Dataset Information

Propionic acid promotes neurite recovery in damaged multiple sclerosis neurons

ABSTRACT: Neurodegeneration in the autoimmune disease multiple sclerosis (MS) still poses a major therapeutic challenge. Effective drugs that target the inflammation can only partially reduce accumulation of neurological deficits and conversion to progressive disease forms. Diet and the associated gut microbiome are currently being discussed as crucial environmental risk factors that determine disease onset and subsequent progression. In people with MS (pwMS), supplementation of the short-chain fatty acid (SCFA) propionic acid (PA), as microbial metabolite derived from the fermentation of a high-fiber diet, has previously been shown to regulate inflammation accompanied by neuroprotective properties. We set out to determine, whether the neuroprotective impact of PA is a direct mode of action of SCFAs on central nervous system (CNS) neurons.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine, Neuron, Generation Of Neurons, Cell Culture

DISEASE(S): Multiple Sclerosis

SUBMITTER: Gereon Poschmann

LAB HEAD: Gereon Poschmann

PROVIDER: PXD040184 | Pride | 2024-06-22

REPOSITORIES: Pride

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Propionic acid promotes neurite recovery in damaged multiple sclerosis neurons.

Gisevius Barbara B Duscha Alexander A Poschmann Gereon G Stühler Kai K Motte Jeremias J Fisse Anna Lena AL Augustyniak Sanja S Rehm Adriana A Renk Pia P Böse Celina C Hubert Diana D Peters Kathrin K Jagst Michelle M Gömer André A Todt Daniel D Bader Verian V Tokic Marianne M Hirschberg Sarah S Krogias Christos C Trampe Nadine N Coutourier Charlotta C Winnesberg Carmen C Steinmann Eike E Winklhofer Konstanze K Gold Ralf R Haghikia Aiden A

Brain communications 20240603 3

Neurodegeneration in the autoimmune disease multiple sclerosis still poses a major therapeutic challenge. Effective drugs that target the inflammation can only partially reduce accumulation of neurological deficits and conversion to progressive disease forms. Diet and the associated gut microbiome are currently being discussed as crucial environmental risk factors that determine disease onset and subsequent progression. In people with multiple sclerosis, supplementation of the short-chain fatty ...[more]

PMID: 38894951

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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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