In October of 2020, researchers from around the world met online for the sixth annual International Workshop on Microbiome in HIV Pathogenesis, Prevention, and Treatment. New research was presented on the roles of the microbiome on immune response and HIV transmission and pathogenesis and the potential for alterations in the microbiome to decrease transmission and affect comorbidities. This article presents a summary of the findings reported.
Get full access to this article
View all access options for this article.
References
1.
WilliamsB, MirmonsefP, BoucherCAB, et al.: A summary of the first HIV microbiome workshop 2015. AIDS Res Hum Retroviruses, 2016; 32:935–941.
2.
WilliamsB, GhoshM, BoucherCAB, et al.: A summary of the second annual HIV microbiome workshop. AIDS Res Hum Retroviruses, 2017; 33:1258–1264.
3.
WilliamsB, BoucherC, BushmanF, et al.: A summary of the third annual HIV microbiome workshop. AIDS Res Hum Retroviruses, 2018; 34:828–834.
4.
WilliamsB, GhoshM, BoucherCAB, et al.: A summary of the fourth annual virology education HIV microbiome workshop. AIDS Res Hum Retroviruses, 2020; 36:349–356.
5.
Sherrill-MixS, ConnorsK, AldrovandiGM, et al.: A summary of the fifth annual Virology Education HIV Microbiome workshop. AIDS Res Hum Retroviruses, 2020; 36:886–895.
6.
Van BelleghemJ, DabrowskaK, VaneechoutteM, BarrJ, BollykyP: Interactions between bacteriophage, bacteria, and the mammalian immune system. Viruses, 2018; 11:10.
7.
ZhangL, ForstCV, GordonA, et al.: Characterization of antibiotic resistance and host-microbiome interactions in the human upper respiratory tract during influenza infection. Microbiome, 2020; 8:39.
8.
DoudnaJA, CharpentierE: The new frontier of genome engineering with CRISPR-Cas9. Science, 2014; 346:1258096.
9.
GulinoK, RahmanJ, BadriM, MortonJ, BonneauR, GhedinE: Initial mapping of the New York City wastewater virome. mSystems, 2020; 5:e00876-19.
10.
MorrisonCS, ChenP-L, KwokC, et al.: Hormonal contraception and the risk of HIV acquisition: An individual participant data meta-analysis. PLoS Med, 2015; 12:e1001778.
11.
Evidence for Contraceptive Options and HIV Outcomes (ECHO) TrialConsortium: HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: A randomised, multicentre, open-label trial. Lancet, 2019; 394:303–313.
12.
HapgoodJP: ECHO: Context and limitations. Lancet, 2020; 395:e22.
ThurmanAR, SchwartzJL, RavelJ, et al.: Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/levonorgestrel vaginal rings. PLoS One, 2019; 14:e0217229.
18.
YangL, HaoY, HuJ, et al.: Differential effects of depot medroxyprogesterone acetate administration on vaginal microbiome in hispanic white and black women. Emerg Microbes Infect, 2019; 8:197–210.
19.
HaddadLB, WallKM, KilembeW, et al.: Bacterial vaginosis modifies the association between hormonal contraception and HIV acquisition. AIDS, 2018; 32:595–604.
20.
WesselsJM, FelkerAM, DupontHA, KaushicC: The relationship between sex hormones, the vaginal microbiome and immunity in HIV-1 susceptibility in women. Dis Model Mech, 2018; 11:dmm035147.
21.
Abdool KarimQ, Abdool KarimSS, FrohlichJA, et al.: Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science, 2010; 329:1168–1174.
22.
Noël-RomasL, PernerM, MolatlhegiR, et al.: Vaginal microbiome-hormonal contraceptive interactions associate with the mucosal proteome and HIV acquisition. PLoS Pathog, 2020; 16:e1009097.
23.
SullivanPS, SalazarL, BuchbinderS, SanchezTH: Estimating the proportion of HIV transmissions from main sex partners among men who have sex with men in five US cities. AIDS, 2009; 23:1153–1162.
KelleyCF, KraftCS, de ManTJB, et al.: The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: Implications for HIV transmission and prevention. Mucosal Immunol, 2017; 10:996–1007.
26.
KelleyCF, PollackI, YacoubR, et al.: Condomless receptive anal intercourse is associated with markers of mucosal injury in a cohort of men who have sex with men. SSRN Electron J, 2020. DOI: 10.2139/ssrn.3710617.
27.
HaalandRE, FountainJ, HuY, et al.: 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. J Int AIDS Soc, 2018; 21:e25199.
28.
