Search

Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium globally. Endocervical and vaginal microbiome interactions are rarely examined within the context of Ct or among vulnerable populations. We evaluated 258 vaginal and 92 paired endocervical samples from Fijian women using metagenomic shotgun sequencing. Over 37% of the microbiomes could not be classified into sub-community state types (subCSTs). We, therefore, developed subCSTs IV-D0, IV-D1, IV-D2, and IV-E-dominated primarily by Gardnerella vaginalis-to improve classification. Among paired microbiomes, the endocervix had a significantly higher alpha diversity and, independently, higher diversity for high-risk human papilloma virus (HPV) genotypes compared to low-risk and no HPV. Ct-infected endocervical networks had smaller clusters without interactions with potentially beneficial Lactobacillus spp. Overall, these data suggest that G. vaginalis may generate polymicrobial biofilms that predispose to and/or promote Ct and possibly HPV persistence and pathogenicity. Our findings expand on the existing repertoire of endocervical and vaginal microbiomes and fill in knowledge gaps regarding Pacific Islanders.

Gender-affirming hormone therapy (GAHT) is often prescribed to transgender (TG) adolescents to alleviate gender dysphoria, but the effect of GAHT on the growing skeleton is unclear. We found GAHT to improve trabecular bone structure via increased bone formation in young male mice and not to affect trabecular structure in female mice. GAHT modified gut microbiome composition in both male and female mice. However, fecal microbiota transfers (FMTs) revealed that GAHT-shaped gut microbiome was a communicable regulator of bone structure and turnover in male, but not in female mice. Mediation analysis identified 2 species of Bacteroides as significant contributors to the skeletal effects of GAHT in male mice, with Bacteroides supplementation phenocopying the effects of GAHT on bone. Bacteroides have the capacity to expand Treg populations in the gut. Accordingly, GAHT expanded intestinal Tregs and stimulated their migration to the bone marrow (BM) in male but not in female mice. Attesting to the functional relevance of Tregs, pharmacological blockade of Treg expansion prevented GAHT-induced bone anabolism. In summary, in male mice GAHT stimulated bone formation and improved trabecular structure by promoting Treg expansion via a microbiome- mediated effect, while in female mice, GAHT neither improved nor impaired trabecular structure., Introduction About 80% of people who are transgender (TG) and people who are gender nonbinary in the US are on long-term gender-affirming hormone therapy (GAHT) to alleviate gender dysphoria and/ [...]

Heart failure (HF) is a significant health burden, with two major clinical subtypes: HF with reduced (HFrEF) and preserved ejection fraction (HFpEF). Blood pressure and lipid profile are established risk factors of HF. We performed univariable and multivariable Mendelian randomization (MR) analyses to assess potential causal effects of blood pressures and lipids on HF subtypes. Genetic instruments for blood pressures and lipids were derived from genome-wide association studies (GWASs) among the European participants of the UK Biobank. GWAS summaries of HFrEF and HFpEF were obtained from the meta-analysis of the European participants from the Million Veteran Program and the Vanderbilt University DNA Databank. Systolic blood pressure exhibited a supportive MR association primarily with HFpEF (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.04–1.23), while diastolic blood pressure had an independent MR association with HFrEF (OR, 1.43; 95% CI, 1.13–1.77). MR associations also supported the observation that higher levels of low-density lipoprotein cholesterol increase the risk for both subtypes (HFrEF OR, 1.10 and 95% CI, 1.05–1.17; HFpEF OR, 1.05 and 95% CI, 1.02–1.09). These findings underscore differences in HF subtype-specific risk profiles and mechanisms, which may lead to different interventional strategies for different HF subtypes. [ABSTRACT FROM AUTHOR]

The use of Monte‐Carlo (MC) p$$ p $$‐values when testing the significance of a large number of hypotheses is now commonplace. In large‐scale hypothesis testing, we will typically encounter at least somep$$ p $$‐values near the threshold of significance, which require a larger number of MC replicates than p$$ p $$‐values that are far from the threshold. As a result, some incorrect conclusions can be reached due to MC error alone; for hypotheses near the threshold, even a very large number (eg, 106$$ 1{0}^6 $$) of MC replicates may not be enough to guarantee conclusions reached using MC p$$ p $$‐values. Gandy and Hahn (GH)6‐8 have developed the only method that directly addresses this problem. They defined a Monte‐Carlo error rate (MCER) to be the probability that any decisions on accepting or rejecting a hypothesis based on MC p$$ p $$‐values are different from decisions based on idealp$$ p $$‐values; their method then makes decisions by controlling the MCER. Unfortunately, the GH method is frequently very conservative, often making no rejections at all and leaving a large number of hypotheses "undecided". In this article, we propose MERIT, a method for large‐scale MC hypothesis testing that also controls the MCER but is more statistically efficient than the GH method. Through extensive simulation studies, we demonstrate that MERIT controls the MCER while making more decisions that agree with the ideal p$$ p $$‐values than GH does. We also illustrate our method by an analysis of gene expression data from a prostate cancer study. [ABSTRACT FROM AUTHOR]

