Comprehensive analysis of gut microbiota of a healthy population and covariates affecting microbial variation in two large Japanese cohorts

Abstract Background Inter-individual variations in gut microbiota composition are observed even among healthy populations. The gut microbiota may exhibit a unique composition depending on the country of origin and race of individuals. To comprehensively understand the link between healthy gut microbiota and host state, it is beneficial to conduct large-scale cohort studies. The aim of the present study was to elucidate the integrated and non-redundant factors associated with gut microbiota composition within the Japanese population by 16S rRNA sequencing of fecal samples and questionnaire-based covariate analysis. Results A total of 1596 healthy Japanese individuals participated in this study via two independent cohorts, NIBIOHN cohort (n = 954) and MORINAGA cohort (n = 642). Gut microbiota composition was described and the interaction of these microorganisms with metadata parameters such as anthropometric measurements, bowel habits, medical history, and lifestyle were obtained. Thirteen genera, including Alistipes, Anaerostipes, Bacteroides, Bifidobacterium, Blautia, Eubacterium halli group, Faecalibacterium, Fusicatenibacter, Lachnoclostridium, Parabacteroides, Prevotella_9, Roseburia, and Subdoligranulum were predominant among the two cohorts. On the basis of univariate analysis for overall microbiome variation, 18 matching variables exhibited significant association in both cohorts. A stepwise redundancy analysis revealed that there were four common covariates, Bristol Stool Scale (BSS) scores, gender, age, and defecation frequency, displaying non-redundant association with gut microbial variance. Conclusions We conducted a comprehensive analysis of gut microbiota in healthy Japanese individuals, based on two independent cohorts, and obtained reliable evidence that questionnaire-based covariates such as frequency of bowel movement and specific dietary habit affects the microbial composition of the gut. To our knowledge, this was the first study to investigate integrated and non-redundant factors associated with gut microbiota among Japanese populations.

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Comprehensive Analysis of Gut Microbiota of a Healthy Population and Covariates Affecting Microbial Variation in Two Large Japanese Cohorts

10.21203/rs.3.rs-89427/v1 ◽

2020 ◽

Author(s):

Jonguk Park ◽

Kumiko Kato ◽

Haruka Murakami ◽

Koji Hosomi ◽

Kumpei Tanisawa ◽

...

Keyword(s):

Gut Microbiota ◽

Large Scale ◽

Univariate Analysis ◽

Comprehensive Analysis ◽

Healthy Population ◽

Microbiota Composition ◽

Microbial Composition ◽

Factors Associated ◽

Japanese Cohort ◽

Gut Microbiota Composition

Abstract Background: Inter-individual variations in gut microbiota composition are observed even among healthy populations. As gut microbiota in Japanese populations exhibit a unique composition compared to others, it is informative to conduct large-scale Japanese cohort studies for a comprehensive understanding of the association between healthy gut microbiota and host status. The aim of the present study was to elucidate the integrated and non-redundant factors associated with gut microbiota composition within the Japanese population by 16S rRNA sequencing of fecal samples and questionnaire-based covariate analysis. Results: A total of 1,596 healthy Japanese individuals participated in this study via two independent cohorts, NIBIOHN cohort (n = 954) and MORINAGA cohort (n = 642). Gut microbiota composition was described and the interaction of these microorganisms with metadata parameters such as anthropometric measurements, bowel habits, medical history, and lifestyle were obtained. Thirteen genera, including Alistipes, Anaerostipes, Bacteroides, Bifidobacterium, Blautia, Eubacterium halli group, Faecalibacterium, Fusicatenibacter, Lachnoclostidium, Parabacteroides, Prevotella_9, Roseburia and Subdoligranurum were predominant among the two cohorts. On the basis of univariate analysis for overall microbiome variation, 18 matching variables exhibited significant association in both cohorts. A stepwise redundancy analysis revealed that there were four common covariates, Bristol Stool Scale (BSS) scores, gender, age, and defecation frequency, displaying non-redundant association with gut microbial variance.Conclusions: We conducted a comprehensive analysis of gut microbiota in healthy Japanese individuals, based on two independent cohorts, and obtained reliable evidence that questionnaire-based covariates such as frequency of bowel movement and dietary intake affects the microbial composition of the gut. To our knowledge, this was the first study to investigate integrated and non-redundant factors associated with gut microbiota among Japanese populations.

