Microbiome and tryptophan metabolomics analysis in adolescent depression: roles of the gut microbiota in the regulation of tryptophan-derived neurotransmitters and behaviors in human and mice

Abstract

Background Adolescent depression is becoming one of the major public health concerns, because of its increased prevalence and risk of significant functional impairment and suicidality. Clinical depression commonly emerges in adolescence; therefore, the prevention and intervention of depression at this stage is crucial. Recent evidence supports the importance of the gut microbiota (GM) in the modulation of multiple functions associated with depression through the gut-brain axis (GBA). However, the underlying mechanisms remain poorly understood. Therefore, in the current study, we aimed to screen the microbiota out from healthy and depressive adolescents, delineate the association of the targeted microbiota and the adolescent depression, address the salutary effects of the targeted microbiota on anti-depressive behaviors in mice involving the metabolism of the tryptophan (Trp)-derived neurotransmitters along the GBA. Results Here, we found the gut microbiota from healthy adolescent volunteers, first diagnosis patients of adolescent depression, and sertraline interveners after first diagnosis displayed significant difference, the relative abundance of Faecalibacterium, Roseburia, Collinsella, Blautia, Phascolarctobacterium, Lachnospiraceae-unclassified decreased in adolescent depressive patients, while restored after sertraline treatment. Of note, the Roseburia abundance exhibited a high efficiency in predicting adolescent depression. Intriguingly, transplantation of the fecal microbiota from healthy adolescent volunteers to the chronic restraint stress (CRS)-induced adolescent depressed mice significantly ameliorated mouse depressive behaviors, in which the Roseburia exerted critical roles, since its effective colonization in the mouse colon resulted in remarkably increased 5-HT level and reciprocally decreased kynurenine (Kyn) toxic metabolites quinolinic acid (Quin) and 3-hydroxykynurenine (3-HK) levels in both the mouse brain and colon. The specific roles of the Roseburia were further validated by the target bacteria transplantation mouse model, Roseburia intestinalis (Ri.) was gavaged to mice and importantly, it dramatically ameliorated CRS-induced mouse depressive behaviors, increased 5-HT levels in the brain and colon via promoting tryptophan hydroxylase-2 (TPH2) or -1 (TPH1) expression. Reciprocally, Ri. markedly restrained the limit-step enzyme responsible for kynurenine (indoleamine2,3-dioxygenase 1, IDO1) and quinolinic acid (3-hydroxyanthranilic acid 3,4-dioxygenase, 3HAO) generation, thereby decreased Kyn and Quin levels. Additionally, Ri. administration exerted a pivotal role in the protection of CRS-induced synaptic loss, microglial activation, and astrocyte maintenance. Conclusions This study is the first to delineate the beneficial effects of Ri. on adolescent depression by balancing Trp-derived neurotransmitter metabolism and improving synaptogenesis and glial maintenance, which may yield novel insights into the microbial markers and therapeutic strategies of GBA in adolescent depression.

Affective Symptoms in Pregnancy are Associated with the Vaginal Microbiome

“…We further extended the association of individual taxa and CSTs with affective symptoms and predicted biological pathway abundance derived from 16S rRNA taxa. Our prediction of functional pathway abundances 55 (Figure 3) identified significant correlations of multiple taxon with the Ltryptophan and L-phenylalanine functional pathways, the precursors of serotonin, dopamine, and norepinephrine --key neurotransmitters associated with depression [63][64][65] . A single taxon, Peptoniphilus, was significantly correlated with both functional pathways.…”

Cervicovaginal microbiota long‐term dynamics and prediction of different outcomes in persistent human papillomavirus infection

“…Microbial genomic DNA was extracted from cervical samples according to the instructions of the Genomic DNA Extraction Kit 19 . (Omega, Inc.), and the extracted products were tested for concentration and then stored at −80°C.…”

“…Microbial genomic DNA was extracted from cervical samples according to the instructions of the Genomic DNA Extraction Kit. 19 (Omega, Inc.), and the extracted products were tested for concentration and then stored at −80°C. The primer sequences for amplifying the 16S rRNA V3-V4 variable region were as follows: 341 F (5′-CCTACGGGNGGCWGCAG-3) and 805 R (5′-GACTACHVGGGTATCTAATCC-3).…”

Treatment of preterm brain injury via gut‐microbiota–metabolite–brain axis

“…56 Intestinal Lactobacillus improved synaptogenesis and maintained glial homeostasis by balancing the metabolism of tryptophan-derived neurotransmitters, increasing the levels of 5-HT in brain and colon, and increasing the levels of BDNF and gamma-aminobutyric acid receptors in the hippocampus and amygdala. 57,58 In addition, SCFAs can stimulate the synthesis and secretion of 5-HT in intestine, which plays a role in regulating motility, neurodevelopment and differentiation, and emotion. 59 Moreover, colonization of Lactobacillus or supplementation of SCFAs can increase the level of GABA in the hippocampus of mice, regulate the level of specific neurotransmitters in hippocampus of brain, and play a role in enhancing memory.…”

“…The diversity of bile acid is decreased in germ‐free and antibiotic‐treated rats, and bile acid metabolites can activate receptors and act as signal molecules in the host, which can affect HPA axis and play a role in the brain 56 . Intestinal Lactobacillus improved synaptogenesis and maintained glial homeostasis by balancing the metabolism of tryptophan‐derived neurotransmitters, increasing the levels of 5‐HT in brain and colon, and increasing the levels of BDNF and gamma‐aminobutyric acid receptors in the hippocampus and amygdala 57,58 . In addition, SCFAs can stimulate the synthesis and secretion of 5‐HT in intestine, which plays a role in regulating motility, neurodevelopment and differentiation, and emotion 59 .…”