Latest research progress on anti-microbial effects, mechanisms of action, and product developments of dietary flavonoids: A systematic literature review Jincan Luo a,b,1 , Jinhai Luo c,1 , Zhili Sheng d,1 , Zhonghao Fang a,b , Yu Fu b , Nannan Wang b , Bao Yang d,** , Baojun Xu c,* a National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China b Guangzhou National Laboratory, International Bio-Island, Guangzhou, 510005, China c Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong, 519087, China d Guangdong Provincial Key Laboratory of Applied Botany, State Key Laboratory of Plant Diversity and Prominent Crops, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, 510650, China ARTICLE INFO Handling Editor: Dr AR Jambrak Keywords: Flavonoid Antimicrobial resistance Antimicrobial effects ATP Membrane disruption Biofilm formation Clinical trial ABSTRACT Background: With the end of the COVID-19 pandemic, antimicrobial resistance has become increasingly severe and threatens global human health. There is an urgent need for new types of antibacterial drugs. Flavonoids, the largest class of secondary metabolites in plants, are widely present in various kinds of fruits and vegetables, and their antibacterial activity is increasingly being valued. Scope and approach: We conducted a comprehensive search using relevant keywords from four well-known da- tabases: ScienceDirect, Google Scholar, and Wiley Online Library, systematically summarizing the latest mech- anisms, clinical studies, and product development over the past five years by which dietary flavonoids have achieved antimicrobial effects. Evaluate the quality of included studies using eligibility and exclusion criteria. Key findings and conclusions: The dietary flavonoids exert antibacterial effects through different mechanisms, including membrane disruption, biofilm formation, inhibition of cell envelope synthesis, inhibition of nucleic acid synthesis, inhibition of electron transport chain and ATP synthesis, antibacterial action of flavonoid-metal complexes, and inhibition of bacterial toxins. The anti-microbial flavonoids include flavanols, chalcones, fla- vones, flavanone, biflavones, isoflavones, and dihydrochalcones. The latest clinical studies and product devel- opment of flavonoids derived from the food in this review have further demonstrated the promising potential of dietary flavonoids in antibacterial applications. More progress in related fields in the future may make flavonoids the primary source for addressing antimicrobial resistance. 1. Introduction Antimicrobial resistance (AMR) is an area that all countries attach great importance to. It will lead to increased incidence rate, mortality, and medical costs (Cassini et al., 2019). The increase in antibiotic resistance rate is caused by various factors, including an increase in antibiotic use rate, especially in developing countries, and the excessive use of antibiotics is related to the rise in antibiotic resistance rate (Godman et al., 2021). The global pandemic of COVID-19 in the past few years has intensified the widespread overuse of antibiotics. People are worried about the differential diagnosis between infections such as tuberculosis and influenza, cough, fever, and bacterial upper respiratory tract infections caused by COVID-19 (Majumder et al., 2020). Over 70% of COVID-19 patients receive antibiotic treatment, including * Corresponding author. Food Science and Technology Program, BNU-HKBU United International College, 2000, Jintong Road, Tangjiawan, Zhuhai, Guangdong, 519087, China. ** Corresponding author. Guangdong Provincial Key Laboratory of Applied Botany, State Key Laboratory of Plant Diversity and Prominent Crops, South China Botanical Garden, Chinese Academy of Sciences. Postal address: 723 Xingke Road, Tianhe District, Guangzhou, 510650, China. E-mail addresses: yangbao@scbg.ac.cn (B. Yang), baojunxu@uic.edu.cn (B. Xu). 1 Three authors have equal contribution to this paper. Contents lists available at ScienceDirect Trends in Food Science & Technology journal homepage: www.elsevier.com/locate/tifs https://doi.org/10.1016/j.tifs.2024.104839 Received 4 October 2024; Received in revised form 3 December 2024; Accepted 9 December 2024 Trends in Food Science & Technology 156 (2025) 104839 Available online 12 December 2024 0924-2244/© 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.