Regulatory effect of herbal monomers on human gut bacteria

Xenobiotics, including natural compounds, can impact gut bacterial community. Herbal monomers (HMs) are pharmacologically active natural compounds derived from traditional Chinese medicine (TCM) and are increasingly likely to interact with the gut microbiota due to their low bioavailability. However, the natural compounds-microbiota interactions at the system scale has not yet been elucidated. Here, We screened 484 HM compounds against 47 representative gut bacterial strains, and verify the extent of disturbance of 24 anticommensal HM compounds on human complete microbiota. We found that 31.6% of HM compounds were active against at least one strain (ie anticommensal activity), particularly, quinones compounds have the strongest anticommensal activity (almost all compounds were active against at least one strain). HM compounds classes exhibited distinct inhibition spectra, including saturated fatty acid compounds specifically againsted Lactobacillus, and hemin concentration-dependently promoted Fusobacterium nucleatum, etc. The effect of HM compounds on complete microbiota were significantly positively correlated with the number of hits against strains in the screening, suggesting that HM compounds with broader anticommensal activity may cause greater disturbance to the bacterial community. To identify the mainly common molecular or chemical features that contribute to anticommensal activity, we constructed a random forest classifier model. AATS3i and XlogP3 were significantly correlated with the anticommensal activity of the HM compounds. Our results enrich the resource library on the natural compounds-microbiota interaction, providing references for the mechanism by which microbiota-mediated HMs affect the host organism.