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1
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Wang TG, Tian L, Zhang XL, Zhang L, Zhao XL, Kong DS. Gradient inflammation in the pancreatic stump after pancreaticoduodenectomy: Two case reports and review of literature. World J Clin Cases 2024; 12:1649-1659. [PMID: 38576729 PMCID: PMC10989426 DOI: 10.12998/wjcc.v12.i9.1649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 12/26/2023] [Accepted: 03/07/2024] [Indexed: 03/25/2024] Open
Abstract
BACKGROUND Postoperative pancreatic fistula (POPF) contributes significantly to morbidity and mortality after pancreaticoduodenectomy (PD). However, the underlying mechanisms remain unclear. This study explored this pathology in the pancreatic stumps and elucidated the mechanisms of POPF following PD. CASE SUMMARY Pathological analysis and 16S rRNA gene sequencing were performed on specimens obtained from two patients who underwent complete pancreatectomy for grade C POPF after PD. Gradient inflammation is present in the pancreatic stump. The apoptosis was lower than that in the normal pancreas. Moreover, neutrophil-dominated inflammatory cells are concentrated in the ductal system. Notably, neutrophils migrated through the ductal wall in acinar duct metaplasia-formed ducts. Additionally, evidence indicates that gut microbes migrate from the digestive tract. Gradient inflammation occurs in pancreatic stumps after PD. CONCLUSION The mechanisms underlying POPF include high biochemical activity in the pancreas, mechanical injury, and digestive reflux. To prevent POPF and address pancreatic inflammation and reflux, breaking the link with anastomotic dehiscence is practical.
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Affiliation(s)
- Tie-Gong Wang
- Department of Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Liang Tian
- Department of Pathology, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Xiao-Ling Zhang
- Department of Pathology, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Lei Zhang
- Department of Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - Xiu-Lei Zhao
- Department of Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
| | - De-Shuai Kong
- Department of Surgery, Cangzhou Central Hospital, Cangzhou 061000, Hebei Province, China
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2
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Kenger EB, Eren F, Ozlu T, Gunes FE. Analysis of microbiota profile and nutritional status in male professional football players. J Sports Med Phys Fitness 2023; 63:1235-1243. [PMID: 37486255 DOI: 10.23736/s0022-4707.23.15103-6] [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: 07/25/2023]
Abstract
BACKGROUND The interest in the effect of gut microbiota on athlete health has increased in recent years. Available data indicate a relationship between gut microbiota composition and physical activity, suggesting that changes in the microbiota may contribute to the host's physical performance. Studies show that leaky gut syndrome is highly correlated with upper respiratory infections and gastrointestinal disorders in endurance sports. This study aims to reveal the relationship between microbiota profiles, and the nutritional status of football players who perform endurance exercises. METHODS Twenty male professional football players playing in one of the Turkish Football Federation Second League clubs participated in the study. Fecal samples were collected and stored at -86 °C, and the fecal microbiota was analyzed through 16s rRNA gene sequencing. The body composition of the football players was measured using a bioelectrical impedance analyzer. In addition, the 3-day food intake of the participants was recorded with the help of a dietitian. RESULTS In the microbiota of football players, four phyla, 10 genera, and four species with densities above 1% were found. Body fat percentage was observed to be negatively correlated with the species of Faecalibacterium prausnitzii and Bacteroides vulgatus and the genus of Faecalibacterium (P<0.05). Considering the nutritional status, the fat intake was found to be positively correlated with Actinobacteria and Blautia coccoides; energy and fiber intake with Prevotella and Prevotella copri (P<0.05). In addition, there was a negative correlation between carbohydrate intake and Faecalibacterium (P<0.05). CONCLUSIONS Our study is the first to reveal the microbiota profile of professional Turkish football players. It was found that football players' nutritional status and anthropometric measurements of are significantly related to phylum, genus and species ranks in the microbiota. These results support the bidirectional interaction between microbiota and sports. The relationship between microbiota and sports health/performance is thought to be further clarified with future studies.
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Affiliation(s)
- Emre B Kenger
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Bahcesehir University, Istanbul, Türkiye -
| | - Fatih Eren
- Institute of Gastroenterology, Marmara University, Istanbul, Türkiye
| | - Tugce Ozlu
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Bahcesehir University, Istanbul, Türkiye
| | - Fatma E Gunes
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Medeniyet University, Istanbul, Türkiye
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3
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Wei ZG, Chen X, Zhang XD, Zhang H, Fan XG, Gao HY, Liu F, Qian Y. Comparison of Methods for Biological Sequence Clustering. IEEE/ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2023; 20:2874-2888. [PMID: 37028305 DOI: 10.1109/tcbb.2023.3253138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/19/2023]
Abstract
Recent advances in sequencing technology have considerably promoted genomics research by providing high-throughput sequencing economically. This great advancement has resulted in a huge amount of sequencing data. Clustering analysis is powerful to study and probe the large-scale sequence data. A number of available clustering methods have been developed in the last decade. Despite numerous comparison studies being published, we noticed that they have two main limitations: only traditional alignment-based clustering methods are compared and the evaluation metrics heavily rely on labeled sequence data. In this study, we present a comprehensive benchmark study for sequence clustering methods. Specifically, i) alignment-based clustering algorithms including classical (e.g., CD-HIT, UCLUST, VSEARCH) and recently proposed methods (e.g., MMseq2, Linclust, edClust) are assessed; ii) two alignment-free methods (e.g., LZW-Kernel and Mash) are included to compare with alignment-based methods; and iii) different evaluation measures based on the true labels (supervised metrics) and the input data itself (unsupervised metrics) are applied to quantify their clustering results. The aims of this study are to help biological analyzers in choosing one reasonable clustering algorithm for processing their collected sequences, and furthermore, motivate algorithm designers to develop more efficient sequence clustering approaches.
