-
Journal of Molecular Medicine (Berlin,... Oct 2021A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of...
A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). The anti-microbial ELISA assays follow on prior human brain tissue RNA sequencing studies that established multiple sclerosis (MS) microbial candidates. Lysates included in the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans. CSF responses from patients with demyelinating diseases (DD, N = 14) were compared to those with other neurological diseases (OND, N = 8) and controls (N = 13). Commercial positive and negative control CSF specimens were run with each assay. ELISA index values were derived for each specimen against each of the 10 bacterial lysates. CSF reactivity was significantly higher in the DD group compared to the controls against Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Four of the 11 tested DD group subjects had elevated antibody indexes against at least one of the 10 bacterial species, suggesting intrathecal antibody production. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. KEY MESSAGES: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases, including multiple sclerosis and acute disseminated encephalomyelitis. CSF reactivity was significantly higher in the demyelination group compared to the controls against the bacteria Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Several of the demyelination subjects had elevated antibody indexes against at least one of the 10 antigens, suggesting at least limited intrathecal production of anti-bacterial antibodies. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients.
Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Autoantibodies; Bacteria; Cerebrospinal Fluid; Female; Humans; Immunoglobulin G; Male; Middle Aged; Multiple Sclerosis; Polyradiculoneuropathy; Young Adult
PubMed: 34100959
DOI: 10.1007/s00109-021-02085-z -
International Journal of Infectious... Nov 2020To investigate symptoms of infections and their risk factors among French medical students undertaking an internship abroad.
OBJECTIVES
To investigate symptoms of infections and their risk factors among French medical students undertaking an internship abroad.
METHODS
Clinical follow up, and qPCR-based respiratory, gastrointestinal, and vaginal pathogen carriages were prospectively assessed pre-travel and post-travel, in a cohort of medical students departing from Marseille, France.
RESULTS
293 students were included. 63.5%, 35.8%, and 3.6% of students reported gastrointestinal, respiratory, and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli and Enteropathogenic E. coli was 40.9% and 18.6%, respectively. A significant increase was observed for rhinovirus and Streptococcus pneumoniae by comparing the prevalence of pathogens in pre-travel and post-travel samples. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 12.9% and 13.9%, respectively. Being female, primarily traveling to Vietnam, and living in basic accommodation conditions were independent risk factors for reporting respiratory symptoms. Students reporting respiratory symptoms were three times more likely to acquire S. pneumoniae. Traveling primarily to north India and Senegal were independent risk factors for diarrhea.
CONCLUSION
This study makes it possible to identify the leading infectious diseases linked to travel in a group of French medical students undertaking an internship abroad and the risk factors on which to base targeting students for reinforced pre-travel advice.
Topics: Actinobacteria; Adult; Carrier State; Diarrhea; Escherichia coli; Female; France; Humans; India; Infections; Male; Risk Factors; Senegal; Students, Medical; Travel; Vietnam; Young Adult
PubMed: 32890724
DOI: 10.1016/j.ijid.2020.08.075 -
Cytokine Jan 2021Recent studies suggest that alterations in the vaginal microbiome allow for the assessment of the risk for spontaneous preterm birth (PTB), the leading cause of neonatal...
BACKGROUND
Recent studies suggest that alterations in the vaginal microbiome allow for the assessment of the risk for spontaneous preterm birth (PTB), the leading cause of neonatal morbidity and mortality worldwide. However, the associations between the local immune response and the vaginal microbiome are still poorly understood. Herein, we characterize the vaginal host immune-microbiome interactions in women who ultimately underwent PTB and in those who delivered at term.
METHODS
Vaginal fluid samples from 52 pregnant women (of whom 18 underwent PTB and 34 delivered at term) were collected between 10 and 32 weeks of gestation in a case-control study. Concentrations of 33 immune mediators were determined using sensitive and specific immunoassays. The previously published 16S rRNA gene sequence and bacterial phylotype data of these subjects were utilized in this study. Linear mixed effects models were utilized to test associations between vaginal immune mediator concentrations and bacterial phylotype relative abundances.
RESULTS
1) In the overall study population, vaginal concentrations of CXCL10, CCL2, CCL3, SLP1 and VEGF negatively correlated with non-Lactobacillus, Community State Type IV (CST IV) members of the vaginal microbiome; 2) CXCL10, in particular, negatively correlated with 15 bacterial phylotypes, most of which are typical members of CST IV, such as Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae; 3) Gemella spp., also members of CST IV, negatively correlated with vaginal concentrations of VEGF, CCL2, CCL3, SLPI, and CXCL10; 4) when comparing PTB cases to term controls, five soluble immune mediators (CCL26, CCL22, CCL2, CXCL10, and IL-16), especially CCL26, were negatively correlated with five typical members of CST IV: Sneathia sanguinegens, Parvimonas micra, Veillonellaceae, BVAB2, and Gemella spp.; and 5) Sneathia sanguinegens had stronger negative associations with all five soluble immune mediators (CCL26, CCL22, CCL2, CXCL10, and IL-16) in PTB cases than in term controls.
