Fungal feelings: The gut mycobiome in irritable bowel syndrome and inflammatory bowel disease

Abdominal pain is among the most debilitating symptoms of irritable bowel syndrome (IBS), and often originates from enhanced sensitivity to colorectal distension (i.e., visceral hypersensitivity). Recently, it was shown that patients with IBS have altered intestinal fungal compositions (i.e., gut mycobiome) compared to healthy volunteers. A causal role for the gut mycobiome was additionally shown in an IBS-like rodent model for visceral hypersensitivity. Gut fungi have also been linked to severity of disease for patients with inflammatory bowel disease (IBD). Since patients with IBD in remission may experience abdominal pain resembling that of IBS, it is likely that similar mechanisms are involved. We aimed to further elucidate mycobiome-related mechanisms contributing to intestinal symptoms for patients with IBS and IBD through various approaches. First, we showed that modulation of the gut fungi in IBS-like rats with miltefosine decreases visceral hypersensitivity. We next investigated fecal samples of normo- and hypersensitive IBS patients, but found no differences in the fungal composition. We thus sought a functional explanation, and hence cultured fecal samples of IBS patients and healthy volunteers. We observed genetic and functional diversity variation among feces-derived Candida albicans isolates. Alike observations were made for patients with IBD in remission suffering from persistent abdominal pain. Last, fecal microbiota transplantation is currently investigated to decrease intestinal inflammation. We determined that abundance of the yeast genus Filobasidium in fecal material for transplantation associated with response to fecal microbiota transplantation in patients with ulcerative colitis. Our findings emphasize the relevance of the gut mycobiome in IBS and IBD, both in active disease and remission.