Microbial-Derived Antioxidants in Intestinal Inflammation: A Systematic Review of Their Therapeutic Potential García Mansilla, María José Rodríguez Sojo, María Jesús Roxana Lista, Andrea Ayala Mosqueda, Ciskey Vanessa Ruiz Malagón, Antonio Jesús Ho Plagaro, Ailec Gálvez Peralta, Julio Juan Rodríguez Nogales, Alba Rodríguez Sánchez, María José Dysbiosis Gut Inflammation Microbial-derived antioxidants Microbiome This work was funded by the Junta de Andalucía (CTS 164), the Instituto de Salud Carlos III (Spain), Ministerio de Ciencia e Innovación (Spain) and Fondo Europeo de Desarrollo Regional (FEDER), from the European Union, through the research grants PI18/00826, PY20-01157, PI20/01447, B-CTS-664-UGR20, PI19/01058, PI24/02089 and JDC2022-049478-I, CD23/00117, IFI21/00030. Supplementary Materials: The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/antiox14030321/s1, PRISMA 2020 Checklist [42]. The potential of microbial-derived antioxidants to modulate intestinal inflammation is increasingly recognized, which is especially important in inflammatory bowel diseases (IBD). Oxidative stress, a major contributor to chronic intestinal inflammation, is the result of an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses. This systematic review explores the role of microbial-derived antioxidants in alleviating IBD. Among the main findings are certain compounds, such as exopolysaccharides (EPS) and short-chain fatty acids (SCFAs), which have demonstrated their ability to neutralize ROS and strengthen the integrity of the intestinal barrier, thereby attenuating inflammatory responses. These antioxidants offer the dual benefit of mitigating oxidative stress and rebalancing the gut microbiota, which is often disrupted in IBD. Evidence from preclinical and clinical studies provides a better understanding of the mechanisms involved in the effects of these microbial antioxidants. Conventional treatments for IBD primarily focus on immune modulation. In this context, the integration of microbial-derived antioxidants could offer a complementary approach by addressing both oxidative damage and gut dysbiosis. Further research and clinical trials are essential to establish standardized treatment guidelines and clarify the long-term efficacy of these promising therapeutic agents. 2025-03-12T11:05:33Z 2025-03-12T11:05:33Z 2025-03-06 journal article García Mansilla, M.J.; Rodríguez Sojo, M.J.; Lista, A.R.; Ayala Mosqueda, C.V.; Ruiz Malagón, A.J.; Ho Plagaro, A.; Gálvez, J.; Rodríguez Nogales, A.; Rodríguez Sánchez, M.J. Microbial-Derived Antioxidants in Intestinal Inflammation: A Systematic Review of Their Therapeutic Potential. Antioxidants 2025, 14, 321. https://doi.org/10.3390/antiox14030321 https://hdl.handle.net/10481/103002 10.3390/antiox14030321 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI