Abstract
To assess the safety and efficacy of oral immune interventions, it is important and required by regulation to assess the impact of those interventions not only on the immune system, but also on other organs such as the gut as the porte d'entrée. Despite clear indications that the immune system interacts with several physiological functions of the gut, it is still unknown which pathways and molecules are crucial to assessing the impact of nutritional immune interventions on gut functioning. Here we used a network-based systems biology approach to clarify the molecular relationships between immune system and gut functioning and to identify crucial biomarkers to assess effects on gut functions upon nutritional immune interventions. First, the different gut functionalities were categorized based on literature and EFSA guidance documents. Moreover, an overview of the current assays and methods to measure gut function was generated. Secondly, gut-function related biological processes and adverse events were selected and subsequently linked to the physiological functions of the GI tract. Thirdly, database terms and annotations from the Gene ontology database and the Comparative Toxicogenomics Database (CTD) related to the previously selected gut-function related processes were selected. Next, database terms and annotations were used to identify the pathways and genes involved in those gut functionalities. In parallel, information from CTD was used to identify immune disease related genes. The resulting lists of both gut and immune function genes showed an overlap of 753 genes out of 1,296 gut-function related genes indicating the close gut-immune relationship. Using bioinformatics enrichment tools DAVID and Panther, the identified gut-immune markers were predicted to be involved in motility, barrier function, the digestion and absorption of vitamins and fat, regulation of the digestive system and gastric acid, and protection from injurious or allergenic material. Concluding, here we provide a promising systems biology approach to identify genes that help to clarify the relationships between immune system and gut functioning, with the aim to identify candidate biomarkers to monitor nutritional immune intervention assays for safety and efficacy in the general population. This knowledge helps to optimize future study designs to predict effects of nutritional immune intervention on gut functionalities.
Highlights
A well balanced immune system is key for overall health and well-being, the concept of boosting immunity is gaining in popularity as today’s complex world presents many potential health challenges
The gut being the porte d’entrée of oral immunotherapy has been selected as one of the key priority organs to include in this study
Despite established association studies that immunotherapy can influence gut functioning [12,13,14,15,16], it is still largely unknown which immune and gut function-related pathways and biomarkers are crucial to monitor in relation to gut functioning upon nutritional immune interventions
Summary
A well balanced immune system is key for overall health and well-being, the concept of boosting immunity is gaining in popularity as today’s complex world presents many potential health challenges These health challenges range from environmental pollution, infections, the use of medication, the harmful effects of lifestyle stress and the effects of intense physical workouts on the body’s natural ability to stay healthy. Besides beneficial effects of oral immunotherapy and – prophylaxis on the functioning of the immune system itself [1,2,3,4,5,6,7,8,9,10], (re/un) balancing the immune system may generate dis-immune toxicities These so-called “immune-related adverse events” can come forward in the immune system itself [recently addressed in [11]], resulting in, for instance, increased incidences or severity of inflammatory diseases, but may affect other immune system-interacting organ systems. Despite established association studies that immunotherapy can influence gut functioning [12,13,14,15,16], it is still largely unknown which immune and gut function-related pathways and biomarkers are crucial to monitor in relation to gut functioning upon nutritional immune interventions
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