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The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.
Zhang, T, Zhang, J, Duan, L
Nutrients. 2023;15(7)
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Inflammatory bowel disease (IBD), largely classified as Crohn’s disease (CD) or ulcerative colitis (UC), is a chronic intestinal inflammatory disorder mediated by genetic, immune, microbial, and environmental factors. The aim of this study was to summarise the efficacy of different genetically modified probiotics compared to wild-type probiotics in the treatment of IBD in animal models and patients and to investigate the specific effects and main mechanisms involved. This study was a systematic review of forty-five preclinical studies and one clinical study. Results showed a protective effect of genetically modified organisms (gm) probiotics in colitis. Several protective mechanisms have been identified: reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of the activity of oxidative stress in the colon, improvement of intestinal barrier integrity, modulation of the diversity and composition of gut microbiota, and production of favourable metabolites, including short-chain fatty acids, by beneficial bacteria. Authors concluded that gm probiotics are more effective and safer than wild-type probiotics, to facilitate clinical translation.
Expert Review
Conflicts of interest:
None
Take Home Message:
Conclusions of this review were largely based on mouse models and although treatment using probiotics is generally considered safe in humans, with only minor side-effects (flatulence), practitioners need to be aware that in an IBD population the use of GM formulations might not be completely without risk.
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
This paper summarises the efficacy of specific genetically modified (GM) probiotic formulations for Inflammatory Bowel Disease (IBD) when compared to wild type probiotics. The aim was to ascertain what specific effects and mechanisms such probiotics have on IBD symptomatology.
Methods
- A total of 46 published articles were included; 45 mouse experimental models (induced acute or chronic colitis) (n=15-130) and 1 human IBD population clinical trial (n=10)
- The effect of GM probiotics were compared to placebo and wild-type probiotics in trials including preclinical studies, randomised controlled trials and cohort studies
- Animals received probiotics via gastric gavage (105 - 4 x 1012 CFU) for 3-6 weeks
- The human placebo-uncontrolled trial lasted 7 days and patients received 10 GM capsules of L.lactis (1 x 1010 CFU) twice daily.
Results
- GM probiotics that secrete immunoregulatory cytokines such as IL-10 appear to reduce intestinal damage
- The human trial using GM L.lactis resulted in 5 patients who went into complete clinical remission (CDAI, <150) with 3 patients exhibiting a clinical response (decrease in CDAI, >70). with only minor adverse events (flatulence)
- However, human cytokines that promote intestinal barrier function and epithelial restitution were not enhanced with oral administration of probiotics
- Two studies concluded that GM L.lactis and S.boulardii, that secrete atrial natriuretic peptide, might be the most effective options in supporting colitis
- GM L.casei resulted in faster recovery from weight loss in acute colitis models
- Superoxide dismutase (SOD) producing GM L.fermentum increased SOD activity by almost eightfold compared to the wild type
- GM Lact. fermentum furthermore showed a higher survival rate and lower disease activity index (P <0·05) in colitis models
- GM L.lactis improved gut microbial composition and GM S.cerevisiae improved microbial diversity whilst reducing the Firmicutes to Bacteroides ratio
- GM E.coli significantly reduced weight loss, colon shortening plus lower disease activity and histological changes (P < 0.05).
Conclusion
Despite the heterogeneity of the trials, GM probiotics appear to play a notable part in ameliorating IBD symptomatology and disease severity when compared to wild-type probiotics. Human efficacy and potential adverse effects require more in-depth trials to ascertain safety and optimal dosages.
Clinical practice applications:
- Probiotics species used in the trials included S.thermophilus, E.coli, L.lactis, B.ovatus, S.boulardii, L.fermentum, B.longhum, L.casei, L.plantarum, and S.cerevisiae. Wild-types of some of these are already available to use in clinical practice
- Note that oral administration in the human trial showed no significant health outcome, therefore efficacy and safety need to be ascertained on an individual patient level
- Colonisation of beneficial bacteria in the gut of IBD patients might be difficult and any form of supplementation therefore needs to be closely monitored.
