Human gut homeostasis and regeneration: the role of the gut microbiota and its metabolites

Abstract

The healthy human gut is a balanced ecosystem where host cells and representatives of the gut microbiota interact and communicate in a bidirectional manner at the gut epithelium. As a result of these interactions, many local and systemic processes necessary for host functionality, and ultimately health, take place. Impairment of the integrity of the gut epithelium diminishes its ability to act as an effective gut barrier, can contribute to conditions associated to inflammation processes and can have other negative consequences. Pathogens and pathobionts have been linked with damage of the integrity of the gut epithelium, but other components of the gut microbiota and some of their metabolites can contribute to its repair and regeneration. Here, we review what is known about the effect of bacterial metabolites on the gut epithelium and, more specifically, on the regulation of repair by intestinal stem cells and the regulation of the immune system in the gut. Additionally, we explore the potential therapeutic use of targeted modulation of the gut microbiota to maintain and improve gut homeostasis as a mean to improve health outcomes.

Keywords:

• Gut microbiota
• host-microbiota interactions
• stem cells
• wound healing
• tissue regeneration
• metabolites

Acknowledgements

Figures 1–3 created with Biorender.com. Authors would like to thank Amy Fitzpatrick for fruitful discussions.

Author contributions

CMA-G and EG-G conceived and designed the manuscript. CMA-G and EG-G wrote the manuscript. JSE and PDC critically revised the manuscript. All authors contributed to the article and approved the submitted version.

Disclosure statement

While engaged in this review, CMA-G and JSE were employed by a research centre that belongs to a food company (Grupo Empresarial Nutresa). EG-G and PDC report no conflict of interest.

Additional information

Funding

This work was supported by Enterprise Ireland and the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 847402 awarded to EGG. Research in the goup of PDC is funded through Science Foundation Ireland (SFI) under grant number SFI/12/RC/2273, and SFI together with the Irish Department of Agriculture, Food and the Marine, SFI/16/RC/3835 (VistaMilk), by the Enterprise Ireland funded Food Health Ireland project and by the European Commission under the Horizon 2020 program under grant number 818368 (MASTER).