scholarly journals Relationship between the Oral and Vaginal Microbiota of South African Adolescents with High Prevalence of Bacterial Vaginosis

2020 ◽  
Vol 8 (7) ◽  
pp. 1004 ◽  
Author(s):  
Christina Balle ◽  
Rachel Esra ◽  
Enock Havyarimana ◽  
Shameem Z. Jaumdally ◽  
Katie Lennard ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
South African ◽  
Bacterial Species ◽  
Hypervariable Region ◽  
Vaginal Microbiota ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Prevotella Intermedia ◽  
Increased Risk ◽  
High Prevalence

Bacterial vaginosis (BV) and periodontal disease (PD) are characterised as bacterial dysbioses. Both are associated with an increased risk of poor pregnancy outcomes, yet it is unknown whether PD and BV are related. We characterised the oral microbiota of young South African females with a high prevalence of BV and investigated the association between oral communities and vaginal microbiota. DNA was extracted from vaginal lateral wall, saliva and supragingival plaque samples from 94 adolescent females (aged 15–19 years). 16S rRNA gene sequencing of the V4 hypervariable region was performed for analysis of the oral and vaginal microbiota and BV status was determined by Nugent scoring. The core oral microbiota was predominately comprised of Firmicutes followed by Proteobacteria and Bacteroidetes. The salivary microbiota of participants with BV was more diverse than those with lactobacillus-dominated communities (p = 0.030). PD-associated bacterial species, including Prevotella intermedia and Porphyromonas endodontalis were enriched in the supragingival microbiota of women with non-optimal vaginal communities compared to those with Lactobacillus-dominant communities, while Pseudomonas aeruginosa and Prevotella intermedia were enriched in the saliva of women with non-optimal vaginal microbiota. These data suggest a relationship between oral and vaginal dysbiosis, warranting further investigation into whether they are casually related.

scholarly journals Impact of preconception vaginal microbiota on women’s risk of spontaneous preterm birth: protocol for a prospective case-cohort study

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e035186 ◽  
Author(s):  
Erica M Lokken ◽  
Kishorchandra Mandaliya ◽  
Sujatha Srinivasan ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Umbilical Cord ◽  
Bacterial Species ◽  
Vaginal Microbiota ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Rrna Gene ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

IntroductionBacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria present around conception may lead to SPTB by compromising the protective effects of cervical mucus, colonising the endometrial surface before fetal membrane development, and causing low-level inflammation in the decidua, placenta and fetal membranes. This protocol describes a prospective case-cohort study addressing this hypothesis.Methods and analysisHIV-seronegative Kenyan women with fertility intent are followed from preconception through pregnancy, delivery and early postpartum. Participants provide monthly vaginal specimens during the preconception period for vaginal microbiota assessment. Estimated date of delivery is determined by last menstrual period and first trimester obstetrical ultrasound. After delivery, a swab is collected from between the fetal membranes. Placenta and umbilical cord samples are collected for histopathology. Broad-range 16S rRNA gene PCR and deep sequencing of preconception vaginal specimens will assess species richness and diversity in women with SPTB versus term delivery. Concentrations of key bacterial species will be compared using quantitative PCR (qPCR). Taxon-directed qPCR will also be used to quantify bacteria from fetal membrane samples and evaluate the association between bacterial concentrations and histopathological evidence of inflammation in the fetal membranes, placenta and umbilical cord.Ethics and disseminationThis study was approved by ethics committees at Kenyatta National Hospital and the University of Washington. Results will be disseminated to clinicians at study sites and partner institutions, presented at conferences and published in peer-reviewed journals. The findings of this study could shift the paradigm for thinking about the mechanisms linking vaginal microbiota and prematurity by focusing attention on the preconception vaginal microbiota as a mediator of SPTB.

scholarly journals Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
Katie Lennard ◽  
Smritee Dabee ◽  
Shaun L. Barnabas ◽  
Enock Havyarimana ◽  
Anna Blakney ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
South African ◽  
Adolescent Females ◽  
Gardnerella Vaginalis ◽  
Rrna Gene ◽  
Vaginal Microbiome ◽  
Microbial Composition ◽  
Content Type ◽  
Specificity And Sensitivity ◽  
Increased Risk

