HIV ile Yaşayan Bireylerde Kronik Enflamasyon ve Mikrobiyota İlişkisi

İnsan immün yetmezlik virüsü (HIV) enfeksiyonunda antiretroviral tedavi ile viral replikasyon tespit edilemeyen düzeylere indirilmiş olsa da, hastalığının ilerlemesi ile ilişkili kronik persistan enflamasyonun ömür boyu devam ettiği bilinmektedir. Enflamasyon, immün sistemin hasarlı dokuları onarmak için oluşturduğu bir tepki olup bu yanıtın yavaş ilerleyip uzun süre devam etmesi kronik enflamasyon olarak adlandırılır. Birçok çalışmada HIV ile yaşayan bireylerde mikrobiyota disbiyozu ve mikrobiyal translokasyonun enflamasyon patogenezinde önemli rol oynadığı gösterilmiştir. Devam eden kronik enflamasyon ve mikrobiyota ilişkisinin daha net bir şekilde ortaya konulması ve beraberinde mikrobiyotayı değiştirme amaçlı terapötik müdahale çalışmaları HIV enfeksiyonu tedavisinde nispeten yeni araştırılan bir alandır ve bu alandaki gelişmeler HIV enfeksiyonunun insan vücudu üzerindeki uzun dönem hasarlarının önlenmesinde umut vadetmektedir. Bu yazıda HIV enfeksiyonunda görülen kronik enflamasyon nedenleri ve mekanizması, mikrobiyata disbiyozunun etkisi değerlendirilecektir.

Relationship to Chronic Inflammation and Microbiota in Individuals with HIV

Although viral replication has been reduced to undetectable levels with antiretroviral treatment in human immunodeficiency virus (HIV) infection, chronic persistent inflammation associated with the progression of the disease is known to persist throughout life. Inflammation is a response created by the immune system to repair damaged tissues, and the slow progress of this response and its continuation for a long time is called chronic inflammation. Many studies have shown that microbiota dysbiosis and microbial translocation play an important role in the pathogenesis of inflammation in individuals living with HIV. The ongoing chronic inflammation and microbiota relationship and therapeutic intervention studies aiming at changing the microbiota are a relatively newly researched area in the treatment of HIV infection, and advances in this area show promise in preventing HIV infection’s long-term damage to the human body. In this article, the causes and mechanism of chronic inflammation seen in HIV infection and the effect of microbiota dysbiosis will be evaluated.

