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BACKGROUND: Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case-control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease. METHODS: A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes' sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis. RESULTS: Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p-values > 0.05; beta-diversity: PERMANOVA, both R 2 < 0.0007, p-values > 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p-values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes' sequence reads were not significantly different between groups (all FDR p-values > 0.05). CONCLUSIONS: Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date.
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Endometriose , Microbioma Gastrointestinal , Humanos , Endometriose/microbiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Adulto , Estudos de Casos e Controles , Estônia/epidemiologia , Estudos de Coortes , Pessoa de Meia-Idade , Metagenômica , Disbiose/microbiologia , Adulto JovemRESUMO
The beneficial effects of physical activity (PA) on gut microbiome have been reported, nevertheless the findings are inconsistent, with the main limitation of subjective methods for assessing PA. It is well accepted that using an objective assessment of PA reduces the measurement error and also allows objective assessment of sedentary behavior (SB). We aimed to study the associations between accelerometer-assessed behaviors (i.e., SB, light-intensity physical activity [LPA] and moderate-to-vigorous physical activity [MVPA]) with the gut microbiome using compositional data analysis, a novel approach that enables to study these behaviors accounting for their inter-dependency. This cross-sectional study included 289 women from the Northern Finland Birth Cohort 1966. Physical activity was measured during 14 days by wrist-worn accelerometers. Analyses based on the combined effect of MVPA and SB, and compositional data analyses in association with the gut microbiome data were performed. The microbial alpha- and beta-diversity were not significantly different between the MVPA-SB groups, and no differentially abundant microorganisms were detected. Compositional data analysis did not show any significant associations between any movement behavior (relative to the others) on microbial alpha-diversity. Butyrate-producing bacteria such as Agathobacter and Lachnospiraceae CAG56 were significantly more abundant when reallocating time from LPA or SB to MVPA (γ = 0.609 and 0.113, both p-values = 0.007). While PA and SB were not associated with microbial diversity, we found associations of these behaviors with specific gut bacteria, suggesting that PA of at least moderate intensity (i.e., MVPA) could increase the abundance of short-chain fatty acid-producing microbes.
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Acelerometria , Exercício Físico , Microbioma Gastrointestinal , Comportamento Sedentário , Humanos , Feminino , Microbioma Gastrointestinal/fisiologia , Estudos Transversais , Exercício Físico/fisiologia , Pessoa de Meia-Idade , FinlândiaRESUMO
BACKGROUND: The effects of physical activity and sedentary behavior on human health are well known, however, the molecular mechanisms are poorly understood. Growing evidence points to physical activity as an important modulator of the composition and function of microbial communities, while evidence of sedentary behavior is scarce. We aimed to synthesize and meta-analyze the current evidence about the effects of physical activity and sedentary behavior on microbiome across different body sites and in different populations. METHODS: A systematic search in PubMed, Web of Science, Scopus and Cochrane databases was conducted until September 2022. Random-effects meta-analyses including cross-sectional studies (active vs. inactive/athletes vs. non-athletes) or trials reporting the chronic effect of physical activity interventions on gut microbiome alpha-diversity in healthy individuals were performed. RESULTS: Ninety-one studies were included in this systematic review. Our meta-analyses of 2632 participants indicated no consistent effect of physical activity on microbial alpha-diversity, although there seems to be a trend toward a higher microbial richness in athletes compared to non-athletes. Most of studies reported an increase in short-chain fatty acid-producing bacteria such as Akkermansia, Faecalibacterium, Veillonella or Roseburia in active individuals and after physical activity interventions. CONCLUSIONS: Physical activity levels were positively associated with the relative abundance of short-chain fatty acid-producing bacteria. Athletes seem to have a richer microbiome compared to non-athletes. However, high heterogeneity between studies avoids obtaining conclusive information on the role of physical activity in microbial composition. Future multi-omics studies would enhance our understanding of the molecular effects of physical activity and sedentary behavior on the microbiome.
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The molecular mechanisms behind the potential 'anti-aging' effects of exercise remain to be elucidated. Janssens et al. studied the lipidome of different mouse tissues and human skeletal muscle. They identified an evolutionary conserved 'lipid aging' signature, characterized by bis(monoacylglycero)phosphate accumulation, which, at the muscle level, can be attenuated by exercise.
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PURPOSE OF REVIEW: The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS: The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY: The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.
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Endometriose , Microbioma Gastrointestinal , Síndrome do Ovário Policístico , Saúde Reprodutiva , Humanos , Feminino , Microbioma Gastrointestinal/fisiologia , Endometriose/microbiologia , Síndrome do Ovário Policístico/microbiologia , Genitália Feminina/microbiologia , Neoplasias dos Genitais Femininos/microbiologia , Infertilidade Feminina/microbiologia , Doenças dos Genitais Femininos/microbiologiaRESUMO
PURPOSE OF REVIEW: The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS: The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY: The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.
