scholarly journals Markers of metabolic health and gut microbiome diversity: findings from two population-based cohort studies

Diabetologia ◽  
2021 ◽  
Author(s):  
Semi Zouiouich ◽  
Erikka Loftfield ◽  
Inge Huybrechts ◽  
Vivian Viallon ◽  
Panayiotis Louca ◽  
...  

Abstract Aims/hypothesis The gut microbiome is hypothesised to be related to insulin resistance and other metabolic variables. However, data from population-based studies are limited. We investigated associations between serologic measures of metabolic health and the gut microbiome in the Northern Finland Birth Cohort 1966 (NFBC1966) and the TwinsUK cohort. Methods Among 506 individuals from the NFBC1966 with available faecal microbiome (16S rRNA gene sequence) data, we estimated associations between gut microbiome diversity metrics and serologic levels of HOMA for insulin resistance (HOMA-IR), HbA1c and C-reactive protein (CRP) using multivariable linear regression models adjusted for sex, smoking status and BMI. Associations between gut microbiome diversity measures and HOMA-IR and CRP were replicated in 1140 adult participants from TwinsUK, with available faecal microbiome (16S rRNA gene sequence) data. For both cohorts, we used general linear models with a quasi-Poisson distribution and Microbiome Regression-based Kernel Association Test (MiRKAT) to estimate associations of metabolic variables with alpha- and beta diversity metrics, respectively, and generalised additive models for location scale and shape (GAMLSS) fitted with the zero-inflated beta distribution to identify taxa associated with the metabolic markers. Results In NFBC1966, alpha diversity was lower in individuals with higher HOMA-IR with a mean of 74.4 (95% CI 70.7, 78.3) amplicon sequence variants (ASVs) for the first quartile of HOMA-IR and 66.6 (95% CI 62.9, 70.4) for the fourth quartile of HOMA-IR. Alpha diversity was also lower with higher HbA1c (number of ASVs and Shannon’s diversity, p < 0.001 and p = 0.003, respectively) and higher CRP (number of ASVs, p = 0.025), even after adjustment for BMI and other potential confounders. In TwinsUK, alpha diversity measures were also lower among participants with higher measures of HOMA-IR and CRP. When considering beta diversity measures, we found that microbial community profiles were associated with HOMA-IR in NFBC1966 and TwinsUK, using multivariate MiRKAT models, with binomial deviance dissimilarity p values of <0.001. In GAMLSS models, the relative abundances of individual genera Prevotella and Blautia were associated with HOMA-IR in both cohorts. Conclusions/interpretation Overall, higher levels of HOMA-IR, CRP and HbA1c were associated with lower microbiome diversity in both the NFBC1966 and TwinsUK cohorts, even after adjustment for BMI and other variables. These results from two distinct population-based cohorts provide evidence for an association between metabolic variables and gut microbial diversity. Further experimental and mechanistic insights are now needed to provide understanding of the potential causal mechanisms that may link the gut microbiota with metabolic health. Graphical abstract

2020 ◽  
Author(s):  
Nicholas D. Youngblut ◽  
Jacobo de la Cuesta-Zuluaga ◽  
Ruth E. Ley

AbstractTree-based diversity measures incorporate phylogenetic or phenotypic relatedness into comparisons of microbial communities. This improves the identification of explanatory factors compared to tree-agnostic diversity measures. However, applying tree-based diversity measures to metagenome data is more challenging than for single-locus sequencing (e.g., 16S rRNA gene). The Genome Taxonomy Database (GTDB) provides a genome-based reference database that can be used for species-level metagenome profiling, and a multi-locus phylogeny of all genomes that can be employed for diversity calculations. Moreover, traits can be inferred from the genomic content of each representative, allowing for trait-based diversity measures. Still, it is unclear how metagenome-based assessments of microbiome diversity benefit from incorporating phylogeny or phenotype into measures of diversity. We assessed this by measuring phylogeny-based, trait-based, and tree-agnostic diversity measures from a large, global collection of human gut metagenomes composed of 33 studies and 3348 samples. We found phylogeny- and trait-based alpha diversity to better differentiate samples by westernization, age, and gender. PCoA ordinations of phylogeny- or trait-based weighted UniFrac explained more variance than tree-agnostic measures, which was largely a result of these measures emphasizing inter-phylum differences between Bacteroidaceae (Bacteroidota) and Enterobacteriaceae (Proteobacteria) versus just differences within Bacteroidaceae (Bacteroidota). The disease state of samples was better explained by tree-based weighted UniFrac, especially the presence of Shiga toxin-producing E. coli (STEC) and hypertension. Our findings show that metagenome diversity estimation benefits from incorporating a genome-derived phylogeny or traits.ImportanceEstimations of microbiome diversity are fundamental to understanding spatiotemporal changes of microbial communities and identifying which factors mediate such changes. Tree-based measures of diversity are widespread for amplicon-based microbiome studies due to their utility relative to tree-agnostic measures; however, tree-based measures are seldomly applied to shotgun metagenomics data. We evaluated the utility of phylogeny-, trait-, and tree-agnostic diversity measures on a large scale human gut metagenome dataset to help guide researchers with the complex task of evaluating microbiome diversity via metagenomics.


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2364 ◽  
Author(s):  
Xiaozhong Zhong ◽  
Janas M. Harrington ◽  
Seán R. Millar ◽  
Ivan J. Perry ◽  
Paul W. O’Toole ◽  
...  

Emerging evidence links the gut microbiota with several chronic diseases. However, the relationships between metabolic syndrome (MetS), obesity and the gut microbiome are inconsistent. This study aimed to investigate associations between gut microbiota composition and diversity and metabolic health status in older adults (n = 382; median age = 69.91 [± 5 years], male = 50.79%) with and without obesity. Gut microbiome composition was determined by sequencing 16S rRNA gene amplicons. Results showed that alpha diversity and richness, as indicated by the Chao1 index (p = 0.038), phylogenetic diversity (p = 0.003) and observed species (p = 0.038) were higher among the metabolically healthy non-obese (MHNO) individuals compared to their metabolically unhealthy non-obese (MUNO) counterparts. Beta diversity analysis revealed distinct differences between the MHNO and MUNO individuals on the phylogenetic distance scale (R2 = 0.007, p = 0.004). The main genera contributing to the gut composition among the non-obese individuals were Prevotella, unclassified Lachnospiraceae, and unclassified Ruminococcaceae. Prevotella, Blautia, Bacteroides, and unclassified Ruminococcaceae mainly contributed to the variation among the obese individuals. Co-occurrence network analysis displayed different modules pattern among different metabolic groups and revealed groups of microbes significantly correlated with individual metabolic health markers. These findings confirm relationships between metabolic health status and gut microbiota composition particularly, among non-obese older adults.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Kirsten Grond ◽  
Courtney C. Kurtz ◽  
Jasmine Hatton ◽  
Michelle M. Sonsalla ◽  
Khrystyne N. Duddleston

Abstract Background Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) are obligate hibernators and are only active 4–5 months annually. During this period, squirrels rapidly acquire fat for use during hibernation. We investigated how the gut microbiome changed over the active season in the mucosa and lumen of two gut sections: the cecum and ileum. We sequenced the 16S rRNA gene to assess diversity and composition of the squirrel gut microbiome and used differential abundance and network analyses to identify relationships among gut sections. Results Microbial composition significantly differed between the cecum and ileum, and within the ileum between the mucosa and lumen. Cecum mucosa and lumen samples did not differ in alpha diversity and composition, and clustered by individual squirrel. Ileum mucosa and lumen samples differed in community composition, which can likely be attributed to the transient nature of food-associated bacteria in the lumen. We did not detect a shift in microbiome diversity and overall composition over the duration of the active season, indicating that the squirrel microbiome may be relatively robust to changes in physiology. Conclusions Overall, we found that the 13-lined ground squirrel microbiome is shaped by microenvironment during the active season. Our results provide baseline data for new avenues of research, such as investigating potential differences in microbial function among these physiologically unique gut environments.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert C. Kaplan ◽  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Daniela Sotres-Alvarez ◽  
Martha L. Daviglus ◽  
...  

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.