Considerations for future research:
- More evidence is needed to demonstrate that GM probiotic formulations result in significantly improved outcomes when compared to wild-types
- Future randomised placebo-controlled trials need to include larger cohorts to determine supplement efficacy
- Longer periods of intervention are needed to confirm efficacy, safety, and tolerance for both Crohn’s Disease and Colitis
- Optimal GM probiotic formulation, doses, and means of application need to be identified.
Abstract
BACKGROUND Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). OBJECTIVE This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. METHODS PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. RESULTS Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. CONCLUSIONS Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.
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Lack of association between endocrine disrupting chemicals and male fertility: A systematic review and meta-analysis.
Martínez, MÁ, Marquès, M, Salas-Huetos, A, Babio, N, Domingo, JL, Salas-Salvadó, J
Environmental research. 2023;217:114942
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Exposure to natural or synthetic chemicals is directly related to environmental conditions, dietary and other lifestyle factors. Some of these chemicals are named endocrine disrupting chemicals (EDCs) because of their capability to interfere with the endocrine system. The aim of this study was to summarise and explore the association between exposure to EDCs and human male fertility indicators. This study is a systematic review and meta-analysis of seven studies; 4 assessed bisphenol A (BPA) in urine and sperm quality parameters, while 3 articles evaluated PCB153 [polychlorinated biphenyls] in serum and sperm quality parameters. Results show that there weren’t any positive or inverse associations between BPA or PCB153 and the sperm parameters analysed. Authors conclude that the systematic review showed a high disparity between studies, making difficult a consensus on the possible detrimental effect of the 12 groups of EDCs on male fertility. Thus, no conclusive statements can be drawn. Further studies are needed in order to provide more robust data.
Abstract
The incidence of infertility currently affects about 15% of the world's population. Male factors are estimated to be responsible for up to 40-50% of these cases. While the cause of these reproductive disorders is still unclear, the exposure to a family of ubiquitous compounds in our daily life, named endocrine disrupting chemicals (EDCs) could be involved. This paper was aimed at performing a systematic review and meta-analysis of population studies exploring whether human male exposure to EDCs affects male fertility. Clinical and observational studies assessing the exposure to EDCs along with sperm quality, the most common reproductive disorders, sperm DNA damage, sperm oxidative stress, fertilization rate, implantation rate, clinical pregnancy rate, live birth rate, and miscarriage rate were included. The quality assessment tool from the NHLBI-NIH was used to assure that studies met standardized quality criteria. Sensitivity analysis and heterogeneity among studies was assessed. Overall, the 32 selected articles, including 7825 individuals in the systematic review, explored 12 families of EDCs. The results revealed a high heterogeneity among studies in relation to the association between exposure to EDCs and the endpoints analyzed. Meta-analyses were performed with data from 7 articles including 479 individuals, 4 articles assessing the association between BPA in urine and sperm quality, and 3 articles evaluating PCB153 in serum and sperm quality. In the meta-analysis, we identified an unpredicted significant positive association between PCB153 exposure and sperm concentration. However, it would not be clinically relevant. No positive or inverse associations were found neither for BPA, nor for PCB153 and the rest of sperm parameters analyzed. The high disparity between studies made difficult to draw conclusions on the potential harmful effects of EDCs on male fertility. Consequently, to delineate the potential relationship that EDCs can have on male fertility, an important condition stressing the health system, further investigations are required.
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Lifestyle-, environmental-, and additional health factors associated with an increased sperm DNA fragmentation: a systematic review and meta-analysis.
