Negative Correlation between Expression Level and Evolutionary Rate of Long Intergenic Noncoding RNAs

Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The functions of the lncRNAs remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into the mode of evolution and the functional range of the lncRNA, they can be compared with much better characterized protein-coding genes. The evolutionary rate of the protein-coding genes shows a universal negative correlation with expression: highly expressed genes are on average more conserved during evolution than the genes with lower expression levels. This correlation was conceptualized in the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether long intergenic ncRNAs (lincRNAs) follow the same evolutionary trend and indeed detected a moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse lincRNA genes. The magnitude of the correlation for the lincRNAs is similar to that for equal-sized sets of protein-coding genes with similar levels of sequence conservation. Additionally, the expression level of the lincRNAs is significantly and positively correlated with the predicted extent of lincRNA molecule folding (base-pairing), however, the contributions of evolutionary rates and folding to the expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be a general feature of gene evolution that might be caused by similar deleterious effects of protein and RNA misfolding and/or other factors, for example, the number of interacting partners of the gene product

Microbiome Therapeutics for Food Allergy

The prevalence of food allergies continues to rise, and with limited existing therapeutic options there is a growing need for new and innovative treatments. Food allergies are, in a large part, related to environmental influences on immune tolerance in early life, and represent a significant therapeutic challenge. An expanding body of evidence on molecular mechanisms in murine models and microbiome associations in humans have highlighted the critical role of gut dysbiosis in the pathogenesis of food allergies. As such, the gut microbiome is a rational target for novel strategies aimed at preventing and treating food allergies, and new methods of modifying the gastrointestinal microbiome to combat immune dysregulation represent promising avenues for translation to future clinical practice. In this review, we discuss the intersection between the gut microbiome and the development of food allergies, with particular focus on microbiome therapeutic strategies. These emerging microbiome approaches to food allergies are subject to continued investigation and include dietary interventions, pre- and probiotics, microbiota metabolism-based interventions, and targeted live biotherapeutics. This exciting frontier may reveal disease-modifying food allergy treatments, and deserves careful study through ongoing clinical trials

Microbiome Therapeutics for Food Allergy

The prevalence of food allergies continues to rise, and with limited existing therapeutic options there is a growing need for new and innovative treatments. Food allergies are, in a large part, related to environmental influences on immune tolerance in early life, and represent a significant therapeutic challenge. An expanding body of evidence on molecular mechanisms in murine models and microbiome associations in humans have highlighted the critical role of gut dysbiosis in the pathogenesis of food allergies. As such, the gut microbiome is a rational target for novel strategies aimed at preventing and treating food allergies, and new methods of modifying the gastrointestinal microbiome to combat immune dysregulation represent promising avenues for translation to future clinical practice. In this review, we discuss the intersection between the gut microbiome and the development of food allergies, with particular focus on microbiome therapeutic strategies. These emerging microbiome approaches to food allergies are subject to continued investigation and include dietary interventions, pre- and probiotics, microbiota metabolism-based interventions, and targeted live biotherapeutics. This exciting frontier may reveal disease-modifying food allergy treatments, and deserves careful study through ongoing clinical trials

Fetal exposures and perinatal influences on the stool microbiota of premature infants

<div><p></p><p><i>Objective</i>: To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants.</p><p><i>Methods</i>: Forty-nine serial stool samples were obtained weekly from nine extremely premature infants enrolled in a prospective longitudinal study. Sequencing of the bacterial 16S rRNA gene from stool samples was performed to approximate the intestinal microbiome. Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development.</p><p><i>Results</i>: Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e. prolonged preterm premature rupture of membranes (PPPROM) and chorioamnionitis exposure, were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures, irrespective of exposure to postnatal antibiotics. Compared with those delivered by Caesarean section, vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points, with lower abundance of many genera, most in the family <i>Enterobacteriaceae</i>.</p><p><i>Conclusions</i>: We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment. Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants, with findings persisting over time.</p></div

Fetal exposures and perinatal influences on the stool microbiota of premature infants

<div><p></p><p><i>Objective</i>: To test the hypothesis that maternal complications significantly affect gut colonization patterns in very low birth weight infants.</p><p><i>Methods</i>: Forty-nine serial stool samples were obtained weekly from nine extremely premature infants enrolled in a prospective longitudinal study. Sequencing of the bacterial 16S rRNA gene from stool samples was performed to approximate the intestinal microbiome. Linear mixed effects models were used to evaluate relationships between perinatal complications and intestinal microbiome development.</p><p><i>Results</i>: Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e. prolonged preterm premature rupture of membranes (PPPROM) and chorioamnionitis exposure, were found to have a relatively higher abundance of potentially pathogenic bacteria in the stool across all time points compared to subjects without those exposures, irrespective of exposure to postnatal antibiotics. Compared with those delivered by Caesarean section, vaginally delivered subjects were found to have significantly lower diversity of stool microbiota across all time points, with lower abundance of many genera, most in the family <i>Enterobacteriaceae</i>.</p><p><i>Conclusions</i>: We identified persistently increased potential pathogen abundance in the developing stool microbiota of subjects exposed to a non-sterile uterine environment. Maternal complications appear to significantly influence the diversity and bacterial composition of the stool microbiota of premature infants, with findings persisting over time.</p></div