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4
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Li Y, Xu Y, Le Roy C, Hu J, Steves CJ, Bell JT, Spector TD, Gibson R, Menni C, Rodriguez-Mateos A. Interplay between the (Poly)phenol Metabolome, Gut Microbiome, and Cardiovascular Health in Women: A Cross-Sectional Study from the TwinsUK Cohort. Nutrients 2023; 15:1900. [PMID: 37111123 PMCID: PMC10141398 DOI: 10.3390/nu15081900] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/11/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Dietary (poly)phenol consumption is inversely associated with cardiovascular disease (CVD) risk in epidemiological studies, but little is known about the role of the gut microbiome in this relationship. METHODS In 200 healthy females, aged 62.0 ± 10.0 years, from the TwinsUK cohort, 114 individual (poly)phenol metabolites were measured from spot urine using ultra-high-performance liquid chromatography-mass spectrometry. The associations between metabolites, the gut microbiome (alpha diversity and genera), and cardiovascular scores were investigated using linear mixed models adjusting age, BMI, fibre, energy intake, family relatedness, and multiple testing (FDR < 0.1). RESULTS Significant associations were found between phenolic acid metabolites, CVD risk, and the gut microbiome. A total of 35 phenolic acid metabolites were associated with the Firmicutes phylum, while 5 metabolites were associated with alpha diversity (FDR-adjusted p < 0.05). Negative associations were observed between the atherosclerotic CVD (ASCVD) risk score and five phenolic acid metabolites, two tyrosol metabolites, and daidzein with stdBeta (95% (CI)) ranging from -0.05 (-0.09, -0.01) for 3-(2,4-dihydroxyphenyl)propanoic acid to -0.04 (-0.08, -0.003) for 2-hydroxycinnamic acid (FDR-adjusted p < 0.1). The genus 5-7N15 in the Bacteroidetes phylum was positively associated with the same metabolites, including 3-(3,5-dihydroxyphenyl)propanoic acid, 3-(2,4-dihydroxyphenyl)propanoic acid, 3-(3,4-dihydroxyphenyl)propanoic acid), 3-hydroxyphenylethanol-4-sulfate, and 4-hydroxyphenylethanol-3-sulfate)(stdBeta (95% CI): 0.23 (0.09, 0.36) to 0.28 (0.15, 0.42), FDR-adjusted p < 0.05), and negatively associated with the ASCVD score (stdBeta (95% CI): -0.05 (-0.09, -0.01), FDR-adjusted p = 0.02). Mediation analysis showed that genus 5-7N15 mediated 23.8% of the total effect of 3-(3,4-dihydroxyphenyl)propanoic acid on the ASCVD score. CONCLUSIONS Coffee, tea, red wine, and several vegetables and fruits, especially berries, are the most abundant food sources of phenolic acids that have the strongest associations with CVD risk. We found that the gut microbiome, particularly the genus 5-7N15, partially mediates the negative association between urinary (poly)phenols and cardiovascular risk, supporting a key role of the gut microbiome in the health benefits of dietary (poly)phenols.
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Affiliation(s)
- Yong Li
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Yifan Xu
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Caroline Le Roy
- Department of Twin Research and Genetic Epidemiology, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Jiaying Hu
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Claire J. Steves
- Department of Twin Research and Genetic Epidemiology, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Jordana T. Bell
- Department of Twin Research and Genetic Epidemiology, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Tim D. Spector
- Department of Twin Research and Genetic Epidemiology, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Rachel Gibson
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Cristina Menni
- Department of Twin Research and Genetic Epidemiology, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
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5
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Bonin A, Guerrieri A, Ficetola GF. Optimal sequence similarity thresholds for clustering of molecular operational taxonomic units in DNA metabarcoding studies. Mol Ecol Resour 2023; 23:368-381. [PMID: 36052659 DOI: 10.1111/1755-0998.13709] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 08/08/2022] [Accepted: 08/25/2022] [Indexed: 01/04/2023]
Abstract
Clustering approaches are pivotal to handle the many sequence variants obtained in DNA metabarcoding data sets, and therefore they have become a key step of metabarcoding analysis pipelines. Clustering often relies on a sequence similarity threshold to gather sequences into molecular operational taxonomic units (MOTUs), each of which ideally represents a homogeneous taxonomic entity (e.g., a species or a genus). However, the choice of the clustering threshold is rarely justified, and its impact on MOTU over-splitting or over-merging even less tested. Here, we evaluated clustering threshold values for several metabarcoding markers under different criteria: limitation of MOTU over-merging, limitation of MOTU over-splitting, and trade-off between over-merging and over-splitting. We extracted sequences from a public database for nine markers, ranging from generalist markers targeting Bacteria or Eukaryota, to more specific markers targeting a class or a subclass (e.g., Insecta, Oligochaeta). Based on the distributions of pairwise sequence similarities within species and within genera, and on the rates of over-splitting and over-merging across different clustering thresholds, we were able to propose threshold values minimizing the risk of over-splitting, that of over-merging, or offering a trade-off between the two risks. For generalist markers, high similarity thresholds (0.96-0.99) are generally appropriate, while more specific markers require lower values (0.85-0.96). These results do not support the use of a fixed clustering threshold. Instead, we advocate careful examination of the most appropriate threshold based on the research objectives, the potential costs of over-splitting and over-merging, and the features of the studied markers.
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Affiliation(s)
- Aurélie Bonin
- Department of Environmental Science and Policy, University of Milan, Milan, Italy.,Argaly, Bâtiment Clean space, Sainte-Hélène-du-Lac, France
| | - Alessia Guerrieri
- Department of Environmental Science and Policy, University of Milan, Milan, Italy
| | - Gentile Francesco Ficetola
- Department of Environmental Science and Policy, University of Milan, Milan, Italy.,LECA, Laboratoire d'Ecologie Alpine, Univ. Grenoble Alpes, CNRS, Univ. Savoie Mont Blanc, Grenoble, France
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6
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Combrink L, Humphreys IR, Washburn Q, Arnold HK, Stagaman K, Kasschau KD, Jolles AE, Beechler BR, Sharpton TJ. Best practice for wildlife gut microbiome research: A comprehensive review of methodology for 16S rRNA gene investigations. Front Microbiol 2023; 14:1092216. [PMID: 36910202 PMCID: PMC9992432 DOI: 10.3389/fmicb.2023.1092216] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 01/18/2023] [Indexed: 02/24/2023] Open
Abstract
Extensive research in well-studied animal models underscores the importance of commensal gastrointestinal (gut) microbes to animal physiology. Gut microbes have been shown to impact dietary digestion, mediate infection, and even modify behavior and cognition. Given the large physiological and pathophysiological contribution microbes provide their host, it is reasonable to assume that the vertebrate gut microbiome may also impact the fitness, health and ecology of wildlife. In accordance with this expectation, an increasing number of investigations have considered the role of the gut microbiome in wildlife ecology, health, and conservation. To help promote the development of this nascent field, we need to dissolve the technical barriers prohibitive to performing wildlife microbiome research. The present review discusses the 16S rRNA gene microbiome research landscape, clarifying best practices in microbiome data generation and analysis, with particular emphasis on unique situations that arise during wildlife investigations. Special consideration is given to topics relevant for microbiome wildlife research from sample collection to molecular techniques for data generation, to data analysis strategies. Our hope is that this article not only calls for greater integration of microbiome analyses into wildlife ecology and health studies but provides researchers with the technical framework needed to successfully conduct such investigations.
