Oropharyngeal microbiota in HIV infection: trends and problems in the epoch of antiretroviral therapy
DOI: https://dx.doi.org/10.18565/epidem.2020.10.1.98-106
Matuzkova A.N., Pshenichnaya N.Yu., Aleshukina A.V., Ryndich A.A., Suladze A.G., Tverdokhlebova T.I., Zhuravlev A.S., Dontsov D.V.
1) Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia;
2) National Research Medical Center of Phthisiopulmonology and Infectious Diseases, Ministry of Health of Russia, Moscow, Russia;
3) I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia;
4) Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don, Russia
Objective. To study the features of the oropharyngeal microbiota and systemic inflammation in HIV-infected patients during antiretroviral therapy (ART) and to assess the possibility of their correction with amino dihydrophthalazinedione sodium (ADPNa).
Subjects and methods. The investigation enrolled 100 HIV-infected patients who received ART. The concentration of lipopolysaccharide-binding protein (LBP) was studied by ELISA. The composition of the oropharyngeal microbiota was determined on a VITEK-2 bacteriological analyzer by the compact disc diffusion method, as well as by mass spectrometry. The patients were randomized into 2 groups. In addition to standard ART, sublingual ADPNa tablets were prescribed for Group 1 patients. The efficiency of therapy was evaluated after 4 weeks according to the time course of changes in the concentration of LBP and in the composition of the oropharyngeal microflora.
Results. The vast majority of patients showed an overgrowth of opportunistic microorganisms, including Staphylococcus aureus and yeast-like fungi of the genus Candida. When an immunomodulator with an anti-inflammatory effect of ADPNa was added to standard ART, there was a more rapid decrease in the blood concentration of LBP and in the number of potential pathogens in the oropharyngeal microbiota.
Conclusion. The cycle use of ADPNa reduces the activity of endotoxinemia and normalizes the oropharyngeal microbiota.
Literature
- Ghannoum M. A., Mukherjee P. K., Jurevic R. J., Retuerto M., Brown R. E., Sikaroodi M., Webster-Cyriaque J., Gillevet P. M. Metabolomics reveals differential levels of oral metabolites in HIV-infected patients: toward novel diagnostic targets. Omics А Journal of Integrative Biology. 2013; 17(1): 5–15. DOI: 10.1089/omi.2011.0035.
- Shiboski C. H., Patton L.L., Webster Cyriaque J.Y., Greenspan D., Traboulsi R.S., Ghannoum M., Jurevic R., Phelan J.А., Reznik D., Greenspan J.S. The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints. J. Оral Pathol. Med. 2009; 38(6): 481–8. DOI: 10.1111/j.1600-0714.2009.00749.x.
- Dandekar S., George M.D., Bäumler A.J. Th17 cells, HIV and the gut mucosal barrier. Current Оpinion in HIV and AIDS 2010; 5(2): 173–8. DOI: 10.1097/COH.0b013e328335eda3.
- Sankaran S., George M.D., Reay E., Guadalupe M., Flamm J., Prindiville T., Dandekar S. Rapid onset of intestinal epithelial barrier dysfunction in primary human immunodeficiency virus infection is driven by an imbalance between immune response and mucosal repair and regeneration. J. Virol. 2008; 82 (1): 538–45. DOI: 10.1128/JVI.01449-07.
- George M. D. Verhoeven D., Sankaran S., Glavan T., Reay E., Dandekar S. Heightened cytotoxic responses and impaired biogenesis contribute to early pathogenesis in the oral mucosa of simian immunodeficiency virus-infected rhesus macaques. Clin. Vaccine Immunol. 2009; 16(2): 277–81. DOI: 10.1128/CVI.00265-08.
- Крюков А.И., Кунельская Н.Л., Гуров А.В., Изотова Г.Н., Старостина А.Е., Лапченко А.С. Клинико-микробиологическая характеристика дисбиотических изменений слизистой оболочки полости рта и ротоглотки. Медицинский совет 2016; (6): 32–5.
Kryukov A.I., Kunel'skaya N.L., Gurov A.V., Izotova G.N., Starostina A.E., Lapchenko A.S. [Clinical and microbiological characteristics of dysbiotic changes in the mucous membrane of the oral cavity and oropharynx]. Medicinskij sovet 2016; (6): 32–5. (In Russ.).
- Alexopoulou L., Kontoyiannis D. Contribution of microbial-associated molecules in innate mucosal responses. Cellular and molecular life sciences: CMLS 2005; 62(12): 1349–358. DOI: 10.1007/s00018-005-5039-x .
