While antibiotics can be life-saving, their adverse long-term consequences, such as the development of antibiotic resistance and perturbations of the gut microbiome, have moved to the forefront of scientific attention.

Previous research found microbiome condition in the early stages of life to be crucial for health in later years. In particular, a lifelong elevated risk for the emergence of inflammatory bowel disease was associated with offspring microbiome alterations caused by maternal perinatal and postnatal antibiotic exposure.

Less is known about the preconception phase, or whether there could be a mechanistic link between maternal antibiotic use at such an early stage and an increased inflammatory bowel disease susceptibility in the offspring.

Transgenerational Effects of Antibiotic Exposure

Professor Yuzhu Chen and colleagues at Peking University Third Hospital and Nanjing Medical University examined the transgenerational effects – in this case, the transmission of physiological attributes from one generation to the next – of maternal antibiotic use via an holistic procedure involving animals and humans. 

Based on experimental murine models, the researchers revealed that antibiotic alteration of the maternal microbiome even prior to conception can lead to impaired gut microbiome development, immaturity of the colonic mucosa and enhanced susceptibility to inflammatory conditions like colitis in the next generation.

Offspring of antibiotic-treated female mice exhibited alterations in their gut microbial composition, a phenomenon that could already be observed in the mothers. This suggests a heightened mother-to-offspring transmission of microbial strains and, consequently, an inherited microbial community imbalance. The initial microbiome shapes further microbial composition and has far-reaching health implications, so it is likely that maternal preconceptional microbiome shifts, along with the elevated microbial transmission to offspring, may have lifelong detrimental consequences for offspring health.

Additional tests confirmed this: offspring were found to persistently retain more maternal microbial strains than control groups.

Instead of the normal diversification of the composition over time, an unusual microbial maturation pattern was observed in offspring of preconceptionally antibiotic-exposed females. There was no development towards a balanced and complex microbial ecosystem; instead, the gut microbiome followed an atypical developmental path, exhibiting early determination of the gut microbiome composition with fewer new microbial strains appearing in adulthood. 

Immature Mucosa Increases Inflammatory Condition Risks

These microbiome alterations have significant implications for gut health, being associated with immaturity of the intestinal mucosa.

The gut mucosa serves as a barrier, shielding intestine contents from surrounding tissues and thereby protecting the body from potentially harmful particles and substances. At the same time, it enables contact of the microbiome with the host’s immune system, regulating immune homeostasis. A compromised interaction between the intestinal mucosa and the microbial communities is linked to immunological disorders and inflammatory bowel disease.

In this study, the researchers found that offspring from mothers that underwent antibiotic treatment before conception showed signs of immaturity of the intestinal mucosa and hampered barrier function, which persisted into adulthood and were associated with an elevated risk of the inflammatory condition colitis. 

One of the more well-known examples is colitis ulcerosa, which is chronic and represents a type of inflammatory bowel disease characterized by an inflammatory pattern in the colon. In the current study, the role of the microbiome for colitis development was examined via fecal microbiota transplantation and experimentally induced colitis. Indeed, in offspring of mothers that were exposed to antibiotics before conception, more severe intestinal inflammation was noticed compared to control groups. This indicates an increased susceptibility to inflammation.

It is worth noting that the disease did not develop spontaneously, but could be induced by low-level stimulation.

To ensure the findings resonate with human physiological processes, a clinical cohort study with human participants was conducted, specifically involving children with inflammatory bowel disease and their mothers as well as a respective control group. Observations such as the characteristic gut microbiome disruptions and shared microbial patterns in antibiotic-exposed mothers and their children, as well as deterministic tendencies in microbial community assembly, align with the results obtained from animal experiments. 

Antibiotics versus Microbiome – Getting ahead of the Intergenerational Transmission Cascade

These results support the assumption that the maternal microbiome and its alteration due to antibiotic exposure may be a pivotal starting point for the intervention and minimization of long-term health consequences in offspring.

Liping Duan, the lead author of the work, puts it as follows: “Our research reveals that the often-overlooked preconception period is a critical window. Maternal antibiotic use even before pregnancy can durably alter the offspring’s gut microbial ‘succession plan’, leading to persistent intestinal immaturity and a lifelong increased risk of colitis. This underscores the urgent need for judicious antibiotic use and microbiome monitoring in women planning pregnancy.”

The team’s future research may include larger birth-cohorts and information on maternal nutrition and preconception datasets to address the challenges posed by the antagonistic relationship between antibiotics and the gut microbiome. Mitigating detrimental microbial transmissions across generations remains an essential objective for preserving the health of mothers and children.  

Reference: Y. Chen et al., Maternal Preconception Antibiotic Exposure Disrupts Microbial Succession: A Transgenerational Risk for Offspring Gut Mucosal Immaturity and Colitis Susceptibility, Advanced Science (2026). DOI: 10.1002/advs.202516931

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