An emerging paradigm suggests that gut glycosylation is a key force in maintaining the homeostatic relationship between the gut and its microbiota. Nevertheless, it is unclear how gut glycosylation contributes to the HIV-associated microbial translocation and inflammation that persist despite viral suppression and contribute to the development of several comorbidities. We examined terminal ileum, right colon, and sigmoid colon biopsies from HIV-infected virally-suppressed individuals and found that gut glycomic patterns are associated with distinct microbial compositions and differential levels of chronic inflammation and HIV persistence. In particular, high levels of the pro-inflammatory hypo-sialylated T-antigen glycans and low levels of the anti-inflammatory fucosylated glycans were associated with higher abundance of glycan-degrading microbial species (in particular, Bacteroides vulgatus), a less diverse microbiome, higher levels of inflammation, and higher levels of ileum-associated HIV DNA. These findings are linked to the activation of the inflammasome-mediating eIF2 signaling pathway. Our study thus provides the first proof-of-concept evidence that a previously unappreciated factor, gut glycosylation, is a force that may impact the vicious cycle between HIV infection, microbial translocation, and chronic inflammation.

一种新兴的范例表明，肠道糖基化是维持肠道与其微生物群之间稳态关系的关键力量。然而，目前尚不清楚肠道糖基化如何导致 HIV 相关微生物易位和炎症，尽管病毒受到抑制，但炎症仍然存在，并导致多种合并症的发生。我们检查了来自 HIV 感染的病毒抑制个体的末端回肠、右结肠和乙状结肠活检，发现肠道糖组学模式与不同的微生物组成和不同水平的慢性炎症和 HIV 持续存在有关。尤其，Bacteroides vulgatus)，微生物组多样性较低，炎症水平较高，回肠相关 HIV DNA 水平较高。这些发现与炎症小体介导的 eIF2 信号通路的激活有关。因此，我们的研究提供了第一个概念验证证据，证明以前未被重视的因素肠道糖基化是一种可能影响 HIV 感染、微生物易位和慢性炎症之间恶性循环的力量。