Study provides potential way to treat inflammatory bowel disease
Findings of a new study by researchers from Weill Cornell Medicine in the USA would lead to novel treatments for patients with inflammatory bowel diseases. The researchers have identified a group of immune cells, known as CX3CR1
+ mononuclear phagocytes, that are responsible for controlling the populations of fungi in the intestines. Impairment in these cells' function appears to be associated with Crohn's disease, one of the two most common inflammatory bowel diseases.
You can read the full paper (CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi) in the journal Science.
In our intestines, there are diverse microbes, including bacteria, fungi, and viruses. This community of microbes is referred to as the gut microbiome. The connection between the gut microbiome and our health is not new. Accumulating evidence supports the metabolic, protective, and trophic roles of the gut microbiome. Certain species of gut microbes facilitate food digestion, promote nutrient absorption, modulate metabolism and immunity, and suppress pathogen growth. In contrast, some gut microbes are considered "bad" -- they can make you sick under certain conditions.
Numerous studies have been carried out to better understand the link between the gut microbiome and health. But most of these studies are about gut bacteria. The current study, however, looks at gut fungi. The corresponding author of the current study, Dr. Iliyan Iliev from Weill Cornell Medicine, noted that they had developed more effective approaches to examine fungal DNA. These approaches allowed them better understand the connection between gut fungi, immunity, and inflammatory disease. They discovered that CX3CR1+ mononuclear phagocytes, which are a part of the body's immune system, function as a major regulator of gut fungi. CX3CR1 is a cell surface receptor that binds the chemokine CX3CL1. The researchers found that CX3CR1+ mononuclear phagocytes are critical for the initiation of innate and adaptive immune responses to intestinal fungi. Ablation of CX3CR1+ mononuclear phagocytes in mice changed the composition of their gut fungi and caused colitis, and the illness could be rescued by treatment with antifungal agents. The researchers also investigated patients with Crohn's disease. They identified a mutation in the gene that encodes CX3CR1 and confirmed that the mutation is related to impairments in antifungal responses, including a reduced production of antibodies against fungi.
These data, collectively, indicate that CX3CR1+ mononuclear phagocytes play a key role in maintaining the balance between gut fungi and host immunity, and that lack of CX3CR1+ mononuclear phagocytes or dysfunction of these cells may contribute to inflammatory bowel disease. The study leads to a hypothesis that antifungal therapy may be a way to treat inflammatory bowel disease. Furthermore, the study demonstrates the important effect of gut fungi on human health, highlighting the need for further investigation into gut fungi.
Dr. Iliyan has been studying the complex interactions between commensal microbes and the host immune system for about 15 years. His research is aimed to elucidate how the composition and metabolism of fungal microbiota would influence the host immunity and bacterial populations in the gut.
In addition to Weill Cornell Medicine, the study also involves researchers from Cedars-Sinai Medical Center in the USA, Universidad Complutense de Madrid in Spain, and European Institute of Oncology in Italy.