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Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques
Nichole R. Klatt, … , Jacob D. Estes, Jason M. Brenchley
Nichole R. Klatt, … , Jacob D. Estes, Jason M. Brenchley
Published January 16, 2013
Citation Information: J Clin Invest. 2013;123(2):903-907. https://doi.org/10.1172/JCI66227.
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Brief Report Article has an altmetric score of 19

Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques

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Abstract

HIV infection results in gastrointestinal (GI) tract damage, microbial translocation, and immune activation, which are not completely ameliorated with suppression of viremia by antiretroviral (ARV) therapy. Furthermore, increased morbidity and mortality of ARV-treated HIV-infected individuals is associated with these dysfunctions. Thus, to enhance GI tract physiology, we treated SIV-infected pigtail macaques with ARVs, probiotics, and prebiotics or with ARVs alone. This synbiotic treatment resulted in increased frequency and functionality of GI tract APCs, enhanced reconstitution and functionality of CD4+ T cells, and reduced fibrosis of lymphoid follicles in the colon. Thus, ARV synbiotic supplementation in HIV-infected individuals may improve GI tract immunity and thereby mitigate inflammatory sequelae, ultimately improving prognosis.

Authors

Nichole R. Klatt, Lauren A. Canary, Xiaoyong Sun, Carol L. Vinton, Nicholas T. Funderburg, David R. Morcock, Mariam Quiñones, Clayton B. Deming, Molly Perkins, Daria J. Hazuda, Michael D. Miller, Michael M. Lederman, Julie A. Segre, Jeffrey D. Lifson, Elias K. Haddad, Jacob D. Estes, Jason M. Brenchley

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Figure 1

PP-treated animals have increased expression of APC-related genes.

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PP-treated animals have increased expression of APC-related genes.
(A) T...
(A) Top 200 genes based on P value for contrast between RNA extractions from colonic CD45+ leukocytes from animals treated with ARV alone (left) and animals treated with ARV+PP (right). The complete linkage method was used for hierarchical cluster analysis. Rows, normalized expression value for single genes; columns, each sample; red, upregulated; blue, downregulated gene expression based on Z-score (see legend below). (B) Fold change of selected upregulated genes in colonic leukocytes in animals treated with ARV+PP (top) or ARV alone (bottom). P values are indicated over each bar. (C) Frequency of HLA-DR+CD45+, live APCs in the colon. (D) MFI of HLA-DR on live CD45+ APCs. (E) Percentages of live, HLA-DR+CD45+ APCs in the colon producing IL-23 after mitogenic stimulation. Circles, ARV+PP-treated PTM with suppressed viremia; squares, ARV+PP-treated slow responder PTM; triangles, ARV-alone–treated PTM. Horizontal bars represent median. All data analyzed from necropsy samples (∼day 315 after SIV).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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