Akkermansia muciniphila and environmental enrichment reverse cognitive impairment associated with high-fat high-cholesterol consumption in rats

Abstract

Nonalcoholic steatohepatitis (NASH) is one of the most prevalent diseases globally. A high-fat, high-cholesterol (HFHC) diet leads to an early NASH model. It has been suggested that gut microbiota mediates the effects of diet through the microbiota–gut–brain axis, modifying the host’s brain metabolism and disrupting cognition. Here, we target NASH-induced cognitive damage by testing the impact of environmental enrichment (EE) and the administration of either Lacticaseibacillus rhamnosus GG (LGG) or Akkermansia muciniphila CIP107961 (AKK). EE and AKK, but not LGG, reverse the HFHC-induced cognitive dysfunction, including impaired spatial working memory and novel object recognition; however, whereas AKK restores brain metabolism, EE results in an overall decrease. Moreover, AKK and LGG did not induce major rearrangements in the intestinal microbiota, with only slight changes in bacterial composition and diversity, whereas EE led to an increase in Firmicutes and Verrucomicrobia members. Our findings illustrate the interplay between gut microbiota, the host’s brain energy metabolism, and cognition. In addition, the findings suggest intervention strategies, such as the administration of AKK, for the management of the cognitive dysfunction related to NASH.

Selenomethionine Ameliorates Cognitive Impairment, Decreases Hippocampal Oxidative Stress and Attenuates Dysbiosis in D-Galactose-Treated Mice

“…It promoted the reduction of Aβ 40–42 levels in the cerebral cortex and relieved impairment of spatial learning and memory in APP/PS1 Alzheimer’s disease model mice [ 63 ]. It reversed the high-fat, high-cholesterol-diet-induced cognitive dysfunction and restored brain metabolism in rats [ 64 ]. Previous studies showed dietary Se increased the relative abundance of Akkermansia [ 19 , 65 ].…”

Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome

“…Increases in Verrucomicrobia level suppress neurodegeneration [ 62 ]. Verrucomicrobia reverses cognitive dysfunction including impaired spatial working memory and recognition of new objects, restores brain metabolism [ 63 ], and alleviates memory impairment caused by high fat in mice [ 64 ]. Patients with cognitive impairment had a lower abundance of Tenericutes [ 65 ].…”

The Therapeutic Role of Exercise and Probiotics in Stressful Brain Conditions

“…Last two decades’ research have evidenced the impact of probiotics on gut microbiota physiology, establishing a clear strain-specificity and population- or diseases-specificity and knocking over the traditional concept of the “golden-strain” [ 208 ]. In recent years, different and specific probiotics strains have emerged by their beneficial effects in particular stages of life or diseases [ 16 , 208 , 209 ]. With respect to mechanisms of action, they have been described in different ways by which probiotics work, including the enhancement of the epithelial barrier, increased adhesion to intestinal mucosa and concomitant inhibition of pathogen adhesion, bacteriocins and acids production, the inhibition of bacterial translocation, anti-inflammatory substances production and immune system modulation, vitamins and neurotransmitters production, effect on calcium-dependent potassium channels in intestinal sensory neurons, and the induction of opioid and cannabinoid receptors in intestinal epithelial cells, among others [ 209 , 210 ] (see Figure 3 ).…”

“…On the other hand, over the last two decades, the gut microbiota has emerged as an important organ with key functions such as the training of host immunity, digesting food, regulating gut endocrine, and neurological functions [ 14 , 15 ]. Evidence continues to demonstrate that the gut microbiota is particularly implicated in brain physiology and behavior, affecting host mental health [ 16 , 17 , 18 ]. New advances on the techniques for its analyses have allowed for knowing deeply the gut microbiome on different human conditions (age- or healthy-related) [ 19 , 20 , 21 ]; however, a “gold standard” reference of a human gut microbiota composition is not yet known.…”