Szabó, A, Váncsa, S, Hegyi, P, Váradi, A, Forintos, A, Filipov, T, Ács, J, Ács, N, Szarvas, T, Nyirády, P, et al
Reproductive biology and endocrinology : RB&E. 2023;21(1):5
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The World Health Organization defines infertility as regular unprotected sexual intercourse without achieving conception within a year. In recent years, there has been a growing demand for functional, objective parameters reflecting fertility status more clearly than classical parameters. Of these, sperm DNA fragmentation (SDF) and the DNA fragmentation index – denoting the percentage of sperm with damaged DNA – seem to be of utmost importance. The aim of this study was to investigate all risk factors that may potentially be increasing SDF. This study is a systematic review and meta-analysis of one hundred and ninety articles. The earliest studies were published in 2003, and the latest in 2021. Results show that several modifiable risk factors negatively affect SDF, namely; a. health conditions: varicocele [when veins become enlarged inside the pouch of skin that holds the testicles] and impaired glucose tolerance, b. infections: Chlamydia, c. malignancies: testicular tumours, and d. lifestyle factors: smoking, alcohol consumption and body mass index. Authors conclude that several lifestyle-, environmental-, and additional health factors are associated with increased SDF.
Abstract
INTRODUCTION Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an evidence-based test for fertility evaluations depicting fertility more clearly than standard semen parameters. Therefore, we aimed to summarize the potential prognostic factors of a higher SDF. METHODS We conducted a systematic search in three medical databases and included studies investigating any risk factors for SDF values. We calculated mean differences (MD) in SDF with 95% confidence interval (CI) for exposed and non-exposed individuals. RESULTS We included 190 studies in our analysis. In the group of associated health conditions, varicocele (MD = 13.62%, CI: 9.39-17.84) and impaired glucose tolerance (MD = 13.75%, CI: 6.99-20.51) had the most significant increase in SDF. Among malignancies, testicular tumors had the highest impact, with a maximum of MD = 11.3% (CI: 7.84-14.76). Among infections, the overall effects of both Chlamydia and HPV were negligible. Of lifestyle factors, smoking had the most disruptive effect on SDF - an increase of 9.19% (CI: 4.33-14.06). Different periods of sexual abstinence did not show significant variations in SDF values. Age seemed to have a more drastic effect on SDF from age 50 onwards, with a mean difference of 12.58% (CI: 7.31-17.86). Pollution also had a detrimental effect - 9.68% (CI: 6.85-12.52). CONCLUSION Of the above risk factors, varicocele, impaired glucose tolerance, testicular tumors, smoking, pollution, and paternal age of over 50 were associated with the highest SDF. TRIAL REGISTRATION CRD42021282533.
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The effectiveness of interventions during the first 1,000 days to improve energy balance-related behaviors or prevent overweight/obesity in children from socio-economically disadvantaged families of high-income countries: a systematic review.
Lioret, S, Harrar, F, Boccia, D, Hesketh, KD, Kuswara, K, Van Baaren, C, Maritano, S, Charles, MA, Heude, B, Laws, R
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(1):e13524
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The first 1,000 days is an opportune time to support parents, as primary caregivers and role model, to promote a healthy lifestyle and prevent obesity for their children. The aim of this study was to update the current evidence on the effectiveness of family-based interventions implemented during pregnancy and up to 2 years of age to improve energy balance-related behaviours and growth, or prevent overweight (OW)/ obesity (OB), in children growing up in families experiencing socio-economic disadvantage. This study is a systematic review of thirty-three studies which corresponded to 24 distinct interventions. Of the 24 interventions, nearly all were (cluster) randomised controlled trials; three had a quasi-experimental design. Results show that there is some effectiveness on behavioural and anthropometric outcomes in young children when programmes target and are tailored to families experiencing socioeconomic disadvantage. Authors conclude that a holistic, multilevel and proportionate interventions are likely to more effective and sustainably address the issue of social inequalities and inequities. Additionally, more thorough process evaluation of such complex interventions using mixed methods is needed to better understand why interventions worked or not, by which mechanisms of action (if any), for whom and in which context.
