Colonization resistance

Colonization resistance is the mechanism whereby the human microbiome protects itself against incursion by new and often harmful microorganisms.[1][2]

Colonization resistance was first identified in 1967, and it was initially referred to as antibiotic-associated susceptibility. It was observed that animals being treated with the antibiotic streptomycin were susceptible to Salmonella enterica at doses 10,000 fold lower than the standard minimal infectious dose.[3] This led to investigations about the mechanisms utilized by endogenous microbial populations that conferred protection against exogenous pathogens attempting to colonize the gut flora.

It has been observed that colonization resistance can occur within the host in a 'direct' or 'indirect' manner.[4] The former refers to particular components of the microbiota directly competing with exogenous pathogens for nutritional niches (e.g. E. coli directly competes with Citrobacter rodentium for carbohydrates in the intestinal lumen[5]) or by producing growth inhibitors (e.g. Bacteroides thuringiensis can secrete bacteriocin that directly targets spore-forming Clostridioides difficile, thus inhibiting its growth through an unknown mechanism),[6] that directly inhibits the colonizing pathogen. Indirect colonization resistance is thought to be mediated through the induction of immune responses in the host that concomitantly inhibit the colonizing pathogen. An example of this has been observed with B. thetaiotaomicron, which can induce the host to produce antimicrobial C-type lectins REGIIIγ and REGIIIβ, both anti-microbial peptides that target gram-positive bacteria.[7]

Scientists found that gut infections increase its microbiota's resistance to subsequent infections, that taurine is used in as a nutrient to nourish and train the microbiota for this by potentiating its production of sulfide and that the exogenous supply of taurine can induce this microbiota alteration.[8][9]

References

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  1. ^ Wilson, Michael (2005). Microbial inhabitants of humans: their ecology and role in health and disease. Cambridge University Press. ISBN 978-0-521-84158-0.
  2. ^ Trevor Lawley and Alan Walker, "Intestinal colonization resistance", Immunology, volume 38, pages 1-11, 2013.
  3. ^ Bohnhoff M, Miller CP (1962). "Enhanced Susceptibility to Salmonella Infection in Streptomycin-Treated Mice". Journal of Infectious Diseases. 111 (2): 117–127. doi:10.1093/infdis/111.2.117. PMID 13968487.(subscription required)
  4. ^ Buffie CG, Pamer EG (2013). "Microbiota-mediated colonization resistance against intestinal pathogens". Nature Reviews Immunology. 13 (11): 790–801. doi:10.1038/nri3535. PMC 4194195. PMID 24096337.
  5. ^ Kamada N, Kim YG, Sham HP, Vallance BA, Puente JL, Martens EC, Núñez G (2012). "Regulated virulence controls the ability of a pathogen to compete with the gut microbiota". Science. 336 (6086): 1325–1329. Bibcode:2012Sci...336.1325K. doi:10.1126/science.1222195. PMC 3439148. PMID 22582016.
  6. ^ Rea MC, Sit CS, Clayton E, O'Connor PM, Whittal RM, Zheng J, Vederas JC, Ross RP, Hill C (2010). "Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile". Proceedings of the National Academy of Sciences of the United States of America. 107 (20): 9352–9357. doi:10.1073/pnas.0913554107. PMC 2889069. PMID 20435915.
  7. ^ Cash HL, Whitham CV, Behrendt CL, Hooper LV (25 August 2006). "Symbiotic bacteria direct expression of an intestinal bactericidal lectin". Science. 313 (5790): 1126–1130. Bibcode:2006Sci...313.1126C. doi:10.1126/science.1127119. PMC 2716667. PMID 16931762.
  8. ^ "NIH scientists identify nutrient that helps prevent bacterial infection". National Institutes of Health (NIH). 15 January 2021. Retrieved 13 February 2021.
  9. ^ Stacy, Apollo; Andrade-Oliveira, Vinicius; McCulloch, John A.; Hild, Benedikt; Oh, Ji Hoon; Perez-Chaparro, P. Juliana; Sim, Choon K.; Lim, Ai Ing; Link, Verena M.; Enamorado, Michel; Trinchieri, Giorgio; Segre, Julia A.; Rehermann, Barbara; Belkaid, Yasmine (4 February 2021). "Infection trains the host for microbiota-enhanced resistance to pathogens". Cell. 184 (3): 615–627.e17. doi:10.1016/j.cell.2020.12.011. ISSN 0092-8674. PMC 8786454. PMID 33453153.