Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila

Abstract

Obesity is one of the most serious public health challenges in the world. Obesity during early life has been associated with an increased risk of neurodevelopmental disorders, including deficits in learning and memory, yet the underlying mechanisms remain unclear. Here, we show that early life high-fat diet (HFD) feeding impairs hippocampus-dependent contextual/spatial learning and memory, and alters the gut microbiota, particularly by depleting Akkermansia muciniphila (A. muciniphila), in mice. Transplantation of the HFD microbiota confers hippocampus-dependent learning and memory deficits to mice fed a chow diet. Oral treatment of HFD-fed mice with the gut commensal A. muciniphila corrects gut permeability, reduces hippocampal microgliosis and proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6) expression, and restores neuronal development and synapse plasticity, thus ameliorates defects in learning and memory. Interestingly, treatment of mice with lipopolysaccharide (LPS) mimics HFD-induced hippocampus-dependent cognitive impairment in chow-fed mice. In line with these findings, pharmacologic blockade of Toll-like receptor 4 (TLR4) signalling or antibiotics treatment both effectively prevent hippocampus-dependent learning and memory deficits in HFD-fed mice. Collectively, our findings demonstrate an unexpected pivotal role of gut microbiota in HFD-induced cognitive deficits and identify a potential probiotic therapy for obesity associated with cognitive dysfunction during early life.

High Fat High Calories Diet (HFD) Increase Gut Susceptibility to Carcinogens by Altering the Gut Microbial Community

“…Most of these bacteria are already reported probiotics. The reduction of these bacteria may cause intestinal microenvironment disorders, and the intestinal mucosa barrier to resist external invasion will decrease, leading to increased susceptibility to carcinogenic factors [20][21]. After using DMH, the proportion of rumenococcus, Candida, Clostridium IV, and Enterobacter bacteria in the high-fat diet group decreased further, further indicating that the decrease in the proportion of these bacteria is an important cause of the increased intestinal susceptibility to carcinogens the reason.…”

5‐Heptadecylresorcinol, a Biomarker for Whole Grain Rye Consumption, Ameliorates Cognitive Impairments and Neuroinflammation in APP/PS1 Transgenic Mice

“…It is widely accepted that gut microbiota dysbiosis was correlated with the development and progress of AD. [ 28 ] The microbial diversity was decreased in AD participants, including reduced ACE, Chao1, and Shannon index. [ 18 ] AR‐C17 treatment could modulate the abundance of gut microbiota.…”

“…suggested that oral treatment of Akkermansia could modulate gut permeability, reduce neuroinflammation, and restore neuronal function, thus ameliorating cognitive deficits in HFD‐fed mice. [ 28 ] Meanwhile, Lactobacillus consumption could improve physiological function and cognitive ability of aged mice. [ 30 ] Moreover, Clostridium are positively associated with obesity, insulin resistance, and AD development.…”

Dietary Supplementation of Black Rice Anthocyanin Extract Regulates Cholesterol Metabolism and Improves Gut Microbiota Dysbiosis in C57BL/6J Mice Fed a High‐Fat and Cholesterol Diet

“…Hypercholesterolemia associated with obesity, cardiovascular disease, low‐grade inflammation, and gut microbiota dysbiosis is considered a vital risk health factor to human. [ 1 ] Numerous drugs have been permitted for the treatment of hypercholesterolemia. Nevertheless, many of these drugs have been withdrawn attributed to severe side‐effects, such as easy rebound, heart diseases, reduction of body immunity, and other disorders.…”