Caesarean birth: sex-specific effects on the microbiota

Previous studies have already shown that caesarean delivery alters microbial colonisation in the first days of life. At the same time, numerous studies indicate that males and females do not always respond in the same way to disruptions in the microbiota or the gut barrier.

A research team coordinated by INRAE set out to understand how these two factors — delivery mode and sex — interact over the course of development, and whether this interaction could affect susceptibility to intestinal diseases such as colitis¹ in adulthood.

Using a mouse model, the scientists tracked changes in the microbiota and the gut barrier from birth through to adulthood. The results show that in the earliest days of life, delivery mode is the dominant factor: mice born by caesarean section display a distinct immune and microbial signature, regardless of sex. However, this changes over time, and as the animals grow, the trajectories of males and females diverge markedly. Only male mice born by caesarean section develop increased susceptibility to colitis in adulthood. This difference is accompanied by specific alterations in the gut microbiota, including an early abundance and a later decrease of bacteria capable of producing butyrate (a bacterial metabolite with important health implications). Gut barrier-microbiota interactions also differ, with males showing reduced epithelial resistance, indicating altered permeability.

 Mode of delivery thus appears to “programme” sex-specific microbial and immune trajectories, with effects that only become evident later in life. These findings highlight the importance of considering both sex and early microbial imprinting when developing effective strategies for gut health.

Building on this work, a study will soon be published on the identification of probiotics tailored to caesarean birth, based on research conducted in conventional mice and in mice that received human microbiota. Other diseases, such as asthma, will also be explored in a new research project, again with the aim of better understanding how delivery mode and sex influence the risk of disease development.

1. Colitis is an inflammation of the colon that typically causes abdominal pain, often accompanied by fever or diarrhoea.