Multiple sclerosis (MS) is a putative autoimmune disease of the central nervous system (CNS), of which pathogenesis could be linked with dysbiosis in gut microbiota. Works have demonstrated that regulatory cell populations, including iNKT cells, MAIT cells and regulatory T cells (Treg), are significantly altered in MS. It is possible that disrupted balance between autoreactive and regulatory cells may be caused by dysbiosis at least partially. We previously reported that oral administration of a sphingosine-truncated analog of α-galactosylceramide, OCH, would selectively induce IL-4 production from iNKT cells, thereby preventing the development of experimental autoimmune encephalomyelitis (EAE) (Nature 2001). To explore the potential value of OCH as a therapeutic agent for MS, we have completed a first-in-human phase 1 study of OCH in 15 healthy subjects (HS) and 9 patients with MS. To evaluate the effect of OCH in vivo, flow cytometer and DNA microarray analyses were conducted for peripheral blood samples obtained at various time points after oral OCH treatment. Unexpectedly high concentrations of OCH were detected in the recipients’ blood, indicating absorption of OCH from gut is better in human than rodents. Subsequently, we have observed a number of favorable changes in the blood of the HS and MS, which included (i) a significant increase of T reg [CD45RA-Foxp3+ effector/activated regulatory T cells] at 6 h, (ii) upregulation of immunoregulatory genes (MAFB and IL4I1) at 6 and 24 h, (iii) downregulation of immune-activating genes (NR4A2, FOS, and FOSB) at 6 and 24 h, and (iv) downregulation of GZMB and killer cell immunoglobulin-like receptors. Three of the patients received weekly oral administration of OCH for three months without any adverse events. The results are promising and would validate a need for phase 2 study.