The herbal medicinal product STW-5 is used in functional gastrointestinal diseases like dyspepsia and irritable bowel syndrome. The aim of the study is to investigate how gut bacteria metabolize STW-5 constituents, and how STW-5 is influencing gut microbial community composition, in order to elucidate the role of the human gut microbiome for the activity of STW-5.
Eingereicht von: Univ.-Prof. Dr. Rudolf Bauer
Firma/Universität: Universität Graz
Kooperationspartner: Medizinische Universität Graz; Steigerwald Arzneimittelwerk GmbH
The microbial community in the human distal gut has an enormous metabolic capacity. Gut microbial community composition underlies a strong inter-individual variability and is strongly influenced not only by genetic but also by external factors, like health status, eating habits, and medication. Herbal medicinal products are very likely to interact with human gut microbiota, since many constituents, like phenolic compounds, are poorly absorbed. In the past, interaction with gut microbiota often remained unconsidered when searching for the bioactive principles of herbal medicinal products.
The research team has established a collaborative research platform between the Center of Interactive Microbiome Research at Medical University of Graz and the Institute of Pharmaceutical Sciences at University of Graz, which is analyzing both, the impact of herbal extracts on microbial communities in the gut, and the changes of the metabolic profile caused by the bacteria during incubation with herbal medicinal products by using OMICS technologies. In order to mimic oral, gastric and small intestinal phase we are subsequently subjecting STW-5 to the respective enzyme and buffer mixes according to the InfoGest consensus method. The STW-5 pretreated in this way is subjected to in-vitro fermentation by fecal samples from healthy donors and IBS patients under physiological conditions. Metabolic profile changes are monitored over time by LC-HRMS analysis, and microbiome shifts by 16S rRNA gene sequencing.
Plant constituents/drugs not absorbed in the upper gastrointestinal tract interact with the microbial community residing in the distal gut, resulting in
- (potentially beneficial) reshaping of gut microbial community composition, and
- formation of (potentially bioactive) microbial metabolites from the plant constituents/drug
The tesearch team suggest that for the bioactivity of herbal medicines/drugs, these interactions may play a bigger role than estimated so far.
Relevant microorganisms and their functions can be identified by stable isotope probing. After incubation with stable-isotope-labeled compounds, their uptake by microorganisms is followed and key microorganisms are identified (microbiome analysis, targeted metabolomics, metagenomics).
Microbial metabolites may have higher bioactivity than the original drug/plant compounds. Active etabolites shall be isolated and identified.