300, 600, and 1,200 ppm) in their basic diet. The growth performance and morphology of intestine were then determined. Modification of the gut microbiota and their function were analyzed using 16S rDNA sequencing. Metabolite identification was performed using the LC-MS method. The results showed that body weight decreased with an increasing supplemental level of ε-polylysine from 5 to 7 weeks (P < 0.05), but no significant difference was observed after 8 weeks (P > 0.05). Supplementation with 1,200 ppm ε-polylysine changed the morphology of the jejunum and ileum, increased the villus length, decreased the crypt depth of the jejunum, and decreased the villus length and crypt depth of the ileum (P < 0.05). ε-Polylysine shifted the intestine microbiota by changing alpha diversity (Chao 1, observed species, Shannon, and Simpson indices) and varied at different times. ε-polylysine decreased Firmicutes and increased Bacteroidetes at 4 week, but increased Firmicutes and decreased Bacteroidetes at 10 week. ε-Polylysine regulated genera associated with lipid metabolism such as Parabacteroides, Odoribacter, Akkermansia, Alistipes, Lachnospiraceae UCG-001, Collinsella, Ruminococcaceae, and Intestinimonas. During the adult period, the genera Alistipes, Lachnospiraceae UCG-001, and Streptomyces were positively associated with PC, PE, LysoPC, LysoPE, 1-Arachidonoylglycerophosphoinositol and OHOHA-PS (R > 0.6, P < 0.001), but changes in Blautia, Christensenellaceae R-7 group, Odoribacter, Allobaculum, Ruminococcaceae UCG-004, Ruminococcaceae UCG-005, and Lachnospiraceae UCG-010 were negatively correlated with glycerophospholipid metabolites (R < −0.6, P < 0.001). The abundance of glycerophospholipid metabolites, including PC, PE, lysoPC, and lysoPE, were decreased by ε-polylysine. Furthermore, ε-polylysine reduced the incidence of the genera including Ruminococcus, Prevotella, Prevotellaceae, Butyricimonas, and Escherichia-Shigella and reduced the abundance of Faecalibaculum, Christensenellaceae R-7 group, Coriobacteriaceae UCG-002. In conclusion, ε-polylysine modified gut microbiota composition and function while also restraining pathogenic bacteria. The glycerophospholipid metabolism pathway and associated metabolites may be regulated by intestinal bacteria.
Collapse
Affiliation(s)
- Xuelei Zhang
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China.,Department of Animal Nutrition and Feed Science, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China
| | - Baoyang Xu
- Department of Animal Nutrition and Feed Science, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China
| | - Zhenping Hou
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Chunlin Xie
- Department of Animal Nutrition and Feed Science, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China
| | - Yaorong Niu
- Department of Animal Nutrition and Feed Science, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China
| | - Qiuzhong Dai
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| | - Xianghua Yan
- Department of Animal Nutrition and Feed Science, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, China
| | - Duanqin Wu
- Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, China
| |
Collapse
|
33
|
Feng Y, Cao H, Hua J, Zhang F. Anti-Diabetic Intestinal Mechanisms: Foods, Herbs, and Western Medicines. Mol Nutr Food Res 2022; 66:e2200106. [PMID: 35481618 DOI: 10.1002/mnfr.202200106] [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: 02/20/2022] [Revised: 04/16/2022] [Indexed: 12/12/2022]
Abstract
The role of intestinal factors in the pathogenesis of diabetes, such as a decrease in the incretin effect, has recently attracted considerable attention. An imbalance in the gut microbiota inhibits the secretion of incretins, which are metabolic hormones can reduce blood glucose levels, and promotes the occurrence and development of diabetes. Numerous studies have demonstrated that foods are environmental factors that are important in the modulation of gut microbial-mediated glucose metabolism. In general, functional foods trigger the gut microbiota to produce beneficial metabolites or reduce harmful products through metabolic pathways and then regulate glucose and lipid metabolism. Recent studies have shown that similar to functional foods, the regulatory effects of some herbs and Western medicines are closely related to alterations in the gut microbiota. In this review, the intestinal mechanism of foods, herbs, and Western medicine in affecting the process of glucose metabolism is summarized.