CONCLUSIONS
The assessment of vaginal host immune-microbiome interactions revealed that specific soluble immune mediators, mainly CXCL10, negatively correlated with typical members of CST IV of the vaginal microbiome. Sneathia sanguinegens, in particular, had stronger negative associations with different immune mediators, including CXCL10 and CCL26, in women who ultimately underwent PTB compared to those who delivered at term. These findings provide insight into the vaginal host immune-microbiome interactions in normal and complicated pregnancies.
Topics: Adult; Black or African American; Bacteria; Case-Control Studies; Chemokine CCL26; Chemokine CXCL10; Cohort Studies; Cytokines; Female; Host-Pathogen Interactions; Humans; Infant, Newborn; Microbiota; Pregnancy; Premature Birth; RNA, Ribosomal, 16S; Vagina; Young Adult
PubMed: 33032107
DOI: 10.1016/j.cyto.2020.155316 -
Frontiers in Public Health 2020Abnormal vaginal microbiota (AVM), including bacterial vaginosis (BV), is caused by a microbiota imbalance. Nugent scoring is the gold standard for the laboratory...
Abnormal vaginal microbiota (AVM), including bacterial vaginosis (BV), is caused by a microbiota imbalance. Nugent scoring is the gold standard for the laboratory diagnosis of BV; however, it is somewhat subjective to interpret, and challenging to distinguish bacteria. Hence, there is a need for improved technologies for the accurate diagnosis of AVM. To this end, next-generation sequencing (NGS) technology has been shown to yield comprehensive information on the pathophysiology of AVM. Hence, to evaluate the relationship between microbiota composition and the pathophysiology of AVM and its clinical significance, we characterized vaginal swab samples from 212 pregnant Korean women using both Nugent scoring and NGS analysis. Of these, the Nugent scoring identified 175 subjects (82.5%; 175/212) with normal flora (NF), 20 (9.4%; 20/212) with intermediate flora (IF), and 17 (8.0%; 17/212) with BV. NGS analysis followed by the characterization of vaginal microbiota composition, as represented by alpha and beta diversity, revealed the relative abundance of specific bacterial taxa at the genus and species level. Moreover, we identified all five predominant community state types (CSTs) along with three smaller CSTs. Analysis of the vaginal microbiota revealed the dominance of one or two spp. in the NF group. Meanwhile, the IF and BV groups were dominated by the genera , and . These two groups also showed higher alpha diversity than the NF group ( < 0.05). Principal coordinate analysis (PCoA) indicated that the NF group was significantly different from the AVM groups ( < 0.05), whereas no significant difference was observed between IF and BV groups ( = 0.25). Lastly, to investigate the characteristics of vaginal microbiota based on taxonomic composition, the IF and BV groups (AVM groups) were reclassified using the unweighted pair group method with arithmetic mean (UPGMA) clustering. Consequently, they were reclassified into BV1 -dominated), BV2-1 (-dominated), BV2-2 ( s1 or s2 and -dominated), and BV3 [mixed population of , and other bacteria ( < 0.05)]. Collectively, these findings could serve to advance the current understanding regarding AVM pathophysiology.
Topics: Actinobacteria; Female; Humans; Lactobacillus; Microbiota; Pregnancy; Republic of Korea
PubMed: 33194936
DOI: 10.3389/fpubh.2020.507024 -
Frontiers in Microbiology 2022An association between the vaginal microbiome and preterm birth has been reported. However, in practice, it is difficult to predict premature birth using the microbiome...
An association between the vaginal microbiome and preterm birth has been reported. However, in practice, it is difficult to predict premature birth using the microbiome because the vaginal microbial community varies highly among samples depending on the individual, and the prediction rate is very low. The purpose of this study was to select markers that improve predictive power through machine learning among various vaginal microbiota and develop a prediction algorithm with better predictive power that combines clinical information. As a multicenter case-control study with 150 Korean pregnant women with 54 preterm delivery group and 96 full-term delivery group, cervicovaginal fluid was collected from pregnant women during mid-pregnancy. Their demographic profiles (age, BMI, education level, and PTB history), white blood cell count, and cervical length were recorded, and the microbiome profiles of the cervicovaginal fluid were analyzed. The subjects were randomly divided into a training ( = 101) and a test set ( = 49) in a two-to-one ratio. When training ML models using selected markers, five-fold cross-validation was performed on the training set. A univariate analysis was performed to select markers using seven statistical tests, including the Wilcoxon rank-sum test. Using the selected markers, including spp., , , , , and , machine learning models (logistic regression, random forest, extreme gradient boosting, support vector machine, and GUIDE) were used to build prediction models. The test area under the curve of the logistic regression model was 0.72 when it was trained with the 17 selected markers. When analyzed by combining white blood cell count and cervical length with the seven vaginal microbiome markers, the random forest model showed the highest test area under the curve of 0.84. The GUIDE, the single tree model, provided a more reasonable biological interpretation, using the 10 selected markers (, , , , , , , , , and ), and the covariates produced a tree with a test area under the curve of 0.77. It was confirmed that the association with preterm birth increased when and increased (AUC = 0.77), which could also be explained by the fact that as the number of increased, the association with preterm birth was high (AUC = 0.77). Our study demonstrates that several candidate bacteria could be used as potential predictors for preterm birth, and that the predictive rate can be increased through a machine learning model employing a combination of cervical length and white blood cell count information.
