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Though the microbiome’s impact on immune system homeostasis is well documented, the effect of circulating T cells on the gut microbiome remains unexamined. We analyzed data from 50 healthy volunteers in a pilot trial of aspirin, using immunophenotyping and 16S rRNA sequencing to evaluate the effect of baseline T cells on microbiome changes over 6 weeks. We employed an unsupervised sparse canonical correlation analysis (sCCA) and used multivariable linear regression models to evaluate the association between selected T cell subsets and selected bacterial genera after adjusting for covariates. In the cross-sectional analysis, percentages of naïve CD4+ T cells were positively associated with a relative abundance of <i>Intestinimonas</i>, and the percentage of activated CD8+ T cells was inversely associated with <i>Cellulosibacter</i>. In the longitudinal analysis, the baseline percentages of naïve CD4+ T cells and activated CD4+ T cells were inversely associated with a 6-week change in the relative abundance of <i>Clostridium_XlVb</i> and <i>Anaerovorax</i>, respectively. The baseline percentage of terminal effector CD4+ T cells was positively associated with the change in <i>Flavonifractor</i>. Notably, the microbiome taxa associated with T cell subsets exclusively belonged to the <i>Bacillota phylum</i>. These findings can guide future experimental studies focusing on the role of T cells in impacting gut microbiome homeostasis.