Fig. 3: SIM01-induced Bifidobacterium increase in the gut after 3 months of treatment is associated with higher neutralizing antibodies at 6 months after BioNTech mRNA vaccination.

A, B The correlation between the fold change of three Bifidobacterium in the gut after 3 months of SIM01 treatment and the anti-spike receptor-binding domain (RBD) (A) or the neutralizing antibody sVNT (%) (B) at 1 month after the second dose of BioNTech was examined using Spearman’s correlation test. C The correlation between the fold change of three Bifidobacterium in the gut after 3 months of SIM01 treatment and the neutralizing antibody sVNT (%) at 6 months after the second dose of BioNTech was examined using Spearman’s correlation test. N = 75. D The correlation between the anti-spike receptor-binding domain (RBD) at 1 month after the second dose of BioNTech and the neutralizing antibody sVNT (%) at 6 months after the second dose of BioNTech was examined using Spearman’s correlation test. Regression lines with 95% CI (orange area) were shown on scatter plots. E Logistic regression based on fold change of individual Bifidobacterium species or a combined model based on fold change of all three Bifidobacterium species adjusting age, gender, and T2D status was used to calculate the odds ratio (OR, 95% Confidence interval) values for the for high (≥60%, n = 32) vs. low sVNT levels (<60%, n = 43) responders among BioNTech (BNT162b2) vaccines at 6 month after second dose within SIM01 arm. Each OR was presented as a dot with a bar showing the 95% CI. p < 0.05 was presented as an orange dot. OR, odds ratio; T2D, type 2 diabetes mellitus; fc fold change. F AUROC (95% CI) values of models based on combined fold change of three species contained in SIM01 for high (≥60%) vs. low sVNT levels (<60%) at 6-month postvaccination adjusting age, gender, and T2D status. p.v., postvaccination. G The volcano plot shows the differential pathway between two groups of subjects with the non-increase or increase SIM01 species in the gut after 3 months of treatment within the SIM01 arm. Maaslin2 was used for identification after adjusting the gender, age, and T2D status. p < 0.05, FDR < 0.25. H Correlations between the fold change of the relative abundance of SIM01-contained three species and the fold change of differential metabolites between baseline and 1-month postvaccination in BioNTech vaccinees. The label within each frame: · indicated p < 0.1, * indicated p < 0.05, ** indicated p < 0.01 based on Spearman correlation analysis. The color indicates the correlation Rho value. I AUROC (95% CI) values of models based on the combined fold change of three species contained in SIM01 and the fold change of three metabolites between baseline and 1-month postvaccination for high (≥60%) vs. low sVNT levels (<60%) at 6-month postvaccination, adjusting age, gender, and T2D status. p.v. postvaccination, T2D type 2 diabetes mellitus.