Key Laboratory of Dairy Science, Ministry of Education, Food College, Northeast Agriculture University, Harbin, China.
J Food Biochem. 2021 Oct;45(10):e13662. doi: 10.1111/jfbc.13662. Epub 2021 May 14.
Our previous study has confirmed that Lactobacillus acidophilus KLDS 1.0738 (La KLDS 1.0738) could alleviate β-lactoglobulin (β-Lg)-induced allergic inflammation. This study further explored its molecular regulation mechanism through an in vitro macrophage model. β-Lg-induced macrophages were treated with strains of viable or non-viable L. acidophilus and Toll-like receptor 4 (TLR4) inhibitor or miR-146a inhibitor. Our results revealed that β-Lg stimulation led to the increased expression of TLR4/NF-κB signal pathway in macrophages. Similar to TLR4 inhibitor treatment, La KLDS 1.0738 interventions significantly reduced the allergic inflammation by inhibition of TLR4 pathway, which was superior to the commercial L. acidophilus GMNL-185 strains (La GMNL-185) or the control, especially in living L. acidophilus-treated group. Furthermore, La KLDS 1.0738 strains could remarkably reduce transduction of TLR4 and inflammatory cytokine production, which was closely associated with up-regulation of miR-146a levels. MiR-146a inhibitor attenuated the alleviative effect of La KLDS 1.0738, indicating miR-146a might be a crucial mediator of L. acidophilus strains to reduce β-Lg-induced inflammation in macrophages through TLR4 pathway. In conclusion, these observations highlighted that probiotics might regulate host miRNA levels to down-regulate TLR4/NF-κB-dependent inflammation. PRACTICAL APPLICATIONS: Cow's milk allergy (CMA) is one of the most common diseases of food allergy, which has a high prevalence in infants and young children. La KLDS 1.0738 has been shown to be effective in alleviating β-Lg-induced allergic inflammation. Our study further found that treatment with La KLDS 1.0738 could suppress the TLR4/NF-κB signaling pathway via modulating miR-146a expression, thereby reducing the overexpression of downstream inflammatory factors. This study not only elucidates the specific pathway of La KLDS 1.0738 to relieve allergic inflammation, but also provides a new insight into the molecular mechanism for the remission and treatment of CMA by probiotics.
我们之前的研究已经证实嗜酸乳杆菌 KLDS 1.0738（La KLDS 1.0738）可以缓解β-乳球蛋白（β-Lg）诱导的过敏炎症。本研究通过体外巨噬细胞模型进一步探讨了其分子调节机制。用活菌或死菌嗜酸乳杆菌和 Toll 样受体 4（TLR4）抑制剂或 miR-146a 抑制剂处理β-Lg 诱导的巨噬细胞。我们的结果表明，β-Lg 刺激导致巨噬细胞中 TLR4/NF-κB 信号通路的表达增加。与 TLR4 抑制剂处理相似，La KLDS 1.0738 干预通过抑制 TLR4 途径显著减轻过敏炎症，优于商业嗜酸乳杆菌 GMNL-185 菌株（La GMNL-185）或对照，特别是在活嗜酸乳杆菌处理组中。此外，La KLDS 1.0738 菌株可显著降低 TLR4 和炎症细胞因子的转导和产生，这与 miR-146a 水平的上调密切相关。miR-146a 抑制剂减弱了 La KLDS 1.0738 的缓解作用，表明 miR-146a 可能是嗜酸乳杆菌菌株通过 TLR4 途径减轻巨噬细胞中β-Lg 诱导的炎症的关键介质。总之，这些观察结果表明，益生菌可能通过调节宿主 miRNA 水平来下调 TLR4/NF-κB 依赖性炎症。实际应用：牛奶过敏（CMA）是最常见的食物过敏之一，在婴儿和幼儿中发病率很高。La KLDS 1.0738 已被证明可有效缓解β-Lg 诱导的过敏炎症。我们的研究进一步发现，La KLDS 1.0738 治疗可通过调节 miR-146a 表达抑制 TLR4/NF-κB 信号通路，从而减少下游炎症因子的过度表达。这项研究不仅阐明了 La KLDS 1.0738 缓解过敏炎症的具体途径，还为益生菌缓解和治疗 CMA 的分子机制提供了新的见解。
