Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögrenâs syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. Case-case study including Sjögren's patients with high fatigue (n=24) and patients with low fatigue levels (n=24)
Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögren’s syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array.
Project description:Background Alterations of the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain-resolved, integrated multi-omic analyses of saliva and stool samples collected from eight families with multiple cases of type 1 diabetes mellitus (T1DM). Results We identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensal Streptococcus salivarius in the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiont Streptococcus mutans. The decrease in S. salivarius in the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes including Enterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of the Enterobacteria as well as in the human gut proteome. Finally, we were able to follow transmitted strain-variants from the oral cavity to the gut at the metagenomic, metatranscriptomic and metaproteomic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract. Conclusions Alterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of “oral-to-gut” transfer of Streptococcus salivarius. Our results indicate that the observed oral-cavity-driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi-omic analyses, we resolve strain-variant “mouth-to-gut” transfer in a disease context.
Project description:Fatigue is a debilitating condition with a significant impact on patients’ quality of life. Fatigue is frequently reported by patients suffering from primary Sjo ̈gren’s Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.