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

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.

Lipids, lipoprotein distribution and depressive symptoms: the Multi-Ethnic Study of Atherosclerosis.

Previous studies suggest lower concentrations of total and high-density lipoprotein (HDL) cholesterol to be predictive of depression. We therefore investigated the relationship of lipids and lipoprotein distribution with elevated depressive symptoms (EDS) in healthy men and women from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were followed up over a 9.5-year period. EDS were defined as a Center for Epidemiological Studies Depression (CES-D) score ⩾16 and/or use of antidepressant drugs. Lipoprotein distribution was determined from plasma using nuclear magnetic resonance spectroscopy. Among 4938 MESA participants (mean age=62 years) without EDS at baseline, 1178 (23.9%) developed EDS during follow-up. In multivariable Cox regression analyses, lower total, low-density lipoprotein (LDL) and non-HDL cholesterol concentrations at baseline were associated with incident EDS over 9.5 years (hazards ratio (HR)=1.11-1.12 per s.d. decrease, all P<0.01), after adjusting for demographic factors, traditional risk factors including LDL cholesterol, HDL cholesterol and triglycerides. Lipoprotein particle subclasses and sizes were not associated with incident EDS. Among participants without EDS at both baseline and visit 3, a smaller increase in total or non-HDL cholesterol between these visits was associated with lower risk of incident EDS after visit 3 (HR=0.88-0.90 per s.d. decrease, P<0.05). Lower baseline concentrations of total, LDL and non-HDL cholesterol were significantly associated with a higher risk of incident EDS. However, a short-term increase in cholesterol concentrations did not help to reduce the risk of EDS. Further studies are needed to replicate our findings in cohorts with younger participants.

Short-term exposure to a diet high in fat and sugar, or liquid sugar, selectively impairs hippocampal-dependent memory, with differential impacts on inflammation.

Chronic high-energy diets are known to induce obesity and impair memory; these changes have been associated with inflammation in brain areas crucial for memory. In this study, we investigated whether inflammation could also be related to diet-induced memory deficits, prior to obesity. We exposed rats to chow, chow supplemented with a 10% sucrose solution (Sugar) or a diet high in fat and sugar (Caf+Sugar) and assessed hippocampal-dependent and perirhinal-dependent memory at 1 week. Both high-energy diet groups displayed similar, selective hippocampal-dependent memory deficits despite the Caf+Sugar rats consuming 4-5 times more energy, and weighing significantly more than the other groups. Extreme weight gain and excessive energy intake are therefore not necessary for deficits in memory. Weight gain across the diet period however, was correlated with the memory deficits, even in the Chow rats. The Sugar rats had elevated expression of a number of inflammatory genes in the hippocampus and WAT compared to Chow and Caf+Sugar rats but not in the perirhinal cortex or hypothalamus. Blood glucose concentrations were also elevated in the Sugar rats, and were correlated with the hippocampal inflammatory markers. Together, these results indicate that liquid sugar can rapidly elevate markers of central and peripheral inflammation, in association with hyperglycemia, and this may be related to the memory deficits in the Sugar rats.