SEARCH · PubMed Health

Results for “Vaginal microbiome”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

17 recordsLinked to original sources

PubMed2026

Species and strain sharing in the vaginal microbiome of mothers and their adult daughters.

The vaginal microbiome is key for women's health. However, its establishment, interindividual variation and dynamics remain poorly understood. Here, we investigate bacterial relatedness at species and strain level in adult mother-daughter pairs from the large-scale citizen-science program Isala. Using metagenomic sequencing with quality control including 16S rRNA profile comparison, along with targeted culturing, we assess intergenerational microbiome sharing. At species level, daughters' vaginal microbiomes are significantly more similar to their mothers' than to those of unrelated mothers, with a strong mother-daughter correlation in Lactobacillus crispatus dominance. Strain-level analyses of metagenomes and isolate genomes reveal intraspecies diversity in L. crispatus, with up to two strains observed within the same host, and support intergenerational vaginal bacteria sharing. SNV counts in shared L. crispatus strains show no correlation with daughters' ages. Together, these findings suggest that maternal transmission, host factors, and (shared) environment collectively shape the vaginal microbiome, providing fundamental ecological insights into vaginal microbiome dynamics and perspectives toward lactobacilli-based applications.

CP: microbiology↗

PubMed2026

Expanding vaginal microbiome pangenomes via a custom MIDAS database reveals Lactobacillus crispatus accessory genes associated with cervical dysplasia.

The vaginal microbiome plays a central role in reproductive health. Vaginal microbiome dysbiosis is associated with many adverse reproductive health outcomes, but most studies have focused on associations at the species level. The potential contribution of intraspecies microbial variation, especially gene content differences across bacterial strains, remains underexplored in reproductive health contexts. The Metagenomic Intra-Species Diversity Analysis (MIDAS) framework enables such analyses, but depends on comprehensive reference databases. We constructed a MIDAS-compatible pangenome database from over 18,000 genomes in the Vaginal Microbiome Genome Collection (VMGC). Compared to the Genome Taxonomy Database (GTDB)-derived reference, the VMGC-derived database expanded the pangenomes of prevalent vaginal species, better capturing vaginal-specific intraspecies diversity. Applying this database to vaginal samples from a cervical dysplasia cohort, we identified 13 Lactobacillus crispatus accessory genes significantly associated with cervical dysplasia, including a HicAB toxin-antitoxin system, three transcriptional regulators, and three phage-derived genes. These findings highlight the utility of body site-specific reference resources and shotgun metagenomic sequencing for uncovering intraspecies microbial variation relevant to reproductive health.IMPORTANCEThe vaginal microbiome plays a critical role in reproductive health, and different bacteria from the same species can carry different genes that influence how the strains interact with the host and other microbes. These strain-level differences are often overlooked when microbiomes are analyzed only at the species level. Existing genomic reference databases are heavily biased toward gut and environmental bacteria, leaving the genetic diversity of vaginal microbes understudied. We built a specialized reference database from over 18,000 vaginal bacterial genomes that better reflects this diversity. We then applied this resource to quantify gene-level variation in vaginal samples from a cervical dysplasia cohort. Focusing on Lactobacillus crispatus, a prevalent and often beneficial vaginal species, we identified 13 genes that were more common in women with cervical dysplasia than in controls. This work demonstrates that body site-specific genomic resources are essential for uncovering strain-level bacterial differences relevant to reproductive health.

Lactobacillus crispatus↗

PubMed2026

VISTA: a classifier for metagenomic subspecies and community state typing of the vaginal microbiome.

Metagenomic community state types (mgCSTs) capture within-species genetic and functional diversity and community structure of the vaginal microbiome, enabling precise links between microbiome composition, function, and health-related risk. VISTA, the Vaginal Inference of Subspecies and Typing Algorithm, is a two-step classifier that assigns mgCSTs to vaginal metagenomes, providing standardized, scalable classifications.

bioinformatics↗

PubMed2024

Water source, latrine type, and rainfall are associated with detection of non-optimal and enteric bacteria in the vaginal microbiome: a prospective observational cohort study nested within a cluster randomized controlled trial.

