Nurturing 'Colonization Resistance' for Holistic Health?

What is 'colonization resistance' and why should you care about it?

The Human Microbiome Project fueled research exploring 'colonization resistance', protection that healthy gut microbes (microbiota) provide against many pathogens. Searches in PubMed identified nearly 3,000 papers on this topic in the most recent 5-year period and only 39 papers in the previous period. Why is interest expanding?

Scientists now have the methods and tools to identify key microbes (commensals or mutuaiists that do not harm the host) from healthy gut microbiota that protect against some pathogens, including many pathogens that are acquired in hospitals (C. difficile and other pathogens enriched in nosocomial environments).

Tools of microbiome analysis are also being applied to identify microbial biomarkers predictive of one of the primary killers of preterm infants in NICUs around the world, necrotizing enterocolitis. Click here to see recent study (Dobbler et al., 2017) that identified the Enterobacteriaceae family (with dominating species Citrobacter koseri and Klebsiella pneumoniae) as causing necrotizing enterocolitis in Brazilian preterm infants. Other conditions associated with the disease include low species diversity of the microbiota, low abundance of Lactobacillus spp. (some strains used in fermenting cheese, meats, and yogurt and as probiotics), and altered microbial-network structures.

This important work could support microbiota-based screening approaches for early detection of preterm infants at higher risk of developing potentially fatal necrotizing enterocolitis in NICU environments. The work could also support future human clinical trials for potential probiotcs to nurture or restore a microbiota supporting colonization resistance.

How does a healthy gut microbiota protect us?

Complex groups or consortia of microbes form networks that cooperate with and enhance the activity of the epithelial cells lining the gut and the immune cells patrolling the gut. Some direct mechanisms are independent of host factors, including competition with pathogens for nutrients and access to host cells, as well as production of antimicrobial products. Some indirect mechanisms include stimulating host immune and epithelial cells to maintain barriers (physical, chemical, and cellular defenses) against pathogens.

When the normally diverse protective microbiota is disturbed by antibiotics, drugs, or stresses in various environments, susceptibility to pathogens greatly increases. Immunocompromised patients are even more susceptible, with abnormal microbiota, loss of colonization resistance, and higher susceptibility to low pathogen loads or doses present in hospital environments.

Click here for an excellent review by Sohn Kim, April Covington, and Eric Pamer (2017) about the intestinal microbiota that will deepen your knowledge of mechanisms for nurturing and restoring colonization resistance.

Click here for abstract of first paper in the Society for Risk Analysis journal Risk Analysis on the microbiota, dose-response assessment, and the impact of colonization resistance on approaches for biologically relevant dose-response modeling for hosts with normal and disturbed microbiota. The figure below from this paper suggests the need for balancing studies based on the traditional disease triangle of epidemiology (host, pathogen, and environment interactions predictive of disease) to a more holistic health triangle that includes the microbiota.

Traditional medical approaches using antibiotics may exacerbate nosocomial infections, shifting from acute to chronic or recurring disease, delaying or preventing pathogen clearance. Cornell Professor Rod Dietert, selected as a microbiome hero for 2018 by a World Microbiome Day committee, recommends a shift to 'Minding our Microbes' (the theme for the 2018 World Microbiome Day) to restore colonization resistance, minimize disease, and maximize health as the future of holistic medicine.

Curious to learn more about microbiomes in humans over lifecycles and in other animals, plants, soils, marine environments, and foods?

Click to explore the World Microbiome Day website or to access their Glossary of Microbiome Terms.

Figure from World Microbiome Day website.

Please post a comment or question below!

Your input is most welcome. I am happy to blog about topics of my passionate interests (microbiota of humans, animals, and foods, microbiota benefits and risks), and to learn with you about microbiota in plants, soils, and marine environments.

As an alum of the SUNY College of Environmental Science and Forestry, mychorrhizal symbiosis and specificity of colonization of tree roots by ectomychorrhizal fungi were the topic of my first MS thesis many many years ago! Give me a reason to update my knowledge with your comment or question!

Key References

Coleman M, Elkins C, Gutting B, Mongodin E, Solano‐Aguilar G, Walls I. 2018. Microbiota and Dose Response: Evolving Paradigm of Health Triangle. Risk Analysis. 38(10):2013-2028.

Dobbler PT, Procianoy RS, Mai V, Silveira RC, Corso AL, Rojas BS, Roesch LF. 2017. Low microbial diversity and abnormal microbial succession is associated with necrotizing enterocolitis in preterm infants. Frontiers in microbiology 8:2243.

Kim S, Covington A, Pamer EG. 2017. The intestinal microbiota: antibiotics, colonization resistance, and enteric pathogens. Immunological Reviews 279(1):90-105.