Zinc and Cobalt exposure influence Akkermansia muciniphila growth and short-chain fatty acid metabolism

ABSTRACT Akkermansia muciniphila is a probiotic bacterium that has been proposed as a potential intervention for depression. A. muciniphila is a common mucin degrader, producing short fatty chain acids (SCFAs), including acetate, butyrate, and propionate, which can help regulate mood via the gut-brain axis. However, the interplay between A. muciniphila and other neuroactive environmental exposures is unclear. The objective of this study was to assess the effects of Zn and Co exposure, individually and together, on A. muciniphila growth and SCFA production. Minimum Inhibitory Concentration (MIC) was calculated for each metal, and sub-MIC exposure testing at high and low levels was conducted with single and combined metals. Growth curves were measured for each exposure condition, and SCFAs were measured using liquid chromatography-mass spectroscopy. Growth and SCFA production were compared between exposures and controls using paired t-tests and linear regression models. All p-values were corrected using FDR adjustments (q-values). A. muciniphila was tolerant to both metal exposures, with MICs at 750mg/L for Zn and 4,000 mg/L for Co. Growth at 24-and 48-hours was only significantly reduced upon exposure to high levels of Co, alone and in combination with Zn. Production of propionate significantly increased with high and low Zn exposures alone and in combination with low Co exposure (q-values <0.01), and significantly decreased with high Co exposure alone and in combination with Zn (q-values <0.01). Overall, A. muciniphila was metal tolerant, supporting its use as a probiotic in the presence of other neuroactive metal exposures.