Microbial short-chain fatty acids (SCFA) regulate intestinal functions via free-fatty acid (FFA) receptors type 2 and 3. Though the caecum is the most important fermentation chamber in many species, it is unknown whether this signaling system is modulated in dependence on the rate of fermentation within the lumen of this part of the large intestine. Thus, we asked the question whether alteration of the microbiota composition by antibiotic treatment or high-fiber diet affects the SCFA/FFA signaling using rat caecum as model system. SCFA concentrations and microbiota were analyzed in caecal samples from untreated rats, following vancomycin treatment, or after feeding with a high-fiber diet. Oral and aboral caecal segments were harvested for Ussing chamber experiments paralleled by Ca