In vitro vs. in vivo studies on the interaction of natural products with the gut microbiota: the example of STW 5

The gut microbiota is increasingly seen to be a key factor in the therapeutic action of natural products. This is especially the case in functional diseases with a multifactorial etiology, as e.g. Irritable Bowel Syndrome (IBS) and functional dyspepsia (FD). Given the raising numbers of microbiota studies in preclinical models, it is a matter of current discussion, whether in vitro models well predict the in vivo situation. The objective of this study is to compare in vitro to in vivo data for a medicinal product with clinically proven therapeutic efficacy in IBS and FD, STW 5. A comprehensive literature review was conducted using PubMed and other scientific databases to collate data on STW 5’s impact on the gut microbiome at phyla and genera levels. In vitro studies demonstrated an increase in Enterococcus and Firmicutes and a decrease in Clostridium , Bacteroides, Blautia and Proteobacteria, with no change in Lactobacillus [1, 2]. In vivo studies in Wistar rat models of a healthy GI tract, UC and FD showed minor increases in Firmicutes, Bacteroidetes, Lactobacillus and Blautia and a significant decrease e.g. in Actinobacteria, Bacteroides , Bifidobacterium , and Prevotella, dependent from the model [3-5]. The different responses of some genera like Blautia and Enterococcus to STW 5 in in vitro models as compared to in vivo models highlight the complexity of its interactions with the microbiota, underscoring its multi-target mechanism of action. The identification of consistent microbial shifts associated with STW 5 provides mechanistic insights in its clinically proven health benefits. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany