Cafeteria diet and probiotic therapy: cross talk among memory, neuroplasticity, serotonin receptors and gut microbiota in the rat

Abstract

The western diet is known to have detrimental effects on cognition and the gut microbiota, but few studies have investigated how these may be related. Here, we examined whether a probiotic could prevent diet-induced memory deficits. Rats were pre-exposed to vehicle, low or high doses of VSL#3 for 2 weeks before half were switched from chow to a cafeteria diet (Caf) for 25 days; VSL#3 treatment continued until death. High-dose VSL#3 prevented the diet-induced memory deficits on the hippocampal-dependent place task, but the probiotic caused deficits on the perirhinal-dependent object task, irrespective of diet or dose. No differences were observed in anxiety-like behaviour on the elevated plus maze. Gut microbial diversity was dramatically decreased by Caf diet and here, VSL#3 was able to increase the abundance of some taxa contained in the probiotic such as Streptococcus and Lactobacillus and also other taxa including Butyrivibrio, which were decreased by the Caf diet. This affected the predicted profile of microbial metabolic pathways related to antioxidant and bile biosynthesis, and fat and carbohydrate metabolism. In the hippocampus, the Caf diet increased the expression of many genes related to neuroplasticity and serotonin receptor (5HT) 1A, which was normalised in Caf-High rats. Distance-based linear modelling showed that these genes were the best predictors of place memory, and related to microbiota principal component (PC) 1. Neuroplasticity genes in the perirhinal cortex were also affected and related to PC1 but object memory performance was correlated with perirhinal 5HT2C expression and microbiota PC3. These results show that probiotics can be beneficial in situations of gut dysbiosis where memory deficits are evident but may be detrimental in healthy subjects.

Metabolic, Molecular, and Behavioral Effects of Western Diet in Serotonin Transporter-Deficient Mice: Rescue by Heterozygosity?

“…Similar to the changes in the expression of serotonin receptors induced by WD reported here were previously reported. For example, cafeteria and high-energy diets decreased brain expression of Htr2c receptor in rats (Lopez-Esparza et al, 2015;Beilharz et al, 2018). Mice exposed to high-fat diet displayed changes in the expression of Htr2a in the olfactory nucleus and of Htr2c in the medial amygdaloid nucleus (Huang et al, 2004).…”

Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

“…In addition, minocycline has antibiotic activity and has been recently reported to reduce some effects of high-fat diet in rats through altering food intake and the gut microbiome composition 27 . Given the role of the gut microbiome in diet-induced cognitive impairment 11,28,29 , it is important to examine the effects of minocycline on microbiome composition and to investigate potential behavioral associations as these have not been previously studied.…”

Commentary: Microbial panaceas: does development have the answer? – reflections on Cowan, Dinan, & Cryan (2020)

“…Not only are we still trying to move past correlations and understand the complex web of causality, but there are fundamental aspects of the microbiota–gut–brain axis that we do not yet understand. For example, while manipulating the microbiota with probiotics is generally seen to have only positive (or in the worst case, negligible) outcomes for human health, some animal models have shown that probiotic treatment can produce unexpected (and possibly undesirable outcomes) on memory (Beilharz et al, ). Considering these data and the early stage of current research in the microbiota–gut–brain axis, caution is warranted in translating potential therapeutics from emerging findings.…”