Timo A Thumann1, Eva-Maria Pferschy-Wenzig2, Christine Moissl-Eichinger3, Rudolf Bauer4. 1. Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4, 8010, Graz, Austria; BioTechMed, Mozartgasse 12, 8010, Graz, Austria. Electronic address: timo.thumann@uni-graz.at. 2. Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4, 8010, Graz, Austria; BioTechMed, Mozartgasse 12, 8010, Graz, Austria. Electronic address: eva-maria.wenzig@uni-graz.at. 3. BioTechMed, Mozartgasse 12, 8010, Graz, Austria; Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria. Electronic address: christine.moissl-eichinger@medunigraz.at. 4. Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 4, 8010, Graz, Austria; BioTechMed, Mozartgasse 12, 8010, Graz, Austria. Electronic address: rudolf.bauer@uni-graz.at.
Abstract
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.
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.
Authors: Alexander Bertuccioli; Marco Cardinali; Marco Biagi; Sara Moricoli; Ilaria Morganti; Giordano Bruno Zonzini; Giovanna Rigillo Journal: Microorganisms Date: 2021-11-25