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Impact of enteric bacterial infections at and beyond the epithelial barrier

Abstract

The mucosal lining of the gut has co-evolved with a diverse microbiota over millions of years, leading to the development of specialized mechanisms to actively limit the invasion of pathogens. However, some enteric microorganisms have adapted against these measures, developing ways to hijack or overcome epithelial micro-integrity mechanisms. This breach of the gut barrier not only enables the leakage of host factors out of circulation but can also initiate a cascade of detrimental systemic events as microbiota, pathogens and their affiliated secretions passively leak into extra-intestinal sites. Under normal circumstances, gut damage is rapidly repaired by intestinal stem cells. However, with substantial and deep perturbation to the gut lining and the systemic dissemination of gut contents, we now know that some enteric infections can cause the impairment of host regenerative processes. Although these local and systemic aspects of enteric disease are often studied in isolation, they heavily impact one another. In this Review, by examining the journey of enteric infections from initial establishment to systemic sequelae and how, or if, the host can successfully repair damage, we will tie together these complex interactions to provide a holistic overview of the impact of enteric infections at and beyond the epithelial barrier.

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Fig. 1: Commensal maintenance and pathogenic depletion of the mucous gel bilayer.
Fig. 2: Cell contact and polarity cleavage or displacement by enteric pathogens.
Fig. 3: Gut permeability induced by enteric pathogens.
Fig. 4: Effects of bacteria on intestinal stem cells.
Fig. 5: A holistic understanding of enteric infections and host effects.

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Acknowledgements

The authors thank the referees for their helpful comments on this work. The authors also thank H. Abud for stimulating discussions about intestinal stem cells. The authors would also like to acknowledge that, due to space limitations, many important studies and citations could not be included.

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A.P.R., S.J.M. and D.L. researched data for the article. All authors substantially contributed to the discussion of content. A.P.R. wrote the manuscript. S.J.M. and D.L. reviewed or edited the manuscript before submission.

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Correspondence to Dena Lyras.

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Glossary

Goblet cells

Intestinal epithelial cells with the primary function to synthesize and secrete mucous.

Bacteraemia

An infection of the bloodstream.

Sepsis

An overactivation of the immune response following infection that causes inflammation throughout the body and can be life threatening.

Haemolytic uraemic syndrome

A syndrome most commonly caused by infection, which leads to kidney damage, blood cell lysis and retention of kidney filtrates.

Paneth cells

Specialized epithelial cells located at the small intestinal crypt base that secrete stem cell-supporting factors.

Stem cell niche

Specific microenvironment at the base of the intestinal crypt that promotes an undifferentiated, self-renewable state.

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Rogers, A.P., Mileto, S.J. & Lyras, D. Impact of enteric bacterial infections at and beyond the epithelial barrier. Nat Rev Microbiol (2022). https://doi.org/10.1038/s41579-022-00794-x

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