ObjectiveThe human gut microbiota plays important roles in human health but is also known to be highly diverse between populations from different regions. Yet most studies inadequately account for ...this regional diversity in their analyses. This study examines the extent to which geographical variation can act as a confounding variable for studies that associate the microbiota with human phenotypic variation.DesignPopulation-based study.SettingChina.Participants2164 participants from 15 province-level divisions in China.Primary and secondary outcome measuresWe analysed the impact of geographic location on associations between the human gut microbiota and 72 host factors representing a wide variety of environmental-level, household-level and individual-level factors.ResultsWhile the gut microbiota varied across a wide range of host factors including urbanisation, occupation and dietary variables, the geographic region (province/megacity) of the participants explained the largest proportion of the variance (17.9%). The estimated effect sizes for other host factors varied substantially by region with little evidence of a reproducible signal across different areas as measured by permutational multivariate analysis of variance and random forest models.ConclusionsOur results suggest that geographic variation is an essential factor that should be explicitly considered when generalising microbiota-based models to host phenotype across different populations.
Animal studies have revealed gut microbial and metabolic pathways of blood pressure (BP) regulation, yet few epidemiological studies have collected microbiota and metabolomics data in the same ...individuals. In a population-based, Chinese cohort who did not report antihypertension medication use (30-69 years, 54% women), thus minimizing BP treatment effects, we examined multivariable-adjusted (eg, diet, physical activity, smoking, kidney function), cross-sectional associations between measures of gut microbiota (16S rRNA ribosomal ribonucleic acid, N=1003), and plasma metabolome (liquid chromatography-mass spectrometry, N=434) with systolic (SBP, mean SD=126.0 17.4 mm Hg) and diastolic BP (DBP 80.7 (10.7) mm Hg). We found that the overall microbial community assessed by principal coordinate analysis varied by SBP and DBP (permutational multivariate ANOVA
<0.05). To account for strong correlations across metabolites, we first examined metabolite patterns derived from principal component analysis and found that a lipid pattern was positively associated with SBP (linear regression coefficient 95% CI per 1 SD pattern score: 2.23 0.72-3.74 mm Hg) and DBP (1.72 0.81-2.63 mm Hg). Among 1104 individual metabolites, 34 and 39 metabolites were positively associated with SBP and DBP (false discovery rate-adjusted linear model
<0.05), respectively, including linoleate, palmitate, dihomolinolenate, 8 sphingomyelins, 4 acyl-carnitines, and 2 phosphatidylinositols. Subsequent pathway analysis showed that metabolic pathways of long-chain saturated acylcarnitine, phosphatidylinositol, and sphingomyelins were associated with SBP and DBP (false discovery rate-adjusted Fisher exact test
<0.05). Our results suggest potential roles of microbiota and metabolites in BP regulation to be followed up in prospective and clinical studies.
Background
The aim of the study was to investigate the role of the gut microbiota in weight regain or suboptimal weight loss following Roux-en-Y gastric bypass (RYGB).
Materials and Methods
The gut ...microbiota composition in post-RYGB patients who experienced successful weight loss (SWL,
n
= 6), post-RYGB patients who experienced poor weight loss (PWL,
n
= 6), and non-surgical controls (NSC,
n
= 6) who were age- and BMI-matched to the SWL group (NSC,
n
= 6) were characterized through 16S rRNA gene sequencing. To further investigate the impact of the gut microbiota on weight profile, human fecal samples were transplanted into antibiotic-treated mice.
Results
Orders of Micrococcales and Lactobacillales were enriched in SWL and PWL groups compared to the NSC group. No significant difference was observed in the gut microbiota composition between PWL and SWL patients. However, transfer of the gut microbiota from human patients into antibiotic-treated mice resulted in significantly greater weight gain in PWL recipient mice compared to SWL recipient mice. A few genera that were effectively transferred from humans to mice were associated with weight gain in mice. Among them,
Barnesiella
was significantly higher in PWL recipient mice compared to SWL and NSC recipient mice.
Conclusion
These results indicate that the gut microbiota are at least functionally, if not compositionally, different between PWL and SWL patients. Some taxa may contribute to weight gain after surgery. Future studies will need to determine the molecular mechanisms behind the effects of the gut bacteria on weight regain after RYGB.
Epidemiological studies suggest a positive association between obesity and fecal short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary carbohydrates, while animal models ...suggest increased energy harvest through colonic SCFA production in obesity. However, there is a lack of human population-based studies with dietary intake data, plasma SCFAs, gut microbial, and anthropometric data. In 490 Chinese adults aged 30-68 years, we examined the associations between key plasma SCFAs (butyrate/isobutyrate, isovalerate, and valerate measured by non-targeted plasma metabolomics) with body mass index (BMI) using multivariable-adjusted linear regression. We then assessed whether overweight (BMI ≥ 24 kg/m
) modified the association between dietary-precursors of SCFAs (insoluble fiber, total carbohydrates, and high-fiber foods) with plasma SCFAs. In a sub-sample (
= 209) with gut metagenome data, we examined the association between gut microbial SCFA-producers with BMI. We found positive associations between butyrate/isobutyrate and BMI (
-value < 0.05). The associations between insoluble fiber and butyrate/isobutyrate differed by overweight (
-value < 0.10). There was no statistical evidence for an association between microbial SCFA-producers and BMI. In sum, plasma SCFAs were positively associated with BMI and that the colonic fermentation of fiber may differ for adults with versus without overweight.
Introduction
Urbanization is associated with major changes in environmental and lifestyle exposures that may influence metabolic signatures.
Objectives
We investigated cross-sectional urban and rural ...differences in plasma metabolome analyzed by liquid chromatography/mass spectrometry platform in 500 Chinese adults aged 25–68 years from two neighboring southern Chinese provinces.
Methods
We first examined the overall metabolome differences by urban and rural residential location, using Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) and random forest classification. We then tested the association between urbanization status and individual metabolites using a linear regression adjusting for age, sex, and province and conducted pathway analysis (Fisher’s exact test) to identify metabolic pathways differed by urbanization status.
Results
We observed distinct overall metabolome by urbanization status in OPLS-DA and random forest classification. Using linear regression, out of a total of 1108 unique metabolite features identified in this sample, we found that 266 metabolites were differed by urbanization status (positive false discovery rate-adjusted p-value, q-value < 0.05). For example, the following metabolites were positively associated with urbanization status: caffeine metabolites from xanthine metabolism, hazardous pollutants like 4-hydroxychlorothalonil and perfluorooctanesulfonate, and metabolites implicated in cardiometabolic diseases, such as branched-chain amino acids. In pathway analysis, we found that xanthine metabolism pathways differed by urbanization status (q-value = 1.64E−04).
Conclusion
We detected profound differences in host metabolites by urbanization status. Urban residents were characterized by metabolites signaling caffeine metabolism and toxic pollutants and metabolites on known pathways to cardiometabolic disease risks, compared to their rural counterparts. Our findings highlight the importance of considering urbanization in metabolomics analysis.
Anorexia nervosa, a severe psychiatric illness, is associated with an intestinal microbial dysbiosis. Individual microbial signatures dominate in healthy samples, even over time and under controlled ...conditions, but whether microbial markers of the disorder overcome inter-individual variation during the acute stage of illness or renourishment is unknown. We characterized daily changes in the intestinal microbiota in three acutely ill patients with anorexia nervosa over the entire course of hospital-based renourishment and found significant, patient-specific changes in microbial composition and diversity. Even in a state of pathology, individual microbial signatures persist in accounting for the majority of intestinal microbial variation.
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