Evidence map›Paper›PMID 35042542›Full record

ArticleMicrobiome2022

Immune milieu and microbiome of the distal urethra in Ugandan men: impact of penile circumcision and implications for HIV susceptibility.

Ronald M Galiwango, Daniel E Park, Sanja Huibner, Abigail Onos, Maliha Aziz, Kelsey Roach, Aggrey Anok, James Nnamutete, Yahaya Isabirye, John Bosco Wasswa and 6 more

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Microbiome, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. HIV Transmission and Immunology of the Male Reproductive Tract.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  4. Review
  5. Anaerobe-Driven Inflammation and Epithelial Barrier Disruption in Genital HIV Acquisition.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Understanding the Associations of Urogenital Microbiomes With Fertility and In Vitro Fertilization.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025
    Review
  17. Article
  18. Review
  19. The Prevalence of Antibiotic Tolerance inPathogens (Basel, Switzerland) · 2024
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Ronald M GaliwangoDepartments of Immunology and Medicine, University of Toronto, St. George Campus, Medical Sciences Building, 1 King's College Circle, Room 6356, Toronto, Ontario, M5S1A8, Canada.
Daniel E ParkGeorge Washington Milken Institute School of Public Health, Washington, DC, USA.
Sanja HuibnerDepartments of Immunology and Medicine, University of Toronto, St. George Campus, Medical Sciences Building, 1 King's College Circle, Room 6356, Toronto, Ontario, M5S1A8, Canada.
Abigail OnosGeorge Washington Milken Institute School of Public Health, Washington, DC, USA.
Maliha AzizDepartments of Immunology and Medicine, University of Toronto, St. George Campus, Medical Sciences Building, 1 King's College Circle, Room 6356, Toronto, Ontario, M5S1A8, Canada.
Kelsey RoachGeorge Washington Milken Institute School of Public Health, Washington, DC, USA.
Aggrey AnokRakai Health Sciences Program, Kalisizo, Uganda.
James NnamuteteRakai Health Sciences Program, Kalisizo, Uganda.
Yahaya IsabiryeRakai Health Sciences Program, Kalisizo, Uganda.
John Bosco WasswaRakai Health Sciences Program, Kalisizo, Uganda.
Deo MaleRakai Health Sciences Program, Kalisizo, Uganda.
Godfrey KigoziRakai Health Sciences Program, Kalisizo, Uganda.
Aaron A R TobianJohns Hopkins University, Baltimore, MD, USA.
Jessica L ProdgerWestern University, London, Ontario, Canada.
Cindy M LiuGeorge Washington Milken Institute School of Public Health, Washington, DC, USA.
Rupert KaulDepartments of Immunology and Medicine, University of Toronto, St. George Campus, Medical Sciences Building, 1 King's College Circle, Room 6356, Toronto, Ontario, M5S1A8, Canada. Rupert.kaul@utoronto.ca.ORCID 0000-0002-1586-4093
Rakai Health Sciences Program · UGMilken Institute · USUniversity of New Brunswick · CAJohns Hopkins University · USWestern University · CA

Funding

The role of penile bacteria and inflammation in HIV susceptibility; Rakai, UgandaR01AI123002 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI LIU, CINDY · 2016 to 2020
$3.3M
Penile Microbiome, Inflammation and HIV Susceptibility During Sexual Debut and Maturation Among Male AdolescentsR01AI128779 · NIAID · JOHNS HOPKINS UNIVERSITY · PI TOBIAN, AARON A · 2017 to 2020
$2.1M
Male Circumcision and Use of Foreskin Tissues for HIV Prevention in UgandaD43TW009578 · FIC · JOHNS HOPKINS UNIVERSITY · PI GRAY, RONALD H · 2013 to 2017
$1.3M
FIC NIH HHS D43 TW009578NIAID NIH HHS R01 AI128779
6 · The paper itself

Abstract

backgroundCoronal sulcus (CS) anaerobe abundance and IL-8 levels are linked to HIV acquisition, and are dramatically reduced after penile circumcision (PC). The distal urethra may be the site of some HIV acquisition before PC, and presumably most acquisition post PC. We describe the immune milieu and microbiome of the distal urethra in uncircumcised Ugandan men, and define the impact of PC. Participants consisted of HIV-negative, genital symptom-free adult Ugandan men undergoing PC (n = 51). Urethral and coronal sulcus swabs were collected at baseline and at 6- and 12-months post-PC. Soluble immune factors were quantified by multiplex ELISA, and bacterial abundance assessed by 16S rRNA qPCR and sequencing.

resultsAt baseline, the urethra was enriched compared to the CS for most cytokines (including IL-8 and MIP-1β) and soluble E-cadherin (sE-cadherin, an epithelial disruption marker), although CS levels of IL-1α and IL-1β were higher. Baseline total bacterial abundance was ≥ 20-fold higher in the CS than the urethra (median 27,100 vs. 1200 gene copies/swab, p = 0.001), and anaerobes comprised 58% of CS bacteria vs. 42% of urethral bacteria. PC did not alter urethral IL-8 (median 806 at baseline vs. 1130 pg/ml at 12 months; p = 0.062) and urethral sE-cadherin increased (113,223 vs. 158,385 pg/ml, p = 0.009), despite five- and sevenfold drops in total bacterial and anaerobe abundance after PC, respectively. However, PC dramatically reduced CS levels of sE-cadherin (15,843 vs. 837 pg/ml, p < 0.001) and most cytokines (IL-8; 34 vs. 3 pg/ml, p < 0.001), while reducing total bacterial and anaerobe abundance by 13-fold and 60-fold, respectively (both P ≤ 0.004).

conclusionsThe urethra is immunologically rich with characteristics of an HIV-susceptible tissue site. However, PC had no impact on urethral immunology and may have reduced epithelial integrity, despite modest reductions in total bacteria and anaerobes, suggesting that HIV protection from PC is not mediated via immune or microbiome alterations in the urethra. Video abstract.

Indexed as

HIV InfectionsMicrobiotaAdultHumansMaleRNA, Ribosomal, 16SUgandaUrethraRNA, Ribosomal, 16SCoronal sulcusCytokinesHIVMicrobiomePenile circumcisionPenile urethraUganda

Identifiers

PMID35042542
PMCPMC8764836
OpenAlexW4205659437

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.