Rectal Microbiome Alterations Associated With Oral Human Immunodeficiency Virus Pre-Exposure Prophylaxis

From BugSigDB
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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Fulcher JA, Li F, Cook RR, Zabih S, Louie A, Okochi H, Tobin NH, Gandhi M, Shoptaw S, Gorbach PM, Aldrovandi GM
Journal
Open forum infectious diseases
Year
2019
Keywords:
men who have sex with men (MSM), pre-exposure prophylaxis (PrEP), rectal microbiome
Background: Oral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is highly effective for HIVprevention, yet long-term effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM). Methods: This cross-sectional analysis included HIV-negative MSM either on PrEP (n = 37) or not (n = 37) selected from an ongoing cohort using propensity score matching. Rectal swabs were used to examine microbiome composition using 16S ribosomal ribonucleic acid gene sequencing, and associations between PrEP use and microbiota abundance were examined. Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants (n = 15). Results: Pre-exposure prophylaxis use was associated with a significant increase in Streptococcus abundance (adjusted P = .015). Similar associations were identified using least absolute shrinkage and selection operator (LASSO) regression, confirming the increase in Streptococcus and also showing increased Mitsuokella, Fusobacterium, and decreased Escherichia/Shigella. Increased Fusobacterium was significantly associated with increasing TFV exposure. Conclusions: Oral TDF/FTC for PrEP is associated with rectal microbiome changes compared to well matched controls, specifically increased Streptococcus and Fusobacterium abundance. This study highlights the need for future investigations of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP.

Experiment 1


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks, Chikamso, Victoria

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Rectum Intestinum rectum,Rectal sac,Terminal portion of intestine,Terminal portion of large intestine,Rectum,rectum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV/AIDS pre-exposure prophylaxis AIDS pre-exposure prophylaxis,HIV pre-exposure prophylaxis,HIV/AIDS pre-exposure prophylaxis,hIV/AIDS pre-exposure prophylaxis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV-negative MSM not on PrEP
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV-negative MSM on PrEP
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
HIV-negative Men who have sex with men (MSM) on HIV pre-exposure prophylaxis (PrEP)
Group 0 sample size Number of subjects in the control (unexposed) group
37
Group 1 sample size Number of subjects in the case (exposed) group
37

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
Linear Regression
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age, alcohol drinking, drug dependence, ethnic group, nicotine dependence, obesity, anal intercourse, marijuana, race

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Michael Lutete

Revision editor(s): WikiWorks

Source: Figure 1, Figure 2, Text

Description: Pre-exposure prophylaxis use associates with differential abundance of specific bacterial genera

Abundance in Group 1: increased abundance in HIV-negative MSM on PrEP

NCBI Quality ControlLinks
Streptococcus
Fusobacterium
Mitsuokella

Revision editor(s): WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: Michael Lutete

Revision editor(s): WikiWorks

Source: Figure 1, Figure 2, Text

Description: Pre-exposure prophylaxis use associates with differential abundance of specific bacterial genera

Abundance in Group 1: decreased abundance in HIV-negative MSM on PrEP

NCBI Quality ControlLinks
Escherichia
Shigella

Revision editor(s): WikiWorks

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks, Chikamso, Victoria

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test
Zero-inflated negative binomial regression Statistical test: "Zero-inflated negative binomial regression" is not in the list (ANCOM, ANOSIM, ANOVA, Beta Binomial Regression, Chi-Square, Cox Proportional-Hazards Regression, Dunn's test, DESeq2, edgeR, Fisher's Exact Test, ...) of allowed values.
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Michael Lutete

Revision editor(s): WikiWorks

Source: Figure 2, Text

Description: Pre-exposure prophylaxis use associates with differential abundance of specific bacterial genera

Abundance in Group 1: increased abundance in HIV-negative MSM on PrEP

NCBI Quality ControlLinks
Streptococcus

Revision editor(s): WikiWorks