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Viable bacterial colonization is highly limited in the human intestine in utero

Abstract

The intestinal immune system must tolerate commensal bacteria which perform essential functions for the survival of the host. The development of intestinal immunity and the progressive colonization with bacteria, fungi, and protists (collectively known as the microbiota) occurs in concert to select for these valuable functions. Intestinal adaptive immunity develops in the human fetal intestine by 11-14 weeks gestation, yet whether viable microbes exist in utero and interact with the intestinal immune system is unknown. Bacterial-like morphology was identified in pockets of human fetal meconium at mid-gestation by scanning electron microscopy (n=4) and a sparse bacterial signal was detected by 16S rRNA sequencing (n=40 of 50) compared to environmental controls (n=87). Eighteen taxa were enriched in fetal meconium with Micrococcaceae (n=9) and Lactobacillus (n=6) the most abundant. Fetal intestines dominated by Micrococcaceae exhibited distinct patterns of T cell composition and epithelial transcription. Fetal Micrococcus luteus, isolated only in the presence of monocytes, grew on placental hormones, remained viable within antigen presenting cells, limited inflammation ex vivo, and possessed genomic features linked with survival in the fetus. Thus, viable bacteria are highly limited in the fetal intestine at mid-gestation, though strains with immunomodulatory capacity are detected in subsets of specimens. Future studies will investigate whether fetal bacteria could be utilized to rationally seed microbiomes and repurposed for drug delivery to the fetus.

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