BACKGROUND & AIMS Variants in genes that regulate autophagy have been associated with Crohn’s disease (CD). Defects in autophagy-mediated removal of pathogenic microbes could contribute to pathogenesis of CD. We investigated the role of the micro-RNAs (miRs) MIR106B and MIR93 in induction of autophagy and bacterial clearance in human cell lines, and the correlation between MIR106B and autophagy-related gene 16L1 (ATG16L1) expression in tissues from patients with CD. METHODS We studied the ability of MIR106B and MIR93 to regulate ATG transcripts in human cancer cell lines (HCT116, SW480, HeLa, and U2OS) using luciferase report assays and bioinformatics analyses; MIR106B and MIR93 mimics and antagonists were transfected into cells to modify levels of miRs. Cells were infected with LF82, a CD-associated adherent-invasive strain of Escherichia coli, and monitored by confocal microscopy and for colony-forming units. Colon tissues from 41 healthy individuals (controls), 22 with active CD, 16 with inactive CD, and 7 with chronic inflammation were assessed for levels of MIR106B and ATG16L1 by in situ hybridization and immunohistochemistry. RESULTS Silencing Dicer 1, an essential processor of miRs, increased levels of ATG protein and formation of autophagosomes in cells, indicating that miRs regulate autophagy. Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1 mRNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; these increased following expression of ectopic ATG16L1. In contrast, MIR106B and MIR93 antagonists increased formation of autophagosomes. Levels of MIR106B were increased in intestinal epithelia from patients with active CD, whereas levels of ATG16L1 were reduced, compared with controls. Levels of CMYC were also increased in intestinal epithelia of patients with active CD, compared with controls. These alterations could impair removal of CD-associated bacteria by autophagy. CONCLUSIONS In human cell lines, MIR106B and MIR93 reduce levels of ATG16L1 and autophagy, and prevent autophagy-dependent eradication of intracellular bacteria. This process also appears to be altered in colon tissues from patients with active CD.
Gut microbiota is symbiotic and interdependent with human body. Intestinal probiotics are colonized in the human gastrointestinal tract, which can improve the host intestinal microenvironment and enhance the intestinal function and immune function of the human body. A small number of opportunistic pathogens exist in the intestinal tract. Once the number of pathogens exceeds the threshold of intestinal tolerance, the intestinal micro-ecological balance can be destroyed, and various diseases may thus develop. Pregnancy is a special status with different physiologic changing stages. In the meanwhile, alterations in the gut microbiome populations occur, which can promote the differentiation, development, and maturation of fetal organs by affecting maternal metabolism. Compared with normal pregnant women, great changes in the gastrointestinal function and gut microbiome may take place in pregnant women with pregnancy-related complications, in which these changes include the number, species, and intestinal translocation. The composition of the maternal gut microbiome could contribute to pregnancy and obstetric outcomes, and long-term health of mother and child. The relationships of pregnancy to gut microbiome have attracted an increasing attention in recent years. This article will provide a summary review of the research studies of gut microbiome in normal pregnant women versus abnormal pregnancy women with complications.
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