A novel gastrointestinal microbiome modulator from soy pods reduces absorption of dietary fat in mice.

OBJECTIVE: Simplification of diets, low in variety but high in energy, contributes to the loss in diversity observed in the obese gastrointestinal (GI) microbiome. A novel GI microbiome modulator (GIMM) as a dietary intervention was developed. METHODS: Mice were fed either an obesogenic diet (ObD) or an ObD containing 15% activated soy pod fiber (ObD-ASPF) for 30 days. The diets were isocaloric and balanced for macronutrient content. ASPF is a novel fiber preparation from whole soy pods that is activated to produce glyceollins. RESULTS: Mice fed ObD-ASPF did not gain body fat. This was associated with decreased absorption of calories (P < 0.05) and increased fecal excretion of triglycerides, which may be attributed to decreased bile acid secretion (P < 0.05). A shift (P < 0.05) in abundances of microbiota in 10 genera was observed. Mice fed ObD-ASPF had elevated plasma concentrations of the anti-inflammatory IL-10 (P < 0.05) and decreased (P < 0.05) plasma concentrations of the neutrophil chemoattractant CXCL1. CONCLUSIONS: A novel dietary intervention derived from soy pods that acts to hinder absorption of dietary fat and glucose in mice was developed. More studies with this GIMM in animal models of diet-induced nonalcoholic fatty liver diseases, type 2 diabetes, and autism are needed.

Involvement of interleukin-18 in the pathogenesis of human eosinophilic esophagitis.

IL-18 is induced in food allergy and EoE is food allergen-induced disease. Therefore, we tested the hypothesis whether IL-18 is involved in food allergen-induced EoE pathogenesis. Accordingly, we examined normal SPT+ and SPT- EoE patient blood and biopsy samples for IL-18, IL-18Rα, ICAM and VCAM expression. Herein, we show increased IL-18 level is highly significant in food allergen SPT+ compared to SPT- EoE patients. We also report that IL-18Rα+ cells and mRNA levels are induced in the esophageal biopsies of EoE patients and blood IL-18 levels correlate with esophageal eosinophilia (P<0.01). Additionally, we report that the levels of esophageal eosinophil and mast cells correlate with ICAM expression in human EoE. Mechanistically, we show that IL-18 in vitro stimulates iNKT cells and endothelial cells and induce eosinophil active cytokines IL-5 and IL-13. We provide the evidence that IL-18 is critical cytokine involved in activation of iNKT cells and ICAM in promoting human EoE.

Celiac and Non-Celiac Forms of Gluten Sensitivity: Shifting Paradigms of an Old Disease.

Gluten sensitivity is one of the prominent features of celiac disease (CD) which is an autoimmune disorder characterized by damaged lining of the small intestine. CD was known already to ancient Greeks as κοιλιακός (keeleeakoss) i.e. disease of the abdominal cavity hence celiac. Focus of this Commentary article is on rather complex definition of CD and its emerging new forms the example of which is non-celiac gluten sensitivity. It is becoming evident that to formulate more effective treatments, these associations and newly identified disease entities deserve attention from both academic and clinical communities.

Tumor necrosis factor receptor 1 functions as a tumor suppressor.

Tumor necrosis factor (TNF) is a key player in inflammatory bowel disease and has been variably associated with carcinogenesis, but details of the cross talk between inflammatory and tumorigenic pathways remain incompletely understood. It has been shown that, in C57BL/6 mice, signaling via TNF receptor 1 (TNFR1) is protective from injury and inflammation in experimental colitis. Therefore, we hypothesized that loss of TNFR1 signaling would confer increased risk of developing colitis-associated carcinoma. Using three models of murine tumorigenesis based on repeated bouts of inflammation or systemic tumor initiator, we sought to determine the roles of TNF and TNFR1 with regard to neoplastic transformation in the colon in wild-type (WT), TNFR1 knockout (R1KO), and TNF knockout (TNFKO) mice. We found R1KO animals to have more severe disease, as defined by weight loss, hematochezia, and histology. TNFKO mice demonstrated less weight loss but were consistently smaller, and rates and duration of hematochezia were comparable to WT mice. Histological inflammation scores were higher and neoplastic lesions occurred more frequently and earlier in R1KO mice. Apoptosis is not affected in R1KO mice although epithelial proliferation following injury is more ardent even before tumorigenesis is apparent. Lastly, there is earlier and more intense expression of activated ß-catenin in these mice, implying a connection between TNFR1 and Wnt signaling. Taken together, these findings show that in the context of colitis-associated carcinogenesis TNFR1 functions as a tumor suppressor, exerting this effect not via apoptosis but by modulating activation of ß-catenin and controlling epithelial proliferation.

Retrospective analysis of clinical and laboratory factors associated with lymphoma in simian AIDS.

A nonhuman primate model for AIDS-associated Non-Hodgkin's lymphoma (AIDS-NHL) has been described in which animals inoculated with simian immunodeficiency virus (SIV) develop simian AIDS (SAIDS) and SAIDS-NHL. The objective of the present study was to describe statistically the major trends observed in clinical and laboratory data collected longitudinally on a large cohort of nonhuman primates that developed SAIDS-NHL. Clinical and laboratory data were collected longitudinally on each animal from the time of SIV infection throughout progression to lymphoma. Data were analyzed retrospectively with regard to species, gender, age at SIV inoculation, survival, cause of death, CD4+ T-cell and B-cell counts, SIV antigenemia, persistent lymphoid hyperplasia and lymphocryptovirus infection. Median survival time (354 days: 95% CI 309-388) was not related to gender, age at SIV inoculation, cause of death, or RhLCV infection. Survival was not related to CD4+ T-cell count at the time of SIV infection (P = 0.5531), but increased survival was significantly related to a slower rate of CD4+ T-cell decline (P = 0.0256). A B-cell expansion was observed at the midpoint of disease. A steep rise in SIV antigenemia was detected in the first 21 days of infection followed by a rapid decline. This pattern did not occur in animals inoculated with SIV as infants or yearlings. Of 45 cases, 9 exhibited marked, persistent lymphoid hyperplasia. These results describe trends identified in clinical and laboratory factors associated with SAIDS-NHL in the largest collection of such samples in the world. The results contribute to an understanding of the etiology of SAIDS-NHL and to the future development of useful predictors of SAIDS- or AIDS-related lymphoma.