BACKGROUND: Less than one-third of sub-Saharan Africans have access to improved water sources. In US, Indian, and African studies, Bacterial vaginosis (BV) is increased among women with poor water, sanitation, and hygiene (WASH). We examined water source, sanitation (latrine type), and rainfall in relation to the vaginal microbiome (VMB). METHODS: In a cluster randomized controlled trial of menstrual cups and cash transfer, we measured the impact of cups on VMB via 16S rRNA gene amplicon sequencing in a subset of 436 adolescent girls. We analyzed how self-reported water source and latrine type at home related to VMB over 18-months, examining community state type I (CST-I, L. crispatus dominant) vs. other CST; alpha diversity; targeted taxa (coliform and other water-related pathogens); and non-targeted taxa via machine learning approaches. Mixed effects multivariable longitudinal models were adjusted for intervention arm, age, socioeconomic status, sexual activity, and cluster-level school WASH and rainfall (in millimeters). RESULTS: Adjusting for all covariates in all models: (1) the odds of CST-I were increased among participants with piped water (vs. pond), and decreased with traditional pit latrine vs. flush toilet. (2) Alpha diversity varied by water source and latrine type without consistent trends. (3) Coliform bacteria relative abundance (RA) was higher among participants with traditional pit or ventilated improved pit latrines vs. flush toilet, and higher among participants relying on stream vs. pond water. Streptococcus agalactiae RA was higher among participants with non-flush toilets, while Bacteroides fragilis RA was lower with non-flush toilets. (4) Key taxa from non-targeted analyses associated with water source and latrine type included typical vaginal bacteria, opportunistic pathogens, and urinary tract pathobionts. (6) Increased rainfall was associated with decreased odds of CST-I. TRIAL REGISTRATION: ClinicalTrials.gov NCT03051789, February 14, 2017.

Adolescent↗

PubMed2026

Intra-individual genetic diversity of vaginal Lactobacillus crispatus revealed through citizen science-driven isolation and pangenome analysis.

AIMS: A vaginal microbiome dominated by Lactobacillus crispatus is associated with positive reproductive and sexual health outcomes, yet intra-individual genetic diversity within this species remains largely unexplored. This study characterized inter- and intra-individual genomic variation in L. crispatus strains isolated through a citizen science initiative and assessed implications for multi-strain probiotic development. METHODS AND RESULTS: Fifty-three women participated in this citizen science project. Self-sampling resulted in 48 shotgun metagenomes. Twenty-two participants isolated their own L. crispatus strains using selective enrichment and LAMP-based species confirmation, resulting in 53 whole-genome-sequenced isolates. Lactobacillus crispatus dominated 20 of 48 metagenomes (50.1%-99.6% relative abundance). Pangenome analysis revealed 3456 gene families, of which 43.7% were core and 56.3% accessory. A 14-kb plasmid harbouring a Fic-domain toxin-antitoxin protein, but devoid of antimicrobial resistance genes, was present in 44 of 53 strains. Strains from the same individual clustered closely together yet harboured 1-123 gene differences. Intra-individual variation was observed in the pullulanase type I gene required for glycogen degradation: 40 strains were predicted to grow on glycogen, six showed genetic disruptions with unknown consequences, and seven were predicted to lack this ability entirely. Variation within individuals was also found for bacteriocin classes and CRISPR-Cas genes. CONCLUSIONS: Substantial functional diversity exists within L. crispatus, even among strains from the same individual, supporting the rationale for multi-strain vaginal probiotics. This citizen science approach enabled discovery of host-specific adaptations while ensuring participant ownership of their strains.

Female↗

PubMed2026

A Mobile Glycosylation Locus Modulates Cell Wall Architecture in Lactobacillus crispatus.

Lactobacillus crispatus dominance in the vaginal microbiome is associated with beneficial health outcomes, yet strain-level variation and its implications remain poorly understood. Here, we resolve the genomic context of three glycosyltransferase gene fragments (GT1-3) previously linked with dysbiotic states. Long-read resequencing revealed that GT1-3 are part of a ~18.7 kb Wzx/Wzy-dependent cell wall polysaccharide (CWPS) locus, containing several IS256-family transposases. Serial propagation in vitro produced isolates with 4.1 kb excised via a composite transposon encompassing the GT3, UDP-galactopyranose mutase, flippase, and hypothetical protein, demonstrating structural plasticity. Transmission electron microscopy showed a ~20%-25% thinner peptidoglycan layer in the derived strains, while FT-IR and monosaccharide analysis indicated no gross changes. Molecular dynamics simulations suggest that GT3 contributes to the structural stability of the glycosyltransferase complex, without compromising catalytic function. Together, these findings establish the CWPS locus as a mobile, structurally plastic element that directly influences cell wall architecture in L. crispatus.

Lactobacillus crispatus↗

PubMed2026

Lactobacillus iners at the nexus of microbiota, immunity, and pregnancy.

Pregnancy induces a dynamic reconfiguration of the vaginal microbiome, typically marked by increased dominance of Lactobacillus species and reduced microbial diversity. Among these bacteria, Lactobacillus iners stands out for its unique genomic traits, controversial associations with vaginal health, and frequent presence across all stages of gestation. This review synthesizes current literature on the maternal microbiome with a focus on L. iners, exploring its strain-level diversity, metabolic idiosyncrasies, and inflammatory potential. We discuss how host factors such as ethnicity, sexual activity, maternal age, and especially obesity, influence microbial composition, and evaluate conflicting data surrounding L. iners in contexts like in vitro fertilization, preterm birth, and postpartum recovery. Emerging evidence suggests that L. iners may act as a transitional species, whose effect on pregnancy outcomes depends on its abundance, genetic features, and interactions with the host immune system. We also assess limitations of current animal models and propose future directions for understanding this enigmatic bacterium. Unraveling the role of L. iners will be essential to predicting, preventing, and managing adverse pregnancy outcomes in diverse populations.

Humans↗

PubMed2026

Human Milk Oligosaccharides Modulate Nitrogen Utilization in Lactobacillus crispatus in a Glucose-Dependent Manner.

The vaginal microbiome's transition to a dysbiotic state increases susceptibility to pathogens like group B Streptococcus. While human milk oligosaccharides are established prebiotics in the neonatal gut, their impact on the vaginal niche remains largely unexplored. This study investigated the effects of pooled human milk oligosaccharides on the growth and physiology of vaginal (Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners) and gut-derived (Lactobacillus reuteri, Lactobacillus rhamnosus) commensals. Growth analyses revealed that human milk oligosaccharides significantly and selectively stimulated growth across all vaginal strains tested, whereas gut commensals exhibited variable or inhibited growth. Carbohydrate utilization assays and comparative genomics against Bifidobacterium infantis showed that Lactobacillus crispatus and Lactobacillus reuteri lack the canonical metabolic machinery to catabolize human milk oligosaccharides. Instead, nitrogen utilization assays identified a glucose-dependent pathway where human milk oligosaccharides are associated with the depletion of primary amines and amino acids in Lactobacillus crispatus supernatants. These results suggest that human milk oligosaccharides act as noncatabolic modulators of vaginal lactobacilli. Collectively, these in vitro findings may warrant investigation of human milk oligosaccharides as modulators of vaginal commensal physiology in more complex experimental systems.

Humans↗

PubMed2025

Impact of the maternal microbiome on neonatal immune development.

Historically, multigenerational health and disease transmission have primarily focused on genetic inheritance. However, the discovery that beneficial microorganisms known as commensal microbiota outnumber human genes tenfold has reshaped this perspective, highlighting their critical role in maintaining homeostasis and protecting against pathogens. Unlike the human genome, commensal microbiota is not genetically inherited but is acquired anew with each generation. with initial gut colonization playing a pivotal role in shaping an infant's immune system, neurodevelopment, and long-term health, all heavily influenced by maternal factors. In this review, we examine emerging research on maternal microbial influences on the fetus beginning in utero. We provide an updated overview of the current insights into the impact of the vaginal microbiome during parturition on offspring immunity and discuss the potential long-term health implications for infants born via cesarean section. We explore the advantages and limitations of techniques designed to mitigate these effects, such as vaginal seeding and emphasize that the development of the neonatal immune system is a dynamic process influenced by maternal factors beyond birth, including the transfer of microbiota through breast milk and skin contact. Finally, we present gaps in current research and propose future research directions to deepen our understanding of the impacts of the maternal microbiome on her child. Together, these insights demonstrate how maternal influence on offspring health and immunity extends beyond genetic factors, encompassing the transmission of microbiota, which, in turn, has profound long-term implications for health and disease resilience, offering a novel perspective on intergenerational health dynamics.

