Optimizing Precision Probiotics for Mitigating Graft-Versus-Host Disease

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Precision probiotics offer therapeutic potential but face challenges due to strain-specific variations.
• Graft-versus-host disease (GVHD) is a serious autoimmune complication after allogeneic stem cell transplantation.

Purpose of the Study:

• To optimize and validate a six-species precision probiotic therapy for GVHD in a preclinical model.
• To investigate strain-to-strain variability in short-chain fatty acid (SCFA) production among key gut microbiota species.

Main Methods:

• Isolated and characterized strains of *B. longum*, *C. bolteae*, and *Blautia* spp. from human stem cell transplant patients.
• Assessed in vitro SCFA production and co-culture interactions.
• Compared efficacy of "optimized" vs. "standard" probiotic consortia in a mouse model of GVHD.

Main Results:

• Significant strain-to-strain variability in SCFA production was observed.
• *B. longum* augmented butyrate production by *C. bolteae* and *Blautia* in co-culture.
• Optimized probiotics mitigated GVHD, increased survival (p=0.013), and elevated intestinal SCFAs (p<0.001) compared to standard probiotics.

Conclusions:

• Strain selection is critical for maximizing the therapeutic efficacy of precision probiotics.
• An optimized precision probiotic approach shows promise for managing GVHD and potentially other inflammatory conditions.