Collapse
Affiliation(s)
- Yuwei Feng
- Nutritional Department, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China.,Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Hong Cao
- Nutritional Department, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China.,Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.,Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China.,Department of Endocrinology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
| | - Jiao Hua
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.,Hospital Infection-Control Department, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China
| | - Feng Zhang
- Nutritional Department, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China.,Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.,Clinical Assessment Center of Functional Food, Affiliated Hospital of Jiangnan University, Wuxi, 214122, China.,Chinese Society of Nutritional Oncology, Beijing, 100022, China
| |
Collapse
|
34
|
Papadopoulos PD, Tsigalou C, Valsamaki PN, Konstantinidis TG, Voidarou C, Bezirtzoglou E. The Emerging Role of the Gut Microbiome in Cardiovascular Disease: Current Knowledge and Perspectives. Biomedicines 2022; 10:biomedicines10050948. [PMID: 35625685 PMCID: PMC9139035 DOI: 10.3390/biomedicines10050948] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/27/2022] [Accepted: 03/28/2022] [Indexed: 01/27/2023] Open
Abstract
The collection of normally non-pathogenic microorganisms that mainly inhabit our gut lumen shapes our health in many ways. Structural and functional perturbations in the gut microbial pool, known as “dysbiosis”, have been proven to play a vital role in the pathophysiology of several diseases, including cardiovascular disease (CVD). Although therapeutic regimes are available to treat this group of diseases, they have long been the main cause of mortality and morbidity worldwide. While age, sex, genetics, diet, tobacco use, and alcohol consumption are major contributors (World Health Organization, 2018), they cannot explain all of the consequences of CVD. In addition to the abovementioned traditional risk factors, the constant search for novel preventative and curative tools has shed light on the involvement of gut bacteria and their metabolites in the pathogenesis of CVD. In this narrative review, we will discuss the established interconnections between the gut microbiota and CVD, as well as the plausible therapeutic perspectives.
Collapse
Affiliation(s)
- Panagiotis D. Papadopoulos
- Master Programme Food, Nutrition and Microbiome, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (P.D.P.); (E.B.)
| | - Christina Tsigalou
- Master Programme Food, Nutrition and Microbiome, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (P.D.P.); (E.B.)
- Laboratory of Microbiology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
- Correspondence:
| | - Pipitsa N. Valsamaki
- Nuclear Medicine Department, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece;
| | | | | | - Eugenia Bezirtzoglou
- Master Programme Food, Nutrition and Microbiome, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (P.D.P.); (E.B.)
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| |
Collapse
|
35
|
Qin S, He Z, Wu Y, Zeng C, Zheng Z, Zhang H, Lv C, Yuan Y, Wu H, Ye J, Liu Z, Shi M. Instant Dark Tea Alleviates Hyperlipidaemia in High-Fat Diet-Fed Rat: From Molecular Evidence to Redox Balance and Beyond. Front Nutr 2022; 9:819980. [PMID: 35223953 PMCID: PMC8875000 DOI: 10.3389/fnut.2022.819980] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/05/2022] [Indexed: 12/30/2022] Open
Abstract
Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. However, the molecular mechanism underlying its regulatory effect on hyperlipidaemia is rarely studied. In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. The results showed that the major bioactive components in IDT were include 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. Rats fed with IDT (0.27–0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p < 0.01). Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. For instance, Ruminococcaceae_UCG-005 was significantly correlated with body weight, TG, HDL-C, Nfr2, FABP3, SCD1, Cyp4a1, and Kcnn2. Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia.
Collapse
Affiliation(s)
- Si Qin
- Lab of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, China
- *Correspondence: Si Qin
| | - Zhilan He
- Lab of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, China
| | - Yuanjie Wu
- Hunan Tea Group Co. LTD, Changsha, China
| | - Chaoxi Zeng
- Lab of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, China
| | - Zhibing Zheng
- Lab of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, China
| | - Haowei Zhang
- Lab of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, China
| | - Chenghao Lv
- Lab of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, China
| | - Yong Yuan
- Hunan Tea Group Co. LTD, Changsha, China
| | - Haoren Wu
- Hunan Tea Group Co. LTD, Changsha, China
| | - Jianhui Ye
- Tea Research Institute, Zhejiang University, Hangzhou, China
| | - Zhonghua Liu
- Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, China
- Zhonghua Liu
| | - Meng Shi
- Lab of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha, China
- Meng Shi
| |
Collapse
|
36
|
Craciun CI, Neag MA, Catinean A, Mitre AO, Rusu A, Bala C, Roman G, Buzoianu AD, Muntean DM, Craciun AE. The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus. Biomedicines 2022; 10:308. [PMID: 35203519 PMCID: PMC8869176 DOI: 10.3390/biomedicines10020308] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/15/2022] [Accepted: 01/26/2022] [Indexed: 02/04/2023] Open
Abstract
Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its associations with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the composition of gut microbiota, but it is unclear how this, in turn, may influence metabolism. The main objective of this review is to evaluate the pathogenetic association between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.
