Magnesium Oxide Reduces Anxiety-like Behavior in Mice by Inhibiting Sulfate-Reducing Bacteria

The gut microbiota–brain axis allows for bidirectional communication between the microbes in our gastrointestinal (GI) tract and the central nervous system. Psychological stress has been known to disrupt the gut microbiome (dysbiosis) leading to anxiety-like behavior. Pathogens administered into the gut have been reported to cause anxiety. Whether commensal bacteria affect the gut–brain axis is not well understood. In this study, we examined the impact of a commensal sulfate-reducing bacteria (SRB) and its metabolite, hydrogen sulfide (H₂S), on anxiety-like behavior. We found that mice gavaged with SRB had increased anxiety-like behavior as measured by the open field test. We also tested the effects of magnesium oxide (MgO) on SRB growth both in vitro and in vivo using a water avoidance stress (WAS) model. We found that MgO inhibited SRB growth and H₂S production in a dose-dependent fashion. Mice that underwent psychological stress using the WAS model were observed to have an overgrowth (bloom) of SRB (Deferribacterota) and increased anxiety-like behavior. However, WAS-induced overgrowth of SRB and anxiety-like behavioral effects were attenuated in animals fed a MgO-enriched diet. These findings supported a potential MgO-reversible relationship between WAS-induced SRB blooms and anxiety-like behavior.