Fig. 1: Intestinal microbiota-mediated drug permeability screening revealed the potential dependency on microbiota for N-acetylcysteine (NAC).
a Schematic workflow of the microbiota-mediated oral drug permeability screening platform. Created in BioRender. Dai, C. (2025) https://BioRender.com/r8tvfj3. For each drug with individual variable permeability, single-pass intestinal perfusion (SPIP) model was conducted in age-matched specific pathogen-free (SPF) and germ-free (GF) rats. n  =  6 per group (the same applies hereinafter). After 2 h perfusion at 15-min intervals, the perfused and unperfused intestinal segments of rats were collected for microbiological detection, and the permeability of drugs was determined by SPIP. b Microbiota-drug-metabolite interaction network identified in this study. Left network: Effects of intestinal bacteria on drug permeability. Significant interactions in two independent screenings (n = 3 per screen) were validated in a follow-up assay (n = 3; FDR-corrected P < 0.05) are shown (Spearman’s rank tests). Right network: Differential intestinal metabolites between SPF and GF rats of drug exposure detected by two independent screenings (Spearman’s rank tests). c Z factor of intestinal microbiota effect on the given drugs in each SPF-GF rats pair, n = 6SPF * 6GF = 36. The value of Z factor > 0.5 indicates the positive effect. d 2 h of intestinal Peff-values for NAC (top panel), Lithium carbonate (middle panel) and Penicillin vk (bottom panel) were monitored at 15-min intervals. Data are the means ± SD. Source data are provided as a Source Data file.
