Age-related changes, influencing factors and crosstalk between vaginal and gut microbiota: a cross-sectional comparative study of pre- and postmenopausal women

Objective: The ideal vaginal environment is maintained by Lactobacillus species, which keep the vagina clean and free of infections, including sexually transmitted diseases and human papilloma virus infection. Other reported health benefits of Lactobacillus include a favorable impact on fertility and immunity, leading to a reduced risk of gynecological malignancies. Age-related decline in estrogen affects the population of Lactobacillus, leading to dominance of pathogenic flora and increased diversity in vaginal microbiota. In this study, we compared the differences between the vaginal microbiota of premenopausal and postmenopausal women. In addition, we examined the relationships between vaginal and gut microbiota, as well as their relationships to sex hormones and equol producing ability. Methods: This was a cross-sectional study of 35 premenopausal and 35 postmenopausal women, ranging from 27 to 76 years of age. We compared parameters such as the composition of the gut and vaginal microbiota, vaginal pH, sex hormones in the blood (estradiol and follicular stimulating hormone), and urinary equol concentration. Results: In the vaginal microbiota of premenopausal women, Lactobacillus species constituted approximately 71.98%, and pathogenic flora constituted approximately 16.87%. They were 10.08% and 26.78%, respectively, in the vaginal microbiota of postmenopausal women. Therefore, the proportion of Lactobacillus was significantly low, whereas microbial diversity and vaginal pH were significantly high (p<0.0001) in postmenopausal women. The compositions of the vaginal microbiota were significantly different in pre- and postmenopausal women. However, such differences were not noticeable in the gut microbiota. Urinary equol production had no significant correlation with vaginal microbiota, although it had significant relationships with gut microbiota in postmenopausal women. There were significant correlations among bacterial species in the gut and vaginal microbiota, especially in postmenopausal women. In both groups, the proportions of vaginal Lactobacillus were inversely correlated with vaginal microbial diversity and vaginal pH. Conclusion: Postmenopausal women had significantly low lactobacillus and high pathogenic flora in their vaginal flora, whereas such age-related differences were not identified in gut microbiota. There were significant correlations among the bacterial species inhabiting the gut and vaginal microbiota, especially in postmenopausal women, indicating potential crosstalk between each other.

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Microbial Diversity Profiling of Gut Microbiota of Macropus giganteus Using Three Hypervariable Regions of the Bacterial 16S rRNA

Microorganisms ◽

10.3390/microorganisms9081721 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1721

Author(s):

Christian O’Dea ◽

Roger Huerlimann ◽

Nicole Masters ◽

Anna Kuballa ◽

Cameron Veal ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Microbial Diversity ◽

Surface Waters ◽

Bacterial Species ◽

Rrna Gene ◽

Faecal Contamination ◽

Hypervariable Regions ◽

Geographical Regions ◽

V3 Region

Animal faecal contamination of surface waters poses a human health risk, as they may contain pathogenic bacteria or viruses. Of the numerous animal species residing along surface waterways in Australia, macropod species are a top contributor to wild animals’ faecal pollution load. We characterised the gut microbiota of 30 native Australian Eastern Grey Kangaroos from six geographical regions (five kangaroos from each region) within South East Queensland in order to establish their bacterial diversity and identify potential novel species-specific bacteria for the rapid detection of faecal contamination of surface waters by these animals. Using three hypervariable regions (HVRs) of the 16S rRNA gene (i.e., V1–V3, V3–V4, and V5–V6), for their effectiveness in delineating the gut microbial diversity, faecal samples from each region were pooled and microbial genomic DNA was extracted, sequenced, and analysed. Results indicated that V1-V3 yielded a higher taxa richness due to its larger target region (~480 bp); however, higher levels of unassigned taxa were observed using the V1-V3 region. In contrast, the V3–V4 HVR (~569 bp) attained a higher likelihood of a taxonomic hit identity to the bacterial species level, with a 5-fold decrease in unassigned taxa. There were distinct dissimilarities in beta diversity between the regions, with the V1-V3 region displaying the highest number of unique taxa (n = 42), followed by V3–V4 (n = 11) and V5–V6 (n = 8). Variations in the gut microbial diversity profiles of kangaroos from different regions were also observed, which indicates that environmental factors may impact the microbial development and, thus, the composition of the gut microbiome of these animals.

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Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention

Clinical and Vaccine Immunology ◽

10.1128/cvi.00762-14 ◽

2015 ◽

Vol 22 (5) ◽

pp. 526-538 ◽

Cited By ~ 42

Author(s):

Jordan K. Kyongo ◽

Tania Crucitti ◽

Joris Menten ◽

Liselotte Hardy ◽

Piet Cools ◽

...

Keyword(s):

Proinflammatory Cytokines ◽

Genital Tract ◽

Bacterial Species ◽

Vaginal Microbiota ◽

African Women ◽

Sexually Active ◽

Cross Sectional ◽

Content Type ◽

Immune Mediators ◽

Sub Saharan

ABSTRACTData on immune mediators in the genital tract and the factors that modulate them in sub-Saharan women are limited. Cervicovaginal lavage (CVL) samples from 430 sexually active women from Kenya, South Africa, and Rwanda were analyzed for 12 soluble immune mediators using Bio-Plex and Meso Scale Discovery multiplex platforms, as well as single enzyme-linked immunosorbent assays. Ten bacterial species were quantified in vaginal swab samples. Bacterial vaginosis (BV) was defined by Nugent scoring. CVL samples from HIV-infected women showed a clear-cut proinflammatory profile. Pregnant women, adolescents, and women engaging in traditional vaginal practices differed in specific soluble markers compared to reference groups of adult HIV-negative women. Cervical mucus, cervical ectopy, abnormal vaginal discharge, and having multiple sex partners were each associated with an increase in inflammatory mediators. The levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12(p70), and IL-8 were elevated, whereas the IL-1RA/IL-1(α+β) ratio decreased in women with BV. The level of gamma interferon-induced protein 10 was lower in BV-positive than in BV-negative women, suggesting its suppression as a potential immune evasion mechanism by BV-associated bacteria.Lactobacillus crispatusandLactobacillus vaginaliswere associated with decreased proinflammatory cytokines and each BV-associated species with increased proinflammatory cytokines. Remarkably, thein vitroanti-HIV activity of CVL samples from BV-positive women was stronger than that of BV-negative women. In conclusion, we found significant associations of factors, including vaginal microbiota, which can influence immune mediators in the vaginal environment in sexually active women. These factors need to be considered when establishing normative levels or pathogenic cutoffs of biomarkers of inflammation and associated risks in African women.

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Dietary modulation of the gut microbiota – a randomised controlled trial in obese postmenopausal women

British Journal Of Nutrition ◽

10.1017/s0007114515001786 ◽

2015 ◽

Vol 114 (3) ◽

pp. 406-417 ◽

Cited By ~ 70

Author(s):

Lena K. Brahe ◽

Emmanuelle Le Chatelier ◽

Edi Prifti ◽

Nicolas Pons ◽

Sean Kennedy ◽

...

Keyword(s):

Insulin Sensitivity ◽

Gut Microbiota ◽

Postmenopausal Women ◽

Relative Abundance ◽

Controlled Trial ◽

Bacterial Species ◽

Daily Intake ◽

Oral Glucose ◽

Linear Regression Models ◽

Metabolic Markers

The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions withLactobacillus paracaseiF19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single-blinded, parallel-group intervention of 6-week duration, with a daily intake of eitherL. paracaseiF19 (9·4 × 1010colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test (P< 0·05) and improved insulin sensitivity measured by Matsuda index (P< 0·05). Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species (P< 0·01), including decreased relative abundance of eightFaecalibacteriumspecies. These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity. The intake ofL. paracaseiF19 did not modulate metabolic markers compared with placebo. In conclusion, flaxseed mucilage improves insulin sensitivity and alters the gut microbiota; however, the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species.

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Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia

Nutrients ◽

10.3390/nu11071633 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1633 ◽

Cited By ~ 36

Author(s):

Andrea Ticinesi ◽

Antonio Nouvenne ◽

Nicoletta Cerundolo ◽

Pamela Catania ◽

Beatrice Prati ◽

...

Keyword(s):

Gut Microbiota ◽

Physical Function ◽

Muscle Mass ◽

Physical Performance ◽

Microbiota Composition ◽

Physical Frailty ◽

Deficit Accumulation ◽

Cross Sectional ◽

Age Related ◽

And Function

Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as Faecalibacterium and Bifidobacterium, and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.

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Novel associations between sex hormones and diabetic vascular complications in men and postmenopausal women: a cross-sectional study

Cardiovascular Diabetology ◽

10.1186/s12933-019-0901-6 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 7

Author(s):

Chiyu Wang ◽

Wen Zhang ◽

Yuying Wang ◽

Heng Wan ◽

Yi Chen ◽

...

