New advances in the pathophysiology of intestinal ion transport and barrier function in diarrhea and the impact on therapy

Abstract

Diarrhea remains a continuous threat to human health worldwide. Scaling up the best practices for diarrhea prevention requires improved therapies. Diarrhea results from dysregulation of normal intestinal ion transport functions. Host–microbe contact is a key determinant of this response. Underlying mechanisms in the disease state are regulated by intracellular signals that modulate the activity of individual transport proteins responsible for ion transport and barrier function. Similarly, virulence factors of pathogens and their complex interaction with the host has shed light on the mechanism of enteric infection. Great advances in our understanding of the pathophysiologic mechanisms of epithelial transport, and host–microbe interaction have been made in recent years. Application of these new advances may represent strategies to decrease pathogen attachment, enhance intestinal cation absorption, decrease anion secretion and repair barrier function. This review highlights the new advances and better understanding in the pathophysiology of diarrheal diseases and their impact on therapy.

Keywords::

• diarrhea
• ion transport
• microbial interaction
• pathophysiology
• tight junction and therapy

Acknowledgements

We thank GB Nair, then director of the National Institute of Cholera & Enteric Diseases, Kolkata, for his invaluable feedback in the preparation of an article outline. The authors also thank Nick C Zachos and Nadia Ameen for helping to edit the text.

Financial & competing interests disclosure

This work was supported by the Government of India, Ministry of Science & Technology, Department of Biotechnology grant (BT/HRD/35/02/07/2009) to KM Hoque, Scientist & Ramalingaswami Fellow. IA Sheikh is a recipient of Indian Council of Medical Research (ICMR) Junior Research Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.