ABSTRACTYoung African females are at an increased risk of HIV acquisition, and genital inflammation or the vaginal microbiome may contribute to this risk. We studied these factors in 168 HIV-negative South African adolescent females aged 16 to 22 years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters (subtypes), one of which was strongly associated with genital inflammation. In a multivariate model, the microbiome compositional subtype and hormonal contraception were significantly associated with genital inflammation. We identified 40 taxa significantly associated with inflammation, including those reported previously (Prevotella,Sneathia,Aerococcus,Fusobacterium, andGemella) as well as several novel taxa (including increased frequencies of bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3,Prevotella amnii,Prevotella pallens,Parvimonas micra,Megasphaera,Gardnerella vaginalis, andAtopobium vaginaeand decreased frequencies ofLactobacillus reuteri,Lactobacillus crispatus,Lactobacillus jensenii, andLactobacillus iners). Women with inflammation-associated microbiomes had significantly higher body mass indices and lower levels of endogenous estradiol and luteinizing hormone. Community functional profiling revealed three distinct vaginal microbiome subtypes, one of which was characterized by extreme genital inflammation and persistent bacterial vaginosis (BV); this subtype could be predicted with high specificity and sensitivity based on the Nugent score (≥9) or BVAB1 abundance. We propose that women with this BVAB1-dominated subtype may have chronic genital inflammation due to persistent BV, which may place them at a particularly high risk for HIV infection.

scholarly journals Associations between dietary micronutrient intake and molecular-Bacterial Vaginosis

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Susan Tuddenham ◽  
Khalil G. Ghanem ◽  
Laura E. Caulfield ◽  
Alisha J. Rovner ◽  
Courtney Robinson ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Hormonal Contraception ◽  
Amplicon Sequencing ◽  
Vaginal Microbiota ◽  
Rrna Gene ◽  
Cross Sectional ◽  
Micronutrient Intake ◽  
Increased Risk ◽  
Sectional Analysis ◽  
Reproductive Aged Women

Abstract Objectives Bacterial vaginosis (BV), a clinical condition characterized by decreased vaginal Lactobacillus spp., is difficult to treat. We examined associations between micronutrient intake and a low-Lactobacillus vaginal microbiota as assessed by molecular methods (termed “molecular-BV”). Methods This cross-sectional analysis utilized data collected at the baseline visit of the Hormonal Contraception Longitudinal Study, a cohort of reproductive-aged women followed over 2 years while initiating or ceasing hormonal contraception (HC). The Block Brief 2000 Food Frequency Questionnaire was administered and micronutrient intakes were ranked. Vaginal microbiota composition was assessed using 16S rRNA gene amplicon sequencing and clustered into community state types (CSTs) based on the types and relative abundance of bacteria detected. Associations between the lowest estimated quartile intake of nutrients and having a low-Lactobacillus CST (molecular-BV) were evaluated by logistic regression. Separate models were built for each nutrient controlling for age, body mass index, behavioral factors, HC use and total energy intake. We also conducted a literature review of existing data on associations between micronutrient intakes and BV. Results Samples from 104 women were included in this analysis. Their mean age was 25.8 years (SD 4.3), 29.8% were African American, 48.1% were using HC, and 25% had molecular-BV. In adjusted multivariable analyses, the lowest quartile of betaine intake was associated with an increased odds of molecular-BV (aOR 9.2, p value < 0.01, [CI 2.4–35.0]). Conclusions This is the first study to assess the association between estimated micronutrient intake and molecular-BV. Lower energy-adjusted intake of betaine was associated with an increased risk of molecular-BV. Betaine might have direct effects on the vaginal microenvironment or may be mediated through the gut microbiota. Additional research is needed to determine reproducibility of this finding and whether improved intake of select micronutrients such as betaine decreases the risk of BV and its sequelae.

scholarly journals Medroxyprogesterone acetate mediated alteration in the vaginal microbiota and microenvironment in a Kenyan sex worker cohort

2018 ◽  
Author(s):  
Jocelyn M. Wessels ◽  
Julie Lajoie ◽  
Maeve I. J. Hay Cooper ◽  
Kenneth Omollo ◽  
Allison M. Felker ◽  
...  
Keyword(s):  
Bacterial Diversity ◽  
Medroxyprogesterone Acetate ◽  
Sex Workers ◽  
Bacterial Species ◽  
Vaginal Microbiota ◽  
Target Cells ◽  
Rrna Gene ◽  
Vaginal Colonization ◽  
Increased Risk ◽  
Hiv 1