Collapse
Affiliation(s)
- Cristian-Ioan Craciun
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.-I.C.); (A.-D.B.)
| | - Maria-Adriana Neag
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.-I.C.); (A.-D.B.)
| | - Adrian Catinean
- Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Andrei-Otto Mitre
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Adriana Rusu
- Department of Diabetes, Nutrition, Metabolic Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.R.); (C.B.); (G.R.); (A.-E.C.)
| | - Cornelia Bala
- Department of Diabetes, Nutrition, Metabolic Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.R.); (C.B.); (G.R.); (A.-E.C.)
| | - Gabriela Roman
- Department of Diabetes, Nutrition, Metabolic Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.R.); (C.B.); (G.R.); (A.-E.C.)
| | - Anca-Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.-I.C.); (A.-D.B.)
| | - Dana-Maria Muntean
- Department of Pharmaceutical Technology and Biopharmaceutics, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Anca-Elena Craciun
- Department of Diabetes, Nutrition, Metabolic Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.R.); (C.B.); (G.R.); (A.-E.C.)
| |
Collapse
|
37
|
Wang D, Liu J, Zhou L, Zhang Q, Li M, Xiao X. Effects of Oral Glucose-Lowering Agents on Gut Microbiota and Microbial Metabolites. Front Endocrinol (Lausanne) 2022; 13:905171. [PMID: 35909556 PMCID: PMC9326154 DOI: 10.3389/fendo.2022.905171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 06/14/2022] [Indexed: 11/30/2022] Open
Abstract
The current research and existing facts indicate that type 2 diabetes mellitus (T2DM) is characterized by gut microbiota dysbiosis and disturbed microbial metabolites. Oral glucose-lowering drugs are reported with pleiotropic beneficial effects, including not only a decrease in glucose level but also weight loss, antihypertension, anti-inflammation, and cardiovascular protection, but the underlying mechanisms are still not clear. Evidence can be found showing that oral glucose-lowering drugs might modify the gut microbiome and thereby alter gastrointestinal metabolites to improve host health. Although the connections among gut microbial communities, microbial metabolites, and T2DM are complex, figuring out how antidiabetic agents shape the gut microbiome is vital for optimizing the treatment, meaningful for the instruction for probiotic therapy and gut microbiota transplantation in T2DM. In this review, we focused on the literatures in gut microbiota and its metabolite profile alterations beneficial from oral antidiabetic drugs, trying to provide implications for future study in the developing field of these drugs, such as combination therapies, pre- and probiotics intervention in T2DM, and subjects with pregestational diabetes and gestational diabetes mellitus.
Collapse
Affiliation(s)
- Dongmei Wang
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Jieying Liu
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
- Department of Medical Research Center, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Liyuan Zhou
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Qian Zhang
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Ming Li
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Xinhua Xiao
- Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
- *Correspondence: Xinhua Xiao,
| |
Collapse
|
38
|
Dike KS, Okafor CP, Ohabughiro BN, Maduwuba MC, Ezeokoli OT, Ayeni KI, Okafor CM, Ezekiel CN. Analysis of bacterial communities of three cassava-based traditionally fermented Nigerian foods (abacha, fufu and garri). Lett Appl Microbiol 2021; 74:452-461. [PMID: 34850410 DOI: 10.1111/lam.13621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/27/2021] [Accepted: 11/13/2021] [Indexed: 11/26/2022]
Abstract
Globally, cassava is an important food crop that contributes significantly to food security. In Nigeria, cassava can be traditionally processed into abacha (fermented strips), fufu (submerged-fermented porridge) and garri (solid-state fermented farinated granules) for human consumption. Despite the widespread consumption of these foods, there is a major knowledge gap in understanding their core bacterial diversity. This study, therefore, applied next-generation sequencing of 16S rRNA gene to delineate the bacterial diversity in abacha, fufu and garri. Amplicon sequence variants belonging to nine phyla were present in the three foods. Firmicutes dominated the bacterial community of abacha and fufu, whereas, Proteobacteria was the dominant phylum in garri. At genus level taxa, Lactococcus, Lysinibacillus and Pseudomonas dominated the bacterial community in abacha, fufu and garri, respectively. Other dominant phylotypes reported in the foods belonged to Bacillus, Clostridium sensu stricto (cluster 1), Cupriavidus, Enterobacter, Sphingomonas and Staphylococcus. To the best of our knowledge, Clostridium sensu stricto cluster 1 and Lysinibacillus in fufu, and Brevundimonas, Cupriavidus, Sphingomonas and Strenotrophomomas in garri are reported for the first time. Although some potential pathogenic genera were recorded, the foods contained potentially functional species that could be explored to improve artisanal food production, food security and safeguard consumer health.
