scholarly journals Almond Snacking for 8 wk Increases Alpha-Diversity of the Gastrointestinal Microbiome and Decreases Bacteroides fragilis Abundance Compared with an Isocaloric Snack in College Freshmen

2019 ◽  
Vol 3 (8) ◽  
Author(s):  
Jaapna Dhillon ◽  
Zhaoping Li ◽  
Rudy M Ortiz
Keyword(s):  
Gut Microbiome ◽  
College Freshmen ◽  
Bacteroides Fragilis ◽  
Alpha Diversity ◽  
Control Group ◽  
Dietary Regimen ◽  
Unifrac Distance ◽  
Fecal Microbiome ◽  
Microbiome Diversity ◽  
Cardiometabolic Disorders

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.

scholarly journals An interventional Soylent diet increases the Bacteroidetes to Firmicutes ratio in human gut microbiome communities: a randomized controlled trial

2017 ◽  
Author(s):  
Ryan H. Hsu ◽  
Dylan M. McCormick ◽  
Mitchell J. Seitz ◽  
Lauren M. Lui ◽  
Harneet S. Rishi ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Controlled Trial ◽  
Alpha Diversity ◽  
Diet Group ◽  
Positive Health ◽  
Unifrac Distance ◽  
Liquid Meal ◽  
Regular Diet ◽  
Rdna Sequencing

AbstractOur knowledge of the relationship between the gut microbiome and health has rapidly expanded in recent years. Diet has been shown to have causative effects on microbiome composition, which can have subsequent implications on health. Soylent 2.0 is a liquid meal replacement drink that satisfies nearly 20% of all recommended daily intakes per serving. This study aims to characterize the changes in gut microbiota composition resulting from a short-term Soylent diet. Fourteen participants were separated into two groups: 5 in the regular diet group and 9 in the Soylent diet group. The regular diet group maintained a diet closely resembling self-reported regular diets. The Soylent diet group underwent three dietary phases: A) a regular diet for 2 days, B) a Soylent-only diet (five servings of Soylent daily and water as needed) for 4 days, and C) a regular diet for 4 days. Daily logs self-reporting diet, Bristol stool ratings, and any abdominal discomfort were electronically submitted. Eight fecal samples per participant were collected using fecal sampling kits, which were subsequently sent to uBiome, Inc. for sample processing and V4 16S rDNA sequencing. Reads were clustered into operational taxonomic units (OTUs) and taxonomically identified against the GreenGenes 16S database. We find that an individual’s alpha-diversity is not significantly altered during a Soylent-only diet. In addition, principal coordinate analysis using the unweighted UniFrac distance metric shows samples cluster strongly by individual and not by dietary phase. Among Soylent dieters, we find a significant increase in the ratio of Bacteroidetes to Firmicutes abundance, which is associated with several positive health outcomes, including reduced risks of obesity and intestinal inflammation.

scholarly journals Simulated manned Mars exploration: effects of dietary and diurnal cycle variations on the gut microbiome of crew members in a controlled ecological life support system

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7762 ◽  
Author(s):  
Hai-Sheng Dong ◽  
Pu Chen ◽  
Yan-Bo Yu ◽  
Peng Zang ◽  
Zhao Wei
Keyword(s):  
Support System ◽  
Gut Microbiome ◽  
Large Scale ◽  
Life Support ◽  
Alpha Diversity ◽  
Life Support System ◽  
Fecal Microbiome ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

