Gut bacteria Akkermansia is associated with reduced risk of obesity: evidence from the American Gut Project

Qi Zhou, Yanfeng Zhang, Xiaoxia Wang, Ruiyue Yang, Xiaoquan Zhu, Ying Zhang, Chen Chen, Huiping Yuan, Ze Yang, Liang Sun, Qi Zhou, Yanfeng Zhang, Xiaoxia Wang, Ruiyue Yang, Xiaoquan Zhu, Ying Zhang, Chen Chen, Huiping Yuan, Ze Yang, Liang Sun

Abstract

Background: Gut bacteria Akkermansia has been shown an anti-obesity protective effect in previous studies and may be used as promising probiotics. However, the above effect may be confounded by common factors, such as sex, age and diets, which should be verified in a generalized population.

Methods: We used datasets from the American Gut Project to strictly reassess the association and further examined the effect of aging on it. A total of 10,534 participants aged 20 to 99 years from the United States and the United Kingdom were included. The relative abundance of Akkermansia was assessed based on 16S rRNA sequencing data. Obesity (body mass index, BMI ≥ 30 kg/m2) risks were compared across Akkermansia quintiles in logistic models with adjustment for common confounders. Restricted cubic splines were used to examine dose response effects between Akkermansia, obesity and age. A sliding-windows-based algorithm was used to investigate the effect of aging on Akkermansia-obesity associations.

Results: The median abundance of Akkermansia was 0.08% (interquartile range: 0.006-0.93%), and the prevalence of obesity was 11.03%. Nonlinear association was detected between Akkermansia and obesity risk (P = 0.01). The odds ratios (95% confidence interval) for obesity across the increasing Akkermansia quintiles (referencing to the first quintile) were 1.14 (0.94-1.39), 0.94 (0.77-1.15), 0.70 (0.56-0.85) and 0.79 (0.64-0.96) after adjusting for age and sex (P for trend < 0.001). This association remained unchanged after further controlling for smoking, alcohol drinking, diet, and country. The odds ratios (95% CI) of Akkermansia were 0.19 (0.03-0.62) and 0.77 (0.64-0.91) before and over 40 years, respectively, indicating that the protective effect of Akkermansia against obesity was not stable with aging.

Conclusion: High relative abundance of Akkermansia is associated with low risk of obesity and the association declines with aging.

Keywords: 16S rRNA; Akkermansia; Body mass index; Gut microbiota; Obesity; Probiotics.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

© The Author(s) 2020.

Figures

Fig. 1
Fig. 1
The association between BMI and relative abundance of Akkermansia. a Pearson correlation between BMI (as a continuous variable) and Akkermansia abundance. b The Wilcoxon rank-sum test was used to analyze the Akkermansia differences between three BMI categories, namely Normal, Overweight, and Obesity. The log10-transformed Akkemancia relative abundance was used in plots
Fig. 2
Fig. 2
Odds ratio of obesity by relative abundance of Akkermansia. Lines represent odds ratios and 95% CI based on restricted cubic splines for relative abundance of Akkermansia with knots at the 50th and 90th percentiles. Odds ratios were estimated using a logistic regression model after adjustment for age, sex, diet type, smoking and alcohol drinking and country; P for non-linearity = 0.01. Bars represent the numbers of participants according to 100-equally-sized bins of Akkermansia abundance
Fig. 3
Fig. 3
Stratified analyses of the associations between fecal relative abundance (%) of Akkermansia and obesity. aRange of the relative abundances of Akkermansia was revealed by median (interquartile range). bAdjusted for age, sex, diet type, smoking and alcohol drinking and country, stratifying factors excepted
Fig. 4
Fig. 4
The effect of aging on Akkermansia-obesity associations. a The changing ORs (between Akkermansia and obesity) with age in sliding window analysis. The OR represented obesity risks of elevating of per 10% Akkermansia abundance in age- and sex-adjusted (a), or in fully adjusted logistic regression models (b). Lines represent odds ratios and 95% CI

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