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

Justine Smout1,2, Till-Robin Lesker3, Lisa Hoenicke1

  • 1Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Frontiers in Immunology
|May 6, 2026
PubMed

Insights

Multistrain probiotics altered preterm infants' gut microbes, leading to reduced immune cell development in mice. This may increase susceptibility to early-life infections, highlighting complex probiotic effects.

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.

Keywords:
early lifeimmunologyinfectionmicrobiotapreterm

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