Abstract:The hormonal contraceptive Medroxyprogesterone Acetate (MPA) is associated with increased risk of Human Immunodeficiency Virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent Scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria believed to protect against STIs. Furthermore, increased diversity of the vaginal microbiota correlated with activation of vaginal HIV-1 target cells. Results were recapitulated in humanized mice where MPA treatment was associated with increased diversity of the vaginal microbiota, low glycogen, and enhanced HIV-1 susceptibility. Together these results suggest MPA-induced hypo-estrogenism may alter key metabolic components necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota. Bacterial diversity in the vaginal microbiota correlates with activation of HIV-1 target cells, which might thus contribute to enhanced susceptibility to HIV-1.

scholarly journals Temporal Changes in Vaginal Microbiota and Genital Tract Cytokines Among South African Women Treated for Bacterial Vaginosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andile Mtshali ◽  
James Emmanuel San ◽  
Farzana Osman ◽  
Nigel Garrett ◽  
Christina Balle ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
South African ◽  
Relative Abundance ◽  
Genital Tract ◽  
Vaginal Microbiota ◽  
African Women ◽  
Response To Treatment ◽  
Rrna Gene ◽  
Short Term ◽  
South African Women

The standard treatment for bacterial vaginosis (BV) with oral metronidazole is often ineffective, and recurrence rates are high among African women. BV-associated anaerobes are closely associated with genital inflammation and HIV risk, which underscores the importance of understanding the interplay between vaginal microbiota and genital inflammation in response to treatment. In this cohort study, we therefore investigated the effects of metronidazole treatment on the vaginal microbiota and genital cytokines among symptomatic South African women with BV [defined as Nugent score (NS) ≥4] using 16S rRNA gene sequencing and multiplex bead arrays. Among 56 BV-positive women, we observed short-term BV clearance (NS &lt;4) in a proportion of women six weeks after metronidazole treatment, with more than half of these experiencing recurrence by 12 weeks post-treatment. BV treatment temporarily reduced the relative abundance of BV-associated anaerobes (particularly Gardnerella vaginalis and Atopobium vaginae) and increased lactobacilli species (mainly L. iners), resulting in significantly altered mucosal immune milieu over time. In a linear mixed model, the median concentrations of pro-inflammatory cytokines and chemokines were significantly reduced in women who cleared BV compared to pre-treatment. BV persistence and recurrence were strongly associated with mucosal cytokine profiles that may increase the risk of HIV acquisition. Concentrations of these cytokines were differentially regulated by changes in the relative abundance of BVAB1 and G. vaginalis. We conclude that metronidazole for the treatment of BV induced short-term shifts in the vaginal microbiota and mucosal cytokines, while treatment failures promoted persistent elevation of pro-inflammatory cytokine concentrations in the genital tract. These data suggest the need to improve clinical management of BV to minimize BV related reproductive risk factors.

scholarly journals 16S rRNA Long-Read Sequencing of the Granulation Tissue from Nonsmokers and Smokers-Severe Chronic Periodontitis Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Rebecca Chowdhry ◽  
Neetu Singh ◽  
Dinesh Kumar Sahu ◽  
Ratnesh Kumar Tripathi ◽  
Archana Mishra ◽  
...  
Keyword(s):  
16S Rrna ◽  
Granulation Tissue ◽  
Ketone Bodies ◽  
Bacterial Species ◽  
Rrna Gene ◽  
Differential Abundance ◽  
Streptobacillus Moniliformis ◽  
Increased Risk ◽  
Long Read ◽  
Significant Enrichment

