Project description:Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N?=?116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.
Project description:Vaginal bacterial communities are thought to help prevent sexually transmitted infections. Bacterial vaginosis (BV) is a common clinical syndrome in which the protective lactic acid-producing bacteria (mainly species of the Lactobacillus genus) are supplanted by a diverse array of anaerobic bacteria. Epidemiologically, BV has been shown to be an independent risk factor for adverse outcomes including preterm birth, development of pelvic inflammatory disease, and acquisition of sexually transmitted infections. Longitudinal studies of the vaginal microbiome using molecular techniques such as 16S ribosomal DNA analysis may lead to interventions that shift the vaginal microbiota toward more protective states.
Project description:The vaginal microbiome is believed to influence host health by providing protection from pathogens and influencing reproductive outcomes such as fertility and gestational length. In humans, age-associated declines in diversity of the vaginal microbiome occur in puberty and persist into adulthood. Additionally, menstruation has been associated with decreased microbial community stability. Adult female baboons, like other non-human primates (NHPs), have a different and highly diverse vaginal microbiome compared to that of humans, which is most commonly dominated by Lactobacillus spp. We evaluated the influence of age, reproductive cycling status (cycling vs. non-cycling) and menstruation on the vaginal microbiome of 38 wild-caught, captive female olive baboons (Papio anubis) by culture-independent sequencing of the V3-V5 region of the bacterial 16S rRNA gene. All baboons had highly diverse vaginal microbial communities. Adult baboons had significantly lower microbial diversity in comparison to subadult baboons, which was attributable to decreased relative abundance of minor taxa. No significant differences were detected based on cycling state or menstruation. Predictive metagenomic analysis showed uniformity in relative abundance of metabolic pathways regardless of age, cycle stage, or menstruation, indicating conservation of microbial community functions. This study suggests that selection of an optimal vaginal microbial community occurs at puberty. Since decreased diversity occurs in both baboons and humans at puberty, this may reflect a general strategy for selection of adult vaginal microbial communities. Comparative evaluation of vaginal microbial community development and composition may elucidate mechanisms of community formation and function that are conserved across host species or across microbial community types. These findings have implications for host health, evolutionary biology, and microbe-host ecosystems.
Project description:Human microbiota plays an indispensable role in physiology, nutrition and most significantly, in imparting immunity. The role of microbiota has remained cryptic for years, until recently meticulous studies revealed the interaction and dynamics of these microbial communities. This diversified state is governed by hormonal, behavioral and physio-chemical changes in the genital tract. Many inclusive studies have revealed "Lactobacillus" to be the most dominant member of vaginal flora in most of the healthy, reproductive age group and pregnant females. A total of five community state types have been described, out of which four are dominated by Lactobacillus while the fifth one by facultative or strict anaerobic species. A variation between species stability and gestational age has also been revealed. Studies have divulged a significant higher stability of vaginal microbiota in early stages of pregnancy and the same increased subsequently. Inter-species and racial variation has shown women belonging to White, Asian, and Caucasian race to harbor more of the anaerobic flora. The vaginal microbiome in pregnancy play a significant role in preterm and spontaneous labor. This Lactobacillus-rich microbiome falls tremendously, becoming more diverse in post-partum period. Apart from these known bacterial communities in human vagina, other microbial communities have also been traced. The major fragment is constituted by vaginal viral virome and very little information exists in relation to vaginal mycobiome. Studies have revealed the abundance of ds DNA viruses in vaginal microbiome, followed by ssDNA, and few unidentified viruses. The eukaryotic viruses detected were very few, with Herpesvirales, and Papillomaviridae being the only pathogenic ones. This flora is transmitted to infants either via maternal gut, vagina or breast milk. Recent studies have given an insight for vaginal microbiome, dissociating the old concept of "healthy" and "diseased." However, more extensive studies are required to study evolution of virome and mycobiome in relation to their association with bacterial communities; to establish and decode full array of vaginal virome under the influence of genotypic and environmental factors, using novel bioinformatic, multi-omic, statistical model, and CRISPR/Cas approaches.
Project description:Vaginally administered antiviral agents may reduce the risk of HIV and HSV acquisition. Delivery of these drugs using intravaginal rings (IVRs) holds the potential benefits of improving adherence and decreasing systemic exposure, while maintaining steady-state drug levels in the vaginal tract. Elucidating how IVRs interact with the vaginal microbiome constitutes a critical step in evaluating the safety of these devices, as shifts the vaginal microbiome have been linked with several disease states. To date, clinical IVR trials have relied on culture-dependent methods that omit the high diversity of unculturable microbial population. Longitudinal, culture-independent characterization of the microbiota in vaginal samples from 6 women with recurrent genital HSV who used an acyclovir IVR was carried out and compared to the communities developing in biofilms on the IVR surface. The analysis utilized Illumina MiSeq sequence datasets generated from bar-coded amplicons of 16S rRNA gene fragments. Specific taxa in the vaginal communities of the study participants were found to be associated with the duration of recurrent genital HSV status and the number of HSV outbreaks. Taxonomic comparison of the vaginal and IVR biofilm communities did not reveal any significant differences, suggesting that the IVRs were not systematically enriched with members of the vaginal microbiome. Device usage did not alter the participants' vaginal microbial communities, within the confines of the current study design. Rigorous, molecular analysis of the effects of intravaginal devices on the corresponding microbial communities shows promise for integration with traditional approaches in the clinical evaluation of candidate products.