Collapse
Affiliation(s)
- K S Dike
- Department of Microbiology, Imo State University, Owerri, Nigeria
| | - C P Okafor
- Department of Microbiology, Imo State University, Owerri, Nigeria
| | - B N Ohabughiro
- Department of Microbiology, Imo State University, Owerri, Nigeria
| | - M C Maduwuba
- Department of Microbiology, Imo State University, Owerri, Nigeria
| | - O T Ezeokoli
- Department of Microbiology and Biochemistry, University of the Free State, Bloemfontein, South Africa
| | - K I Ayeni
- Department of Microbiology, Babcock University, Ilishan Remo, Nigeria
| | - C M Okafor
- Department of Applied Microbiology and Brewing, Nnamdi Azikiwe University, Awka, Nigeria
| | - C N Ezekiel
- Department of Microbiology, Babcock University, Ilishan Remo, Nigeria
| |
Collapse
|
39
|
Juárez-Fernández M, Román-Sagüillo S, Porras D, García-Mediavilla MV, Linares P, Ballesteros-Pomar MD, Urioste-Fondo A, Álvarez-Cuenllas B, González-Gallego J, Sánchez-Campos S, Jorquera F, Nistal E. Long-Term Effects of Bariatric Surgery on Gut Microbiota Composition and Faecal Metabolome Related to Obesity Remission. Nutrients 2021; 13:nu13082519. [PMID: 34444679 PMCID: PMC8397959 DOI: 10.3390/nu13082519] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/16/2021] [Accepted: 07/19/2021] [Indexed: 12/17/2022] Open
Abstract
Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.
Collapse
Affiliation(s)
- María Juárez-Fernández
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
| | - Sara Román-Sagüillo
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
| | - David Porras
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
| | - María Victoria García-Mediavilla
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Pedro Linares
- Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, 24071 León, Spain; (P.L.); (B.Á.-C.)
| | - María Dolores Ballesteros-Pomar
- Departamento de Endocrinología y Nutrición, Complejo Asistencial Universitario de León, 24071 León, Spain; (M.D.B.-P.); (A.U.-F.)
| | - Ana Urioste-Fondo
- Departamento de Endocrinología y Nutrición, Complejo Asistencial Universitario de León, 24071 León, Spain; (M.D.B.-P.); (A.U.-F.)
| | - Begoña Álvarez-Cuenllas
- Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, 24071 León, Spain; (P.L.); (B.Á.-C.)
| | - Javier González-Gallego
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Sonia Sánchez-Campos
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Francisco Jorquera
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, 24071 León, Spain; (P.L.); (B.Á.-C.)
| | - Esther Nistal
- Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24007 León, Spain; (M.J.-F.); (S.R.-S.); (D.P.); (M.V.G.-M.); (J.G.-G.); (S.S.-C.); (F.J.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Correspondence: ; Tel.: +34-9-8729-1997
| |
Collapse
|
40
|
Lim JJ, Li X, Lehmler HJ, Wang D, Gu H, Cui JY. Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice. Toxicol Sci 2021; 177:168-187. [PMID: 32544245 DOI: 10.1093/toxsci/kfaa090] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Polychlorinated biphenyls (PCBs) are ubiquitously detected and have been linked to metabolic diseases. Gut microbiome is recognized as a critical regulator of disease susceptibility; however, little is known how PCBs and gut microbiome interact to modulate hepatic xenobiotic and intermediary metabolism. We hypothesized the gut microbiome regulates PCB-mediated changes in the metabolic fingerprints and hepatic transcriptome. Ninety-day-old female conventional and germ-free mice were orally exposed to the Fox River Mixture (synthetic PCB mixture, 6 or 30 mg/kg) or corn oil (vehicle control, 10 ml/kg), once daily for 3 consecutive days. RNA-seq was conducted in liver, and endogenous metabolites were measured in liver and serum by LC-MS. Prototypical target genes of aryl hydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor were more readily upregulated by PCBs in conventional conditions, indicating PCBs, to the hepatic transcriptome, act partly through the gut microbiome. In a gut microbiome-dependent manner, xenobiotic, and steroid metabolism pathways were upregulated, whereas response to misfolded proteins-related pathways was downregulated by PCBs. At the high PCB dose, NADP, and arginine appear to interact with drug-metabolizing enzymes (ie, Cyp1-3 family), which are highly correlated with Ruminiclostridium and Roseburia, providing a novel explanation of gut-liver interaction from PCB-exposure. Utilizing the Library of Integrated Network-based Cellular Signatures L1000 database, therapeutics targeting anti-inflammatory and endoplasmic reticulum stress pathways are predicted to be remedies that can mitigate PCB toxicity. Our findings demonstrate that habitation of the gut microbiota drives PCB-mediated hepatic responses. Our study adds knowledge of physiological response differences from PCB exposure and considerations for further investigations for gut microbiome-dependent therapeutics.