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Comprehensive Analysis of Gut Microbiota of A Healthy Population and Covariates Affecting Microbial Variation in Two Large Japanese Cohorts

10.21203/rs.3.rs-103500/v1 ◽

2020 ◽

Author(s):

Jonguk Park ◽

Kumiko Kato ◽

Haruka Murakami ◽

Koji Hosomi ◽

Kumpei Tanisawa ◽

...

Keyword(s):

Gut Microbiota ◽

Large Scale ◽

Univariate Analysis ◽

Comprehensive Analysis ◽

Healthy Population ◽

Microbiota Composition ◽

Microbial Composition ◽

Factors Associated ◽

Japanese Cohort ◽

Gut Microbiota Composition

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Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz075 ◽

2019 ◽

Vol 110 (2) ◽

pp. 316-329 ◽

Cited By ~ 15

Author(s):

Geoffrey Istas ◽

Eleanor Wood ◽

Melanie Le Sayec ◽

Claudia Rawlings ◽

Jeeyoung Yoon ◽

...

Keyword(s):

Gut Microbiota ◽

Vascular Function ◽

Cardiovascular Health ◽

Controlled Trial ◽

Healthy Population ◽

Microbiota Composition ◽

Double Blind ◽

Phenolic Metabolites ◽

Healthy Men ◽

Gut Microbiota Composition

ABSTRACT Background Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. Objectives The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. Methods A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. Results Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9% ± 0.4% (95% CI: 0.13%, 1.72%) and 1.2% ± 0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1% ± 0.3%, P = 0.003) and 12 wk later (1.5% ± 0.4%, P = 0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P = 0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P = 0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. Conclusions In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961.

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The gut microbiota profile of adults with kidney disease: A systematic review of the literature

10.21203/rs.2.10470/v1 ◽

2019 ◽

Author(s):

Jordan Stanford ◽

Karen Charlton ◽

Anita Stefoska-Needham ◽

Rukayat Ibrahim ◽

Kelly Lambert

Keyword(s):

Systematic Review ◽

Kidney Disease ◽

Gut Microbiota ◽

Cochrane Library ◽

Uremic Toxin ◽

Healthy Controls ◽

Microbiota Composition ◽

Dietary Intakes ◽

Microbial Composition ◽

Gut Microbiota Composition

Abstract Background There is mounting evidence that individuals with kidney disease have an abnormal gut microbiota composition. No studies to date have summarised the evidence to categorise how the gut microbiota profile of individuals with kidney disease may differ from healthy controls. Synthesis of this evidence is important to inform future clinical trials. This systematic review aims to characterise differences of the gut microbiota composition in adults with kidney disease, as well as to describe the functional capacity of the gut microbiota and reporting of diet as a confounder in these studies. Methods Included studies were those that investigated the gut microbial community in adults with any type of kidney disease and compared this to the profile of healthy controls. Six scientific databases (CINHAL, Medline, PubMed, Scopus, Web of Science, Cochrane Library) as well as selected grey literature sources were searched up until August 2018. Quality assessment was undertaken independently by three authors. The system of evidence level criteria was employed to quantitatively evaluate the alteration of microbiota by strictly considering the number, methodological quality and consistency of the findings. Additional findings relating to altered functions of the gut microbiota, dietary intakes and dietary methodologies used were qualitatively summarised. Results Sixteen articles, reporting 15 studies met the eligibility criteria and included a total of 540 adults with kidney disease and 1117 healthy controls. Compared to healthy controls, individuals with kidney disease had increased abundances of Enterobacteriaceae, and decreased abundances of Coprococcus and Prevotella. Adults with kidney stones also had an altered microbial composition with variations to Bacteroides, Lachnospiraceae NK4A136 group, Ruminiclostridium 5 group, Dorea, Enterobacter, Christensenellaceae and its genus Christensenellaceae R7 group. Altered microbial functions in adults with kidney disease were reported, particularly in the context of metabolic pathways relating to urea and uremic toxin generation. Only three of the 16 articles accounted for diet, and of these studies only two used a valid dietary assessment method. Conclusions The gut microbiota profile of adults with kidney disease differs from healthy controls. Future study designs should include adequate reporting of important confounders such as dietary intakes to assist with interpretation of findings.

