GUT MICROBIOME CHANGES ASSOCIATED WITH HIGHER AND LONGER-LASTING ANTIBODY TITERS FOLLOWING COVID-19 VACCINATION

ABSTRACT

Background: COVID-19 associated gut microbiome dysbiosis has been strongly linked to more severe disease and has most recently been shown to persist long after symptomatic recovery. While studies have correlated the depletion of gut commensals, like Faecalibacterium and Bifidobacterium, to disease severity, little is known about specific microbes that may be protective against disease, especially in the context of vaccination against SARS-CoV-2. We aimed to characterize changes in the gut microbiota following COVID-19 vaccination and associate them with antibody titers against SARS-CoV-2. Methods: We obtained paired stool samples from a cohort of 8 patients, the first sample taken within 10 days before the beginning of their COVID-19 mRNA vaccine series and the second taken within 10 days after their second vaccine. 16s rRNA gene sequencing and principal coordinate analysis were performed. In parallel, blood samples were also collected at 1, 3, 6, and 12 months to enumerate serum IgG antibody titers. Patients were stratified into 2 groups—medium and high—based on IgG titers following vaccination, wherein the `high' response group maintained significantly higher titers beyond 6 months follow-up. We used linear discriminant analysis effect size (LefSe) to estimate which microbes significantly differed at baseline between the 2 response groups. Results: The gut microbiome composition differed before and after vaccination for all patients, with medium responders showing significant differences by both Bray-Curtis dissimilarity (p = 0.04, pairwise PERMANOVA) and unweighted UniFrac (p = 0.03, pairwise PERMANOVA) beta diversity metrics (Figure 1), while differences within high responders were non-significant. The most abundant families present before vaccination in all subjects included Lachnospiraceae, Bacteroidaceae, Ruminococcaceae, and Enterobacteriaceae. Following vaccination, a stark contraction in the relative abundance of the family Bacteroidaceae occurred in all subjects, and in the majority of cases was accompanied by a concomitant increase in the abundance of Lachnospiraceae. The relative abundances of Ruminococcaceae, Bifidobacteriaceae, and Streptococcaceae were also increased in the majority of post-vaccination samples. Post-vaccination samples were also increased in community evenness and community richness for both response groups. LefSe analysis indicated that the orders Bifidobacteriales and Lactobacillales were significantly associated with high responders (Figure 2). Conclusion: Altogether, these findings demonstrate an association between the gut microbiota and COVID-19 immunity and highlight a potential link between specific taxa and the strength of humoral responses following vaccination. (Figure Presented) (Figure Presented)