Abstract
This narrative systematic review examined effectiveness of interventions during pregnancy and up to 2 years of age in improving energy balance-related behaviors or prevent overweight/obesity in children from families experiencing socio-economic disadvantage. We identified 24 interventions, from 33 articles, since 1990. Overall, despite their heterogeneity and variability in internal and external validity, there was some evidence of beneficial impact of interventions on obesity risk (4/15), and associated behaviors, e.g.: breastfeeding (9/18), responsive feeding (11/16), diet (7/8), sedentary (1/3) and movement (4/7) behaviors, and sleep (1/2). The most effective interventions aimed at promoting breastfeeding commenced antenatally; this was similar for the prevention of obesity, provided the intervention continued for at least 2 years postnatally and was multi-behavioral. Effective interventions were more likely to target first-time mothers and involve professional delivery agents, multidisciplinary teams and peer groups. Among ethnic/racial minorities, interventions delivered by lay agents had some impact on dietary behavior but not weight outcomes. Co-creation with stakeholders, including parents, and adherence to theoretical frameworks were additional ingredients for more pragmatic, inclusive, non-judgmental, and effective programs. The growing body of evidence on obesity prevention interventions targeting families experiencing socio-economic disadvantage is promising for reducing early inequalities in obesity risk.
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Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.
Chávez-Hidalgo, LP, Martín-Fernández-de-Labastida, S, M de Pancorbo, M, Arroyo-Izaga, M
World journal of gastroenterology. 2023;29(7):1219-1234
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Colorectal cancer (CRC) is the third most frequent type of cancer and yet has the second highest mortality rate in cancer patients worldwide. Hence there is an urgency to understand more about dietary and lifestyle factors that can help to prevent this type of cancer. It is known that folate has a preventive function in CRC, possibly due to its role in DNA methylation. Methylation is the addition of methyl groups to DNA, which influences gene expression and regulation. This systematic review investigated how folate and other dietary methyl groups and methyl influencers such as B vitamins and alcohol influence the development of CRC, whilst also considering various genetic variants in methyl-metabolising enzymes (polymorphisms). The analysis included a total of 19 case-control and cohort studies and highlighted that potential interactions between methyl donor nutrients, genetic variants, and alcohol influence CRC risk. For most, high levels of folate intake were considered a protective factor, while high alcohol consumption proved to be a risk factor. Yet these interactions appear to be complex, with gender, genetic variations and folate status appearing to contribute to variable and, in some cases, contradictory outcomes. The authors suggested in their findings that Vitamin B6, Vitamin B3 (Niacin), and alcohol may affect CRC by influencing its risk by acting on both the genetic code itself and the epigenetic factors that control gene activity. Further research is needed to better understand the complexity of these mechanisms, and to help clarify the influence of methyl group donors as epigenetic regulators of gene activity in CRC development.
Abstract
BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
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Effectiveness of Therapeutic Patient Education Interventions in Obesity and Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Correia, JC, Waqas, A, Huat, TS, Gariani, K, Jornayvaz, FR, Golay, A, Pataky, Z
Nutrients. 2022;14(18)
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Obesity and diabetes mellitus (DM) account for the highest burden of non-communicable diseases. Obesity is also highly comorbid with type 2 DM with a prevalence of 8.5% among adults around the globe. The aims of this study were to present (a) a critical synthesis of the theoretical basis and development of therapeutic patient education (TPE) interventions for obesity and diabetes, and (b) quantitative evidence for the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. This study is a systematic review and meta-analysis of fifty-four randomised controlled trials. Results show that: - TPE interventions bring about significant improvements in biomedical outcomes among patients with DM and obesity. - there weren’t significant differences in the quality of life of participants undergoing TPE interventions (inconclusive as only data from two studies were considered). - interventions delivered through different media and delivery formats may be equally effective. Authors conclude that the use of electronic media such as short messaging services, website-based educational programs and animation media can be used to deliver TPE effectively.
Abstract
Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis present a critical synthesis of the development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus qualitatively synthesized. Out of these, 47 were included in the quantitative synthesis. There was substantial heterogeneity in the reporting of these outcomes (I2 = 88.35%, Q = 317.64), with a significant improvement noted in serum HbA1c levels (standardized mean difference (SMD) = 0.272, 95% CI: 0.118 to 0.525, n = 7360) and body weight (SMD = 0.526, 95% CI: 0.205 to 0.846, n = 1082) in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (p < 0.001). These interventions should be implemented in healthcare and community settings to improve the health outcomes in patients suffering from obesity and DM.
