University of Oulu

Zouiouich, S., Loftfield, E., Huybrechts, I. et al. Markers of metabolic health and gut microbiome diversity: findings from two population-based cohort studies. Diabetologia 64, 1749–1759 (2021).

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

Saved in:
Author: Zouiouich, Semi1; Loftfield, Erikka2; Huybrechts, Inge1;
Organizations: 1Section of Nutrition and Metabolism, International Agency for Research on Cancer-WHO, Lyon, France
2Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
3Department of Twin Research, King’s College London, London, UK
4Research Unit of Biomedicine, Medical Research Center (MRC), University of Oulu, University Hospital, Oulu, Finland
5Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland
6Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
7Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
8Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland
9Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link:
Language: English
Published: Springer Nature, 2021
Publish Date: 2021-10-12


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.

see all

Series: Diabetologia
ISSN: 0012-186X
ISSN-E: 1432-0428
ISSN-L: 0012-186X
Volume: 64
Issue: 8
Pages: 1749 - 1759
DOI: 10.1007/s00125-021-05464-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
3111 Biomedicine
Funding: This work was supported by the International Agency for Research on Cancer, WHO, France and the National Cancer Institute, USA.
Copyright information: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit