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Butyrate, but not Propionate, Rescues Maternal Diet-Induced Neurocognitive Deficits in Offspring

ABSTRACT: Fiber diet plays a beneficial role in neurocognitive disorders, like dementia and Alzheimer’s Disease. However, insufficient fiber consumption in public increases the concern about public health, particularly about neurocognitive diseases. To survey the association between fiber dietary and neurocognitive performances, mice were subjected to normal-fiber diet or low-fiber diet during gestation, and the neurocognitive functions of the offspring were assessed. We found that maternal low-fiber diet impaired the cognitive functions, and the impairments can be reversed by butyrate, rather than propionate intake. Mechanism studies showed that HDAC4 might become the most potential mediator in butyrate-dependent neurocognitive improvement. Besides, using human maternal serum and paired umbilical cord blood samples, we demonstrated that the SCFA levels in offspring are positively correlated with levels in maternal serum. Those results provide a solid basis for not only maternal fiber diet regulates neurocognitive functions in offspring through altering SCFA levels, but clinical practice in SCFAs-dependent maternal intervention for offspring health.

ORGANISM(S): feces metagenome

PROVIDER: GSE147022 | GEO | 2020/08/25

REPOSITORIES: GEO

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Project description:Background: Acetate, propionate, and butyrate are the main short-chain fatty acids (SCFA) produced in the colon as a result of microbial fermentation of dietary fibers. An increasing amount of evidence suggests that these SCFA have major health benefits. The composition of the microbiota is altered by dietary fat, and this is believed to impact SCFA production. Currently it is unknown whether host gene expression responses to SCFA are modulated by fat content of the diet. The aim of this study was to compare the changes in colonic gene expression profiles after acetate, propionate and butyrate infusions between a low fat and high fat diet. Methods: Male C57BL/6J mice were fed semi-synthetic low fat (10 energy%) or high fat (45 E%) diets starting 2 weeks before the SCFA treatment period. During treatment, mice received a rectal infusion of either an acetate, propionate, butyrate, or a saline (control) solution for 6 consecutive days, after which colon was subjected to gene expression profiling. Unsupervised visualization of the dataset was performed using Independent Principal Component Analysis. For each SCFA, similarities of its effects on a low fat and a high fat diet were assessed using Rank-Rank Hypergeometric Overlap. In addition, differentially expressed genes were identified, and gene set enrichment analysis was performed to determine functional implications of the regulated genes. Results: Taking into account the complete dataset, we observed that more variation in gene expression profiles was explained by fat content of the diet than by SCFA treatment. Gene expression responses to acetate and butyrate were similar on the low fat versus high fat diet, but were opposite for propionate. Functionally the expression changes reflected differential modulation of several metabolic processes; genes involved in oxidative phosphorylation, lipid catabolism, lipoprotein metabolism and cholesterol transport were suppressed by acetate and butyrate treatment, whereas propionate treatment resulted in changes in fatty acid and sterol biosynthesis, and in amino acid and carbohydrate metabolism. Conclusions: We demonstrated that dietary fat content impacts the colonic gene expression response to propionate, and to a lesser extent to acetate and butyrate. The study demonstrates that knowledge on diet composition is essential when studying effects of SCFAs on metabolism.

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Butyrate, but not Propionate, Rescues Maternal Diet-Induced Neurocognitive Deficits in Offspring

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