According to a new research from Weill Cornell Medicine, individual Candida albicans yeast strains in the human gut are as different from each other, and some C. albicans strains may damage the gut of patients with inflammatory bowel disease (IBD).
The researchers, who published their findings on Nature on March 16, used a variety of methods to analyze strains, or genetic variants, of Candida from the colonies of people with or without ulcerative colitis, a chronic, relapsing, and remitting inflammation of the colon and rectum, and one of the principal forms of IBD. They found that certain strains, which they call high-damaging, produce a powerful candidalysin that damages immune cells.
So, such strains were retained to their high-damaging properties when they were removed from the patient''s gut and triggered pro-inflammatory immunity when colonized in mice, replicating certain disease hallmarks, according to senior author Dr. Iliyan Iliev, an associate professor in immunology in medicine at the Division of Gastroenterology and Hepatology and a scientist at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.
IBD affects approximately 3.1 million people in the United States and can greatly affect patients'' quality of life. However, they may not always be effective using steroids, according to a new study. mice with the medication to suppress intestinal inflammation failed in the absence of high-damaging C. albicans strains.
C. albicans strains do not cause spontaneous intestinal inflammation in a host with intact immunity, according to Dr. Iliev. They expand in the intestines when inflammation is present and can be a factor that impacts therapy therapy in our patients.
Most studies of the human microbiome in healthy individuals and those with IBD have focused on bacteria and viruses, but recent research by Dr. Iliev and others has demonstrated that intestinal fungi play an important role in regulating immunity at outside surfaces, including the intestines and lungs, due to their promising immune-stimulating abilities. While the collective community of fungi in the body, known as the mycobiota, has been linked to several diseases, including IBD, however, researchers have previously discovered that
Candida strains, although highly diverse in both patients with and without colitis, were on average more abundant in IBD patients. However, that did not explain disease outcomes in individual patients. So, the investigators set forth a strategy to identify the characteristics of these strains that cause damage and how they relate to each patient.
The researchers discovered that severe disease was associated with the presence of high-damaging Candida strains in patients with ulcerative colitis, which proved to be having a significant impact on the immune system. All of the bacteria are immune cells called macrophages, triggering a storm of the pro-inflammatory cytokine IL-1.
The researchers studied macrophages in the presence of Candida strains and found that the ability of the strains to induce IL-1 corresponded closely to the severity of colitis in the patients.
The first author, Dr. Xin Li, who was a Charles H. Revson postdoctoral fellow at the time of the study, said that a cell-damaging toxin candidalysin from high damaging C. albicans strains during the yeast-hypheryl morphogenesis stimulated pathogenic immunological responses in the gut.
Experiments in mice demonstrated that candidalysin-producing high-damaging strains induced the expansion of a population of T cells called Th17 cells and other immune cells associated with inflammation, such as neutrophils.
Neutrophils contribute to tissue damage, and their accumulation is a hallmark of active IBD, according to Dr. Ellen Scherl, the Jill Roberts Professor of Inflammatory Bowel Disease at Weill Cornell Medicine and a gastroenterologist at New York-Presbyterian/Weill Cornell Medical Center. These factors may, in part, be influenced by a fungal toxin released by yeast strains in certain patients.
The blocking of IL-1 signaling had a significant effect in reducing colitis signs in mice that harbored these highly pro-inflammatory strains. Other recent studies have linked IBD to IL-1 in a general manner, indicating that drugs are being investigated as possible IBD therapies.
Nevertheless, we do not know whether specific strains are acquired by specific patients during the course of disease, or if they have always been there and become a problem during episodes of active illness, according to Dr. Iliev.
The researchers are continuing to examine the mechanisms that regulate the persistence of candidalysin-producing strains in the affected colon of certain IBD patients, as well as ways to select patients for therapy targeting the mycobiome.