Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect Pr<scp>EP</scp> drug concentrations: results from a randomized trial in men who have sex with men

Haaland, Richard E.; Fountain, Jeffrey J.; Hu, Yingtian; Holder, Angela; Dinh, Chuong; Hall, LaShonda; Pescatore, Nicole A.; Heeke, Sheila; Hart, Clyde E.; Xu, Jiahui; Hu, Yi‐Juan; Kelley, Colleen F.

doi:10.1002/jia2.25199

Cited by 15 publications

(10 citation statements)

References 46 publications

(63 reference statements)

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“…We found very little bacterial protein-based compositional similarity between matching neovaginal and rectal profiles based on bacterial proteins measured, although we were underpowered to properly evaluate this comparison. The rectal microbial profiles observed in our study were similar to those of other studies particularly those that examined rectal/anal microbiomes of CW as well as men who have sex with men where Prevotella and Bacteroides were most abundant [24][25][26].…”

Section: Discussionsupporting

confidence: 84%

The neovaginal microbiome of transgender women post-gender reassignment surgery

et al. 2020

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Background: Gender reassignment surgery is a procedure some transgender women (TW) undergo for genderaffirming purposes. This often includes the construction of a neovagina using existing penile and scrotal tissue and/ or a sigmoid colon graft. There are limited data regarding the composition and function of the neovaginal microbiome representing a major gap in knowledge in neovaginal health. Results: Metaproteomics was performed on secretions collected from the neovaginas (n = 5) and rectums (n = 7) of TW surgically reassigned via penile inversion/scrotal graft with (n = 1) or without (n = 4) a sigmoid colon graft extension and compared with secretions from cis vaginas (n = 32). We identified 541 unique bacterial proteins from 38 taxa. The most abundant taxa in the neovaginas were Porphyromonas (30.2%), Peptostreptococcus (9.2%), Prevotella (9.0%), Mobiluncus (8.0%), and Jonquetella (7.2%), while cis vaginas were primarily Lactobacillus and Gardnerella. Rectal samples were mainly composed of Prevotella and Roseburia. Neovaginas (median Shannon's H index = 1.33) had higher alpha diversity compared to cis vaginas (Shannon's H = 0.35) (p = 7.2E−3, Mann-Whitney U test) and were more similar to the non-Lactobacillus dominant/polymicrobial cis vaginas based on beta diversity (perMANOVA, p = 0.001, r 2 = 0.342). In comparison to cis vaginas, toll-like receptor response, amino acid, and shortchain fatty acid metabolic pathways were increased (p < 0.01), while keratinization and cornification proteins were decreased (p < 0.001) in the neovaginal proteome. Conclusions: Penile skin-lined neovaginas have diverse, polymicrobial communities that show similarities in composition to uncircumcised penises and host responses to cis vaginas with bacterial vaginosis (BV) including increased immune activation pathways and decreased epithelial barrier function. Developing a better understanding of microbiome-associated inflammation in the neovaginal environment will be important for improving our knowledge of neovaginal health.

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Section: Discussionsupporting

confidence: 84%

The neovaginal microbiome of transgender women post-gender reassignment surgery

et al. 2020

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“…This is consistent with prior evidence that neutrophils and IL-17-producing cells are important inflammatory mediators within the gastrointestinal (GI) mucosa [16,17]. We also discovered a microbiome that was enriched for the Prevotellaceae over Bacteroidaceae family, and in another study [18], that repeated rectal hyperosmolar lubricant application was associated with a microbiome shift favouring Prevotellaceae over Bacteroidaceae. We hypothesize that this distinct rectal mucosal immune milieu could be attributed to repeated mucosal immune responses to intercourse with antigenic mucosal exposure to the gut microbiome during intercourse and/or semen exposure, and/or rectal product use [19,20].…”

Section: Introductionsupporting

confidence: 91%

Condomless receptive anal intercourse is associated with markers of mucosal inflammation in a cohort of men who have sex with men in Atlanta, Georgia

et al. 2021

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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 April 2015. 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 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 rectal lumen, 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 epithelial Ki67 (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 inflammation 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.

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“…Many of these lubricants are hyperosmolar and have been linked to epithelial damage in the distal colon as well as to an increased risk of acquisition of rectal gonorrhea and chlamydia [117,118]. A small study of MSM randomized to apply daily hyperosmolar rectal lubricant (N = 20), take daily oral pre-exposure prophylaxis (PrEP) (N = 19) or both (N = 21) for 7 days found that lubricant users had a decrease in the genus Bacteroides (p = 0.01) and a non-significant increase in the genus Prevotella (p = 0.09) in rectal mucosal swabs [119]. There is no other available data on this topic to our knowledge.…”

Section: Non-us/europementioning

confidence: 99%

HIV, Sexual Orientation, and Gut Microbiome Interactions

2020

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Recent studies have raised interest in the possibility that dysbiosis of the gut microbiome (i.e., the communities of bacteria residing in the intestine) in HIV-infected patients could contribute to chronic immune activation, and, thus, to elevated mortality and increased risk of inflammation-related clinical diseases (e.g., stroke, cardiovascular disease, cancer, long-bone fractures, and renal dysfunction) found even in those on effective antiretroviral therapy. Yet, to date, a consistent pattern of HIV-associated dysbiosis has not been identified. What is becoming clear, however, is that status as a man who has sex with men (MSM) may profoundly impact the structure of the gut microbiota, and that this factor likely confounded many HIVrelated intestinal microbiome studies. However, what factor associated with MSM status drives these gut microbiota-related changes is unclear, and what impact, if any, these changes may have on the health of MSM is unknown. In this review, we outline available data on changes in the structure of the gut microbiome in HIV, based on studies that controlled for MSM status. We then examine what is known regarding the gut microbiota in MSM, and consider possible implications for research and the health of this population. Lastly, we discuss knowledge gaps and needed future studies.

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Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect PrEP drug concentrations: results from a randomized trial in men who have sex with men

Cited by 15 publications

References 46 publications

The neovaginal microbiome of transgender women post-gender reassignment surgery

The neovaginal microbiome of transgender women post-gender reassignment surgery

Condomless receptive anal intercourse is associated with markers of mucosal inflammation in a cohort of men who have sex with men in Atlanta, Georgia

HIV, Sexual Orientation, and Gut Microbiome Interactions

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