Zhao Caijun, Bao Lijuan, Shan Ruping, Zhao Yihong, Wu Keyi, Shang Shan, Li Haiqi, Liu Yi, Chen Ke, Zhang Naisheng, Ye Cong, Hu Xiaoyu, Fu Yunhe
Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
Adv Sci (Weinh). 2025 Mar;12(9):e2411985. doi: 10.1002/advs.202411985. Epub 2025 Jan 14.
Microbial transmission from mother to infant is important for offspring microbiome formation and health. However, it is unclear whether maternal gut inflammation (MGI) during lactation influences mother-to-infant microbial transmission and offspring microbiota and disease susceptibility. In this study, it is found that MGI during lactation altered the gut microbiota of suckling pups by shaping the maternal microbiota in the gut and mammary glands. MGI-induced changes in the gut microbiota of suckling pups lasted into adulthood, resulting in the exacerbation of acute liver failure (ALF) caused by acetaminophen (APAP) in offspring. Specifically, MGI reduced the abundance of Lactobacillus reuteri (L. reuteri) and its metabolite indole-3-acetic acid (IAA) level in adult offspring. L. reuteri and IAA alleviated ALF in mice by promoting intestinal IL-22 production. Mechanistically, IL-22 limits APAP-induced excessive oxidative stress and ferroptosis by activating STAT3. The intestinal abundances of L. reuteri and IAA are inversely associated with the progression of patients with ALF. Overall, the study reveals the role of MGI in mother-to-infant microbial transmission and disease development in offspring, highlighting potential strategies for intervention in ALF based on the IAA-IL-22-STAT3 axis.
微生物从母亲向婴儿的传播对于后代微生物群的形成和健康至关重要。然而，哺乳期母亲肠道炎症（MGI）是否会影响母婴间的微生物传播、后代微生物群及疾病易感性尚不清楚。在本研究中，发现哺乳期的MGI通过塑造母亲肠道和乳腺中的微生物群，改变了哺乳幼崽的肠道微生物群。MGI诱导的哺乳幼崽肠道微生物群变化持续至成年期，导致后代因对乙酰氨基酚（APAP）引起的急性肝衰竭（ALF）加重。具体而言，MGI降低了成年后代中罗伊氏乳杆菌（L. reuteri）的丰度及其代谢产物吲哚-3-乙酸（IAA）水平。罗伊氏乳杆菌和IAA通过促进肠道IL-22的产生减轻小鼠的ALF。从机制上讲，IL-22通过激活STAT3限制APAP诱导的过度氧化应激和铁死亡。罗伊氏乳杆菌和IAA的肠道丰度与ALF患者的病情进展呈负相关。总体而言，该研究揭示了MGI在母婴微生物传播及后代疾病发展中的作用，突出了基于IAA-IL-22-STAT3轴干预ALF的潜在策略。
