The serotonin signalling system plays a key role in the modulation of bidirectional brain-gut interactions involved in cognition, emotions, emesis and digestive functions. Although alterations within the serotonergic system are assumed to contribute to conditions like irritable bowel syndrome (IBS) and eating disorders, its role in their pathomechanism still remains enigmatic. Patients often concomitantly suffer from anxiety and depression. 5-HT₃ receptor antagonists are beneficial in the treatment of these conditions, but not all patients respond satisfyingly (Walstab et al., 2010a, Niesler 2011). We therefore hypothesized that 5-HT₃ receptor variants may influence 5-HT₃ signalling in the brain-gut axis and thereby modify susceptibility to both, neurogastrointestinal and psychiatric disorders.
Our research focus in the past comprised the serotonin receptor system, in particular the serotonin type 3 receptor (5-HT₃ R) diversity and its role in the aetiology of neuropsychiatric and neurogastrointestinal disorders. In our efforts to elucidate the heterogeneity of 5-HT₃ receptors, we isolated and characterized three novel 5-HT3 (HTR3) genes (Niesler et al, 2003; 2007; Walstab et al., 2010b).
We have identified HTR3 variants involved in depression and anxiety as well as anorexia and IBS and in individual drug response which may serve as pharmacogenetic and biomarkers in the future (Niesler et al. 2001a;Niesler et al. 2001b;Frank et al., 2004; Kapeller et al., 2008; 2009; Fasching et al., 2008; Hammer et al., 2009; Hammer et al. 2010; Kilpatrick et al., 2011).
To gain further insight into the pathomechanism of disease and the role of 5-HT₃ receptors, we established 5-HT3 specific antibodies and confirmed expression of all 5-HT₃ receptor subunits in the human enteric nervous system, 'the little brain of the gut', and the gut mucosa (Kapeller et al., 2011).

We have recently established the German IBSNet, in which five centers collect IBS samples to unravel genetic causes of IBS. We are currently characterising 5-HT₃ receptor distribution and composition in the human gastrointestinal tract and the brain in order to identify tissue specific subtypes which we aim to target by microRNAs (transcript level) and specific drugs or antibodies (protein level) in order to establish novel treatment strategies for IBS.