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Efficacy of probiotics or synbiotics in critically ill patients: A systematic review and meta-analysis.
Lou, J, Cui, S, Huang, N, Jin, G, Chen, C, Fan, Y, Zhang, C, Li, J
Clinical nutrition ESPEN. 2024;59:48-62
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The intestinal microbiota is a complex microbial community that plays an irreplaceable role in human life. Intestinal dysbiosis is very common in patients with critical illnesses. The aim of this study was to assess the efficacy and safety of probiotics or synbiotics in preventing ventilator associated pneumonia (VAP) in critically ill patients in the intensive care unit (ICU). This study was a systematic review and meta-analysis of thirty-three trials (n=4 retrospective studies and n=29 randomised controlled studies). A total of 7886 patients were grouped into the probiotics or synbiotics group (n= 4065) and control group (n= 3821). Results showed that probiotics or synbiotics significantly reduced the incidence of VAP and sepsis, as well as the duration of mechanical support, length of hospital stay, length of ICU stay, and ICU morality. Authors concluded that probiotics or synbiotics supplementation plays a beneficial role in critically ill patients and presents a novel approach to the management of critical diseases.
Abstract
BACKGROUND This latest systematic review and meta-analysis aim to examine the effects of probiotic and synbiotic supplementation in critically ill patients. METHODS Relevant articles were retrieved from PubMed, Embase, the Cochrane Database, and the Web of Science. The primary output measure was the incident of ventilator-associated pneumonia, and the secondary outputs were diarrhea, Clostridium diffusion infection (CDI), incident of sepsis, incident of hospital acquired pneumonia, duration of mechanical exploitation, ICU mortality rate, length of ICU stay, in hospital mortality, and length of hospital stay. Data were pooled and expressed as Relative Risk(RR) and Standardized Mean Difference (SMD) with a 95 % confidence interval (CI). RESULTS 33 studies were included in this systematic review and meta-analysis, with 4065 patients who received probiotics or synbiotics (treatment group) and 3821 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced incidence of ventilation-associated pneumonia (VAP) (RR = 0.80; 95 % CI: 0.67-0.96; p = 0.021, I2 = 52.5 %) and sepsis (RR = 0.97; 95 % CI: 0.66-1.42; p = 0.032, I2 = 54.4 %), As well as significantly increased duration of mechanical exploitation (SMD = -0.47; 95 % CI: -0.74-0.20, p = 0.012, I2 = 63.4 %), ICU mobility (RR = 0.95; 95 % CI: 0.71-1.27; p = 0.004, I2 = 62.8 %), length of ICU stay (SMD = -0.29; 95 % CI: -0.58-0.01; p = 0.000, I2 = 82.3 %) and length of hospital stay (SMD = -0.33; 95 % CI: -0.57-0.08, p = 0.000, I2 = 74.2 %) than the control group. There were no significant differences in diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality between the two groups. CONCLUSION Our meta-analysis showed that probiotic and synbiotic supplements are beneficial for critically ill patients as they significantly reduce the incidence of ventilator associated pneumonia and sepsis, as well as the duration of mechanical exploitation, length of hospital stay, length of ICU stay, and ICU mortality. However, this intervention has minimal impact on diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality in critically ill patients.
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A randomized controlled trial of an oral probiotic to reduce antepartum group B Streptococcus colonization and gastrointestinal symptoms.
