MICROBIOME: Episode 4 LIVE
In this study, we sought to evaluate the spectrum of events that occur in vaginal microbial communities prior to, during and after episodes of BV by characterizing the composition and dynamics of vaginal bacterial communities using high-throughput 454 pyrosequencing of barcoded V1 to V3 regions of 16S rRNA genes. To do this, we conducted a high-resolution prospective study in which samples were collected daily from 135 women of reproductive age over two menstrual cycles. Behaviors and events that took place before, during and after BV episodes were recorded. Herein we report our initial findings on the daily composition and relative abundance of bacteria in vaginal samples from 25 women, 15 of whom experienced symptomatic BV (SBV), 6 who were diagnosed with asymptomatic BV (ABV) and 4 who remained healthy during the 10-week study. These women were selected on the basis of their clinical examinations and the longitudinal patterns of changes in Nugent scores.
MICROBIOME: Episode 4 LIVE
Unexpectedly, the vaginal microbiota prior to SBV mainly comprised strict anaerobes, such as Atopobium, Prevotella, Megasphaera, BV-associated bacterium 2 and the facultative anaerobe G. vaginalis, and the vaginal pH was elevated (>4.5) (Figure 1). During the 2- to 9-week interval prior to the diagnosis of SBV, a few symptoms were reported in daily diaries, but none of these prompted participants to immediately seek medical attention. Women who were diagnosed with ABV harbored vaginal microbiota that lacked significant proportions of Lactobacillus spp. and had symptoms similar to those of patients who ultimately were diagnosed with SBV (Figure 1A and B). Of note, Lactobacillus iners was consistently present in women who had SBV or ABV, albeit in low proportions (Figure 1 and Additional file 4: Figure S1). In most women, the treatment of SBV reduced the proportion of facultative and strict anaerobes and increased the relative proportions of Lactobacillus spp. (mainly L. iners) (Figure 1D to F). This effect was short-lived, however, and, in most individuals, the community returned to its pretreatment state within 2 to 4 weeks. Community dynamics in women who had ABV or SBV appeared to be highly personalized, with some women experiencing rapid shifts in community composition (Figure 1A, F and G) and others harboring stable, but Lactobacillus spp.-depleted, microbiota (Figure 1B to E and H). The vaginal microbiota of women who did not have SBV or ABV were consistently dominated by Lactobacillus spp. or Bifidobacterium, but were not always stable in terms of the dominant species of Lactobacillus present.
Early-life exposure to household pets has the capacity to reduce risk for overweight and allergic disease, especially following caesarean delivery. Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health. To investigate the impact of pre- and postnatal pet exposure on infant gut microbiota following various birth scenarios, this study employed a large subsample of 746 infants from the Canadian Healthy Infant Longitudinal Development Study (CHILD) cohort, whose mothers were enrolled during pregnancy between 2009 and 2012. Participating mothers were asked to report on household pet ownership at recruitment during the second or third trimester and 3 months postpartum. Infant gut microbiota were profiled with 16S rRNA sequencing from faecal samples collected at the mean age of 3.3 months. Two categories of pet exposure (i) only during pregnancy and (ii) pre- and postnatally were compared to no pet exposure under different birth scenarios.
Our study revealed that pet exposure significantly increased species richness in the phylum Firmicutes, composed of families like the Clostridiaceae, Lachnospiraceae and Ruminococcaceae. These families of the Firmicutes are obligate anaerobes which reduce the oxidative state of the gut ; they are common constituents of the gut microbiota of healthy infants and severely depleted in malnourished infants . In particular, we found Ruminococcus, or Oscillospira, belonging to the Ruminococcaceae, to be more abundant (median levels and levels above the median) among infants exposed to pets pre- and postnatally across all birth scenarios. Associations with ruminococcal abundance above the median were independent of all covariates, but attenuated after adjustment for breastfeeding status and maternal race. Prenatal pet exposure alone was sufficient to produce associations with Ruminococcus or Oscillospira, even under conditions of undisturbed gut microbiota following vaginal birth and no IAP. Of note, enrichment in faecal Oscillospira was among the few changes observed for pet ownership within infants delivered by scheduled CS.