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Affiliation(s)
- Leigh Combrink
- Department of Microbiology, Oregon State University, Corvallis, OR, United States.,Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, United States.,School of Natural Resources and the Environment, University of Arizona, Tucson, AZ, United States
| | - Ian R Humphreys
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Quinn Washburn
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Holly K Arnold
- Department of Microbiology, Oregon State University, Corvallis, OR, United States.,Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, United States
| | - Keaton Stagaman
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Kristin D Kasschau
- Department of Microbiology, Oregon State University, Corvallis, OR, United States
| | - Anna E Jolles
- Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, United States.,Department of Integrative Biology, Oregon State University, Corvallis, OR, United States
| | - Brianna R Beechler
- Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, United States
| | - Thomas J Sharpton
- Department of Microbiology, Oregon State University, Corvallis, OR, United States.,Department of Statistics, Oregon State University, Corvallis, OR, United States
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7
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Wei ZG, Zhang XD, Cao M, Liu F, Qian Y, Zhang SW. Comparison of Methods for Picking the Operational Taxonomic Units From Amplicon Sequences. Front Microbiol 2021; 12:644012. [PMID: 33841367 PMCID: PMC8024490 DOI: 10.3389/fmicb.2021.644012] [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: 12/19/2020] [Accepted: 02/17/2021] [Indexed: 12/31/2022] Open
Abstract
With the advent of next-generation sequencing technology, it has become convenient and cost efficient to thoroughly characterize the microbial diversity and taxonomic composition in various environmental samples. Millions of sequencing data can be generated, and how to utilize this enormous sequence resource has become a critical concern for microbial ecologists. One particular challenge is the OTUs (operational taxonomic units) picking in 16S rRNA sequence analysis. Lucky, this challenge can be directly addressed by sequence clustering that attempts to group similar sequences. Therefore, numerous clustering methods have been proposed to help to cluster 16S rRNA sequences into OTUs. However, each method has its clustering mechanism, and different methods produce diverse outputs. Even a slight parameter change for the same method can also generate distinct results, and how to choose an appropriate method has become a challenge for inexperienced users. A lot of time and resources can be wasted in selecting clustering tools and analyzing the clustering results. In this study, we introduced the recent advance of clustering methods for OTUs picking, which mainly focus on three aspects: (i) the principles of existing clustering algorithms, (ii) benchmark dataset construction for OTU picking and evaluation metrics, and (iii) the performance of different methods with various distance thresholds on benchmark datasets. This paper aims to assist biological researchers to select the reasonable clustering methods for analyzing their collected sequences and help algorithm developers to design more efficient sequences clustering methods.
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Affiliation(s)
- Ze-Gang Wei
- Institute of Physics and Optoelectronics Technology, Baoji University of Arts and Sciences, Baoji, China
- Key Laboratory of Information Fusion Technology of Ministry of Education, School of Automation, Northwestern Polytechnical University, Xi’an, China
| | - Xiao-Dan Zhang
- Institute of Physics and Optoelectronics Technology, Baoji University of Arts and Sciences, Baoji, China
| | - Ming Cao
- Faculty of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, China
- School of Mathematics and Statistics, Shaanxi Xueqian Normal University, Xi’an, China
| | - Fei Liu
- Institute of Physics and Optoelectronics Technology, Baoji University of Arts and Sciences, Baoji, China
| | - Yu Qian
- Institute of Physics and Optoelectronics Technology, Baoji University of Arts and Sciences, Baoji, China
| | - Shao-Wu Zhang
- Key Laboratory of Information Fusion Technology of Ministry of Education, School of Automation, Northwestern Polytechnical University, Xi’an, China
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8
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Menni C, Zhu J, Le Roy CI, Mompeo O, Young K, Rebholz CM, Selvin E, North KE, Mohney RP, Bell JT, Boerwinkle E, Spector TD, Mangino M, Yu B, Valdes AM. Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes. Gut Microbes 2020; 11:1632-1642. [PMID: 32576065 PMCID: PMC7524143 DOI: 10.1080/19490976.2020.1778261] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 03/10/2020] [Accepted: 05/21/2020] [Indexed: 02/03/2023] Open
Abstract
Type 2 diabetes (T2D) is associated with reduced gut microbiome diversity, although the cause is unclear. Metabolites generated by gut microbes also appear to be causative factors in T2D. We therefore searched for serum metabolites predictive of gut microbiome diversity in 1018 females from TwinsUK with concurrent metabolomic profiling and microbiome composition. We generated a Microbial Metabolites Diversity (MMD) score of six circulating metabolites that explained over 18% of the variance in microbiome alpha diversity. Moreover, the MMD score was associated with a significantly lower odds of prevalent (OR[95%CI] = 0.22[0.07;0.70], P = .01) and incident T2D (HR[95%CI] = 0.31[0.11,0.90], P = .03). We replicated our results in 1522 individuals from the ARIC study (prevalent T2D: OR[95%CI] = 0.79[0.64,0.96], P = .02, incident T2D: HR[95%CI] = 0.87[0.79,0.95], P = .003). The MMD score mediated 28%[15%,94%] of the total effect of gut microbiome on T2D after adjusting for confounders. Metabolites predicting higher microbiome diversity included 3-phenylpropionate(hydrocinnamate), indolepropionate, cinnamoylglycine and 5-alpha-pregnan-3beta,20 alpha-diol monosulfate(2) of which indolepropionate and phenylpropionate have already been linked to lower incidence of T2D. Metabolites correlating with lower microbial diversity included glutarate and imidazole propionate, of which the latter has been implicated in insulin resistance. Our results suggest that the effect of gut microbiome diversity on T2D is largely mediated by microbial metabolites, which might be modifiable by diet.
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Affiliation(s)
- Cristina Menni
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Jialing Zhu
- School of Public Health, University of Texas Health Science Center, Houston, TX, USA
| | - Caroline I Le Roy
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Olatz Mompeo
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Kristin Young
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
| | - Casey M. Rebholz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Elizabeth Selvin
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Kari E. North
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
| | | | - Jordana T Bell
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Eric Boerwinkle
- School of Public Health, University of Texas Health Science Center, Houston, TX, USA
- Baylor College of Medicine, Houston, TX, USA
| | - Tim D Spector
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Massimo Mangino
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Bing Yu
- School of Public Health, University of Texas Health Science Center, Houston, TX, USA
| | - Ana M Valdes
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
- School of Medicine, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
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9
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Yang R, Liu H, Bai C, Wang Y, Zhang X, Guo R, Wu S, Wang J, Leung E, Chang H, Li P, Liu T, Wang Y. Chemical composition and pharmacological mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19): In silico and experimental study. Pharmacol Res 2020; 157:104820. [PMID: 32360484 PMCID: PMC7194979 DOI: 10.1016/j.phrs.2020.104820] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 04/05/2020] [Accepted: 04/07/2020] [Indexed: 01/08/2023]
Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45 %), glycosides (15 %), carboxylic acids (10 %), and saponins (5 %). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.
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Affiliation(s)
- Ruocong Yang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Bei San Huan East Road, Beijing, 100029, China
| | - Hao Liu
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Chen Bai
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Bei San Huan East Road, Beijing, 100029, China
| | - Yingchao Wang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Xiaohui Zhang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Rui Guo
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Siying Wu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Bei San Huan East Road, Beijing, 100029, China
| | - Jianxun Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Bei San Huan East Road, Beijing, 100029, China
| | - Elaine Leung
- Macau University of Science & Technology, Macau, China
| | - Hang Chang
- Lawrence Berkeley National Laboratory, University of California, USA
| | - Peng Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Bei San Huan East Road, Beijing, 100029, China
| | - Tiegang Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Bei San Huan East Road, Beijing, 100029, China.
| | - Yi Wang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
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10
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Consumption of Stilbenes and Flavonoids is Linked to Reduced Risk of Obesity Independently of Fiber Intake. Nutrients 2020; 12:nu12061871. [PMID: 32585900 PMCID: PMC7353284 DOI: 10.3390/nu12061871] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/15/2020] [Accepted: 06/18/2020] [Indexed: 02/06/2023] Open
Abstract
Background: Polyphenol consumption is implicated in gut microbiome composition and improved metabolic outcomes, but it is unclear whether the effect is independent of dietary fiber. Methods: We investigated the links between (poly)phenol intake, gut microbiome composition (16s RNA) and obesity independently of fiber intake in UK women (n = 1810) and in a small group of UK men (n = 64). Results: (Poly)phenol intakes correlated with microbiome alpha diversity (Shannon Index) after adjusting for confounders and fiber intake. Moreover, flavonoid intake was significantly correlated with the abundance of Veillonella, (a genus known to improve physical performance), and stilbene intake with that of butyrate-producing bacteria (Lachnospira and Faecalibacterium). Stilbene and flavonoid intake also correlated with lower odds of prevalent obesity (Stilbenes: Odds Ratio (95% Confidence Interval) (OR(95%CI)) = 0.80 (0.73, 0.87), p = 4.90 × 10−7; Flavonoids: OR(95%CI) = 0.77 (0.65, 0.91), p = 0.002). Formal mediation analyses revealed that gut microbiome mediates ~11% of the total effect of flavonoid and stilbene intake on prevalent obesity. Conclusions: Our findings highlight the importance of (poly)phenol consumption for optimal human health.
