Comparison of vaginal microbiota between women with inflammatory bowel disease and healthy controls.

BACKGROUND: The gut microbiota in patients with inflammatory bowel disease are perturbed in both composition and function. The vaginal microbiome and its role in the reproductive health of women with inflammatory bowel disease is less well described. OBJECTIVE: We aim to compare the vaginal microbiota of women with inflammatory bowel disease to healthy controls. METHODS: Women with inflammatory bowel disease enrolled in a longitudinal cohort study provided self-collected vaginal swabs. Healthy controls underwent provider-collected vaginal swabs at routine gynecologic exams. All participants completed surveys on health history, vulvovaginal symptoms and gastrointestinal symptoms, if applicable. Microbiota were characterized by sequencing the V4 region of the 16S rRNA gene. Associations between patient characteristics and microbial community composition were evaluated by PERMANOVA and Principal Components Analysis. Lactobacillus dominance of the microbial community was compared between groups using chi-square and Poisson regression. RESULTS: The cohort included 54 women with inflammatory bowel disease (25 Ulcerative colitis, 25 Crohn's Disease) and 26 controls. A majority, 72 (90%) were White; 17 (31%) with inflammatory bowel disease and 7 (27%) controls were postmenopausal. The composition of the vaginal microbiota did not vary significantly by diagnosis or severity of inflammatory bowel disease but did vary by menopausal status (p = 0.042). There were no significant differences in Shannon Diversity Index between healthy controls and women with IBD in premenopausal participants. There was no difference in proportion of Lactobacillus dominance according to diagnosis in premenopausal participants. A subgroup of postmenopausal women with Ulcerative colitis showed a significant higher alpha diversity and a lack of Lactobacillus dominance in the vaginal microbiome. CONCLUSIONS: Menopausal status had a larger impact on vaginal microbial communities than inflammatory bowel disease diagnosis or severity.

Angiomodulin (IGFBP7) is a cerebral specific angiocrine factor, but is probably not a blood-brain barrier inducer.

BACKGROUND: Several secreted factors have been identified as drivers of cerebral vasculature development and inducers of blood-brain barrier (BBB) differentiation. Vascular endothelial growth factor A (VEGF-A) is central for driving cerebral angiogenesis and Wnt family factors (Wnt7a, Wnt7b and norrin) are central for induction and maintenance of barrier properties. Expressed by developing neural tissue (neuron and glia progenitors), they influence the formation of central nervous system (CNS) vascular networks. Another type of factors are tissue-specific paracrine factors produced by endothelial cells (ECs), also known as 'angiocrine' factors, that provide instructive signals to regulate homeostatic and regenerative processes. Very little is known about CNS angiocrine factors and their role in BBB development. Angiomodulin (AGM) was reported to be expressed by developing vasculature and by pathological tumor vasculature. Here we investigated AGM in the developing CNS and its function as a potential BBB inducer. METHODS: We analyzed microarray data to identify potential angiocrine factors specifically expressed at early stages of barrier formation. We then tested AGM expression with immunofluorescence and real-time PCR in various organs during development, post-natal and in adults. Permeability induction with recombinant proteins (Miles assay) was used to test potential interaction of AGM with VEGF-A. RESULTS: Several angiocrine factors are differentially expressed by CNS ECs and AGM is a prominent CNS-specific angiocrine candidate. Contrary to previous reports, we found that AGM protein expression is specific to developing CNS endothelium and not to highly angiogenic developing vasculature in general. In skin vasculature we found that AGM antagonizes VEGF-A-induced vascular hyperpermeability. Finally, CNS AGM expression is not specific to BBB vasculature and AGM is highly expressed in non-BBB choroid-plexus vasculature. CONCLUSIONS: We propose AGM as a developmental CNS vascular-specific marker. AGM is not a pan-endothelial marker, nor a general marker for developing angiogenic vasculature. Thus, AGM induction in the developing CNS might be distinct from its induction in pathology. While AGM is able to antagonize VEGF-A-induced vascular hyperpermeability in the skin, its high expression levels in non-BBB CNS vasculature does not support its potential role as a BBB inducer. Further investigation including loss-of-function approaches might elucidate AGM function in the developing CNS.