Collapse
Affiliation(s)
- Joe Jongpyo Lim
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195
| | - Xueshu Li
- Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242; and
| | - Hans-Joachim Lehmler
- Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa 52242; and
| | - Dongfang Wang
- Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Scottsdale, Arizona 85259
| | - Haiwei Gu
- Arizona Metabolomics Laboratory, School of Nutrition and Health Promotion, College of Health Solutions, Arizona State University, Scottsdale, Arizona 85259
| | - Julia Yue Cui
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195
| |
Collapse
|
41
|
Chen Y, Peng L, Shi S, Guo G, Wen H. Boeravinone B alleviates gut dysbiosis during myocardial infarction-induced cardiotoxicity in rats. J Cell Mol Med 2021; 25:6403-6416. [PMID: 34028176 PMCID: PMC8256339 DOI: 10.1111/jcmm.16620] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 04/21/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Myocardial infarction (MI) is the most common heart disease, and also, it is one of the leading causes of death from cardiovascular disease. It is well known that MI causes additional injury during blood flow restoration in ischaemic myocardium. Boeravinone B (BB) is a well-known antioxidant and anti-inflammatory drug. We investigated the cardioprotective effect of BB drug against isoproterenol (ISO)-induced MI in rats in this experimental study, along with we analysed its underlying mechanism. Adult Sprague Dawley (SD) rats were treated subcutaneously with ISO (45 mg/kg), then divided into groups and then given BB drug was administered orally. The cardioprotective effect of BB on ISO-induced MI rats was analysed by estimating the heart injury markers, antioxidant pro-inflammatory cytokines and inflammatory parameters. We also detected quantified expression of inflammation and apoptosis-related marker protein family. We estimated the effect of BB drug on GUT microbiota in ISO-induced MI rats and scrutinized the histopathological variations in heart tissues. BB treatment significantly (P < .001) diminished the level of heart markers such as lactate dehydrogenase (LDH), troponin (TnT), creatine kinase (CK) and creatine kinase isoenzymes MB (CK-MB). BB treatment also altered the antioxidant parameters and reduced the pro-inflammatory cytokines in the serum and tissues. Additionally, the histopathological aspects demonstrated that the pathological changes observed in the heart tissue of the ISO group rats were suppressed by the BB treatment to varying degrees. Furthermore, the expressions of caspase-3, p53, caspase-9, Bax, interleukin-6 (IL-6), cytochrome C, neutrophil gelatinase-associated lipocalin (NGAL), tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB) and interleukin-1β (IL-1β) in the heart tissue were down-regulated whereas the Bcl-2 expression seemed to be enhanced. BB treatment not only alleviated ISO-induced gut dysbiosis by its enhanced specified Firmicutesto-Bacteroidetes (F/B) ratio but also maintained the relative abundance of major bacteria such as Clostridium IV, Butyricicoccus, Clostridium XIVs, Akkermansia and Roseburia. Collectively, our findings showed that the BB drug acted against myocardial infraction and prevented the damage by reducing the oxidative stress and controlling the inflammatory pathways, and gut microbiota.
Collapse
Affiliation(s)
- Yu Chen
- Department of CardiologySichuan Academy of Medical Science &Sichuan Provincial People's HospitalChengduChina
| | - Lei Peng
- Department of NephrologySichuan Academy of Medical Science & Sichuan Provincial People's HospitalChengduChina
| | - Shaoqing Shi
- Department of Pulmonary and Critical Care MedicineThe First Affiliated Hospital of Kunming Medical UniversityKunmingChina
| | - Gang Guo
- Department of Talent HighlandFirst Affiliated Hospital of Xi’an Jiao Tong UniversityXianChina
| | - Heling Wen
- Department of CardiologySichuan Academy of Medical Science &Sichuan Provincial People's HospitalChengduChina
| |
Collapse
|
42
|
Zhen J, Sun Y, Zhao P, Li C, Wang H, Li Y, Zhao L, Wang L, Huang G, Xu A. Abundance alteration of nondominant species in fecal-associated microbiome of patients with SAPHO syndrome. BMC Microbiol 2021; 21:161. [PMID: 34053449 PMCID: PMC8166064 DOI: 10.1186/s12866-021-02221-2] [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: 06/21/2020] [Accepted: 05/06/2021] [Indexed: 11/18/2022] Open
Abstract
Background SAPHO syndrome is a group of symptoms consisting of synovitis, acne, pustulosis, hyperostosis and osteosis. There is no specific laboratory index assist in the diagnosis of SAPHO because of its highly heterogeneous clinical manifestations. Pathogenic microorganisms had been identified in biopsies of some SAPHO cases and particular gene mutations were also linked to the occurrence of SAPHO. It is largely unknown whether intestinal microbiome plays a role in pathogenesis of SAPHO. To explore the intestinal microbiome structure of SAPHO syndrome, fecal samples from 17 SAPHO patients and 14 healthy controls (HC) were collected for 16S rDNA sequencing. Results Our results showed that there was no significant difference in alpha indexes and beta diversity between SAPHO and HC samples, while there were 14 operational taxonomic units (OTUs) in the Wilcoxon rank-sum test and 42 OTUs in the MetagenomeSeq analysis showed significant difference in distribution between the SAPHO and HC groups, 3 of which in Firmicutes were also observed in the random forest analysis and used to construct a receiver operating characteristic curve to evaluate the diagnostic value, the area under the curve was 0.86. Conclusion Fecal-associated microbiome in the SAPHO samples was characterized by the alteration in abundance of some nondominant species, and the 3 selected OTUs in Firmicutes could serve as candidate biomarkers for SAPHO syndrome diagnosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12866-021-02221-2.
