Background: Dietary intervention with prebiotics can cause changes in the colonic microbiota and their metabolic activities. Aim: The present study investigated whether the response to prebiotic dosing is influenced by the baseline metabolic activity and bifidobacteria counts. Methods: The 4-wk effect of lactulose (10g b.i.d. (n=29)) and oligofructose-enriched inulin (OF-IN: 10g b.i.d. (n=19)) was evaluated in healthy human volunteers. Lactose-[(15)N, (15)N]-ureide was used to study the colonic NH(3)-metabolism. Urine (48-h) and faeces (72-h) were collected and analysed for p-cresol and (15)N-content by gas chromatography-mass spectrometry and isotope ratio mass spectrometer, respectively. Faecal bifidobacteria were quantified by real-time PCR. Results: After the 4-wk prebiotic administration period, the urinary excretion of p-cresol and (15)N was significantly decreased in both groups (p<0.05) corresponding with a significantly higher faecal excretion of (15)N (p<0.05). The decrease in urinary (15)N and p-cresol excretion significantly correlated with baseline (15)N and p-cresol levels (p<0.05), indicating that subjects with higher baseline levels showed a higher response to prebiotic dosing. Furthermore a significant correlation was seen between baseline bifidobacteria counts and the effect of prebiotic intake (p<0.05). Conclusions: The response to prebiotic dosing as indicated by the fate of NH(3), p-cresol and bifidobacteria is determined by the initial colonic conditions.