Humans↗

PubMed2025

Identification of Sample Processing Errors in Microbiome Studies Using Host Genetic Profiles.

In microbiome studies, sample processing errors are frequent and difficult to detect, especially in large studies involving multiple sites, personnel, and sample types. We present two complementary approaches to identify such errors using host DNA profiled via metagenomic sequencing of microbiome samples. The first approach compares host SNPs inferred from metagenomics to independently obtained genotypes (e.g., microarray genotypes) to match samples to their donors, while the second method compares metagenomics-inferred SNPs between samples to identify samples supplied by the same donor. Furthermore, we demonstrate that combining these methods with experimental metadata provides greater confidence in the identification of errors. Analyzing a longitudinal vaginal microbiome dataset, we demonstrate the ability of our approach to identify mislabeled samples. Using subsampling, we further show that our methods are robust to low sequencing coverage. Overall, our analysis highlights the frequency of processing errors in microbiome studies. We therefore recommend applying error-detection methods in all studies with suitable data.

Journal Article↗

PubMed2026

Metabolic reprogramming and taxonomic drivers in bacterial vaginosis: A large-scale metagenomic meta-analysis.

OBJECTIVE: Bacterial vaginosis (BV) represents a profound ecological shift from a Lactobacillus-dominated microbiota to a diverse polymicrobial biofilm associated with adverse outcomes. While taxonomic signatures are well-documented, the functional mechanisms driving this transition remain obscured. This study elucidates the genomic potential for metabolic reprogramming and the putative "functional handover" underpinning the stability of the dysbiotic state. METHODS: A computational meta-analysis of 3557 vaginal microbiomes from diverse global cohorts was performed using the standardized MGnify pipeline. A high-resolution subset of 187 whole-genome shotgun (WGS) metagenomes was stratified to compare functional potential across demographic groups. Taxon-function interaction networks were constructed, utilizing a dual-filter statistical approach (p < 0.05 and effect size ranking), to map the shift from homeostatic maintenance to dysbiotic metabolic potential. RESULTS: BV was characterized by a fundamental shift from "maintenance" pathways to high-turnover "growth-oriented" genomic repertoires. While ABC transporter-like domains were present in healthy communities, dysbiosis was marked by a quantitative expansion and diversification of these systems alongside P-loop NTPases. Network analysis revealed a putative "functional handover": while Gardnerella serves as the adherent structural scaffold, the metabolic burden appears to be associated with secondary anaerobes, specifically BVAB1 and Sneathia, which exhibit strong genomic correlations with nutrient transport and stress response pathways. Crucially, microbiomes from women of African ancestry (Black cohort) exhibited a distinct functional profile with genomic signatures consistent with functions previously associated with resistome expansion (e.g., tetracycline/macrolide resistance), contrasting with Asian cohorts. CONCLUSION: BV is a state of metabolic reprogramming where genomic functional dominance is transferred from Lactobacillus to a cooperative network of anaerobic opportunists. Identifying BVAB1 and Sneathia as candidate metabolic engines, supported by a Gardnerella scaffold, challenges current therapeutic paradigms and highlights the potential for precision medicine targeting specific functional drivers and resistome profiles across diverse populations.

Humans↗

PubMed2024

Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

Vaginosis, Bacterial↗

PubMed2026

Maternal Tuberculosis and Infant Gut and Immune Development: Implications for Maternal-Child Health.

