Puértolas-Balint Fabiola, Prasoodanan P K Vishnu, Holmberg Sandra M, Schröder Björn O
Department of Molecular Biology, Umeå University, Umeå, Sweden.
The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
Gut Microbes. 2025 Dec;17(1):2536095. doi: 10.1080/19490976.2025.2536095. Epub 2025 Aug 4.
The small intestinal mucosa has the delicate task of allowing absorption of nutrients and limiting microbial colonization at the mucosal surface through production of antimicrobial peptides and proteins (AMPs). However, while environmental factors, including different diets, have been shown to alter AMP expression, the results from the literature are conflicting on their specific impact. Moreover, the interdependence between diet, AMPs, and metabolic health is largely unexplored. The aim of this study was thus to investigate the effect of obesogenic diets, obesity itself, and other variables, including mouse vendor, microbiota composition, and sex, on intestinal AMP expression. By using different dietary interventions in mice, we here show that prolonged intake of an obesogenic Western-style diet had a stronger impact on AMP expression than diet-independent obesity. Additionally, when comparing AMP expression under different diets in mice of both sexes from different vendors, the combined contribution of these factors had the strongest impact on absolute AMP transcript numbers, but also on the variability in small intestinal microbiota composition at the mucosa and content. Finally, we identified a novel host-microbe interaction, in which the gut commensal bloomed upon WSD-feeding and specifically induced the expression of the AMP Reg3g. Our findings thus reveal that the experimental setup, defined by mouse vendor, sex, and diet type, has a major influence on small-intestinal AMP expression. These findings could partly explain the discrepancy in the literature regarding the effect of diets on AMP expression, preventing any accurate generalization about the impact of diet on the antimicrobial response.
小肠黏膜肩负着一项精细的任务，即通过产生抗菌肽和蛋白质（AMPs）来实现营养物质的吸收，并限制微生物在黏膜表面的定植。然而，尽管包括不同饮食在内的环境因素已被证明会改变AMPs的表达，但文献中的结果在其具体影响方面存在冲突。此外，饮食、AMPs和代谢健康之间的相互依存关系在很大程度上尚未得到探索。因此，本研究的目的是调查致肥胖饮食、肥胖本身以及其他变量，包括小鼠供应商、微生物群组成和性别，对肠道AMPs表达的影响。通过在小鼠中使用不同的饮食干预措施，我们在此表明，长期摄入致肥胖的西式饮食对AMPs表达的影响比与饮食无关的肥胖更强。此外，当比较来自不同供应商的雌雄小鼠在不同饮食条件下的AMPs表达时，这些因素的综合作用对绝对AMPs转录本数量影响最大，同时也对黏膜和内容物中小肠微生物群组成的变异性影响最大。最后，我们确定了一种新的宿主-微生物相互作用，其中肠道共生菌在喂食西式饮食时大量繁殖，并特异性地诱导抗菌肽Reg3g的表达。因此，我们的研究结果表明，由小鼠供应商、性别和饮食类型定义的实验设置对小肠AMPs表达有重大影响。这些发现可以部分解释文献中关于饮食对AMPs表达影响的差异，避免对饮食对抗菌反应影响的任何准确概括。
