A modern toolbox to elucidate the role of the human microbiome in modulating mycobacterial gut infections

Inflammatory bowel diseases (IBDs) are a major public and veterinary health concern, but the causes are poorly understood. In this review, we discuss the potential of mycobacteria as causative factors for such diseases. We focus on similarities between the most common human IBD, Crohn's disease, and a common IBD in cattle, Johne's disease. Both are multifactorial diseases, leading to a chronic hyperinflammatory immune response of the intestines. However, the underlying genetic and environmental factors, such as variations in the intestinal microbiome, are still poorly understood. While Johne's disease has been shown to be caused by Mycobacterium avium subsp. paratuberculosis, the likeliness of mycobacteria as a causative factor of Crohn's disease is still heavily debated. In this review, we summarize the advances in research that could be used to further investigate the role of mycobacteria in intestinal diseases and to give better estimations about which mycobacterial species are most probably hazards for health. New advances in molecular, genetic and imaging methods give hope for better diagnostics, disease prevention, and development of new therapeutics. In addition, these techniques offer researchers a toolbox and general model systems for better understanding the mechanisms of intestinal diseases caused by mycobacteria and the role of the microbiome in the control of disease progression.