BACKGROUND: Maternal tuberculosis (TB) during pregnancy involves chronic infection, immune activation, and antimicrobial therapy, which may alter the maternal gut, vaginal, and breast milk microbiomes and influence neonatal immune development. METHODS: We conducted a narrative review of studies identified through PubMed and GoogleScholar addressing the maternal TB-microbiome-infant immunity axis. Where evidence from pregnant women with TB was limited, findings were extrapolated from non-pregnant TB populations, antibiotic exposure studies, and broader maternal-infant microbiome research. RESULTS: Maternal TB and its treatment may alter gut, vaginal, and breast milk microbiomes and the immune-metabolic composition of milk. These changes could influence perinatal microbial transmission, mucosal maturation, and infant immune responses, including vaccine responsiveness, BCG immunogenicity, and IGRA conversion. Treatment timing, antibiotic exposure, and maternal nutrition may modify these effects. CONCLUSION: Understanding the maternal TB-microbiome-immune axis may help optimize infant immune outcomes. Longitudinal mother-infant studies, multi-omic analyses, and mechanistic models are needed to clarify these interactions and evaluate microbiome informed strategies, including nutritional optimization, targeted probiotics/prebiotics, and antibiotic stewardship.

Infant gut colonization↗

PubMed2026

Successful Live Birth Following Treatment of Persistent Endometrial Dysbiosis and Recurrent Chronic Endometritis: A Case Report.

CASE: To study the cause of recurrent endometritis, which recurred after standard antibiotic therapy, we report the case of a 40-year-old woman with a history of recurrent pregnancy, preterm birth, and CE. The endometritis recurred following a standard antibiotic regimen. OUTCOME: Microbiome analysis via 16S rRNA gene sequencing revealed persistent dysbiosis in both vaginal and endometrial samples despite antibiotic regimens. Whole-exome sequencing (WES) identified rare variants in TRPV3 and CD36, potentially associated with epithelial barrier dysfunction. Following an extended course of antibiotic therapy, the woman gave birth to a healthy baby at GA 32 weeks. CONCLUSIONS: This case highlights the possibility that barrier gene variants may be associated with persistent endometrial dysbiosis and recurrence of CE. An intensive antibiotic regimen may help achieve a viable pregnancy in patients with recurrent CE following standard antibiotic therapy.

antibiotics↗

PubMed2022

Identification of shared bacterial strains in the vaginal microbiota of related and unrelated reproductive-age mothers and daughters using genome-resolved metagenomics.

It has been suggested that the human microbiome might be vertically transmitted from mother to offspring and that early colonizers may play a critical role in development of the immune system. Studies have shown limited support for the vertical transmission of the intestinal microbiota but the derivation of the vaginal microbiota remains largely unknown. Although the vaginal microbiota of children and reproductive age women differ in composition, the vaginal microbiota could be vertically transmitted. To determine whether there was any support for this hypothesis, we examined the vaginal microbiota of daughter-mother pairs from the Baltimore metropolitan area (ages 14-27, 32-51; n = 39). We assessed whether the daughter's microbiota was similar in composition to their mother's using metataxonomics. Permutation tests revealed that while some pairs did have similar vaginal microbiota, the degree of similarity did not exceed that expected by chance. Genome-resolved metagenomics was used to identify shared bacterial strains in a subset of the families (n = 22). We found a small number of bacterial strains that were shared between mother-daughter pairs but identified more shared strains between individuals from different families, indicating that vaginal bacteria may display biogeographic patterns. Earlier-in-life studies are needed to demonstrate vertical transmission of the vaginal microbiota.

Child↗

PubMed2026

The Puerperium in the Modern Dairy Cow: A Review.

