Table 5.

Model Validation Summary

Perturbation	Experimental observations	Simulation design	Simulation result	Comments
Food consumption	Total, conjugated BAs↑, FGF-19↑, C4↓ in the systemic plasma9	Default parameter values	∼2-fold total BA↑, driven by conjugated BAs, ∼35% FGF-19↑ and 70% C4↓ in systemic plasma (Figure 3)	Gallbladder emptying depends on food fat content18; hence, parameter kemptGB can be changed to reflect different food types
Fasting (short term)	Total BAs and FGF-19↓, C4↑ in the systemic plasma34	Time-dependent functions are fixed on fasting values: ${\text{tf}}_{\text{GB}}^{\text{empt}}$= 0, ${\text{tf}}_{\text{CIRC}}^{\text{tr}}$ = 1, ${\text{tf}}_{\text{INT}}^{\text{tr}}$ = 1, ${\text{tf}}_{\text{INT}}^{\text{mbt}}$ = 1	∼2-fold total BA↓, 2.75-fold C4↑, and 60% FGF-19↓ in systemic plasma (Figure 6)	Additional modifications are required to reproduce prolonged fasting (1) - parameter ksyn should be decreased to reflect BA synthesis reduction55; (2) rate VfillGB should be modified to limit gallbladder filling
SIBO	Total and unconjugated BAs↑ in systemic plasma54	10-fold increase in parameter kdcjLINT, from default value	∼2.2-fold total BAs↑ in systemic plasma (Figure 4)	Deconjugation and unconjugated BA absorption in the duodenojejunal compartment should be introduced to reflect severe SIBO
BA malabsorption (after ileostomy or cholestiramine treatment)	FGF-19↓ and C4↑ in systemic plasma, increased fecal BA loss5	Parameter fabsLINTvariation from default value to 0	Up to 25-fold total colonic BA ↑, up to 16-fold systemic C4↑ (Figure 5)	Parameters ktrintcol, kexcan be modified to reflect accelerated colonic motility in patients with BA-induced diarrhea5
Antibiotic treatment	Secondary BAs↓ in systemic plasma43	10-fold decrease in parameter kdcjCOL, from default value	∼7-fold DCA fraction ↓ (Figure 4)	–
Cholecystectomy	Preservation of meal-induced daily BA oscillations, CA and CDCA pool↓33	Parameter ${\text{fr}}_{\text{GB}}^{\text{fill}}$ was nullified, parameter kdcjLINT was changed for patients with SIBO/CST	Preservation of meal-induced BA-oscillations, no change in CA and CDCA fractions (Figure 7)	–

SIBO, small intestine bacterial overgrowth.