Microbiome, Dietary and Quality of Life Analysis of People Living With CVID Treated With or Without Immunoglobulins.

Our research group focusses on finding evidence-based diet strategies to overcome immune dysregulation either due to immune checkpoint inhibitors (ICI) or common variable immunodeficiency (CVID) (Figure 1). CVID is an inborn error of immunity, which is defined, among other factors, by a low level of immunoglobulins, resulting in an increased risk of infections, auto-immune/inflammatory diseases, and cancer. The gut microbiome (GM) plays a crucial role in maintaining immune homeostasis and modulating the host's innate and adaptive immune responses. Modulation of the GM can be achieved by dietary interventions that have been demonstrated to change the composition of the GM within 2 weeks (Oliver et al., 2021). The intake of more than 30 different plant products (vegetables, fruits, seeds and grains) on a weekly basis is associated with a more diverse microbiome in healthy adults (McDonald et al., 2018). Although direct proof of a link between diet and functioning of the immune system is lacking, it is striking that in a retrospective study, melanoma patients treated with immune checkpoint inhibitors (ICI) had a better overall survival when they consumed enough fibers without taking probiotics (Spencer et al., 2021). Currently, we have included 54 of 60 foreseen patients receiving ICI in an interventional study (FORX-01 (NCT05832606)) at our centre, providing them weekly with 30 different plants to be integrated in their diet (funded by Delhaize and FWO). The aim is to measure if the interventional group develops less immune-related adverse events (= side effects of ICI) by changing their GM. Similarly, we hypothesize that introducing a fiber-rich diet in patients with CVID will result in a more diverse GM leading to a decrease in autoimmune disorders and infections and as such lead to an improvement of quality of life. To challenge this hypothesis, we plan to organize a similar diet trial, called KNIVES. To prepare this study, we will first perform an observational study to describe the microbiome of people with CVID (DELICIOUS) followed at UZ Brussel.