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Unlike probiotics, postbiotics offer a safer, more stable alternative while retaining potent bioactivity. IBD, encompassing Crohn\u2019s disease and ulcerative colitis, is characterized by chronic gastrointestinal inflammation, epithelial barrier dysfunction, and immune dysregulation. Recent evidence links mitochondrial dysfunction marked by impaired energy metabolism, oxidative stress, and apoptosis with the pathogenesis and persistence of IBD. Postbiotics have shown the ability to modulate mitochondrial health through multiple mechanisms. SCFAs such as butyrate serve as primary energy substrates for colonocytes, enhancing mitochondrial respiration and promoting biogenesis. They improve mitochondrial function and boost ATP production. Moreover, postbiotics reduce oxidative damage by regulating antioxidant defenses. These antioxidant actions limit epithelial apoptosis and preserve cellular integrity. In addition, postbiotics regulate mitophagy and help maintain mitochondrial quality and reduce inflammation. Structural components such as lipoteichoic acid and peptidoglycan have been shown to interact with mitochondrial pathways and modulate inflammatory responses. Collectively, this review explores the interplay between mitochondrial dysfunction, IBD, and preventive approach using postbiotics. Understanding the connections with postbiotics could open up new avenues for therapeutic interventions aimed at mitigating IBD severity in people with IBD.<\/jats:p>","DOI":"10.3390\/biom15070954","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Postbiotics as Mitochondrial Modulators in Inflammatory Bowel Disease: Mechanistic Insights and Therapeutic Potential"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-6863","authenticated-orcid":false,"given":"Santosh Kumar","family":"Prajapati","sequence":"first","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"},{"name":"Center of Excellence in Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4047-7236","authenticated-orcid":false,"given":"Dhananjay","family":"Yadav","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Katiyar","sequence":"additional","affiliation":[{"name":"Department of Botany, SBN Government PG College, Barwani 451551, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Jain","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"},{"name":"Center of Excellence in Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-1597","authenticated-orcid":false,"given":"Hariom","family":"Yadav","sequence":"additional","affiliation":[{"name":"USF Center for Microbiome Research, Microbiomes Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"},{"name":"Center of Excellence in Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"},{"name":"Department of Internal Medicine, Digestive Diseases and Nutrition, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Asefa, Z., Belay, A., Welelaw, E., and Haile, M. 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