Serotonin Pathway of Tryptophan Metabolism in Small Intestinal Bacterial Overgrowth-A Pilot Study with Patients Diagnosed with Lactulose Hydrogen Breath Test and Treated with Rifaximin.

Small intestinal bacterial overgrowth (SIBO) is a condition associated with diverse clinical conditions and there is no gold standard in its diagnosis and treatment. Tryptophan (Trp) metabolism may be involved in etiology of gastrointestinal diseases and is regulated by intestinal microbiota. In our study we investigated aspects of the serotonin (5-HT) pathway of Trp metabolism in three groups of individuals based on the hydrogen concentration in the lactulose hydrogen breath test (LHBT): controls (<20 ppm) and SIBO patients (≥20 ppm), with diarrhea (SIBO-D) or constipation (SIBO-C). The SIBO-D patients showed an increased serum concentration of 5-HT and small intestinal mucosa mRNA expression of tryptophan hydroxylase 1 (TPH-1), a rate-limiting enzyme in 5-HT biosynthesis. Urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was higher in both group of SIBO patients than controls. A positive correlation between 5-HIAA and LHBT was observed. A two-week treatment with rifaximin decreased hydrogen in LHBT and 5-HIAA concentration in SIBO patients. In conclusion, the serotonin pathway of Trp metabolism may play a role in the pathogenesis of hydrogen-positive SIBO and it may influence the diversification of SIBO into variants with diarrhea or constipation. As urinary 5-HIAA concentration correlates with LHBT, TPH-1 expression in colonic mucosa and TH-5 in serum of SIBO patients, it can be considered as a non-invasive marker of this condition.