The gastrointestinal tract is lined by a single layer of epithelial cells that are involved in digestion and uptake of nutrients on one hand and also act as a barrier against harmful pathogens and antigens (Groschwitz et al., 2016). Increased intestinal permeability as a result of barrier dysfunction is suggested to be a pivotal factor in the pathogenesis of various allergic, inflammatory and metabolic diseases including food allergy, inflammatory bowel disease and obesity (König et al., 2016). Since the control of epithelial permeability is energy dependent, mitochondria ought to be a key element in regulation of barrier integrity (Wang et al., 2014). Several studies have demonstrated the reciprocal relationship between mitochondria and gut microbiota (Saint-Georges.Chaumet et al., 2018; Clark&Mach 2017; Mottawa et al., 2016; Bär et al., 2013). One of the main mechanisms by which the microbiome exerts their effects is through the production of short-chain fatty acids (SCFA) as a consequence of fermenting carbohydrates and proteins (Koh et al., 2016). Propionic acid (PA), butyric acid (BT), and acetic acid are the most abundant SCFAs. A wide range of beneficial effects have been attributed to SCFA (den Besten et al., 2016). For example, treating energy-deprived colonocytes with BT overcomes their deficit in mitochondrial respiration and prevents them from undergoing autophagy (Donohoe et al., 2011). 

Here we aim to understand the mechanisms by which mitochondria affects host microbe interactions and how mitochondrial dysfunction lead to barrier dysfunction and disease. This will help us to extend our primary research to the field of food allergies, intestinal inflammation and metabolic diseases.

Aims: 

1. We aim to investigate the impact of microbiota-mitochondria interaction on the functional and metabolic identities of several intestinal cell entities that shape the barrier function

2. We will address the question of whether bacterial metabolites can boost mitochondrial respiration. Based on the preliminary results, we hypothesize that certain propionate producing- bacteria flourish as result of mitochondrial malfunction. This could be a compensatory mechanism to overcome the harmful consequences associated with low ATP level

3. The development of chronic intestinal inflammation is hypothesized to be strongly linked to pathogenic enteric bacteria in genetically susceptible individuals. We intend to study the ramifications of mitochondrial dysfunction on infection induced colitis animal model