Therapeutic manipulation of the gut microbiome in inflammatory bowel disease

Crohn’s disease (CD) and ulcerative colitis (UC) are idiopathic inflammatory bowel diseases (IBD) characterized by chronic relapsing inflammation of the gut. The peak onset of both diseases is during adolescence and young adulthood. The incidence of IBD is rising worldwide. The conventional treatment options (5-aminosalicylates, thiopurines, methotrexate and/or biological agents as anti-TNF antibodies or vedolizumab) aiming at suppressing the chronic intestinal inflammation are not universally effective. A substantial proportion of patients still requires bowel resection.

The complex pathogenesis of IBD remains largely unknown. Increasing evidence supports the hypothesis that IBD results from an abnormal immune response against the commensal microbiota in a genetically susceptible host, and that environmental factors trigger the onset or reactivation of the disease. Accumulating data show that the microbiota play a pivotal role in the onset and perpetuation of IBD. The overall composition of the gut microbiota and the presence or absence of specific species is important for homeostasis and tolerance of the immune system. Manipulation of the enteric microbiota to restore normobiosis has therapeutic potential in IBD.

In this research project we will try to manipulate the enteric microbiota of UC patients by performing fecal microbiota transplantation (FMT), the transfer of the gastrointestinal microbiota from a donor to a patient. This has been suggested as a promising treatment for patients with IBD. FMT is already an emerging treatment for refractory and recurrent Clostridium difficile infections. We will study the effects of donor variability, the influence of concomitant diet and the importance of repeating FMT. We designed a multicenter interventional study with FMT to answer these questions.

The effect of the fecal and mucosal composition of the microbiota on response to drugs (anti-TNF, anti-integrin and anti IL12/23 agents) and vice versa, the effect of drugs on the composition of the microbiota, is poorly studied. Few studies indicated the microbiota as a potential biomarker to predict therapeutic response. In the second part of this research project we will investigate this aspect, to see if microbial profiles can be used as activity marker or predictor of success in the future.