scholarly journals Interplay between the human gut microbiome and host metabolism

2019 ◽  
Author(s):  
Alessia Visconti ◽  
Caroline I. Le Roy ◽  
Fabio Rosa ◽  
Niccolo Rossi ◽  
Tiphaine C. Martin ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Taxonomic Composition ◽  
Metagenomic Sequencing ◽  
Human Gut ◽  
Metabolic Potential ◽  
Microbial Ecosystem ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing ◽  
Key Species

AbstractThe human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.

scholarly journals Interplay between the human gut microbiome and host metabolism

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Alessia Visconti ◽  
Caroline I. Le Roy ◽  
Fabio Rosa ◽  
Niccolò Rossi ◽  
Tiphaine C. Martin ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Blood Metabolites ◽  
Sequencing Data ◽  
Human Gut ◽  
Metabolic Potential ◽  
Microbial Ecosystem ◽  
Microbial Metabolic Potential ◽  
Host Metabolism

Abstract The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%). Then, using 673 blood and 713 faecal metabolites, we found metabolic pathways to be associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species showed less than 3,000 associations. Finally, we estimated that the microbiome was involved in a dialogue between 71% of faecal, and 15% of blood, metabolites. This study underlines the importance of studying the microbial metabolic potential rather than focusing purely on taxonomy to find therapeutic and diagnostic targets, and provides a unique resource describing the interplay between the microbiome and the systemic and faecal metabolic environments.

scholarly journals Separation of Cohorts on the Basis of Bacterial Type IV Conjugation Systems Identified From Metagenomic Assemblies

2021 ◽  
Author(s):  
Benjamin R Joris ◽  
Tyler S Browne ◽  
Thomas A Hamilton ◽  
David R Edgell ◽  
Gregory B Gloor
Keyword(s):  
North American ◽  
Gut Microbiome ◽  
Metagenomic Sequencing ◽  
Human Gut ◽  
Term Infants ◽  
Human Gut Microbiome ◽  
Type Iv ◽  
Shotgun Metagenomic Sequencing ◽  
Age Related ◽  
Inflammatory Bowel

Abstract BackgroundConjugation enables the exchange of genetic elements throughout environments, including the human gut microbiome. Conjugative elements can carry and transfer clinically relevant metabolic pathways which makes precise identification of these systems in metagenomic samples clinically important. ResultsHere, we outline two distinct methods to identify conjugative elements in the human gut microbiome. We first show that conjugative elements exhibit strong population and age-level stratification. Furthermore, the taxonomic compositions of the conjugative elements differ from the composition of the metagenome assembled genomes, both in terms of the number of assembled elements and the relative abundances of the assembled systems. Finally, we demonstrate that the majority of assembled conjugative elements are not included within metagenomic bins, and that only a small proportion of the binned conjugative systems are included in "high-quality" metagenomic bins. Our findings highlight that conjugative systems differ between a North American inflammatory bowel disease cohort and a cohort of North American pre-term infants, but in a manner different than metagenome assembled genomes, revealing a potential use as an age-related biomarker. Additionally, conjugative systems can distinguish between other geographical-based cohorts. ConclusionsAnalysis of the human gut microbiome by shotgun metagenomic sequencing has revealed numerous connections to human health outcomes. Our findings emphasize the need to identify and analyze conjugative systems outside of standard metagenomic binning pipelines. We suggest that analysis of type IV conjugative systems should be added to the current metagenomic analysis approaches as they contain much information that could explain differences between cohorts beyond those we investigated.

