Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primates.
Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primates.
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DOI：
10.1038/s41598-018-26313-8
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发表时间：
2018-05-23
影响因子：
4.6
通讯作者：
Burgener AD
中科院分区：
文献类型：
--
作者：
Girard L;Birse K;Holm JB;Gajer P;Humphrys MS;Garber D;Guenthner P;Noël-Romas L;Abou M;McCorrister S;Westmacott G;Wang L;Rohan LC;Matoba N;McNicholl J;Palmer KE;Ravel J;Burgener AD
Topical microbicides are being explored as an HIV prevention method for individuals who practice receptive anal intercourse. In vivo studies of these microbicides are critical to confirm safety. Here, we evaluated the impact of a rectal microbicide containing the antiviral lectin, Griffithsin (GRFT), on the rectal mucosal proteome and microbiome. Using a randomized, crossover placebo-controlled design, six rhesus macaques received applications of hydroxyethylcellulose (HEC)- or carbopol-formulated 0.1% GRFT gels. Rectal mucosal samples were then evaluated by label-free tandem MS/MS and 16 S rRNA gene amplicon sequencing, for proteomics and microbiome analyses, respectively. Compared to placebo, GRFT gels were not associated with any significant changes to protein levels at any time point (FDR < 5%), but increased abundances of two common and beneficial microbial taxa after 24 hours were observed in HEC-GRFT gel (p < 2E-09). Compared to baseline, both placebo formulations were associated with alterations to proteins involved in proteolysis, activation of the immune response and inflammation after 2 hours (p < 0.0001), and increases in beneficial Faecalibacterium spp. after 24 hours in HEC placebo gel (p = 4.21E-15). This study supports the safety profile of 0.1% GRFT gel as an anti-HIV microbicide and demonstrates that current placebo formulations may associate with changes to rectal proteome and microbiota.
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影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
15.5
作者：
Fadrosh DW;Ma B;Gajer P;Sengamalay N;Ott S;Brotman RM;Ravel J
通讯作者：
Ravel J
影响因子：
168.9
作者：
Beyrer, Chris;Baral, Stefan D.;van Griensven, Frits;Goodreau, Steven M.;Chariyalertsak, Suwat;Wirtz, Andrea L.;Brookmeyer, Ron
通讯作者：
Brookmeyer, Ron
影响因子：
7.6
作者：
Rohan, Lisa C.;Yang, Haitao;Wang, Lin
通讯作者：
Wang, Lin
影响因子：
8
作者：
Arnold, Kelly B.;Burgener, Adam;McKinnon, Lyle R.
通讯作者：
McKinnon, Lyle R.