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The right bug in the right place: opportunities for bacterial vaginosis treatment.
Wu, S, Hugerth, LW, Schuppe-Koistinen, I, Du, J
NPJ biofilms and microbiomes. 2022;8(1):34
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The vaginal microbiome is generally dominated by Lactobacilli bacteria. However, variations exist, and in some ethnic groups a dominance of non-Lactobacilli species is more common. Lactobacilli produce various antimicrobial substances which keep growth of other bacteria in check. Bacterial vaginosis (BV) is characterized by a disturbance of the vaginal microbe balance and deficiency of Lactobacilli, giving rise to the overgrowth of certain bacteria, such as Gardnerella, Atopobium, Megasphaera, Prevotella, and Sneathia. In some countries, BV can affect over half of the women. This review discusses the advantages and challenges of the current treatment options for BV and postulates directions for future research. The article examines the use of antibiotics, their effectiveness and difficulties in obtaining long-term remission, their negative impact on the existing vaginal microbiome, the risk of antibiotic resistance and the benefits and challenges of local antibiotic applications. Following this, the authors discussed the use of prebiotics and probiotics, possible reasons why clinical trials in the past showed mixed results, and what strains may be of particular importance in vaginal health, with L. crispatus and L. iners being of particular interest here. Considered are also factors that influence and enhance bacterial colonization. Lastly, the article summarizes some current thinking on Vaginal Microbiome Transplantation, which is the transfer of vaginal microbes and fluids from a healthy donor, what benefits they may have, the associated safety risks and legislative challenges. This review is a comprehensive summary of BV treatment options, their current evidence, efficacy and drawbacks, yielding useful information to consider in the clinical management of BV.
Abstract
Bacterial vaginosis (BV) is a condition in which the vaginal microbiome presents an overgrowth of obligate and facultative anaerobes, which disturbs the vaginal microbiome balance. BV is a common and recurring vaginal infection among women of reproductive age and is associated with adverse health outcomes and a decreased quality of life. The current recommended first-line treatment for BV is antibiotics, despite the high recurrence rate. Live biopharmaceutical products/probiotics and vaginal microbiome transplantation (VMT) have also been tested in clinical trials for BV. In this review, we discuss the advantages and challenges of current BV treatments and interventions. Furthermore, we provide our understanding of why current clinical trials with probiotics have had mixed results, which is mainly due to not administering the correct bacteria to the correct body site. Here, we propose a great opportunity for large clinical trials with probiotic strains isolated from the vaginal tract (e.g., Lactobacillus crispatus) and administered directly into the vagina after pretreatment.
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Probiotic treatment with specific lactobacilli does not improve an unfavorable vaginal microbiota prior to fertility treatment-A randomized, double-blinded, placebo-controlled trial.
Jepsen, IE, Saxtorph, MH, Englund, ALM, Petersen, KB, Wissing, MLM, Hviid, TVF, Macklon, N
Frontiers in endocrinology. 2022;13:1057022
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Efforts to improve pregnancy rates remain largely focused on enhancing the quality of the transferred embryo. However, there is increasing awareness of the potential role of the intra-uterine environment as a determinant for success. The aim of this study was to determine if lactobacilli-loaded vaginal capsules are superior to placebo in improving a vaginal microbiota reported as unfavourable to implantation in women scheduled for fertility treatment. This study is a single-centre, two-arm, double-blinded, randomised controlled study. The study enrolled women aged 18–40 years who were referred to the Fertility Clinic and whose vaginal microbiota prior to fertility treatment had been diagnosed as an unfavourable. Participants (n=77) were randomised in a 1:1 ratio to either lactobacilli-loaded vaginal capsules or placebo. Results did not show any significant effect of treatment with lactobacilli-loaded vaginal capsules on the unfavourable vaginal microbiota profile among women referred to fertility treatment. However, the study showed the highly dynamic nature of the vaginal microbiota, with a spontaneous improvement rate of 34.2% (of the patients) one to three months after the baseline sample. Authors conclude that probiotics use for the improvement of vaginal microbiota should be tempered with some caution. More studies of both the vaginal and endometrial microbiota are required to confirm the efficacy of specific vaginal probiotics before they can be considered as a therapeutic solution.