Randomized prospective trial assessing Bifidobacterium-containing probiotic supplementation in metastatic renal cell carcinoma (mRCC) patients receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5078-5078
Author(s):  
Nazli Dizman ◽  
Joann Hsu ◽  
Paulo Gustavo Bergerot ◽  
John D Gillece ◽  
Megan Folkerts ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Kinase Inhibitors ◽  
Randomized Study ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Metagenomic Sequencing ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing ◽  
Pre Treatment ◽  
Endothelial Growth Factor

5078 Background: Studies suggest a link between the gut microbiome and mRCC outcomes, including evidence that mRCC patients (pts) possess a lower abundance of Bifidobacterium spp compared to healthy adults (Pal et al Clin Cancer Res 2015). The aim of this study was to assess if Bifidobacterium-containing probiotics could modulate the gut microbiome and impact rates of clinical benefit (CB) from VEGF-TKIs. Methods: Pts initiating VEGF-TKI therapy for mRCC were randomized to probiotic supplemented (PSu) or probiotic restricted (PRe) treatment arms. Pts in the PSu arm consumed two 4 oz servings of Activia daily. Stool samples were collected prior to therapy and at wks 2, 3, 4 and 12. Gut microbiota composition was assessed using whole genome shotgun metagenomic sequencing (Zhu et al Microbiome 2018). The primary endpoint was change in Bifidobacterium spp with therapy. Microbiome composition was compared across pts with CB (complete/partial response or stable disease) versus no CB (NCB). Results: In total, 20 pts were enrolled. The most frequent VEGF-TKIs were cabozantinib (45%), sunitinib (25%) and lenvatinib (25%). Median progression-free survival (PFS) was 6.5 months (95%CI 0.3-12.9) and CB rate was 75%. Bifidobacterium animalis, the active ingredient of Activia, reached detectable levels in all pts in the PSu arm, but was only detectable in one pt in the PRe arm. CB rate was not significantly different in PSu vs PRe arms (70% vs 80%, p > 0.05), and there was no difference in PFS. LDA effect size (LEfSe) analysis of MetaPhIAn2 data captured 25 enriched species demonstrating an LDA score > 3 in either CB or NCB. Of those with high LDA scores, Barnesiella intesitinihominis and Akkermansia municiphila were the most significant members (p = 7.4 x 10−6 and p = 5.6 10−3, respectively). While 92% of B. intestinihominis positive pts obtained a CB, only 50% of B. intestinihominis negative pts obtained CB (p = 0.036). Conclusions: This is the first prospective randomized study demonstrating modulation of the gut microbiome with probiotics in mRCC. While microbiome modulation by probiotics did not increase CB rates as intended, consecutive stool specimens allowed us to identify an association between B. intesitinihominis, A. municiphila and CB with VEGF-TKIs. In addition to the previously documented association between A. municiphila and immunotherapy outcome (Routy et al. Science 2018), this species may predict activity with VEGF-TKIs. Clinical trial information: NCT02944617 .

Associations between plasma cytokine levels and gut microbiota composition in metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 351-351
Author(s):  
Alex Chehrazi-Raffle ◽  
Nazli Dizman ◽  
Paulo Gustavo Bergerot ◽  
Misagh Karimi ◽  
Joann Hsu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Kinase Inhibitor ◽  
Metagenomic Sequencing ◽  
Salmonella Spp ◽  
Microbial Composition ◽  
Protein Assay ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing ◽  
Cytokine Levels ◽  
Eligibility Requirements

351 Background: Plasma cytokines and the gut microbiome have been shown separately to influence the response to systemic therapy in mRCC. We sought associations between serum cytokines and gut microbial composition in patients (pts) with mRCC. Methods: Eligibility requirements included histologically proven mRCC and an intent to receive either vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) or immune checkpoint inhibitor (ICI). Blood samples were collected prior to treatment initiation and immunologic profiles were evaluated using a Human Cytokine 30-plex protein assay (Invitrogen). Stool was collected at baseline and shotgun metagenomic sequencing was performed to quantify gut microbial populations using previously published methods (Salgia et al Eur Urol 2020). Results: A total of 50 pts were studied (36:14 M:F) with a median age of 67 (range, 32-85). Twenty pts and 30 pts had subsequent initiation of VEGF-TKI and ICI therapy, respectively. Levels of Akkermansia spp were significantly higher in pts who were IL-6 low (P = 0.023). In contrast, pts who were IL-6 high had higher levels of enteric pathogens, including Salmonella spp and Enterococcus spp. Both Akkermansia spp and Bacteroides spp levels were higher in pts who were IL-8 low. Associations between cytokine levels, microbiome composition, and treatment response will be presented. Conclusions: Given studies suggesting the role of Akkermansia spp in enhancing ICI response (Routy et al Science 2018), our data provide a critical link between the gut microbiome and systemic immunomodulation.