KlaseZ, OrtizA, DeleageC, MuddJC, et al.: Dysbiotic bacteria translocate in progressive SIV infection. Mucosal Immunol, 2015; 8:1009–1020.
29.
Noguera-JulianM, RocafortM, GuillénY, et al.: Gut microbiota linked to sexual preference and HIV infection. EBioMedicine, 2016; 5:135–146.
30.
ArmstrongAJS, ShafferM, NusbacherNM, et al.: An exploration of prevotella-rich microbiomes in HIV and men who have sex with men. Microbiome, 2018; 6. 10.1186/s40168-018-0580-7.
31.
OrtizAM, FlynnJK, DiNapoliSR, et al.: Experimental microbial dysbiosis does not promote disease progression in SIV-infected macaques. Nat Med, 2018; 24:1313–1316.
32.
LiSX, SenS, SchneiderJM, et al.: Gut microbiota from high-risk men who have sex with men drive immune activation in gnotobiotic mice and in vitro HIV infection. PLoS Pathog, 2019; 15:e1007611.
33.
ColemanSL, NeffPC, LiSX, et al.: Can gut microbiota of men who have sex with men influence HIV transmission?. Gut Microbes, 2020; 11:610–619.
34.
LozuponeCA, LiM, CampbellTB, et al.: Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe, 2013; 14:329–339.
35.
RayS, NarayananA, GiskeCG, NeogiU, SöennerborgA, NowakP: Altered gut microbiome under antiretroviral therapy: Impact of efavirenz and zidovudine. ACS Infect Dis, 2021; 7:1104–1115.
36.
PimentelM, LemboA, CheyWD, et al.: Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med, 2011; 364:22–32.
37.
ArnoldM, SierraMS, LaversanneM, SoerjomataramI, JemalA, BrayF: Global patterns and trends in colorectal cancer incidence and mortality. Gut, 2016; 66:683–691.
38.
VirostkoJ, CapassoA, YankeelovTE, GoodgameB: Recent trends in the age at diagnosis of colorectal cancer in the US National Cancer Data Base, 2004–2015. Cancer, 2019; 125:3828–3835.
39.
WirbelJ, PylPT, KartalE, et al.: Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med, 2019; 25:679–689.
40.
ThomasAM, ManghiP, AsnicarF, et al.: Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med, 2019; 25:667–678.
41.
WuS, RheeK-J, AlbesianoE, et al.: A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med, 2009; 15:1016–1022.
42.
HousseauF, WuS, WickEC, et al.: Redundant innate and adaptive sources of IL17 production drive colon tumorigenesis. Cancer Res, 2016; 76:2115–2124.
43.
ChungL, Thiele OrbergE, GeisAL, et al.: Bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells. Cell Host Microbe, 2018; 23:203.e5–214.e5.
AllenJ, SearsCL: Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: Contributions to colorectal cancer development. Genome Med, 2019; 11:11.
46.
DejeaCM, WickEC, HechenbleiknerEM, et al.: Microbiota organization is a distinct feature of proximal colorectal cancers. Proc Natl Acad Sci U S A, 2014; 111:18321–18326.
47.
JohnsonCH, DejeaCM, EdlerD, et al.: Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab, 2015; 21:891–897.
48.
DrewesJL, WhiteJR, DejeaCM, et al.: High-resolution bacterial 16s rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia. NPJ Biofilms Microbiomes, 2017; 3:34.
49.
TomkovichS, DejeaCM, WingleeK, et al.: Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic. J Clin Invest, 2019; 129:1699–1712.
50.
DejeaCM, FathiP, CraigJM, et al.: Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science, 2018; 359:592–597.
51.
ZhangJ, HainesC, WatsonAJM, et al.: Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: A matched case-control study. Gut, 2019; 68:1971–1978.
52.
TuddenhamSA, KoayWLA, ZhaoN, WhiteJR, GhanemKG, Sears CL;H.I.V. Microbiome Re-analysis Consortium. The impact of human immunodeficiency virus infection on gut microbiota α-diversity: An individual-level meta-analysis. Clin Infect Dis, 2020; 70:615–627.
53.
SinhaR, Abu-AliG, VogtmannE, et al.: Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium. Nat Biotechnol, 2017; 35:1077–1086.
54.
VermeulenR, SchymanskiEL, BarabásiAL, MillerGW: The exposome and health: Where chemistry meets biology. Science, 2020; 367:392–396.
55.
AtashiliJ, PooleC, NdumbePM, AdimoraAA, SmithJS: Bacterial vaginosis and HIV acquisition: A meta-analysis of published studies. AIDS, 2008; 22:1493–1501.