Abstract
OBJECTIVE To investigate whether treatment with proprietary lactobacilli-loaded vaginal capsules improves an unfavorable vaginal microbiome diagnosed using a commercially available test and algorithm. DESIGN A randomized, double-blinded, placebo-controlled study was conducted in 74 women prior to undergoing fertility treatment at a single university fertility clinic between April 2019 and February 2021. The women were randomly assigned in a 1:1 ratio to receive one vaginal capsule per day for 10 days containing either a culture of more than 108 CFU of Lactobacillus gasseri and more than 108 CFU Lactobacillus rhamnosus (lactobacilli group) or no active ingredient (placebo group). Vaginal swabs for microbiota analysis were taken at enrollment, after treatment and in the cycle following treatment. PARTICIPANTS AND METHODS Women aged 18-40 years who prior to fertility treatment were diagnosed with an unfavorable vaginal microbiota, characterized by either a low relative load of Lactobacillus or a high proportion of disrupting bacteria using the criteria of the IS-pro™ diagnostic system (ARTPred, Amsterdam, the Netherlands), were enrolled in the study. The primary outcome measure was the proportion of women with improvement of the vaginal microbiota after intervention. RESULTS The vaginal microbiota improved after intervention in 34.2% of all participants (lactobacilli group 28.9%, placebo group 40.0%), with no significant difference in the improvement rate between the lactobacilli and placebo groups, RR = 0.72 (95% CI 0.38-1.38). CONCLUSION This study indicates that administering vaginal probiotics may not be an effective means of modulating the vaginal microbiome for clinical purposes in an infertile population. However, a spontaneous improvement rate of 34.2% over a period of one to three months, confirming the dynamic nature of the vaginal microbiota, indicates that a strategy of postponing further IVF treatment to await microbiota improvement may be relevant in some patients, but further research is needed. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT03843112.
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Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.
Siena, M, Laterza, L, Matteo, MV, Mignini, I, Schepis, T, Rizzatti, G, Ianiro, G, Rinninella, E, Cintoni, M, Gasbarrini, A
Microorganisms. 2021;9(3)
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During pregnancy, several adaptations occur in the female organism. In fact, from fertilization until delivery, the maternal body changes and activates a series of physiological transformations to welcome the new life. The microbiota as a component of human bodies is subject to these modifications. This study is a review that focused on gut and reproductive tract microbiota variations during physiologic pregnancy and in case of pregnancy complications, particularly gestational diabetes mellitus (GDM), pre-eclampsia (PE), and preterm birth (PTB). Results show that: - during pregnancy, major changes have been seen in mothers’ gut microbiota. Between the first and third trimester of pregnancy, to support the foetus growth, there is a shift towards communities of microbes implicated in energy production and storage. - in nonpregnant women, vaginal microbiota could be classified into five major types, representing the community state types. - meconium’s microbes seems to be dominated by the Enterobacteriaceae family, suggesting prenatally stepwise colonization. - gut microbiota may contribute to enhanced insulin resistance in early pregnancy (1st and 2nd trimester). - microbiota imbalances in PE women are related not only with blood pressure levels but also with markers of kidney dysfunction. Thus, it is of key importance to understand the role of microbiota and other factors involved in the etiopathogenesis of PE - dysbiosis is related to PTB (however, further studies are necessary to better understand the correlation between this pregnancy complication and the specific microbiota alteration). Authors conclude that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
Abstract
Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
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Vaginal and Anal Microbiome during Chlamydia trachomatis Infections.
Raimondi, S, Candeliere, F, Amaretti, A, Foschi, C, Morselli, S, Gaspari, V, Rossi, M, Marangoni, A
Pathogens (Basel, Switzerland). 2021;10(10)
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Chlamydia trachomatis (CT) is the agent of the most common bacterial sexually transmitted infection (STI) worldwide. This study is a cohort study. The composition of vaginal and anal microbiome in a cohort of sexually active young women was investigated comparing the bacterial composition of CT-infected women (n = 10) to a negative control group (n = 16). Results showed that: - both vaginal and anal ecosystems were characterised by a degree of dysbiosis in case of CT infection, with several changes in the microbial composition compared to CT-negative women. - bacteria dominance was different for patients with anal CT infection (Parvimonas and Pseudomonas), than those of CT-negative women (Escherichia and Enterococcus). - there were significant differences in several functional pathways between CT-positive patients and the control group. Among all, a higher involvement of chorismate and aromatic amino acid biosynthesis, as well as an increase in mixed acid fermentation, were predicted at the vaginal level of CT-positive patients. Authors conclude that their findings could be useful to set up new diagnostic/prognostic tools, to find correlations with the presence of peculiar clinical or behavioural traits, and to evaluate the possibility of a different susceptibility to chlamydial STIs based on microbiome composition.