Collapse
Affiliation(s)
- Jianhua Zhen
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yuxiu Sun
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Pengfei Zhao
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.,Oncology Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China
| | - Chen Li
- Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Hesong Wang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yini Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Lu Zhao
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Li Wang
- Institute of Biology, Henan Academy of Sciences, Zhengzhou, 450008, Henan, China
| | - Guangrui Huang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.
| | - Anlong Xu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.
| |
Collapse
|
43
|
Fang Q, Liu N, Zheng B, Guo F, Zeng X, Huang X, Ouyang D. Roles of Gut Microbial Metabolites in Diabetic Kidney Disease. Front Endocrinol (Lausanne) 2021; 12:636175. [PMID: 34093430 PMCID: PMC8173181 DOI: 10.3389/fendo.2021.636175] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 03/29/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetes is a highly prevalent metabolic disease that has emerged as a global challenge due to its increasing prevalence and lack of sustainable treatment. Diabetic kidney disease (DKD), which is one of the most frequent and severe microvascular complications of diabetes, is difficult to treat with contemporary glucose-lowering medications. The gut microbiota plays an important role in human health and disease, and its metabolites have both beneficial and harmful effects on vital physiological processes. In this review, we summarize the current findings regarding the role of gut microbial metabolites in the development and progression of DKD, which will help us better understand the possible mechanisms of DKD and explore potential therapeutic approaches for DKD.
Collapse
Affiliation(s)
- Qing Fang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Na Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Binjie Zheng
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Fei Guo
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Xiangchang Zeng
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Xinyi Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Dongsheng Ouyang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China
- Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Changsha, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, China
| |
Collapse
|
44
|
Kumar D, Mukherjee SS, Chakraborty R, Roy RR, Pandey A, Patra S, Dey S. The emerging role of gut microbiota in cardiovascular diseases. Indian Heart J 2021; 73:264-272. [PMID: 34154741 PMCID: PMC8322927 DOI: 10.1016/j.ihj.2021.04.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 02/12/2021] [Accepted: 04/24/2021] [Indexed: 02/08/2023] Open
Abstract
There is mounting evidence which suggests the involvement of gut microbiota dysbiosis in the pathogenesis of various cardiovascular diseases (CVD) and associated risk states such as hypertension, type 2 diabetes, obesity and dyslipidaemia, atherosclerosis, heart failure and atrial fibrillation. The current review comprehensively summarizes the various pathogenetic mechanisms of dysbiosis in these conditions and discusses the key therapeutic implications. Further deeper understanding of the pathogenetic links between CVD and gut microbiota dysbiosis can aid in the development of novel microbiota-based targets for the management of CVDs.
Collapse
Affiliation(s)
- Dilip Kumar
- Medica Institute of Cardiac Sciences, Kolkata, India.
| | | | | | | | | | - Soumya Patra
- Medica Institute of Cardiac Sciences, Kolkata, India
| | - Somnath Dey
- Medica Institute of Cardiac Sciences, Kolkata, India
| |
Collapse
|
45
|
Inhibitory Effects of Breast Milk-Derived Lactobacillus rhamnosus Probio-M9 on Colitis-Associated Carcinogenesis by Restoration of the Gut Microbiota in a Mouse Model. Nutrients 2021; 13:nu13041143. [PMID: 33808480 PMCID: PMC8065529 DOI: 10.3390/nu13041143] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/24/2021] [Accepted: 03/27/2021] [Indexed: 01/18/2023] Open
Abstract
Chronic inflammation is a risk factor for colorectal cancer, and inflammatory cytokines secreted from inflammatory cells and active oxygen facilitate tumorigenesis. Intestinal bacteria are thought to regulate tumorigenesis. The longer the breastfeeding period, the lower is the risk of inflammatory bowel disease. Here, we investigated preventive effects of the probiotic Lactobacillus rhamnosus M9 (Probio-M9) on colitis-associated tumorigenesis. An inflammatory colorectal tumor model was established using a 6-week-old male C57BL/6NCrSlc mouse, which was intraperitoneally administered with azoxymethane (AOM: 12 mg/kg body weight). On weeks 2 and 4, 2% dextran sulfate sodium (DSS) was administered to mice for 7 days through drinking water. On weeks 8 and 10, Probio-M9 (2 × 109/day) was orally administered for 7 days. Animals were sacrificed at 20 weeks after AOM administration and immunohistochemical staining and Western blotting was performed. The α-diversity of microflora (Shannon index), principal coordinate analysis, and distribution of intestinal bacterium genera and metabolic pathways were compared. The AOM/DSS group showed weight loss, diarrhea, intestinal shortening, increased number of colon tumors, proliferating tumorigenesis, increased inflammation score, fibrosis, increased CD68+, or CD163+ macrophage cells in the subserosal layer of non-tumor areas. Inflammation and tumorigenesis ameliorated after Probio-M9 treatment. Fecal microbial functions were altered by AOM/DSS treatment. Probio-M9 significantly upregulated the fecal microbial diversity and reversed fecal microbial functions. Thus, Probio-M9 could suppress tumor formation in the large intestine by regulating the intestinal environment and ameliorating inflammation, suggesting its therapeutic potential for treatment of inflammation and colitis-associated tumorigenesis.
Collapse
|
46
|
Li GH, Huang SJ, Li X, Liu XS, Du QL. Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients. World J Gastroenterol 2020; 26:7338-7351. [PMID: 33362388 PMCID: PMC7739160 DOI: 10.3748/wjg.v26.i46.7338] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/09/2020] [Accepted: 11/04/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood.
AIM To investigate the link between the gut microbiota and serum metabolome in ICP patients.
METHODS In this study, a total of 30 patients were recruited, including 15 patients with ICP (disease group) and 15 healthy pregnant patients (healthy group). The serum nontarget metabolomes from both groups were determined. Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups. By comparing the differences in the microbiota and metabolite compositions between the two groups, the relationship between the gut microbiota and serum metabolites was also investigated.
RESULTS The Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis, bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls. In addition, some pathways related to protein metabolism were also enriched in the ICP patients. The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition (beta diversity) between the ICP patients and healthy controls. At the phylum level, we observed that the relative abundance of Firmicutes was higher in the healthy group, while Bacteroidetes were enriched in the disease group. At the genus level, most of the bacteria depleted in ICP are able to produce short-chain fatty acids (e.g., Faecalibacterium, Blautia and Eubacterium hallii), while the bacteria enriched in ICP are associated with bile acid metabolism (e.g., Parabacteroides and Bilophila). Our results also showed that specific genera were associated with the serum metabolome.
CONCLUSION Our study showed that the serum metabolome was altered in ICP patients compared to healthy controls, with significant differences in the bile, taurine and hypotaurine metabolite pathways. Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota, which may further affect the course of progression of ICP.
Collapse
Affiliation(s)
- Guo-Hua Li
- Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Shi-Jia Huang
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Xiang Li
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Xiao-Song Liu
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Qiao-Ling Du
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| |
Collapse
|
47
|
Ding QY, Tian JX, Li M, Lian FM, Zhao LH, Wei XX, Han L, Zheng YJ, Gao ZZ, Yang HY, Fang XY, Tong XL. Interactions Between Therapeutics for Metabolic Disease, Cardiovascular Risk Factors, and Gut Microbiota. Front Cell Infect Microbiol 2020; 10:530160. [PMID: 33194785 PMCID: PMC7644821 DOI: 10.3389/fcimb.2020.530160] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 09/16/2020] [Indexed: 12/11/2022] Open
Abstract
With improved standards of living, the incidence of multiple metabolic disorders has increased year by year, especially major risk factors for cardiovascular disease such as hyperglycemia and hyperlipidemia, continues to increase. Emerging epidemiological data and clinical trials have shown the additional protective effects of some metabolic therapy drugs against cardiovascular diseases. A series of studies have found that these drugs may work by modulating the composition of gut microbiota. In this review, we provide a brief overview of the contribution of the gut microbiota to both metabolic disorders and cardiovascular diseases, as well as the response of gut microbiota to metabolic therapy drugs with cardiovascular benefits. In this manner, we link the recent advances in microbiome studies on metabolic treatment drugs with their cardiovascular protective effects, suggesting that intestinal microorganisms may play a potential role in reducing cardiovascular risk factors. We also discuss the potential of microorganism-targeted therapeutics as treatment strategies for preventing and/or treating cardiovascular disease and highlight the need to establish causal links between therapeutics for metabolic diseases, gut microbiota modulation, and cardiovascular protection.
Collapse
Affiliation(s)
- Qi-You Ding
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Jia-Xing Tian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Min Li
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Feng-Mei Lian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Lin-Hua Zhao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiu-Xiu Wei
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Lin Han
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yu-Jiao Zheng
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Ze-Zheng Gao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Hao-Yu Yang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Xin-Yi Fang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Xiao-Lin Tong
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| |
Collapse
|
48
|
Li H, Fang Q, Nie Q, Hu J, Yang C, Huang T, Li H, Nie S. Hypoglycemic and Hypolipidemic Mechanism of Tea Polysaccharides on Type 2 Diabetic Rats via Gut Microbiota and Metabolism Alteration. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:10015-10028. [PMID: 32811143 DOI: 10.1021/acs.jafc.0c01968] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Diabetes mellitus is a serious threat to human health. Tea is cultivated around the world, and its polysaccharide components are reported to be an effective approach for managing type 2 diabetes with fewer adverse effects than medication. To examine the therapeutic effect of tea polysaccharides on diabetes, a type 2 diabetic rat model was generated. We showed that tea polysaccharides remarkably decreased fasting blood glucose and the levels of total cholesterol, total triglyceride, low-density lipoprotein cholesterol, and free fatty acid of type 2 diabetic rats. 16S rRNA sequencing and metabolomics were used to investigate the variation of gut microbiota and the metabolites profiles of diabetic rats after intervention of tea polysaccharides. We found that tea polysaccharides maintained the diversity of gut microbiota and restored the relative abundance of some bacterial genera (Lachnospira, Victivallis, Roseburia, and Fluviicola) which was reduced by diabetes. According to metabolomics analysis, we found that amino acid and other related metabolites was influenced by tea polysaccharides intervention. Correlation analysis among metabolites, gut microbiota, and parameters of hypoglycemic indicated that tea polysaccharides had hypoglycemic and hypolipidemic effect on type 2 diabetes via the modulation of gut microbiota and the improvement of host metabolism.