Hanson, L, VandeVusse, L, Forgie, M, Malloy, E, Singh, M, Scherer, M, Kleber, D, Dixon, J, Hryckowian, AJ, Safdar, N
American journal of obstetrics & gynecology MFM. 2023;5(1):100748
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Streptococcus agalactiae (or group B Streptococcus [GBS]) is an encapsulated, gram-positive, beta-haemolytic anaerobe that asymptomatically colonizes the genitourinary tract. Vertical transmission of GBS during normal vaginal birth can lead to neonatal colonization and risk for early-onset GBS disease. The aim of this study was to present the findings of a phase II, double-blind, randomised, placebo-controlled trial of an antenatal probiotic intervention to reduce GBS colonization. A secondary aim was to determine if the probiotic intervention reduces gastrointestinal (GI) symptoms of pregnancy. Participants (n=107) were randomly assigned to one of the two groups: probiotic intervention (n=55) or placebo group (n=54). Results show that: - there weren’t any significant differences between the groups in demographic characteristics, perinatal or neonatal outcomes, or intrapartum antibiotic prophylaxis doses. - there wasn’t any significant difference between groups in the presence of the probiotic bacteria on the rectal swabs, whereas the vaginal swabs showed a trend toward greater presence in probiotic group participants. - more probiotic participants took antenatal antibiotics (5/39) compared with controls (1/44). Authors conclude that probiotic bacteria colonisation of the genitourinary tract occurred more in the intervention group than in the control group and significantly reduced GI symptoms of pregnancy.
Abstract
BACKGROUND Probiotics have been suggested as a strategy to reduce antenatal group B Streptococcus colonization. Although probiotics are known to improve gastrointestinal symptoms, this has not been studied during pregnancy. OBJECTIVE This study aimed to evaluate the efficacy of a probiotic to reduce: (1) standard-of-care antenatal group B Streptococcus colonization and colony counts and (2) gastrointestinal symptoms of pregnancy. STUDY DESIGN In a double-blind fashion, 109 healthy adult pregnant people were randomized to Florajen3 probiotic or placebo capsules once daily from 28 weeks' gestation until labor onset. Baseline vaginal and rectal study swabs for group B Streptococcus colony-forming units and microbiome analysis were collected at 28 and 36 weeks' gestation. Standard-of-care vaginal to rectal group B Streptococcus swabs were collected from all participants at 36 weeks' gestation and determined the need for intrapartum antibiotic prophylaxis. Data collection included solicitation of adverse events, demographic information, Antepartum Gastrointestinal Symptom Assessment score, yogurt ingestion, sexual activity, and vaginal cleaning practices. RESULTS A total of 83 participants completed the study to 36 weeks' gestation with no adverse events. Standard-of-care group B Streptococcus colonization was 20.4% in the control group and 15.4% in probiotic group participants (-5%; P=.73). The relative risk for positive standard-of-care vaginal-rectal group B Streptococcus colonization was 1.33 (95% confidence interval, 0.5-3.40) times higher in the control group than in the probiotic group (P=.55). There were no differences in median vaginal (P=.16) or rectal (P=.20) group B streptococcus colony-forming units at baseline or at 36 weeks (vaginal P>.999; rectal P=.56). Antepartum Gastrointestinal Symptom Assessment scores were similar at baseline (P=.19), but significantly decreased in probiotic group participants at 36 weeks (P=.02). No covariates significantly altered group B Streptococcus colonization. Significantly more Florajen3 bacteria components were recovered from the vaginal-rectal samples of probiotic group participants (32%; P=.04) compared with controls. CONCLUSION The findings of this study provided insufficient evidence for the clinical application of the Florajen3 probiotic intervention to reduce standard-of-care vaginal-rectal group B Streptococcus colonization. The prevalence of group B Streptococcus was lower than expected in the study population, and intervention adherence was poor. Probiotic bacteria colonization of the genitourinary tract occurred more in intervention group participants than in controls and significantly reduced gastrointestinal symptoms of pregnancy.
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Orally administrated Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 can restore the vaginal health of patients recovering from bacterial vaginosis.
Qi, F, Fan, S, Fang, C, Ge, L, Lyu, J, Huang, Z, Zhao, S, Zou, Y, Huang, L, Liu, X, et al
Frontiers in immunology. 2023;14:1125239
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Bacterial vaginosis (BV) is a microecological disorder caused by decreased abundance of lactobacilli and an increased abundance of anaerobic bacteria, commonly affecting the female lower genital tract. The aim of this study was to evaluate the effectiveness of oral Chinese-origin probiotic strains (L. gasseri TM13 and L. crispatus LG55), with adjuvant primary treatment in treating Chinese BV patients, and investigate the dynamic of the intestine and vaginal microbiome using metagenomic sequencing. This study was a single-centre, prospective, parallel-group, randomized controlled clinical trial. Participants were randomly assigned to the control or probiotic group using a 1:1 ratio. Results showed that there was no significant difference in BV cure rates between the probiotic and control groups at day 14, day 30, and day 90. In addition, in the BV conversion population, the percentage of people in a transition state was lower in the probiotic group at all three time-points. Hence, oral administration of L. gasseri TM13 and L. crispatus LG55 is effective in restoring the vaginal health of patients recovered from BV. Authors conclude that an individualised intervention approach should be developed to restore the vaginal health of patients recovering from BV.