Abstract
Background.Chlamydia trachomatis (CT) is the agent of the most common bacterial sexually transmitted infection worldwide, with a significant impact on women's health. Despite the increasing number of studies about the vaginal microbiome in women with CT infections, information about the composition of the anal microbiome is still lacking. Here, we assessed the bacterial community profiles of vaginal and anal ecosystems associated or not with CT infection in a cohort of Caucasian young women. Methods. A total of 26 women, including 10 with a contemporary vaginal and ano-rectal CT infection, were enrolled. Composition of vaginal and anal microbiome was studied by 16S rRNA gene profiling. Co-occurrence networks of bacterial communities and metagenome metabolic functions were determined. Results. In case of CT infection, both vaginal and anal environments were characterized by a degree of dysbiosis. Indeed, the vaginal microbiome of CT-positive women were depleted in lactobacilli, with a significant increase in dysbiosis-associated bacteria (e.g., Sneathia, Parvimonas, Megasphaera), whereas the anal microbiota of CT-infected women was characterized by higher levels of Parvimonas and Pseudomonas and lower levels of Escherichia. Interestingly, the microbiome of anus and vagina had numerous bacterial taxa in common, reflecting a significant microbial 'sharing' between the two sites. In the vaginal environment, CT positively correlated with Ezakiella spp. while Gardnerella vaginalis co-occurred with several dysbiosis-related microbes, regardless of CT vaginal infection. The vaginal microbiome of CT-positive females exhibited a higher involvement of chorismate and aromatic amino acid biosynthesis, as well as an increase in mixed acid fermentation. Conclusions. These data could be useful to set up new diagnostic/prognostic tools, offering new perspectives for the control of chlamydial infections.
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Group B Streptococcus and the vaginal microbiome among pregnant women: a systematic review.
Lim, S, Rajagopal, S, Jeong, YR, Nzegwu, D, Wright, ML
PeerJ. 2021;9:e11437
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Variations within the vaginal microbiome have been associated with higher risk for preterm birth and other pregnancy complications. For example, there is a notable lack of discussion of S. agalactiae, commonly referred to as Group B Streptococcus (GBS), a known pathogen associated with poor maternal, foetal, and neonatal outcomes in amplicon-based metagenomic vaginal microbiome studies during pregnancy. The main aim of this study was to determine how often GBS is reported in studies of the vaginal microbiome during pregnancy. This study is a systematic review of forty-five studies. Out of the forty-five studies, 13 (28.9%) reported GBS. Results show that no systematic differences in factors previously known to introduce bias in microbiome studies were associated with the lack of GBS reporting. However, there was considerable heterogeneity in research methods employed across studies. Authors conclude that future studies evaluating the presence of GBS may need to adopt both confirmatory testing for GBS via culture and parallel comparison with results obtained from metagenomic/meta-taxonomic approaches.
Abstract
BACKGROUND Vaginal microbiome studies frequently report diversity metrics and communities of microbiomes associated with reproductive health outcomes. Reports of Streptococcus agalactiae (also known as Group B Streptococcus or GBS), the leading cause of neonatal infectious morbidity and mortality, are notably lacking from the studies of the vaginal microbiome, despite being a known contributor to preterm birth and other complications. Therefore, the purpose of this systematic review was to explore the frequency of GBS reporting in vaginal microbiome literature pertaining to pregnancy and to examine methodological bias that contributes to differences in species and genus-level microbiome reporting. Lack of identification of GBS via sequencing-based approaches due to methodologic or reporting bias may result incomplete understanding of bacterial composition during pregnancy and subsequent birth outcomes. METHODOLOGY A systematic review was conducted following the PRISMA guideline. Three databases (PubMed, CINAHL, and Web of Science) were used to identify papers for review based on the search terms "vaginal microbiome", "pregnancy", and "16S rRNA sequencing". Articles were evaluated for methods of DNA extraction and sequencing, 16S region, taxonomy classification database, number of participants or vaginal specimens, and pregnancy trimester. RESULTS Forty-five research articles reported employing a metagenomic approach or 16S approach for vaginal microbiome analysis during pregnancy that explicitly reported taxonomic composition and were included in this review. Less than 30% of articles reported the presence of GBS (N = 13). No significant differences in methodology were identified between articles that reported versus did not report GBS. However, there was large variability across research methods used for vaginal microbiome analysis and species-level bacterial community reporting. CONCLUSION Considerable differences in study design and data formatting methods may contribute to underrepresentation of GBS, and other known pathogens, in existing vaginal microbiome literature. Previous studies have identified considerable variation in methodology across vaginal microbiome studies. This study adds to this body of work because in addition to laboratory or statistical methods, how results and data are shared (e.g., only analyzing genus level data or 20 most abundant microbes), may hinder reproducibility and limit our understanding of the influence of less abundant microbes. Sharing detailed methods, analysis code, and raw data may improve reproducibility and ability to more accurately compare microbial communities across studies.
