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HAMSAB supplement enhances SCFA production associated with microbiota and immune modulation in type 1 diabetes

ABSTRACT: Purpose: Short chain fatty acids (SCFAs) produced by the gut microbiota have dual beneficial anti-inflammatory and anti-dysbiotic effects associated with the prevention of type 1 diabetes (T1D) in mice. We have conducted a single-arm trial of a dietary supplement (HAMSAB), to determine the effects of increasing SCFA delivery in adults with long-standing T1D. Particularly, we examined blood transcriptome in these patients using RNA-seq. Methods: Blood was collected from patients at baseline and after 6 weeks of HAMSAB supplementation. Whole blood was collected directly into Paxgene or Tempus tubes containing RNA stabilisers and extracted according to the manufacturer's protocol. Next-gene sequencing of patients’ whole blood transcriptome was performed by Genewiz using Illumina NovaSeq platform obtaining sequence depth of 50 million reads/sample. Results: Several signalling pathways including fatty acid oxidation were found to be regulated by HAMSAB

ORGANISM(S): Homo sapiens

PROVIDER: GSE176230 | GEO | 2022/01/26

REPOSITORIES: GEO

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Project description:Both genetic and environmental factors are implicated in Type 1 Diabetes (T1D). Since environmental factors can trigger epigenetic changes, we hypothesized that variations in histone posttranslational modifications (PTMs) at the promoter/enhancer regions of T1D susceptible genes may be associated with T1D. We therefore evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the chromatin-immunoprecipitation-linked-to-microarray approach to profile key histone PTMs, including H3-lysine-4 trimethylation (H3K4me3), H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac at genes within the T1D susceptible loci in lymphocytes, and H3K4me3, H3K9me2, H3K9Ac and H4K16Ac at the IDDM1 region in monocytes of T1D patients and healthy controls separately. We screened for potential variations in histone PTMs using computational methods to compare datasets from T1D and controls. Interestingly, we observed marked variations in H3K9Ac levels at the upstream regions of HLA-DRB1 and HLA-DQB1 within the IDDM1 locus in T1D monocytes relative to controls. Additional experiments with THP-1 monocytes demonstrated increased expression of HLA-DRB1 and HLA-DQB1 in response to interferon- and TNF-treatment that were accompanied by changes in H3K9Ac at the same promoter regions as that seen in the patient monocytes. These results suggest that the H3K9Ac status of HLA-DRB1 and HLA-DQB1, two genes highly associated with T1D, may be relevant to their regulation and transcriptional response towards external stimuli. Thus, the promoter/enhancer architecture and chromatin status of key susceptible loci could be important determinants in their functional association to T1D susceptibility. We evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the ChIP-chip approach to profile key histone PTMs, including histone H3K4me3, H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac, at genes within the T1D susceptible loci in lymphocytes.

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HAMSAB supplement enhances SCFA production associated with microbiota and immune modulation in type 1 diabetes

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