Abstract
UNLABELLED Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV. CLINICAL TRIAL REGISTRATION https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.
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The effect of probiotics on gestational diabetes and its complications in pregnant mother and newborn: A systematic review and meta-analysis during 2010-2020.
Mahdizade Ari, M, Teymouri, S, Fazlalian, T, Asadollahi, P, Afifirad, R, Sabaghan, M, Valizadeh, F, Ghanavati, R, Darbandi, A
Journal of clinical laboratory analysis. 2022;36(4):e24326
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Gestational diabetes (GD) refers to glucose intolerance in pregnant women at 24–28 weeks without a history of diabetes that results in hyperglycaemia. Some studies suggest that probiotics are able to overcome insulin resistance in pregnant women with GD. The aim of this study was to investigate the inhibitory effects of probiotics supplementation on GD among pregnant women based on Randomized Controlled Trial studies during in the last 10 years (2010–2020). This study is a systematic review and meta-analysis of 28 studies. The age range of the pregnant women following the probiotics treatment was 18–40 years. Results show that taking probiotic supplements during pregnancy by women with GD has beneficial effects on the metabolic status, colostrum adiponectin levels, microbiome composition, and the maternal and infant health. However, 4 of the analysed studies did not find any significant effect for the probiotic intervention on the incidence of GD. Authors conclude that more homogeneous studies are needed to generalize the findings of this study. Thus, specific probiotic supplementation may be introduced as one of the adjuvant therapies for GD patients.
Abstract
This study was aimed to evaluate the effect of probiotics consumption on gestational diabetes (GD) and its complications in pregnant mother and newborn. The study was registered on PROSPERO (CRD42021243409) and all the enrolled articles were collected from four databases (Medline, Scopus, Embase, and Google Scholar) as randomized controlled trials (RCTs) from 2010 to 2020. A total of 4865 study participants from 28 selected studies were included in this review. The present meta-analysis showed that the consumption of probiotics supplementation has the potential to decrease GD-predisposing metabolic parameters such as blood glucose level, lipid profile, inflammation, and oxidative markers which may reduce GD occurrence among pregnant women.
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The Clinical, Microbiological, and Immunological Effects of Probiotic Supplementation on Prevention and Treatment of Periodontal Diseases: A Systematic Review and Meta-Analysis.
Gheisary, Z, Mahmood, R, Harri Shivanantham, A, Liu, J, Lieffers, JRL, Papagerakis, P, Papagerakis, S
Nutrients. 2022;14(5)
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Periodontal disease is preventable and reversible in its early stages; however, it can progress to chronic, irreversible states with significant destruction of the tooth-supporting tissues. The cause of periodontal disease is multifactorial with modifiable risk factors, including smoking, unhealthy diet (e.g., a western diet with high sugars and saturated fats), poor oral hygiene, hormonal changes, stress, various medications, and poorly managed comorbidities (e.g., type 2 diabetes), while non-modifiable risk factors include age, sex, and genetics. The aim of this study was to assess the effects on the clinical, microbiological, and immunological outcomes related to periodontal disease prevention and management. This study is systematic review and meta-analysis of randomized clinical trials involving adults with periodontal diseases or healthy volunteers receiving probiotic supplementation (control groups did not receive probiotic supplementation). Results show that probiotic supplementation improved the clinical parameters, reduced the subgingival bacterial counts of specific periodontopathogens, and reduced the gingival crevicular fluid levels of some proinflammatory mediators in periodontal disease patients. Authors conclude that further research is required to better assess the therapeutic and preventive value of probiotic supplementation in patients with gingivitis (early disease), as well as in healthy (without periodontal disease) individuals.