Members of Ruminococcus have also been detected in the stool of neonates and infants  but are reportedly absent in some infants delivered vaginally or by CS . Like the Oscillospira, they are also present in dogs and cats . The role of ruminococci in infant health is also poorly understood. Among their noticeable functions, these microbes stimulate the production and degradation of mucin , vital to the maintenance of an intact microbiota-mucin barrier. They are also fibre degraders  and predominant in formula-fed infants [44, 45]. Yet, ruminococci are still found in breastfed infants and interestingly, their colonization depends on the oligosaccharide content of breast milk . Lastly, they produce ruminococcin A, a bacteriocin which can inhibit various pathogenic species of Clostridium . In our previous study within the same cohort, we observed a strong link between low levels of Ruminococcaceae and food sensitization at age 1, even after adjustment for major microbiota-disrupting events .
Under birth scenarios involving vaginal delivery, Proteobacteria became less abundant in infants with postnatal pet exposure which commenced prenatally. After emergency CS, the following changes with pet exposure were observed for Proteobacteria: reduced species richness, and abundance of Enterobacteriaceae and of Citrobacter. Pet exposure was also significantly associated with reduced Enterobacteriaceae among infants born vaginally without IAP but not exclusively breastfed afterwards. While our findings appear to contradict reports of greater Escherichia coli colonization in the vaginal microbiome of pregnant women who own pets , the timing of microbial changes in the developmental trajectory of infant microbiota is important to consider. Following vaginal delivery, Proteobacteria (especially Enterobacteriaceae) are dominant within 3 months after birth, while Bacteroidetes and Firmicutes become more prevalent as the gut microbiota matures towards an adult-like profile . A bloom of Proteobacteria in the gut can indicate instability in the microbial community ; greater abundance (along with a higher abundance of streptococci) in 6-month-old infants has predicted future adiposity . Using the E/B ratio as an indicator for gut microbiota maturity, we previously reported that a higher ratio predicted food sensitization at age 1 ; in the current study, pet exposure lowered the E/B ratio in vaginally born infants exposed to IAP. Using another ratio to represent gut microbiota maturity in the current study, pet exposure was linked to a higher F/P ratio following vaginal birth in the absence of maternal IAP. Of note, Ruminococcus and Oscillospira were also elevated under these circumstances.
Our current study has several strengths, including the application of high-throughput deep sequencing to profile gut microbiota in a longitudinal population cohort, with a representative and large sample size. Predominance of Proteobacteria in gut microbiota at 3 months and its higher prevalence in CS-delivered infants were consistent with observations in other birth cohorts. Unlike other studies, our study tested the differential impact of pet exposure according to various birth modes, with the aim of providing more translational information for practitioners. Finally, we implemented statistical modelling and sensitivity analyses to explore whether observed associations were attributable to confounding covariates. On the other hand, the use of 16S rRNA sequencing in our study may have resulted in under-representation of organisms such as bifidobacteria. The sensitivity of this technique also did not allow identification at the species level, which is possible with high-throughput microbial culturomics , as well as targeted PCR or phenotypic culturing . Metagenomic sequencing was not conducted, which would enable characterization of the functional properties of microbial changes with pet exposure. Since the majority of households in our study owned at least one dog, a larger sample is required to differentiate the effects of different pet species (e.g. dog and or cat) in future studies.
Methods: This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic. Adult participants with 1 or more prior episodes of rCDI received: 4 RBX7455 capsules twice daily for 4 days (group 1); 4 RBX7455 capsules twice daily for 2 days (group 2); or 2 RBX7455 capsules twice daily for 2 days (group 3). For all groups, the first dose was administered in clinic, with remaining doses self-administered at home. Adverse events were monitored during and for 6 months after treatment. Treatment success was defined as rCDI prevention through 8 weeks after treatment. Participants' microbiome composition was assessed prior to and for 6 months after treatment. 041b061a72