PubMed: 35983325
DOI: 10.3389/fmicb.2022.912853 -
Pathogens (Basel, Switzerland) Jan 2021Healthy women of reproductive age have a vaginal pH around 4.5, whereas little is known about pH in the upper genital tract. A shift in the vaginal microbiota may result...
INTRODUCTION
Healthy women of reproductive age have a vaginal pH around 4.5, whereas little is known about pH in the upper genital tract. A shift in the vaginal microbiota may result in an elevated pH in the upper genital tract. This might contribute to decreased fertility and increased risk of preterm birth. Therefore, we aimed to measure pH in different compartments of the female genital tract in both nonpregnant and pregnant women, stratifying into a normal and abnormal vaginal microbiota.
MATERIAL AND METHODS
In this descriptive study, we included 6 nonpregnant, 12 early-pregnant, and 8 term-pregnant women. A pH gradient was recorded with a flexible pH probe. An abnormal vaginal microbiota was diagnosed by a quantitative polymerase chain reaction technique for ; ; ; bacterial vaginosis-associated bacterium 1, 2, 3, and TM7; and spp. among others.
RESULTS
In all participants we found the pH gradient in the lower reproductive canal to be most acidic in the lower vagina and most alkaline in the upper uterine cavity. Women with an abnormal vaginal microbiota had an increased pH in the lower vagina compared to the other groups.
CONCLUSIONS
There is a pronounced pH gradient within the female genital tract. This gradient is not disrupted in women with an abnormal vaginal microbiota.
PubMed: 33498288
DOI: 10.3390/pathogens10020090 -
PloS One 2019Vaginal dysbiosis has been shown to increase the risk of some adverse birth outcomes. HIV infection may be associated with shifts in the vaginal microbiome. We...
Vaginal dysbiosis has been shown to increase the risk of some adverse birth outcomes. HIV infection may be associated with shifts in the vaginal microbiome. We characterized microbial communities in vaginal swabs collected between 16-20 gestational weeks in the Zambian Preterm Birth Prevention Study to investigate whether HIV and its treatment alter the microbiome in pregnancy. We quantified relative abundance and diversity of bacterial taxa by whole-genome shotgun sequencing and identified community state types (CST) by hierarchical clustering. Associations between exposures-HIV serostatus (HIV+ vs HIV-) and preconceptional ART (ART+ vs ART-)-and microbiome characteristics were tested with rank-sum, and by linear and logistic regression, accounting for sampling by inverse-probability weighting. Of 261 vaginal swabs, 256 (98%) had evaluable sequences; 98 (38%) were from HIV+ participants, 55 (56%) of whom had preconceptional ART exposure. Major CSTs were dominated by: L. crispatus (CST 1; 17%), L.] iners (CST 3; 32%), Gardnerella vaginalis (CST 4-I; 37%), G. vaginalis & Atopobium vaginae (CST 4-II; 5%), and other mixed anaerobes (CST 4-III; 9%). G. vaginalis was present in 95%; mean relative abundance was higher in HIV+ (0.46±0.29) compared to HIV- participants (0.35±0.33; rank-sum p = .01). Shannon diversity was higher in HIV+/ART+ (coeff 0.17; 95%CI (0.01,0.33), p = .04) and HIV+/ART- (coeff 0.37; 95%CI (0.19,0.55), p < .001) participants compared to HIV-. Anaerobe-dominant CSTs were more prevalent in HIV+/ART+ (63%, AOR 3.11; 95%CI: 1.48,6.55, p = .003) and HIV+/ART- (85%, AOR 7.59; 95%CI (2.80,20.6), p < .001) compared to HIV- (45%). Restricting the comparison to 111 women in either CST 3 (L. iners dominance) or CST 1 (L. crispatus dominance), CST 3 frequency was similar in HIV- (63%) and HIV+/ART- participants (67%, AOR 1.31; 95%CI: (0.25,6.90), p = .7), but higher in HIV+/ART+ (89%, AOR 6.44; 95%CI: (1.12,37.0), p = .04). Pregnant women in Zambia, particularly those with HIV, had diverse anaerobe-dominant vaginal microbiota.
