Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation.
Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation.
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艾滋病毒感染中产生丁酸酯的细菌的丰度与微生物易位和免疫激活有关。
DOI：
10.1097/qad.0000000000001366
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发表时间：
2017-02-20
期刊：
影响因子：
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通讯作者：
Wilson CC
中科院分区：
文献类型：
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作者：
Dillon SM;Kibbie J;Lee EJ;Guo K;Santiago ML;Austin GL;Gianella S;Landay AL;Donovan AM;Frank DN;McCARTER MD;Wilson CC
肠道微生物易位（MT）是HIV-1感染期间慢性免疫激活的主要驱动力。HIV-1相关的肠道生态失调，包括粘膜相关致病菌的增加，可能会影响MT，并导致粘膜和全身炎症。因此，了解肠道微生物及其代谢产物（如丁酸盐）在HIV-1感染期间影响免疫细胞功能的机制至关重要。进行了一项横断面研究，以比较未经治疗的慢性HIV-1感染（n=18）和未感染（n=14）研究参与者的结肠活检和粪便中丁酸盐产生细菌物种（BPB）的相对丰度。使用离体人肠细胞培养模型评价外源性添加的丁酸盐对肠T细胞活化和HIV-1感染的影响。在16 S核糖体RNA序列数据集中鉴定物种。用嗜CCR 5的HIV-1Bal感染离体分离的固有层（LP）单核细胞，用肠道革兰氏阴性菌和一系列丁酸盐剂量培养，并测量LP T细胞活化和HIV-1感染水平。总BPB的相对丰度（RA），特别是罗斯拜瑞氏菌，较低的HIV-1感染者与未感染的受试者的结肠粘膜。在HIV-1感染的研究参与者中，R. RA与MT、免疫激活和血管炎症的系统指标呈负相关。外源性丁酸盐抑制肠道革兰氏阴性菌驱动的LP T细胞活化和体外HIV-1感染水平。结肠BPB减少导致的粘膜丁酸盐减少可能会加剧致病菌驱动的肠道T细胞活化和HIV复制，从而导致HIV相关的粘膜发病机制。
Gut microbial translocation (MT) is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence MT and contribute to mucosal and systemic inflammation. Thus, it is critical to understand the mechanisms by which gut microbes and their metabolic products, such as butyrate, influence immune cell function during HIV-1 infection. A cross-sectional study was performed to compare the relative abundance of butyrate-producing bacterial species (BPB) in colonic biopsies and stool of untreated, chronic HIV-1 infected (n=18) and uninfected (n=14) study participants. The effect of exogenously added butyrate on gut T cell activation and HIV-1 infection was evaluated using an ex vivo human intestinal cell culture model. Species were identified in 16S ribosomal RNA sequence datasets. Ex vivo isolated lamina propria (LP) mononuclear cells were infected with CCR5-tropic HIV-1Bal, cultured with enteric Gram-negative bacteria and a range of butyrate doses, and LP T cell activation and HIV-1 infection levels measured. Relative abundance (RA) of total BPB and specifically of Roseburia intestinalis, were lower in colonic mucosa of HIV-1 infected versus uninfected subjects. In HIV-1 infected study participants, R. intestinalis RA inversely correlated with systemic indicators of MT, immune activation and vascular inflammation. Exogenous butyrate suppressed enteric Gram-negative bacteria-driven LP T cell activation and HIV-1 infection levels in vitro. Reductions in mucosal butyrate from diminished colonic BPB may exacerbate pathobiont driven gut T cell activation and HIV replication, thereby contributing to HIV-associated mucosal pathogenesis.