PDF

___

1. Kaur US, Shet A, Rajnala N, et al. High Abundance of genus Prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy. Sci Rep. 2018;8:17679.
2. Herrera S, Martínez-Sanz J, Serrano-Villar S. HIV, Cancer, and the Microbiota: Common Pathways Influencing Different Diseases. Front Immunol. 2019;10:1466.
3. Deeks SG, Tracy R, Douek DC. Systemic effects of inflammation on health during chronic HIV infection. Immunity. 2013;39:633-645.
4. Kuralay F, Çavdar Z. İnflamatuar medyatörlere toplu bir bakış. Genel Tıp Derg. 2006;16:143-152.
5. Highleyman L. Inflammation, immune activation, and HIV. BETA. 2010;22:12-26.
6. Stacey AR, Norris PJ, Qin L, et al. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J Virol. 2009;83:3719-3733.
7. Chevalier MF, Petitjean G, Dunyach-Rémy C, et al. The Th17/Treg ratio, IL- 1RA and sCD14 levels in primary HIV infection predict the T-cell activation set point in the absence of systemic microbial translocation. PLoS Pathog. 2013;9:e1003453.
8. Doisne JM, Urrutia A, Lacabaratz-Porret C, et al. CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J Immunol. 2004;173:2410-2418.
9. Hsue PY, Waters DD. HIV infection and coronary heart disease: mechanisms and management. Nat Rev Cardiol. 2019;16:745-759.
10. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12:1365-1371.
11. Highleyman L. Inflammation, immune activation, and HIV. BETA. 2010;22:12-26.
12. Neuhaus J, Jacobs DR Jr, Baker JV, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV inefction. J Infect Dis. 2010;201:1788-1795.
13. Burdo TH, Lo J, Abbara S, et al. Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis. 2011;204:1227-1236.
14. Sandler NG, Wand H, Roque A, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011;203:780-790.
15. Brenchley JM, Paiardini M, Knox KS, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008;112:2826-2835.
16. Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med. 2010;2:32ra36.
17. Chege D, Sheth PM, Kain T, et al. Sigmoid Th17 populations, the HIV latent reservoir, and microbial translocation in men on long-term antiretroviral therapy. AIDS. 2011;25:741-749.
18. Zevin AS, McKinnon L, Burgener A, et al. Microbial translocation and microbiome dysbiosis in HIV-associated immune activation. Curr Opin HIV AIDS. 2016;11:182-190.
19. Marchetti G, Tincati C, Silvestri G. Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev. 2013;26:2-18.
20. Berg RD. Bacterial translocation from the gastrointestinal tract. Trends Microbiol. 1995;3:149-154.
21. Tancrède CH, Andremont AO. Bacterial translocation and gram-negative bacteremia in patients with hematological malignancies. J Infect Dis. 1985;152:99-103.
22. Beutler B. Tlr4: central component of the sole mammalian LPS sensor. Curr Opin Immunol. 2000;12:20-26.
23. Klatt NR, Funderburg NT, Brenchley JM. Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 2013;21:6-13.
24. Ancuta P, Kamat A, Kunstman KJ, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One. 2008 ;3:e2516.
25. Barclay GR, Scott BB, Wright IH, et al. Changes in anti-endotoxin-IgG antibody and endotoxaemia in three cases of gram-negative septic shock. Circ Shock. 1989;29:93-106.
26. Anderson KV. Toll signaling pathways in the innate immune response. Curr Opin Immunol. 2000;12:13-19.
27. Yılmaz K, Altındiş M. Gastrointestinal Microbiota and Fecal Transplantation. Nobel Med. 2017;13:9-15.
28. Dinh DM, Volpe GE, Duffalo C, et al. Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J Infect Dis. 2015;211:19-27.
29. Ji Y, Zhang F, Zhang R, et al. Changes in intestinal microbiota in HIV-1- infected subjects following cART initiation: influence of CD4+ T cell count. Emerg Microbes Infect. 2018;7:113.
30. Sun Y, Ma Y, Lin P, et al. Fecal bacterial microbiome diversity in chronic HIVinfected patients in China. Emerg Microbes Infect. 2016;5:e31.
31. Bandera A, De Benedetto I, Bozzi G, et al. Altered gut microbiome composition in HIV infection: causes, effects and potential intervention. Curr Opin HIV AIDS. 2018;13:73-80.
32. Noguera-Julian M, Rocafort M, Guillén Y, et al. Gut Microbiota Linked to Sexual Preference and HIV Infection. EBioMedicine. 2016;5:135-146.
33. Nowak RG, Bentzen SM, Ravel J, et al. Rectal microbiota among HIVuninfected, untreated HIV, and treated HIV-infected in Nigeria. AIDS. 2017;31:857-862.
34. Lu W, Feng Y, Jing F, et al. Association Between Gut Microbiota and CD4 Recovery in HIV-1 Infected Patients. Front Microbiol. 2018;9:1451.
35. Dillon SM, Lee EJ, Kotter CV, et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 2014;7:983- 994.
36. Mutlu EA, Keshavarzian A, Losurdo J, et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog. 2014;10:e1003829.
37. Vujkovic-Cvijin I, Dunham RM, Iwai S, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013;5:193ra91.
38. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453:620-625.
39. Vujkovic-Cvijin I, Somsouk M. HIV and the Gut Microbiota: Composition, Consequences, and Avenues for Amelioration. Curr HIV/AIDS Rep. 2019;16:204-213.
40. Manzanares W, Lemieux M, Langlois PL, et al. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. Crit Care. 2016;19:262.
41. Zhang Q, Wu Y, Fei X. Effect of probiotics on body weight and body-mass index: a systematic review and meta-analysis of randomized, controlled trials. Int J Food Sci Nutr. 2015;67:571-580.
42. Uymaz B. Probiotics and Their Use. PAJES. 2010;16:95-104.
43. Karacaer C, Varım C, Toka B, et al. Bağırsak Mikrobiyatası, Probiyotikler ve İrritable Bağırsak Sendromu (İBS). J Hum Rhythm. 2017;3:120-125.
44. Feria MG, Taborda NA, Hernandez JC, et al. Efecto de la terapia con probióticos/prebióticos sobre la reconstitución del tejido linfoide asociado a la mucosa gastrointestinal durante la infección por el virus de la inmunodeficiencia humana-1 [Effects of prebiotics and probiotics on gastrointestinal tract lymphoid tissue in hiv infected patients]. Rev Med Chil. 2017;145:219-229.
45. Villar-García J, Hernández JJ, Güerri-Fernández R, et al. Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial. J Acquir Immune Defic Syndr. 2015;68:256-263.
46. Pinacchio C, Scheri GC, Statzu M, et al. Type I/II Interferon in HIV-1-Infected Patients: Expression in Gut Mucosa and in Peripheral Blood Mononuclear Cells and Its Modification upon Probiotic Supplementation. J Immunol Res. 2018;2018:1738676.
47. Ishizaki A, Bi X, Nguyen LV, et al. Effects of Short-Term Probiotic Ingestion on Immune Profiles and Microbial Translocation among HIV-1-Infected Vietnamese Children. Int J Mol Sci. 2017;18:2185.
48. Hummelen R, Changalucha J, Butamanya NL, et al. Effect of 25 weeks probiotic supplementation on immune function of HIV patients. Gut Microbes. 2011;2:80-85.
49. Salminen MK, Tynkkynen S, Rautelin H, et al. The efficacy and safety of probiotic Lactobacillus rhamnosus GG on prolonged, noninfectious diarrhea in HIV Patients on antiretroviral therapy: a randomized, placebo-controlled, crossover study. HIV Clin Trials. 2004;5:183-191.
50. Carter GM, Esmaeili A, Shah H, et al. Probiotics in Human Immunodeficiency Virus Infection: A Systematic Review and Evidence Synthesis of Benefits and Risks. Open Forum Infect Dis. 2016;3:ofw164.