- Beck J. M., Beck J.M., Schloss P.D., Venkataraman A., Twigg I.H., Jablonski K.A., Bushman F.D. Multicenter comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals. Am. J. Respirat. Crit. Care Med. 2015; 192(11): 1335–44. DOI: 10.1164/rccm.201501-0128OC
- Kistler J. O., Arirachakaran P., Poovorawan Y., Dahlén G., Wade W.G. The oral microbiome in human immunodeficiency virus (HIV)-positive individuals. J. Med. Microbiol. 2015; 64(9): 1094–101. DOI: 10.1099/jmm.0.000128.
- Saxena D., Li Y., Yang L., Pei Z, Poles M., Abrams W.R., Malamud D. Human microbiome and HIV/AIDS. Curr. HIV AIDS Rep. 2012; 9(1): 44–51. DOI: 10.1007/s11904-011-0103-7.
- Mukherjee P.K., Chandra J., Retuerto M., Sikaroodi M., Brown R.E., Jurevic R., Salata R.A., Lederman M.M., Gillevet P.M., Ghannoum M.A. Oral mycobiome analysis of HIV-infected patients: identification of Pichia as an antagonist of opportunistic fungi. PLoS Рathogens 2014; 10(3): e1003996. DOI: 10.1371/journal.ppat.1003996.
- Hegde M.C., Kumar A., Bhat G., Sreedharan S. Oral microflora: a comparative study in HIV and normal patients. Indian J. Otolaryngol. 2014; 66(1): 126–32. DOI: 10.1007/s12070-011-0370-z.
- Dang A. T., Cotton S., Sankaran-Walters S., Li C., Lee C.M., Dandekar S., Paster B.J., George M.D. Evidence of an increased pathogenic footprint in the lingual microbiome of untreated HIV infected patients. BMC Microbiol. 2012; 12(1): 153. DOI: 10.1186/1471-2180-12-153.
- Shiboski C. H., Lee A., Chen H., Webster-Cyriaque J., Seaman T., Landovitz R.J., John M., Reilly N., Naini L., Palefsky J., Jacobson M.A. Human papillomavirus infection in the oral cavity of HIV patients is not reduced by initiating antiretroviral therapy. AIDS (London, England). 2016; 30(10): 1573. DOI: 10.1097/QAD. 0000000000001072.
- Noguera-Julian M. Guillén Y., Peterson J., Reznik D., Harris E.V., Joseph S. J. Oral microbiome in HIV-associated periodontitis. Medicine 2017; 96(12): e5821. DOI: 10.1097/MD.0000000000005821.
- Liljestrand J. M., Paju S., Buhlin K., Persson G.R., Sarna S., Nieminen M.S. Lipopolysaccharide, a possible molecular mediator between periodontitis and coronary artery disease. J. Сlin. Рeriodontol. 2017; 44(8): 784–92. DOI: 10.1111/jcpe.12751.
- Lew W.Y.W., Bayna E., Molle E. D., Dalton N.D., Lai N.C., Bhargava V., Mendiola V., Clopton P., Tang T. Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice. PloS Оne 2013; 8(4): e61057. DOI: 10.1371/journal.pone.0061057
- Бусленко А.О., Пшеничная Н.Ю., Алешукина А.В. Изменение состава микрофлоры кишечника при экспериментальной клебсиеллезной инфекции у лабораторных мышей и ее терапии различными иммуномодулирующими препаратами. Врач-аспирант 2015; 71(4.1): 139–44.
Buslenko A.O., Pshenichnaya N.Yu., Aleshukina A.V. [Changes in the composition of the intestinal microflora in experimental Klebsiella infection in laboratory mice and its treatment with various immunomodulating drugs]. Vrach-aspirant 2015; 71(4.1): 139–44. (In Russ.).
- Покровский А.В., Мхитарова Л.А., Царев В.Н. Прогностическое значение провоспалительных цитокинов при ингаляционном применении галавита в комплексном лечения ХОБ. Вестник Дагестанской государственной медицинской академии 2014; 1(10): 19–23.
Pokrovsky A.V., Mhitarova L.A., Tsarev V.N. [Prognostic value of pro-inflammatory cytokines in case of inhalation use of galavit in the complex treatment of chronic obstructive pulmonary disease]. Vestnik Dagestanskoj gosudarstvennoj medicinskoj akademii 2014; 1(10): 19–23 (In Russ.).
- Бусленко А.О., Алешукина А.В., Пшеничная Н.Ю. Хуказова С.А., Костенко О.Д., Гопаца Г.В., Малышева М.И.Местный цитокиновый профиль у взрослых пациентов с острыми кишечными инфекциями и его коррекция с применением иммуномодулирующей терапии. Эпидемиол. инфекц. болезни. Актуал. вопр. 2017; (4): 58–64.
