Interpretation
In 1985, Lince20 first reported that the FEB is an abnormal ultrasound sign. Slotnick5 classified the strong echo of the intestine into three grades. In this study, all the cases were intestinal hyperechoic grade > 2.
In recent years, the intestinal flora play an important role in a number of diseases, such as premature delivery, obesity.21Therefore,we hypothesized that hyperechogenic bowel might be related to intestinal flora.
The study showed that there were abundant bacteria in the meconium of newborns, which is consistent with the results of Jimenez et al.11A reduction of the α diversity of the intestinal flora is causal of many diseases, including autoimmune diseases, obesity.22-23 In this study there were no significant differences in the α diversity of meconium flora among the three groups and the composition of intestinal flora in the three groups was similar, which may be one of the reasons for the good outcome of most newborns with FEB. Pately et al.24 reported that if the fetus with echogenic bowel can be delivered normally, there are no severe pathologic changes in the intestinal tract after delivery, which may be explained by our experimental results. In this study the structure of intestinal microbiota of the three groups of newborns was similar, withProteobacteria and Firmicutes the two major components of the phylum, which is in agreement with Collado et al.10
What are the acoustic physical reasons for an echogenic bowel? Some researchers believe that the components in the lumen of the intestine are responsible for the formation of echogenic bowel, such as meconium. During the second trimester of pregnancy, echogenic bowel may be caused by the concentration and viscosity of the intestinal secretions. With the gradual release of these concentrated substances into the intestine, the grade of FEB will also decrease.5
IUGR is the main cause of perinatal death and morbidity. IUGR leads to the delayed development of colonic mucosa and the destruction of intestinal mucosal barrier, including intestinal epithelium, mucous layer, and other components.25 Mesenteric ischemia and impaired intestinal motility are the result of fetal blood redistribution in newborns with IUGR, thus there is a preferential supply of blood flow to the heart and brain and reduced blood flow to other organs of the fetus, including the intestine, while FEB is one of the features representing IUGR.26 Sepulveda et al.27 considered that FEB in newborns with IUGR indicates that intestinal peristalsis slows down and meconium is thick due to intestinal ischemia.
CF is an autosomal recessive genetic disease. Because of the incomplete function of the CFTR gene, the airway mucus secretion increases and the mucous membranes thicken, leading to chronic lung infections.28 The prenatal diagnosis of fetuses with FEB requires further consultation with parents whether or not the fetuses have CF because FEB is closely related to the CF pathologic state.29 Thus, the appearance of FEB may also be due to the viscous secretion of mucus. Ultrasound reveals scattering and shows strong echoes of the fetal intestine.
Therefore, we found that the formation of FEB may be related to the secretion of mucus in the intestinal tract. The difference in bacterial abundance in the intestinal tract may promote or inhibit the secretion of mucus. Thus, different concentrations of mucus contributed to intestinal echoes. In the fetal small intestine, mucus is secreted as early as the 10th week gestation. Mucus secretion is helpful for the formation of meconium.30 The surface of the fetal intestinal epithelium is covered with a thick layer of mucus, forming a hydrophilic network structure.30-32 The mucus layer is secreted by goblet cells of the intestinal epithelium.33 Mucus also includes water, ions, and immune mediators, which help to eliminate intestinal pathogens34-35 and maintain the homeostasis of host microorganisms.36 There were significant differences in the abundance of E. coli / Shigella ,Staphylococcus , Methylrod, and Curvibacter among the three groups of newborns, which may have resulted in different concentrations of mucus in the intestine and different intestinal echogenicity. With time, the abundance of bacteria in the intestinal tract changes, the mucus is diluted, and the echo is reduced. Therefore, part of FEB gradually disappears as gestational age increases. Therefore, we speculate that the difference in the abundance of intestinal flora might be related to echogenic bowel.
Caspi et al.8 believe that the bacteria propagate, ferment, and metabolize in the intestine to produce intestinal gas, which is characterized by echogenic bowel after the fetus swallows amniotic fluid. Therefore, we propose that the formation of FEB may be related to the accumulation of intestinal gas, which may be related to intestinal bacteria. In the current study, a different abundance ofGammaproteobacteria , Fusobacteria ,Enterobacteriaceae , and E. coli were detected in the EB and C-EB groups.
Do these bacteria produce gas that makes hyperechogenic bowel? SomeEnterobacteriaceae strains can produce amines.37 Barton et al.38-39 found that many bacteria can decompose cysteine into H2S gas in the colon, including Clostridium , Enterobacter ,E. coli , and Vibrio desulfuricus . This suggest that the reason for the hypergenic bowel may be related to the gas produced by the microbiota. The accumulation of intestinal gas and multiple interfaces lead to FEB. Ljssennagger et al.40 proposed that H2S gas interacts with the intestinal mucous layer to regulate intestinal inflammation. We speculate that the intestinal microbiota might affect the secretion of intestinal mucus and intestinal gas to make a strong intestinal echo.
In this study the abundance of Firmicutes in the EB group was higher than the C-EB and control groups, while the abandance of Fusobacteria in the C-EB and EB groups was significantly lower than the control group. Indiani et al.41 showed that the abundance of Firmicutes was positively correlated with the increase in the weight of children. The higher the abundance ofFirmicutes , the higher the risk of obesity in children. This finding suggests the EB group has a higher risk of obesity in childhood.Fusobacteria is related to premature delivery, adverse pregnancy outcomes, and intra-amniotic infections.42 In this study the abundance of Fusobacteria in the C-EB and EB groups was significantly lower than the control group. Therefore, we cannot give a reasonable explanation. At the genus level, the abundance of E. coli / Shigella in the EB and C-EB groups was significantly lower than the control group. E. coli / Shigella can cause watery diarrhea, dysentery, and other symptoms.43 This means the possibility of diarrhea and other symptoms is lower in the EB and C-EB groups after delivery, which is an extremely interesting result. we do not know the specific reason.