Michiel A. van Nieuwenhoven

Acute tryptophan depletion slows gastric emptying in females.

Serotonin (5-HT) is an important neurotransmitter involved in the brain-gut axis. It is possible to lower the 5-HT level in the body by means of a nutritional intervention using an amino acid mixture; the acute tryptophan depletion (ATD) method. We studied the effect of ATD on gastric emptying in healthy females, who received both ATD and placebo in a random order. Gastric emptying was measured using the [(13)C]octanoic acid breath test. The present data demonstrate significant differences in both gastric emptying and lag phase (Tlag) between the ATD and placebo experiment. Eight out of ten subjects showed a delayed gastric emptying in the ATD experiment. Both the gastric half-emptying time (T1/2) and the Tlag were significantly higher in the ATD experiment. T1/2 in the ATD experiment was 137.2 (range 76.2-634.8) min; T1/2 for the placebo experiment was 98.5 (range 63.7-168.8) min (P=0.028). Tlag in the ATD experiment was 83.7 (range 45.1-356.2) min; Tlag for the placebo experiment was 56.9 (range 23.2-101.2) min (P=0.007). We conclude that lowering the 5-HT level in the body using the ATD method leads to a significantly delayed gastric emptying of a solid meal. Nutritional manipulation of the serotonergic system in healthy volunteers may lead to alterations in gastrointestinal motility.

Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1

BackgroundIn the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.ResultsIn the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.ConclusionsThese results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen.