Search

Dietary intervention is a subject of growing interest in the management of inflammatory bowel disease (IBD), as new incident cases across the globe are rapidly rising, suggesting environmental factors as contributing elements. Dietary components and micronutrients have been associated with IBD pathogenesis or reductions in disease severity. Selenium, a diet-derived essential micronutrient that is important for proper immune system function, has received limited attention in the context of IBD. Selenium deficiency is a common finding in patients with IBD, but few clinical trials have been published to address the consequences of this deficiency. Here, we review the physiological and immunological roles of selenium and its putative role in IBD, and draw attention to knowledge gaps and unresolved issues, with the goal of stimulating more research on selenium in IBD. [ABSTRACT FROM AUTHOR]

The gut microbiome contributes to inflammatory bowel disease (IBD), in which bacteria can be present within the epithelium. Epithelial barrier function is decreased in IBD, and dysfunctional epithelial mitochondria and endoplasmic reticulum (ER) stress have been individually associated with IBD. We therefore hypothesized that the combination of ER and mitochondrial stresses significantly disrupt epithelial barrier function. Here, we treated human colonic biopsies, epithelial colonoids, and epithelial cells with an uncoupler of oxidative phosphorylation, dinitrophenol (DNP), with or without the ER stressor tunicamycin and assessed epithelial barrier function by monitoring internalization and translocation of commensal bacteria. We also examined barrier function and colitis in mice exposed to dextran sodium sulfate (DSS) or DNP and co-treated with DAPK6, an inhibitor of death-associated protein kinase 1 (DAPK1). Contrary to our hypothesis, induction of ER stress (i.e. the unfolded protein response) protected against decreased barrier function caused by the disruption of mitochondrial function. ER stress did not prevent DNP-driven uptake of bacteria; rather, specific mobilization of the ATF6 arm of ER stress and recruitment of DAPK1 resulted in enhanced autophagic killing (xenophagy) of bacteria. Of note, epithelia with a Crohn's disease-susceptibility mutation in the autophagy gene ATG16L1 exhibited less xenophagy. Systemic delivery of the DAPK1 inhibitor DAPK6 increased bacterial translocation in DSS- or DNP-treated mice. We conclude that promoting ER stress-ATF6-DAPK1 signaling in transporting enterocytes counters the transcellular passage of bacteria evoked by dysfunctional mitochondria, thereby reducing the potential for metabolic stress to reactivate or perpetuate inflammation.

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether tuft cells are required for the expulsion of the cestode, Hymenolepis diminuta, from the non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c and C57BL/6 mice infected with H. diminuta expelled the worms by 11 days post-infection (dpi) and displayed DCLK1+ (doublecortin-like kinase 1) tuft cell hyperplasia in the small intestine (not the colon) at 11 dpi. This tuft cell hyperplasia was dependent on IL-4Rα signalling and adaptive immunity, but not the microbiota. Expulsion of H. diminuta was slowed until at least 14 dpi, but not negated, in tuft cell-deficient Pou2f3-/- mice and was accompanied by delayed goblet cell hyperplasia and slowed small bowel transit. Worm antigen and mitogen evoked production of IL-4 and IL-10 by splenocytes from wild-type and Pou2f3-/- mice was not appreciably different, suggesting similar systemic immune reactivity to infection with H. diminuta. Wild-type and Pou2f3-/- mice infected with H. diminuta displayed partial protection against subsequent infection with the nematode Heligmosomoides bakeri. We speculate that, with respect to H. diminuta, enteric tuft cells are important for local immune events driving the rapidity of H. diminuta expulsion but are not critical in initiating or sustaining systemic Th2 responses that provide concomitant immunity against secondary infection with H. bakeri. Author summary: The small intestinal tuft cell is emerging as a versatile sentinel cell type in a variety of infections involving protozoans, nematodes, and certain bacteria. Whether the tuft cell responds to enteric cestode infections and the extent of its involvement in mediating the anti-helminth response is not yet characterized. Using mice infected with Hymenolepis diminuta, we show that tuft cells help accelerate expulsion of this lumen-dwelling cestode, by coordinating local events that form an integral part of the classical "weep and sweep" anti-helminthic response. We further show that although infection with H. diminuta induces both tuft cell hyperplasia as well as protection from subsequent infection with the nematode Heligmosmoides bakeri, the tuft cell is not solely responsible for mediating systemic and other local Th2 responses against H. diminuta. Our work reveals subtle roles for the tuft cell in initiating and coordinating host anti-parasitic activity in cestode infections. At the same time, we show that redundancies exist in the host's mucosal arsenal that ultimately mediate worm expulsion in tuft cell deficient mice. [ABSTRACT FROM AUTHOR]

The current study extended the empirical research on the overlap of vocational interests and personality by (a) testing hypothesized relations between RIASEC interests and the personality dimensions of the HEXACO model, and (b) exploring the HEXACO personality model's predictive advantage over the five-factor model (FFM) in capturing RIASEC interests. Results of correlations based on a sample of 437 college students (157 men and 280 women) revealed support for eight of 21 hypothesized HEXACO-RIASEC relations for men and nine of 21 for women. Results of multiple regressions revealed that HEXACO accounted for more variance in RIASEC interests than did the FFM, and that HEXACO accounted for significant incremental variance beyond that explained by the FFM in four of six RIASEC interests for men and in five of six RIASEC interests for women. (Contains 5 tables.)