Zuffa Simone, Thomas Sydney P, Mohanty Ipsita, El Abiead Yasin, Deleray Victoria, Kvitne Kine Eide, Kousha Armin, Suzuki Emi, Tsai Chih Ming, Nguyen Griffith, Ho Benjamin, Liu George Y, Nizet Victor, Dorrestein Pieter C, Askarian Fatemeh, Tsunoda Shirley M
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, USA.
bioRxiv. 2025 Jun 30:2025.06.30.662372. doi: 10.1101/2025.06.30.662372.
Indirect exposure to antibiotics during early life, via maternal intrapartum antibiotic prophylaxis (IAP) or postpartum maternal antibiotic usage, is increasingly common and has been epidemiologically linked to altered growth and immune developmental trajectories in offspring. Nevertheless, the underlying mechanisms remain poorly understood. Here, we explored the effects of antepartum and postpartum maternal ampicillin administration on the dams' fecal microbiome and metabolic profiles Ampicillin caused a reproducible depletion of beneficial bacterial species belonging to the family, including and , and led to cohort-dependent enrichments of and species. These microbial alterations were accompanied by substantial metabolic remodeling, characterized by elevated fecal acylcarnitines and dysregulation of the bile acids profile. Intriguingly, we identified two previously uncharacterized trihydroxylated bile acids conjugated to a hexose moiety, which appeared to be associated with antibiotic exposure across public metabolomics repositories. These alterations in the fecal maternal microbiome and metabolome coincided with increased weight gain in offspring, suggesting a possible role for maternal antibiotic exposure in shaping early developmental trajectories. Further studies are warranted to elucidate the long-term implications of these changes in infant health.
在生命早期，通过产妇产时抗生素预防性使用（IAP）或产后产妇抗生素使用而间接接触抗生素的情况日益普遍，并且在流行病学上已与后代生长和免疫发育轨迹的改变相关联。然而，其潜在机制仍知之甚少。在此，我们探讨了产前和产后母体给予氨苄青霉素对母鼠粪便微生物组和代谢谱的影响。氨苄青霉素导致属于该菌科的有益细菌种类可重复减少，包括和，并导致特定菌群中菌属和菌种的富集。这些微生物变化伴随着大量的代谢重塑，其特征是粪便酰基肉碱升高和胆汁酸谱失调。有趣的是，我们鉴定出两种先前未表征的与己糖部分共轭的三羟基化胆汁酸，它们似乎与公共代谢组学数据库中的抗生素暴露有关。母鼠粪便微生物组和代谢组的这些变化与后代体重增加同时出现，表明母体抗生素暴露在塑造早期发育轨迹中可能发挥作用。有必要进行进一步研究以阐明这些变化对婴儿健康的长期影响。
