scholarly journals An online atlas of human plasma metabolite signatures of gut microbiome composition

Author(s):  
Koen F. Dekkers ◽  
Sergi Sayols-Baixeras ◽  
Gabriel Baldanzi ◽  
Christoph Nowak ◽  
Ulf Hammar ◽  
...  

The human gut microbiota produces a variety of small compounds, some of which enter the bloodstream and impact host health. Conversely, various exogenous nutritional and pharmaceutical compounds affect the gut microbiome composition before entering circulation. Characterization of the gut microbiota—host plasma metabolite interactions is an important step towards understanding the effects of the gut microbiota on human health. However, studies involving large and deeply phenotyped cohorts that would reveal such meaningful interactions are scarce. Here, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for detailed characterization of the fecal microbiota and plasma metabolome, respectively, of 8,584 participants invited at age 50 to 64 of the Swedish CArdioPulmonary bioImage Study (SCAPIS). After adjusting for multiple comparisons, we identified 1,008 associations between species alpha diversity and plasma metabolites, and 318,944 associations between specific gut metagenomic species and plasma metabolites. The gut microbiota explained up to 50% of the variance of individual plasma metabolites (mean of 4.7%). We present all results as the searchable association atlas "GUTSY" as a rich resource for mining associations, and exemplify the potential of the atlas by presenting novel associations between oral medication and the gut microbiome, and microbiota species strongly associated with levels of the uremic toxin p-cresol sulfate. The association atlas can be used as the basis for targeted studies of perturbation of specific bacteria and for identification of candidate plasma biomarkers of gut flora composition.

2018 ◽  
Vol 103 (4) ◽  
pp. 1491-1501 ◽  
Author(s):  
Filip Ottosson ◽  
Louise Brunkwall ◽  
Ulrika Ericson ◽  
Peter M Nilsson ◽  
Peter Almgren ◽  
...  

Abstract Context Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma metabolome might reflect differences in the gut microbiome. Objective To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota. Design Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography–mass spectrometry. Gut microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region) in fecal samples of 674 study participants. Results BMI was associated with 19 metabolites (P < 0.001 for all), of which glutamate provided the strongest direct association (P = 5.2e-53). By orthogonal partial least squares regression, a metabolite principal component predictive of BMI was constructed (PCBMI). In addition to glutamate, PCBMI was dominated by branched-chain amino acids (BCAAs) and related metabolites. Four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) were associated with both BMI and PCBMI (P < 8.0e-4 for all). When simultaneously regressing PCBMI and metabolite-associated gut bacteria against BMI, only PCBMI remained statistically significant. Conclusions We discovered associations between four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) and BMI-predictive plasma metabolites, including glutamate and BCAAs. Thus, these metabolites could be mediators between gut microbiota and obesity, pointing to potential future opportunities for targeting the gut microbiota in prevention of obesity.


2021 ◽  
Author(s):  
Shaqed Carasso ◽  
Bettina Fishman ◽  
Liel Stelmach Lask ◽  
Tamar Shochat ◽  
Naama Geva-Zatorsky ◽  
...  

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.


mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Ce Yuan ◽  
Michael B. Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.


mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.


2020 ◽  
Author(s):  
Caroline Ivanne Le Roy ◽  
Alexander Kurilshikov ◽  
Emily Leeming ◽  
Alessia Visconti ◽  
Ruth Bowyer ◽  
...  

