Association Between Gut Akkermansia and Metabolic Syndrome is Dose-Dependent and Affected by Microbial Interactions: A Cross-Sectional Study

OBJECTIVE: Akkermansia muciniphila is among the most abundant bacterial species in the human intestine; however, its relationship to metabolic syndrome (MetS)—which is linked to gut dysbiosis—is not known. In this study, we investigated the association between Akkermansia abundance and risk of MetS and its components, as well as dose–response effects and the influence of microbial interactions on the association. METHODS: This cross-sectional study included 6896 Chinese participants aged 18 to 97 years from the Guangdong Gut Microbiome Project. MetS was defined according to Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults criteria. The abundance of Akkermansia was assessed by 16S rRNA sequencing. Logistic regression analysis with adjustment for common confounders was performed to evaluate the association between Akkermansia and MetS and its components. Models with restricted cubic splines and interaction terms were used to examine the dose–response association and microbial interactions, respectively. RESULTS: The prevalence of MetS was 20.4%, and the median abundance of Akkermansia was 0.08% (interquartile range: 0.04–0.93%). Increased Akkermansia abundance was associated with decreased risk of MetS (P(nonlinear)<0.05), but this effect was not observed until the Akkermansia level was 0.2% of the total gut microbiota abundance (odds ratio=0.96, 95% confidence interval: 0.94–0.98). Of the 5 MetS components, obesity and hypertriglyceridemia showed the strongest association with Akkermansia, followed by reduced high-density lipoprotein cholesterol, hypertension, and hyperglycemia. Microbial interaction analyses showed that Ruminococcaceae and Lachnospiraceae were the predominant bacterial families and were not only correlated with Akkermansia abundance but also influenced the Akkermansia–MetS association. CONCLUSION: There is a dose–response association between reduced risk of MetS and increased abundance of Akkermansia. The association between Akkermansia and 5 MetS components is variable and affected by microbial interactions.