Background Changes in gut microbiome are closely related to dietary and environment variations, and diurnal circle interventions impact on human metabolism and the microbiome. Changes in human gut microbiome and serum biochemical parameters during long-term isolation in a controlled ecological life support system (CELSS) are of great significance for maintaining the health of crewmembers. The Green Star 180 project performed an integrated study involving a four-person, 180-day duration assessment in a CELSS, during which variations in gut microbiome and the concentration of serum 25-hydroxyvitamin D, α-tocopherol, retinol and folic acid from the crewmembers were determined. Results Energy intake and body mass index decreased during the experiment. A trade-off between Firmicutes and Bacteroidetes during the study period was observed. Dynamic variations in the two dominant genus Bacteroides and Prevotella indicated a variation of enterotypes. Both the evenness and richness of the fecal microbiome decreased during the isolation in the CELSS. Transition of diurnal circle from Earth to Mars increased the abundance of Fusobacteria phylum and decreased alpha diversity of the fecal microbiome. The levels of serum 25-hydroxyvitamin D in the CELSS were significantly lower than those outside the CELSS. Conclusions The unique isolation process in the CELSS led to a loss of alpha diversity and a transition of enterotypes between Bacteroides and Prevotella. Attention should therefore be paid to the transition of the diurnal circle and its effects on the gut microbiome during manned Mars explorations. In particular, serum 25-hydroxyvitamin D levels require monitoring under artificial light environments and during long-term space flight. Large-scale studies are required to further consolidate our findings.

scholarly journals APOE Genetics Influence Murine Gut Microbiome

2021 ◽  
Author(s):  
Diana J. Zajac ◽  
Stefan J. Green ◽  
Lance A. Johnson ◽  
Steven Estus
Keyword(s):  
Gut Microbiome ◽  
Beta Diversity ◽  
Univariate Analysis ◽  
Microbial Community Composition ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Linear Discriminant ◽  
Fecal Microbiome ◽  
Female Mice ◽  
The Impact

Abstract Background: Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we tested whether these results are confirmed by using mice that were maintained under ideal conditions for microbiome analyses. Methods: To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, APOE3 mice were crossed to APOE2 or APOE4 mice prior to the study, and the resulting heterozygous progeny crossed further to generate the study mice. To maximize environmental homogeneity, mice with mixed genotypes were housed together and used bedding from the cages was mixed and added back as a portion of new bedding. Fecal samples were obtained from mice at three-, five- and seven-months of age, and microbiota analyzed by 16S ribosomal RNA gene amplicon sequencing. APOE2/E2 and APOE2/E3 mice were categorized as APOE2, APOE3/E4 and APOE4/E4 mice were categorized as APOE4, and APOE3/E3 mice were categorized as APOE3. Linear discriminant analysis of Effect Size (LefSe) identified taxa associated with APOE status, depicted as cladograms to show phylogenetic relatedness. The influence of APOE status was tested onalpha-diversity (Shannon H index) and beta-diversity (principal coordinate analyses and PERMANOVA). Individual taxa associated with APOE status were identified by classical univariate analysis. Whether findings in the APOE mice were replicated in humans was evaluated by using published microbiome genome wide association data. Results: Cladograms revealed robust differences with APOE in male mice and limited differences in female mice. The richness and evenness (alpha-diversity) and microbial community composition (beta-diversity) of the fecal microbiome was robustly associated with APOE status in male but not female mice. Classical univariate analysis revealed individual taxa that were significantly increased or decreased with APOE, illustrating a stepwise APOE2-APOE3-APOE4 pattern of association. The Clostridia class, Clostridiales order, Ruminococacceae family and related genera increased with APOE2 status. The Erysipelotrichia phylogenetic branch increased with APOE4 status, a finding that extended to humans.Conclusions: In this study wherein mice were maintained in an ideal fashion for microbiome studies, gut microbiome profiles were strongly and significantly associated with APOE status in male APOE-TR mice. Erysipelotrichia in particular appears to increase with APOE4 in both mice and humans. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on disease-relevant phenotypes, will be necessary to determine if alterations in the gut microbiome represents a novel mechanism whereby APOE alleles impact disease.

scholarly journals Supplementation of Geranylgeraniol and Tocotrienols to High-Fat Diet Shifts the Gut Microbiome Composition and Function in Type 2 Diabetic Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 393-393
Author(s):  
Moamen Elmassry ◽  
Eunhee Chung ◽  
Abdul Hamood ◽  
Chwan-Li Shen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Alpha Diversity ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Microbiome Composition ◽  
And Function