Project description:The microbiome is a regulator of host immunity, metabolism, neurodevelopment, and behavior. During early life, bacterial communities within maternal gut and vaginal compartments can have an impact on directing these processes. Maternal stress experience during pregnancy may impact offspring development by altering the temporal and spatial dynamics of the maternal microbiome during pregnancy. To examine the hypothesis that maternal stress disrupts gut and vaginal microbial dynamics during critical prenatal and postnatal windows, we used high-resolution 16S rRNA marker gene sequencing to examine outcomes in our mouse model of early prenatal stress. Consistent with predictions, maternal fecal communities shift across pregnancy, a process that is disrupted by stress. Vaginal bacterial community structure and composition exhibit lasting disruption following stress exposure. Comparison of maternal and offspring microbiota revealed that similarities in bacterial community composition was predicted by a complex interaction between maternal body niche and offspring age and sex. Importantly, early prenatal stress influenced offspring bacterial community assembly in a temporal and sex-specific manner. Taken together, our results demonstrate that early prenatal stress may influence offspring development through converging modifications to gut microbial composition during pregnancy and transmission of dysbiotic vaginal microbiome at birth.
Project description:The gut microbial community is dynamic during the first 3 years of life, before stabilizing to an adult-like state. However, little is known about the impact of environmental factors on the developing human gut microbiome. We report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, about half of whom received multiple courses of antibiotics during the first 3 years of life. Whereas the gut microbiome of most children born by vaginal delivery was dominated by Bacteroides species, the four children born by cesarean section and about 20% of vaginally born children lacked Bacteroides in the first 6 to 18 months of life. Longitudinal sampling, coupled with whole-genome shotgun sequencing, allowed detection of strain-level variation as well as the abundance of antibiotic resistance genes. The microbiota of antibiotic-treated children was less diverse in terms of both bacterial species and strains, with some species often dominated by single strains. In addition, we observed short-term composition changes between consecutive samples from children treated with antibiotics. Antibiotic resistance genes carried on microbial chromosomes showed a peak in abundance after antibiotic treatment followed by a sharp decline, whereas some genes carried on mobile elements persisted longer after antibiotic therapy ended. Our results highlight the value of high-density longitudinal sampling studies with high-resolution strain profiling for studying the establishment and response to perturbation of the infant gut microbiome.
Project description:Background:Previous studies have indicated that variations in the vaginal microbiome result in symptomatic conditions. Group B Streptococcus (GBS) is a significant neonatal pathogen and maternal vaginal colonization has been recognized as an important risk factor for neonatal disease. Therefore, it is important to discover the relationship between the composition of the vaginal microbiome and GBS colonization. This study explores the potential relationship between the composition of the vaginal microbiome and GBS colonization in non-pregnant Chinese women. Methods:A total of 22 GBS-positive, non-pregnant women and 44 matched GBS-negative women were recruited for the current study. The composition of the vaginal microbiome was profiled by sequencing the 16S rRNA genes. The microbiome diversity and variation were then evaluated. Results:The vaginal microbiome of the 66 subjects enrolled in the current study were compared and the results showed that GBS-positive women exhibited significant vaginal microbial differences compared with the GBS-negative women based on the analysis of similarities (r = 0.306, p < 0.01). The relative abundance of the bacterial genus Lactobacillus (p < 0.01) was significantly lower in the GBS-positive group, while the abundances of the bacterial genera Prevotella (p < 0.01), Megasphaera (p < 0.01), and Streptococcus (p < 0.01) were significantly higher in the GBS-positive group. Discussion:The current study addressed significant variations across the communities of the vaginal microbiome in GBS-positive and GBS-negative women in a Chinese cohort, which paves the way for a larger cohort-based clinical validation study and the development of therapeutic probiotics in the future.
Project description:Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection.
Project description:Bacterial vaginosis (BV) affects 20% of women worldwide and is associated with adverse reproductive health outcomes and increased risk for HIV. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Persistent racial differences in BV and diverse vaginal microbiome composition overlap with racial disparities in risks for HIV and sexually transmitted infection, especially among women of African descent. Risk factors for BV and nonoptimal vaginal microbiome include sexual practices, yet racial differences persist when adjusted for behavioral factors, suggesting a host genetic component. Here, we perform a genome-wide association study on vaginal microbiome traits in Kenyan women. Linear regression and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis, Shannon diversity index, and community state type (CST) with host genetic single nucleotide polymorphisms (SNPs). We identified novel genomic loci associated with the vaginal microbiome traits, though no SNP reached genome-wide significance. During pathway enrichment analysis, Toll-like receptors (TLRs), cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple previously reported genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP (L. iners, Shannon), TLR2 (Shannon, CST), MBL2 (L. iners, G. vaginalis, CST), and MYD88 (L. iners, Shannon). These genetic associations suggest a role for the innate immune system and cell signaling in vaginal microbiome composition and susceptibility to nonoptimal vaginal microbiome.IMPORTANCE Globally, bacterial vaginosis (BV) is a common condition in women. BV is associated with poorer reproductive health outcomes and HIV risk. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Despite many women having similar exposures, the prevalence of BV and nonoptimal vaginal microbiome is increased for women of African descent, suggesting a possible role for host genetics. We conducted a genome-wide association study of important vaginal microbiome traits in Kenyan women. We identified novel genetic loci and biological pathways related to mucosal immunity, cell signaling, and infection that were associated with vaginal microbiome traits; we replicated previously reported loci associated with mucosal immune response. These results provide insight into potential host genetic influences on vaginal microbiome composition and can guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals and across populations.