Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice
Hong Zheng,
Pengtao Xu,
Qiaoying Jiang,
Qingqing Xu,
Yafei Zheng,
Junjie Yan,
Hui Ji,
Jie Ning,
Xi Zhang,
Chen Li,
Limin Zhang,
Yuping Li,
Xiaokui Li,
Weihong Song,
Hongchang Gao
Affiliations
Hong Zheng
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Pengtao Xu
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Qiaoying Jiang
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Qingqing Xu
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Yafei Zheng
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Junjie Yan
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Hui Ji
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Jie Ning
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Xi Zhang
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Chen Li
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Limin Zhang
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences
Yuping Li
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University
Xiaokui Li
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Weihong Song
Institute of Aging, School of Mental Health, Wenzhou Medical University
Hongchang Gao
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University
Abstract Background Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism. Results We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy. Conclusions Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline. Video Abstract