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Mycotoxin-Linked Mutations and Cancer Risk: A Global Health Issue.
Ekwomadu, T, Mwanza, M, Musekiwa, A
International journal of environmental research and public health. 2022;19(13)
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Mycotoxins are toxic substances produced by fungi, which can be found in common foods like maize, wheat, nuts, and foods containing them. Mycotoxins such as aflatoxins, ochratoxin, fumonisins, zearalenone, and some Penicillium toxins can alter genetic material. According to previous studies, they can damage genetic material and affect cell growth. Usage of chemicals such as fertilizers and fungicides is a common practice in the agricultural industry to protect plants from fungus and to feed them. However, fungicides can accelerate mycotoxin production. 16 studies were included in this Systematic Review and 11 in Meta-Analysis. This research looked at the harmful effects of mycotoxins such as aflatoxins, fumonisins, ochratoxin, T2, zearalenone, and some Penicillium toxins in causing cancers. The researchers evaluated the link between aflatoxin exposure and liver cancer, fumonisin B1 exposure and liver cancer, zearalenone exposure and breast cancer, zearalenone exposure and cervical cancer, citrinine and patulin exposure and colorectal cancer, and NEO, HT-2, and T-2 exposure and Oesophageal cancer. This research did not show significant associations between various mycotoxins and cancer risk. As currently, most studies are primarily focused on aflatoxin; more robust studies are needed to assess the cancer risk associated with different mycotoxin exposure. Using the results of this study, healthcare professionals can gain a better understanding of how mycotoxins affect our bodies.
Abstract
Humans continue to be constantly exposed to mycotoxins, mainly through oral exposure (dietary), inhalation, or dermal contact. Recently, it has been of increasing interest to investigate mycotoxin-linked carcinogenicity. This systematic review was conducted to synthesize evidence of the association between mycotoxin-linked mutations and the risk of cancer, to provide an overview of the data linking exposure to different mycotoxins with human cancer risk, and to provide an update on current research on the risk of cancer associated with human exposure to mycotoxins. PRISMA guidelines were used when conducting the systematic review. PubMed, MEDLINE, and CINAHL electronic databases were comprehensively searched to extract the relevant studies published from inception to May 2022. A total of sixteen relevant studies (4907 participants) were identified and included in this review. Of these, twelve studies were from Asia, while four of the studies were conducted in Africa. The overall meta-analysis result found no significant association, although some of the studies confirmed an association between mycotoxin-linked mutations and primary liver cancer risk. Mainly, the experimental studies have shown associations between mycotoxin-linked mutations and cancer risk, and there is a need for researchers to confirm these links in epidemiological studies in order to guide public health policies and interventions.
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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.
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Adverse pregnancy and birth outcomes associated with Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum: a systematic review and meta-analysis.
Jonduo, ME, Vallely, LM, Wand, H, Sweeney, EL, Egli-Gany, D, Kaldor, J, Vallely, AJ, Low, N
BMJ open. 2022;12(8):e062990
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Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum, referred to together as genital mycoplasmas, commonly colonise the urogenital tract in women, and are often found together. These species do not appear to cause symptoms or harmful effects in non-pregnant women. However, studies have reported that colonisation with a genital mycoplasma has been associated with several adverse pregnancy outcomes. The main objective of this study was to investigate the associations between M. hominis, U. urealyticum and/or U. parvum and the risk of pre-term birth, alone and in combination with bacterial vaginosis (BV). This study is a systematic review and meta-analysis of fifty-seven studies. Results show that genital mycoplasmas are associated with several different adverse pregnancy outcomes in univariable analysis only. Authors conclude that since only six of the fifty-seven studies reported multivariable analysis, the current available literature does not allow conclusions about the role of mycoplasmas in adverse pregnancy and birth outcomes, alone or with coexisting BV.
