HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related post-acute sequelae of SARS-CoV-2.
HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related post-acute sequelae of SARS-CoV-2.
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DOI：
10.1038/s41598-023-50027-1
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发表时间：
2024-01-03
影响因子：
4.6
通讯作者：
Maunakea, Alika K.
中科院分区：
文献类型：
--
作者：
Rubas, Noelle C.;Peres, Rafael;Kunihiro, Braden P.;Allan, Nina P.;Phankitnirundorn, Krit;Wells, Riley K.;McCraken, Trevor A.;Lee, Rosa H.;Umeda, Lesley;Conching, Andie;Juarez, Ruben;Maunakea, Alika K.
虽然肥胖是SARS-CoV-2感染后急性后遗症（PASC，“长期COVID”）的一个危险因素，但对这种现象的潜在机制仍知之甚少。为了解决这一知识差距，我们进行了一项为期6周的纵向研究，以检查从SARS-CoV-2感染中恢复的急性期后患者的免疫活性和肠道微生物群失调。每周收集自我报告的症状频率和血液样本，通过ELISA和Luminex评估血浆中的多种生物标志物和免疫细胞谱。在恢复的早期阶段收集来自粪便样品的DNA，用于使用基于16 S的宏基因组测序对肠道微生物组成和多样性进行基线评估。多元回归分析显示，肥胖相关的PASC与持续的促炎性免疫特征和适应性免疫降低有关，与肠道微生物多样性降低相对应。特别是，发现高迁移率族蛋白1（HMGB 1）蛋白的信号传导增强与这种失调相关，其血浆中的上调水平与肥胖症加重的病毒中和作用显著受损相关。这些发现暗示HMGB 1作为PASC的候选生物标志物，具有潜在的风险评估和靶向治疗的应用。
While obesity is a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC, "long-COVID"), the mechanism(s) underlying this phenomenon remains poorly understood. To address this gap in knowledge, we performed a 6-week longitudinal study to examine immune activity and gut microbiome dysbiosis in post-acute stage patients recovering from SARS-CoV-2 infection. Self-reported symptom frequencies and blood samples were collected weekly, with plasma assessed by ELISA and Luminex for multiple biomarkers and immune cell profiling. DNA from stool samples were collected at the early stage of recovery for baseline assessments of gut microbial composition and diversity using 16S-based metagenomic sequencing. Multiple regression analyses revealed obesity-related PASC linked to a sustained proinflammatory immune profile and reduced adaptive immunity, corresponding with reduced gut microbial diversity. In particular, enhanced signaling of the high mobility group box 1 (HMGB1) protein was found to associate with this dysregulation, with its upregulated levels in plasma associated with significantly impaired viral neutralization that was exacerbated with obesity. These findings implicate HMGB1 as a candidate biomarker of PASC, with potential applications for risk assessment and targeted therapies.
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