Antibiotic Exposure and Reduced Short Chain Fatty Acid Production after Hematopoietic Stem Cell Transplant

Area of Science:

• Microbiology
• Gastroenterology
• Immunology

Background:

• Hematopoietic stem cell transplantation (HSCT) is associated with gut microbiome disruption and injury.
• Loss of gut microbial diversity and prolonged antibiotic use increase risks of complications like graft-versus-host disease (GVHD).
• Intestinal commensals producing short-chain fatty acids (SCFAs) may play a role in maintaining gut health and preventing dysbiosis.

Purpose of the Study:

• To longitudinally examine changes in luminal SCFAs in children undergoing allogeneic HSCT.
• To investigate the relationship between SCFA alterations, gut microbiota composition, and antibiotic exposure.
• To explore the association between SCFA levels and the development of GVHD post-HSCT.

Main Methods:

• Longitudinal analysis of fecal SCFA levels in pediatric HSCT recipients.
• Correlation of SCFA concentrations with microbiota data and antibiotic regimens.
• Comparison of SCFA profiles between patients who developed GVHD and those who did not.

Main Results:

• Significant and progressive alterations in butyrate and other SCFAs were observed in stool within 14 days post-HSCT, differing from mouse studies.
• Lower SCFA levels were detected in children receiving antibiotics targeting anaerobic organisms.
• Post-HSCT butyrate and propionate levels on day 14 were lower in children who subsequently developed GVHD.

Conclusions:

• Gut microbiome alterations and SCFA depletion following HSCT may contribute to GVHD pathogenesis.
• Antibiotic use, particularly against anaerobes, impacts SCFA levels and potentially GVHD risk.
• Modulating SCFA production presents a potential therapeutic strategy to mitigate GVHD and improve outcomes after HSCT.