Abstract
(1) Background: Periodontal diseases are a global health concern. They are multi-stage, progressive inflammatory diseases triggered by the inflammation of the gums in response to periodontopathogens and may lead to the destruction of tooth-supporting structures, tooth loss, and systemic health problems. This systematic review and meta-analysis evaluated the effects of probiotic supplementation on the prevention and treatment of periodontal disease based on the assessment of clinical, microbiological, and immunological outcomes. (2) Methods: This study was registered under PROSPERO (CRD42021249120). Six databases were searched: PubMed, MEDLINE, EMBASE, CINAHL, Web of Science, and Dentistry and Oral Science Source. The meta-analysis assessed the effects of probiotic supplementation on the prevention and treatment of periodontal diseases and reported them using Hedge's g standardized mean difference (SMD). (3) Results: Of the 1883 articles initially identified, 64 randomized clinical trials were included in this study. The results of this meta-analysis indicated statistically significant improvements after probiotic supplementation in the majority of the clinical outcomes in periodontal disease patients, including the plaque index (SMD = 0.557, 95% CI: 0.228, 0.885), gingival index, SMD = 0.920, 95% CI: 0.426, 1.414), probing pocket depth (SMD = 0.578, 95% CI: 0.365, 0.790), clinical attachment level (SMD = 0.413, 95% CI: 0.262, 0.563), bleeding on probing (SMD = 0.841, 95% CI: 0.479, 1.20), gingival crevicular fluid volume (SMD = 0.568, 95% CI: 0.235, 0.902), reduction in the subgingival periodontopathogen count of P. gingivalis (SMD = 0.402, 95% CI: 0.120, 0.685), F. nucleatum (SMD = 0.392, 95% CI: 0.127, 0.658), and T. forsythia (SMD = 0.341, 95% CI: 0.050, 0.633), and immunological markers MMP-8 (SMD = 0.819, 95% CI: 0.417, 1.221) and IL-6 (SMD = 0.361, 95% CI: 0.079, 0.644). (4) Conclusions: The results of this study suggest that probiotic supplementation improves clinical parameters, and reduces the periodontopathogen load and pro-inflammatory markers in periodontal disease patients. However, we were unable to assess the preventive role of probiotic supplementation due to the paucity of studies. Further clinical studies are needed to determine the efficacy of probiotic supplementation in the prevention of periodontal diseases.
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The role of probiotics in the treatment of adult atopic dermatitis: a meta-analysis of randomized controlled trials.
Umborowati, MA, Damayanti, D, Anggraeni, S, Endaryanto, A, Surono, IS, Effendy, I, Prakoeswa, CRS
Journal of health, population, and nutrition. 2022;41(1):37
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Allergic diseases, including atopic dermatitis (AD), are serious conditions that disrupt the quality of life of affected individuals. AD is a chronic inflammatory skin disease that is relapsing and whose onset is generally related to a patient’s or family’s atopic history such as asthma and allergic rhinitis. The aim of this study was to assess randomized control trials based on the PICO strategy—population = adult with AD; intervention = probiotic intervention; control = standard therapy; and outcome = clinical manifestations (Scoring Atopic Dermatitis index (SCORAD) evaluation, skin severity, itch severity), quality of life, and/or immune response. This study is a systematic review of six randomised controlled trials involving a total of 241 subjects, including 128 subjects in the probiotics group and 113 subjects in the placebo group. Results show that probiotic supplementation may have the potential to decrease disease severity (SCORAD) in adult AD. Therefore, decrease in disease severity may also improve the quality of life. Authors conclude that based on their findings, probiotics can be used as adjuvant treatment of adult AD.
