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

Abstract

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.

Urine 5-Hydroxyindoleacetic Acid Negatively Correlates with Migraine Occurrence and Characteristics in the Interictal Phase of Episodic Migraine

“…We did not interfere with the diet of enrolled individuals, but we did not observe any difference between the urine concentration of TRP in the patients and the control groups and the 5 ′ -HIAA/TRP ratio was also the same in both groups. Another limitation of our study was to not measure the level of 3-hydroxykynurenine, a product of the KYN pathway of TRP metabolism, especially since this molecule is reported to exert a dual, pro-, or anti-oxidative action in the central nervous system [49]. Moreover, increased conversion of TRP to KYN with a decrease in KYNA/QA ratio suggests that the level of 3-hydroxykynurenine might change [50].…”

Urine 5-Hydroxyindoleacetic Acid Negatively Correlates with Migraine Occurrence and Characteristics in the Interictal Phase of Episodic Migraine

“…In our previous works, we considered tryptophan metabolism in the context of the gut-brainmicrobiota axis [44][45][46][47]. However, those studies were performed on hospital patients, but this study enrolled patients of an outpatient clinic and most of them were not willing to donate blood or undergo the examination of the gut and the microbiota.…”

Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites

“…Rifaximin could inhibit bacterial overgrowth in the small intestine by modifying the intestinal microecology [18]. Therefore, rifaximin has been used to treat small intestinal bacterial overgrowth (SIBO), a heterogeneous syndrome characterized by an increased number and/or abnormal type of bacteria in the small bowel [19,20]. Jian et al [21] showed that rifaximin ameliorated non-alcoholic steatohepatitis in mice through regulating gut microbiome-related BAs.…”