Bi-directional crosstalk between gut microbiota and NKT cells

Abstract

Abstract The gut microbiome interacts with the host, including local and systemic immunity. However, the causal mechanisms are relatively under-explored. In this study, we sought to identify bi-directional crosstalk between gut microbiota and type I and/or type II NKT cells using C57BL/6 WT (wild-type), Traj18-knock out (KO) (lacks only type I NKT cells), or CD1d-KO (lacks both type I and II NKT cells) mice. Mice were co-housed with each other strain in combination from the age of day 30 (9 days after weaning) for 30 days and housed separately again for another 30 days. Fecal pellets collected at the age of days 30, 60, and 90 were sequenced by 16S rRNA (250 bp paired-end, Illumina) sequencing, identifying 1,276 amplicon sequence variants (ASVs) by analysis (QIIME2). Microbes with low frequency (<0.5%) or exhibiting cage effects within a strain at day 30 were filtered out. Comparing the microbial abundances between the different groups (co-housing or not) and time points revealed an interesting phenomenon regarding four ASVs (the closest known species was Muribaculum intestinale strain YL27 (16S pident 86.7–95.6)). They showed differential abundance (limma p-value < 0.05) between strains at day 30 (e.g., an ASV_802 was most abundant in WT mice, then CD1-KO, and lowest in Traj18-KO mice). These closely related bacteria were not transferred to Traj18-KO mice when co-housed with WT or CD1-KO mice. Because the ASV is present in WT and CD1d KO mice, even though the latter also lack type I NKT cells as well as type II, our results suggest the existence of specific microbe(s) that cannot grow well in the presence of unopposed type II NKT cells.