Abstract
BACKGROUND Atopic dermatitis (AD) is chronic inflammatory skin disease that is relapsing and a serious condition that disrupts the quality of life of affected individuals. Probiotics are an immunomodulator that can enhance the immune control of atopic dermatitis. METHODS All randomized controlled trials of probiotics for the treatment of adult AD published before December 2020 were included in this study from the PubMed databases and manual searching. RESULTS Six randomized controlled trials (n = 241) were selected for this meta-analysis study. Probiotics were effective in treating adult patients with AD, indicated by the decrease in Scoring Atopic Dermatitis/SCORAD (Mean Difference (MD) - 7.90, 95% CI - 7.25 to - 6.92; p < 0.00001; I2 = 96%) and improved quality of life (MD - 7.68, 95% CI - 14.08 to - 1.29; p = 0.02; I2 = 47%) which were statistically significant. However, skin severity, itch severity, Dermatology Life Quality Index (DLQI), IL-4, TFN-γ, and IgE showed no significant difference in this meta-analysis study (p > 0.05). LIMITATIONS The study found no available data for side effects of probiotics. STRENGTH This meta-analysis analyzed a total of 241 AD patients of Asian and European origin. CONCLUSION The use of probiotics decreased SCORAD significantly in adult patients with AD. Probiotics can improve the quality of life of patients with AD. The use of probiotics in atopic dermatitis has been widely studied, with controversial results. This meta-analysis suggests that the use of probiotics can improve SCORAD and the quality of life of patients with atopic dermatitis.
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The Efficacy and Safety of Probiotics for Allergic Rhinitis: A Systematic Review and Meta-Analysis.
Luo, C, Peng, S, Li, M, Ao, X, Liu, Z
Frontiers in immunology. 2022;13:848279
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Allergic rhinitis (AR) is characterized by a nasal sensitive inflammation. Common symptoms of AR are nasal itching, sneezing, rhinorrhoea, and nasal congestion. In addition, some patients experience symptoms of allergic rhinoconjunctivitis, such as watery or itchy or red eyes. The aim of this study was to address the effect and safety of probiotics on AR and to explore the possible causes of between-study heterogeneity via subgroup. This study is a systematic review and meta-analysis of twenty-eight randomised controlled trials. Results showed that probiotics supplementation for patients with AR can ameliorate AR symptoms and improve the quality of life. Probiotics supplementation can correct the T helper cell 1/ T helper cell 2 balance. Furthermore, there was no significant change in overall or antigen-specific immunoglobulin E levels between probiotic-treated and placebo-treated subjects. Authors conclude that in spite of the positive results of some outcomes, there is weak evidence that probiotics have a potential benefit in the treatment of AR.
Abstract
Background: Probiotics have proven beneficial in a number of immune-mediated and allergic diseases. Several human studies have evaluated the efficacy and safety of probiotics in allergic rhinitis; however, evidence for their use has yet to be firmly established. Objective: We undertook a systematic review and meta-analysis aiming to address the effect and safety of probiotics on allergic rhinitis. Methods: We systematically searched databases [MEDLINE (PubMed), Embase, and the Cochrane Central Register of Controlled Trials] from inception until June 1, 2021. Qualified literature was selected according to inclusion and exclusion criteria, the data were extracted, and a systematic review and meta-analysis was conducted. Results: Twenty-eight studies were included. The results showed that probiotics significantly relieved allergic rhinitis symptoms (standardized mean difference [SMD], -0.29, 95% confidence interval (CI) [-0.44, -0.13]; p = 0.0003, I 2 = 89%), decreased Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores compared with the control group (SMD, -0.64, 95% CI [-0.79, -0.49], p < 0.00001, I 2 = 97%), and increased T helper cell 1(Th1)/Th2 ratio (mean difference [MD], -2.47, 95% CI [-3.27, -1.68], p < 0.00001, I 2 = 72%). There was no significant change in overall or specific IgE levels between probiotic-treated and placebo-treated subjects (SMD, 0.09, 95% CI [-0.16, 0.34], I 2 = 0%, and SMD, -0.03, 95% CI [-0.18, 0.13], p = 0.72, I 2 = 0%, respectively). Conclusions: To sum up, probiotic supplement seems to be effective in ameliorating allergic rhinitis symptoms and improving the quality of life, but there is high heterogeneity in some results after subgroup analysis and clinicians should be cautious when recommending probiotics in treating allergic rhinitis. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42021242645).
