关键词: COVID-19 SARS-CoV-2 dysbiosis immunisation immunity kidney transplantation microbiota prebiotics

来  源:   DOI:10.3390/vaccines12060608   PDF(Pubmed)

Abstract:
Kidney transplant recipients are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard two-dose vaccination schedules are typically inadequate to generate protective immunity. Gut dysbiosis, which is common among kidney transplant recipients and known to effect systemic immunity, may be a contributing factor to a lack of vaccine immunogenicity in this at-risk cohort. The gut microbiota modulates vaccine responses, with the production of immunomodulatory short-chain fatty acids by bacteria such as Bifidobacterium associated with heightened vaccine responses in both observational and experimental studies. As SCFA-producing populations in the gut microbiota are enhanced by diets rich in non-digestible fibre, dietary supplementation with prebiotic fibre emerges as a potential adjuvant strategy to correct dysbiosis and improve vaccine-induced immunity. In a randomised, double-bind, placebo-controlled trial of 72 kidney transplant recipients, we found dietary supplementation with prebiotic inulin for 4 weeks before and after a third SARS-CoV2 mRNA vaccine to be feasible, tolerable, and safe. Inulin supplementation resulted in an increase in gut Bifidobacterium, as determined by 16S RNA sequencing, but did not increase in vitro neutralisation of live SARS-CoV-2 virus at 4 weeks following a third vaccination. Dietary fibre supplementation is a feasible strategy with the potential to enhance vaccine-induced immunity and warrants further investigation.
摘要:
肾移植受者因SARS-CoV-2感染住院和死亡的风险增加,和标准的两剂量疫苗接种时间表通常不足以产生保护性免疫。肠道菌群失调,这在肾移植受者中很常见,并且已知会影响全身免疫,可能是该高危队列中缺乏疫苗免疫原性的一个促成因素.肠道微生物群调节疫苗反应,在观察和实验研究中,双歧杆菌等细菌产生免疫调节短链脂肪酸与疫苗反应增强有关。由于富含非消化性纤维的饮食增强了肠道微生物群中产生SCFA的群体,膳食补充益生元纤维是纠正菌群失调和提高疫苗诱导免疫力的潜在佐剂策略。在一个随机的,双绑定,72例肾移植受者的安慰剂对照试验,我们发现在第三次SARS-CoV2mRNA疫苗之前和之后的4周饮食补充益生元菊粉是可行的,可容忍,和安全。补充菊粉导致肠道双歧杆菌增加,通过16SRNA测序确定,但在第三次接种疫苗后4周时,活的SARS-CoV-2病毒的体外中和没有增加。膳食纤维补充是一种可行的策略,具有增强疫苗诱导的免疫力的潜力,值得进一步研究。
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