Toxin-secreting Gut Bacterium Emerges As A Driver Of Ulcerative Colitis

A toxin-secreting gut bacterium whitethorn substance ulcerative colitis by sidesplitting protective immune cells that support intestinal homeostasis, according to a caller study. The findings propose imaginable for caller curen strategies. Ulcerative colitis (UC) is simply a chronic inflammatory bowel illness affecting millions of group worldwide successful which nan body's immune strategy attacks nan digestive tract, often causing terrible and recurring symptoms, including abdominal pain, diarrhea, and intestinal bleeding. Although nan underlying causes of UC stay unclear, erstwhile investigation indicates that nonaccomplishment of nan intestinal epithelial obstruction plays an important domiciled successful illness progression.

Intestinal macrophages are important to maintaining nan gut's protective epithelial barrier. Zhihui Jiang and colleagues examined colon biopsies from patients pinch UC and recovered that subepithelial, tissue-resident macrophages were almost wholly absent, moreover successful areas that were not yet showing inflammation. Further experiments successful rodent models confirmed that removing these macrophages made nan colon highly susceptible to inflammation.

Suspecting a microbial cause, Jiang et al. discovered that fecal samples from UC patients contained aerolysin, a pore-forming toxin produced by a version of Aeromonas bacteria, which proved selectively lethal to macrophages but not to epithelial cells. In rodent models, infection pinch this macrophage-toxic bacterium (MTB) sharply worsened colitis, whereas mutant strains lacking aerolysin did not. What's more, MTB infection had nary effect successful mice already depleted of gut-resident macrophages, and neutralizing aerolysin pinch antibodies alleviated illness symptoms.

In a objective study involving 574 participants, Jiang et al. discovered that Aeromonas species were coming successful 72% of UC patients but only ~12% of patient individuals and astir absent successful those pinch Crohn's disease, further linking nan bacterium to illness occurrence. "Directly targeting these microbes and their toxins could beryllium a promising avenue for treating [inflammatory bowel disease] without inhibiting nan patients' immune strategy pinch biologics, specified arsenic antibodies, and steroid drugs," constitute Sonia Modilevsky and Shai Bel successful a related Perspective.