Human Gut Microbiota Metabolism of Dietary Sesquiterpene Lactones: Untargeted Metabolomics Study of Lactucopicrin and Lactucin Conversion In Vitro and In Vivo

• Published in: Molecular nutrition & food research Vol. 64; no. 21; pp. e2000619 - n/a
• Main Authors: García, Carlos J., Beltrán, David, Tomás‐Barberán, Francisco A.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.11.2020
• Subjects: Adult; Asteraceae - chemistry; endive; escarole; Feces - microbiology; Female; Fermentation; food research; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Gut microbiota; gut microbiota metabolism; Humans; In vitro methods and tests; In vivo methods and tests; Intestinal microflora; intestinal microorganisms; Isomers; Lactones; Lactones - metabolism; Lactones - pharmacokinetics; Lactones - urine; Lactuca - chemistry; lettuce (Lactuca sativa); Male; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Microbiota; Microorganisms; nutrition; Phorbols - metabolism; Phorbols - pharmacokinetics; Phorbols - urine; phytochemicals; romaine lettuce; salads; Sesquiterpene lactones; Sesquiterpenes - metabolism; Sesquiterpenes - pharmacokinetics; Sesquiterpenes - urine; sesquiterpenoid lactones; Terpenes; untargeted metabolomics; urine; Vegetables; Vegetables - chemistry; untargeted metabolomics; sesquiterpene lactones; escarole; lettuce (Lactuca sativa); gut microbiota metabolism
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.202000619

Scope Gut microbiota converts dietary phytochemicals into metabolites and modulates their health effects. The microbial metabolism of dietary terpenoids, as the sesquiterpene lactones of leafy vegetables, is unknown. Methods and Results In vitro fermentation of lactucopicrin, lactucin, and romaine lettuce with gut microbiota from independent donors, show their extensive metabolism through untargeted metabolomics of the fecal incubations. Dehydroxylations and double bond hydrogenations are the main catabolic reactions. Isomers of dihydrolactucopicrin, tetrahydrolactucopicrin, and deoxylactucin, are observed after lactucopicrin metabolism. Tetrahydrolactucin and hexahydrolactucin are also found after lactucin metabolism. Lettuce fermentation shows similar metabolic conversions. Phase II conjugates of most of these metabolites are detected in the urine of healthy volunteers after escarole salad intake. Glucuronides, and sulfates, of dihydrolactucopicrin, tetrahydrolactucopicrin, dihydrolactucin, and deoxylactucin, are detected in the urine although with large inter‐subject variability. Conclusion This is the first report on the gut microbiota metabolism of sesquiterpene lactones in humans, and one of the first reports to describe that dietary terpenoids of widely consumed leafy vegetables are extensively catabolized by human gut microbiota. A large inter‐subject variation in the metabolism of sesquiterpene lactones also reflects differences in gut microbiota composition. It suggests that inter‐individual differences in their health effects should be expected. Although the transformation of dietary phenolic compounds by human gut microbiota has been studied, the metabolism of food terpenoids remains unknown. The present study shows that lettuce and escarole terpenoids are transformed by gut microbiota into a new family of derivatives with potential biological effects that should be studied in further work.