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Leveraging host-genetics and gut microbiota to determine immunocompetence in pigs

Animal Microbiome ◽

10.1186/s42523-021-00138-9 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Yuliaxis Ramayo-Caldas ◽

Laura M. Zingaretti ◽

David Pérez-Pascual ◽

Pamela A. Alexandre ◽

Antonio Reverter ◽

...

Keyword(s):

Gut Microbiota ◽

Association Studies ◽

Host Genome ◽

Phenotypic Variance ◽

Microbiota Composition ◽

Microbial Composition ◽

Phagocytic Capacity ◽

Host Genetics ◽

Gut Microbiota Composition ◽

Variance Explained

Abstract Background The gut microbiota influences host performance playing a relevant role in homeostasis and function of the immune system. The aim of the present work was to identify microbial signatures linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs. Results To achieve this goal, we undertook a combination of network, mixed model and microbial-wide association studies (MWAS) for 21 immunity traits and the relative abundance of gut bacterial communities in 389 pigs genotyped for 70K SNPs. The heritability (h2; proportion of phenotypic variance explained by the host genetics) and microbiability (m2; proportion of variance explained by the microbial composition) showed similar values for most of the analyzed immunity traits, except for both IgM and IgG in plasma that was dominated by the host genetics, and the haptoglobin in serum which was the trait with larger m2 (0.275) compared to h2 (0.138). Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and revealed associations between pigs gut microbiota composition and 15 of the analyzed traits. The lymphocytes phagocytic capacity (quantified as mean fluorescence) and the total number of monocytes in blood were the traits associated with the largest number of taxa (6 taxa). Among the associations identified by MWAS, 30% were confirmed by an information theory network approach. The strongest confirmed associations were between Fibrobacter and phagocytic capacity of lymphocytes (r = 0.37), followed by correlations between Streptococcus and the percentage of phagocytic lymphocytes (r = -0.34) and between Megasphaera and serum concentration of haptoglobin (r = 0.26). In the interaction network, Streptococcus and percentage of phagocytic lymphocytes were the keystone bacterial and immune-trait, respectively. Conclusions Overall, our findings reveal an important connection between gut microbiota composition and immunity traits in pigs, and highlight the need to consider both sources of information, host genome and microbial levels, to accurately characterize immunocompetence in pigs.

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Dietary trans-10, cis-12-conjugated linoleic acid alters fatty acid metabolism and microbiota composition in mice

British Journal Of Nutrition ◽

10.1017/s0007114514004206 ◽

2015 ◽

Vol 113 (5) ◽

pp. 728-738 ◽

Cited By ~ 50

Author(s):

Tatiana M. Marques ◽

Rebecca Wall ◽

Orla O'Sullivan ◽

Gerald F. Fitzgerald ◽

Fergus Shanahan ◽

...

Keyword(s):

Lipid Metabolism ◽

Linoleic Acid ◽

Gut Microbiota ◽

Conjugated Linoleic Acid ◽

Control Group ◽

Standard Diet ◽

Microbiota Composition ◽

Microbial Composition ◽

16S Rrna Pyrosequencing ◽

Gut Microbiota Composition

The main aim of the present study was to investigate the effects of dietary trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) on intestinal microbiota composition and SCFA production. C57BL/6 mice (n 8 per group) were fed a standard diet either supplemented with t10c12-CLA (0·5 %, w/w) (intervention) or with no supplementation (control), daily for 8 weeks. Metabolic markers (serum glucose, leptin, insulin and TAG, and liver TAG) were assessed by ELISA commercial kits, tissue long-chain fatty acids and caecal SCFA by GC, and microbial composition by 16S rRNA pyrosequencing. Dietary t10c12-CLA significantly decreased visceral fat mass (P< 0·001), but did not affect body weight (intervention), when compared with no supplementation (control). Additionally, lipid mass and composition were affected by t10c12-CLA intake. Caecal acetate, propionate and isobutyrate concentrations were higher (P< 0·05) in the t10c12-CLA-supplemented group than in the control group. The analysis of the microbiota composition following 8 weeks of t10c12-CLA supplementation revealed lower proportions of Firmicutes (P= 0·003) and higher proportions of Bacteroidetes (P= 0·027) compared with no supplementation. Furthermore, t10c12-CLA supplementation for 8 weeks significantly altered the gut microbiota composition, harbouring higher proportions of Bacteroidetes, including Porphyromonadaceae bacteria previously linked with negative effects on lipid metabolism and induction of hepatic steatosis. These results indicate that the mechanism of dietary t10c12-CLA on lipid metabolism in mice may be, at least, partially mediated by alterations in gut microbiota composition and functionality.

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Differences in the Microbial Composition of Hemodialysis Patients Treated with and without β-Blockers

Journal of Personalized Medicine ◽

10.3390/jpm11030198 ◽

2021 ◽

Vol 11 (3) ◽

pp. 198

Author(s):

Yi-Ting Lin ◽

Ting-Yun Lin ◽

Szu-Chun Hung ◽

Po-Yu Liu ◽

Wei-Chun Hung ◽

...

Keyword(s):

Random Forest ◽

Gut Microbiota ◽

Hemodialysis Patients ◽

Microbiota Composition ◽

Microbial Composition ◽

Α Diversity ◽

Β Blocker ◽

Β Blockers ◽

The Impact ◽

Gut Microbiota Composition

β-blockers are commonly prescribed to treat cardiovascular disease in hemodialysis patients. Beyond the pharmacological effects, β-blockers have potential impacts on gut microbiota, but no study has investigated the effect in hemodialysis patients. Hence, we aim to investigate the gut microbiota composition difference between β-blocker users and nonusers in hemodialysis patients. Fecal samples collected from hemodialysis patients (83 β-blocker users and 110 nonusers) were determined by 16S ribosomal RNA amplification sequencing. Propensity score (PS) matching was performed to control confounders. The microbial composition differences were analyzed by the linear discriminant analysis effect size, random forest, and zero-inflated Gaussian fit model. The α-diversity (Simpson index) was greater in β-blocker users with a distinct β-diversity (Bray–Curtis Index) compared to nonusers in both full and PS-matched cohorts. There was a significant enrichment in the genus Flavonifractor in β-blocker users compared to nonusers in full and PS-matched cohorts. A similar finding was demonstrated in random forest analysis. In conclusion, hemodialysis patients using β-blockers had a different gut microbiota composition compared to nonusers. In particular, the Flavonifractor genus was increased with β-blocker treatment. Our findings highlight the impact of β-blockers on the gut microbiota in hemodialysis patients.

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Comprehensive Analysis Reveals Novel Interactions between Circulating MicroRNAs and Gut Microbiota Composition in Human Obesity

International Journal of Molecular Sciences ◽

10.3390/ijms21249509 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9509

Author(s):

Taís Silveira Assmann ◽

Amanda Cuevas-Sierra ◽

José Ignacio Riezu-Boj ◽

Fermín I. Milagro ◽

J. Alfredo Martínez

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Bacterial Species ◽

Comprehensive Analysis ◽

Microbiota Composition ◽

Human Obesity ◽

Bacterial Dna ◽

Circulating Micrornas ◽

Novel Interactions ◽

Gut Microbiota Composition

Background: The determinants that mediate the interactions between microRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this study was to investigate possible interactions between circulating microRNAs and gut microbiota composition in obesity. Method: The sample comprised 78 subjects with obesity (cases, body mass index (BMI): 30–40 kg/m2) and 25 eutrophic individuals (controls, BMI ≤ 25 kg/m2). The expression of 96 microRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels. Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR correction was used for multiple comparison analyses. Results: A total of 26 circulating microRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p and miR-21-5p) with Bacteroides eggerthi and BMI levels was evidenced (r2 = 0.148, p = 0.004). Moreover, these microRNAs regulate genes that participate in metabolism-related pathways, including fatty acid degradation, insulin signaling and glycerolipid metabolism. Conclusions: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating microRNAs in relation to obesity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts.

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Gut Microbiota Composition and Fecal Metabolic Profiling in Patients With Diabetic Retinopathy

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.732204 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zixi Zhou ◽

Zheng Zheng ◽

Xiaojing Xiong ◽

Xu Chen ◽

Jingying Peng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gut Microbiota ◽

