The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease (IBD). Here we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility t chemically-induced colitis, which was the result of altered responses to indigenous fungi. In humans we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together our findings reveal a novel eukaryotic fungal community in the gut (the “mycobiome”) that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.
Compared to bacteria, the role of fungi within the intestinal microbiota is poorly understood. In this study we investigated whether the presence of a “healthy” fungal community in the gut is important for modulating immune function. Prolonged oral treatment of mice with antifungal drugs resulted in increased disease severity in acute and chronic models of colitis, and also exacerbated the development of allergic airway disease. Microbiota profiling revealed restructuring of fungal and bacterial communities. Specifically, representation of Candida spp. was reduced, while Aspergillus, Wallemia, and Epicoccum spp. were increased. Oral supplementation with a mixture of three fungi found to expand during antifungal treatment (Aspergillus amstelodami, Epicoccum nigrum, and Wallemia sebi) was sufficient to recapitulate the exacerbating effects of antifungal drugs on allergic airway disease. Taken together these results indicate that disruption of commensal fungal populations can influence local and peripheral immune responses and enhance relevant disease states.
Highlights d M. restricta is associated with the colonic mucosa in Crohn's disease (CD) patients d M. restricta exacerbates colitis in wild-type and gnotobiotic mice d M. restricta is found in CD patients with a disease-linked polymorphism in CARD9 d Malassezia-exacerbated colitis in mice requires signaling via CARD9
Stricture of the anastomosis between the bladder neck and membranous urethra after radical prostatectomy can cause significant voiding dysfunction. Of 156 patients undergoing radical prostatectomy for localized prostatic carcinoma 18 had anastomotic stricture for an over-all incidence of 11.5%. The risk factors for anastomotic stricture and the treatment outcome in these patients were analyzed. Excessive intraoperative blood loss, extravasation of urine at the anastomotic site and a prior transurethral prostatic operation significantly contributed to the development of stricture. More than half of the patients did not respond to simple dilation alone. Cold knife incision of the stricture by itself was effective in only 62% of the patients. The remaining patients required periodic dilation to maintain an adequate urine flow. Incision of the stricture with electrocautery resulted in urinary incontinence in all patients.
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