<p>Mental illnesses affect one in five Canadians and often require psychotropic medications. While effective, many psychotropic medications can cause weight gain and metabolic side effects. The gut microbiota, influenced by short-chain fatty acids like acetate, plays a role in mental health via the gut-brain axis and may be disrupted as a result of medication use. This case-series explored the feasibility of acetate supplementation contained in delayed-release capsules as an intervention to alter the gut microbiota and reduce metabolic side effects in people taking psychotropic medication for mood and anxiety disorders. Eleven participants aged 22–32 with medication-related weight gain were evaluated at baseline, across three months of delayed-release acetate supplementation, and at one-month follow-up. Adherence was high, with no serious adverse events. Six participants showed signs of metabolic improvements, including clinically-meaningful changes in cholesterol and weight. Mood and anxiety symptoms meaningfully improved in two participants. 16S rRNA gene sequencing revealed alterations in the gut microbiota at both the individual and group levels following the intervention, including increased relative abundance of butyrate-producing bacteria and functional changes potentially influencing cholesterol metabolism. Microbiota differences were also noted between participants with and without metabolic improvements, both pre- and post-intervention, suggesting a potential “responder” phenotype. These findings support further exploration of the effectiveness of delayed-release acetate as a safe adjunctive therapy to offset metabolic concerns and gut microbiome changes in people on psychotropic medication. Larger studies with longer follow-up are needed to confirm these effects and validate responder subgroups.</p>