People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion, is the interaction between the gut barrier and gut microbes themselves. We evaluated the relationship of gut barrier integrity, as indexed by plasma occludin levels (higher levels corresponding to greater loss of occludin from the gut barrier), to gut microbial diversity. PWH and people without HIV (PWoH) participants were recruited from community sources and provided stool, and 16S rRNA amplicon sequencing was used to characterize the gut microbiome. Microbial diversity was indexed by Faith’s phylogenetic diversity (PD). Participants were 50 PWH and 52 PWoH individuals, mean ± SD age 45.6 ± 14.5 years, 28 (27.5%) women, 50 (49.0%) non-white race/ethnicity. PWH had higher gut microbial diversity (Faith’s PD 14.2 ± 4.06 versus 11.7 ± 3.27; p = 0.0007), but occludin levels were not different (1.84 ± 0.311 versus 1.85 ± 0.274; p = 0.843). Lower gut microbial diversity was associated with higher plasma occludin levels in PWH (r = −0.251; p = 0.0111), but not in PWoH. A multivariable model demonstrated an interaction (p = 0.0459) such that the correlation between Faith’s PD and plasma occludin held only for PWH (r = −0.434; p = 0.0017), but not for PWoH individuals (r = −0.0227; p = 0.873). The pattern was similar for Shannon alpha diversity. Antiretroviral treatment and viral suppression status were not associated with gut microbial diversity (ps > 0.10). Plasma occludin levels were not significantly related to age, sex or ethnicity, nor to current or nadir CD4 or plasma viral load. Higher occludin levels were associated with higher plasma sCD14 and LPS, both markers of microbial translocation. Together, the findings suggest that damage to the gut epithelial barrier is an important mediator of microbial translocation and inflammation in PWH, and that reduced gut microbiome diversity may have an important role.

中文翻译：

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肠道屏障功能和微生物易位的标志物与艾滋病毒感染者下肠道微生物多样性相关

人类免疫缺陷病毒 (HIV) (PWH) 感染者的肠道屏障完整性降低（“肠漏”），导致脂多糖 (LPS) 等微生物抗原扩散（微生物易位）进入循环系统，从而刺激炎症。除了肠道淋巴组织 CD4+ T 细胞耗竭之外，这种干扰的一个潜在来源是肠道屏障和肠道微生物本身之间的相互作用。我们评估了肠道屏障完整性与肠道微生物多样性的关系，以血浆 Occludin 水平为指标（较高的水平对应于肠道屏障中 Occludin 的更大损失）。PWH 和艾滋病毒感染者 (PWoH) 参与者从社区来源招募并提供粪便，并使用 16S rRNA 扩增子测序来表征肠道微生物组。微生物多样性由 Faith 的系统发育多样性 (PD) 索引。参与者包括 50 名 PWH 和 52 名 PWoH 个体，平均 ± SD 年龄 45.6 ± 14.5 岁，28 名 (27.5%) 女性，50 名 (49.0%) 非白人种族/族裔。PWH 具有较高的肠道微生物多样性（Faith 的 PD 14.2 ± 4.06 对比 11.7 ± 3.27；p = 0.0007），但 occludin 水平没有差异（1.84 ± 0.311 对比 1.85 ± 0.274；p = 0.843）。在 PWH 中，较低的肠道微生物多样性与较高的血浆 occludin 水平相关（r = -0.251；p = 0.0111），但在 PWoH 中则不然。多变量模型证明了一种相互作用 ( p = 0.0459)，使得 Faith's PD 和血浆 occludin 之间的相关性仅适用于 PWH (r = -0.434；p = 0.0017)，但不适用于 PWoH 个体 (r = -0.0227；p = 0.873 ) ）。香农阿尔法多样性的模式类似。抗逆转录病毒治疗和病毒抑制状态与肠道微生物多样性无关（ps > 0.10）。血浆occludin水平与年龄、性别或种族没有显着相关，与当前或最低CD4或血浆病毒载量也没有显着相关。较高的 occludin 水平与较高的血浆 sCD14 和 LPS 相关，这两者都是微生物易位的标志。总之，这些发现表明，肠道上皮屏障的损伤是感染者出血后微生物易位和炎症的重要介质，而肠道微生物组多样性的减少可能发挥着重要作用。