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11
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Carvalho CR, Dias AC, Homma SK, Cardoso EJ. Phyllosphere bacterial assembly in citrus crop under conventional and ecological management. PeerJ 2020; 8:e9152. [PMID: 32547860 PMCID: PMC7274167 DOI: 10.7717/peerj.9152] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 04/17/2020] [Indexed: 11/20/2022] Open
Abstract
Divergences between agricultural management can result in different types of biological interactions between plants and microorganisms, which may affect food quality and productivity. Conventional practices are well-established in the agroindustry as very efficient and lucrative; however, the increasing demand for sustainable alternatives has turned attention towards agroecological approaches. Here we intend to explore microbial dynamics according to the agricultural management used, based on the composition and structure of these bacterial communities on the most environmentally exposed habitat, the phyllosphere. Leaf samples were collected from a Citrus crop (cultivated Orange) in Mogi-Guaçu (SP, Brazil), where either conventional or ecological management systems were properly applied in two different areas. NGS sequencing analysis and quantitative PCR allowed us to comprehend the phyllosphere behavior and µ-XRF (micro X-ray fluorescence) could provide an insight on agrochemical persistence on foliar tissues. Our results demonstrate that there is considerable variation in the phyllosphere community due to the management practices used in the citrus orchard, and it was possible to quantify most of this variation. Equally, high copper concentrations may have influenced bacterial abundance, having a relevant impact on the differences observed. Moreover, we highlight the intricate relationship microorganisms have with crop production, and presumably with crop yield as well.
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Affiliation(s)
- Carolinne R Carvalho
- Department of Soil Science, College of Agriculture "Luiz de Queiroz", University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Armando Cf Dias
- Department of Soil Science, College of Agriculture "Luiz de Queiroz", University of São Paulo, Piracicaba, São Paulo, Brazil
| | | | - Elke Jbn Cardoso
- Department of Soil Science, College of Agriculture "Luiz de Queiroz", University of São Paulo, Piracicaba, São Paulo, Brazil
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12
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Hu Y, Xie G, Jiang X, Shao K, Tang X, Gao G. The Relationships Between the Free-Living and Particle-Attached Bacterial Communities in Response to Elevated Eutrophication. Front Microbiol 2020; 11:423. [PMID: 32269552 PMCID: PMC7109266 DOI: 10.3389/fmicb.2020.00423] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 02/27/2020] [Indexed: 11/13/2022] Open
Abstract
Exploring the relationships between free-living (FL) and particle-attached (PA) bacterial communities can provide insight into their connectivity and the partitioning of biogeochemical processes, which is crucial to understanding the elemental cycles and metabolic pathways in aquatic ecosystems. However, there is still intense debate about that whether FL and PA fractions have the same assemblage. To address this issue, we investigated the extent of similarity between FL and PA bacterial communities along the environmental gradients in Lake Wuli, China. Our results revealed that the west Lake Wuli was slightly eutrophic and the east lake was moderately and highly eutrophic. The alpha-diversity of the FL bacterial communities was significantly lower than that of the PA fraction in the west lake, whereas the alpha-diversity of the two fractions was comparable in the east lake. The beta-diversity of both communities significantly differed in the west lake, whereas it resembled that in the east lake. Moreover, functional prediction analysis highlighted the significantly larger differences of metabolic functions between the FL and PA fractions in the west lake than in the east lake. Suspended particles and carbon resource promote the similarity between the FL and PA fractions. Collectively, our result reveals a convergent succession of aquatic communities along the eutrophic gradient, highlighting that the connectivity between FL and PA bacterial communities is nutrient related.
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Affiliation(s)
- Yang Hu
- State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, China
| | - Guijuan Xie
- State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, China
- Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Beijing, China
| | - Xingyu Jiang
- State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, China
- Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Beijing, China
| | - Keqiang Shao
- State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, China
| | - Xiangming Tang
- State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, China
| | - Guang Gao
- State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, China
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13
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The Xylella fastidiosa-Resistant Olive Cultivar "Leccino" Has Stable Endophytic Microbiota during the Olive Quick Decline Syndrome (OQDS). Pathogens 2019; 9:pathogens9010035. [PMID: 31906093 PMCID: PMC7168594 DOI: 10.3390/pathogens9010035] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/26/2022] Open
Abstract
Xylella fastidiosa is a highly virulent pathogen that causes Olive Quick Decline Syndrome (OQDS), which is currently devastating olive plantations in the Salento region (Apulia, Southern Italy). We explored the microbiome associated with X. fastidiosa-infected (Xf-infected) and -uninfected (Xf-uninfected) olive trees in Salento, to assess the level of dysbiosis and to get first insights into the potential role of microbial endophytes in protecting the host from the disease. The resistant cultivar “Leccino” was compared to the susceptible cultivar “Cellina di Nardò”, in order to identify microbial taxa and parameters potentially involved in resistance mechanisms. Metabarcoding of 16S rRNA genes and fungal ITS2 was used to characterize both total and endophytic microbiota in olive branches and leaves. “Cellina di Nardò” showed a drastic dysbiosis after X. fastidiosa infection, while “Leccino” (both infected and uninfected) maintained a similar microbiota. The genus Pseudomonas dominated all “Leccino” and Xf-uninfected “Cellina di Nardò” trees, whereas Ammoniphilus prevailed in Xf-infected “Cellina di Nardò”. Diversity of microbiota in Xf-uninfected “Leccino” was higher than in Xf-uninfected “Cellina di Nardò”. Several bacterial taxa specifically associated with “Leccino” showed potential interactions with X. fastidiosa. The maintenance of a healthy microbiota with higher diversity and the presence of cultivar-specific microbes might support the resistance of “Leccino” to X. fastidiosa. Such beneficial bacteria might be isolated in the future for biological treatment of the OQDS.
