15 research outputs found

    Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

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    <p>Abstract</p> <p>Background</p> <p>Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders.</p> <p>Methods</p> <p>CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.</p> <p>Results</p> <p>Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (<it>P </it>= 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (<it>P </it>= 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (<it>P </it>= 0.0124) and IL-21 (<it>P </it>= 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (<it>P </it>= 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (<it>P </it>= 0.0325) and CD patients (<it>P </it>= 0.0293).</p> <p>Conclusions</p> <p>This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.</p

    Whole-Community Facilitation Regulates Biodiversity on Patagonian Rocky Shores

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    Understanding the factors that generate and maintain biodiversity is a central goal in ecology. While positive species interactions (i.e., facilitation) have historically been underemphasized in ecological research, they are increasingly recognized as playing important roles in the evolution and maintenance of biodiversity. Dominant habitat-forming species (foundation species) buffer environmental conditions and can therefore facilitate myriad associated species. Theory predicts that facilitation will be the dominant community-structuring force under harsh environmental conditions, where organisms depend on shelter for survival and predation is diminished. Wind-swept, arid Patagonian rocky shores are one of the most desiccating intertidal rocky shores ever studied, providing an opportunity to test this theory and elucidate the context-dependency of facilitation.Surveys across 2100 km of southern Argentinean coastline and experimental manipulations both supported theoretical predictions, with 43 out of 46 species in the animal assemblage obligated to living within the matrices of mussels for protection from potentially lethal desiccation stress and predators having no detectable impact on diversity.These results provide the first experimental support of long-standing theoretical predictions and reveal that in extreme climates, maintenance of whole-community diversity can be maintained by positive interactions that ameliorate physical stress. These findings have important conservation implications and emphasize that preserving foundation species should be a priority in remediating the biodiversity consequences of global climate change

    Effect of Xpert MTB/RIF testing introduction and favorable outcome predictors for tuberculosis treatment among HIV infected adults in rural southern Mozambique. A retrospective cohort study.

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    BACKGROUND:Global roll out of Xpert MTB/RIF technology has resulted in dramatic changes in TB diagnosis. However, benefits in resource-limited, high-burden TB/HIV settings, remain to be verified. In this paper we describe the characteristics of a large cohort of TB patients in a rural hospital in Southern Mozambique before and after Xpert MTB/RIF introduction, together with some determinants of favorable treatment outcome. METHODS:We conducted a retrospective cohort study of TB infected patients ≄15 years of age, diagnosed and treated at Carmelo Hospital of ChĂłkwĂš between January 1, 2006 and December 31, 2017. Patient demographic and clinical characteristics, and treatment outcomes were recorded and compared before and after Xpert MTB/RIF, which was introduced in the second semester of 2012. RESULTS:9,655 patients were analyzed, with 44.1% females. HIV testing was conducted in 99.9% of patients, with 82.8% having TB/HIV co-infection. 73.2% of patients had a favorable treatment outcome. No increase was observed in the number of TB patients identified after introduction of Xpert MTB/RIF testing. CONCLUSION:Upon introduction, Xpert testing seemed to have a punctual beneficial effect on TB treatment outcomes, however this effect apparently disappeared shortly afterwards. Challenges remain for integration of TB and HIV care, as worse outcomes are reported for those patients diagnosed with TB shortly after starting ART, and also for those never starting ART. The need of reasonably excluding TB disease before ART start should be highlighted to every health care provider engaged in HIV care

    Biogeographic Variation and Functional Pathways of the Gut Microbiota in Celiac Disease

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    Background & Aims: Genes and gluten are necessary but insufficient to cause celiac disease (CeD). Altered gut microbiota has been implicated as an additional risk factor. Variability in sampling site may confound interpretation and mechanistic insight, as CeD primarily affects the small intestine. Thus, we characterized CeD microbiota along the duodenum and in feces and verified functional impact in gnotobiotic mice. Methods: We used 16S rRNA gene sequencing (Illumina) and predicted gene function (PICRUSt2) in duodenal biopsies (D1, D2 and D3), aspirates, and stool from patients with active CeD and controls. CeD alleles were determined in consented participants. A subset of duodenal samples stratified according to similar CeD risk genotypes (controls DQ2–/– or DQ2+/– and CeD DQ2+/–) were used for further analysis and to colonize germ-free mice for gluten metabolism studies. Results: Microbiota composition and predicted function in CeD was largely determined by intestinal location. In the duodenum, but not stool, there was higher abundance of Escherichia coli (D1), Prevotella salivae (D2), and Neisseria (D3) in CeD vs controls. Predicted bacterial protease and peptidase genes were altered in CeD and impaired gluten degradation was detected only in mice colonized with CeD microbiota. Conclusions: Our results showed luminal and mucosal microbial niches along the gut in CeD. We identified novel microbial proteolytic pathways involved in gluten detoxification that are impaired in CeD but not in controls carrying DQ2, suggesting an association with active duodenal inflammation. Sampling site should be considered a confounding factor in microbiome studies in CeD.Fil: Constante, Marco. Mc Master University; CanadĂĄFil: Libertucci, Josie. Mc Master University; CanadĂĄFil: Galipeau, Heather J.. Mc Master University; CanadĂĄFil: Szamosi, Jake C.. Mc Master University; CanadĂĄFil: Rueda, Gaston. Mc Master University; CanadĂĄFil: Miranda, Pedro M.. Mc Master University; CanadĂĄFil: Pinto Sanchez, Maria Ines. Mc Master University; CanadĂĄFil: Southward, Carolyn M.. Mc Master University; CanadĂĄFil: Rossi, Laura. Mc Master University; CanadĂĄFil: Fontes, Michelle E.. Mc Master University; CanadĂĄFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de Estudios InmunolĂłgicos y FisiopatolĂłgicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios InmunolĂłgicos y FisiopatolĂłgicos; ArgentinaFil: Surette, Michael G.. Mc Master University; CanadĂĄFil: Bercik, Premysl. Mc Master University; CanadĂĄFil: Caminero, Alberto. Mc Master University; CanadĂĄFil: Verdu, Elena F.. Mc Master University; Canad

    Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer.

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    BackgroundHuman breast cancer is a heterogeneous disease classified by molecular subtyping into luminal A, luminal B, HER2-overexpressing, basal-like, claudin-low and normal-breast like. The routinely applied and standardized immunohistochemical-based surrogates of this classification group together the last three entities as triple-negative breast cancer (TNBCs) that show the most diverse and complex heterogeneity and represent a therapeutic challenge.In the present work 156 feline mammary lesions consisting of feline mammary carcinomas (FMCs), benign neoplasms, and hyperplastic/dysplastic tissues were evaluated histologically and by immunohistochemistry for expression of basal and luminal cytokeratins (CK), vimentin, alpha-smooth muscle actin, calponin, estrogen receptor (ER) alpha (a), and progesterone receptor (PR). Thirty-seven FMCs with 27 matched non-neoplastic controls were also investigated for gene expression of ERa, ER beta, PR, and HER2.ResultsA large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs\ubf+\ubftumors, that showed bilineage (luminal and myoepithelial) differentiation. Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor.ConclusionsThese results indicate and potentially explain the high incidence of triple-negative, vimentin\ubf+\ubfaggressive tumors in cats that may used to elucidate some of the challenging features of TNBCs in women
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