Collapse
Affiliation(s)
- Haishan Li
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Qingying Fang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Qixing Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Jielun Hu
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Chao Yang
- Department of Urology and Surgery, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, United States
| | - Tao Huang
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Hu Li
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China
| |
Collapse
|
49
|
Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH. Int J Mol Sci 2020; 21:ijms21165820. [PMID: 32823659 PMCID: PMC7461212 DOI: 10.3390/ijms21165820] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/04/2020] [Accepted: 08/09/2020] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor the occurrence of non-alcoholic steatohepatitis (NASH). Moreover, several therapeutic approaches targeting the gut-pancreas-liver axis, e.g., incretins, showed promising results in NASH treatment. In this review, we describe the role of incretin hormones in NAFLD/NASH pathogenesis and treatment and how metagenomic/metabolomic alterations in the gut microbiota can lead to NASH in the presence of gut barrier modifications favoring the passage of bacteria or bacterial products in the portal circulation, i.e., bacterial translocation.
Collapse
|
50
|
Yang L, Lin H, Lin W, Xu X. Exercise Ameliorates Insulin Resistance of Type 2 Diabetes through Motivating Short-Chain Fatty Acid-Mediated Skeletal Muscle Cell Autophagy. BIOLOGY 2020; 9:biology9080203. [PMID: 32756447 PMCID: PMC7464264 DOI: 10.3390/biology9080203] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 07/28/2020] [Accepted: 08/02/2020] [Indexed: 02/07/2023]
Abstract
Background: Exercise can ameliorate type II diabetes mellitus (T2DM) by regulating intestinal flora metabolites. However, the detailed mechanism needs to be further explored. Methods: A T2DM model using mice was established by feeding them a high-fat diet and giving them subsequent streptozocin injections. Fasting blood glucose and serum insulin were determined by blood glucose meter and radioimmunoassay, respectively. Intestinal flora was measured by 16sRNA sequencing. SCFA content was measured by gas chromatography (GC) or enzyme-linked immunosorbent assay (ELISA). A fluorescently labeled 2-deoxyglucose (2-NBDG) kit was employed to detect glucose uptake capacity, and western blot was utilized to explore the signaling pathway of insulin resistance and cell autophagy. Results: In the T2DM model, along with a reduction in insulin resistance (IR), exercise reversed the decline of intestinal Bacteroidetes and the increase of Firmicutes. For metabolites of Bacteroides, exercise restored the decline in total intestinal and plasma short-chain fatty acids (SCFAs) in T2DM mice. However, the administration of GLPG0974—the inhibitor of G protein-coupled receptor 43 (GPR43), which is the receptor of SCFAs—abolished exercise-mediated alleviation in IR in vivo and acetate-mediated reduction of skeletal muscle IR (SMIR) in vitro. Mechanistically, exercise induced skeletal muscle cell autophagy, thereby ameliorating SMIR, which was neutralized by GLPG0974 exposure. Conclusions: Exercise-mediated SCFAs-upregulation may ameliorate insulin resistance (IR) through increasing autophagy of skeletal muscle cells by binding to GPR43. This study provides a theoretical basis for targeting gut bacterial metabolites to prevent T2DM.
Collapse
Affiliation(s)
- Ling Yang
- National Demonstration Center for Experimental Sports Science Education, School of Physical Education, South China Normal University, Guangzhou 510006, China;
- School of Physical Education, Shao Guan University, Shaoguan 512000, China
| | - Haiqi Lin
- School of Physical Education, South China University of Technology, Guangzhou 510641, China;
| | - Wentao Lin
- Guangzhou Institute of Physical Education, Guangzhou Sport University, Guangzhou 510500, China;
| | - Xiaoyang Xu
- National Demonstration Center for Experimental Sports Science Education, School of Physical Education, South China Normal University, Guangzhou 510006, China;
- Correspondence: ; Tel.: +86-135-0300-9002
| |
Collapse
|