Smoking has been associated with increased risk of periodontitis. The aim of the present study was to compare the periodontal disease severity among smokers and nonsmokers which may help in better understanding of predisposition to this chronic inflammation mediated diseases. We selected deep-seated infected granulation tissue removed during periodontal flap surgery procedures for identification and differential abundance of residential bacterial species among smokers and nonsmokers through long-read sequencing technology targeting full-length 16S rRNA gene. A total of 8 phyla were identified among which Firmicutes and Bacteroidetes were most dominating. Differential abundance analysis of OTUs through PICRUST showed significant (p>0.05) abundance of Phyla-Fusobacteria (Streptobacillus moniliformis); Phyla-Firmicutes (Streptococcus equi), and Phyla Proteobacteria (Enhydrobacter aerosaccus) in nonsmokers compared to smokers. The differential abundance of oral metagenomes in smokers showed significant enrichment of host genes modulating pathways involving primary immunodeficiency, citrate cycle, streptomycin biosynthesis, vitamin B6 metabolism, butanoate metabolism, glycine, serine, and threonine metabolism pathways. While thiamine metabolism, amino acid metabolism, homologous recombination, epithelial cell signaling, aminoacyl-tRNA biosynthesis, phosphonate/phosphinate metabolism, polycyclic aromatic hydrocarbon degradation, synthesis and degradation of ketone bodies, translation factors, Ascorbate and aldarate metabolism, and DNA replication pathways were significantly enriched in nonsmokers, modulation of these pathways in oral cavities due to differential enrichment of metagenomes in smokers may lead to an increased susceptibility to infections and/or higher formation of DNA adducts, which may increase the risk of carcinogenesis.

scholarly journals Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study

Gut ◽  
2016 ◽  
Vol 67 (1) ◽  
pp. 120-127 ◽  
Author(s):  
Xiaozhou Fan ◽  
Alexander V Alekseyenko ◽  
Jing Wu ◽  
Brandilyn A Peters ◽  
Eric J Jacobs ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Case Control Study ◽  
Case Control ◽  
Oral Microbiome ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Increased Risk ◽  
Oral Pathogens ◽  
Nested Case Control ◽  
Control Study

ObjectiveA history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case–control study.DesignWe selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression.ResultsCarriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study.ConclusionsThis study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.

scholarly journals Transition of Bacterial Diversity and Composition in Tongue Microbiota during the First Two Years of Life

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Shinya Kageyama ◽  
Mikari Asakawa ◽  
Toru Takeshita ◽  
Yukari Ihara ◽  
Shunsuke Kanno ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Bacterial Diversity ◽  
Bacterial Species ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Bacterial Composition ◽  
Content Type ◽  
Operational Taxonomic Units ◽  
Rrna Gene Sequencing

ABSTRACTNewborns are constantly exposed to various microbes from birth; hence, diverse commensal bacteria colonize the oral cavity. However, how or when these bacteria construct a complex and stable ecosystem remains unclear. This prospective cohort study examined the temporal changes in bacterial diversity and composition in tongue microbiota during infancy. We longitudinally collected a total of 464 tongue swab samples from 8 infants (age of <6 months at baseline) for approximately 2 years. We also collected samples from 32 children (aged 0 to 2 years) and 73 adults (aged 20 to 29 years) cross-sectionally as control groups. Bacterial diversities and compositions were determined by 16S rRNA gene sequencing. The tongue bacterial diversity in infancy, measured as the number of observed operational taxonomic units (OTUs), rapidly increased and nearly reached the same level as that in adults by around 80 weeks. The overall tongue bacterial composition in the transitional phase, 80 to 120 weeks, was more similar to that of adults than to that of the early exponential phase (EEP), 10 to 29 weeks, according to analysis of similarities. Dominant OTUs in the EEP corresponding toStreptococcus perorisandStreptococcus lactariusexponentially decreased immediately after EEP, around 30 to 49 weeks, whereas several OTUs corresponding toGranulicatella adiacens,Actinomyces odontolyticus, andFusobacterium periodonticumreciprocally increased during the same period. These results suggest that a drastic compositional shift of tongue microbiota occurs before the age of 1 year, and then bacterial diversity and overall bacterial composition reach levels comparable to those in adults by the age of 2 years.IMPORTANCEEvaluating the development of oral microbiota during infancy is important for understanding the subsequent colonization of bacterial species and the process of formation of mature microbiota in the oral cavity. We examined tongue microbiota longitudinally collected from 8 infants and found that drastic compositional shifts in tongue microbiota occur before the age of 1 year, and then bacterial diversity and overall bacterial composition reach levels comparable to those in adults by the age of 2 years. These results may be helpful for preventing the development of various diseases associated with oral microbiota throughout life.

scholarly journals Alterations in Vaginal Microbiota among Pregnant Women with COVID-19

2021 ◽  
Author(s):  
Ebru Celik ◽  
Gulin Ozcan ◽  
Cansel Vatansever ◽  
Erxiati Paerhati ◽  
Mert Ahmet Kuskucu ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Pregnancy Outcomes ◽  
Diversity Index ◽  
Alpha Diversity ◽  
Active Phase ◽  
Adverse Outcomes ◽  
Vaginal Microbiota ◽  
Rrna Gene ◽  
Increased Risk ◽  
Adverse Pregnancy

