Transcript levels of Toll-Like receptors 5, 8 and 9 correlate with inflammatory activity in Ulcerative Colitis

<p>Abstract</p> <p>Background</p> <p>Dysregulation of innate immune response by Toll-Like Receptors (TLRs) is a key feature in Ulcerative Colitis (UC). Most studies have focused on <it>TLR2, TLR3</it>, and <it>TLR4 </it>participation in UC. However, few studies have explored other TLRs. Therefore, the aim of this study was to evaluate the mRNA profiles of <it>TLR1 to 9 </it>in colonic mucosa of UC patients, according to disease activity.</p> <p>Methods</p> <p>Colonic biopsies were taken from colon during colonoscopy in 51 patients with Ulcerative Colitis and 36 healthy controls. mRNA levels of <it>TLR1 to 9, Tollip</it>, inflammatory cytokines <it>IL6 </it>and <it>TNF </it>were assessed by RT-qPCR with hydrolysis probes. Characterization of <it>TLR9 </it>protein expression was performed by Immunohistochemistry.</p> <p>Results</p> <p>Toll-like receptors <it>TLR8, TLR9</it>, and <it>IL6 </it>mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to healthy individuals (p < 0.04). In the UC patients group the <it>TLR2, TLR4, TLR8 </it>and <it>TLR9 </it>mRNA levels were found to be significantly lower in patients with quiescent disease, as compared to those with active disease (p < 0.05), whereas <it>TLR5 </it>showed a trend (p = 0.06). <it>IL6 </it>and <it>TNF </it>mRNA levels were significantly higher in the presence of active disease and help to discriminate between quiescent and active disease (p < 0.05). Also, <it>IL6 </it>and <it>TNF </it>mRNA positively correlate with TLRs mRNA with the exception for <it>TLR3</it>, with stronger correlations for <it>TLR5, TLR8</it>, and <it>TLR9 </it>(p < 0.0001). <it>TLR9 </it>protein expression was mainly in the lamina propria infiltrate.</p> <p>Conclusions</p> <p>This study demonstrates that <it>TLR2, TLR4, TLR8</it>, and <it>TLR9 </it>expression increases in active UC patients, and that the mRNA levels positively correlate with the severity of intestinal inflammation as well as with inflammatory cytokines.</p

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome