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Journal of Physiology and Biochemistry

, Volume 75, Issue 3, pp 299–309 | Cite as

Characterization of gut microbiota composition in HIV-infected patients with metabolic syndrome

  • María Jesús Villanueva-Millán
  • Patricia Pérez-MatuteEmail author
  • Emma Recio-Fernández
  • José-Miguel Lezana Rosales
  • José-Antonio Oteo
Original Article

Abstract

The presence of metabolic syndrome (MS) per se or its separated components in HIV-infected patients contributes to an accelerated aging and increased cardiovascular risk. Gut microbiota (GM) dysbiosis has been linked with chronic inflammation associated with MS in a general non-infected population. However, no studies concerning GM have been performed in HIV-infected patients with MS. The aim of this study was to analyze bacterial translocation, inflammation, and GM composition in HIV-infected patients with and without MS. A total of 51 HIV-infected patients were recruited and classified according to the presence of MS (40 patients without MS and 11 with MS). Markers of bacterial translocation, inflammation, and cardiovascular risk were measured and GM was analyzed using 16S rRNA gene deep sequencing. No differences were observed among both HIV-infected groups in the bacterial translocation markers LBP and sCD14. A tendency to increase the inflammatory markers IL-6 (p = 0.069) and MCP-1 (p = 0.067) was observed in those patients suffering from MS. An increase in the cardiovascular risk markers PAI-1 (p = 0.007) and triglycerides/HDL cholesterol ratio (p < 0.0001) was also found in the MS group. No significant changes were observed at phylum level although a decrease in the abundance of seven genera and seven bacterial species, including some anti-inflammatory bacteria, was observed in HIV-infected patients with MS. To summarize, the presence of MS was not accompanied by major changes in GM, although the reduction observed in some anti-inflammatory bacteria may be clinically useful to develop strategies to minimize inflammation and its future deleterious consequences in these HIV-infected patients.

Keywords

HIV infection Metabolic syndrome Gut microbiota composition Bacterial translocation Inflammation Cardiovascular risk 

Abbreviations

ALT

Alanine aminotransferase

ART

Antiretroviral treatment

AST

Aspartate aminotransferase

BBH

Best blast hit

BLAST

Basic local alignment search tool

BT

Bacterial translocation

CEImLAR

Committee for Ethics in Drug Research in La Rioja

CVD

Cardiovascular diseases

ELISA

Enzyme-linked immunosorbent assay

GALT

Gut-associated lymphoid tissue

HDL

High-density lipoprotein

HIV

Human immunodeficiency virus

HIV+

HIV-infected patients

HOMA-IR

Homeostasis model assessment insulin resistance index

IL6

Interleukin-6

LBP

Lipopolysaccharide-binding protein,

LCA

Lowest common ancestor

LDL

Low-density lipoprotein

MCP-1

Monocyte chemotactic protein-1

MS

Metabolic syndrome

NCEP-ATP III

National Cholesterol Education Program Adult Treatment Program III

PAD

Diastolic blood pressure

PAI-1

Plasminogen activator inhibitor-1

PAS

Systolic blood pressure

PIs

Protease inhibitors

sCD14

Soluble CD14

Notes

Acknowledgments

We would like to thank the physicians from the Infectious Diseases Department (Hospital Universitario San Pedro) and Dr. Ángela Martin Palmero for helping us with patient recruitment and collection of demographic and clinical data.

We would also like to thank all participants of this study.

Authors’ contributions

Study design: P.P.M. and J.A.O. Data collection: P.P.M., J.A.O., and M.J.V.M. Performed the experiments: E.R.F. and M.J.V.M. Analyzed the data: J.M.L.R. and M.J.V.M. Interpretation of the data and wrote the paper: P.P.M., J.A.O., and M.J.V.M. Reviewed and/or edited the manuscript: all authors.

Funding information

This work was supported by Gilead Fellowships 2013 and SEINORTE 2013. MJ Villanueva-Millán was supported by a predoctoral grant from Consejería de Industria, Innovación y Empleo (Government of La Rioja).

Compliance with ethical standards

Conflict of interest

J.A. Oteo has received travel grants from Gilead Sciences, MSD, and Janssen.

Other authors have nothing to declare.

References

  1. 1.
    Alekhin A, Kovach E, Manrique M, Pareja-Tobes P, Pareja E, Tobes R, Pareja-Tobes E (2015) MG7: configurable and scalable 16S metagenomics data analysis. bioRxiv. (preprint).  https://doi.org/10.1101/027714
  2. 2.
    Arndt D, Xia J, Liu Y, Zhou Y, Guo AC, Cruz JA, Sinelnikov I, Budwill K, Nesbo CL, Wishart DS (2012) METAGENassist: a comprehensive web server for comparative metagenomics. Nucleic Acids Res 40(Web Server issue):W88–W95.  https://doi.org/10.1093/nar/gks497 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Beerens H, Romond C (1977) Sulfate-reducing anaerobic bacteria in human feces. Am J Clin Nutr 30(11):1770–1776CrossRefPubMedGoogle Scholar
  4. 4.
    Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12(12):1365–1371CrossRefPubMedGoogle Scholar
  5. 5.
    Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden TL (2009) BLAST+: architecture and applications. BMC Bioinformatics 10:421.  https://doi.org/10.1186/1471-2105-10-421 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A (2011) Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol 17(12):1519–1528.  https://doi.org/10.3748/wjg.v17.i12.1519
  7. 7.
    Caparros-Martin JA, Lareu RR, Ramsay JP, Peplies J, Reen FJ, Headlam HA, Ward NC, Croft KD, Newsholme P, Hughes JD, O'Gara F (2017) Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism. Microbiome. 5(1):95.  https://doi.org/10.1186/s40168-017-0312-4 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J, Fierer N, Owens SM, Betley J, Fraser L, Bauer M, Gormley N, Gilbert JA, Smith G, Knight R (2012) Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J 6(8):1621–1624.  https://doi.org/10.1038/ismej.2012.8 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Carlsson AH, Yakymenko O, Olivier I, Hakansson F, Postma E, Keita AV, Soderholm JD (2013) Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis. Scand J Gastroenterol 48(10):1136–1144.  https://doi.org/10.3109/00365521.2013.828773 CrossRefPubMedGoogle Scholar
  10. 10.
    Castera L, Forns X, Alberti A (2008) Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol 48(5):835–847.  https://doi.org/10.1016/j.jhep.2008.02.008 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cole JR, Wang Q, Fish JA, Chai B, McGarrell DM, Sun Y, Brown CT, Porras-Alfaro A, Kuske CR, Tiedje JM (2014) Ribosomal database project: data and tools for high throughput rRNA analysis. Nucleic Acids Res 42(Database issue):D633–D642.  https://doi.org/10.1093/nar/gkt1244 CrossRefGoogle Scholar
  12. 12.
    Cubero JM, Domingo P, Sambeat M, Ordonez-Llanos J, Rodriguez-Espinosa J, Sanchez-Quesada JL, Perez A (2011) Prevalence of metabolic syndrome among human immunodeficiency virus-infected subjects is widely influenced by the diagnostic criteria. Metab Syndr Relat Disord 9(5):345–351.  https://doi.org/10.1089/met.2010.0129 CrossRefPubMedGoogle Scholar
  13. 13.
    de Groot PF, Frissen MN, de Clercq NC, Nieuwdorp M (2017) Fecal microbiota transplantation in metabolic syndrome: history, present and future. Gut Microbes 8(3):253–267.  https://doi.org/10.1080/19490976.2017.1293224 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Deeks SG, Verdin E, McCune JM (2012) Immunosenescence and HIV. Curr Opin Immunol 24(4):501–506.  https://doi.org/10.1016/j.coi.2012.05.004 CrossRefPubMedGoogle Scholar
