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

Autor: Zouiouich S; Section of Nutrition and Metabolism, International Agency for Research on Cancer-WHO, Lyon, France. semi.zouiouich@nih.gov., Loftfield E; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Huybrechts I; Section of Nutrition and Metabolism, International Agency for Research on Cancer-WHO, Lyon, France., Viallon V; Section of Nutrition and Metabolism, International Agency for Research on Cancer-WHO, Lyon, France., Louca P; Department of Twin Research, King's College London, London, UK., Vogtmann E; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Wells PM; Department of Twin Research, King's College London, London, UK., Steves CJ; Department of Twin Research, King's College London, London, UK., Herzig KH; Research Unit of Biomedicine, Medical Research Center (MRC), University of Oulu, University Hospital, Oulu, Finland.; Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland., Menni C; Department of Twin Research, King's College London, London, UK., Jarvelin MR; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland.; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK., Sinha R; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Gunter MJ; Section of Nutrition and Metabolism, International Agency for Research on Cancer-WHO, Lyon, France.
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2021 Aug; Vol. 64 (8), pp. 1749-1759. Date of Electronic Publication: 2021 Jun 10.
DOI: 10.1007/s00125-021-05464-w
Abstrakt: 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), HbA 1c 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 HbA 1c (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 HbA 1c 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.
Databáze: MEDLINE
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