Effect of short-term dietary intervention on fecal serotonin, gut microbiome-derived tryptophanase, and energy absorption in a randomized crossover trial: an exploratory analysis

Abstract

In this study, we investigated the effects of short-term energy loads on changes in gut microbiome-derived tryptophanase and fecal serotonin levels and their association with variations in energy absorption. This randomized crossover energy-load intervention study included 15 healthy participants subjected to three dietary conditions - overfeeding, control, and underfeeding - for eight days. The effects of the dietary conditions on energy absorption (digestible and metabolizable energy) were assessed using a bomb calorimeter. Fecal serotonin levels were assessed using LC-MS/MS, and the gut microbiota was analyzed using the 16S rRNA gene and metagenomic shotgun analysis. Significant differences were observed in digestible energy (p < 0.001), with higher values in the overfeeding than in the control (p = 0.032) conditions. Furthermore, significant differences were noted in metabolizable energy and gut transit time (p < 0.001), both of which were higher in the overfeeding than in the control (metabolizable energy: p = 0.001; gut transit time: p = 0.014) and underfeeding (metabolizable energy: p < 0.001; gut transit time: p = 0.004) conditions. Fecal serotonin levels differed significantly (p < 0.001), with significantly lower levels in the overfeeding than in the control (p = 0.005) and underfeeding (p < 0.001) conditions. Tryptophanase exhibited significant differences (p = 0.0019), with lower gene abundance in the overfeeding than in the underfeeding (p = 0.001) condition. Tryptophanase positively correlated with Bacteroides abundance under all conditions (correlation coefficient: 0.696-0.896). Intra-individual variability in fecal serotonin levels was significantly negatively associated with digestible energy (β = -0.077, p = 0.019). The findings suggest that short-term energy loads dynamically alter fecal serotonin, Bacteroides, and tryptophanase levels. Moreover, changes in fecal serotonin levels might be indirectly associated with energy absorption.

Keywords: Bacteroides; Energy absorption; digestible energy; gut transit time; metabolizable energy; metagenome shotgun analysis; overfeeding; tryptophanase.

Figure 1.

Study design. As in a previous study, the order of the control (CON), overfeeding (150% of CON), and underfeeding (75% of CON) conditions was randomized. Controlled diets were provided for each 7-day study period. The blue-dye marker was mixed with diets served as breakfast, lunch, and dinner on day 5. Feces were collected from the first appearance of the marker until its disappearance (between 08:00 on day 5 and 12:00 on day 8). Urine samples were collected on days 6 and 7. Blood was drawn while fasting to analyze circulating metabolites.

Figure 2.

Changes in the diversity and composition of the intestinal microbiota due to dietary intervention. Major phyla and genera of the microbiome composition indicate the dominant bacteria with an average bacterial composition ≥1.0% of the relative abundance.

Figure 3.

Changes in digestible energy, metabolizable energy, and gut transit time with dietary interventions.

Figure 4.

Changes in metabolites (serotonin, acetylcholine, epinephrine) in feces and serum due to short-term dietary interventions. Feces and serum metabolomics were analyzed using log transformation.

Figure 5.

Relationship between tryptophanase levels and gut microbiota composition at the genus and species-level Bacteroides for each intervention period.

Figure 6.

Relationships between intra-individual variability in fecal serotonin levels and Bacteroides and tryptophanase. Serotonin levels in feces were analyzed using log transformation.