Human cord blood mononuclear cells alleviate intestinal inflammation and barrier dysfunction by regulating gut metabolites and Th17/Treg balance.

BACKGROUND

Cord blood mononuclear cells (CB-MNCs) are a potential alternative therapy for inflammatory bowel disease (IBD). Gut metabolites, T helper 17 (Th17) and regulatory T (Treg) cells are crucial for intestinal hemeostasis and recovery. However, the role of CB-MNCs in modulating IBD, gut metabolites and the Th17/Treg balance remains unclear.

METHODS

In this study, dextran sodium sulfate (DSS) was used to induce acute colitis in male C57BL/6 J mice, followed by treatment with CB-MNCs, umbilical cord-derived mesenchymal stem cells (UC-MSCs), or mesalazine. The severity of colitis was assessed daily using the disease activity index (DAI), and feces were collected for metabolomic analysis. Upon sacrifice, the colons, mesenteric lymph nodes (MLNs) and spleens of the mice were preserved for further study.

RESULTS

Our findings demonstrated that compared with UC-MSCs and mesalazine, CB-MNCs treatment had superior efficacy in improving clinical symptoms, tissue repair, promoting intestinal regeneration and integrity. While CB-MNCs were equivalent to UC-MSCs and mesalazine in terms of preserving colon length and anti-inflammatory activity. At the molecular level, CB-MNCs exhibited unique and powerful effects. CB-MNCs were found to significantly increase the abundance of cortisol, corticosterone, and several metabolites with anti-inflammatory and antioxidant activities in the feces of colitis mice. CB-MNCs were also more effective than UC-MSCs and mesalazine at maintaining Th17/Treg balance than UC-MSC and mesalazine in colitis mice.

CONCLUSIONS

The intravenous injection of CB-MNCs can alleviate intestinal inflammation and barrier dysfunction by modulating gut metabolites and the Th17/Treg balance. Therefore, CB-MNCs be a promising treatment for IBD.