Environmental enteric dysfunction (EED) remains a major but poorly understood contributor to childhood stunting, impaired mucosal immunity and reduced oral vaccine efficacy in low-resource, high-infectious-burden settings. Increasing evidence suggests that EED is driven not simply by undernutrition, but by chronic intestinal inflammation, epithelial damage and disrupted host–microbe interactions that fundamentally alter gut structure and function.
In this Q&A, Prof. Paul Kelly (Barts & The London School of Medicine, UK) explores how EED-associated epithelial and immune dysfunction compromises gut barrier integrity, nutrient absorption and vaccine responsiveness. He discusses why nutritional interventions alone have limited impact on stunting, considers the role of chronic inflammation in shaping mucosal immune failure, and highlights emerging research and therapeutic strategies aimed at restoring intestinal function.
There are strong associations between structural changes (villus blunting, increased inflammatory cells, secretory cell depletion) and gut barrier dysfunction. We believe these changes are caused by carriage of heavy burdens of polymicrobial infections which cause epithelial damage, allowing barrier failure and perpetuating the inflammatory cascade. However, we cannot be sure about causation as these are largely correlational. It seems likely that cycles of infections, barrier failure and structural change are repeated and potentiate each other. Work on understanding antigen uptake is in its infancy just now.
It is very clear that nutritional interventions alone are simply not enough to treat the consequences of EED, particularly stunting which only ever responds by about one third, at most, to nutritional therapy. Downregulated nutrient transporters would partly explain the refractory nature of stunting.
This is not clear. We think it likely that high levels of inflammation render the mucosal immune system unresponsive to antigens presented by afferent processes.
We need to carry out trials of immunomodulatory strategies, but efforts at reversing the epithelial damage may also be effective.
There were many presentations which demonstrated the power and beauty of spatial transcriptomic analysis in reconstructing the immune response in three dimensions.
About the CESORA Symposium
Advances in Spatial Multi-Omics: Navigating Technological Hurdles to Accelerate Tissue Biology and Infectious Disease Research
The CESORA Symposium is a four-day scientific meeting hosted by the Africa Health Research Institute in Ballito, South Africa. The 2025 programme brought together international leaders in spatial biology, immunology, infectious diseases and bioengineering to advance the application of spatial multi-omics in tissue biology and global health. Sessions covered HIV persistence, HPV biology, tuberculosis, organoid systems, spatial data science and emerging spatial technologies, alongside showcases of CESORA-funded projects. The symposium provides African researchers with training, collaboration opportunities and exposure to cutting-edge spatial omics platforms.
This content has been developed independently by Touch Medical Media for touchINFECTIOUS DISEASES. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Session: CESORA Symposium. Ballito, South Africa, November 2 – 5, 2025.
Disclosures: This short article was prepared by touchINFECTIOUS DISEASES in collaboration with Paul Kelly. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchINFECTIOUS DISEASES utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
Paul Kelly has nothing to disclose in relation to this article.
Cite: Environmental Enteric Dysfunction: Gut Barrier Failure, Stunting and Vaccine Response. touchINFECTIOUS DISEASES. 27 January 2026.
Register now to receive the touchINFECTIOUS DISEASES newsletter!
Don’t miss out on hearing about our latest peer reviewed articles, expert opinions, conference news, podcasts and more.