Buslenko A.O., Aleshukina A.V., Pshenichnaya N.Yu., Hukazova S.A., Kostenko O.D., Gopaca G.V., Malysheva M.I. [Local cytokine profile in adult patients with acute intestinal infections and its correction using immunomodulating therapy]. Èpidemiologiâ i infekcionnye bolezni. Аktual'nye voprosy 2017; (4): 58–64. (In Russ.).
- Бусленко А.О., Пшеничная Н.Ю., Алешукина А.В., Усаткин А.В., Костенко О.Д., Хуказова С.А., Диденко И.В., Усаткина Т.В. Острые кишечные инфекции у взрослых: оценка состояния интестинальной микрофлоры и эффективности аминодигидрофталазиндиона натрия в составе их комплексной терапии. Эпидемиол. инфекц. болезни. Актуал. вопр. 2016; (4): 57–64.
Buslenko A.O., Pshenichnaya N.Yu., Aleshukina A.V., Usatkin A.V., Kostenko O.D., Hukazova S.A., Didenko I.V., Usatkina T.V. [Acute intestinal infections in adults: assessment of the state of intestinal microflora and the effectiveness of sodium aminodihydrophthalazinedione as part of their complex therapy]. Èpidemiologiâ i infekcionnye bolezni. Аktual'nye voprosy 2016; (4): 57–64. (In Russ.).
- Матузкова А.Н., Пшеничная Н.Ю., Суладзе А.Г., Досягаева Л.И., Твердохлебова Т.И., Яговкин Э.А. Клинико-диагностическое значение оценки показателей системного воспаления у больных с ВИЧ-инфекцией. ВИЧ-инфекция и иммуносупрессии 2018; 10(3): 64–71.
Matuzkova A.N., Pshenichnaya N.Yu., Suladze A.G., Досягаева Л.И., Твердохлебова Т.И., Яговкин Э.А. [Clinical and diagnostic value of assessing systemic inflammation in patients with HIV infection]. VICh-infekciya i immunosupressii 2018; 10(3): 64–71. (In Russ.).
- Джораева С.К., Гончаренко В.В., Щеголева Е.В., Щербакова Ю.В., Безрученко А.А. Состав и функции микробиоценозов различных биотопов макроорганизма и клиническая значимость их нарушений. Дерматология и венерология 2015; (2): 5–19.
Dzhoraeva S.K., Goncharenko V.V., Shhegoleva E.V., Shherbakova Yu.V., Bezruchenko A.A. [The composition and functions of microbiocenoses of various biotopes of a macroorganism and the clinical significance of their disorders]. Dermatologiya i venerologiya 2015; (2): 5–19. (In Russ.).
About the Autors
Аnna N. Matuzkova, Infectiologist, Polyclinic Department, Southern District Center for AIDS Prevention and Control, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; е-mail: matuzkova@yandex.ru; ORCID: https://orcid.org/0000-0002-5980-3436
Prof. Natalia Yu. Pshenichnaya, MD; Head, International Department for Organization of Medical Care, National Research Medical Center of Phthisiopulmonology and Infectious Diseases, Ministry of Health of Russia, Moscow, Russia; e-mail: natalia-pshenichnaya@yandex.ru; ORCID: https://orcid.org/0000-0003-2570-711X
Anna V. Aleshukina, MD, Senior Researcher; Head, Laboratory of Virology, Microbiology and Molecular Biological Studies, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: niimicrodouble@yandex.ru; ORCID: https://orcid.org/0000-0002-9797-2441
Antonina A. Ryndich, Cand. Med. Sci.; Head, Southern District Center for AIDS Prevention and Control, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: hivrost@mail.ru; ORCID: https://orcid.org/0000-0002-9568-7794
Aleksandr G. Suladze, Cand. Med. Sci., Infectiologist, Southern District Center for AIDS Prevention and Control, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: hivrost@mail.ru; ORCID: https://orcid.org/0000-0002-9051-1220
Tatiana I. Tverdokhlebova, MD, Associate Professor; Director, Rostov Research Institute of Microbiology and Parasitology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Rostov-on-Don, Russia; e-mail: niimicrodouble@yandex.ru; ORCID: https://orcid.org/0000-0002-4280-6702
Andrey S. Zhuravlev, Student, “Medicine of the Future” Center for Innovative Educational Programs (CIEP), I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia; e-mail: Andrew0898@yandex.ru; ORCID: https://orcid.org/0000-0002-9130-707
Prof. Denis V. Dontsov, MD, Associate Professor, Department of Infection Diseases, Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don, Russia; e-mail: d¬_dontcov@mail.ru; ORCID: https://orcid.org/0000-0003-4938-2962
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