Maternal Preconception Antibiotic Exposure Disrupts Microbial Succession: A Transgenerational Risk for Offspring Gut...

Area of Science:

• Microbiome research
• Developmental biology
• Immunology

Background:

• The early-life microbiome is critical for host development and long-term health.
• Maternal factors significantly influence the offspring microbiome.
• The impact of maternal preconception perturbations on offspring health is not well understood.

Purpose of the Study:

• To investigate whether preconception microbial disruptions affect microbial succession and increase offspring susceptibility to colitis.
• To elucidate the intergenerational mechanisms linking maternal preconception perturbations to offspring health outcomes.

Main Methods:

• Combined animal models and clinical data analysis.
• Investigated the effects of preconception antibiotic exposure on offspring microbial ecology in animals.
• Analyzed gut microbiome and metabolome in children with inflammatory bowel disease (IBD) and their mothers.

Main Results:

• Preconception antibiotic exposure in animals caused long-lasting disruptions in offspring microbial ecology, including enhanced maternal-offspring transmission and altered microbial development.
• These disruptions led to persistent gut mucosal immaturity and increased susceptibility to colitis in adult offspring.
• Clinical studies showed similar alterations in the gut microbiome and metabolome of children with IBD and their mothers, with higher maternal antibiotic exposure linked to these changes.

Conclusions:

• Preconception perturbations can disrupt microbial succession and promote transgenerational propagation of gut mucosal immaturity.
• These disruptions increase offspring susceptibility to colitis, establishing a potential intergenerational mechanism.
• Judicious antibiotic use during the preconception period is crucial for preventing adverse offspring health outcomes.