We propose that several of those gut bacteria that leave the gut are a major problem in human lupus patients. To test this idea, we will
- investigate cohorts of lupus patients for the presence of these and other gut bacteria and for signs of immune reactions towards these bacteria and gut barrier leakiness.
- apply detailed gene scanning studies and statistics to determine which genes and functions of these gut bacteria may play a role in promoting lupus in patients.
- also transfer gut microbes from lupus patients into antibiotic-treated mice.
- identify all human bacteria that leave the gut and reach internal organs.
- we will assess the gut barrier and the immune functions in these animals.
- also use means to predispose these animals to lupus and test if the traveling bacteria worsen disease.
- next use mice that are devoid of all microbes and grown up in sterile bubbles to test the role of these bacteria in the absence of any other bacteria.
- screen the bacteria for gut barrier and organ damaging mechanisms.
We expect to find subsets of lupus patients that carry these bacteria as well as certain immune and gut barrier abnormalities that fit to these bacteria. If true, this discovery would have far-reaching implications for patients in the long run because an entirely new set of lupus diagnostics and treatments could be developed that focus on these invading gut bacteria. This concept could also be applicable to other autoimmune diseases that afflict a large proportion of the general population.
- Project 1: Define microbial taxa enriched in a well-defined cohorts of patients with active SLE and to characterize their gut barrier function and blood reactivities
- Project 2: Test the translocating capacity of whole microbiota as well as previously and newly identified pathobiont candidates in lupus-prone animal models
- Project 3: Dissect the pathogenic mechanisms of selected pathobionts in 3D ex vivo and germ-free in vivo models