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14
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Menni C, Hernandez MM, Vital M, Mohney RP, Spector TD, Valdes AM. Circulating levels of the anti-oxidant indoleproprionic acid are associated with higher gut microbiome diversity. Gut Microbes 2019; 10:688-695. [PMID: 31030641 PMCID: PMC6866703 DOI: 10.1080/19490976.2019.1586038] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The gut microbiome has recently emerged as an important regulator of insulin resistance and abdominal obesity. The tryptophan metabolite generated by the gut microbiome, indoleproprionic acid (IPA) has been shown to predict the onset of type 2 diabetes. IPA is a metabolite produced by gut microbes from dietary tryptophan that exhibits a high degree of inter-individual variation. The microbiome composition parameters that are associated with circulating levels of this potent anti-oxidant have however not been investigated to date in human populations. In 1018 middle-aged women from the TwinsUK cohort, we assessed the relationship between serum IPA levels and gut microbiome composition targeting the 16S rRNA gene. Microbiome alpha-diversity was positively correlated with serum indoleproprionic acid levels (Shannon Diversity: Beta[95%CI] = 0.19[0.13;0.25], P = 6.41 × 10-10) after adjustment for covariates. Sixteen taxa and 12 operational taxonomic units (OTUs) associated with IPA serum levels. Among these are positive correlations with the butyrate-producing Faecalibacterium prausnitzii, the class Mollicutes and the order RF39 of the Tenericutes, and Coprococcus Negative correlations instead were observed with Eubacterium dolichum previously shown to correlate with visceral fat mass and several genera in the Lachnospiraceae family such as Blautia and Ruminococcus previously shown to correlate with obesity. Microbiome composition parameters explained ~20% of the variation in circulating levels of IPA, whereas nutritional and host genetic parameters explained only ~4%. Our data confirm an association between IPA circulating levels and metabolic syndrome parameters and indicate that gut microbiome composition influences IPA levels.
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Affiliation(s)
- Cristina Menni
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK,CONTACT Ana M Valdes School of Medicine, University of Nottingham, Clinical Sciences Bldg, City Hospital, Hucknall Rd, Nottingham NG5 1PB, UK
| | | | - Marius Vital
- Microbial Interactions and Processes, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Robert P. Mohney
- Discovery and Translational Sciences, Metabolon Inc, Raleigh-Durham, NC, USA
| | - Tim D. Spector
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK
| | - Ana M. Valdes
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK,MSK Theme, NIHR Nottingham Biomedical Research Centre, Nottingham, UK,School of Medicine, Nottingham City Hospital, Nottingham, UK
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15
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Wells PM, Williams FMK, Matey-Hernandez ML, Menni C, Steves CJ. 'RA and the microbiome: do host genetic factors provide the link? J Autoimmun 2019; 99:104-115. [PMID: 30850234 PMCID: PMC6470121 DOI: 10.1016/j.jaut.2019.02.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 02/20/2019] [Accepted: 02/20/2019] [Indexed: 12/29/2022]
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterised by painful synovium inflammation, bony erosions, immune activation and the circulation of autoantibodies. Despite recent advances in therapeutics enabling disease suppression, there is a considerable demand for alternative therapeutic strategies as well as optimising those available at present. The relatively low concordance rate between monozygotic twins, 20–30% contrasts with heritability estimates of ∼65%, indicating a substantive role of other risk factors in RA pathogenesis. There is established evidence that RA has an infective component to its aetiology. More recently, differences in the commensal microbiota in RA compared to controls have been identified. Studies have shown that the gut, oral and lung microbiota is different in new onset treatment naïve, and established RA patients, compared to controls. Key taxonomic associations are an increase in abundance of Porphyromonas gingivalis and Prevotella copri in RA patients, compared to healthy controls. Host genetics may provide the link between disease and the microbiome. Genetic influence may be mediated by the host immune system; a differential response to RA associated taxa is suggested. The gut microbiome contains elements which are as much as 30% heritable. A better understanding of the influence of host genetics will shed light onto the role of the microbiome in RA. Here we review the role of the microbiome in RA through the lens of host genetics, and consider future research areas addressing microbiome study design and bioinformatics approaches.
Rheumatoid arthritis (RA) affects 1% of the population and is highly debilitating. RA is ~65% heritable, yet the concordance rate between monozygotic twins is just 20–30%, indicating a substantive role of other risk factors. Studies have shown that the gut, oral and lung microbiome is different in treatment naïve and established RA patients, compared to controls. Current findings suggest an important influence of host genetics on the microbiome, which may contribute to RA via the host immune system. Associations of the microbiome with RA described thus far are confounded by host genetics, and future studies need to take account of this.
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Affiliation(s)
- Philippa M Wells
- The Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK.
| | - Frances M K Williams
- The Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK
| | - M L Matey-Hernandez
- The Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK
| | - Cristina Menni
- The Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK
| | - Claire J Steves
- The Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK; Clinical Age Research Unit, Kings College Hospital Foundation Trust, London, UK
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16
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Abstract
Our understanding of the human gut microbiome continues to evolve at a rapid pace, but practical application of thisknowledge is still in its infancy. This review discusses the type of studies that will be essential for translating microbiome research into targeted modulations with dedicated benefits for the human host.
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Affiliation(s)
- Thomas S B Schmidt
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
| | - Jeroen Raes
- KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute, Herestraat 49, 3000 Leuven, Belgium; VIB, Center for Microbiology, Heerestraat 49, 3000 Leuven, Belgium.
| | - Peer Bork
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany; Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69120 Heidelberg, Germany; Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
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17
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Verdi S, Jackson MA, Beaumont M, Bowyer RCE, Bell JT, Spector TD, Steves CJ. An Investigation Into Physical Frailty as a Link Between the Gut Microbiome and Cognitive Health. Front Aging Neurosci 2018; 10:398. [PMID: 30564113 PMCID: PMC6288358 DOI: 10.3389/fnagi.2018.00398] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 11/19/2018] [Indexed: 12/26/2022] Open
Abstract
The preservation of cognitive abilities with aging is a priority both for individuals and nations given the aging populations of many countries. Recently the gut microbiome has been identified as a new territory to explore in relation to cognition. Experiments using rodents have identified a link between the gut microbiome and cognitive function, particularly that low microbial diversity leads to poor cognition function. Similar studies in humans could identify novel targets to encourage healthy cognition in an aging population. Here, we investigate the association of gut microbiota and cognitive function in a human cohort considering the influence of physical frailty. We analyzed 16S rRNA gene sequence data, derived from fecal samples obtained from 1,551 individuals over the age of 40. Cognitive data was collected using four cognitive tests: verbal fluency (n = 1,368), Deary-Liewald Reaction Time Test (DLRT; n = 873), Mini Mental State Examination (recall; n = 1,374) and Paired Associates Learning from the Cambridge Neuropsychological Test Automated Battery (CANTAB-PAL; n = 405). We use mixed effects models to identify associations with alpha diversity, operational taxonomic units (OTUs) and taxa and performed further analyses adjusting for physical frailty. We then repeated the analyses in a subset of individuals with dietary data, also excluding those using medications shown to influence gut microbiome composition. DLRT and verbal fluency were negatively associated with alpha diversity of the gut microbiota (False-Discovery Rate, FDR, p < 0.05). However, when considering frailty as a covariate, only associations between the DLRT and diversity measures remained. Repeating analyses excluding Proton pump inhibitor (PPI) and antibiotic users and accounting for diet, we similarly observe significant negative associations between the DLRT and alpha diversity measures and a further negative association between DLRT and the abundance of the order Burkholderiales that remains significant after adjusting for host frailty. This highlights the importance of considering concurrent differences in physical health in studies of cognitive performance and suggests that physical health has a relatively larger association with the gut microbiome. However, the frailty independent cognitive-gut microbiota associations that were observed might represent important targets for further research, with potential for use in diagnostic surveillance in cognitive aging and interventions to improve vitality.