56.
AnahtarMN, ByrneEH, DohertyKE, et al.: Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity, 2015; 42:965–976.
57.
GosmannC, AnahtarMN, HandleySA, et al.: Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women. Immunity, 2017; 46:29–37.
58.
BukusiE, ThomasKK, NgutiR, et al.: Topical penile microbicide use by men to prevent recurrent bacterial vaginosis in sex partners: A randomized clinical trial. Sex Transm Dis, 2011; 38:483–489.
59.
McClellandRS, BalkusJE, LeeJ, et al.: Randomized trial of periodic presumptive treatment with high-dose intravaginal metronidazole and miconazole to prevent vaginal infections in HIV-negative women. J Infect Dis, 2015; 211:1875–1882.
60.
FrancisSC, LookerC, VandepitteJ, et al.: Bacterial vaginosis among women at high risk for HIV in Uganda: High rate of recurrent diagnosis despite treatment. Sex Transm Infect, 2016; 92:142–148.
61.
HemmerlingA, HarrisonW, SchroederA, et al.: Phase 1 dose-ranging safety trial of Lactobacillus crispatus CTV-05 for the prevention of bacterial vaginosis. Sex Transm Dis, 2009; 36:564–569.
62.
HemmerlingA, HarrisonW, SchroederA, et al.: Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis. Sex Transm Dis, 2010; 37:745–750.
63.
CohenCR, WierzbickiMR, et al.: Randomized trial of Lactin-V to prevent recurrence of bacterial vaginosis. N Engl J Med, 2020; 382:1906–1915.
64.
LagenaurLA, HemmerlingA, ChiuC, et al.: Connecting the dots: Translating the vaginal microbiome into a drug. J Infect Dis, 2021; 223 (Supplement_3):S296–S306.
65.
HearpsAC, TyssenD, SrbinovskiD, et al.: Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition. Mucosal Immunol, 2017; 10:1480–1490.
66.
Delgado-DiazDJ, TyssenD, HaywardJA, GugasyanR, HearpsAC, TachedjianG: Distinct immune responses elicited from cervicovaginal epithelial cells by lactic acid and short chain fatty acids associated with optimal and non-optimal vaginal microbiota. Front Cell Infect Microbiol, 2020; 9:446.
67.
McMillanA, RulisaS, SumarahM, et al.: A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women. Sci Rep, 2015; 5:14174.
68.
SrinivasanS, MorganMT, FiedlerTL, et al.: Metabolic signatures of bacterial vaginosis. mBio, 2015; 6:e00204-15.
69.
YeomanCJ, ThomasSM, Berg MillerME, et al.: A multi-omic systems-based approach reveals metabolic markers of bacterial vaginosis and insight into the disease. PLoS One, 2013; 8:e56111.
70.
VitaliB, CrucianiF, PiconeG, ParolinC, DondersG, LaghiL: Vaginal microbiome and metabolome highlight specific signatures of bacterial vaginosis. Eur J Clin Microbiol Infect Dis, 2015; 34:2367–2376.
71.
HalperinDT, BaileyRC: Male circumcision and HIV infection: 10years and counting. Lancet, 1999; 354:1813–1815.
72.
AuvertB, TaljaardD, LagardeE, Sobngwi-TambekouJ, SittaR, PurenA: Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 trial. PLoS Med, 2005; 2:e298.
73.
GrayRH, KigoziG, SerwaddaD, MakumbiF, et al.: Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial. Lancet, 2007; 369:657–666.
74.
BaileyRC, MosesS, ParkerCB, et al.: Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial. Lancet, 2007; 369:643–656.
75.
ProdgerJL, GrayRH, ShannonB, et al.: Chemokine levels in the penile coronal sulcus correlate with HIV-1 acquisition and are reduced by male circumcision in Rakai, Uganda. PLoS Pathog, 2016; 12:e1006025.
76.
LiuCM, HungateBA, TobianAAR, et al.: Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria. mBio, 2013; 4:e00076.
77.
LiuCM, ProdgerJL, TobianAAR, et al.: Penile anaerobic dysbiosis as a risk factor for HIV infection. mBio, 2017; 8:e00996-17.
78.
YoderAC, GuoK, DillonSM, et al.: The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria. PLoS Pathog, 2017; 13:e1006226.
79.
HiebertPR, GranvilleDJ: Granzyme B in injury, inflammation, and repair. Trends Mol Med, 2012; 18:732–741.
DillonSM, LeeEJ, KotterCV, et al.: Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection. Mucosal Immunol, 2015; 9:24–37.
