Rapid biotransformation of STW 5 constituents by human gut microbiome from IBS- and non-IBS donors.

STW 5, a blend of nine medicinal plant extracts, exhibits promising efficacy in treating functional gastrointestinal disorders, notably irritable bowel syndrome (IBS). Nonetheless, its effects on the gastrointestinal microbiome and the role of microbiota on the conversion of its constituents are still largely unexplored. This study employed an experimental ex vivo model to investigate STW 5's differential effects on fecal microbial communities and metabolite production in samples from individuals with and without IBS. Using 560 fecal microcosms (IBS patients, n = 6; healthy controls, n = 10), we evaluated the influence of pre-digested STW 5 and controls on microbial and metabolite composition at time points 0, 0.5, 4, and 24 h. Our findings demonstrate the potential of this ex vivo platform to analyze herbal medicine turnover within 4 h with minimal microbiome shifts due to abiotic factors. While only minor taxonomic disparities were noted between IBS- and non-IBS samples and upon treatment with STW 5, rapid metabolic turnover of STW 5 components into specific degradation products, such as 18ß-glycyrrhetinic acid, davidigenin, herniarin, 3-(3-hydroxyphenyl)propanoic acid, and 3-(2-hydroxy-4-methoxyphenyl)propanoic acid occurred. For davidigenin, 3-(3-hydroxyphenyl)propanoic acid and 18ß-glycyrrhetinic acid, anti-inflammatory, cytoprotective, or spasmolytic activities have been previously described. Notably, the microbiome-driven metabolic transformation did not induce a global microbiome shift, and the detected metabolites were minimally linked to specific taxa. Observed biotransformations were independent of IBS diagnosis, suggesting potential benefits for IBS patients from biotransformation products of STW 5. IMPORTANCE: STW 5 is an herbal medicinal product with proven clinical efficacy in the treatment of functional gastrointestinal disorders, like functional dyspepsia and irritable bowel syndrome (IBS). The effects of STW 5 on fecal microbial communities and metabolite production effects have been studied in an experimental model with fecal samples from individuals with and without IBS. While only minor taxonomic disparities were noted between IBS- and non-IBS samples and upon treatment with STW 5, rapid metabolic turnover of STW 5 components into specific degradation products with reported anti-inflammatory, cytoprotective, or spasmolytic activities was observed, which may be relevant for the pharmacological activity of STW 5.

Application of an in vitro digestion model to study the metabolic profile changes of an herbal extract combination by UHPLC-HRMS.

BACKGROUND: STW 5 is a fixed herbal combination containing extracts from nine medicinal plants: bitter candytuft, greater celandine, garden angelica roots, lemon balm leaves, peppermint leaves, caraway fruits, licorice roots, chamomile flowers, and milk thistle fruit. STW 5 is a clinically proven treatment for functional dyspepsia and irritable bowel syndrome. PURPOSE: Using a static in vitro method, we simulated oral, gastric, and small intestinal digestion and analyzed the metabolic profile changes by UHPLC-HRMS to determine the impact of oro-gastro-intestinal digestion on STW 5 constituents. STUDY DESIGN AND METHODS: STW 5 was incubated according to the InfoGest consensus method. Samples of each digestive phase were analyzed by UHPLC-HRMS in ESI positive and negative modes. After data processing, background subtraction, and normalization, the peak areas of detectable compounds were compared to untreated reference samples and recovery ratios were calculated to monitor the metabolic profile of STW 5 during simulated digestion. RESULTS: Although the levels of some constituents were reduced, we did not observe complete degradation of any of the constituents of STW 5 upon in vitro digestion. We did not detect any new metabolites beyond increased levels of caffeic acid and liquiritigenin due to degradation of progenitor compounds. Changes observed in intestinal bioaccessibility ratios were mainly a result of isomerization, hydrolysis, protein binding, and low water solubility. CONCLUSION: The majority of STW 5 constituents are stable towards simulated in vitro digestion and can reach the colon to interact with gut microbiota if they remain unabsorbed in the upper intestinal tract.

The role of gut microbiota for the activity of medicinal plants traditionally used in the European Union for gastrointestinal disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Many medicinal plants have been traditionally used for the treatment of gastrointestinal disorders. According to the monographs published by the Committee on Herbal Medicinal Products (HMPC) at the European Medicines Agency, currently 44 medicinal plants are recommended in the European Union for the treatment of gastrointestinal disorders based on traditional use. The main indications are functional and chronic gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome (IBS), and typical effects of these plants are stimulation of gastric secretion, spasmolytic and carminative effects, soothing effects on the gastrointestinal mucosa, laxative effects, adstringent or antidiarrheal activities, and anti-inflammatory effects. A possible interaction with human gut microbiota has hardly been considered so far, although it is quite likely. AIM OF THE STUDY: In this review, we aimed to identify and evaluate published studies which have investigated interactions of these plants with the gut microbiome. RESULTS: According to this survey, only a minor portion of the 44 medicinal plants considered in EMA monographs for the treatment of gastrointestinal diseases has been studied so far with regard to potential interactions with gut microbiota. We could identify eight relevant in vitro studies that have been performed with six of these medicinal plants, 17 in vivo studies performed in experimental animals involving seven of the medicinal plants, and three trials in humans performed with two of the plants. The most robust evidence exists for the use of inulin as a prebiotic, and in this context also the prebiotic activity of chicory root has been investigated quite intensively. Flaxseed dietary fibers are also known to be fermented by gut microbiota to short chain fatty acids, leading to prebiotic effects. This could cause a health-beneficial modulation of gut microbiota by flaxseed supplementation. In flaxseed, also other compound classes like lignans and polyunsaturated fatty acids are present, that also have been shown to interact with gut microbiota. Drugs rich in tannins and anthocyanins also interact intensively with gut microbiota, since these compounds reach the colon at high levels in unchanged form. Tannins and anthocyanins are intensively metabolized by certain gut bacteria, leading to the generation of small, bioavailable and potentially bioactive metabolites. Moreover, interaction with these compounds may exert a prebiotic-like effect on gut microbiota. Gut microbial metabolization has also been shown for certain licorice constituents, but their potential effects on gut microbiota still need to be investigated in detail. Only a limited amount of studies investigated the interactions of essential oil- and secoiridoid-containing drugs with human gut microbiota. However, other constituents present in some of these drugs, like curcumin (curcuma), shogaol (ginger), and rosmarinic acid have been shown to be metabolized by human gut microbiota, and preliminary data also indicate potential gut microbiome modulatory effects. To conclude, the interaction with gut microbiota is still not fully investigated for many herbal drugs traditionally used for gastrointestinal disorders, which offers a vast field for future research.