Zhang Lin, Wang Shilan, Wong Martin C S, Mok Chris K P, Ching Jessica Y L, Mak Joyce W Y, Chen Chunke, Huo Bing, Yan Shuai, Cheung Chun Pan, Chiu Emily O L, Fung Emily Y T, Cheong Pui Kuan, Chan Francis K L, Ng Siew C
Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, China.
New Cornerstone Science Laboratory, The Chinese University of Hong Kong, Hong Kong SAR, China.
NPJ Biofilms Microbiomes. 2025 Aug 25;11(1):171. doi: 10.1038/s41522-025-00804-9.
The study aims to tackle the seed and soil microbiome and mechanisms that contribute to the effect of synbiotics in enhancing immunogenicity after SARS-CoV-2 vaccination in elderly and diabetic patients. Among 369 subjects who received 3 months of SIM01, a gut microbiota-derived synbiotic formula of three Bifidobacterium strains (B. adolescentis, B. bididum, and B. longum) or a placebo after the SARS-CoV-2 vaccines (mRNA vaccine BNT162b2 (Pfizer-BioNTech) or the inactivated vaccine Sinovac-CoronaVac), we performed metagenomic sequencing in stool samples of 280 vaccinees collected at baseline and 3-month postvaccination and metabonomic sequencing in 276 vaccinees collected at baseline and 1-month postvaccination. The open niche of autochthonous gut microbiota (lower levels of Bifidobacterium and decreased functional potential for carbohydrate metabolism) was associated with enhancing SIM01-contained species. The enrichment of three bifidobacterial species after 3 months of SIM01 intervention (BABBBL_fc) was positively correlated with the level of neutralizing antibodies to the BNT162b2 vaccine at 6-month postvaccination. The fold change of benzoic acid was positively correlated with BABBBL_fc in the BNT162b2 vaccinees, which was also implicated with SARS-CoV-2 surrogate virus neutralization test (sVNT)% levels at 1-month postvaccination. Importantly, SIM01 strain engraftment assessed by StrainPhlAn (A metagenomic strain-level population genomics tool) was associated with a higher fold change of three bifidobacterial species and could be predicted based on the baseline gut microbiome. Therefore, the resident gut microbiome affected the SIM01 engraftment, which was associated with the immunogenicity of SARS-CoV-2 BNT162b2 vaccines.
该研究旨在探讨种子和土壤微生物群以及有助于合生元在老年和糖尿病患者中增强SARS-CoV-2疫苗接种后免疫原性的机制。在369名受试者中，他们在接种SARS-CoV-2疫苗（mRNA疫苗BNT162b2（辉瑞-生物科技）或灭活疫苗科兴新冠疫苗）后接受了3个月的SIM01（一种由三种双歧杆菌菌株（青春双歧杆菌、两歧双歧杆菌和长双歧杆菌）组成的肠道微生物群衍生的合生元配方）或安慰剂，我们对280名在基线和接种后3个月采集粪便样本的疫苗接种者进行了宏基因组测序，并对276名在基线和接种后1个月采集样本的疫苗接种者进行了代谢组学测序。本地肠道微生物群的开放生态位（双歧杆菌水平较低以及碳水化合物代谢功能潜力降低）与增强含SIM01的物种有关。SIM01干预3个月后三种双歧杆菌物种的富集（BABBBL_fc）与接种后6个月时针对BNT162b2疫苗的中和抗体水平呈正相关。苯甲酸的倍数变化与BNT162b2疫苗接种者中的BABBBL_fc呈正相关，这也与接种后1个月时的SARS-CoV-2替代病毒中和试验（sVNT）%水平有关。重要的是，通过StrainPhlAn（一种宏基因组菌株水平群体基因组学工具）评估的SIM01菌株植入与三种双歧杆菌物种的较高倍数变化相关，并且可以根据基线肠道微生物群进行预测。因此，常驻肠道微生物群影响了SIM01的植入，这与SARS-CoV-2 BNT162b2疫苗的免疫原性有关。
