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

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 (<i>p</i> < 0.001), with higher values in the overfeeding than in the control (<i>p</i> = 0.032) conditions. Furthermore, significant differences were noted in metabolizable energy and gut transit time (<i>p</i> < 0.001), both of which were higher in the overfeeding than in the control (metabolizable energy: <i>p</i> = 0.001; gut transit time: <i>p</i> = 0.014) and underfeeding (metabolizable energy: <i>p</i> < 0.001; gut transit time: <i>p</i> = 0.004) conditions. Fecal serotonin levels differed significantly (<i>p</i> < 0.001), with significantly lower levels in the overfeeding than in the control (<i>p</i> = 0.005) and underfeeding (<i>p</i> < 0.001) conditions. Tryptophanase exhibited significant differences (<i>p</i> = 0.0019), with lower gene abundance in the overfeeding than in the underfeeding (<i>p</i> = 0.001) condition. Tryptophanase positively correlated with <i>Bacteroides</i> 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, <i>p</i> = 0.019). The findings suggest that short-term energy loads dynamically alter fecal serotonin, <i>Bacteroides</i>, and tryptophanase levels. Moreover, changes in fecal serotonin levels might be indirectly associated with energy absorption.