Parabacteroides distasonis Properties Linked to the Selection of New Biotherapeutics.

Dysbiotic microbiota is often associated with health issues including inflammatory bowel disease or ulcerative colitis. In order to counterbalance host disorder caused by an alteration in the gut composition, numerous studies have focused on identifying new biotherapeutic products (NBPs). Among the promising NBPs is Parabacteroides distasonis, a gut microbiota member part of the core microbiome that recently has received much attention due to the numerous beneficial properties it brings to its host. In this study, the properties linked to the selection of NBPs were screened in 14 unrelated P. distasonis strains, including resistance to gastric conditions, adherence (Caco-2 model), transepithelial resistance (Caco-2 model), and immunomodulation, on nontreated and LPS-stimulated cells (HT-29 and peripheral blood mononuclear cells (PBMCs)). This approach allowed for the identification of five strains that combined almost all the in vitro biotherapeutic properties tested. However, all the P. distasonis strains induced the overproduction of proinflammatory cytokines on PBMCs, which was counteracted by the overproduction of the anti-inflammatory cytokines. Among these five strains, two particularly retained our attention as a potential NBP, by showing strong health-promoting function, the lowest overproduction of proinflammatory cytokines on PBMCs, and no detrimental effect on the host.

Angiogenin expression during early human placental development; association with blood vessel formation.

The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis.

Angiogenin distribution in human term placenta, and expression by cultured trophoblastic cells.

Human angiogenin is a 14-kDa secreted protein with angiogenic and ribonucleolytic activities. Angiogenin is associated with tumour development but is also present in normal biological fluids and tissues. To further address the physiological role of angiogenin, we studied its expression in situ and in vitro, using the human term placenta as a model of physiological angiogenesis. Angiogenin was immunodetected by light and transmission electron microscopy, and its cellular distribution was established by double immunolabelling with cell markers including von Willebrand factor, platelet/endothelial cell adhesion molecule-1 (PECAM-1), CD34, Tie-2, vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Angiogenin immunoreactivity was detected in villous and extravillous trophoblasts, the trophoblast basement membrane, the endothelial basal lamina, foetal blood vessels, foetal and maternal red blood cells, and amnionic cells. Its expression was confirmed by in situ hybridisation with a digoxygenin-labelled cDNA probe and reverse transcriptase-polymerase chain reaction amplification. Villous cytotrophoblasts, isolated and differentiated in vitro into a functional syncytiotrophoblast, expressed and secreted angiogenin. Given its known biological activities in vitro and its observed pattern of expression, these data suggest that, in human placenta, angiogenin has a role not only in angiogenesis but also in vascular and tissue homeostasis, maternal immune tolerance of the foetus, and host defences.