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Gut Lactobacillales are associated with higher CD4 and less microbial translocation during HIV infection

Pérez-Santiago, Josuéa; Gianella, Saraa; Massanella, Martaa; Spina, Celsa A.a,b; Karris, Maile Y.a; Var, Susanna R.a; Patel, Dereka; Jordan, Parris S.a; Young, Jason A.a; Little, Susan J.a; Richman, Douglas D.a,b; Smith, Davey M.a,b

doi: 10.1097/QAD.0b013e3283611816
Clinical Science

Objective: Early HIV infection is characterized by a dramatic depletion of CD4 T cells in the gastrointestinal tract and translocation of bacterial products from the gut into the blood. In this study, we evaluated if gut bacterial profiles were associated with immune status before and after starting antiretroviral therapy (ART).

Design: We evaluated the gut microbiota of men recently infected with HIV (n = 13) who were participating in a randomized, double-blind controlled trial of combination ART and maraviroc versus placebo and who were followed for 48 weeks.

Methods: To evaluate the gut microbiota of participants, we pyrosequenced the bacterial populations from anal swabs collected before and longitudinally after the initiation of ART. Associations of the gut flora with clinical variables (lymphocyte profiles and viral loads), activation and proliferation markers in peripheral blood mononuclear cells and gut biopsies (measured by flow cytometry) and markers of microbial translocation (lipopolysaccharide and soluble CD14) were performed by regression analyses using R statistical software.

Results: Using pyrosequencing, we identified that higher proportions of Lactobacillales in the distal gut of recently HIV-infected individuals were associated with lower markers of microbial translocation, higher CD4% and lower viral loads before ART was started. Similarly, during ART, higher proportions of gut Lactobacillales were associated with higher CD4%, less microbial translocation, less systemic immune activation, less gut T lymphocyte proliferation, and higher CD4% in the gut.

Conclusion: Shaping the gut microbiome, especially proportions of Lactobacillales, could help to preserve immune function during HIV infection.

Supplemental Digital Content is available in the text

aUniversity of California San Diego, La Jolla

bVeterans Administration San Diego Healthcare System, San Diego, California, USA.

Correspondence to Josué Pérez-Santiago, PhD, University of California San Diego, 9500 Gilman Drive MC 0679, La Jolla, CA 92093–0679, USA. Tel: +1 858 552 8585/1621; fax: +1 858 552 7445; e-mail: joperez@ucsd.edu

Received 7 October, 2012

Revised 6 March, 2013

Accepted 10 March, 2013

In limited form some of these data were presented at the Fred Hutchinson Cancer Research Center retreat from June 14–15, 2012 in Seattle, Washington.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).

© 2013 Lippincott Williams & Wilkins, Inc.