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Implications of the vaginal microbiome and potential restorative strategies on maternal health: a narrative review.
Moumne, O, Hampe, ME, Montoya-Williams, D, Carson, TL, Neu, J, Francois, M, Rhoton-Vlasak, A, Lemas, DJ
Journal of perinatal medicine. 2021;49(4):402-411
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The vaginal microbiome is a complex community of bacteria that maintains and contributes to vaginal health and works together to protect the host from disease. Lactobacilli are the predominant species in a healthy vaginal microbiome. This review sought to summarize current evidence on how changes in the vaginal microbiome composition before and throughout pregnancy influence and contribute to several health conditions. The authors investigated the role of the vaginal microbiome in fertility and in-vitro fertilization (IVF), where evidence is still conflicting, followed by conditions that can present during pregnancy such as preterm labour, gestational diabetes, and preeclampsia. In preterm labour, lower levels of Lactobacillus and its D-lactic acid secretions have been observed as a common denominator; in gestational diabetes, it remains unclear whether the changes in the vaginal microbiome associated with the condition are causative or rather a result of the condition. Little research has been done regarding preeclampsia, but initial studies indicate there may be a link between the condition and the vaginal microbiome. The authors also reviewed the evidence on methods of restoring vaginal health, including oral and vaginally applied probiotics as well as vaginal microbiome transplants (VMT) - the transfer of vaginal secretions from a healthy donor. The paper discusses the evidence on the use of oral and locally applied probiotics for the aforementioned conditions, and the promising potential of VMTs alongside the risks and regulatory challenges that come with it. This review provides a helpful summary of the current understanding of the role of the vaginal microbiome in fertility and throught pregnancy.
Abstract
The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women's health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women's cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.
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Longitudinal Study of the Psoriasis-Associated Skin Microbiome during Therapy with Ustekinumab in a Randomized Phase 3b Clinical Trial.
Loesche, MA, Farahi, K, Capone, K, Fakharzadeh, S, Blauvelt, A, Duffin, KC, DePrimo, SE, Muñoz-Elías, EJ, Brodmerkel, C, Dasgupta, B, et al
The Journal of investigative dermatology. 2018;138(9):1973-1981
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Chronic plaque psoriasis is an immune-mediated disease of the skin and joints. A growing appreciation of the role of the innate immune system in psoriasis pathogenesis stems from the prominent role of inflammatory cytokines and cells associated with innate immunity in the disease and associations observed between psoriasis and genetic variations involved in innate immunity. The aim of this study was to assess changes of the skin microbiome in the setting of a longitudinal phase 3b study of patients receiving up to 2 years of ustekinumab therapy. Results show that prior to treatment, there were minor, body-site specific differences in microbial diversity and composition when comparing lesional with non-lesional skin. Microbial heterogeneity was greater in lesional skin than non-lesional skin. During ustekinumab treatment, the composition of microbiota diverged further between lesional and non-lesional skin across body sites. The divergence observed between lesional and non-lesional skin during ustekinumab treatment varied by body site. Authors conclude that their findings may help inform future study design and it may also have medically relevant implications for diagnostics and therapeutics involving the skin microbiome.
Abstract
Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a phase 3b clinical trial. By sequencing the bacterial 16S ribosomal RNA gene from skin swab samples obtained at six anatomical sites, we identified minor, site-specific differences in microbial diversity and composition between pretreatment lesional and nonlesional skin. During therapy, microbial communities within lesional and nonlesional skin diverged, and body-site dispersion increased, reflecting microbial skin site-specificity. Microbiota demonstrated greater pretreatment heterogeneity in psoriatic lesions than in nonlesional skin, and variance increased as treatment progressed. Microbiota colonizing recurrent lesions did not overlap with pretreatment lesional microbiota, suggesting colonization patterns varied between initial and recurrent psoriatic lesions. While plaque psoriasis does not appear to be associated with specific microbes and/or microbial diversity, this large dataset provides insight into microbial variation associated with (i) disease in different body locations, (ii) initial versus recurrent lesions, and (iii) anti-IL12/23 therapy.
