An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice.

ABSTRACT

The prevalence of obesity and diabetes, and their complicating mental disorders, severely affect public health. This study aimed to investigate the long-term effects of an Akkermansia muciniphila subtype (A. muciniphilasub) on high-fat diet-induced obesity and diabetes, and to evaluate whether this subtype can alleviate their complicated mental disorders. Whole genome sequencing and short chain fatty acid production analysis in supernatant of pure culture were performed. Female adult C57BL/6 mice were fed a high-fat diet or a normal chow diet and were gavaged with A. muciniphilasub or phosphate-buffered saline daily for 10 months. Body weight, food consumption and blood glucose were measured. At the end of the treatment period, all mice were subjected to the Y-maze test, sucrose preference test, analyses of serum, fecal microbiota analysis and histological examination. This A. muciniphilasub had 278 unique genes compared to the type strain (A. muciniphila ATCC BAA-835) and produced short chain fatty acids both. A. muciniphilasub administration significantly reduced body weight gain and improved the spatial memory of high-fat diet-fed mice. A. muciniphilasub increased Nissl bodies in neurons of the hippocampus, and restored the high-fat diet-inhibited tryptophan metabolism. The high-fat diet led to decreased serum 5-hydroxytryptamine and induced depression, which were not alleviated by A. muciniphilasub. A. muciniphilasub increased the relative fecal abundance of Bifidobacterium, and was negatively correlated with the fecal abundance of Bacteroides. The present study demonstrated the beneficial effects of this A. muciniphilasub on body weight, blood glucose control and the alleviation of the memory decay caused by a high-fat diet in mice.