Topics: Adult; Antiretroviral Therapy, Highly Active; Bacteria, Anaerobic; Biodiversity; Cohort Studies; Female; HIV Infections; Humans; Microbiota; Phylogeny; Pregnancy; Vagina; Young Adult; Zambia
PubMed: 31577818
DOI: 10.1371/journal.pone.0223128 -
Travel Medicine and Infectious Disease 2020In France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive...
BACKGROUND
In France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive of infectious diseases and the acquisition of pathogen carriage.
METHODS
Clinical follow up and qPCR based respiratory, gastrointestinal and vaginal pathogen carriage before and after travel were prospectively assessed in a cohort of medical students departing from Marseille, France.
RESULTS
134 students were included. 73.9%, 38.8% and 5.0% of students reported gastrointestinal, respiratory and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC) was 53% and 41%, respectively. The acquisition of respiratory viruses was low but associated with persisting symptoms, while bacterial acquisition ranged from 3.3% for Streptococcus pyogenes to 15.0% for Haemophilus influenzae. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 7.7% and 14.3% respectively. Five students (5.1%) had molecular quantification criteria for bacterial vaginosis on return.
CONCLUSION
This preliminary study demonstrates that besides the known risk of gastrointestinal and respiratory infections and associated changes in intestinal and respiratory microbiota, medical students abroad may also experience changes in vaginal microbiota leading, in some cases, to clinical symptoms or the acquisition of bacterial vaginosis, which may be asymptomatic.
Topics: Asia; Carrier State; Female; France; Gastrointestinal Diseases; Humans; Male; Prospective Studies; Respiratory Tract Infections; South America; Students, Medical; Travel; Vaginal Diseases; Young Adult
PubMed: 31870880
DOI: 10.1016/j.tmaid.2019.101548 -
Viruses Oct 2020Bacterial vaginosis (BV) is characterized by a reduction in spp. abundance and increased abundance of facultative anaerobes, such as spp. BV aetiology is not fully...
Bacterial vaginosis (BV) is characterized by a reduction in spp. abundance and increased abundance of facultative anaerobes, such as spp. BV aetiology is not fully understood; however, bacteriophages could play a pivotal role in the perturbation of the vaginal bacterial community. We investigated the vaginal viral community, including bacteriophages and the association to the bacterial community and BV-status. Vaginal samples from 48 patients undergoing IVF treatment for non-female factor infertility were subjected to metagenomic sequencing of purified virus-like particles. The vaginal viral community was characterized and correlated with the BV-status by Nugent score, bacterial community, structure, and the presence of key vaginal bacterial species. The majority of identified vaginal viruses belonged to the class of double-stranded DNA bacteriophages, with eukaryotic viruses constituting 4% of the total reads. Clear links between the viral community composition and BV ( = 0.006, = 0.26) as well as the presence of ( = 0.001, = 0.43), , spp., and were found ( < 0.002, > 0.15). The eukaryotic viral community also correlated with BV-status ( = 0.018, = 0.20). In conclusion, the vaginal virome was clearly linked with bacterial community structure and BV-status.
Topics: Adult; Bacteria; Bacteriophages; Cross-Sectional Studies; Dysbiosis; Female; Humans; Lactobacillus; Vagina; Vaginosis, Bacterial; Virome; Young Adult
PubMed: 33050261
DOI: 10.3390/v12101143 -
Microorganisms Nov 2020The physiological microbiota of the vagina is responsible for providing a protective barrier, but Some factors can disturb the balance in its composition. At that time,...
The physiological microbiota of the vagina is responsible for providing a protective barrier, but Some factors can disturb the balance in its composition. At that time, the amounts of the genus decrease, which may lead to the development of infection and severe complications during pregnancy. The aim of the study was the analysis of the bacterial composition of the vagina in 32 Caucasian women at each trimester of pregnancy using the next-generation sequencing method and primers targeting V3-V4 regions. In the studied group, the dominant species were and . Statistically significant differences in the quantitative composition between trimesters were observed in relation to , , spp. Out of the 32 patients, 20 demonstrated fluctuations within the genus and 9 of them, at different stages of pregnancy, exhibited the presence of potentially pathogenic microbiota, among others: spp., , and The composition of the vaginal microbiota during pregnancy was subject to partial changes over trimesters. Although in one-third of the studied patients, both the qualitative and quantitative composition of microbiota was relatively constant, in the remaining patients, physiological and potentially pathogenic fluctuations were distinguished.
PubMed: 33217908
DOI: 10.3390/microorganisms8111813