Department of Animal and Food Sciences, Oklahoma State University, Stillwater, OK, United States.
Department of Animal and Food Sciences, Oklahoma State University, Stillwater, OK, United States.
Adv Nutr. 2024 Sep;15(9):100277. doi: 10.1016/j.advnut.2024.100277. Epub 2024 Jul 23.
The escalating threat of antimicrobial resistance underscores the imperative for innovative therapeutic strategies. Host defense peptides (HDPs), integral components of innate immunity, exhibit profound antimicrobial and immunomodulatory properties. Various dietary compounds, such as short-chain fatty acids, vitamins, minerals, sugars, amino acids, phytochemicals, bile acids, probiotics, and prebiotics have been identified to enhance the synthesis of endogenous HDPs without provoking inflammatory response or compromising barrier integrity. Additionally, different classes of these compounds synergize in augmenting HDP synthesis and disease resistance. Moreover, dietary supplementation of several HDP-inducing compounds or their combinations have demonstrated robust protection in rodents, rabbits, pigs, cattle, and chickens from experimental infections. However, the efficacy of these compounds in inducing HDP synthesis varies considerably among distinct compounds. Additionally, the regulation of HDP genes occurs in a gene-specific, cell type-specific, and species-specific manner. In this comprehensive review, we systematically summarized the modulation of HDP synthesis and the mechanism of action attributed to each major class of dietary compounds, including their synergistic combinations, across a spectrum of animal species including humans. We argue that the ability to enhance innate immunity and barrier function without triggering inflammation or microbial resistance positions the nutritional modulation of endogenous HDP synthesis as a promising host-directed approach for mitigating infectious diseases and antimicrobial resistance. These HDP-inducing compounds, particularly in combinations, harbor substantial clinical potential for further exploration in antimicrobial therapies for both human and other animals.
抗菌药物耐药性的不断升级突显了创新治疗策略的必要性。宿主防御肽（HDPs）是先天免疫的重要组成部分，具有强大的抗菌和免疫调节特性。各种膳食化合物，如短链脂肪酸、维生素、矿物质、糖、氨基酸、植物化学物质、胆汁酸、益生菌和益生元，已被确定可增强内源性 HDP 的合成，而不会引发炎症反应或损害屏障完整性。此外，这些化合物的不同类别协同作用可增强 HDP 合成和疾病抵抗力。此外，几种 HDP 诱导化合物或其组合的膳食补充已在实验感染的啮齿动物、兔子、猪、牛和鸡中证明具有强大的保护作用。然而，这些化合物诱导 HDP 合成的功效在不同化合物之间差异很大。此外，HDP 基因的调控以基因特异性、细胞类型特异性和物种特异性的方式发生。在这篇全面的综述中，我们系统地总结了每种主要类别的膳食化合物（包括它们的协同组合）对 HDP 合成的调节作用及其作用机制，涵盖了包括人类在内的多种动物物种。我们认为，增强先天免疫和屏障功能而不引发炎症或微生物耐药性的能力使内源性 HDP 合成的营养调节成为一种有前途的宿主定向方法，可用于减轻传染病和抗菌药物耐药性。这些 HDP 诱导化合物，特别是组合使用，在人类和其他动物的抗菌治疗中具有很大的临床潜力，值得进一步探索。
