Delaroque Clara, Rytter Héloïse, Bonazzi Erica, Huillet Marine, Ellero-Simatos Sandrine, Chatonnat Eva, Hao Fuhua, Patterson Andrew, Chassaing Benoit
Microbiome-Host Interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France.
Mucosal microbiota in chronic inflammatory diseases, INSERM U1016, CNRS UMR 8104, Université Paris Cité, Paris, France.
Nat Commun. 2025 Jul 29;16(1):6954. doi: 10.1038/s41467-025-62397-3.
Early-life acquisition of microbiota and, consequently, immune system development, both lastingly impacts health. Accordingly, we hypothesized that disturbing the microbiota of lactating mothers via consumption of dietary emulsifiers might alter the microbiota, and perhaps the immune system, of their offspring, thereby increasing susceptibility to microbiota-mediated diseases, including colitis and metabolic syndrome. Here we report that, in mice, maternal consumption of carboxymethylcellulose and polysorbate-80 resulted in transient alterations in offspring microbiotas that were necessary and sufficient to increase proneness to colitis and metabolic syndrome in young adulthood. Offspring microbiome alterations induced by maternal emulsifier consumption resulted in elevated levels of pro-inflammatory flagellin, bacterial encroachment, and premature closure of goblet cell associated antigens passages (GAPs). The latter event was linked to phenotypic outcome in that pharmacologically preventing GAP closure eliminated the detrimental of maternal emulsifier consumption. Collectively, these results illustrate the potential of dietary emulsifiers to drive transgenerational microbiota alteration and, consequently, hastened immune development that increases susceptibility to inflammatory diseases.
生命早期微生物群的获得以及随之而来的免疫系统发育,都会对健康产生持久影响。因此,我们推测,哺乳期母亲通过食用膳食乳化剂扰乱微生物群,可能会改变其后代的微生物群,甚至可能改变其免疫系统,从而增加对微生物群介导疾病(包括结肠炎和代谢综合征)的易感性。在此我们报告,在小鼠中,母体食用羧甲基纤维素和聚山梨酯80会导致后代微生物群的短暂改变,这对于增加成年早期患结肠炎和代谢综合征的倾向是必要且充分的。母体食用乳化剂引起的后代微生物组改变导致促炎性鞭毛蛋白水平升高、细菌侵入以及杯状细胞相关抗原通道(GAPs)过早关闭。后一事件与表型结果相关,因为药理学上阻止GAP关闭消除了母体食用乳化剂的有害影响。总体而言,这些结果说明了膳食乳化剂驱动跨代微生物群改变的可能性,进而加速免疫发育,增加对炎症性疾病的易感性。