82.
DillonSM, KibbieJ, LeeEJ, et al.: Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation. AIDS, 2017; 31:511–521.
83.
TrøseidM, AndersenGO, BrochK, HovJR: The gut microbiome in coronary artery disease and heart failure: Current knowledge and future directions. EBioMedicine, 2020; 52:102649.
84.
KoethRA, WangZ, LevisonBS, et al.: Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med, 2013; 19:576–585.
85.
Wilson TangWH, WangZ, LevisonBS, et al.: Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med, 2013; 368:1575–1584.
86.
TrøseidM, UelandT, HovJR, et al.: Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med, 2015; 277:717–726.
87.
LiXS, ObeidS, KlingenbergR, et al.: Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: A prognostic marker for incident cardiovascular events beyond traditional risk factors. Eur Heart J, 2017; 38:814–824.
88.
TrøseidM: Gut microbiota and acute coronary syndromes: Ready for use in the emergency room?. Eur Heart J, 2017; 38:825–827.
89.
HaissmanJM, KnudsenA, HoelH, et al.: Microbiota-dependent marker TMAO is elevated in silent ischemia but is not associated with first-time myocardial infarction in HIV infection. J Acquir Immune Defic Syndr, 2016; 71:130–136.
90.
GelpiM, VestadB, HansenSH, et al.: Impact of human immunodeficiency virus-related gut microbiota alterations on metabolic comorbid conditions. Clin Infect Dis, 2020; 71:e359–e367.
91.
Vujkovic-CvijinI, SomsoukM: HIV and the gut microbiota: Composition, consequences, and avenues for amelioration. Curr HIV/AIDS Rep, 2019; 16:204–213.
92.
PetersenC, BellR, KlagKA, et al.: T cell-mediated regulation of the microbiota protects against obesity. Science, 2019; 365.
93.
HoelH, UelandT, KnudsenA, et al.: Soluble markers of interleukin 1 activation as predictors of first-time myocardial infarction in HIV-infected individuals. J Infect Dis, 2020; 221:506–509.
94.
Storm-LarsenC, StiksrudB, EriksenC, et al.: Microbial translocation revisited: Targeting the endotoxic potential of gut microbes in HIV-infected individuals. AIDS, 2019; 33:645–653.
95.
ZhengD, LiwinskiT, ElinavE: Interaction between microbiota and immunity in health and disease. Cell Res, 2020; 30:492–506.
96.
SkellyAN, SatoY, KearneyS, HondaK: Mining the microbiota for microbial and metabolite-based immunotherapies. Nat Rev Immunol, 2019; 19:305–323.
97.
BrenchleyJM, SchackerTW, et al.: CD T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med, 2004; 200:749–759.
98.
GuillénY, Noguera-JulianM, RiveraJ, et al.: Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection. Mucosal Immunol, 2018; 12:232–246.
99.
GonçalvesE, GuillénY, LamaJR, et al.: Host transcriptome and microbiota signatures prior to immunization profile vaccine humoral responsiveness. Front Immunol, 2021; 12.
100.
BorgognoneA, Noguera-JulianM, OriolB, et al.Gut microbiome signatures linked to HIV-1 reservoir size and viremia control. bioRxiv, 2021. 10.1101/2021.10.03.462590.
101.
PulendranB: Systems vaccinology: Probing humanity's diverse immune systems with vaccines. Proc Natl Acad Sci U S A, 2014; 111:12300–12306.
102.
QuerecTD, AkondyRS, LeeEK, et al.: Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol, 2008; 10:116–125.
103.
LiS, SullivanNL, RouphaelN, et al.: Metabolic phenotypes of response to vaccination in humans. Cell, 2017b;169:862.e17–877.e17.
104.
NakayaHI, WrammertJ, LeeEK, et al.: Systems biology of vaccination for seasonal influenza in humans. Nat Immunol, 2011; 12:786–795.
105.
OhJZ, RavindranR, ChassaingB, et al.: TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity, 2014; 41:478–492.
106.
HaganT, CorteseM, RouphaelN, et al.: Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell, 2019; 178:1313.e13–1328.e13.
107.
BasuS, ChwastiakLA, BruceRD: Clinical management of depression and anxiety in HIV-infected adults. AIDS, 2005; 19:2057–2067.
108.
BeerL, TieY, PadillaM, ShouseRL: Generalized anxiety disorder symptoms among persons with diagnosed HIV in the United States. AIDS, 2019; 33:1781–1787.
109.
BravoJA, ForsytheP, ChewMV, et al.: Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci, 2011; 108:16050–16055.