Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin-15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and have a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). Although the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S ribosomal RNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (villin-IL-15 transgenic (v-IL-15tg) mice) shows distinct changes in the composition of the intestinal bacteria. Although some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate-producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate-induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.

Enzymatic digestion, or hydrolysis, has been proposed for treating gluten-containing foods and beverages to make them safe for persons with celiac disease (CD). There are no validated testing methods that allow the quantitation of all the hydrolyzed or fermented gluten peptides in foods and beverages that might be harmful to CD patients, making it difficult to assess the safety of hydrolyzed products. This study examines an ELISA-based method to determine whether serum antibody binding of residual peptides in a fermented barley-based product is greater among active-CD patients than a normal control group, using commercial beers as a test case. Sera from 31 active-CD patients and 29 nonceliac control subjects were used to assess the binding of proteins from barley, rice, traditional beer, gluten-free beer, and enzymatically treated (gluten-removed) traditional beer. In the ELISA, none of the subjects' sera bound to proteins in the gluten-free beer. Eleven active-CD patient serum samples demonstrated immunoglobulin A (IgA) or immunoglobulin G (IgG) binding to a barley extract, compared to only one nonceliac control subject. Of the seven active-CD patients who had an IgA binding response to barley, four also responded to traditional beer, and two of these responded to the gluten-removed beer. None of the nonceliac control subjects' sera bound to all three beer samples. Binding of protein fragments in hydrolyzed or fermented foods and beverages by serum from active-CD patients, but not nonceliac control subjects, may indicate the presence of residual peptides that are celiac-specific.

Tang et al. show that cytotoxic effector cells produce and respond to cysteinyl leukotrienes to allow target cell killing dependent on NKG2D and IL-15. They further demonstrate a role for cysteinyl leukotrienes in celiac disease pathogenesis.

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