Interactions between hawthorn extract WS® 1442 and human intestinal microbiota in vitro

Extracts from different parts of hawthorn species (Crataegus sp, Rosaceae) are therapeutically used mainly for the treatment of cardiovascular disorders. Phenolic constituents like procyanidins, flavanes and flavonoid glycosides are supposed to be the main bioactive constituents. Many of these compounds are not absorbed in the upper intestinal tract. Thus, their metabolization by gut microbiota may lead to formation of potentially bioactive metabolites.

The aim of this study was to investigate, which compounds are metabolized by gut microbiota, and whether the extract has an influence on gut microbial community composition. WS® 1442, a special hydroethanolic extract from leaves with flowers of officinal hawthorn species, was incubated with 10% human fecal suspension (HFS) under anoxic conditions at two different concentrations (0.45 and 2.25 mg/ml HFS). At 0.5, 4 and 24h of incubation, samples were taken and analysed by LC-DAD-HRMS and by 16S RNA gene sequencing.

The degree of microbial degradation was found to be strongly dependent on compound class and extract concentration. Flavanes and procyanidins were readily metabolized, and at 4 and 24h, their putative metabolites dihydroxyphenyl-γ-valerolactone, dihydroxyphenylvaleric acid and 3-(3-hydroxyphenyl)-propionic acid were detectable [1,2]. Flavonoid-O-glycosides were metabolized much faster than C-glycosyl-flavones. The degradation of C-glycosylflavones was strongly influenced by extract concentration. At 0.45 mg/ml, the C-glycosidic bond was cleaved to a much higher degree than at 2.25 mg/ml, indicating that too high extract concentrations might inhibit relevant microbial enzymatic activity.

The observed changes in the extract's metabolic profile were accompanied by shifts in microbial community composition. In particular, WS®1442 addition supported the increase of sugar-degrading beneficial microorganisms, like Faecalibacterium and Bacteroides.

We thank Dr. Willmar Schwabe GmbH & Co. KG for financial support.

[1] Appledoorn, et al, J Agric Food Chem 2009, 57, 1084 – 92.

[2] Tagakaki, A, Nanjo, F, J Agric Food Chem, 2013, 61, 4927 – 35.