Psyllium as a Mechanical Sequestrant: Redefining Canine Bile Acid Kinetics and the Hepatic Synthesis Response via High-Resolution LC-MS/MS Profiling

• Psyllium gel acts as a mechanical bile acid sequestrant in vivo. • High-resolution LC-MS/MS defines postprandial BA kinetics. • Psyllium disrupts native kinetics via gel matrix entrapment. • Hepatic synthesis increases to compensate for sequestration. • Hydrocolloid binding prevents diarrhea despite high BA load. Routine enzymatic bile acid (BA) assays often mask crucial compositional shifts. This study characterized postprandial serum BA kinetics and the metabolic effects of psyllium hydrocolloid supplementation (0.2 g/kg BW) in healthy dogs using high-sensitivity LC-MS/MS. Six dogs participated in a prospective, within-subject comparison study. Postprandial kinetics were sampled over 12 hours (control) and 8 hours (psyllium). In the control phase, a novel biphasic kinetic curve was identified (peaks at ∼2 and 3–5 h), reflecting gallbladder release and enterohepatic recycling. Psyllium supplementation disrupted this pattern, increasing total BA exposure (AUC) by 24.8% ( P < 0.05). This rise was driven by a 33.3% increase in the primary BA fraction ( P = 0.031), while secondary BAs remained stable. Consequently, the primary/secondary ratio increased significantly ( P < 0.001). Despite the high primary BA load—typically associated with secretory diarrhea—fecal consistency remained normal. Furthermore, psyllium selectively increased lithocholic acid while decreasing taurodeoxycholic acid. Results demonstrate that psyllium acts as a mechanical sequestrant. The viscous hydrocolloid gel traps bile acids, preventing reabsorption and triggering a compensatory hepatic synthesis overshoot. This explains the net increase in circulating primary BAs. Crucially, the gel matrix reduces the bioactivity of free bile acids and binds water, uncoupling the high primary BA load from pathological outcomes (diarrhea). This establishes psyllium as a functional hydrocolloid modulator of the gut-liver axis.