Type 1 diabetes mellitus (T1D) is an autoimmune disease defined by destroyed pancreatic β-cells. which results in impaired insulin secretion and hyperglycemia, but one complication of T1D gets less attention than the others: cognitive dysfunction. Previous studies reported that modification of gut microbiota can reduce the incidence of T1D. So, researchers from Wenzhou Medical University hypothesized that modified gut microbiota may also affect cognitive function in T1D. Using an induced mouse model of T1D, researchers modified the microbiota with an antibiotic and measured the impact of these microbial changes on cognitive performance. Antibiotic-treated mice (TD1V) had a disrupted microbiome and altered host metabolic phenotypes. Antibiotic-treated mice (blue) also showed greater cognitive impairment than induced T1D alone (red). The antibiotic treatment depleted acetate-producing bacteria, which lead to long-term acetate deficiency. This deficiency then resulted in a reduction of synaptophysin in the hippocampus. Acetate supplementation or fecal microbiota transplantation led to recovery of hippocampal synaptophysin levels. This effect was dependent on vagus nerve function. These results suggest a novel protective role of microbe-generated acetate in cognitive function and suggest that long-term acetate deficiency is a risk factor for cognitive decline.