scholarly journals Plasticity in the Human Gut Microbiome Defies Evolutionary Constraints

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Andres Gomez ◽  
Ashok Kumar Sharma ◽  
Elizabeth K. Mallott ◽  
Klara J. Petrzelkova ◽  
Carolyn A. Jost Robinson ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Evolutionary History ◽  
Taxonomic Composition ◽  
Primate Species ◽  
Human Populations ◽  
Human Gut ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Subsistence Patterns ◽  
Analysis Of Variation

ABSTRACT The gut microbiome of primates, including humans, is reported to closely follow host evolutionary history, with gut microbiome composition being specific to the genetic background of its primate host. However, the comparative models used to date have mainly included a limited set of closely related primates. To further understand the forces that shape the primate gut microbiome, with reference to human populations, we expanded the comparative analysis of variation among gut microbiome compositions and their primate hosts, including 9 different primate species and 4 human groups characterized by a diverse set of subsistence patterns (n = 448 samples). The results show that the taxonomic composition of the human gut microbiome, at the genus level, exhibits increased compositional plasticity. Specifically, we show unexpected similarities between African Old World monkeys that rely on eclectic foraging and human populations engaging in nonindustrial subsistence patterns; these similarities transcend host phylogenetic constraints. Thus, instead of following evolutionary trends that would make their microbiomes more similar to that of conspecifics or more phylogenetically similar apes, gut microbiome composition in humans from nonindustrial populations resembles that of generalist cercopithecine monkeys. We also document that wild cercopithecine monkeys with eclectic diets and humans following nonindustrial subsistence patterns harbor high gut microbiome diversity that is not only higher than that seen in humans engaging in industrialized lifestyles but also higher compared to wild primates that typically consume fiber-rich diets. IMPORTANCE The results of this study indicate a discordance between gut microbiome composition and evolutionary history in primates, calling into question previous notions about host genetic control of the primate gut microbiome. Microbiome similarities between humans consuming nonindustrialized diets and monkeys characterized by subsisting on eclectic, omnivorous diets also raise questions about the ecological and nutritional drivers shaping the human gut microbiome. Moreover, a more detailed understanding of the factors associated with gut microbiome plasticity in primates offers a framework to understand why humans following industrialized lifestyles have deviated from states thought to reflect human evolutionary history. The results also provide perspectives for developing therapeutic dietary manipulations that can reset configurations of the gut microbiome to potentially improve human health.

scholarly journals Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy upon microbiome composition

2019 ◽  
Vol 79 (1) ◽  
pp. 132-140 ◽  
Author(s):  
Jian Yin ◽  
Peter Richard Sternes ◽  
Mingbang Wang ◽  
Jing Song ◽  
Mark Morrison ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Metagenomic Sequencing ◽  
Healthy Controls ◽  
Hla B27 ◽  
Clinical Genetic ◽  
Shotgun Metagenomics ◽  
Microbiome Composition ◽  
Shotgun Metagenomic Sequencing

ObjectivesDiverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome.MethodsThe stools from a case–control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray.ResultsPrevious reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients.ConclusionThese findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

scholarly journals A unique and reliable fecal DNA extraction method for 16S rRNA gene and shotgun metagenomic sequencing in the analysis of the human gut microbiome

2020 ◽  
Author(s):  
Céline Elie ◽  
Magali Perret ◽  
Karen Louis ◽  
Asmaà Fritah-Lafont ◽  
Philippe Leissner ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Dna Extraction ◽  
Gut Microbiome ◽  
High Throughput Sequencing ◽  
Rrna Gene ◽  
Metagenomic Sequencing ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Shotgun Metagenomic Sequencing

