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Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.
Akinsuyi, OS, Roesch, LFW
Microbiology spectrum. 2023;11(3):e0032223
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Osteoporosis (OP) is the most common metabolic bone disease associated with aging. Microbiome dysbiosis leading to impaired intestinal immune responses and subsequent production of osteoclastogenic cytokines has been proposed as the mechanism by which gut microbes are associated with osteoporosis. The aim of this study was to identify gut bacteria consistently associated with osteoporosis across different cohorts. This study was a meta-analysis of five studies. Results showed that gut microbial dysbiosis in osteoporosis patients is associated with functional changes, which result in significant changes in metabolites that play a key role in bone metabolism. Authors concluded that their findings set the stage for future studies to provide more comprehensive knowledge on how dysbiosis in the gut microbiome contributes to osteoporosis.
Abstract
Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens Clostridium sensu stricto, Bacteroides, and Intestinibacter was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera Collinsella, Megasphaera, Agathobaculum, Mediterraneibacter, Clostridium XIV, and Dorea, were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including Limosilactobacillus, were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. IMPORTANCE Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.
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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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Association between physical activity and changes in intestinal microbiota composition: A systematic review.
Aya, V, Flórez, A, Perez, L, Ramírez, JD
PloS one. 2021;16(2):e0247039
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The human gut flora or microbiota is made up of many different microorganisms, including bacteria, fungi, and viruses. Researchers still find it difficult to clearly define what constitutes a healthy gut flora. This is made more challenging by the fact that the array of microorganisms in the gut are influenced by multiple internal and external factors. Such as diet, sleep, circadian rhythm, age, and physical activity, and they also change with disease. This review sought to gather the current evidence on how physical activity (external factor) impacts the microbial make-up of the gut in healthy humans and the conferred metabolic benefits on the human host. The review included 17 studies with the findings from athletes and exercise intervention programs. Whereby some research demonstrates a consistent beneficial relationship between a favourable microbiota composition and exercise, the authors felt unable to draw a firm conclusion due to the complexity of the microbial system and other influencing factors. The authors called for further, larger scaled studies, that should distinguish between different types of exercise (i.e. endurance and high-intensity training) and age groups, as well as incorporating more information on the subject's diet and lifestyle factors. Of clinical relevance could be the potential of physical activity as a modulator gut microbiome composition.
Abstract
INTRODUCTION The intestinal microbiota comprises bacteria, fungi, archaea, protists, helminths and viruses that symbiotically inhabit the digestive system. To date, research has provided limited data on the possible association between an active lifestyle and a healthy composition of human microbiota. This review was aimed to summarize the results of human studies comparing the microbiome of healthy individuals with different physical activity amounts. METHODS We searched Medline/Ovid, NIH/PubMed, and Academic Search Complete between August-October 2020. Inclusion criteria comprised: (a) cross-sectional studies focused on comparing gut microbiome among subjects with different physical activity levels; (b) studies describing human gut microbiome responses to any type of exercise stimulus; (c) studies containing healthy adult women and men. We excluded studies containing diet modifications, probiotic or prebiotic consumption, as well as studies focused on diabetes, hypertension, cancer, hormonal dysfunction. Methodological quality and risk of bias for each study were assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool. The results from cross-sectional and longitudinal studies are shown independently. RESULTS A total of 17 articles were eligible for inclusion: ten cross-sectional and seven longitudinal studies. Main outcomes vary significantly according to physical activity amounts in longitudinal studies. We identified discrete changes in diversity indexes and relative abundance of certain bacteria in active people. CONCLUSION As literature in this field is rapidly growing, it is important that studies incorporate diverse methods to evaluate other aspects related to active lifestyles such as sleep and dietary patterns. Exploration of other groups such as viruses, archaea and parasites may lead to a better understanding of gut microbiota adaptation to physical activity and sports and its potentially beneficial effects on host metabolism and endurance.
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Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: A meta-analysis and supporting evidence.
Zhang, L, Rana, I, Shaffer, RM, Taioli, E, Sheppard, L
Mutation research. Reviews in mutation research. 2019;781:186-206
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Glyphosate is a highly effective broad-spectrum herbicide that is typically applied in mixtures known as glyphosate-based herbicides (GBHs). Glyphosate and its metabolites persist in food, water, and dust, potentially indicating that everyone may be exposed ubiquitously. The objective of this study was to focus on an a priori hypothesis - the highest biologically relevant exposure to GBHs, i.e., higher levels, longer durations and/or with sufficient lag and latency, will lead to increased risk of non-Hodgkin lymphoma (NHL) in humans. This study is a meta-analysis of six studies (one cohort and five case-control control studies) with almost 65,000 participants. Results demonstrated a significantly increased NHL risk in highly GBH-exposed individuals. Authors conclude that the overall evidence from human, animal, and mechanistic studies presented in this study, supports a compelling link between exposures to GBHs and increased risk for NHL.