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Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.
Zuo, T, Wong, SH, Lam, K, Lui, R, Cheung, K, Tang, W, Ching, JYL, Chan, PKS, Chan, MCW, Wu, JCY, et al
Gut. 2018;67(4):634-643
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The microbiome and its effects on health have received plenty of attention and research. A lot less is known about the virome, the collection of viruses in and on our bodies. This pilot observational study looked at the connection between the viruses and bacteria in the guts of patients with Clostridium difficile infection (CDI), compared to healthy controls, and changes and treatment outcomes observed after faecal microbiota transplantation (FMT) compared to vancomycin treatment. The study showed that, compared to healthy household controls, people with CDI had significant viral dysbiosis, in particular higher abundance but lower diversity, richness and evenness of the bacteriophage (a virus that infects bacteria) Caudovirales, the most abundant intestinal bacteriophage in humans. FMT changed both, the composition of the microbiome as well as the virome, whilst antibiotic treatment did not affect the bacteriophage composition. Treatment outcome with FMT depended on changes in Caudivirales. Although a small pilot study, according to the authors, this is the biggest study into the importance of intestinal viruses, and their correlation with the microbiome, in disease and for treatment outcomes. The authors point out that, as this was an observational study, it is not possible to ascertain whether the altered virome is a cause or a consequence of the disease.
Abstract
OBJECTIVE Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI. DESIGN Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response. RESULTS Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone. CONCLUSIONS In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI. TRIAL REGISTRATION NUMBER NCT02570477.
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Disruption of the Gut Ecosystem by Antibiotics.
Yoon, MY, Yoon, SS
Yonsei medical journal. 2018;59(1):4-12
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The gut microbiome is a complex ecosystem of different micro-organisms, such as bacteria, viruses and fungi, living in the human intestines. It’s involved in numerous functions, such as extracting energy and nutrition from food, protecting against disease-causing microorganisms, and supporting the immune system of the host, and therefore affecting human health and disease. This paper is a review of studies on the effects of antibiotics on the gut microbiota. It outlines how different types of antibiotics can alter the intestinal environment and the composition of the microbes, resulting in various physiological changes that can trigger disease. Relevant mechanisms, such as inflammatory response and the use of intestinal nutrients by infectious bacteria are discussed. Finally, it discusses faecal microbiota transplantation (FMT) and probiotics as treatment approaches, aimed at restoring a disturbed intestinal environment.
Abstract
The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.
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Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.
Brown, RG, Marchesi, JR, Lee, YS, Smith, A, Lehne, B, Kindinger, LM, Terzidou, V, Holmes, E, Nicholson, JK, Bennett, PR, et al
BMC medicine. 2018;16(1):9
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Preterm premature rupture of the membranes (PPROM) is a pregnancy complication in which the amniotic sac ruptures before week 37 of the pregnancy, leading to an increased risk of infection and premature birth. Women who experience PPROM are usually given antibiotics to help prevent infections which, left untreated, could endanger their babies’ lives. It is thought that disturbances in the mum’s vaginal bacteria may be related to the risk of PPROM. In this study, researchers examined the vaginal bacteria of women with PPROM, before and after antibiotic treatment. A total of 250 pregnant women who had been identified as at risk of a premature birth were included in the study. Disturbance of the normal vaginal bacteria, characterised by low levels of Lactobacillus, was present in a third of women who went on to develop PPROM. This disturbance of the normal vaginal bacteria was made worse by antibiotic treatment particularly in women initially colonised by Lactobacillus spp. Lower levels of Lactobacillus and increased abundance of Sneathia spp. were associated with an increased likelihood of funisitis (inflammation of the umbilical cord) and sepsis in the newborn. The authors concluded that the composition of the vaginal microbiota is a risk factor for PPROM and is associated with unfavourable short-term outcomes for the mother and newborn. This highlights vaginal microbiota as a potentially modifiable risk factor for PPROM and they suggest that the routine use of antibiotics such as erythromycin for PPROM should be re-examined.
Abstract
BACKGROUND Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. METHODS We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. RESULTS In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. CONCLUSIONS Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.