Abstract Background: Yoghurt contains live bacteria that could contribute via modulation of the gut microbiota to its reported beneficial effects such as reduced body weight gain and lower incidence of type 2 diabetes. To date, the association between yoghurt consumption and the composition of the gut microbiota is underexplored. Here we used clinical variables, metabolomics, 16S rRNA and shotgun metagenomic sequencing data collected on over 1000 predominantly female UK twins to define the link between the gut microbiota and yoghurt-associated health benefits. Results: According to food frequency questionnaires (FFQ), 73% of subjects consumed yoghurt. Consumers presented a healthier diet pattern (healthy eating index: beta = 2.17±0.34; P = 2.72x10-10) and improved metabolic health characterised by reduced visceral fat (beta = -28.18±11.71 g; P = 0.01). According to 16S rRNA gene analyses and whole shotgun metagenomic sequencing approach consistent taxonomic variations were observed with yoghurt consumption. More specifically, we identified higher abundance of species used as yoghurt starters Streptococcus thermophilus (beta = 0.41±0.051; P = 6.14x10-12) and sometimes added Bifidobacterium animalis subsp. lactis (beta = 0.30±0.052; P = 1.49x10-8) in the gut of yoghurt consumers. Replication in 1103 volunteers from the LifeLines-DEEP cohort confirmed the increase of S. thermophilus among yoghurt consumers. Using food records collected the day prior to faecal sampling we showed that increase in these two yoghurt bacteria could be transient. Metabolomics analysis revealed that B. animalis subsp. lactis was associated with 13 faecal metabolites including a 3-hydroxyoctanoic acid, known to be involved in the regulation of gut inflammation.Conclusions: Yoghurt consumption is associated with reduced visceral fat mass and changes in gut microbiome including transient increase of yoghurt-contained species (i.e. S. thermophilus and B. lactis).


Gut ◽  
2021 ◽  
pp. gutjnl-2020-324015
Author(s):  
Yating Wan ◽  
Tao Zuo ◽  
Zhilu Xu ◽  
Fen Zhang ◽  
Hui Zhan ◽  
...  

ObjectiveThe gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD.DesignWe performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model.ResultsASD and chronological age had the most significant and largest impacts on children’s faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum.ConclusionsGut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1595-1595
Author(s):  
Sabrina Trudo ◽  
Rosa Moreno ◽  
Jeong Hoon Pan ◽  
Daniel Gallaher ◽  
Jae Kyeom Kim ◽  
...  

Abstract Objectives Cruciferous (CRU; rich in glucosinolates) and apiaceous (API; rich in furanocoumarins) vegetable intake decrease colon cancer risk markers, likely through different mechanisms. Previous reports suggest background diets influence efficacy of bioactives. Here, we determined the effects on the composition of the gut microbiome of CRU and API supplementation to different background diets, diet-induced obesity (DIO) and the total western diet (TWD). Methods C57BL/6J male mice were fed standard diet (AIN93G), DIO, DIO with 21% (w/w) CRU (DIO + CRU), DIO with 21% (w/w) API (DIO + API), TWD, TWD with CRU (TWD + CRU), or TWD with API (TWD + API). After 12 weeks, cecal contents were collected for 16S rRNA sequencing and data analyzed by mothur. Results There were no differences in body weight gain except mice fed DIO + CRU gained more than mice fed AIN-93G or TWD. Lachnospiraceae was increased by CRU supplementation to both DIO and TWD and by API supplementation to TWD. CRU increased alpha diversity [Shannon Index, number of observed Operational Taxonomic Unit (OTUs)] compared to DIO and TWD. Regarding beta diversity, DIO + CRU showed distinct cluster compared to DIO (Bray-Curtis, ANOSIM, R = 0.35, P &lt; 0.001; Jaccard distance, R = 0.47, P &lt; 0.001). TWD + CRU showed distinct cluster compared to TWD (Bray-Curtis, R = 0.59, P &lt; 0.001; Jaccard distance, R = 0.62, P &lt; 0.001). API did not change alpha diversity, but did affect beta diversities with distinct clusters between API groups and their basal diet groups (Jaccard distance, R = 0.36 and 0.31 for DIO and TWD, respectively, P &lt; 0.05). Among top 25 discriminating features between DIO and TWD and their supplementation of API and CRU, there were 9 shared OTUs including Lachnospiraceae, Clostridium XlVa, Clostridiales, Eisenbergiella, and Clostridium IV. Akkermansia were decreased in DIO + CRU compared with DIO. In TWD panel, Bifidobacterium and Erysipelotrichaceae decreased in TWD + CRU, while Turicibacter were identified as TWD + CRU signature. Erysipelotrichaceae and Bifidobacterium differentiated AIN-93G, DIO, and TWD. Conclusions CRU supplementation of DIO and TWD altered gut microbiome composition with some differences based on background diet. API also altered composition, albeit to a lesser extent. Funding Sources University of Arkansas, Fulbright Nicaragua Fellow.


Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 294 ◽  
Author(s):  
Anna Shmagel ◽  
Ryan Demmer ◽  
Daniel Knights ◽  
Mary Butler ◽  
Lisa Langsetmo ◽  
...  

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6658 ◽  
Author(s):  
Bing Zhang ◽  
Jing Ren ◽  
Daode Yang ◽  
Shuoran Liu ◽  
Xinguo Gong

Background The gut microbiota plays an important role in host immunity and metabolic homeostasis. Although analyses of gut microbiotas have been used to assess host health and foster disease prevention and treatment, no comparative comprehensive study, assessing gut microbiotas among several species of farmed snake, is yet available. In this study, we characterized and compared the gut microbiotas of four species of farmed snakes (Naja atra, Ptyas mucosa, Elaphe carinata, and Deinagkistrodon acutus) using high-throughput sequencing of the 16S rDNA gene in southern China and tested whether there was a relationship between gut microbiotal composition and host species. Results A total of 629 operational taxonomic units across 22 samples were detected. The five most abundant phyla were Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, and Actinobacteria, while the five most abundant genera were Bacteroides, Cetobacterium, Clostridium, Plesiomonas, and Paeniclostridium. This was the first report of the dominance of Fusobacteria and Cetobacterium in the snake gut. Our phylogenetic analysis recovered a relatively close relationship between Fusobacteria and Bacteroidetes. Alpha diversity analysis indicated that species richness and diversity were highest in the gut microbiota of D. acutus and lowest in that of E. carinata. Significant differences in alpha diversity were detected among the four farmed snake species. The gut microbiotas of conspecifics were more similar to each other than to those of heterospecifics. Conclusion This study provides the first comparative study of gut microbiotas among several species of farmed snakes, and provides valuable data for the management of farmed snakes. In farmed snakes, host species affected the species composition and diversity of the gut microbiota.


2020 ◽  
Vol 52 (7) ◽  
pp. 280-292 ◽  
Author(s):  
Katherine A. Maki ◽  
Larisa A. Burke ◽  
Michael W. Calik ◽  
Miki Watanabe-Chailland ◽  
Dagmar Sweeney ◽  
...  

The gut microbiota, via the production of metabolites entering the circulation, plays a role in blood pressure regulation. Blood pressure is also affected by the characteristics of sleep. To date, no studies have examined relationships among the gut microbiota/metabolites, blood pressure, and sleep. We hypothesized that fragmented sleep is associated with elevated mean arterial pressure, an altered and dysbiotic gut microbial community, and changes in fecal metabolites. In our model system, rats were randomized to 8 h of sleep fragmentation during the rest phase (light phase) or were undisturbed (controls) for 28 consecutive days. Rats underwent sleep and blood pressure recordings, and fecal samples were analyzed during: baseline ( days −4 to −1), early sleep fragmentation ( days 0–3), midsleep fragmentation ( days 6–13), late sleep fragmentation ( days 20–27), and recovery/rest ( days 28–34). Less sleep per hour during the sleep fragmentation period was associated with increased mean arterial pressure. Analyses of gut microbial communities and metabolites revealed that putative short chain fatty acid-producing bacteria were differentially abundant between control and intervention animals during mid-/late sleep fragmentation and recovery. Midsleep fragmentation was also characterized by lower alpha diversity, lower Firmicutes:Bacteroidetes ratio, and higher Proteobacteria in intervention rats. Elevated putative succinate-producing bacteria and acetate-producing bacteria were associated with lower and higher mean arterial pressure, respectively, and untargeted metabolomics analysis demonstrates that certain fecal metabolites are significantly correlated with blood pressure. These data reveal associations between sleep fragmentation, mean arterial pressure, and the gut microbiome/fecal metabolome and provide insight to links between disrupted sleep and cardiovascular pathology.


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