The vagino-cervical microbiome as a woman’s life history

Abstract

The vagina contains at least a billion microbial cells, which are dominated byLactobacilli. Here we perform metagenomic shotgun sequencing on cervical samples from 1148 women. Factors such as pregnancy, delivery histories and breast-feeding were all more important than menstrual cycle in shaping the microbiome. Bifidobacterium breve was seen with older age at sexual debut;Lactobacillus crispatus negatively correlated with pregnancy history; potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, contraceptives were also identified. Other features such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Gut and oral microbiome, plasma vitamins, metals, amino acids and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact. Highlights:Shotgun sequencing of 1148 vagino-cervical samples reveal subtypes; 1Other omics such as moods and skin features could be predicted by the vagino-cervical 2 bacteria; 3Factors such as delivery mode and breast-feeding associate with the vagino-cervical 4 microbiome; 5With dwindled Lactobacilli, postmenopausal samples are relatively enriched for viruses. 6 7 3 4 vulvovaginal candidiasis (Bradford and Ravel, 2017). The over 90% of human 30 sequences in female reproductive tract samples, in contrast to 1% in feces (Li et al., 31 2018; Methé et al., 2012; Wang and Jia, 2016), has made metagenomic shotgun 32 sequencing more expensive. Most studies of the vaginal microbiota used 16S rRNA 33 gene amplicon sequencing, which lacked a view of the overall microorganism 34 communities including bacteria, archaea, viruses and fungi (Byrd et al., 2018), as well 35 as the functional capacity encoded. Besides infection, studies on current sexual activity 36 and the menstrual cycle occurred naturally to the vaginal microbiota field (Gajer et al., 37 2012; Ravel et al., 2010). However, lasting impacts from other potentially important 38 factors such as sexual debut, pregnancy and breast-feeding have not been looked at in 39 a reasonably large cohort. 40 41 As a sizable reservoir of microbes instead of a transient entity, the female reproductive 42 tract microbiota might also reflect conditions in other body sites. It is however not clear 43 whether other omics in circulation or in the intestine cross-talks with the vagino-cervical 44 microbiome. Intersecting with hormones, metabolic and immune functions, we find it 45intriguing to explore the potential link of the vagino-cervical microbiome to the brain and 46 the face. 47 5 data, immune indices, physical fitness test, facial skin imaging, as well as female life 53 history questionnaire, lifestyle questionnaire, and psychological questionnaire (Figure 1). 54Our work pinpoints other metadata or omics that can predict or be predicted from the 55 microbiota in the female reproductive tr...

A genome-wide association study for gut metagenome in Chinese adults illuminates complex diseases

“…Due to the emphasis on diet in early studies and recently on medication, MWAS 1,31 have received even more controversy than GWAS. Besides diet and medication, we also took into account physical activity in this 4D-SZ cohort 44,45 . Here we find that fecal biomarkers previously reported by MWAS studies on colorectal cancer and metabolic diseases have some associations with host genetics, whereas some taxa especially some spore-forming bacteria lacked host genetic associations.…”

“…632 individuals were enlisted in the discovery cohort and 663 individuals were enlisted in the replication cohort, as part of the larger effort of 4D-SZ study 44,45 . Questionnaires were collected through a cell phone application.…”

Over 50000 metagenomically assembled draft genomes for the human oral microbiome reveal new taxa

“…In order to substantially increase the amount of oral microbiome data, we shotgun sequenced 2284 saliva and 391 tongue dorsum samples from the 4D-SZ cohort 3, 12, 22 , 671 saliva samples from five ethnic groups of Yunnan province, producing over 43.19 terabytes of sequence data ( Supplementary Table 1 ). Together with 808 published samples from 5 studies 6, 23–26 that have not been used for metagenomic assembly ( Supplementary Table 1 ), a total of 4,154 oral samples with metagenomic data were obtained.…”

“…A number of taxa with compact genomes were identified in this study, such as CPR and Mollicutes. Mollicutes such as Mycoplasma and Ureaplasma are well known in the female reproductive tract 22 . Much remains to be elucidated for the metabolic requirement of small bacteria in the oral microbiome.…”

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

“…to maintain a balanced pH for themselves. The top one for gut microbes may be glutamate decarboxylase (produces GABA (γ-aminobutyric acid) from glutamate), while histidine decarboxylase in the female reproductive tract might contribute to menstrual pains 75 . Besides, recent studies identified tyrosine decarboxylases in gut microbes that could digest the medication levodopa used to treat Parkinson’s disease 76, 77 .…”