Abstract Background: The maintenance of vaginal microbiota is an important factor to achieve ideal pregnancy outcomes. Coronavirus disease (COVID-19) has been shown to have potential adverse effects on pregnancy and neonatal outcomes. Pregnancy itself is a risk factor for the severity of COVID-19, with an increased risk of intensive care unit (ICU) admission, maternal morbidity, and mortality. the role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in vaginal microbiome composition in pregnant women with COVID-19 has not yet been investigated. Therefore, we anticipate that COVID-19 may unfavorably affect the composition of the vaginal microbiota, resulting in adverse pregnancy outcomes. We aimed to describe the alterations of the composition of vaginal microbiota in pregnant women with COVID-19.Results: A prospective case-control study was conducted among 19 pregnant women with COVID-19 and 28 healthy controls matched according to the gestational week and age. The vaginal swabs were collected during the active phase of infection and consecutively, within a month after recovering from infection. In three patients, longitudinal samples before, in the course, and after infection were also obtained. The microbiome alterations were examined by 16S rRNA gene sequencing. We indicated that COVID-19 was associated with vaginal dysbiosis during pregnancy, which was indicated by an increased alpha diversity index. There was a significantly decrease in Firmicutes (P=0.007) and Lactobacillus (P=0.019) with an increase in Bacteroidetes (P=0.024) in the COVID-19 group. In the moderate/severe group, increased amounts of Ureaplasma and vanishing of Lactobacillus gasseri were found in women, compared to the asymptomatic or mild group (P=0.001). In longitudinal analysis, elevation of Actinobacteria with reduction of Firmicutes and Bacteroides were indicated during the active phase. Conclusions: The study revealed vaginal dysbiosis with a low abundance of Lactobacillus and an increase in Bacteroidetes in relation to SARS-CoV-2 infection. Vaginal dysbiosis in COVID-19 could be a contributing factor in pregnancy adverse outcomes. Trial registration: clinicaltrials, Registered 15 November 2019, https://www.clinicaltrials.gov/ct2/show/NCT04165252?cond=microbiota&cntry=TR&draw=3&rank=12

scholarly journals Gastric Microbiota in Helicobacter pylori-Negative and -Positive Gastritis Among High Incidence of Gastric Cancer Area

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 504 ◽  
Author(s):  
Boldbaatar Gantuya ◽  
Hashem B. El-Serag ◽  
Takashi Matsumoto ◽  
Nadim J. Ajami ◽  
Khasag Oyuntsetseg ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Bacterial Species ◽  
Rrna Gene ◽  
Linear Discriminant ◽  
Haemophilus Parainfluenzae ◽  
Increased Risk ◽  
Comparison Groups ◽  
H Pylori ◽  
Gastric Microbiota

Helicobacter pylori (H. pylori) related chronic gastritis is a well-known major etiological factor for gastric cancer development. However, H. pylori-negative gastritis (HpN) is not well described. We aimed to examine gastric mucosal microbiota in HpN compared to H. pylori-positive gastritis (HpP) and H. pylori-negative non-gastritis group (control). Here, we studied 11 subjects with HpN, 40 with HpP and 24 controls. We performed endoscopy with six gastric biopsies. Comparison groups were defined based on strict histological criteria for the disease and H. pylori diagnosis. We used 16S rRNA gene amplicon sequencing to profile the gastric microbiota according to comparison groups. These results demonstrate that the HpP group had significantly lower bacterial richness by the operational taxonomic unit (OTU) counts, and Shannon and Simpson indices as compared to HpN or controls. The linear discriminant analysis effect size analysis showed the enrichment of Firmicutes, Fusobacteria, Bacteroidetes and Actinobacteria at phylum level in the HpN group. In the age-adjusted multivariate analysis, Streptococcus sp. and Haemophilus parainfluenzae were at a significantly increased risk for HpN (odds ratio 18.9 and 12.3, respectively) based on abundance. Treponema sp. was uniquely found in HpN based on occurrence. In this paper, we conclude that Streptococcus sp., Haemophilus parainfluenzae and Treponema sp. are candidate pathogenic bacterial species for HpN. These results if confirmed may have important clinical implications.

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