Clinic of Infectious Diseases, Department of Health Sciences, University of Milan, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Milan, Italy.
Biochemistry Laboratory, Department of Health Sciences, University of Milan, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Milan, Italy.
Front Immunol. 2021 Feb 26;12:639291. doi: 10.3389/fimmu.2021.639291. eCollection 2021.
We explored the long-term effects of cART on markers of gut damage, microbial translocation, and paired gut/blood microbiota composition, with a focus on the role exerted by different drug classes. We enrolled 41 cART naïve HIV-infected subjects, undergoing blood and fecal sampling prior to cART (T0) and after 12 (T12) and 24 (T24) months of therapy. Fifteen HIV-uninfected individuals were enrolled as controls. We analyzed: (i) T-cell homeostasis (flow cytometry); (ii) microbial translocation (sCD14, EndoCab, 16S rDNA); (iii) intestinal permeability and damage markers (LAC/MAN, I-FABP, fecal calprotectin); (iv) plasma and fecal microbiota composition (alpha- and beta-diversity, relative abundance); (v) functional metagenome predictions (PICRUSt). Twelve and twenty four-month successful cART resulted in a rise in EndoCAb ( = 0.0001) and I-FABP ( = 0.039) vis-à-vis stable 16S rDNA, sCD14, calprotectin and LAC/MAN, along with reduced immune activation in the periphery. Furthermore, cART did not lead to substantial modifications of microbial composition in both plasma and feces and metabolic metagenome predictions. The stratification according to cART regimens revealed a feeble effect on microbiota composition in patients on NNRTI-based or INSTI-based regimens, but not PI-based regimens. We hereby show that 24 months of viro-immunological effective cART, while containing peripheral hyperactivation, exerts only minor effects on the gastrointestinal tract. Persistent alteration of plasma markers indicative of gut structural and functional impairment seemingly parallels enduring fecal dysbiosis, irrespective of drug classes, with no effect on metabolic metagenome predictions.
我们探讨了 cART 对肠道损伤标志物、微生物易位和肠道/血液微生物群落组成的长期影响，重点关注不同药物类别所发挥的作用。我们招募了 41 名 cART 初治的 HIV 感染者，在 cART 前（T0）、12 个月（T12）和 24 个月（T24）时进行血液和粪便采样。同时招募了 15 名 HIV 未感染者作为对照。我们分析了：（i）T 细胞稳态（流式细胞术）；（ii）微生物易位（sCD14、EndoCAb、16S rDNA）；（iii）肠道通透性和损伤标志物（LAC/MAN、I-FABP、粪便钙卫蛋白）；（iv）血浆和粪便微生物群落组成（alpha 和 beta 多样性、相对丰度）；（v）功能宏基因组预测（PICRUSt）。12 个月和 24 个月成功的 cART 导致 EndoCAb（=0.0001）和 I-FABP（=0.039）升高，而 16S rDNA、sCD14、钙卫蛋白和 LAC/MAN 稳定，外周免疫激活减少。此外，cART 并没有导致血浆和粪便中微生物组成和代谢宏基因组预测发生实质性改变。根据 cART 方案进行分层，发现基于 NNRTI 或 INSTI 的方案对患者的微生物组成影响较弱，但基于 PI 的方案没有影响。我们在此表明，24 个月的病毒学和免疫学有效 cART 虽然能控制病毒，但外周的过度激活仅对胃肠道产生较小的影响。血浆标志物持续改变表明肠道结构和功能受损，与药物类别无关，粪便微生物失调持续存在，但对代谢宏基因组预测没有影响。