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Affiliation(s)
- Serena Verdi
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
- Neuropsychopharmacology Unit, Centre for Psychiatry, Division of Brain Sciences, Imperial College London, London, United Kingdom
| | - Matthew A. Jackson
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
| | - Michelle Beaumont
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
| | - Ruth C. E. Bowyer
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
| | - Jordana T. Bell
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
| | - Tim D. Spector
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
| | - Claire J. Steves
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
- Clinical Age Research Unit, Department of Clinical Gerontology, King’s College Hospital, NHS Foundation Trust, London, United Kingdom
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18
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Müller R, Nebel ME. GeFaST: An improved method for OTU assignment by generalising Swarm's fastidious clustering approach. BMC Bioinformatics 2018; 19:321. [PMID: 30208838 PMCID: PMC6134716 DOI: 10.1186/s12859-018-2349-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 08/29/2018] [Indexed: 01/19/2023] Open
Abstract
Background Massive genomic data sets from high-throughput sequencing allow for new insights into complex biological systems such as microbial communities. Analyses of their diversity and structure are typically preceded by clustering millions of 16S rRNA gene sequences into OTUs. Swarm introduced a new clustering strategy which addresses important conceptual and performance issues of the popular de novo clustering approach. However, some parts of the new strategy, e.g. the fastidious option for increased clustering quality, come with their own restrictions. Results In this paper, we present the new exact, alignment-based de novo clustering tool GeFaST, which implements a generalisation of Swarm’s fastidious clustering. Our tool extends the fastidious option to arbitrary clustering thresholds and allows to adjust its greediness. GeFaST was evaluated on mock-community and natural data and achieved higher clustering quality and performance for small to medium clustering thresholds compared to Swarm and other de novo tools. Clustering with GeFaST was between 6 and 197 times as fast as with Swarm, while the latter required up to 38% less memory for non-fastidious clustering but at least three times as much memory for fastidious clustering. Conclusions GeFaST extends the scope of Swarm’s clustering strategy by generalising its fastidious option, thereby allowing for gains in clustering quality, and by increasing its performance (especially in the fastidious case). Our evaluations showed that GeFaST has the potential to leverage the use of the (fastidious) clustering strategy for higher thresholds and on larger data sets. Electronic supplementary material The online version of this article (10.1186/s12859-018-2349-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Robert Müller
- International Research Training Group "Computational Methods for the Analysis of the Diversity and Dynamics of Genomes", Bielefeld University, Bielefeld, Germany. .,Faculty of Technology, Bielefeld University, Bielefeld, Germany.
| | - Markus E Nebel
- International Research Training Group "Computational Methods for the Analysis of the Diversity and Dynamics of Genomes", Bielefeld University, Bielefeld, Germany.,Faculty of Technology, Bielefeld University, Bielefeld, Germany.,IMADA, Southern Denmark University, Odense, Denmark
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19
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Jackson MA, Verdi S, Maxan ME, Shin CM, Zierer J, Bowyer RCE, Martin T, Williams FMK, Menni C, Bell JT, Spector TD, Steves CJ. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun 2018; 9:2655. [PMID: 29985401 PMCID: PMC6037668 DOI: 10.1038/s41467-018-05184-7] [Citation(s) in RCA: 394] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 06/18/2018] [Indexed: 12/12/2022] Open
Abstract
The human gut microbiome has been associated with many health factors but variability between studies limits exploration of effects between them. Gut microbiota profiles are available for >2700 members of the deeply phenotyped TwinsUK cohort, providing a uniform platform for such comparisons. Here, we present gut microbiota association analyses for 38 common diseases and 51 medications within the cohort. We describe several novel associations, highlight associations common across multiple diseases, and determine which diseases and medications have the greatest association with the gut microbiota. These results provide a reference for future studies of the gut microbiome and its role in human health.
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Affiliation(s)
- Matthew A Jackson
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, OX3 7FY, UK.
| | - Serena Verdi
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
| | - Maria-Emanuela Maxan
- Clinical Age Research Unit, King's College Hospital Foundation Trust, London, SE5 9RS, UK
| | - Cheol Min Shin
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jonas Zierer
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
- Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, 85764, Neuherberg, Germany
| | - Ruth C E Bowyer
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
| | - Tiphaine Martin
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
- Department of Oncological Sciences, Tisch Institute of Cancer, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Frances M K Williams
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
| | - Cristina Menni
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
| | - Jordana T Bell
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
| | - Tim D Spector
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
| | - Claire J Steves
- Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
- Clinical Age Research Unit, King's College Hospital Foundation Trust, London, SE5 9RS, UK.
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20
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Menni C, Lin C, Cecelja M, Mangino M, Matey-Hernandez ML, Keehn L, Mohney RP, Steves CJ, Spector TD, Kuo CF, Chowienczyk P, Valdes AM. Gut microbial diversity is associated with lower arterial stiffness in women. Eur Heart J 2018; 39:2390-2397. [PMID: 29750272 PMCID: PMC6030944 DOI: 10.1093/eurheartj/ehy226] [Citation(s) in RCA: 161] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 12/06/2017] [Accepted: 04/06/2018] [Indexed: 12/11/2022] Open
Abstract
Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness. Methods and results We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 × 10-4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing-two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3-12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing.
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Affiliation(s)
- Cristina Menni
- Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas' Hospital, London, UK
| | - Chihung Lin
- Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Fuxing Street, Guishan Dist., Taoyuan City, Taiwan
| | - Marina Cecelja
- Department of Clinical Pharmacology, British Heart Foundation Centre, King’s College London, St Thomas' Hospital, London, UK
| | - Massimo Mangino
- Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas' Hospital, London, UK
- NIHR Biomedical Research Centre at Guy’s and St Thomas’ Foundation Trust, St Thomas’ Hospital, London, UK
| | - Maria Luisa Matey-Hernandez
- Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas' Hospital, London, UK
| | - Louise Keehn
- Department of Clinical Pharmacology, British Heart Foundation Centre, King’s College London, St Thomas' Hospital, London, UK
| | | | - Claire J Steves
- Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas' Hospital, London, UK
| | - Tim D Spector
- Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas' Hospital, London, UK
| | - Chang-Fu Kuo
- Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Fuxing Street, Guishan Dist., Taoyuan City, Taiwan
- School of Medicine, Nottingham City Hospital, Hucknall Road, Nottingham, UK
| | - Phil Chowienczyk
- Department of Clinical Pharmacology, British Heart Foundation Centre, King’s College London, St Thomas' Hospital, London, UK
| | - Ana M Valdes
- Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas' Hospital, London, UK
- School of Medicine, Nottingham City Hospital, Hucknall Road, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Queen's Medical Centre, Derby Rd, Nottingham, UK
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Zierer J, Jackson MA, Kastenmüller G, Mangino M, Long T, Telenti A, Mohney RP, Small KS, Bell JT, Steves CJ, Valdes AM, Spector TD, Menni C. The fecal metabolome as a functional readout of the gut microbiome. Nat Genet 2018; 50:790-795. [PMID: 29808030 PMCID: PMC6104805 DOI: 10.1038/s41588-018-0135-7] [Citation(s) in RCA: 452] [Impact Index Per Article: 64.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 04/05/2018] [Indexed: 01/07/2023]
Abstract
The human gut microbiome plays a key role in human health 1 , but 16S characterization lacks quantitative functional annotation 2 . The fecal metabolome provides a functional readout of microbial activity and can be used as an intermediate phenotype mediating host-microbiome interactions 3 . In this comprehensive description of the fecal metabolome, examining 1,116 metabolites from 786 individuals from a population-based twin study (TwinsUK), the fecal metabolome was found to be only modestly influenced by host genetics (heritability (H2) = 17.9%). One replicated locus at the NAT2 gene was associated with fecal metabolic traits. The fecal metabolome largely reflects gut microbial composition, explaining on average 67.7% (±18.8%) of its variance. It is strongly associated with visceral-fat mass, thereby illustrating potential mechanisms underlying the well-established microbial influence on abdominal obesity. Fecal metabolic profiling thus is a novel tool to explore links among microbiome composition, host phenotypes, and heritable complex traits.
