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Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status
Open accessAbstract
The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity. To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/AIDS [HIV] (n = 12), other disease controls [ODC] (n = 14) and in cerebral surgical resections for epilepsy [SURG] (n = 6). Deep sequencing of cerebral white matter-derived RNA from the HIV (n = 4) and ODC (n = 4) patients and SURG (n = 2) groups revealed bacterially-encoded 16 s RNA sequences in all brain specimens with α-proteobacteria representing over 70% of bacterial sequences while the other 30% of bacterial classes varied widely. Bacterial rRNA was detected in white matter glial cells by in situ hybridization and peptidoglycan immunoreactivity was also localized principally in glia in human brains. Analyses of amplified bacterial 16 s rRNA sequences disclosed that Proteobacteria was the principal bacterial phylum in all human brain samples with similar bacterial rRNA quantities in HIV and ODC groups despite increased host neuroimmune responses in the HIV group. Exogenous viruses including bacteriophage and human herpes viruses-4, -5 and -6 were detected variably in autopsied brains from both clinical groups. Brains from SIV- and SHIV-infected macaques displayed a profile of bacterial phyla also dominated by Proteobacteria but bacterial sequences were not detected in experimentally FIV-infected cat or RAG1⁻/⁻ mouse brains. Intracerebral implantation of human brain homogenates into RAG1⁻/⁻ mice revealed a preponderance of α-proteobacteria 16 s RNA sequences in the brains of recipient mice at 7 weeks post-implantation, which was abrogated by prior heat-treatment of the brain homogenate. Thus, α-proteobacteria represented the major bacterial component of the primate brain's microbiome regardless of underlying immune status, which could be transferred into naïve hosts leading to microbial persistence in the brain.
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“The same bacterial sequences were detected in the brains of immunocompromised mice, weeks after human brain tissue transplantation but not in mice given heat-treated tissue, suggesting the bacterial sequences in the human brain samples were viable [133].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [133]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“A pioneering study investigating microbial infiltration into the brains of people living with HIV, found bacterial sequences present in both “healthy” and HIV brains at a similar distribution [133].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [133]
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Self-citationNovosphingobium Aromaticivorans: A Potential Initiator of Primary Biliary Cirrhosis
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Shigeta, S., Yasunaga, Y., Honzumi, K., Okamura, H.-O., Kumata, R., & Seiji, E. N. D. O. (1978) · Journal of Clinical Pathology · doi:10.1136/jcp.31.2.156 · Cited by 74 · cited 1×
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Horowitz, H. W., Gilroy, S. A., Feinstein, S. A., & Gilardi, G. L. (1990) · Journal of Clinical Microbiology · doi:10.1128/jcm.28.1.143-145.1990 · Cited by 72 · cited 1×
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“components of the normal flora in Peyer’s patches [33], but members have also been implicated in endocarditis [34], bacteremia [35,36] and meningitis with or without ventriculitis in neonates [37,38], HIV-infected persons [39], other immuno-”
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“components of the normal flora in Peyer’s patches [33], but members have also been implicated in endocarditis [34], bacteremia [35,36] and meningitis with or without ventriculitis in neonates [37,38], HIV-infected persons [39], other immuno-”
BackgroundOccurrence of an α-galacturonosyl-ceramide in the dioxin-degrading bacteriumSphingomonas wittichii
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BackgroundReinke, S. N., Resch, L., Maingat, F. G., Branton, W. G., Jackson, A. C., Holt, R. A., Slupsky, C. M., Marrie, T. J., Sykes, B. D., & Power, C. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis479 · Cited by 24 · cited 1×
“HIV-1 sequence-specific tags were also detected in brain specimens from the HIV group but other viral RNA sequences were infrequently detected by deep sequencing in the present specimens with the exception of the specimen from the ODC patient (ODC4) diagnosed with rabies encephalitis, from which in excess of 20,000 ra…”
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“compromised adults [40] or following invasive surgery [41].”
BackgroundUrinary tract infection associated with Comamonas acidovorans
Ojeda-Vargas, M., Suárez-Alonso, A., Pérez-Cervantes, M. D. L. A., Suárez-Gil, E., & Monzón-Moreno, C. (1999) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.1999.tb00170.x · Cited by 23 · cited 1×
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BackgroundXenoinfection of nonhuman primates by feline immunodeficiency virus
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“components of the normal flora in Peyer’s patches [33], but members have also been implicated in endocarditis [34], bacteremia [35,36] and meningitis with or without ventriculitis in neonates [37,38], HIV-infected persons [39], other immuno-”
BackgroundInfectious Keratitis Manifesting as a White Plaque on the Cornea
Cho, B.-J., & Lee, Y. B. (2002) · Archives of Ophthalmology · doi:10.1001/archopht.120.8.1091 · Cited by 17 · cited 1×
“For example, an organism similar to many of the 16 s V8 region sequences, Delftia acidovorans has been implicated in endocarditis [27], bacteremia [28,29], corneal keratitis [30] and urinary tract”
BackgroundMeningitis caused by Alcaligenes xylosoxidans in a patient with HIV/AIDS
Espinoza‐Gómez, F., Newton-Sánchez, O. A., Melnikov, V. L., Virgen-González, O., & Unrau, J. (2007) · The Brazilian Journal of Infectious Diseases · doi:10.1590/s1413-86702007000600015 · Cited by 13 · cited 1×
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“Brain tissues from simian (SIV; n = 10) [48] or simian-human immunodeficiency virus-infected (SHIV; n = 3) [49] or FIVchallenged adult cynomolgus macaques (n = 2) [50] were analyzed by initial preparation of RNA followed by RT-PCR amplification of cDNA and sequencing.”
MethodSelf-citationA case of endocarditis of difficult diagnosis in dialysis: could “pest” friends be involved?
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“components of the normal flora in Peyer’s patches [33], but members have also been implicated in endocarditis [34], bacteremia [35,36] and meningitis with or without ventriculitis in neonates [37,38], HIV-infected persons [39], other immuno-”
BackgroundManjra, A. I., Moosa, A., & Bhamjee, A. (1989) · PubMed · Cited by 9
Salha, M.-D., Cheynier, R., Halwani, R., McGrath, H., Langaee, T. Y., Yassine‐Diab, B., Fournier, J., Parenteau, M., Edgar, J. B., Ko, D. S.-W., et al. (2008) · Virology · doi:10.1016/j.virol.2008.04.031 · Cited by 4 · cited 1×
“Brain tissues from simian (SIV; n = 10) [48] or simian-human immunodeficiency virus-infected (SHIV; n = 3) [49] or FIVchallenged adult cynomolgus macaques (n = 2) [50] were analyzed by initial preparation of RNA followed by RT-PCR amplification of cDNA and sequencing.”
MethodSelf-citationOccurrence of an α-galacturonosyl-ceramide in the dioxin-degrading bacterium Sphingomonas wittichii
Kawahara, K. (2002) · FEMS Microbiology Letters · doi:10.1016/s0378-1097(02)00912-6
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BackgroundResultInfluential
Metadata
- Authors
- Branton, W. G., Ellestad, K. K., Maingat, F., Wheatley, B. M., Rud, E., Warren, R. L., Holt, R. A., Surette, M. G., & Power, C.
- Affiliations
- University of Alberta (CA)
- Health Canada (CA)
- BC Cancer Agency (CA)
- McMaster University (CA)
- Corresponding author
- Power, Christopher
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-23
- Volume
- 8
- Issue
- 1
- Pages
- e54673
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3552853
- OpenAlex
- W2057381259
- Cited by
- 149
- References
- 60
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 14 · 2023: 17 · 2022: 15 · 2021: 10 · 2020: 12 · 2019: 12 · 2018: 16 · 2017: 11 · 2016: 12 · 2015: 13 · 2014: 2 · 2013: 4
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Alberta Innovates
- Health Canada
- Canadian Institutes of Health Research (G118160525)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- HIV/AIDS, Alphaproteobacteria, Proteobacteria, bacterial 16S rRNA, peptidoglycan, herpesvirus, bacteriophages, simian immunodeficiency virus, SHIV, FIV, Rag1-deficient mice, microbial persistence, neuroimmune response, epilepsy surgery
- MeSH terms
- Acquired Immunodeficiency Syndrome, Animals, Autopsy, Cats, Female, Humans, Male, Neuroglia, RNA, Bacterial, RNA, Ribosomal, Feline Acquired Immunodeficiency Syndrome, Mice, Knockout, Alphaproteobacteria, Central Nervous System Bacterial Infections, Mice, Cerebrum
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