1. Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer’s disease
- Author
-
Feifan Wu, Zhi Lu, Yongzheng Peng, Wanting Liu, Lulu Deng, Zihao Ou, and Dongquan Huang
- Subjects
0301 basic medicine ,Blood Glucose ,medicine.medical_specialty ,Amyloid ,Endocrinology, Diabetes and Metabolism ,Blood lipids ,Mice, Transgenic ,Carbohydrate metabolism ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Insulin resistance ,Alzheimer Disease ,Internal medicine ,mental disorders ,Internal Medicine ,medicine ,Animals ,Humans ,Lipid-storage diseases ,Cognitive Dysfunction ,Maze Learning ,lcsh:RC620-627 ,Amyloid beta-Peptides ,biology ,Bacteria ,business.industry ,Probiotics ,Lipid metabolism ,Akkermansia ,medicine.disease ,biology.organism_classification ,Lipid Metabolism ,Peptide Fragments ,Gastrointestinal Microbiome ,lcsh:Nutritional diseases. Deficiency diseases ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Glucose ,Amine Oxidase (Copper-Containing) ,Steatosis ,Insulin Resistance ,business ,030217 neurology & neurosurgery ,Akkermansia muciniphila ,Dyslipidemia - Abstract
Objective Alzheimer’s disease (AD) is a global health problem without effective methods to alleviate the disease progression. Amyloid β-protein (Aβ) is widely accepted as a key biomarker for AD. Metabolic syndromes, including obesity and insulin resistance, are key high risk factors for AD. Akkermansia muciniphila (Akk), the only representative human gut microbe in the genus Verrucomicrobia, can prevent the weight gain caused by a high-fat diet, repair the damaged integrity of the intestinal epithelium barrier, reduce endotoxin levels in blood and improve insulin resistance. The aim of this study is to explore the impact of Akk administration in AD model mice in different diets. Methods APP/PS1 mice were fed either a normal chow diet or a high-fat diet and were treated with Akk by gavage each day for 6 months. The impacts of Akk on glucose metabolism, intestinal barrier and lipid metabolism in the mouse model of AD were determined. Changes in brain pathology and neuroethology were also analyzed. Results Akk effectively reduced the fasting blood glucose and serum diamine oxidase levels, and alleviated the reduction of colonic mucus cells in APP/PS1 mice. After treatment with Akk, the APP/PS1 mice showed obviously reduced blood lipid levels, improved hepatic steatosis and scapular brown fat whitening. Moreover, Akk promoted the reduction of Aβ 40–42 levels in the cerebral cortex of APP/PS1 mice, shortened the study time and improved the completion rate in Y-maze tests. Conclusion Akk effectively improved glucose tolerance, intestine barrier dysfunction and dyslipidemia in AD model mice. Our study results suggested that Akk could delay the pathological changes in the brain and relieve impairment of spatial learning and memory in AD model mice, which provides a new strategy for prevention and treatment of AD., APP/PS1 mice display alterations in physiological processes after treated with Akk. It is showed that the damaged integrity of the intestinal epithelium barrier is repaired, leading to obviously reduced blood glucose and lipid levels, improved hepatic steatosis, insulin resistance and scapular brown fat whitening, which are beneficial to reduce Aβ 40–42 levels in the brain of APP/PS1 mice.
- Published
- 2020