The puerperium represents a critical physiological period during which the bovine reproductive tract transitions from pregnancy to renewed fertility. In the modern high-producing dairy cow, this transition is challenged by profound metabolic, endocrine, immunological, and structural demands that collectively influence uterine health, ovarian function, and subsequent reproductive performance. This review examines current understanding of the physiology of the puerperium in dairy cattle, with particular emphasis on uterine involution, immune clearance of postpartum contamination, endocrine regulation, and resumption of ovarian cyclicity. Further, it contrasts high-yielding Holsteins with fertility selected dairy populations. Normal uterine involution involves coordinated myometrial contraction, tissue remodelling, endometrial regeneration, and tightly regulated inflammatory responses. Failure of these processes predisposes cows to postpartum uterine disorders, including retained fetal membranes, metritis, endometritis (purulent vaginal discharge with cytological confirmation), and pyometra, which remain major contributors to subfertility and economic loss. Central to the pathophysiology of puerperal disease is negative energy balance, which disrupts immune competence, alters hepatic steroid metabolism, impairs ovarian signalling, and compromises oocyte and embryo quality. Emerging evidence highlights the complex interplay between metabolism, immunity, and the uterine microbiome, shifting current perspectives away from pathogen-centric models toward host resilience. Advances in biomarkers, genomic selection, and precision monitoring offer new opportunities for targeted reproductive management. Ultimately, optimisation of transition period management remains the cornerstone of supporting physiological puerperal recovery and sustaining reproductive efficiency in modern dairy systems.

Animals↗

PubMed2025

Investigation of associations between the neonatal gut microbiota and severe viral lower respiratory tract infections in the first 2 years of life: a birth cohort study with metagenomics.

BACKGROUND: Early-life gut microbiota affects immune system development, including the lung immune response (gut-lung axis). We aimed to investigate whether gut microbiota composition in neonates in the first week of life is associated with hospital admissions for viral lower respiratory tract infections (vLRTIs). METHODS: The Baby Biome Study (BBS) is a prospective birth cohort, which enrolled mother-baby pairs between Jan 1, 2016, and Dec 31, 2017, at three UK hospitals. In the present study, we only included BBS babies with a sequenced first-week stool sample and successful data linkage. Stool was collected in the first week of life for shotgun-metagenomic sequencing. We examined the following microbiota features: alpha diversity (Chao1, Shannon, and Simpson indices) and community structures (cluster-partitioning against medoids method). The participants were followed up through linkage to the Hospital Episode Statistics-Admitted Patient Care (HES-APC) database to determine vLRTI hospital admission incidence in the first 2 years of life. We used Poisson mixed-effects models for univariable and multivariable analyses to evaluate the association between microbiota features and vLRTI hospital admission incidence, adjusting for confounders identified through direct acyclic graphs. FINDINGS: 3305 (95%) of the 3476 BBS-enrolled babies for whom consent to data linkage was obtained were included in the present study. 1111 (34%) babies had a first-week sequenced stool sample, of whom 1082 (97%; 564 born vaginally and 518 born by caesarean section) were successfully linked to HES-APC, and had median follow-up of 2·0 years (IQR 1·4-2·9). Most babies were born at term (996 [92%] ≥37 weeks gestational age and 1070 [99%] >35 weeks gestational age) and healthy (1050 [97%] had no comorbidities), and 520 (48%) were female and 562 (52%) were male. Higher first-week gut microbiota alpha diversity was associated with reduced rates of vLRTI hospital admission (Chao1 Index adjusted hazard ratio [HR] 0·92 [95% CI 0·85-0·99]; Shannon Index adjusted HR 0·57 [0·33-0·98]; and Simpson Index adjusted HR 0·36 [0·11-1·20]). Three microbiota clusters were identified. Cluster 1 had a mixed composition and cluster 2 was dominated by Bifidobacterium breve, with both clusters observed in babies born vaginally and by caesarean section. Cluster 3 was found only in vaginally born babies and was dominated by Bifidobacterium longum. Having cluster 1 (mixed) or cluster 2 (B breve dominated) was independently associated with increased rates of vLRTI hospital admission compared with cluster 3 (B longum dominated; cluster 1 [mixed] 3·05 [1·25-7·41] and cluster 2 [B breve dominated] 2·80 [1·06-7·44]). INTERPRETATION: We report observational evidence that first-week gut microbiota differences are associated with clinically severe vLRTI in young children. This study identified bacterial species that could be of interest for vLRTI prevention. This finding has important implications for the design of future research and intervention strategies. FUNDING: The Wellcome Trust and Wellcome Sanger Institute core funding.

Humans↗