The association of maternal factors with the neonatal microbiota and health.

The human microbiome plays a crucial role in human health. However, the influence of maternal factors on the neonatal microbiota remains obscure. Herein, our observations suggest that the neonatal microbiotas, particularly the buccal microbiota, change rapidly within 24-48 h of birth but begin to stabilize by 48-72 h after parturition. Network analysis clustered over 200 maternal factors into thirteen distinct groups, and most associated factors were in the same group. Multiple maternal factor groups were associated with the neonatal buccal, rectal, and stool microbiotas. Particularly, a higher maternal inflammatory state and a lower maternal socioeconomic position were associated with a higher alpha diversity of the neonatal buccal microbiota and beta diversity of the neonatal stool microbiota was influenced by maternal diet and cesarean section by 24-72 h postpartum. The risk of admission of a neonate to the newborn intensive care unit was associated with preterm birth as well as higher cytokine levels and probably higher alpha diversity of the maternal buccal microbiota.

Antibody Response to the Sneathia vaginalis Cytopathogenic Toxin A during Pregnancy.

Sneathia vaginalis is a Gram-negative vaginal species that is associated with pregnancy complications. It produces cytopathogenic toxin A (CptA), a pore-forming toxin. To determine whether CptA is expressed in vivo and to examine the mucosal Ab response to the toxin, we examined human midvaginal swab samples obtained during pregnancy for IgM, IgA, and IgG Abs with CptA affinity. This subcohort study included samples from 93 pregnant people. S. vaginalis relative abundance was available through 16S rRNA survey. There were 22 samples from pregnancies that resulted in preterm birth in which S. vaginalis relative abundance was <0.005%, 22 samples from pregnancies that resulted in preterm birth with S. vaginalis ≥0.005%, 24 samples from pregnancies that resulted in term birth with S. vaginalis <0.005%, and 25 samples from pregnancies that resulted in term birth with S. vaginalis ≥0.005%. IgM, IgA, and IgG with affinity for CptA were assessed by ELISA. The capacity for the samples to neutralize CptA was quantified by hemolysis assay. All three Ab isotypes were detectable within different subsets of the samples. There was no significant association between relative abundance of S. vaginalis and the presence of any Ab isotype. The majority of vaginal swab samples containing detectable levels of anti-CptA Abs neutralized the hemolytic activity of CptA, with the strongest correlation between IgA and neutralizing activity. These results demonstrate that S. vaginalis produces CptA in vivo and that CptA is recognized by the host immune defenses, resulting in the production of Abs with toxin-neutralizing ability.

Characteristics of vaginal microbes and classification of the vaginal microbiome.

Background: The vaginal microbiome (VMB) has been classified into several discrete community state types, some of which have been associated with adverse human health conditions. However, the roles of the many vaginal bacteria in modulating the VMB and health remain unclear. Methods: The associations among the vaginal taxa and other vaginal taxa, the vaginal pH, and the host gene expression responses were determined by calculating the correlation among the relative abundance of the vaginal taxa, the association between the vaginal pH and the predominant taxon in the VMB, and the correlation between the relative abundance of the vaginal taxa and human gene expression at the transcriptional level, respectively. Using these associations, an alternative more informative method, the biological vagitype (BVT), is proposed to classify community state types of the VMB. Findings: Most Lactobacillus spp., with the exception of Lactobacillus iners , show significant correlations with host gene expression profiles and negative associations with dysbiosis-associated vaginal taxa. Many non- Lactobacillus spp. exhibit varied correlations with Lactobacillus spp., the vaginal pH, and host gene expression. Compared to other dysbiotic taxa, including Candidatus Lachnocurva vaginae, Gardnerella vaginalis has a stronger positive correlation with vaginal pH and a stronger negative correlation with Lactobacillus spp. Most dysbiosis-associated taxa are associated with stress responses of the host at the transcriptional level, but the genus Mycoplasma has a uniquely strong positive correlation with host immune responses. The association between BVTs of the VMBs and host characteristics, e.g., race/ethnicity, microbial infection, smoking, antibiotics, high blood pressure, economic state, diet, and others, was examined. The BVT classification method improved overall performance in associating specific vaginal microbial populations with host characteristics and phenotypes. Interpretation: This study sheds light on the biological characteristics of the vaginal microbiota, including some less abundant or still unculturable taxa. Since the BVT method was established based on these biological characteristics, the classification outcome of the VMB may have more clinical relevance. Because the BVT method performs better in associating specific vaginal community types with diseases, e.g., bacterial vaginosis and gonorrhea, it could be beneficial for the predictive modeling of adverse health. Funding: This work was supported by grants [UH3AI083263, U54HD080784, and R01HD092415] from the National Institutes of Health; and support from the [GAPPS BMGF PPB] grant from the Global Alliance to Prevent Prematurity and Stillbirth. We would also like to thank the Office of Research on Women's Health at NIH for their generous support. Research in context: Evidence before this study: The vaginal microbiome (VMB) refers to the community of microorganisms in the female lower reproductive tract. The VMB is often a simple ecosystem dominated by a single species. The most predominant bacteria in the VMB include several Lactobacillus species and two non- Lactobacillus species, i.e., Candidatus Lachnocurva vaginae and Gardnerella vaginalis. Lactobacillus species produce lactic acid to lower the vaginal pH and inhibit the growth of disease-associated bacteria. Thus, the predominance of protective Lactobacilli, i.e., L. crispatus, L. jensenii , and L. gasseri , in the VMB is associated with overall vaginal health. However, the role of L. iners in promoting a healthy vaginal ecosystem is less clear. Actually, the biological and health relevance of many bacteria in the female lower reproductive tract is largely unknown. Some bacteria have low relative abundances, e.g., Peptostreptococcus and Coriobacteriaceae spp.; and others are not yet culturable, e.g., Candidatus Lachnocurva vaginae and BVAB TM7. When abundance of a taxon is low, its association with a host characteristic is a challenge. Previous methods to classify the VMB were based simply on their microbial compositions, and the biological characteristics of the vaginal bacteria were largely ignored. Thus, classification of these VMBs into biologically relevant community types, as described herein, should be helpful in determining their relevance to women's reproductive health. Added value of this study: This study examines three biological characteristics of bacteria in the VMB, i.e., the associations among different bacterial taxa, the vaginal pH, and the host response. Based on these three characteristics, the influence of these bacteria, particularly low abundant and unculturable bacteria, on vaginal health is evaluated. L. iners seems to be neutral in maintaining overall vaginal health. Gardnerella vaginalis is apparently more easily inhibited by Lactobacillus spp. than Candidatus Lachnocurva vaginae because of its stronger positive correlation with vaginal pH and negative correlation with Lactobacillus . The genus of Mycoplasma has a unique positive correlation with local immune responses, implying a role for Mycoplasma in promoting inflammation. Compared with previous methods to classify the VMB, a new method, considering the above three biological characteristics of bacteria in the VMB, has been established. The new method performs better in associating specific vaginal communities with host characteristics and phenotypes; e.g., bacterial vaginosis and gonorrhea. Implications of all the available evidence: Accurate biological classification of the VMB is fundamental for assessing its impact on women's health. Our classification scheme represents a step further toward that correct classification, eventually leading to new strategies for clinical assessment of the potential use of the VMB to diagnose or predict women's reproductive health.