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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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The vaginal microbiome and the risk of preterm birth: a systematic review and network meta-analysis.
Gudnadottir, U, Debelius, JW, Du, J, Hugerth, LW, Danielsson, H, Schuppe-Koistinen, I, Fransson, E, Brusselaers, N
Scientific reports. 2022;12(1):7926
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Preterm birth is a major cause of neonatal mortality and morbidity. Many factors can trigger premature labour onset, including preterm premature rupture of membranes, infections and microbial invasion of the amniotic cavity. The vaginal microbiome is thought to protect from such infections. The aim of this study was to assess the association between the vaginal microbiome and the risk of preterm birth. This study is a systematic review and meta-analysis of 17 cohort studies. The number of pregnancies per study ranged between 38 and 539, with 8 and 107 preterm births. Results show that women with a “low-lactobacilli” vaginal microbiome composition were at higher risk of preterm birth (spontaneous and overall) compared to women with L. crispatus (microbiome) dominant microbiome compositions. Authors conclude that the diversity of the vaginal microbiome seems to play a part in the risk of preterm birth.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The diversity of the vaginal microbiome is reported to play a part in the risk of preterm births.
- Practitioners could consider testing the virginal microbiome for low Lactobacilli or the dominance of Gardnerella and Prevotella and then recommending a probiotic supplement to pregnant patients who have low Lactobacilli vaginal microbiome.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A systematic review and network meta-analysis was conducted to investigate the association between vaginal microbiome and risk of preterm births.
Methodology
- Seventeen longitudinal cohort studies were included. Seven originated from North America, three from Europe, two from South America, three from Asia, and two from Africa. The number of pregnancies per study ranged between 38 and 539, with 8 and 107 preterm births. 16S Sequencing techniques were used to identify the microbial species. Preterm birth was defined as birth before 37 weeks of gestation.
- Microbiome community state types (CSTs) were grouped into five categories based on dominating species: L. crispatus, L. gasseri, L. iners,“low-lactobacilli” and L. jensenii. “Low-lactobacilli” was defined as an increased diversity of anaerobic or mixture of aerobe and facultative anaerobe bacteria (such as Gardnerella and Prevotella) based on the cut-offs and categorization used in the individual studies.
Results
Primary clinical outcomes were:
- Among women who delivered preterm, the pooled proportion with “low-lactobacilli” was 0.41 (95% CI 0.30-0.53) compared to 0.29 (95% CI 0.20-0.38) of women with full-term deliveries.
- The risk of preterm births was higher among women with “low-lactobacilli” compared to L. crispatus (OR 1.69, 95%CI 1.15 -2.49).”Low-lactobacilli” included Garnerella and Provotella, both of which are known to promote inflammatory cytokines and are commonly found in vaginal microbiome just before preterm premature rupture of membranes (PPROM).
Clinical practice applications:
- The diversity of the vaginal microbiome is reported to play an important role in the risk of preterm births.
- Women with low Lactobacilli seem to be at a greater risk of delivering preterm compared to women with L. crispatus dominant microbiome.
- Based on this study, practitioners could therefore consider testing the vaginal microbiome of their patients for low Lactobacilli and/or the dominance of Gardnerella and Prevotella.
- Practitioners may also consider recommending specific probiotic supplementation during pregnancy to increase the dominance of Lactobacilli and L. crispatus vaginal microbiome.
Considerations for future research:
- In the past, researchers have grouped the microbiome into categories based on dominating species, which is not ideal. Therefore, further studies are needed where individual microbiome sequencing data is used to make comparisons.
- Additionally, longitudinal studies are needed with higher sample sizes to investigate the natural changes of the vaginal microbiome during pregnancy and the physiological mechanisms underlying these apparent different risk profiles.
- Furthermore, randomized-controlled trials are needed to establish if pregnant women could benefit from specific probiotic supplementation during pregnancy.
Abstract
Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest.