The gut microbiome in human immunodeficiency virus infection
HIV/AIDS causes severe dysfunction of the immune system through CD4+ T cell depletion, leading to dysregulation of both the adaptive and innate immune arms. A primary target for viral infection is the gastrointestinal tract, which is a reservoir of CD4+ T cells. In addition to being a major immune hub, the human gastrointestinal tract harbors trillions of commensal microorganisms, the microbiota, which have recently been shown to play critical roles in health. Alterations in the composition and function of microbiota have been implicated in a variety of ‘multi-factorial’ disorders, including infectious, autoimmune, metabolic, and neoplastic disorders. It is widely accepted that, in addition to its direct role in altering the gastrointestinal CD4+ T cell compartment, HIV infection is characterized by gut microbiota compositional and functional changes. Herein, we review such alterations and discuss their potential local and systemic effects on the HIV-positive host, as well as potential roles of novel microbiota-targeting treatments in modulating HIV progression and associated adverse systemic manifestations.
Keywords:
Microbiota, Dysbiosi,s Gastrointestinal tract, AIDS, HIV, Anti-retroviral therapy, CD4+ T cells
Autoři:
Gili Zilberman-Schapira† 1; Niv Zmora† 1; Shlomik Itav† 1; Stavros Bashiardes† 1; Hila Elinav 2*; Eran Elinav 1*
Působiště autorů:
Department of Immunology, Weizmann Institute of Science, 34 Herzl Street, Rehovot 76100, Israel
1; Hadassah AIDS Center, Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
2
Vyšlo v časopise:
BMC Medicine 2016, 14:83
Kategorie:
Minireview
prolekare.web.journal.doi_sk:
https://doi.org/10.1186/s12916-016-0625-3
© 2016 Zilberman-Schapira et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0625-3
Souhrn
HIV/AIDS causes severe dysfunction of the immune system through CD4+ T cell depletion, leading to dysregulation of both the adaptive and innate immune arms. A primary target for viral infection is the gastrointestinal tract, which is a reservoir of CD4+ T cells. In addition to being a major immune hub, the human gastrointestinal tract harbors trillions of commensal microorganisms, the microbiota, which have recently been shown to play critical roles in health. Alterations in the composition and function of microbiota have been implicated in a variety of ‘multi-factorial’ disorders, including infectious, autoimmune, metabolic, and neoplastic disorders. It is widely accepted that, in addition to its direct role in altering the gastrointestinal CD4+ T cell compartment, HIV infection is characterized by gut microbiota compositional and functional changes. Herein, we review such alterations and discuss their potential local and systemic effects on the HIV-positive host, as well as potential roles of novel microbiota-targeting treatments in modulating HIV progression and associated adverse systemic manifestations.
Keywords:
Microbiota, Dysbiosi,s Gastrointestinal tract, AIDS, HIV, Anti-retroviral therapy, CD4+ T cells
Zdroje
1. Fauci AS. HIV and AIDS: 20 years of science. Nat Med. 2003;9(7):839–43.
2. Paiardini M, Müller-Trutwin M. HIV-associated chronic immune activation. Immunol Rev. 2013;254(1):78–101.
3. Gadhamsetty S, Beltman JBB, de Boer RJJ. What do mathematical models tell us about killing rates during HIV-1 infection? Immunol Lett. 2015;168(1):1–6.
4. Ipp H, Zemlin AE, Erasmus RT, Glashoff RH. Role of inflammation in HIV-1 disease progression and prognosis. Crit Rev Clin Lab Sci. 2014;51(2):98–111.
5. Hernandez-Vargas EA, Middleton RH. Modeling the three stages in HIV infection. J Theor Biol. 2013;320:33–40.
6. Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet Elsevier Ltd. 2014;384(9939):258–71.
7. Cooper A, García M, Petrovas C, Yamamoto T, Koup RA, Nabel GJ. HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature. 2013;498(7454):376–9.
8. Doitsh G, Galloway NLK, Geng X, Yang Z, Monroe KM, Zepeda O, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2013;505(7484):509–14.
9. Parmentier M. CCR5 and HIV Infection, a View from Brussels. Front Immunol. 2015;6:295.
10. Brenchley JM. CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract. J Exp Med. 2004;200(6):749–59.
11. Marchetti G, Tincati C, Silvestri G. Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev. 2013;26(1):2–18.
12. Klatt NR, Funderburg NT, Brenchley JM. Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 2013;21(1):6–13.
13. Epple H, Allers K, Tröger H, Kühl A, Erben U, Fromm M, et al. Acute HIV Infection Induces Mucosal Infiltration With CD4+ and CD8+ T Cells, Epithelial Apoptosis, and a Mucosal Barrier Defect. Gastroenterology. 2010; 139(4):1289–300.e2. Elsevier Inc.
14. Nazli A, Chan O, Dobson-Belaire WN, Ouellet M, Tremblay MJ, Gray-Owen SD, et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog. 2010;6(4):e1000852.
15. Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol. 2009;9(4):235–45.
16. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.
17. Bhaijee F, Subramony C, Tang S-J, Pepper DJ. Human immunodeficiency virus-associated gastrointestinal disease: common endoscopic biopsy diagnoses. Patholog Res Int. 2011;2011:247923.
18. Cabada MM, White AC. Treatment of cryptosporidiosis: do we know what we think we know? Curr Opin Infect Dis. 2010;23(5):494–9.
19. Sun H-Y, Chen M-Y, Wu M-S, Hsieh S-M, Fang C-T, Hung C-C, et al. Endoscopic appearance of GI mycobacteriosis caused by the Mycobacterium avium complex in a patient with AIDS: case report and review. Gastrointest Endosc. 2005;61(6):775–9.
20. Sharpstone D, Gazzard B. Gastrointestinal manifestations of HIV infection. Lancet (London, England). 1996;348(9024):379–83.
21. Montessori V, Press N, Harris M, Akagi L, Montaner JSG. Adverse effects of antiretroviral therapy for HIV infection. Can Med Assoc J. 2004;170(2):229–38.
22. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science. 2012;336(6086):1262–7.
23. Dinh DM, Volpe GE, Duffalo C, Bhalchandra S, Tai AK, Kane AV, et al. The Intestinal Microbiota, Microbial Translocation and Systemic Inflammation in Chronic HIV Infection. J Infect Dis. 2014;211:19–27.
24. Lozupone CA, Rhodes ME, Neff CP, Fontenot AP, Campbell TB, Palmer BE. HIV-induced alteration in gut microbiota: driving factors, consequences, and effects of antiretroviral therapy. Gut Microbes. 2014;5(4):562–70.
25. Zoetendal EG, Rajilic-Stojanovic M, de Vos WM. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut. 2008; 57(11):1605–15.
26. Nowak P, Troseid M, Avershina E, Barqasho B, Neogi U, Holm K, et al. Gut microbiota diversity predicts immune status in HIV-1 infection. Aids. 2015;29:1.
27. Lozupone CA, Li M, Campbell TB, Flores SC, Linderman D, Gebert MJ, et al. Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe. 2013;14(3):329–39.
28. Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 2014; 7(4):983–94.
29. Mutlu EA, Keshavarzian A, Losurdo J, Swanson G, Siewe B, Forsyth C, et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog. 2014;10(2):e1003829.
30. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–8.
31. Nava GM, Friedrichsen HJ, Stappenbeck TS. Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J. 2011;5(4):627–38.
32. Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013;5(193):193ra91.
33. Ellis CL, Ma Z-M, Mann SK, Li C-S, Wu J, Knight TH, et al. Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J Acquir Immune Defic Syndr. 2011;57(5):363–70.
34. Olubajo B, Mitchell-Fearon K, Ogunmoroti O. A Comparative Systematic Review of the Optimal CD4 Cell Count Threshold for HIV Treatment Initiation. Interdiscip Perspect Infect Dis. 2014;2014:625670.
35. Pérez-Santiago J, Gianella S, Massanella M, Spina CA, Karris MY, Var SR, et al. Gut Lactobacillales are associated with higher CD4 and less microbial translocation during HIV infection. AIDS. 2013;27(12):1921–31.
36. Monaco CL, Gootenberg DB, Zhao G, Handley SA, Ghebremichael MS, Lim ES, et al. Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome. Cell Host Microbe. 2016;19(3):311–22.
37. Vázquez-Castellanos JF, Serrano-Villar S, Latorre A, Artacho A, Ferrús ML, Madrid N, et al. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals. Mucosal Immunol. 2014;8(4):760–72.
38. Takeda K, Kaisho T, Akira S. Toll-Like Receptors. Annu Rev Immunol. 2003; 21(1):335–76.
39. McHardy IH, Li X, Tong M, Ruegger P, Jacobs J, Borneman J, et al. HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota. Microbiome. 2013;1(1):26.
40. Langille MGI, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol. 2013;31(9):814–21. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
41. Abubucker S, Segata N, Goll J, Schubert AM, Izard J, Cantarel BL, et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput Biol. 2012;8(6):e1002358.
42. Burgener A, McGowan I, Klatt NR. HIV and mucosal barrier interactions: consequences for transmission and pathogenesis. Curr Opin Immunol Elsevier Ltd. 2015;36:22–30.
