Identification of Gut Microbiome Signatures Associated with Serotonin Pathway in Tryptophan Metabolism of Patients Undergoing Hemodialysis

Abstract

Serotonin, a tryptophan metabolite, exerts a significant influence on both brain and gut functionality. While previous research has elucidated the intricate dynamics of the gut-brain axis, the interplay between serotonin pathway metabolites and gut microbiota in individuals undergoing hemodialysis remains largely unexplored. Therefore, this study aimed to investigate gut microbiota composition corresponding to serotonin pathway metabolite levels among patients with hemodialysis. A total of 85 patients undergoing hemodialysis were selected. Their gut microbiota was analyzed using shotgun metagenomic sequencing profiling. The serotonin pathway metabolites, including 5-hydroxytryptophan (5-HTP), serotonin, 5-methoxytryptophan (5-MTP), 5-methoxytryptamine, melatonin, and 6-hydroxymelatonin, were analyzed with the liquid chromatograph-tandem mass spectrometer. The robust linear discriminant analysis Effect Size (LEfSe) was employed to reveal the gut microbiota signature according to levels of serotonin pathway metabolites. A significant β-diversity difference in 5-Methoxytryptamine (p = 0.037) was found, while no variance in α-diversity was detected. Using LefSe analysis, we identified an enriched Tannerellaceae family in the high-hydroxytryptophan (5-HTP) group, the Odoribacteraceae family in the high-serotonin group, the Eubacteriales order in the high-5-methoxytryptophan (5-MTP) group, the Prevotella copri species in the high-5-Methoxytryptamine group, and the Clostridium genus in the high-melatonin group. In contrast, an enriched Clostridiaceae family in the low-5-HTP group, the Clostridiaceae family in the low-serotonin group, and the Bacteroides ovatus species in the low-5-MTP group were found. Distinct gut microbiota signatures linked to serotonin pathway metabolites were identified in patients undergoing hemodialysis. These findings provide insights for future gut-brain axis research and may guide methods to modulate gut microbiota to influence serotonin metabolites.

Keywords: chronic kidney disease; end-stage renal disease; gut microbiota; hemodialysis; tryptophan metabolism.

Figure 1

Alpha Diversity Corresponding to Different Levels of Serotonin Metabolites from the Tryptophan Pathway: (A) 5-HTP, (B) Serotonin, (C) 5-MTP, (D) 5-Methoxytryptamine, (E) Melatonin, and (F) 6-Hydroxymelatonin.

Figure 2

Beta Diversity Corresponding to Different Levels of Serotonin Metabolites from the Tryptophan Pathway: (A) 5-HTP, (B) Serotonin, (C) 5-MTP, (D) 5-Methoxytryptamine, (E) Melatonin, and (F) 6-Hydroxymelatonin.