Gut lactate-producing bacteria promote CD4 T cell recovery on Anti-retroviral therapy in HIV-infected patients.
Gut lactate-producing bacteria promote CD4 T cell recovery on Anti-retroviral therapy in HIV-infected patients.
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DOI：
10.1016/j.csbj.2021.05.021
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发表时间：
2021
影响因子：
6
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
Lyu W;Meng Q;Xiao J;Li J;Wang J;Qiu Z;Song X;Zhu H;Shao C;Chu Y;Zhou Q;Li T;Jean-Pierre R;Yu J;Han Y;Kang Y
抗逆转录病毒疗法（ART）有效地抑制了HIV感染患者的病毒复制，但15-20%的患者（称为免疫无应答者）无法实现CD 4+细胞恢复正常值。肠道微生物群组成已被证明会影响宿主免疫力。在此，为了鉴定可能影响HIV感染患者中CD 4恢复的肠道微生物剂，我们利用“准配对队列”方法来分析来自免疫应答者（IR）和免疫无应答者（INR）的肠道宏基因组数据。该方法鉴定了IR中链球菌属和相关产乳酸菌（LAB）的显著富集。在验证队列中，观察到这些LAB的丰度与ART后CD 4+恢复之间的正相关性，并且基于这些LAB的预测模型在预测免疫恢复方面表现良好。最后，使用抗体诱导的CD 4+细胞耗竭的无菌小鼠模型的实验表明，补充产乳酸盐嗜热链球菌强烈促进CD 4恢复。总之，我们的研究确定了一组LAB与增强ART后HIV感染患者的免疫恢复相关，并在小鼠模型中促进CD 4+细胞恢复。这些发现有利于补充LAB共生体作为改善HIV感染患者CD 4+细胞计数的治疗策略。
Anti-retroviral therapy (ART) effectively suppresses viral replication in HIV-infected patients, however CD4 + cell restoration to normal value is not achieved by 15–20% of patients who are called immune non-responders. Gut microbiota composition has been shown to influence host immunity. Herein, to identify intestinal microbial agents that may influence the CD4 recovery in HIV-infected patients, we utilized a “Quasi-paired cohort” method to analyze intestinal metagenome data from immunological responders (IRs) and immunological non-responders (INRs). This method identified significant enrichment for Streptococcus sp. and related lactate-producing bacteria (LAB) in IRs. In a validation cohort, positive correlations between the abundance of these LAB and the post-ART CD4 + recovery was observed, and a prediction model based on these LAB performed well in predicting immune recovery. Finally, experiments using a germ-free mouse model of antibody-induced CD4 + cell depletion showed that supplementation with a lactate-producing commensal Streptococcus thermophilus strongly promoted CD4 recovery. In conclusion, our study identified a group of LAB that was associated with enhanced immune recovery in post-ART HIV-infected patients and promotes CD4 + cell restoration in a mouse model. These findings favour supplementation of LAB commensal as a therapeutic strategy for CD4 + cell count improvement in HIV-infected patients.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.5049/ebp.2006.4.1.53
发表时间：
2006-03-01
期刊：
Electrolyte & blood pressure : E & BP
影响因子：
--
作者：
Kang, Kyung Pyo;Lee, Sik;Kang, Sung Kyew
通讯作者：
Kang, Sung Kyew
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
64.5
作者：
Fischbach MA
通讯作者：
Fischbach MA
影响因子：
9.8
作者：
Haas R;Smith J;Rocher-Ros V;Nadkarni S;Montero-Melendez T;D'Acquisto F;Bland EJ;Bombardieri M;Pitzalis C;Perretti M;Marelli-Berg FM;Mauro C
通讯作者：
Mauro C