Pathobiont

Overview

Pathobiont is a term for a microorganism that is a normal resident of a host’s microbiome but has the capacity to become pathogenic under certain conditions. In other words, a pathobiont is a commensal or symbiotic microbe with latent pathogenic potential.^[1] The term was originally coined in 2008 by immunologist Sarkis K. Mazmanian to describe how Helicobacter hepaticus (ordinarily a harmless gut bacterium in mice) could induce intestinal inflammation (colitis) if the host’s genetic or environmental conditions were altered. [x][x] Unlike classic pathogens that typically originate outside the host or invariably cause disease, pathobionts normally coexist peacefully within the host’s microbiome and only provoke disease when the host-microbe balance is disturbed. For example, Mazmanian and colleagues defined an intestinal pathobiont as “a symbiont that is able to promote pathology only when specific genetic or environmental conditions are altered in the host”.^[2]

Distinction from Opportunistic Pathogens

A key aspect of the definition is that pathobionts are indigenous members of the normal microbiota, in contrast to opportunistic pathogens which are often acquired from external sources. Pathobionts tend to be long-term colonizers that usually cause no harm in immunocompetent hosts. In contrast, opportunistic pathogens (e.g., Pseudomonas aeruginosa or Candida in hospital settings) are often environmental or transient microbes that cause disease when they access a susceptible host.[x] In healthy individuals, a pathobiont may even contribute to normal microbiome functions, but it carries the “pathogenic switch” that can be flipped by changes in the host or environment. [x] Thus, pathobionts occupy a gray area between purely beneficial commensals and overt pathogens, underscoring the spectrum of microbe–host relationships beyond the oversimplistic “good vs. bad” dichotomy.

Pathobiont Transition from Commensal to Pathogenic

Pathobionts illustrate how a normally benign microbe can transition to a disease-causing agent. This transition is conditional, requiring specific triggers that disrupt the normal host-microbe homeostasis. Perturbations such as host gene mutations, environmental stressors, or infections can disrupt the balanced microbiome (“dysbiosis”) and compromise the mucus barrier. This allows certain native microbes to exploit new niches and nutrients. For example, mucin-degrading bacteria thinning the protective mucus, or altered bile acids favoring specific organisms. The expanded pathobionts (illustrated below with C. difficile as an example) produce virulence factors like toxins that damage the epithelium and provoke immune responses. The host’s pattern-recognition receptors detect the pathobiont and trigger an inflammatory cascade (e.g. inflammasome activation, cytokine release), recruiting immune cells (Th17 cells, neutrophils, etc.) to the site. This inflammation further disturbs the ecosystem, often reinforcing the dominance of the pathobiont and perpetuating disease. In effect, pathobionts remain harmless commensals until a “perfect storm” of host and environmental factors tips them into pathogenic behavior.^[3] Important factors that enable a commensal organism to act as a pathogen include:

Microbiological Perspective

From a microbiological standpoint, pathobionts are part of the normal flora and often perform ordinary microbial functions (metabolizing dietary compounds, contributing to colonization resistance, etc.) under baseline conditions. Ecologically, they fit into the complex community of the microbiome, interacting with other microbes and the host. Under homeostasis, pathobionts are kept in check by factors like microbial competition, limited nutrient availability, and host immune surveillance. For example, in a healthy gut, H. hepaticus coexists with other bacteria and does not provoke inflammation; it even appears to have evolved mechanisms (like a type VI secretion system) to limit its own population and avoid triggering host responses.^[9] This suggests that many pathobionts engage in a delicate “truce” with the host: they occupy a niche but actively avoid causing harm, which in turn allows them to persist long-term. However, ecological disturbances can upset this balance.

Pathobionts from an Ecological Perspective

In microbiome ecology terms, pathobionts often behave as “niche opportunists.” When a disturbance (dysbiosis) occurs, they can expand their niche aggressively. The expansion of Bilophila on a high-fat diet (noted above) is one clear ecological example.^[10] Another example is Escherichia coli in the context of IBD: certain strains of E. coli (such as adherent-invasive E. coli found in Crohn’s disease patients) may be normal colonizers in low abundance, but under inflammatory conditions, they bloom and adhere to the gut lining, exacerbating disease. These organisms seek out available niches, such as adhering to exposed mucosal surfaces or using by-products of inflammation (like ethanolamine or nitrates) as nutrients, which gives them a competitive edge when the normal commensals are weakened. Researchers sometimes refer to this behavior as “niche-seeking” or “dysbiosis-driven expansion” of pathobionts.^[11]

FAQs

References

1. A microbial symbiosis factor prevents intestinal inflammatory disease.. Mazmanian, S., Round, J. & Kasper, D.. ( Nature 453, 620–625 (2008).)
2. A microbial symbiosis factor prevents intestinal inflammatory disease.. Mazmanian, S., Round, J. & Kasper, D.. ( Nature 453, 620–625 (2008).)
3. Label or Concept - What Is a Pathobiont?. Jochum L, Stecher B.. (Trends Microbiol. 2020 Oct;28(10):789-792.)
4. A pathobiont of the microbiota balances host colonization and intestinal inflammation.. Chow J, Mazmanian SK.. (Cell Host Microbe. 2010 Apr 22;7(4):265-276.)
5. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice.. Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB.. (Nature. 2012 Jul 5;487(7405):104-8.)
6. Pathobionts: mechanisms of survival, expansion, and interaction with host with a focus on Clostridioides difficile.. Chandra H, Sharma KK, Tuovinen OH, Sun X, Shukla P.. (Gut Microbes. 2021 Jan-Dec;13(1):1979882.)
7. Translocation of a gut pathobiont drives autoimmunity in mice and humans. .. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA.. (Science. 2018 Mar 9;359(6380):1156-1161)
8. Pathobionts: mechanisms of survival, expansion, and interaction with host with a focus on Clostridioides difficile.. Chandra H, Sharma KK, Tuovinen OH, Sun X, Shukla P.. (Gut Microbes. 2021 Jan-Dec;13(1):1979882.)
9. A pathobiont of the microbiota balances host colonization and intestinal inflammation.. Chow J, Mazmanian SK.. (Cell Host Microbe. 2010 Apr 22;7(4):265-276.)
10. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice.. Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB.. (Nature. 2012 Jul 5;487(7405):104-8.)
11. A pathobiont of the microbiota balances host colonization and intestinal inflammation.. Chow J, Mazmanian SK.. (Cell Host Microbe. 2010 Apr 22;7(4):265-276.)