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Introduction: The female reproductive tract harbours unique microbial communities (known as microbiota) which have been associated with reproductive functions in health and disease. While endometrial microbiome studies have shown that the uterus possesses higher bacterial diversity and richness compared to the vagina, the knowledge regarding the composition of the Fallopian tubes (FT) is lacking, especially in fertile women without any underlying conditions. Methods: To address this gap, our study included 19 patients who underwent abdominal hysterectomy for benign uterine pathology, and 5 women who underwent tubal ligation as a permanent contraceptive method at Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA). We analyzed the microbiome of samples collected from the FT and endometrium using 16S rRNA gene sequencing. Results: Our findings revealed distinct microbiome profiles in the endometrial and FT samples, indicating that the upper reproductive tract harbors an endogenous microbiome. However, these two sites also shared some similarities, with 69% of the detected taxa Being common to both. Interestingly, we identified seventeen bacterial taxa exclusively present in the FT samples, including the genera Enhydrobacter, Granulicatella, Haemophilus, Rhizobium, Alistipes, and Paracoccus, among others. On the other hand, 10 bacterial taxa were only found in the endometrium, including the genera Klebsiella, Olsenella, Oscillibacter and Veillonella (FDR <0.05). Furthermore, our study highlighted the influence of the endometrial collection method on the findings. Samples obtained transcervically showed a dominance of the genus Lactobacillus, which may indicate potential vaginal contamination. In contrast, uterine samples obtained through hysterescopy revealed higher abundance of the genera Acinetobacter, Arthrobacter, Coprococcus, Methylobacterium, Prevotella, Roseburia, Staphylococcus, and Streptococcus. Discussion: Although the upper reproductive tract appears to have a low microbial biomass, our results suggest that the endometrial and FT microbiome is unique to each individual. In fact, samples obtained from the same individual showed more microbial similarity between the endometrium and FT compared to samples from different women. Understanding the composition of the female upper reproductive microbiome provides valuable insights into the natural microenvironment where processes such as oocyte fertilization, embryo development and implantation occur. This knowledge can improve in vitro fertilization and embryo culture conditions for the treatment of infertility.
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Infertilidade , Útero , Feminino , Humanos , RNA Ribossômico 16S/genética , Endométrio , Vagina/microbiologia , Bactérias/genéticaRESUMO
Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting reproductive-aged women, but the cause remains unclear. Recent evidence has linked microbial composition with PCOS; however, the results are inconsistent. The aim of this systematic review was to gather current knowledge of the microbes across body sites (oral cavity, blood, vagina/cervix, gut) in women with PCOS, and meta-analyse the microbial diversity in PCOS. For this purpose, a systematic search using PubMed, Web of Science, Cochrane and Scopus was carried out. After selection, 34 studies met the inclusion criteria. Most of the studies associated changes in the microbiome with PCOS, whereas heterogeneity of the studies in terms of ethnicity, body mass index (BMI) and methodology, among other confounders, made it difficult to corroborate this relationship. In fact, 19 out of 34 of the studies were categorised as having high risk of bias when the quality assessment was conducted. Our meta-analysis on the gut microbiome of 14 studies demonstrated that women with PCOS possess significantly lower microbial alpha diversity compared with controls (SMDâ¯=â¯-0.204; 95% CI -0.360 to -0.048; Pâ¯=â¯0.010; I2â¯=â¯5.508, by Shannon Index), which may contribute to the development of PCOS. Nevertheless, future studies should specifically overcome the shortcomings of the current studies by through well planned and conducted studies with larger sample sizes, proper negative and positive controls and adequate case-control matching.
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Síndrome do Ovário Policístico , Humanos , Feminino , Adulto , Índice de Massa Corporal , PubMed , ReproduçãoRESUMO
[This corrects the article DOI: 10.3389/fped.2022.917152.].
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Background: The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are poorly understood. We aimed to synthesize the current knowledge of the association of sedentary behavior and physical activity (acute and chronic effects) with gene expression and epigenetic modifications in children and adolescents. Methods: PubMed, Web of Science, and Scopus databases were systematically searched until April 2022. A total of 15 articles were eligible for this review. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews and/or a modified version of the Downs and Black checklist. Results: Thirteen studies used candidate gene approach, while only 2 studies performed high-throughput analyses. The candidate genes significantly linked to sedentary behavior or physical activity were: FOXP3, HSD11B2, IL-10, TNF-α, ADRB2, VEGF, HSP70, SOX, and GPX. Non-coding Ribonucleic acids (RNAs) regulated by sedentary behavior or physical activity were: miRNA-222, miRNA-146a, miRNA-16, miRNA-126, miR-320a, and long non-coding RNA MALAT1. These molecules are involved in inflammation, immune function, angiogenic process, and cardiovascular disease. Transcriptomics analyses detected thousands of genes that were altered following an acute bout of physical activity and are linked to gene pathways related to immune function, apoptosis, and metabolic diseases. Conclusion: The evidence found to date is rather limited. Multidisciplinary studies are essential to characterize the molecular mechanisms in response to sedentary behavior and physical activity in the pediatric population. Larger cohorts and randomized controlled trials, in combination with multi-omics analyses, may provide the necessary data to bring the field forward. Systematic Review Registration: [www.ClinicalTrials.gov], identifier [CRD42021235431].
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Mycoplasma penetrans has gained increased attention in relation to sexually transmitted infections, however, its pathogenic potential and prevalence in different populations remains to be elucidated. Among 293 Chlamydia trachomatis positive rectal samples submitted for lymphogranuloma venereum typing, M. penetrans was detected by PCR in 13.4% of 231 male samples.
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Choline kinase α1 (ChoKα1) has become an excellent antitumor target. Among all the inhibitors synthetized, the new compound Ff35 shows an excellent capacity to inhibit ChoKα1 activity. However, soluble Ff35 is also capable of inhibiting choline uptake, making the inhibitor not selective for ChoKα1. In this study, we designed a new protocol with the aim of disentangling whether the Ff35 biological action is due to the inhibition of the enzyme and/or to the choline uptake. Moreover, we offer an alternative to avoid the inhibition of choline uptake caused by Ff35, since the coupling of Ff35 to novel biomimetic magnetic nanoparticles (BMNPs) allows it to enter the cell through endocytosis without interacting with the choline transporter. This opens the possibility of a clinical use of Ff35. Our results indicate that Ff35-BMNPs nanoassemblies increase the selectivity of Ff35 and have an antiproliferative effect. Also, we demonstrate the effectiveness of the tandem Ff35-BMNPs and hyperthermia.