Keyword(s):

Postmenopausal Women ◽

Sex Hormones ◽

Vascular Complications ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Diabetic Vascular Complications ◽

Novel Associations

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Gut and Vagina Microbiota Associated With Estrus Return of Weaning Sows and Its Correlation With the Changes in Serum Metabolites

Frontiers in Microbiology ◽

10.3389/fmicb.2021.690091 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jia Zhang ◽

Min Liu ◽

Shanlin Ke ◽

Xiaochang Huang ◽

Shaoming Fang ◽

...

Keyword(s):

Gut Microbiota ◽

Sex Hormones ◽

16S Rrna Gene Sequencing ◽

Vaginal Microbiota ◽

Rrna Gene ◽

Metabolome Analysis ◽

Galactose Metabolism ◽

Serum Metabolites ◽

Rrna Gene Sequencing ◽

Functional Capacities

More and more studies have indicated that gut microbiota takes part in the biosynthesis and metabolism of sex hormones. Inversely, sex hormones influence the composition of gut microbiota. However, whether microbiota in the gut and vagina is associated with estrus return of weaning sows is largely unknown. Here, using 16S rRNA gene sequencing in 158 fecal and 50 vaginal samples, we reported the shifts in the gut and vaginal microbiota between normal return and non-return sows. In fecal samples, Lactobacillus and S24-7 were enriched in normal return sows, while Streptococcus luteciae, Lachnospiraceae, Clostridium, and Mogibacterium had higher abundance in non-return sows. In vaginal swabs, the operational taxonomic units (OTUs) annotated to Clostridiales, Ruminoccaceae, and Oscillospira were enriched in normal return sows, while those OTUs annotated to Campylobacter, Anaerococcus, Parvimonas, Finegoldia, and Dorea had higher abundances in non-return sows. Co-abundance group (CAG) analysis repeated the identification of the bacterial taxa associated with the estrus return of weaning sows. The predicted functional capacities in both gut and vaginal microbiome were changed between normal return and non-return sows. Serum metabolome profiles were determined by non-targeted metabolome analysis in seven normal return and six non-return sows. The metabolite features having higher abundance in normal return sows were enriched in the pathways Steroid hormone biosynthesis, Starch and sucrose metabolism, Galactose metabolism, and Vitamin B6 metabolism, while the metabolite features belonging to organic acids and derivatives, indoles and derivatives, sulfoxides, and lignans and neolignans had significantly higher abundance in non-return sows. Correlation analysis found that the changes in gut microbiota were associated with the shifts of serum metabolites and suggested that certain bacteria might affect estrus return of weaning sow through serum metabolites. These findings may provide new insights for understanding the role of the gut and vaginal microbiota in sow return to estrus after weaning.

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Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-02799 ◽

2018 ◽

Vol 103 (7) ◽

pp. 2552-2562 ◽

Cited By ~ 43

Author(s):

María Insenser ◽

Mora Murri ◽

Rosa del Campo ◽

M Ángeles Martínez-García ◽

Elena Fernández-Durán ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Gut Microbiota ◽

Bacterial Diversity ◽

Sex Hormones ◽

Polycystic Ovary ◽

Tolerance Test ◽

Cross Sectional Study ◽

Oral Glucose ◽

Ovary Syndrome ◽

Cross Sectional

Abstract Context Gut microbiota play a major role in health and disease by influencing physiology, metabolism, nutrition, and immune function. Objective To evaluate the composition of gut microbiota in women with polycystic ovary syndrome (PCOS), focusing on the influence of sex, sex hormones and obesity on the associations found. Design Cross-sectional study. Setting Academic hospital. Participants We recruited 15 women with PCOS, 16 nonhyperandrogenic control women, and 15 control men. Participants were classified as nonobese (<30 kg/m2) or obese (≥30 kg/m2) according to their body mass index. Interventions Standardization of diet for 3 consecutive days (at least 300 g of carbohydrates per day) followed by fecal sampling and a standard 75-g oral glucose tolerance test. Main Outcome Measures Analysis of bacterial abundance and composition of gut microbiota by massive sequencing of 16S ribosomal DNA amplicons in a MiSeq platform (Illumina). Results α Bacterial diversity was reduced in women compared with men, and β diversity was reduced particularly in obese patients with PCOS. Women with PCOS presented with specific abnormalities in gut microbiota consisting of an increased abundance of the Catenibacterium and Kandleria genera. When all participants as a whole were considered, indexes of bacterial diversity and the abundance of several bacterial genera correlated positively with serum androgen concentrations and negatively with estradiol levels. Conclusions The diversity and composition of the gut microbiota of young adults are influenced by the combined effects of sex, sex hormone concentrations, and obesity, presenting with specific abnormalities in women with PCOS.

