ABSTRACT
The impacts of individual commensal microbes on immunity and disease can differ dramatically depending on the surrounding microbial context; however, the specific bacterial combinations that dictate divergent immunological outcomes remain largely undefined. Here, we characterize an immunostimulatory Allobaculum species from an inflammatory bowel disease patient that exacerbates colitis in gnotobiotic mice. Allobaculum inversely associates with the taxonomically divergent immunostimulatory species Akkermansia muciniphila in human-microbiota-associated mice and human cohorts. Co-colonization with A. muciniphila ameliorates Allobaculum-induced intestinal epithelial cell activation and colitis in mice, whereas Allobaculum blunts the A.muciniphila-specific systemic antibody response and reprograms the immunological milieu in mesenteric lymph nodes by blocking A.muciniphila-induced dendritic cell activation and T cell expansion. These studies thus identify a pairwise reciprocal interaction between human gut bacteria that dictates divergent immunological outcomes. Furthermore, they establish a generalizable framework to define the contextual cues contributing to the "incomplete penetrance" of microbial impacts on human disease.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Animals , Germ-Free Life , Humans , Inflammatory Bowel Diseases/microbiology , Intestines/microbiology , Mice , VerrucomicrobiaABSTRACT
OBJECTIVE: Major depressive disorder is associated with abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Studies using hair cortisol to measure the effect of antidepressants on the HPA axis are lacking. The aim of this study was to explore the long-term effects of antidepressants on hair cortisol concentration (HCC). METHODS: Participants were 42 patients and 36 healthy individuals. The patients took antidepressants for 4 weeks. Patient HCC was measured pre-treatment and post-treatment. The HCC of healthy controls was also measured. RESULTS: Patient post-treatment HCC (mean ± standard deviation: 34.40 ± 32.57 pmol/mg) was significantly higher than patient pre-treatment HCC (17.42 ± 12.40 pmol/mg) and healthy control HCC (10.22 ± 7.99 pmol/mg). No significant correlation was found between Hamilton Depression Rating Scale scores and HCC at pre-treatment or post-treatment. CONCLUSIONS: Hair cortisol concentration analysis could be used to monitor the dynamics of the effects of antidepressants on the HPA axis.