肠道菌群通过碳水化合物的发酵产生的短链脂肪酸（SCFAs）对调节宿主生理起着至关重要的作用。其中，醋酸、丙酸和丁酸在各种生物过程中是关键因素。最近的研究揭示了它们在免疫和炎症反应中的重要功能。例如，丁酸减少干扰素-γ（IFN-γ）生成细胞的发展，同时促进调节性T（Treg）细胞的发展。丙酸通过树突状细胞（DCs）抑制Th2免疫反应的启动。值得注意的是，SCFAs对M2巨噬细胞的极化具有抑制作用，强调了它们的免疫调节特性和治疗潜力。在哮喘动物模型中，丁酸和丙酸都抑制了M2极化途径，从而减轻了过敏性气道炎症。此外，肠道菌群的菌群失调导致SCFAs产生改变，与前列腺癌进展有关。SCFAs诱导癌细胞自噬，并促进巨噬细胞的M2极化，加速肿瘤进展。操纵菌群产生SCFAs具有癌症治疗的前景。此外，SCFAs通过抑制组蛋白去乙酰化酶，增强缺氧诱导因子1（HIF-1）的表达，从而增加抗菌效应物质的产生，并改善巨噬细胞介导的微生物消除能力。这突显了SCFAs的抗菌潜力以及它们在宿主防御机制中的作用。本综述对SCFAs在各种疾病中与巨噬细胞活动的功能方面和潜在机制的最新研究进行了深入分析。这包括传染性疾病和癌症。通过阐明SCFAs和巨噬细胞功能之间错综复杂的相互作用，本综述旨在为人们理解其治疗潜力并为以SCFAs为靶向治疗疾病管理的未来干预措施铺平道路。版权所有 © 2023作者。由Elsevier Masson SAS出版。保留所有权利。

Short-chain fatty acids (SCFAs) derived from the fermentation of carbohydrates by gut microbiota play a crucial role in regulating host physiology. Among them, acetate, propionate, and butyrate are key players in various biological processes. Recent research has revealed their significant functions in immune and inflammatory responses. For instance, butyrate reduces the development of interferon-gamma (IFN-γ) generating cells while promoting the development of regulatory T (Treg) cells. Propionate inhibits the initiation of a Th2 immune response by dendritic cells (DCs). Notably, SCFAs have an inhibitory impact on the polarization of M2 macrophages, emphasizing their immunomodulatory properties and potential for therapeutics. In animal models of asthma, both butyrate and propionate suppress the M2 polarization pathway, thus reducing allergic airway inflammation. Moreover, dysbiosis of gut microbiota leading to altered SCFA production has been implicated in prostate cancer progression. SCFAs trigger autophagy in cancer cells and promote M2 polarization in macrophages, accelerating tumor advancement. Manipulating microbiota- producing SCFAs holds promise for cancer treatment. Additionally, SCFAs enhance the expression of hypoxia-inducible factor 1 (HIF-1) by blocking histone deacetylase, resulting in increased production of antibacterial effectors and improved macrophage-mediated elimination of microorganisms. This highlights the antimicrobial potential of SCFAs and their role in host defense mechanisms. This comprehensive review provides an in-depth analysis of the latest research on the functional aspects and underlying mechanisms of SCFAs in relation to macrophage activities in a wide range of diseases, including infectious diseases and cancers. By elucidating the intricate interplay between SCFAs and macrophage functions, this review aims to contribute to the understanding of their therapeutic potential and pave the way for future interventions targeting SCFAs in disease management.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.