Abstract
Glyphosate is the most widely used broad-spectrum systemic herbicide in the world. Recent evaluations of the carcinogenic potential of glyphosate-based herbicides (GBHs) by various regional, national, and international agencies have engendered controversy. We investigated whether there was an association between high cumulative exposures to GBHs and increased risk of non-Hodgkin lymphoma (NHL) in humans. We conducted a new meta-analysis that includes the most recent update of the Agricultural Health Study (AHS) cohort published in 2018 along with five case-control studies. Using the highest exposure groups when available in each study, we report the overall meta-relative risk (meta-RR) of NHL in GBH-exposed individuals was increased by 41% (meta-RR = 1.41, 95% confidence interval, CI: 1.13-1.75). For comparison, we also performed a secondary meta-analysis using high-exposure groups with the earlier AHS (2005), and we calculated a meta-RR for NHL of 1.45 (95% CI: 1.11-1.91), which was higher than the meta-RRs reported previously. Multiple sensitivity tests conducted to assess the validity of our findings did not reveal meaningful differences from our primary estimated meta-RR. To contextualize our findings of an increased NHL risk in individuals with high GBH exposure, we reviewed publicly available animal and mechanistic studies related to lymphoma. We documented further support from studies of malignant lymphoma incidence in mice treated with pure glyphosate, as well as potential links between glyphosate / GBH exposure and immunosuppression, endocrine disruption, and genetic alterations that are commonly associated with NHL or lymphomagenesis. Overall, in accordance with findings from experimental animal and mechanistic studies, our current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs and increased risk for NHL.
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Effect of Probiotics on Metabolic Outcomes in Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Taylor, BL, Woodfall, GE, Sheedy, KE, O'Riley, ML, Rainbow, KA, Bramwell, EL, Kellow, NJ
Nutrients. 2017;9(5)
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The gut microbiota is an important ecosystem consisting of both residential and pathogenic bacteria. The microbiota produce bioactive compounds shown to benefit host metabolism. A variety of factors influence the gut microbiome, including host genetics, illness, antibiotic use, dietary patterns, weight loss and pregnancy. Throughout pregnancy the gut microbiota undergoes significant changes. The aim of this study is to determine the effect of 6-8-week probiotic supplementation versus placebo on glucose homeostasis, lipid levels and gestational weight gain in pregnant women diagnosed with gestational diabetes mellitus. This study is a systemic review based on four randomised controlled trials involving 288 participants. All studies included healthy pregnant women, age range between 18 – 40 years, who were diagnosed with gestational diabetes mellitus at 24 – 30 weeks gestation by oral glucose tolerance test. The study found that a 6 – 8-week probiotic intervention did not improve fasting blood glucose or LDL-cholesterol levels. However, probiotic supplementation in women with gestational diabetes mellitus was associated with significant reductions in insulin resistance. Authors conclude that while probiotic supplementation resulted in a significant reduction in insulin resistance in pregnant women with gestational diabetes mellitus, there was no significant effect on fasting blood glucose or LDL-cholesterol.
Abstract
The metabolic effects of probiotic administration in women with gestational diabetes mellitus (GDM) is unknown. The objective of this review was to investigate the effect of probiotics on fasting plasma glucose (FPG), insulin resistance (HOMA-IR) and LDL-cholesterol levels in pregnant women diagnosed with GDM. Seven electronic databases were searched for RCTs published in English between 2001 and 2017 investigating the metabolic effects of a 6-8 week dietary probiotic intervention in pregnant women following diagnosis with GDM. Eligible studies were assessed for risk of bias and subjected to qualitative and quantitative synthesis using a random effects model meta-analyses. Four high quality RCTs involving 288 participants were included in the review. Probiotic supplementation was not effective in decreasing FBG (Mean Difference = -0.13; 95% CI -0.32, 0.06, p = 0.18) or LDL-cholesterol (-0.16; 95% CI -0.45, 0.13, p = 0.67) in women with GDM. However, a significant reduction in HOMA-IR was observed following probiotic supplementation (-0.69; 95% CI -1.24, -0.14, p = 0.01). There were no significant differences in gestational weight gain, delivery method or neonatal outcomes between experimental and control groups, and no adverse effects of the probiotics were reported. Probiotic supplementation for 6-8 weeks resulted in a significant reduction in insulin resistance in pregnant women diagnosed with GDM. The use of probiotic supplementation is promising as a potential therapy to assist in the metabolic management of GDM. Further high quality studies of longer duration are required to determine the safety, optimal dose and ideal bacterial composition of probiotics before their routine use can be recommended in this patient group.