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Affiliation(s)
- Jonas Zierer
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK
- Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
- Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA
| | - Matthew A Jackson
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Gabi Kastenmüller
- Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
| | - Massimo Mangino
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK
- NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK
| | - Tao Long
- Human Longevity, Inc, San Diego, CA, USA
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | | | | | - Kerrin S Small
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Jordana T Bell
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Claire J Steves
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Ana M Valdes
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham, UK
- School of Medicine, University of Nottingham, Nottingham, UK
| | - Tim D Spector
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK.
| | - Cristina Menni
- Department for Twin Research & Genetic Epidemiology, King's College London, London, UK.
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22
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Feranchuk S, Belkova N, Potapova U, Kuzmin D, Belikov S. Evaluating the use of diversity indices to distinguish between microbial communities with different traits. Res Microbiol 2018; 169:254-261. [PMID: 29800679 DOI: 10.1016/j.resmic.2018.03.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 03/11/2018] [Accepted: 03/14/2018] [Indexed: 02/07/2023]
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23
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Yang JW, Wu W, Chung CC, Chiang KP, Gong GC, Hsieh CH. Predator and prey biodiversity relationship and its consequences on marine ecosystem functioning-interplay between nanoflagellates and bacterioplankton. ISME JOURNAL 2018; 12:1532-1542. [PMID: 29703955 DOI: 10.1038/s41396-018-0111-3] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 02/19/2018] [Accepted: 03/05/2018] [Indexed: 01/30/2023]
Abstract
The importance of biodiversity effects on ecosystem functioning across trophic levels, especially via predatory-prey interactions, is receiving increased recognition. However, this topic has rarely been explored for marine microbes, even though microbial biodiversity contributes significantly to marine ecosystem function and energy flows. Here we examined diversity and biomass of bacteria (prey) and nanoflagellates (predators), as well as their effects on trophic transfer efficiency in the East China Sea. Specifically, we investigated: (i) predator diversity effects on prey biomass and trophic transfer efficiency (using the biomass ratio of predator/prey as a proxy), (ii) prey diversity effects on predator biomass and trophic transfer efficiency, and (iii) the relationship between predator and prey diversity. We found higher prey diversity enhanced both diversity and biomass of predators, as well as trophic transfer efficiency, which may arise from more balanced diet and/or enhanced niche complementarity owing to higher prey diversity. By contrast, no clear effect was detected for predator diversity on prey biomass and transfer efficiency. Notably, we found prey diversity effects on predator-prey interactions; whereas, we found no significant diversity effect on biomass within the same trophic level. Our findings highlight the importance of considering multi-trophic biodiversity effects on ecosystem functioning in natural ecosystems.
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Affiliation(s)
- Jinny Wu Yang
- Institute of Oceanography, National Taiwan University, Taipei, Taiwan
| | - Wenxue Wu
- Institute of Oceanography, National Taiwan University, Taipei, Taiwan.,Division of Life Science, The Hong Kong University of Science and Technology, Kowloon, Hong Kong
| | - Chih-Ching Chung
- Institute of Marine Environment and Ecology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan
| | - Kuo-Ping Chiang
- Institute of Marine Environment and Ecology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan
| | - Gwo-Ching Gong
- Institute of Marine Environment and Ecology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan
| | - Chih-Hao Hsieh
- Institute of Oceanography, National Taiwan University, Taipei, Taiwan. .,Institute of Ecology and Evolutionary Biology, Department of Life Science, National Taiwan University, Taipei, Taiwan. .,Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan. .,National Center for Theoretical Sciences, Taipei, Taiwan.
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24
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Bowyer RCE, Jackson MA, Pallister T, Skinner J, Spector TD, Welch AA, Steves CJ. Use of dietary indices to control for diet in human gut microbiota studies. MICROBIOME 2018; 6:77. [PMID: 29695307 PMCID: PMC5918560 DOI: 10.1186/s40168-018-0455-y] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 03/28/2018] [Indexed: 05/22/2023]
Abstract
BACKGROUND Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition. RESULTS All three indices were independently validated using established measures of health, and all were significantly associated with microbiota measures; the HEI had the highest t values in models of alpha diversity measures, and had the highest number of associations with microbial taxa. Beta diversity analyses showed the HEI explained the greatest variance of microbiota composition. In paired tests between twins discordant for dietary index score, the HEI was associated with the greatest variation of taxa and twin dissimilarity. CONCLUSIONS We find that the HEI explains the most variance in, and has the strongest association with, gut microbiota composition in a western (UK) population, suggesting that it may be the best summary measure to capture gut microbiota variance attributable to habitual diet in comparable populations.
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Affiliation(s)
- Ruth C. E. Bowyer
- The Department of Twin Research, Kings College London, 3-4th Floor South Wing Block D, St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH UK
| | - Matthew A. Jackson
- The Department of Twin Research, Kings College London, 3-4th Floor South Wing Block D, St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH UK
| | - Tess Pallister
- The Department of Twin Research, Kings College London, 3-4th Floor South Wing Block D, St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH UK
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), 150 Cours Albert Thomas, 69008 Lyon, France
| | - Jane Skinner
- Norwich Medical School 2.02, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ UK
| | - Tim D. Spector
- The Department of Twin Research, Kings College London, 3-4th Floor South Wing Block D, St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH UK
| | - Ailsa A. Welch
- Norwich Medical School 2.02, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ UK
| | - Claire J. Steves
- The Department of Twin Research, Kings College London, 3-4th Floor South Wing Block D, St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH UK
- Clinical Age Research Unit, Kings College Hospital Foundation Trust, London, UK
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25
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Jackson MA, Bonder MJ, Kuncheva Z, Zierer J, Fu J, Kurilshikov A, Wijmenga C, Zhernakova A, Bell JT, Spector TD, Steves CJ. Detection of stable community structures within gut microbiota co-occurrence networks from different human populations. PeerJ 2018; 6:e4303. [PMID: 29441232 PMCID: PMC5807925 DOI: 10.7717/peerj.4303] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 01/10/2018] [Indexed: 12/20/2022] Open
Abstract
Microbes in the gut microbiome form sub-communities based on shared niche specialisations and specific interactions between individual taxa. The inter-microbial relationships that define these communities can be inferred from the co-occurrence of taxa across multiple samples. Here, we present an approach to identify comparable communities within different gut microbiota co-occurrence networks, and demonstrate its use by comparing the gut microbiota community structures of three geographically diverse populations. We combine gut microbiota profiles from 2,764 British, 1,023 Dutch, and 639 Israeli individuals, derive co-occurrence networks between their operational taxonomic units, and detect comparable communities within them. Comparing populations we find that community structure is significantly more similar between datasets than expected by chance. Mapping communities across the datasets, we also show that communities can have similar associations to host phenotypes in different populations. This study shows that the community structure within the gut microbiota is stable across populations, and describes a novel approach that facilitates comparative community-centric microbiome analyses.
