Several lines of evidence support the link between maternal inflammation during pregnancy and increased likelihood of neurodevelopmental and psychiatric disorders in offspring. This longitudinal study seeks to advance understanding regarding implications of systemic maternal inflammation during pregnancy, indexed by plasma IL-6 concentrations, for large-scale brain system development and emerging executive function (EF) skills in offspring. Maternal IL-6 was assessed during pregnancy, functional MRI acquired in neonates, and working memory (an important component of EF) examined at 2-years-of-age. Functional connectivity within and between multiple neonatal brain networks can be modeled to estimate maternal IL-6 concentrations during pregnancy. Brain regions heavily weighted in these models overlap significantly with those supporting working memory in a large meta-analysis. Maternal IL-6 also directly accounts for a portion of the variance of working memory at two-years-of-age. Findings highlight the association of maternal inflammation during pregnancy with the developing functional architecture of the brain and emerging EF.

Objectives: Traditionally, the urinary tract has been thought to be sterile in the absence of a clinically identifiable infection. However, recent evidence suggests that the urinary tract harbors a variety of bacterial species, known collectively as the urinary microbiome, even when clinical cultures are negative. Whether these bacteria promote urinary health or contribute to urinary tract disease remains unknown. Emerging evidence indicates that a shift in the urinary microbiome may play an important role in urgency urinary incontinence (UUI). The goal of this prospective pilot study was to determine how the urinary microbiome is different between women with and without UUI. We also sought to identify if characteristics of the urinary microbiome are associated with UUI severity.Methods: We collected urine from clinically well-characterized women with UUI (n = 10) and normal bladder function (n = 10) using a transurethral catheter to avoid bacterial contamination from external tissue. To characterize the resident microbial community, we amplified the bacterial 16S rRNA gene by PCR and performed sequencing using Illumina MiSeq. Sequences were processed using the workflow package QIIME. We identified bacteria that had differential relative abundance between UUI and controls using DESeq2 to fit generalized linear models based on the negative binomial distribution. We also identified relationships between the diversity of the urinary microbiome and severity of UUI symptoms with Pearson's correlation coefficient.Results: We successfully extracted and sequenced bacterial DNA from 95% of the urine samples and identified that there is a polymicrobial community in the female bladder in both healthy controls and women with UUI. We found the relative abundance of 14 bacteria significantly differed between control and UUI samples. Furthermore, we established that an increase in UUI symptom severity is associated with a decrease in microbial diversity in women with UUI.Conclusions: Our study provides further characterization of the urinary microbiome in both healthy controls and extensively phenotyped women with UUI. Our results also suggest that the urinary microbiome may play an important role in the pathophysiology of UUI and that the loss of microbial diversity may be associated with clinical severity.

Many recent studies have now shown that even under healthy conditions, the bladder and urinary tract harbors its own microbial community, collectively known as the urinary microbiota. This contradicts the long held notion that urine is a sterile environment in the absence of an acute infection. Given this relatively new discovery, many basic questions which are critical for our understanding of the role that the urinary microbiota plays in human health and disease remain unanswered. As this is an emerging area of study, optimized techniques and protocols to identify microorganisms in the urinary tract are still being established. This is made more challenging for the urinary microbiota given its low microbial biomass. A clear understanding of the unique technical considerations of low microbial biomass samples, as well the impact of key elements of experimental design and computational analysis on downstream interpretation will improve the interpretability and comparability of results across methods and studies both for the urinary microbiota as well as other sites of low microbial abundance.