Probiotic-conditioned microbiota from preterm infants modulate immune response to pathogen challenge in a...

Area of Science:

• Microbiology
• Immunology
• Neonatal Research

Background:

• Early-life microbial exposures profoundly influence immune system development and long-term health.
• The PRIMAL trial showed probiotics altered preterm infant gut microbiota but didn't impact sepsis rates, leaving immunological effects unclear.

Purpose of the Study:

• To investigate the immunological consequences of probiotic-induced gut microbiota shifts in very preterm infants.
• To determine how these altered microbial communities affect immune cell development and infection susceptibility.

Main Methods:

• Germ-free mice were colonized with human gut microbiota from probiotic- or placebo-treated preterm infants.
• Immune cell populations were analyzed at steady-state and following enteropathogenic *Escherichia coli* challenge.
• Microbiota stability and transmission across generations were assessed.

Main Results:

• Probiotic-conditioned microbiota led to reduced innate immune cell populations in mouse pups, especially in the colon.
• Adaptive immune subsets were less affected by the probiotic-altered microbiota.
• Mice with probiotic-conditioned microbiota showed impaired growth and bacterial clearance upon *E. coli* infection.

Conclusions:

• Probiotic-induced shifts in human gut microbiota can attenuate immune cell development and compromise early-life infection outcomes in a murine model.
• These findings reveal complex, context-dependent effects of probiotics on the neonatal microbiota-immune axis.
• Mechanistic insights are provided into how early-life interventions in preterm infants may influence infection susceptibility.