Abstract Objectives In recent years, characterization of gut microbiota composition and function were linked to the progression of type 2 diabetes mellitus. Recent evidence showed that Geranylgeraniol, an isoprenoid found in fruits, vegetables, and grains, improves glucose homeostasis. Similarly, Tocotrienols, a subfamily of vitamin E, also contains anti-diabetic properties. In this study, we examined the combined effect of geranylgeraniol and tocotrienols on the composition and function of gut microbiome in obese male mice. Methods Forty male C57BL/6J mice were assigned to 4 groups in a factorial design as follows: high-fat diet (HFD) (control group), HFD + geranylgeraniol [400 mg/kg diet] (GG group), HFD + tocotrienols [400 mg/kg diet] (TT group), and HFD + geranylgeraniol + tocotrienols (G + T group) for 14 weeks. 16S rRNA gene sequencing was done from cecal samples and microbiome and data analysis was performed with QIIME2 and PICRUSt2. Results Across all groups, the most abundant phyla were Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. There was no difference in alpha diversity among different groups. Different treatments influenced the relative abundance of certain bacteria. In the Bacteroidetes phylum, the relative abundance of family S24–7 increased in the TT group only. In the Firmicutes phylum, the relative abundance of family Lachnospiraceae was reduced upon the supplementation of geranylgeraniol or tocotrienols; individually or in combination. In Verrucomicrobia phylum, Akkermansia muciniphila relative abundance was reduced in the TT group but increased in the G + T group. The results of functional profiling of the gut microbiome revealed that geranylgeraniol supplementation caused an increase in the proportion of biosynthetic pathways related to purine, pyrimidine, and inosine-5’-phosphate and hexitol fermentation, and a decrease in the proportion of pathways involved in the biosynthesis of isoleucine, valine, histidine, arginine, and chorismate. The G + T group increased pathways related to thiamine diphosphate biosynthesis, and decreased others involved into sulfur oxidation and methylerythritol phosphate. Conclusions The influence of geranylgeraniol and tocotrienols supplementation on gut microbiome composition and function, suggests a prebiotic potential for the potential of geranylgeraniol and tocotrienols. Funding Sources American River Nutrition, LLC, Hadley, MA.

scholarly journals Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients

Science ◽  
2017 ◽  
Vol 359 (6371) ◽  
pp. 97-103 ◽  
Author(s):  
V. Gopalakrishnan ◽  
C. N. Spencer ◽  
L. Nezi ◽  
A. Reuben ◽  
M. C. Andrews ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Human Cancer ◽  
Alpha Diversity ◽  
Fecal Microbiome ◽  
Functional Differences ◽  
Programmed Cell Death 1 ◽  
Melanoma Patients ◽  
Immune Profiling

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti–programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

scholarly journals A Comprehensive Assessment of Demographic, Environmental and Host Genetic Associations with Gut Microbiome Diversity in Healthy Individuals

2019 ◽  
Author(s):  
Petar Scepanovic ◽  
Flavia Hodel ◽  
Stanislas Mondot ◽  
Valentin Partula ◽  
Allyson Byrd ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Gut Microbiome ◽  
Genetic Factors ◽  
European Ancestry ◽  
Healthy Individuals ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Microbiome Diversity ◽  
Α Diversity ◽  
Host Genetic

ABSTRACTBackgroundThe gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1,000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20 – 69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.ResultsAmong 110 demographic, clinical and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between >5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics.ConclusionIn a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals.

scholarly journals Covariation of the Fecal Microbiome with Diet in Nonpasserine Birds

mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Kangpeng Xiao ◽  
Yutan Fan ◽  
Zhipeng Zhang ◽  
Xuejuan Shen ◽  
Xiaobing Li ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Dietary Diversity ◽  
Basal Diet ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Future Health ◽  
Amino Acid Synthesis ◽  
Fecal Samples ◽  
Fecal Microbiome ◽  
Microbiome Diversity