  15. 15.
    Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, Margolick JB (2007) HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci 62(11):1279–1286CrossRefPubMedGoogle Scholar
  16. 16.
    Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, Gianella S, Siewe B, Smith DM, Landay AL, Robertson CE, Frank DN, Wilson CC (2014) An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol 7(4):983–994.  https://doi.org/10.1038/mi.2013.116 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Eeg-Olofsson K, Gudbjornsdottir S, Eliasson B, Zethelius B, Cederholm J (2014) The triglycerides-to-HDL-cholesterol ratio and cardiovascular disease risk in obese patients with type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR). Diabetes Res Clin Pract 106(1):136–144.  https://doi.org/10.1016/j.diabres.2014.07.010 CrossRefPubMedGoogle Scholar
  18. 18.
    Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A (2014) Gut microbiota and metabolic syndrome. World J Gastroenterol 20(43):16079–16094.  https://doi.org/10.3748/wjg.v20.i43.16079 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Gonzalez-Quintela A, Alonso M, Campos J, Vizcaino L, Loidi L, Gude F (2013) Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: the role of obesity. PLoS One 8(1):e54600.  https://doi.org/10.1371/journal.pone.0054600 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gori A, Tincati C, Rizzardini G, Torti C, Quirino T, Haarman M, Ben Amor K, van Schaik J, Vriesema A, Knol J, Marchetti G, Welling G, Clerici M (2008) Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis. J Clin Microbiol 46(2):757–758CrossRefPubMedGoogle Scholar
  21. 21.
    Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, Xu A, Chavakis T, Bornstein AB, Ehrhart-Bornstein M, Lamounier-Zepter V, Lohmann T, Wolf T, Bornstein SR (2013) Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J 13(6):514–522.  https://doi.org/10.1038/tpj.2012.43 CrossRefPubMedGoogle Scholar
  22. 22.
    Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 112(17):2735–2752.  https://doi.org/10.1161/CIRCULATIONAHA.105.169404 CrossRefPubMedGoogle Scholar
  23. 23.
    Haro C, Garcia-Carpintero S, Alcala-Diaz JF, Gomez-Delgado F, Delgado-Lista J, Perez-Martinez P, Rangel Zuniga OA, Quintana-Navarro GM, Landa BB, Clemente JC, Lopez-Miranda J, Camargo A, Perez-Jimenez F (2016) The gut microbial community in metabolic syndrome patients is modified by diet. J Nutr Biochem 27:27–31.  https://doi.org/10.1016/j.jnutbio.2015.08.011 CrossRefPubMedGoogle Scholar
  24. 24.
    Jerico C, Knobel H, Montero M, Ordonez-Llanos J, Guelar A, Gimeno JL, Saballs P, Lopez-Colomes JL, Pedro-Botet J (2005) Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors. Diabetes Care 28(1):132–137CrossRefPubMedGoogle Scholar
  25. 25.
    Kaur J (2014) A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014:943162.  https://doi.org/10.1155/2014/943162 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Klatt NR, Funderburg NT, Brenchley JM (2013) Microbial translocation, immune activation, and HIV disease. Trends Microbiol 21(1):6–13.  https://doi.org/10.1016/j.tim.2012.09.001 CrossRefPubMedGoogle Scholar
  27. 27.
