Homeostasis of the gut barrier and potential biomarkers

Jerry M. Wells*, Robert J. Brummer, Muriel Derrien, Thomas T. MacDonald, Freddy Troost, Patrice D. Cani, Vassilia Theodorou, Jan Dekker, Agnes Méheust, Willem M. De Vos, Annick Mercenier, Arjen Nauta, Clara L. Garcia-Rodenas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

106 Citations (Scopus)

Abstract

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of micro- bial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overre- action to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the micro- biota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by pro- longed mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell- dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.
Original languageEnglish
Pages (from-to)G171-G193
JournalAmerican Journal of Physiology. Gastrointestinal and Liver Physiology
Volume312
Issue number3
DOIs
Publication statusPublished - 2017

Keywords

  • Antimicrobial peptides
  • Epithelial permeability
  • Gut barrier
  • Microbiota

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    Wells, J. M., Brummer, R. J., Derrien, M., MacDonald, T. T., Troost, F., Cani, P. D., Theodorou, V., Dekker, J., Méheust, A., De Vos, W. M., Mercenier, A., Nauta, A., & Garcia-Rodenas, C. L. (2017). Homeostasis of the gut barrier and potential biomarkers. American Journal of Physiology. Gastrointestinal and Liver Physiology, 312(3), G171-G193. https://doi.org/10.1152/ajpgi.00048.2015