Correction: Beneficial bacteria inhibit cachexia.

[This corrects the article DOI: 10.18632/oncotarget.7730.].

Dietary supplementation of encapsulated organic acids enhances performance and modulates immune regulation and morphology of jejunal mucosa in piglets.

The aim of the study was to test two encapsulated regimens containing organic acids and/or zinc oxide (ZnO) on weaned piglet performance and jejunal mucosa morphology and immunity. For that, weaned piglets were allocated to treatments including control, supplemented with encapsulated organic acids (ACID group), and supplemented with organic acids and ZnO, both encapsulated (ACIDplus group). Antibiotics were used at similar concentrations in all groups during the first two weeks, but withdrawn from the ACIDplus group during the last three weeks of the experiment. ZnO was given with feed in the Control and ACID groups only during the first two weeks. The experimental period lasted 5 weeks. Piglets from the ACID group exhibited higher average daily gain compared to other groups during the last 3 weeks of the experiment (P<0.05). The ACIDplus group performed similarly with controls. The mucosal height of jejunum was higher in both ACID (P<0.01) and ACIDplus groups compared to controls (P<0.05). Immunohistochemical analysis of jejunal mucosa, showed higher numbers of neutrophils in ACID and ACIDplus groups compared to controls (P<0.01 and P<0.001, respectively). Treatments had the opposite effect on mucosal regulatory T-cells (Foxp3-positive cells) in jejunum, being higher (P<0.001) in control group compared to ACID and ACIDplus groups. The number of CD3-positive cells was higher (P<0.05) in the ACIDplus and control groups compared to the ACID group. In conclusion, the encapsulated products used had beneficial effects on growth performance coexisting with improvements on jejunal histomorphology and modulation of mucosal immunity.

Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report.

PURPOSE: CYLD is a tumor suppressor that has been linked to the development of various human malignancies, including colon cancer. The tumor-suppressing function of CYLD is associated with its deubiquitinating activity, which maps to the carboxyl-terminal region of the protein. In the present study we evaluated the role of intestinal epithelial CYLD in colitis-associated cancer using a conditional mouse CYLD inactivation model. METHODS: In order to evaluate the role of CYLD in intestinal epithelial carcinogenesis, mice (IEC-Cyld (Δ9) mice) that carry a mutation that eliminates the deubiquitinating domain of CYLD in intestinal epithelial cells (IEC) were generated by crossing Villin-Cre transgenic mice to previously generated mice carrying a loxP-flanked Cyld exon 9 (Cyld (flx9) mice). RESULTS: We found that IEC-Cyld (Δ9) mice did not present spontaneous intestinal abnormalities up to one year of age. However, upon challenge with a combination of genotoxic (AOM) and pro-inflammatory (DSS) agents we found that the number of adenomas in the IEC-Cyld (Δ9) mice was dramatically increased compared to the control mice. Inactivation of CYLD in intestinal epithelial cells did not affect the classical nuclear factor-kappaB (NF-κB) and c-Jun kinase (JNK) activation pathways under physiological conditions, suggesting that these pathways do not predispose CYLD-deficient intestinal epithelia to colorectal cancer development before the onset of genotoxic and/or pro-inflammatory stress. CONCLUSIONS: Our findings underscore a critical tumor-suppressing role for functional intestinal epithelial CYLD in colitis-associated carcinogenesis. CYLD expression and its associated pathways in intestinal tumors may be exploited for future prognostic and therapeutic purposes.

Beneficial bacteria inhibit cachexia.

Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny.

Evaluation of the possible transmission of BSE and scrapie to gilthead sea bream (Sparus aurata).

In transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrP(Sc)) of the host-encoded cellular prion protein (PrP(C)). While the precise mechanism of the PrP(C) to PrP(Sc) conversion is not understood, it is clear that host PrP(C) expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish. Here we show that while gilthead sea bream (Sparus aurata) orally challenged with brain homogenates prepared either from a BSE infected cow or from scrapie infected sheep developed no clinical prion disease, the brains of TSE-fed fish sampled two years after challenge did show signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs. Remarkably, the deposits developed much more rapidly and extensively in fish inoculated with BSE-infected material than in the ones challenged with the scrapie-infected brain homogenate, with numerous deposits being proteinase K-resistant. These plaque-like aggregates exhibited congophilia and birefringence in polarized light, consistent with an amyloid-like component. The neurodegeneration and abnormal deposition in the brains of fish challenged with prion, especially BSE, raises concerns about the potential risk to public health. As fish aquaculture is an economically important industry providing high protein nutrition for humans and other mammalian species, the prospect of farmed fish being contaminated with infectious mammalian PrP(Sc), or of a prion disease developing in farmed fish is alarming and requires further evaluation.