Food and Microbiota Metabolites Associate with Cognitive Decline in Older Subjects: A 12‐Year Prospective Study

Abstract

Scope: Diet is considered an important modulator of cognitive decline and dementia, but the available evidence is, however, still fragmented and often inconsistent. Methods and Results: The article studies the long-term prospective Three-City Cohort, which consists of two separate nested case-control sample sets from different geographic regions (Bordeaux, n = 418; Dijon, n = 424). Cognitive decline is evaluated through five neuropsychological tests (Mini-Mental State Examination, Benton Visual Retention Test, Isaac's Set Test, Trail-Making Test part A, and Trail-Making Test part B).The food-related and microbiota-derived circulating metabolome is studied in participants free of dementia at baseline, by subjecting serum samples to large-scale quantitative metabolomics analysis. A protective association is found between metabolites derived from cocoa, coffee, mushrooms, red wine, the microbial metabolism of polyphenol-rich foods, and cognitive decline, as well as a negative association with metabolites related to unhealthy dietary components, such as artificial sweeteners and alcohol. Conclusion: These results provide insight into the early metabolic events that are associated with the later risk to develop cognitive decline within the crosstalk between diet, gut microbiota and the endogenous metabolism, which can help identify potential targets for preventive and therapeutic strategies to preserve cognitive health.

Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline

“…In turn, FFAs are thought to participate in the pathogenesis of AD by stimulating the assembly of amyloid plaques and tau filaments [ 25 ], as well as by inducing inflammation and insulin resistance [ 26 ]. In agreement with recent studies, we furthermore found increased levels of various ACs among CD cases [ 27 – 31 ], suggestive of incomplete fatty acid β-oxidation. A large body of evidence has demonstrated that glucose hypometabolism is a primary hallmark of CD, AD and other neurodegenerative disorders, which starts decades before the onset of clinical symptoms [ 2 ].…”

The Effects of Consuming White Button Mushroom Agaricus bisporus on the Brain and Liver Metabolome Using a Targeted Metabolomic Analysis

“…Similar changes in inflammatory lipid species have also been found in Parkinson's disease [43] and Multiple sclerosis [44], as well as metabolic diseases such as type 2 diabetes [45], non-alcoholic steatohepatitis [46] and non-alcoholic fatty liver [47] where liver biopsies and high serum levels of sphingomyelins have been used as biomarkers of visceral adipose tissue and hepatic triglyceride content [47,48]. A protective association between metabolites reflecting the consumption of mushroom and brain health have been proposed in a prospective cognitive decline study with humans [18] and after oral administration of the mushroom derived antioxidant ergothioneine in a recognition memory study in rodents [17]. This information provides additional evidence for improved mental health through diets that alter the gut microbiome to positively interact with the central nervous system.…”

“…Edible mushroom derived proteins lectins [2], amino acid ergothioneine [4], flavonoids [5] and polysaccharides categorized as glucans with β-type glycosidic bonds have been proposed as bioactive components responsible for regulation of the gut microbiome, modulation of the host immune response, hypolipidemic and anti-oxidant activity [6][7][8][9][10][11]. In addition, neuroprotective and antiageing properties of mushroom and isolated compounds like ergothioneine have been proposed for use against age related disorders [12][13][14][15][16][17][18], through the anti-inflammatory action purportedly regulated by changes in the composition of the intestinal microbiome. However, more preclinical evidence is required to understand the potential mechanism of action of dietary mushroom in treatment or neurological disease prevention.…”

“…Several neurobiological mechanisms have linked the consumption of unhealthy diets such as westernized-diet (WD) or diets rich in saturated fats with alterations in the gut microbiome that potentially contribute to marked differences in the brain lipidome and cognitive dysfunction [22][23][24]; however, research into the potential benefits of healthy diets in modulating these microbiome-brain interactions are only starting to emerge [23]. A comprehensive assessment of the impact of diet on brain health through metabolomics analysis recently suggested a protective association between metabolites derived from polyphenol rich foods and reversal of cognitive decline [18]. There also appears to be a role for microbiome-derived metabolites in gut-brain communication and regulation of brain function [25].…”

Ergothioneine, where are we now?

“…No specific deficiency disease has yet been identified for ET, which makes it hard to formally classify it as a vitamin. Perhaps, however, deficiency diseases are staring us in the face: low blood or plasma levels of ET are correlated with increased risk of frailty [16][17][18], cardiovascular disease [19], mild cognitive impairment [18,[20][21][22], dementia [22,23] and Parkinson's disease [24]. Indeed, ET has many neuroprotective properties [4,5,18,26,27], as reviewed in detail in this special issue [18,25,26].…”