Abstract Background: The gut microbiome is widely analyzed using high-throughput sequencing, such as 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing (SMS). DNA extraction is known to have a large impact on the metagenomic analyses. The aim of this study was to select a unique and best performing DNA extraction protocol for both metagenomic sequencing methods. In that context, four commonly used DNA extraction methods were compared for the analysis of the gut microbiota. Commercial versions were evaluated against modified protocols using a stool preprocessing device (SPD, bioMérieux) in order to facilitate DNA extraction. Stool samples from nine healthy volunteers and nine patients with a Clostridium difficile infection were extracted with all protocols and sequenced with both metagenomic methods. Protocols were ranked using wet- and dry-lab criteria, including quality controls of the extracted genomic DNA, alpha-diversity, accuracy using a mock community of known composition and repeatability across technical replicates.Results: Independently of the sequencing methods used, SPD significantly improved efficiency of the four tested protocols compared with their commercial version, in terms of extracted DNA quality, accuracy of the predicted composition of the microbiota (notably for Gram-positive bacteria), sample alpha-diversity, and experimental repeatability. The best overall performance was obtained for the S-DQ protocol, SPD combined to the DNeasy PowerLyser PowerSoil protocol from QIAGEN.Conclusion: Based on this evaluation, we recommend to use the S-DQ protocol, to obtain standardized and high quality extracted DNA in the human gut microbiome studies.

scholarly journals The Reactobiome Unravels a New Paradigm in Human Gut Microbiome Metabolism

2021 ◽  
Author(s):  
Gholamreza Bidkhori ◽  
Sunjae Lee ◽  
Lindsey A. Edwards ◽  
Emmanuelle Le Chatelier ◽  
Mathieu Almeida ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
New Paradigm ◽  
Human Gut ◽  
Metabolic Potential ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Environmental Interactions ◽  
Stratification Method ◽  
One Year ◽  
Computational Platform

AbstractChanges in microbial metabolism have been used as the main approach to assess function and elucidate environmental and host-microbiome interactions. This can be hampered by uncharacterised metagenome species and lack of metabolic annotation. To address this, we present a comprehensive computational platform for population stratification based on microbiome composition, the underlying metabolic potential and generation of metagenome species and community level metabolic models. We revisit the concepts of enterotype and microbiome richness introducing the reactobiome as a stratification method to unravel the metabolic features of the human gut microbiome. The reactobiome encapsulates resilience and microbiome dysbiosis at a functional level. We describe five reactotypes in healthy populations from 16 countries, with specific amino acid, carbohydrate and xenobiotic metabolic features. The validity of the approach was tested to unravel host-microbiome and environmental interactions by applying the reactobiome analysis on a one-year Swedish longitudinal cohort, integrating gut metagenomics, plasma metabolomics and clinical data.

scholarly journals Metagenomic analysis reveals the signature of gut microbiota associated with human chronotypes

2021 ◽  
Author(s):  
Shaqed Carasso ◽  
Bettina Fishman ◽  
Liel Stelmach Lask ◽  
Tamar Shochat ◽  
Naama Geva-Zatorsky ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Precision Medicine ◽  
Mood Disorders ◽  
Chronic Diseases ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Metagenomic Analysis ◽  
Metagenomic Sequencing ◽  
Diurnal Activity ◽  
Microbiome Composition

Patterns of diurnal activity differ substantially between individuals, with early risers and late sleepers being examples of extreme chronotypes. Growing evidence suggests that the late chronotype significantly impacts the risk of developing mood disorders, obesity, diabetes, and other chronic diseases. Despite the vast potential of utilizing chronotype information for precision medicine, the factors that shape chronotypes remain poorly understood. Here, we assessed whether chronotypes are associated with different gut microbiome composition. Using metagenomic sequencing, we established a distinct signature associated with chronotype that involves two bacterial genera Alistipes (elevated in "larks") and Lachnospira (elevated in "owls). We have identified four metabolic pathways (e.g. gluconegonesis) that were associated with early chronotype.

scholarly journals Taxonomic signatures of cause-specific mortality risk in human gut microbiome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aaro Salosensaari ◽  
Ville Laitinen ◽  
Aki S. Havulinna ◽  
Guillaume Meric ◽  
Susan Cheng ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Gut Microbiome ◽  
Human Gut ◽  
Cross Sectional ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Non Invasive ◽  
Sequencing Technologies

AbstractThe collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.

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