Influence of the intestinal microbiota and antibiotic therapy on the regulation of enteroendocrine cells of the gastrointestinal tract

• Applicant: Dr. Soraya Mousavi
• Subject Area: Gastroenterology ; Endocrinology, Diabetology, Metabolism
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556926858

In addition to nutrient absorption, the gastrointestinal tract acts as an immune organ and an important barrier that protects the body from the harmful effects of luminal contents. Although enteroendocrine cells (EECs) make up only 1% of the intestinal epithelial cells, their hormonal function makes the gut one of the most important organs of the endocrine system. The EECs produce hormones such as glucagon-like peptide (GLP)-1 and serotonin, whose effects are of central importance. In vitro studies have shown that the activation and thereby the release of gut hormones such as GLP-1 or serotonin is strongly dependent on bacterial metabolites and that the composition of the gut microbiota plays a crucial role. The composition of the human gut microbiota is individually unique and is continuously altered by diet, exercise, medication, intestinal inflammation, tumor disease, and antibiotic use. The composition of the intestinal microbiota shows a pronounced resilience, and after changes, the original individual microbiota composition usually returns. However, if the resilience is eliminated, e.g. by long-term use of medication such as antibiotics, the microbial composition changes permanently into a state known as dysbiosis. Research over the past few decades has shown that this change affects physiological and immunomodulatory functions throughout the body. In addition to the regulation of the basic metabolism, neuronal processes are also influenced by bacterial metabolites via the so-called "gut-brain axis", which are of fundamental importance for maintaining health. Hormonal signals from the EECs play an important role in these systemic effects of the intestinal microbiota, although the underlying mechanisms are largely unclear. This project aims to investigate the diverse interactions of the EECs with bacterial metabolites of the intestinal microbiota after antibiotic therapy, which can lead to changes in hormone release in the intestine and thus undesirable side effects. Furthermore, it will be investigated whether hormone production altered by antibiotic therapy results from a disruption in the interactions between bacterial molecules or metabolites and EECs and whether this disruption can be corrected by recolonizing the intestine with probiotics. Additionally, we will investigate the role of specific receptors for bacterial metabolites (e.g. aryl hydrocarbon receptor (AhR) and butyrate receptor) in the regulation of hormone production by the EECs by using knockout mice. Furthermore, it will be clarified whether therapeutic approaches with AhR agonists and short-chain fatty acids such as butyrate can counteract the metabolite deficiency caused by antibiotic therapy.

• DFG Programme: Research Grants