Metabolic Phenotype ◽

Healthy Population ◽

Healthy Controls ◽

Microbiota Composition ◽

Gut Microbiota Composition

Recent evidence suggests there is a link between metabolic diseases and gut microbiota. To investigate the gut microbiota composition and fecal metabolic phenotype in diabetic retinopathy (DR) patients. DNA was extracted from 50 fecal samples (21 individuals with type 2 diabetes mellitus-associated retinopathy (DR), 14 with type 2 diabetes mellitus but without retinopathy (DM) and 15 sex- and age-matched healthy controls) and then sequenced by high-throughput 16S rDNA analysis. Liquid chromatography mass spectrometry (LC-MS)-based metabolomics was simultaneously performed on the samples. A significant difference in the gut microbiota composition was observed between the DR and healthy groups and between the DR and DM groups. At the genus level, Faecalibacterium, Roseburia, Lachnospira and Romboutsia were enriched in DR patients compared to healthy individuals, while Akkermansia was depleted. Compared to those in the DM patient group, five genera, including Prevotella, were enriched, and Bacillus, Veillonella, and Pantoea were depleted in DR patients. Fecal metabolites in DR patients significantly differed from those in the healthy population and DM patients. The levels of carnosine, succinate, nicotinic acid and niacinamide were significantly lower in DR patients than in healthy controls. Compared to those in DM patients, nine metabolites were enriched, and six were depleted in DR patients. KEGG annotation revealed 17 pathways with differentially abundant metabolites between DR patients and healthy controls, and only two pathways with differentially abundant metabolites were identified between DR and DM patients, namely, the arginine-proline and α-linolenic acid metabolic pathways. In a correlation analysis, armillaramide was found to be negatively associated with Prevotella and Subdoligranulum and positively associated with Bacillus. Traumatic acid was negatively correlated with Bacillus. Our study identified differential gut microbiota compositions and characteristic fecal metabolic phenotypes in DR patients compared with those in the healthy population and DM patients. Additionally, the gut microbiota composition and fecal metabolic phenotype were relevant. We speculated that the gut microbiota in DR patients may cause alterations in fecal metabolites, which may contribute to disease progression, providing a new direction for understanding DR.

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P162 CRITICAL ROLES OF DIETARY SIMPLE SUGARS IN COLITIS PATHOGENESIS

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.101 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S39-S40

Author(s):

Victoria Godfrey ◽

Hasan Zaki

Keyword(s):

Gut Microbiota ◽

Bacterial Species ◽

Western Diet ◽

Dietary Habit ◽

Rrna Gene ◽

Microbiota Composition ◽

Germ Free ◽

High Sugar ◽

Gut Microbiota Composition

Abstract The incidence of inflammatory bowel disease (IBD) is strikingly high in Western countries, implicating the role of Western diet in its etiology and pathogenesis. Western diet is characterized by high fat, low fiber, and high sugar. Despite clinical evidence of an association between high sugar diet and IBD susceptibility, the precise role of dietary simple sugars such as glucose, fructose, and sucrose in colitis pathogenesis is unknown. Using dextran sodium sulfate (DSS) and IL10-deficient mouse models of colitis, we studied the effect of simple sugars in colitis susceptibility. Mice were given high glucose, fructose or sucrose in their drinking water or left untreated before and during colitis induced by DSS. Sugar-fed mice exhibited increased colitis susceptibility evidenced by higher body weight loss, diarrhea, rectal bleeding, and severe histopathological changes in the colon as compared to those of sugar-untreated colitic mice. Pre-colitis dietary habit of sugar consumption was critical since sugar pretreated mice were susceptible to DSS-induced colitis even without high sugar diet intake during DSS administration. Consistent with these findings, there were higher incidence of spontaneous colitis development in Il10-/- mice following consumption of high sugar. To understand the underlying mechanism, we evaluated the effect of high sugar diet on intestinal epithelial cell death, inflammation, epithelial barrier permeability, and gut microbiota composition in healthy mice. We did not observe any major pathological changes and apoptosis in the colon of sugar-fed mice. Inflammatory responses, activation of inflammatory signaling pathways, and the expression of tight junction proteins were comparable between control and sugar-fed mice. Interestingly, gut microbiota composition of sugar-fed mice was altered as measured by 16S rRNA gene sequencing of DNA isolated from feces. Microbial species richness was reduced and relative abundance of several bacterial species was either increased or decreased in sugar-fed mice. We further confirmed that sugar-induced alteration of gut microbiota is responsible for exacerbated colitis by using antibiotics or germ-free mice. Mice receiving antibiotics during high-sugar intake did not show increased DSS-colitis susceptibility. Similarly, high-sugar diet did not induce overt colitis pathogenesis in germ-free mice. These findings demonstrate a critical role of dietary caloric sugars in the predisposition and promotion of colitis and could be implicated in the treatment and management of IBD.

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