Akkermansia Muciniphila and Environmental Enrichment Reverse Cognitive Impairment Associated With High-fat High-cholesterol Consumption Through the Gut-brain Axis

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. 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.Results: 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 produces 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 entailed an increase in Firmicutes and Verrucomicrobia members.Conclusions: Our findings illustrate the interplay between gut microbiota, the host’s brain energy metabolism, and cognition, and they suggest intervention strategies, such as the administration of AKK, for the management of the cognitive dysfunction related to NASH.

The gut microbiota of environmentally enriched mice regulates visual cortical plasticity

“…For instance, physical exercise is an important EE component capable of modulating brain plasticity (van Praag et al, 2000); however, it cannot explain the full ocular dominance plasticity enhancement observed in EE rodents (Baroncelli et al, 2012). Some studies demonstrated changes in the microbiota composition and diversity of rodents after physical exercise, and an increase in the Bacteroidetes phylum and the Lachnospiraceae family (Evans et al, 2014;Mika et al, 2015), and recently EE has been shown to modulate the gut microbiota composition in adult rats (Higarza et al, 2021). Changes in bacteria families after diet or physical exercise were also correlated to behavioral alterations.…”

Antibiotic Disruption of the Gut Microbiota Enhances the Murine Hepatic Dysfunction Associated With a High-Salt Diet

“…Strikingly, in this study, the microbiota of the HSPEN group was extremely abundant with Akkermansia species (Figure 4C). Previous studies have indicated that Akkermansia may be regulated by bile acids and increased levels of bile acids can reduce the population of Akkermansia in mice (Higarza et al, 2021;Keshavarz Azizi Raftar et al, 2021). This finding seems to be in contradiction with the acknowledged enrichment of probiotic species within this genus.…”