Science —

It’s time to rethink how we identify disease-causing microbes

Modern disease theory must account for communities of commensal bacteria.

At the turn of the last century, German physician Robert Koch identified four critical criteria for determining whether or not a particular microbe causes a disease. The ideas behind them were crucial for advancing medicine and formalizing the germ theory of disease. Over the last century, these postulates have been updated as medicine has advanced.

In what may end up being the most recent of these updates, biologists Allyson Byrd and Julia Segre propose some adjustments to these classic medical postulates intended to bring them in line with analytic techniques based on DNA sequencing and the most current understanding of bacterial communities. Just as the previous updates to Koch’s postulates did, these proposed amendments incorporate cutting-edge scientific knowledge and add nuance to our understanding of the causes of disease.

Koch’s original postulates are that, if a microorganism causes a disease, then:

  1. For every single case of the disease, the microorganism will be present.
  2. Healthy people will not carry the microorganism—if they did, they would be sick.
  3. The microorganism can be isolated and cultured in a lab, then used to infect new people.
  4. The microorganism can be re-isolated from a person who was experimentally infected.

These four postulates have been used by scientists and doctors for years to demonstrate that a given microorganism is the cause of a disease, though they have been updated as medicine has progressed. For example, once knowledge of asymptomatic carriers became more commonplace—think "typhoid Mary"—these individuals became a known exception to Koch’s postulates. Additionally, certain pathogens, like prions, are known exceptions to Koch’s second postulate.

In more recent years, DNA sequencing and other analytic advancements have improved our ability to identify microorganisms, and incorporation of these techniques into Koch’s postulates would bolster their usefulness. Additionally, scientists have begun to understand the complex microbiome that inhabits our bodies, which also has an effect on disease progression.

In human bodies, there are a wide variety of bacteria that naturally inhabit the gut, mouth, and other areas. These bacteria, known as commensal microorganisms, find an inviting environment within the human body and can provide the body with some benefit.

Some commensal organisms have the ability to protect their host from infection by another microorganism, either by inhibiting the intruder’s growth or by activating the host’s immune system. Communities of commensal microbes can also influence infection rates, sometimes providing even a more robust protective effect.

Although we’ve had some knowledge of infection resistance due to commensal organisms, previous adaptations of Koch’s postulates did not address one potential outcome of their activity: cases where the presence of a pathogen does not cause an infection but possibly turns someone into a disease carrier.

In fact, the presence of commensal organisms and their ability to fight off disease challenges the postulate that a pathogenic microorganism will always induce disease in an infected host. DNA sequencing has revealed the presence of disease-causing bacteria in many healthy individuals.

So, Byrd and Segre argue that certain steps must be taken to provide more accurate and modern diagnoses of disease-pathogen relationships. They call for DNA sequencing of all bacterial members of a microbial community in sick and healthy people, combined with the use of computational models that can assess which microbes are necessary or sufficient for the development of a disease. This should occur in conjunction with tests for the presence or absence of the microbe in both symptomatic and asymptomatic individuals, since strong commensal bacterial communities could affect a microbe’s ability to cause an infection.

The use of DNA sequencing for both infected and uninfected persons could provide important insight into which commensal bacteria may play a role in providing the host with immunity against a pathogen, as well as provide insight into which bacterial communities bestow the most susceptibility to hosts. The important role of commensal bacterial communities in granting a type of immunity to individuals has only recently begun to be fully understood, and this bacterial DNA sequencing approach recommended by Bryd and Segre would further develop our knowledge.

This opinion piece by Byrd and Segre addresses some modern issues with Koch’s postulates, and it proposes adjustments to remedy these limitations. Even though science has progressed, Koch’s postulates have remained remarkably relevant, considering that they were proposed over a century ago.

However, they need to account for advancements in scientific knowledge—how could Koch have predicted the use of DNA sequencing to identify microorganisms, when the structure of DNA wasn’t even discovered in his lifetime? Byrd and Segre make some compelling arguments about how to improve these postulates so that they remain current as medicine advances.

Science, 2016. DOI: 10.1126/science.aad6753  (About DOIs).

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