2019 ◽  
Vol 3 (8) ◽  
Author(s):  
Jaapna Dhillon ◽  
Zhaoping Li ◽  
Rudy M Ortiz

ABSTRACT Background Changes in gut microbiota are associated with cardiometabolic disorders and are influenced by diet. Almonds are a rich source of fiber, unsaturated fats, and polyphenols, all nutrients that can favorably alter the gut microbiome. Objectives The aim of this study was to examine the effects of 8 wk of almond snacking on the gut (fecal) microbiome diversity and abundance compared with an isocaloric snack of graham crackers in college freshmen. Methods A randomized, controlled, parallel-arm, 8-wk intervention in 73 college freshmen (age: 18–19 y; 41 women and 32 men; BMI: 18–41 kg/m2) with no cardiometabolic disorders was conducted. Participants were randomly allocated to either an almond snack group (56.7 g/d; 364 kcal; n = 38) or graham cracker control group (77.5 g/d; 338 kcal/d; n = 35). Stool samples were collected at baseline and 8 wk after the intervention to assess primary microbiome outcomes, that is, gut microbiome diversity and abundance. Results Almond snacking resulted in 3% greater quantitative alpha-diversity (Shannon index) and 8% greater qualitative alpha-diversity (Chao1 index) than the cracker group after the intervention (P < 0.05). Moreover, almond snacking for 8 wk decreased the abundance of the pathogenic bacterium Bacteroides fragilis by 48% (overall relative abundance, P < 0.05). Permutational multivariate ANOVA showed significant time effects for the unweighted UniFrac distance and Bray–Curtis beta-diversity methods (P < 0.05; R2 ≤ 3.1%). The dietary and clinical variables that best correlated with the underlying bacterial community structure at week 8 of the intervention included dietary carbohydrate (percentage energy), dietary fiber (g), and fasting total and HDL cholesterol (model Spearman rho = 0.16; P = 0.01). Conclusions Almond snacking for 8 wk improved alpha-diversity compared with cracker snacking. Incorporating a morning snack in the dietary regimen of predominantly breakfast-skipping college freshmen improved the diversity and composition of the gut microbiome. This trial was registered at clinicaltrials.gov as NCT03084003.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Car Reen Kok ◽  
Bradford Brabec ◽  
Maciej Chichlowski ◽  
Cheryl Harris ◽  
Nancy Moore ◽  
...  

Abstract Objectives Infant feeding practices play a central role in development of gut microbiome and community structure. Our goal was to test the hypothesis that diets with intact or extensively hydrolyzed proteins or free amino acids may differentially affect the intestinal microbiota composition and immune reactivity. Methods This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota outcomes from Baseline (1-7 days of age) up to 60 days of age in healthy term infants. Infants received mother's own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: amino-acid based (AAF; n = 25) or extensively hydrolyzed cow's milk protein (EHF; n = 28). Neither study formula included added Lactobacillus rhamnosus GG. DNA was extracted (Baseline, Day 30, Day 60), 16S rRNA genes were amplified and sequenced (Illumina MiSeq), and exact amplicon sequence variants (ASV) were assigned using the DADA2 model. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis distance) and differential abundance in taxa were analyzed. Relative ASV enrichment (Baseline vs Day 60) was visualized using heat maps and taxa abundance was analyzed by DESEq2 in R (ver 3.4.3). Results Complete stool data (all study time points) were available for 49 participants. Baseline alpha diversity measures were similar among groups. The HM group remained stable throughout the study. However, alpha diversity measures by Day 60 were significantly higher for AAF and EHF groups compared to HM. Significant group differences in beta diversity at Day 60 were detected (P < 0.001); AAF and EHF clustered more closely compared to the HM group. Relative Bifidobacterium abundance increased over time and was significantly enriched at Day 60 in the HM group (Figure, A). At Day 60, a significant increase in members of Firmicutes was detected for AAF and EHF groups; a decrease in Enterobacteriaceae (Escherichia) was observed for EHF (Figure, B). Conclusions Distinct patterns of early neonatal microbiome establishment were demonstrated for infants receiving mother's own milk compared to amino acid-based or extensively hydrolyzed protein infant formulas. Providing different sources of dietary protein early in life may impact gut microbiome development. Funding Sources Mead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs


2019 ◽  
Vol 10 (7) ◽  
pp. 811-821
Author(s):  
J. Shibayama ◽  
M. Goto ◽  
T. Kuda ◽  
M. Fukunaga ◽  
H. Takahashi ◽  
...  