    Lassenius MI, Pietilainen KH, Kaartinen K, Pussinen PJ, Syrjanen J, Forsblom C, Porsti I, Rissanen A, Kaprio J, Mustonen J, Groop PH, Lehto M (2011) Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care 34(8):1809–1815.  https://doi.org/10.2337/dc10-2197 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Laval L, Martin R, Natividad JN, Chain F, Miquel S, Desclee de Maredsous C, Capronnier S, Sokol H, Verdu EF, van Hylckama Vlieg JE, Bermudez-Humaran LG, Smokvina T, Langella P (2015) Lactobacillus rhamnosus CNCM I-3690 and the commensal bacterium Faecalibacterium prausnitzii A2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice. Gut Microbes 6(1):1–9.  https://doi.org/10.4161/19490976.2014.990784 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lim MY, You HJ, Yoon HS, Kwon B, Lee JY, Lee S, Song YM, Lee K, Sung J, Ko G (2017) The effect of heritability and host genetics on the gut microbiota and metabolic syndrome. Gut. 66(6):1031–1038.  https://doi.org/10.1136/gutjnl-2015-311326 CrossRefPubMedGoogle Scholar
  30. 30.
    Marchetti G, Tincati C, Silvestri G (2013) Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev 26(1):2–18.  https://doi.org/10.1128/CMR.00050-1226/1/2 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Marotta T, Russo BF, Ferrara LA (2010) Triglyceride-to-HDL-cholesterol ratio and metabolic syndrome as contributors to cardiovascular risk in overweight patients. Obesity (Silver Spring) 18(8):1608–1613.  https://doi.org/10.1038/oby.2009.446oby CrossRefGoogle Scholar
  32. 32.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28(7):412–419CrossRefPubMedGoogle Scholar
  33. 33.
    Medina DA, Pedreros JP, Turiel D, Quezada N, Pimentel F, Escalona A, Garrido D (2017) Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients. PeerJ. 5:e3443.  https://doi.org/10.7717/peerj.3443 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Miquel S, Martin R, Rossi O, Bermudez-Humaran LG, Chatel JM, Sokol H, Thomas M, Wells JM, Langella P (2013) Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol 16(3):255–261.  https://doi.org/10.1016/j.mib.2013.06.003 CrossRefPubMedGoogle Scholar
  35. 35.
    Naidu S, Ponnampalvanar S, Kamaruzzaman SB, Kamarulzaman A (2017) Prevalence of metabolic syndrome among people living with HIV in developing countries: a systematic review. AIDS Patient Care STDs 31(1):1–13.  https://doi.org/10.1089/apc.2016.0140 CrossRefPubMedGoogle Scholar
  36. 36.
    Nasi M, Pinti M, De Biasi S, Gibellini L, Ferraro D, Mussini C, Cossarizza A (2014) Aging with HIV infection: a journey to the center of inflammAIDS, immunosenescence and neuroHIV. Immunol Lett 162(1 Pt B):329–333.  https://doi.org/10.1016/j.imlet.2014.06.012 CrossRefPubMedGoogle Scholar
  37. 37.
    Nasi M, De Biasi S, Gibellini L, Bianchini E, Pecorini S, Bacca V, Guaraldi G, Mussini C, Pinti M, Cossarizza A (2017) Ageing and inflammation in patients with HIV infection. Clin Exp Immunol 187(1):44–52.  https://doi.org/10.1111/cei.12814 CrossRefPubMedGoogle Scholar
  38. 38.
    Nguyen KA, Peer N, Mills EJ, Kengne AP (2016) A meta-analysis of the metabolic syndrome prevalence in the global HIV-infected population. PLoS One 11(3):e0150970.  https://doi.org/10.1371/journal.pone.0150970 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Nolan JA, Skuse P, Govindarajan K, Patterson E, Konstantinidou N, Casey PG, MacSharry J, Shanahan F, Stanton C, Hill C, Cotter PD, Joyce SA, Gahan CGM (2017) The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles. Am J Physiol Gastrointest Liver Physiol 312(5):G488–G497.  https://doi.org/10.1152/ajpgi.00149.2016 CrossRefPubMedGoogle Scholar
  40. 40.
    Odamaki T, Kato K, Sugahara H, Hashikura N, Takahashi S, Xiao JZ, Abe F, Osawa R (2016) Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol 16:90.  https://doi.org/10.1186/s12866-016-0708-5 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Palacios R, Santos J, Gonzalez M, Ruiz J, Marquez M (2007) Incidence and prevalence of the metabolic syndrome in a cohort of naive HIV-infected patients: prospective analysis at 48 weeks of highly active antiretroviral therapy. Int J STD AIDS 18(3):184–187.  https://doi.org/10.1258/095646207780132415 CrossRefPubMedGoogle Scholar
  42. 42.
    Rios-Covian D, Ruas-Madiedo P, Margolles A, Gueimonde M, de Los Reyes-Gavilan CG, Salazar N (2016) Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol 7:185.  https://doi.org/10.3389/fmicb.2016.00185 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Riviere A, Selak M, Lantin D, Leroy F, De Vuyst L (2016) Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front Microbiol 7:979.  https://doi.org/10.3389/fmicb.2016.00979 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Sandler NG, Douek DC (2012) Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol 10(9):655–666.  https://doi.org/10.1038/nrmicro2848 CrossRefPubMedGoogle Scholar
  45. 45.
    Sato J, Kanazawa A, Ikeda F, Yoshihara T, Goto H, Abe H, Komiya K, Kawaguchi M, Shimizu T, Ogihara T, Tamura Y, Sakurai Y, Yamamoto R, Mita T, Fujitani Y, Fukuda H, Nomoto K, Takahashi T, Asahara T, Hirose T, Nagata S, Yamashiro Y, Watada H (2014) Gut dysbiosis and detection of “live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care 37(8):2343–2350.  https://doi.org/10.2337/dc13-2817 CrossRefPubMedGoogle Scholar
  46. 46.
    Smith RL, de Boer R, Brul S, Budovskaya Y, van Spek H (2012) Premature and accelerated aging: HIV or HAART? Front Genet 3:328.  https://doi.org/10.3389/fgene.2012.00328 CrossRefPubMedGoogle Scholar
  47. 47.
    Sun L, Yu Z, Ye X, Zou S, Li H, Yu D, Wu H, Chen Y, Dore J, Clement K, Hu FB, Lin X (2010) A marker of endotoxemia is associated with obesity and related metabolic disorders in apparently healthy Chinese. Diabetes Care 33(9):1925–1932.  https://doi.org/10.2337/dc10-0340 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Villanueva-Millan MJ, Perez-Matute P, Recio-Fernandez E, Lezana Rosales JM, Oteo JA (2017) Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV-infected patients. J Int AIDS Soc 20(1):21526.  https://doi.org/10.7448/IAS.20.1.21526 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Vital M, Penton CR, Wang Q, Young VB, Antonopoulos DA, Sogin ML, Morrison HG, Raffals L, Chang EB, Huffnagle GB, Schmidt TM, Cole JR, Tiedje JM (2013) A gene-targeted approach to investigate the intestinal butyrate-producing bacterial community. Microbiome 1(1):8.  https://doi.org/10.1186/2049-2618-1-8 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Vital M, Karch A, Pieper DH (2017) Colonic butyrate-producing communities in humans: an overview using omics data. mSystems 2(6).  https://doi.org/10.1128/mSystems.00130-17
  51. 51.
    Worm SW, Lundgren JD (2011) The metabolic syndrome in HIV. Best Pract Res Clin Endocrinol Metab 25(3):479–486.  https://doi.org/10.1016/j.beem.2010.10.018 CrossRefPubMedGoogle Scholar
  52. 52.
    Zhang C, Zhang M, Wang S, Han R, Cao Y, Hua W, Mao Y, Zhang X, Pang X, Wei C, Zhao G, Chen Y, Zhao L (2010) Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 4(2):232–241.  https://doi.org/10.1038/ismej.2009.112 CrossRefPubMedGoogle Scholar

Copyright information

© University of Navarra 2019

Authors and Affiliations

  1. 1.Infectious Diseases, Microbiota and Metabolism Unit, Infectious Diseases DepartmentCenter for Biomedical Research of La Rioja (CIBIR)LogroñoSpain
  2. 2.Infectious Diseases DepartmentHospital Universitario San PedroLogroñoSpain

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