ABSTRACT Opportunistic feeding and multiple other environment factors can modulate the gut microbiome, and bias conclusions, when wild animals are used for studying the influence of phylogeny and diet on their gut microbiomes. Here, we controlled for these other confounding factors in our investigation of the magnitude of the effect of diet on the gut microbiome assemblies of nonpasserine birds. We collected fecal samples, at one point in time, from 35 species of birds in a single zoo as well as 6 species of domestic poultry from farms in Guangzhou city to minimize the influences from interfering factors. Specifically, we describe 16S rRNA amplicon data from 129 fecal samples obtained from 41 species of birds, with additional shotgun metagenomic sequencing data generated from 16 of these individuals. Our data show that diets containing native starch increase the abundance of Lactobacillus in the gut microbiome, while those containing plant-derived fiber mainly enrich the level of Clostridium. Greater numbers of Fusobacteria and Proteobacteria are detected in carnivorous birds, while in birds fed a commercial corn-soybean basal diet, a stronger inner-connected microbial community containing Clostridia and Bacteroidia was enriched. Furthermore, the metagenome functions of the microbes (such as lipid metabolism and amino acid synthesis) were adapted to the different food types to achieve a beneficial state for the host. In conclusion, the covariation of diet and gut microbiome identified in our study demonstrates a modulation of the gut microbiome by dietary diversity and helps us better understand how birds live based on diet-microbiome-host interactions. IMPORTANCE Our study identified food source, rather than host phylogeny, as the main factor modulating the gut microbiome diversity of nonpasserine birds, after minimizing the effects of other complex interfering factors such as weather, season, and geography. Adaptive evolution of microbes to food types formed a dietary-microbiome-host interaction reciprocal state. The covariation of diet and gut microbiome, including the response of microbiota assembly to diet in structure and function, is important for health and nutrition in animals. Our findings help resolve the major modulators of gut microbiome diversity in nonpasserine birds, which had not previously been well studied. The diet-microbe interactions and cooccurrence patterns identified in our study may be of special interest for future health assessment and conservation in birds.

scholarly journals Gut Microbiome Composition and Metabolomic Profiles of Wild and Captive Chinese Monals (Lophophorus Lhuysii)

2020 ◽  
Author(s):  
Dandan Jiang ◽  
Xin He ◽  
Marc Valitutto ◽  
Li Chen ◽  
Qin Xu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Bacterial Species ◽  
Bird Species ◽  
Alpha Diversity ◽  
Integrated Approach ◽  
Rrna Gene ◽  
Metabolomic Profile ◽  
Liquid Chromatograph ◽  
Fecal Microbiome ◽  
Microbiome Composition

Abstract Background：The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains of southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolomics of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal rRNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatograph (UHPLC) based metabolomics were used to examine the fecal microbiome composition and the metabolomic profile of Chinese monals. Results: The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial species in the two groups showed remarkable differences at all levels. Metabolomic profiling revealed a concurrent difference, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, these metabolites in difference are have a strong correlation with the main microbe in genus level.Conclusions: Various factors related to diet and environmental conditions played a crucial role in shaping the gut microbiome composition and metabolomic profile. Through this study, we have established a baseline for a normal gut microbiome and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive specimens has an impact on their overall health and reproduction.

scholarly journals A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals

Microbiome ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Petar Scepanovic ◽  
◽  
Flavia Hodel ◽  
Stanislas Mondot ◽  
Valentin Partula ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Gut Microbiome ◽  
Genetic Factors ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Microbiome Diversity ◽  
Host Genetic

Abstract Background The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20–69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition. Results Among 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics. Conclusion In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals. Trial registration ClinicalTrials.gov identifier NCT01699893

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 ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Sequence Data ◽  
Alpha Diversity ◽  
Population Based ◽  
Metabolic Health ◽  
Rrna Gene ◽  
Diversity Measures ◽  
Microbiome Diversity ◽  
Metabolic Variables ◽  
Faecal Microbiome

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

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