Introduction: Oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is highly effective in preventing HIV infection among men who have sex with men (MSM). The effects of consistent personal lubricant use in the rectum on tissue PrEP drug concentrations and the rectal microbiota are unknown. We investigated rectal PrEP drug concentrations and the microbiota in MSM before and after repeated rectal application of a hyperosmolar lubricant. Methods: We randomized 60 HIV-negative MSM to apply 4 mL of hyperosmolar rectal lubricant daily (n = 20), take daily oral TDF/FTC (n = 19), or both (n = 21) for seven days. Blood, rectal biopsies and rectal secretions were collected via rigid sigmoidoscopy before and on day 8 after product use. Tenofovir (TFV) and FTC as well as their intracellular metabolites tenofovirdiphosphate (TFV-DP), FTC-triphosphate (FTC-TP) were measured by HPLC-mass spectrometry. Rectal mucosal microbiota was sequenced with 16S rRNA sequencing using Illumina MiSeq. Results: Seven days of lubricant application was not associated with differences in PrEP drug concentrations in rectal tissue or secretions. Lubricant use was associated with a decrease in the relative abundance of the Bacteroides genus (p = 0.01) and a non-significant increase in the Prevotella genus (p = 0.09) in the rectum. PrEP drug concentrations in rectal tissue and secretions were not associated with microbiota composition or diversity either before or after lubricant use. Conclusions: Repeated rectal application of a hyperosmolar lubricant does not affect mucosal PrEP drug concentrations but is associated with changes in the rectal microbiome. Keywords: lubricant; men who have sex with men; pre-exposure prophylaxis; anti-retroviral agents; HIV; gut microbiota, 1 | INTRODUCTION Daily oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is highly effective in preventing HIV infection, particularly among men who have sex with [...]

Objective: Electronic cigarettes have increased in popularity globally. Vaping may be associated with oral symptoms and pathologies including dental and periodontal damage, both of which have an underlying microbial etiology. The primary aim of this pilot study, therefore, was to compare the oral microbiome of vapers and non‐vapers. Subjects and Methods: This secondary data analysis had a cross‐sectional comparative descriptive design and included data for 36 adults. Bacterial 16S rRNA genes were extracted and amplified from soft tissue oral swab specimens and taxonomically classified using the Human Oral Microbiome Database. Results: Data for 18 vapers and 18 non‐vapers were included in this study. Almost 56% of the vapers also smoked conventional cigarettes. Beta diversity differences were identified between vapers and non‐vapers. Vapers had a significantly higher relative abundance of an unclassified species of Veillonella compared with non‐vapers. Dual users had higher alpha diversity compared with exclusive vapers. Beta diversity was also associated with dual use. Multiple OTUs were identified to be associated with dual use of e‐cigarettes and conventional cigarettes. Conclusions: Vapers exhibit an altered oral microbiome. Dual use of electronic cigarettes and conventional cigarettes is associated with the presence of several known pathogenic microbes. [ABSTRACT FROM AUTHOR]

Introduction: We previously showed that the rectal mucosal immune environment among men who have sex with men (MSM) engaging in condomless receptive anal intercourse (CRAI) is immunologically distinct from that of men who do not engage in anal intercourse (AI). Here, we further examined these differences with quantitative immunohistochemistry to better understand the geographic distribution of immune markers of interest. Methods: We enrolled a cohort of MSM engaging in CRAI (n = 41) and men who do not engage in AI (n = 21) between October 2013 and April2015. Participants were healthy, HIV-negative men aged 18-45 from the metro Atlanta area. We performed rectal mucosal sampling via rigid sigmoidoscopy during two study visits separated by a median of nine weeks and timed with sexual activity for MSM engaging in CRAI. We used standardized, automated immunohistochemistry and quantitative image analysis to investigate the rectal mucosal distribution of neutrophils (MPO), IL-17-producing cells (IL-17) and [T.sub.regs] (FOXP3) in the lamina propria, and cellular proliferation (Ki67) and adherens junction protein (E-cadherin) in the epithelium. We examined associations between biomarker expression and the rectal mucosal microbiota composition by 16s rRNA sequencing. Results: Relative to the colonic crypt base, IL-17, FOXP3, and MPO expression increased towards the rectallumen, while Ki67 decreased and E-cadherin was more uniformly distributed. Throughout the rectal mucosa distribution examined, MSM engaging in CRAI had higher mean lamina propria MPO expression (p = 0.04) and epithelialKi67 (p = 0.04) compared to controls. There were no significant differences in IL-17, FOXP3 or E-cadherin expression. We found no significant associations of the five biomarkers with the global rectal microbiota composition or the individual taxa examined. Conclusions: Understanding the mucosal distribution of inflammatory mediators can enhance our knowledge of the earliest events in HIV transmission. Neutrophil enrichment and crypt epithelial cell proliferation likely represent sub-clinical inflam-mation in response to CRAI in the rectal mucosa of MSM, which could increase the risk for HIV acquisition. However, the contributory role of the microbiota in mucosal inflammation among MSM remains unclear. HIV prevention may be enhanced by interventions that reduce inflammation or capitalize on the presence of specific inflammatory mechanisms during HIV exposure. Keywords: men who have sex with men; rectal mucosa; HIV transmission; receptive anal intercourse; mucosal immunology; microbiome, 1 | INTRODUCTION From 2013 to 2017 in the United States, 72% of new HIV infections occurred among men who have sex with men (MSM), with approximately 70% attributed to [...]