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Expression data from human regulatory T cells of short chain fatty acid propionic acid treated MS patients

ABSTRACT: Expression data from human regulatory T cells of short chain fatty acid propionic acid treated MS patients

PROVIDER: PRJNA561621 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10022008.fastq.gz	Fastqsanger.gz
	SRR10022009.fastq.gz	Fastqsanger.gz
	SRR10022010.fastq.gz	Fastqsanger.gz
	SRR10022011.fastq.gz	Fastqsanger.gz
	SRR10022012.fastq.gz	Fastqsanger.gz

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Expression data from human regulatory T cells of short chain fatty acid propionic acid treated MS patients

Project description:Short chain fatty acids were shown to affect regulatory immune response in context of autoimmune diseases like multiple sclerosis (MS). Recent studys in an animal model of MS revealed significant impact of short chain fatty acid propionate (PA) on the differentiation towards regulatory Tcells (Treg). In a translational proof of concept study PA was administered to relapse remitting MS patients. We observed an increase of Treg in peripheral blood as well as functional improvement in Treg suppressive capacity beside a decrease of proinflammatory Thelper1 and 17 cells. To investigate underlying mechanisms of the observed shift in immune cell balance, intensive transcriptomic analysis on isolated Treg from whole blood PBMC of PA treated relapse remitting MS patients was performed at baseline, 14 days and 90 days of treatment.

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Project description: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.

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Project description:Folic acid deficiency is common worldwide and is linked to intestinal flora imbalance. The intestinal microbial utilization of folic acid based on model animals faces the challenges of repeatability and individual variability. In this study, we built an in vitro fecal slurry culture model deficient in folic acid. We examined the effects of supplementation with different forms of folic acid (5-methyltetrahydrofolate and non-reduced folic acid) on the modulation of intestinal flora. 16S rDNA gene sequencing showed alpha diversity increased after folic acid supplementation compared to fermentation samples with folic acid deficiency. In the non-reduced folic acid (FA) group, the relative abundance of the Firmicutes phylum dropped to 56.7%, whereas in the 5-methyltetrahydrofolate (MTHF) supplementation group, it grew to 64.9%. Lactobacillus genera became more prevalent, reaching 22.8% and 30.8%, respectively. Additionally, Bifidobacterium and Pedioccus, two common probiotic bacteria, were in higher abundance. Short-chain fatty acids (SCFAs) analysis showed that supplementation with folic acid (non-reduced folic acid, 5-methyltetrahydrofolate) decreased acetic acid and increased the fermentation yield of isobutyric acid. The in vitro fecal slurry culture model developed in this study can be utilized as a human folic acid deficiency model for studying intestinal microbiota and demonstrated that both 5-methyltetrahydrofolate and non-reduced folic acid have effects on the regulation of intestinal microecology.

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