43. Hirbod T, Kong X, Kigozi G, Ndyanabo A, Serwadda D, Prodger JL, et al. HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men. PLoS Pathog. 2014;10(10):e1004416.
44. Cohen CR, Lingappa JR, Baeten JM, Ngayo MO, Spiegel CA, Hong T, et al. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med. 2012;9(6):e1001251.
45. Marconi C, Santos-Greatti MMV, Parada CMGL, Pontes A, Pontes AG, Giraldo PC, et al. Cervicovaginal levels of proinflammatory cytokines are increased during chlamydial infection in bacterial vaginosis but not in lactobacillidominated flora. J Low Genit Tract Dis. 2014;18(3):261–5.
46. Masson L, Mlisana K, Little F, Werner L, Mkhize NN, Ronacher K, et al. Defining genital tract cytokine signatures of sexually transmitted infections and bacterial vaginosis in women at high risk of HIV infection: a crosssectional study. Sex Transm Infect. 2014;90(8):580–7.
47. Anahtar MNN, Byrne EHH, Doherty KEE, Bowman BAA, Yamamoto HSS, Soumillon M, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity. 2015;42(5): 965–76. Elsevier Inc.
48. Nunn KL, Wang Y, Harit D, Humphrys MS, Ma B, Cone R, et al. Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus -Dominant Microbiota. MBio. 2015;6(5):1–9.
49. Kyongo JK, Crucitti T, Menten J, Hardy L, Cools P, Michiels J, et al. Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and
Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention. Clin Vaccine Immunol. 2015;22(5):526–38.
50. Liu CM, Osborne BJW, Hungate B a, Shahabi K, Huibner S, Lester R, et al. The semen microbiome and its relationship with local immunology and viral load in HIV infection. PLoS Pathog. 2014;10(7):e1004262.
51. Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382(9903):1525–33.
52. Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system. J Acquir Immune Defic Syndr. 2012;60(4):351–8.
53. Trøseid M, Manner IW, Pedersen KK, Haissman JM, Kvale D, Nielsen SD. Microbial translocation and cardiometabolic risk factors in HIV infection. AIDS Res Hum Retroviruses. 2014;30(6):514–22.
54. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63.
55. Srinivasa S, Fitch KV, Lo J, Kadar H, Knight R, Wong K, et al. Plaque burden in HIV-infected patients is associated with serum intestinal microbiotagenerated trimethylamine. AIDS. 2015;29:443–52.
56. Haissman JM, Knudsen A, Hoel H. KjÆr A. Berge RK, et al. Microbiotadependent marker TMAO is elevated in silent ischemia but is not associated with first-time myocardial infarction in HIV infection. J Acquir Immune Defic Syndr: Kristoffersen US; 2015.
57. Siedner MJ, Kim J-H, Nakku RS, Bibangambah P, Hemphill L, Triant VA, et al. Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy. J Infect Dis. 2016;213(3):370–8.
58. Byakwaga H, Boum Y, Huang Y, Muzoora C, Kembabazi A, Weiser SD, et al. The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral therapy. J Infect Dis. 2014;210(3):383–91.
59. Mehraj V, Routy J-P. Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests. Int J Tryptophan Res. 2015;8:41–8.
60. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576–85.
61. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. Crosstalk
between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066–71.
62. Deeks SG, Tracy R, Douek DC. Systemic Effects of Inflammation on Health during Chronic HIV Infection. Immunity. 2013;39(4):633–45. Elsevier Inc.
63. Shulzhenko N, Morgun A, Hsiao W, Battle M, Yao M, Gavrilova O, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med. 2011;17(12):1585–93.
64. Brown RE, Ghannoum MA, Mukherjee PK, Gillevet PM, Sikaroodi M. Quorum-Sensing Dysbiotic Shifts in the HIV-Infected Oral Metabiome. PLoS One. 2015;10(4):e0123880.
65. Victoriano AFB, Imai K, Okamoto T. Interaction between endogenous bacterial flora and latent HIV infection. Clin Vaccine Immunol. 2013;20(6):773–9.
66. Cunningham-Rundles S, Ahrné S, Johann-Liang R, Abuav R, Dunn-Navarra A-M, Grassey C, et al. Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection. Nutrients. 2011;3(12):1042–70.
67. Trois L, Cardoso EM, Miura E. Use of probiotics in HIV-infected children: a randomized double-blind controlled study. J Trop Pediatr. 2008;54(1):19–24.
68. d’Ettorre G, Ceccarelli G, Giustini N, Serafino S, Calantone N, De Girolamo G, et al. Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the “Probio-HIV” Clinical Trial. PLoS One. 2015;10(9):e0137200.
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