To clarify the effect of rice bran (RB) and fermented RB (FRB) in a high-sucrose and low-dietary fibre diet on the gut microbiome, the in vitro bile acid-lowering capacity and caecal microbiota of ICR mice fed with 20% RB or FRB diets for two weeks were determined. The caecal microbiome was analysed by 16S rRNA gene amplicon sequencing. The in vitro bile acid-lowering capacity was high for FRB. In mouse experiments, triacylglycerol and total cholesterol were generally lower with FRB, although the faecal frequency was highest in mice fed with RB. The Shannon-Wiener and Simpson’s indices for alpha-diversity in the microbiome of mice fed with RB and FRB, were higher than mice fed the control diet. At the phylum level in the caecal microbiome, Firmicutes and Bacteroidetes were high with FRB and RB, respectively. At the operational taxonomic unit level, some bacterial groups related to diabetes and gut toxicity, such as Lachnospiraceae and Enterorhabdus mucosicola, were high for RB but not for FRB diets. These results suggest that FRB, rather than RB, intake improve the intestinal environment and blood lipid condition.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Beatrice Kennedy ◽  
Sari Peura ◽  
Ulf Hammar ◽  
Silvia Vicenzi ◽  
Anna Hedman ◽  
...  

AbstractEarly life determinants of the oral microbiota have not been thoroughly elucidated. We studied the association of birth and early childhood characteristics with oral microbiota composition using 16 S ribosomal RNA (rRNA) gene sequencing in a population-based Swedish cohort of 59 children sampled at 6, 12 and 24 months of age. Repeated-measurement regression models adjusted for potential confounders confirmed and expanded previous knowledge about the profound shift of oral microbiota composition in early life. These alterations included increased alpha diversity, decreased beta diversity and alteration of bacterial composition with changes in relative abundance of 14 of the 20 most common operational taxonomic units (OTUs). We also found that birth characteristics, breastfeeding and antibiotic use were associated with overall phyla distribution and/or with the relative abundance of specific OTUs. Further, we detected a novel link between morning salivary cortisol level, a physiological marker of neuroendocrine activity and stress, and overall phyla distribution as well as with decreased abundance of the most common OTU mapped to the Streptococcaceae family. In conclusion, a major part of the maturation of the oral microbiome occurs during the first two years of life, and this development may be influenced by early life circumstances.


Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 569-577 ◽  
Author(s):  
Yiran Wei ◽  
Yanmei Li ◽  
Li Yan ◽  
Chunyan Sun ◽  
Qi Miao ◽  
...  

ObjectiveThe significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.DesignWe performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.ResultsThe gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.ConclusionOur study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sang Gil Lee ◽  
Cao Lei ◽  
Melissa Melough ◽  
Junichi Sakaki ◽  
Kendra Maas ◽  
...  

Abstract Objectives Blackcurrant, an anthocyanin-rich berry, has multiple health benefits. The purpose of this study was to examine the impacts of blackcurrant supplementation and aging on gut bacterial communities in female mice. Methods Three-month and 18-month old female mice were provided standard chow diets with or without anthocyanin-rich blackcurrant extract (BC) (1% w/w) for four months. Upon study completion, fecal samples were collected directly from the animals’ colons. Microbiome DNA was extracted from the fecal samples and the V3-V4 regions of their 16S rRNA gene were amplified and sequenced using Results Taxonomic analysis showed a significantly decrease in alpha diversity in aged female mice, compared to young counterparts. BC consumption did not alter the alpha diversity in either young or aged mice compared to control diets. For beta diversity, we observed the clustering was associated with age but not diet. The phylogenic abundance analysis showed that the relative abundance of several phyla, including Firmicutes, Bacteroidetes, Cyanobacteria, Proteobacteria, and Tenericutes was higher in aged compared to young mice. Among them, the abundance of Firmicutes was downregulated by BC in the young but not the aged mice. The abundance of Bacteroidetes was increased by BC in both the young and the aged groups. Noticeably, Verrucomicrobia was the only phylum whose relative abundance was upregulated in the aged female mice compared to the young mice. Meanwhile, its relative abundance in the aged group was suppressed by BC. Interestingly, Desulfovibrio, which is the most representative sulfate-reducing genus, was detectable only in young female mice, and BC increased its relative abundance. Conclusions Our results characterized the gut microbiome compositions in young and aged female mice, and indicated that the gut microbiome of young and aged female mice responded differently to four month BC administration. Through additional research, the microbial alterations observed in this study should be further investigated to inform our understanding of the effect of BC on the gut microbiome, the possible health benefits related to these changes, and the differing effects of BC supplementation across populations. Funding Sources This study was supported by the USDA NIFA Seed Grant (#2016-67018-24492) and the University of Connecticut Foundation Esperance Funds to Dr. Ock K. Chun. We thank the National Institute on Aging for providing aged mice for the project and Just the Berries Ltd. for providing the blackcurrant extract.


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