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Affiliation(s)
- Matthew A Jackson
- Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom
| | - Marc Jan Bonder
- University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, Netherlands
| | - Zhana Kuncheva
- Department of Mathematics, Imperial College London, London, United Kingdom
| | - Jonas Zierer
- Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom.,Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany
| | - Jingyuan Fu
- University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, Netherlands.,University Medical Center Groningen, Department of Pediatrics, University of Groningen, Groningen, Netherlands
| | - Alexander Kurilshikov
- University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, Netherlands
| | - Cisca Wijmenga
- University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, Netherlands.,K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway
| | - Alexandra Zhernakova
- University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, Netherlands
| | - Jordana T Bell
- Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom
| | - Tim D Spector
- Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom
| | - Claire J Steves
- Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom
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26
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Le Roy CI, Beaumont M, Jackson MA, Steves CJ, Spector TD, Bell JT. Heritable components of the human fecal microbiome are associated with visceral fat. Gut Microbes 2018; 9:61-67. [PMID: 28767316 PMCID: PMC5914912 DOI: 10.1080/19490976.2017.1356556] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 07/06/2017] [Accepted: 07/10/2017] [Indexed: 02/07/2023] Open
Abstract
Obesity and its associated diseases are one of the major causes of death worldwide. The gut microbiota has been identified to have essential regulatory effects on human metabolism and obesity in particular. In a recent study we provided some insights into the link between the gut microbiota (GM) and adiposity, as well as host genetic modulation of these processes. Our results identify novel evidence of association between 6 adiposity phenotypes and faecal microbial operational taxonomic units (OTUs). Accumulation of visceral fat, a key risk factor for cardio-metabolic disease, has the strongest and most pervasive signature on the gut microbiota of the factors we examined. Furthermore, we observe that the adiposity-associated OTUs were classified as heritable and in some cases were also associated with host genetic variation at obesity-associated human candidate genes FHIT, TDRG1 and ELAVL4. This addendum confirms our previously published results in the TwinsUK cohort using a different approach to OTU clustering and multivariate analysis, and discusses further the importance of considering the GM as a complex ecosystem.
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Affiliation(s)
- Caroline I. Le Roy
- Department of Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Michelle Beaumont
- Department of Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Matthew A. Jackson
- Department of Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Claire J. Steves
- Department of Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Timothy D. Spector
- Department of Twin Research & Genetic Epidemiology, King's College London, London, UK
| | - Jordana T. Bell
- Department of Twin Research & Genetic Epidemiology, King's College London, London, UK
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27
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Whelan FJ, Surette MG. A comprehensive evaluation of the sl1p pipeline for 16S rRNA gene sequencing analysis. MICROBIOME 2017; 5:100. [PMID: 28807046 PMCID: PMC5557527 DOI: 10.1186/s40168-017-0314-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 07/21/2017] [Indexed: 05/11/2023]
Abstract
BACKGROUND Advances in next-generation sequencing technologies have allowed for detailed, molecular-based studies of microbial communities such as the human gut, soil, and ocean waters. Sequencing of the 16S rRNA gene, specific to prokaryotes, using universal PCR primers has become a common approach to studying the composition of these microbiota. However, the bioinformatic processing of the resulting millions of DNA sequences can be challenging, and a standardized protocol would aid in reproducible analyses. METHODS The short-read library 16S rRNA gene sequencing pipeline (sl1p, pronounced "slip") was designed with the purpose of mitigating this lack of reproducibility by combining pre-existing tools into a computational pipeline. This pipeline automates the processing of raw 16S rRNA gene sequencing data to create human-readable tables, graphs, and figures to make the collected data more readily accessible. RESULTS Data generated from mock communities were compared using eight OTU clustering algorithms, two taxon assignment approaches, and three 16S rRNA gene reference databases. While all of these algorithms and options are available to sl1p users, through testing with human-associated mock communities, AbundantOTU+, the RDP Classifier, and the Greengenes 2011 reference database were chosen as sl1p's defaults based on their ability to best represent the known input communities. CONCLUSIONS sl1p promotes reproducible research by providing a comprehensive log file, and reduces the computational knowledge needed by the user to process next-generation sequencing data. sl1p is freely available at https://bitbucket.org/fwhelan/sl1p .
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Affiliation(s)
- Fiona J. Whelan
- Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W, Hamilton, Canada
| | - Michael G. Surette
- Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W, Hamilton, Canada
- Department of Medicine, McMaster University, 1280 Main St. W, Hamilton, Canada
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28
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Menni C, Jackson MA, Pallister T, Steves CJ, Spector TD, Valdes AM. Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. Int J Obes (Lond) 2017; 41:1099-1105. [PMID: 28286339 PMCID: PMC5500185 DOI: 10.1038/ijo.2017.66] [Citation(s) in RCA: 234] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Revised: 02/15/2017] [Accepted: 03/05/2017] [Indexed: 12/16/2022]
Abstract
Background: Cross-sectional studies suggest that the microbes in the human gut have a role in obesity by influencing the human body’s ability to extract and store calories. The aim of this study was to assess if there is a correlation between change in body weight over time and gut microbiome composition. Methods: We analysed 16S ribosomal RNA gene sequence data derived from the faecal samples of 1632 healthy females from TwinsUK to investigate the association between gut microbiome measured cross-sectionally and longitudinal weight gain (adjusted for caloric intake and baseline body mass index). Dietary fibre intake was investigated as a possible modifier. Results: Less than half of the variation in long-term weight change was found to be heritable (h2=0.41 (0.31, 0.47)). Gut microbiota diversity was negatively associated with long-term weight gain, whereas it was positively correlated with fibre intake. Nine bacterial operational taxonomic units (OTUs) were significantly associated with weight gain after adjusting for covariates, family relatedness and multiple testing (false discovery rate <0.05). OTUs associated with lower long-term weight gain included those assigned to Ruminococcaceae (associated in mice with improved energy metabolism) and Lachnospiraceae. A Bacterioides species OTU was associated with increased risk of weight gain but this appears to be driven by its correlation with lower levels of diversity. Conclusions: High gut microbiome diversity, high-fibre intake and OTUs implicated in animal models of improved energy metabolism are all correlated with lower term weight gain in humans independently of calorie intake and other confounders.
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Affiliation(s)
- C Menni
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - M A Jackson
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - T Pallister
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - C J Steves
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - T D Spector
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - A M Valdes
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.,Academic Rheumatology, University of Nottingham, Nottingham, UK
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