Age-Dependent Alterations in Intestinal Barrier Function: Involvement of Microbiota and TLR4 Signaling

作者：Yakun Xing, Xing-Yu Zhao, Xin-Yu Li, Jiawei Zheng, Wu-Yang Huang · 发表于：Biology · 年份：2026 · DOI：10.3390/biology15050441 · 被引用次数：5 · 研究领域：Medicine

Simple Summary The intestinal barrier, a crucial defense system against pathogens and toxins, undergoes dynamic changes throughout a lifespan. While age-related gut decline and systemic inflammation are well-documented, a systematic understanding of how the gut microbiota and host immune signaling coordinately evolve from infancy to old age remains limited. This study comprehensively investigated these interactions across major developmental stages, including pups, adults, middle-aged, and old age in mouse models. It was found that microbial diversity and beneficial metabolites peak in adulthood, while inflammatory signals progressively increase with aging. Crucially, the immune receptor Toll-like receptor 4 (TLR4) was identified as a key driver of age-related gut deterioration. These findings reveal that aging disrupts the delicate host–microbe dialogue, leading to barrier dysfunction and chronic inflammation. Targeting this interaction, especially through TLR4 modulation, presents a promising strategy to support gut health and promote healthier aging.