Intestinal Absorption Characteristics and Reciprocal Interactions of <i>Forsythiae Fructus</i> and <i>Lonicerae Japonicae Flos</i>-Containing Chinese Herbal Formulation with Human Gut Microbiome

The intestinal absorption of active herbal constituents plays an important role in the biomedical efficacy of Traditional Chinese Medicine (TCM) formulations after oral administration. TCM compounds with low oral bioavailability can reach the distal intestine and then interact with intestinal flora, influencing the botanical pharmacological effects. In this study, <i>in vitro</i> digestion and an <i>ex vivo</i> Ussing chamber model were utilized to evaluate the intestinal absorption behavior of <i>Forsythiae Fructus</i>-<i>Lonicerae Japonicae Flos</i>-containing Yinqiao Jiedu Granule (YQJDG). It was found that the jejunum exhibited active absorption effects for some components of the formula, while the oral bioavailability of other herbal ingredients was low. Through further research using a combined UPLC-MS/MS and 16S rDNA sequencing technique, we studied the existence of the reciprocal interactions between YQJDG and gut microbiome. The <i>in vitro</i> fecal fermentation results showed that YQJDG significantly impacted the microbial community composition. The YQJDG markedly increased the abundance of beneficial microorganisms, such as <i>Parabacteroides distasonis</i> and <i>Streptococcus gallolyticus</i> subsp. <i>Macedonicus,</i> and suppressed the abundance of conditional pathogens including <i>Prevotella steorerea, Haemophilus parainfluenzae</i>, and <i>Bacteroides</i>. These effects may potentially contribute to the body's immune functions and anti-inflammatory capacities. UPLC-MS/MS analysis suggested that the fecal microbiota chemically transformed constituents with low bioavailability to more readily absorbed potentially active metabolites. These findings provided valuable insights into the absorption characteristics of YQJDG and its interaction with the gut microbiome, further facilitating our understanding of precise pharmacological mechanisms of action of this Chinese herbal formulation.