Mitochondrial Function in Inflammatory Bowel Diseases

Mitochondria are central to intestinal epithelial health through their roles in energy production, redox homeostasis and regulation of cell death. In inflammatory bowel diseases (IBD), perturbations of mitochondrial function manifest as impaired oxidative phosphorylation, excessive production of reactive oxygen species and altered mitochondrial dynamics. Such dysfunction undermines epithelial barrier integrity, disrupts Paneth cell secretory activity and skews mucosal immune responses. Mitochondrial impairment also shapes the luminal environment by altering host–microbe cross-talk: deficiencies in short-chain fatty acid utilisation and mitochondrial chaperones promote dysbiosis and amplify mucosal inflammation. Genetic variation in mitochondrial DNA influences susceptibility to IBD by modulating epithelial metabolism and microbiota composition. Collectively, these insights highlight mitochondria as both targets and mediators of mucosal injury, with therapeutic implications ranging from mitochondrial antioxidants and biogenesis enhancers to dietary modulation of microbiota-derived metabolites.

Research from Nature Portfolio

Foundational systems-level analyses in new-onset Crohn’s disease reveal downregulation of mitochondrial proteins involved in hydrogen sulfide detoxification alongside expansion of sulfide-producing gut bacteria, establishing a causal link between altered host mitochondrial proteome and colonic inflammation. Complementary work in intestinal stem cell niches demonstrates that loss of key mitochondrial chaperones triggers an unfolded protein response, leading to stem cell dysfunction and compensatory hyperproliferation via paracrine WNT signalling—mechanisms that mirror epithelial repair and dysplasia in chronic inflammation. In murine models, mtDNA mutations affecting ATP synthase also reshape gut microbial communities, suggesting that host mitochondrial genotype can drive metabolic and inflammatory phenotypes through microbiota modulation.

Mitochondrial Function in Inflammatory Bowel Diseases publication trend

The graph below shows the total number of articles in mitochondrial function in inflammatory bowel diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Electron transport chain: Series of protein complexes in the mitochondrial inner membrane that transfer electrons to generate a proton gradient for ATP synthesis.

Oxidative phosphorylation: Process in which ATP is produced from ADP and inorganic phosphate using energy derived from the electron transport chain.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage proteins, lipids and DNA when not regulated.

Paneth cell: Specialized epithelial cell in the small intestine that secretes antimicrobial peptides and supports the stem cell niche.

Short-chain fatty acids: Microbial metabolites such as butyrate that serve as energy substrates for epithelial cells and modulate inflammation.

Mitochondrial unfolded protein response (MT-UPR): Adaptive signalling cascade activated by accumulation of unfolded proteins in mitochondria to restore proteostasis.

References

1. Interplay of gut microbiota and host epithelial mitochondrial dysfunction is necessary for the development of spontaneous intestinal inflammation in mice. Microbiome (2023).
2. Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3. Gut Microbes (2023).
3. Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease. Nature Communications (2016).
4. Mitochondrial function controls intestinal epithelial stemness and proliferation. Nature Communications (2016).
5. Mitochondrial dysfunction in inflammatory bowel disease. Frontiers in Cell and Developmental Biology (2015).
6. Intestinal epithelial cell metabolism at the interface of microbial dysbiosis and tissue injury. Mucosal Immunology (2022).
7. Mitochondrial gene polymorphism is associated with gut microbial communities in mice. Scientific Reports (2017).