What we do
Human interactions with the microbiota are mediated by chemistry. Chemical signals are important in the establishment and maintenance of mutualism. We study the chemically-mediated interactions between gut microbiota and the gut. We seek to identify the specific molecules that function as signals mediating (1) the gut health with a main focus on changes in gut motility but also gut-brain axis, (2) bacterial ecosystem and its metabolic interactions. For example, we recently showed how bacterial metabolisation of the food supplement 5-hydroxytryptophan into a compound, which is a potent stimulant of gut motility (1).
In parallel, we look into interactions between gut bacteria and medication, which impact the effectiveness of treatment. For example, we uncovered that gut microbiota can be a threat for the effectiveness of medication for Parkinson’s patients and this can likely be circumvented by dietary interventions that change our gut microbes (2,3).
Figure 1. Overview of the research questions
Techniques we apply
We use pure bacterial strains isolated from human gut, co-cultures, and human fecal slurry from healthy subjects and patients to perform fermentation experiments. We rely on chromatographic techniques, such as high performance liquid chromatography, to isolate and identify bioactive metabolites. We apply classical microbiology and bio-chemistry techniques to characterize bacterial enzymes involved in this metabolism.
To study potential interactions between bacterial metabolites and changes in gut motility, we employ an ex-vivo system (organ bath). Moreover, we use several in vitro models cell culture models to decipher this metabolic interaction between the microbes and their host. Examples of these models include primary epithelial cells (organoids), macrophages, and enteric neurons, in addition to several reporter cell lines that we develop to overexpress receptors of interest. In some cases, we test whether our working model based on ex vivo tests are translatable in complex biological environment using in vivo rodent models through close collaboration with GELIFES institute.
1. Waclawiková, B., Bullock, A., Schwalbe, M., Aranzamendi, C., Nelemans, S.A., van Dijk, G., El Aidy, S. Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels. PLoS biology. (2021) 19(1) e3001070.
2. van Kessel SP, Frye AK., El-Gendy AO, Castejon M, Keshavarzian A, van Dijk GJ, El Aidy S. Gut bacterial tyrosine decarboxylases restrict the bioavailability of levodopa, the primary treatment in Parkinson’s disease. Nature Communications (in press; doi: 10.1038/s41467-019-08294-y).
3. van Kessel, S.P., de Jong, H.R., Winkel, S.L., van Leeuwen, S.S., Nelemans, S.A., Permentier,H., Keshavarzian, A., El Aidy,S. Bacterial deamination of residual levodopa medication for Parkinson's disease elicits inhibitory effect on gut motility. BMC Biol. (2020) 18:137.