Human skin epidermis functions as a physical, chemical, and immune barrier against the external environment, retains internal moisture, while also providing a protective niche for its resident microbiota, known as the skin microbiome. Cooperation between the microbiota, host skin cells, and the immune system is critical for the maintenance of skin health, and a disruption to this delicate interplay, such as by pathogen invasion or a breach in the skin barrier, often leads to impaired skin function, such as eczema. Microbial metabolites and products (something I named “postbiotics” in my 2019 paper), including microbial exosomes, have been identified to mediate these interactions, particularly those involved in skin-microbe communication and defensive symbiosis, where the microbes and skin work together to ward off pathogen colonization. 

Given the small size, ubiquity, and complexity of the microbiota, scientists have had great difficulty in understanding the role of microorganisms in the health and diseases of humans. Before the germ theory of disease was accepted and bacteria were successfully cultured from human tissues, Semmelweis dramatically reduced the mortality rate of pregnant women by simply introducing hand washing in his clinic, and in the late 1800s, Lister pioneered antiseptic surgical procedures. By the early 1900s, the idea that humans are colonized by microorganisms in the hours after birth was well accepted. However, given the inability to fulfill Koch’s postulates in some dermatological diseases, the significance of the skin microbiota in health and disease remains under investigation. Understanding the microbiome’s role in health and disease requires the following:

1. The organism must be shown to be invariably present in characteristic form and arrangement in the diseased tissue.
2. The organism, which from its relationship to the diseased tissue appears to be responsible for the disease, must be isolated and grown in pure culture.
3. The pure culture must be shown to induce the disease experimentally.
4. The organism should be re-isolated from the experimentally infected subject [this postulate was added after Loeffler].

Fulfilling these criteria in Koch’s postulates is difficult if for only meeting criteria #2, where isolating and then culturing the microorganism can be very difficult. Likewise, #3 is difficult because it requires purposely infecting people. Often the criteria are fulfilled in animal models of the disease, but not humans.

While Koch’s postulates are valuable in helping to understand infectious diseases, the concept is reductionistic. That is, diseases are multifactorial. Koch’s postulates will look for one pathogen involved in the disease, while the disease may involve not only other pathogens, but also other health aspects of the host such as environmental exposures and one’s health status. My point is that any disease, including infectious diseases, are multifactorial. Exploring one of many factors will not be predictive of transmission or of outcomes. For example, if we look at acne, P. acnes is one factor in the disorder. And P. acnes exists in different forms, with a distinctly different phenotype in the acneic lesion versus the normal areas of skin. Further, bacteriophage are involved. These are viruses that infect bacteria, in this case, infecting P. acnes. The P. Acnes variants in the acneic lesion areas of the skin don’t contain an immune system called CRISPR. Therefore, these bacteria become infected with bacteriophage and harbor these inflammatory viruses. This is one of the reasons why we believe the NeoGenesis product called MB-1 is helpful to acneic skin. MB-1 contains skin identical bacteria that possess the CRISPR system and are likely killing the inflammatory bacteriophage. So the MB-1 helps to populate the skin with symbiotic bacteria, out competing inflammatory bacteria, and also introduces CRISPR containing bacteria that kill the inflammatory bacteriophage. Considering MB-1, it’s like showing the opposite of Koch’s postulates. The organisms we use to make MB-1 are present in normal skin (1), and the bacteria in MB-1 seem to be responsible for reducing the disorder when applied to the affected area of skin (2). However, 3 and 4 of Koch’s “opposite postulates” are difficult to perform. We’d have to isolate the MB-1 bacteria from the skin, culture them, and then apply the cultured bacteria to acneic skin, showing the cultured MB-1 bacteria reduce the acneic lesion. This is the sort of difficult work that scientists are currently performing to understand infectious diseases.

There are new techniques being employed, such as genomics (Next Generation Sequencing), so that the genetic fingerprint of pathogens can be used to identify what is or has been present in the infected tissue. For example, bacteria that once populated the area of skin under investigation but have now died and are no longer present, often leave a genetic fingerprint of their past colonization. This technique alone has brought a wealth of information about skin disease. I’ll have more to say about the skin’s microbiome in future posts. We understand much about it, and I’ll share some of the complexities in the weeks to come.