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Cross-sectional and prospective relationships of endogenous progestogens and estrogens with glucose metabolism in men and women: a KORA F4/FF4 Study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001951 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001951

Author(s):

Lina Hui Ying Lau ◽

Jana Nano ◽

Alexander Cecil ◽

Florian Schederecker ◽

Wolfgang Rathmann ◽

...

Keyword(s):

Postmenopausal Women ◽

Sex Hormones ◽

Positive Association ◽

Population Based ◽

Sensitivity Analyses ◽

German Population ◽

Fasting Insulin ◽

Cross Sectional ◽

Female Sex ◽

Female Sex Hormones

IntroductionRelationships between endogenous female sex hormones and glycemic traits remain understudied, especially in men. We examined whether endogenous 17α-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and free estradiol (fE2) were associated with glycemic traits and glycemic deterioration.Research design and methods921 mainly middle-aged and elderly men and 390 perimenopausal/postmenopausal women from the German population-based Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort study were followed up for a median of 6.4 years. Sex hormones were measured at baseline using mass spectrometry. We calculated regression coefficients (β) and ORs with 95% CIs using multivariable-adjusted linear and logistic regression models for Z-standardized hormones and glycemic traits or glycemic deterioration (ie, worsening of categorized glucose tolerance status), respectively.ResultsIn the cross-sectional analysis (n=1222 men and n=594 women), in men, 17-OHP was inversely associated with 2h-glucose (2hG) (β=−0.067, 95% CI −0.120 to −0.013) and fasting insulin (β=−0.074, 95% CI −0.118 to −0.030), and positively associated with Quantitative Insulin Sensitivity Check Index (QUICKI) (β=0.061, 95% CI 0.018 to 0.105). Progesterone was inversely associated with fasting insulin (β=−0.047, 95% CI −0.088 to −0.006) and positively associated with QUICKI (β=0.041, 95% CI 0.001 to 0.082). E2 was inversely associated with fasting insulin (β=−0.068, 95% CI −0.116 to −0.020) and positively associated with QUICKI (β=0.059, 95% CI 0.012 to 0.107). fE2 was positively associated with glycated hemoglobin (HbA1c) (β=0.079, 95% CI 0.027 to 0.132). In women, 17-OHP was positively associated with fasting glucose (FG) (β=0.068, 95% CI 0.014 to 0.123). fE2 was positively associated with FG (β=0.080, 95% CI 0.020 to 0.141) and HbA1c (β=0.121, 95% CI 0.062 to 0.180). In the sensitivity analyses restricted to postmenopausal women, we observed a positive association between 17-OHP and glycemic deterioration (OR=1.518, 95% CI 1.033 to 2.264).ConclusionsInter-relations exist between female sex hormones and glucose-related traits among perimenopausal/postmenopausal women and insulin-related traits among men. Endogenous progestogens and estrogens appear to be involved in glucose homeostasis not only in women but in men as well. Further well-powered studies assessing causal associations between endogenous female sex hormones and glycemic traits are warranted.

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A multidisciplinary approach to mental illness: do inflammation, telomere length and microbiota form a loop? A protocol for a cross-sectional study on the complex relationship between inflammation, telomere length, gut microbiota and psychiatric disorders

BMJ Open ◽

10.1136/bmjopen-2019-032513 ◽

2020 ◽

Vol 10 (1) ◽

pp. e032513 ◽

Cited By ~ 2

Author(s):

Mirko Manchia ◽

Pasquale Paribello ◽

Carlo Arzedi ◽

Alberto Bocchetta ◽

Paola Caria ◽

...

Keyword(s):

Gut Microbiota ◽

Psychiatric Disorders ◽

Telomere Length ◽

Cross Sectional Study ◽

University Hospital ◽

Sectional Study ◽

Cross Sectional ◽

Telomere Shortening ◽

Age Related ◽

The University

IntroductionSevere psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.Methods and analysisA cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychiatric controls. Each group includes individuals suffering, or not, from age-related comorbidities, to account for the impact of these medical conditions on the biological make-up of recruited patients. The inflammatory state, microbiota composition and telomere length (TL) are assessed.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5 September 2018). The study is conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki, and in compliance with the relevant Italian national legislation. Written, informed consent is obtained from all participants. Participation in the study is on a voluntary basis only. Patients will be part of the dissemination phase of the study results, during which a local conference will be organised and families of patients will also be involved. Moreover, findings will be published in one or more research papers and presented at national and international conferences, in posters or oral communications.

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