Abstract
OBJECTIVES Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum (genital mycoplasmas) commonly colonise the urogenital tract in pregnant women. This systematic review aims to investigate their role in adverse pregnancy and birth outcomes, alone or in combination with bacterial vaginosis (BV). METHODS We searched Embase, Medline and CINAHL databases from January 1971 to February 2021. Eligible studies tested for any of the three genital mycoplasmas during pregnancy and reported on the primary outcome, preterm birth (PTB) and/or secondary outcomes low birth weight (LBW), premature rupture of membranes (PROM), spontaneous abortion (SA) and/or perinatal or neonatal death (PND).Two reviewers independently screened titles and abstracts, read potentially eligible full texts and extracted data. Two reviewers independently assessed risks of bias using published checklists. Random effects meta-analysis was used to estimate summary ORs (with 95% CIs and prediction intervals). Multivariable and stratified analyses were synthesised descriptively. RESULTS Of 57/1194 included studies, 39 were from high-income countries. In meta-analysis of unadjusted ORs, M. hominis was associated with PTB (OR 1.87, 95% CI 1.49 to 2.34), PROM, LBW and PND but not SA. U. urealyticum was associated with PTB (OR 1.84, 95% CI 1.34 to 2.55), PROM, LBW, SA and PND. U. parvum was associated with PTB (1.60, 95% CI 1.12 to 2.30), PROM and SA. Nine of 57 studies reported any multivariable analysis. In two studies, analyses stratified by BV status showed that M. hominis and U. parvum were more strongly associated with PTB in the presence than in the absence of BV. The most frequent source of bias was a failure to control for confounding. CONCLUSIONS The currently available literature does not allow conclusions about the role of mycoplasmas in adverse pregnancy and birth outcomes, alone or with coexisting BV. Future studies that consider genital mycoplasmas in the context of the vaginal microbiome are needed. PROSPERO REGISTRATION NUMBER CRD42016050962.
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Prenatal exposure to phthalate and decreased body mass index of children: a systematic review and meta-analysis.
Lee, DW, Lim, HM, Lee, JY, Min, KB, Shin, CH, Lee, YA, Hong, YC
Scientific reports. 2022;12(1):8961
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Phthalates are widely used chemicals to improve the utility of plastics and personal care products. Phthalates can be classified as high-molecular-weight phthalates and low-molecular-weight phthalates. The aim of this study was to clarify whether prenatal and postnatal exposures to phthalates are associated with physical growth as measured by body composition indices in children. This study is a systematic literature review and meta-analysis of 39 studies about the association of phthalates with body composition indices among children. Results showed that prenatal exposure to phthalates is significantly associated with low body mass index in children, but not with body fat mass. In addition, prenatal phthalate exposure may affect the disturbance of normal growth of children rather than act as an obesogen. Authors conclude that it is necessary to administer stricter and broader regulations on phthalates in living environments.
Abstract
Phthalates are well-known endocrine-disrupting chemicals. Many detrimental health effects of phthalates were investigated, but studies on the association of phthalates with obesity in children showed inconsistent results. Thus, this systematic review and meta-analysis were performed to clarify whether prenatal and postnatal exposures to phthalates are associated with physical growth disturbances in children. We performed the systematic review and meta-analysis following the PRISMA 2020 statement guidelines, and found 39 studies that met our inclusion criteria, including 22 longitudinal and 17 cross-sectional studies. We observed a significant negative association between the prenatal exposure to DEHP and the body mass index (BMI) z-score of the offspring (β = - 0.05; 95% CI: - 0.10, - 0.001) in the meta-analysis, while no significant association between the prenatal exposure to DEHP and the body fat percentage of the offspring was observed (β = 0.01; 95% CI: - 0.41, 0.44). In the systematic review, studies on the association between phthalates exposure in childhood and obesity were inconsistent. Prenatal exposure to phthalates was found to be associated with decreased BMI z-score in children, but not associated with body fat percentage. Our findings suggest that phthalates disturb the normal muscle growth of children, rather than induce obesity, as previous studies have hypothesized.