Cell https://doi.org/10.1016/j.cell.2021.04.039 (2021)
Bacteria have been detected in fetal tissues, indicating that they are able to cross the placental barrier, but whether these bacteria are viable and how they affect the developing immune system in utero is a matter of debate. Research published in Cell addresses this controversy with paired microbiome and T cell mass cytometry data from multiple human organs. The researchers isolated blood and tissue from lung, skin, intestines, thymus, liver and lymph nodes to compare adults with the second-trimester fetus. 16S ribosomal RNA sequencing data show low levels of Flavobacteria, Staphylococci, Prevotella and Lactobacilli (and others) in many of the fetal tissues and inside the intestinal lumen, a finding supported by microscopy imaging showing bacterial cocci localized primarily within meconium-associated mucin-like structures from week 14 of gestation. Importantly, many bacterial strains were isolated and cultured, indicating bacteria are viable within these tissues. CyTOF/UMAP (cytometry time of flight/uniform manifold approximation and projection) cluster analysis then shows that during the second trimester there are abundant regulatory T cell populations in the fetal tissues, as well as a sizeable pool of cytotoxic T cells and effector memory T cells. Furthermore, T cells from mesenteric lymph nodes could mount memory responses to bacterial stimulation ex vivo. All of these results suggest that development of the human fetal immune system is guided by the microbiome from as early as the second trimester.
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