Successive infection

Successive infection is a model that attempts to account for how the microbiome dysbiosis characteristic of many inflammatory diagnoses develops. To hear me describe the successive infectious process in person, please watch this speech I gave at the Ljubljana International Congress on Autoimmunity in 2010. If not, read this summary.

Here I describe how pathogens can slow the human immune response in order to better survive. Any pathogen that slows immune activity allows other pathogens to better survive in the same immunocompromised host. This creates a snowball effect, where it becomes progressively easier for the host to acquire pathogens as the strength of the immune response decreases. This process has been termed successive infection.

Successive infection

Each person undergoing successive infection acquires a unique mix of pathogens.

As successive infection occurs, pathogens incorporated into the microbiome may increasingly shift a person’s microbial communities away from a state of health. Eventually, this person might present with the symptoms of an inflammatory diagnosis. However, because so many microbes have the potential to cause disease, it is unlikely that any two people undergoing successive infection acquire the exact same mix of pathogens. Instead, the symptoms any one person develops vary based on their unique infectious history; symptoms reflect the tissue, species, and virulence of the pathogens they have acquired over time.

Certainly both physicians and patients know that no two people with the same inflammatory diagnosis ever report the exact same symptoms. For example, inflammation caused by the disease systemic lupus erythematosus can affect many different body systems — including the joints, skin, kidneys, blood cells, brain, heart and lungs. But few people with lupus suffer from symptoms in all these areas. In fact, the most distinctive sign of lupus, a facial rash across both cheeks, occurs in many but not all cases of lupus.

Successive infection does not necessarily lead to an increase in microbiome diversity. In fact, the opposite is often true. Many studies of microbiome dysbiosis show that, in disease, microbial populations become less diverse over time. One reason why this may occur is because pathogens are very competitive. Certain pathogens may outcompete larger populations of other less aggressive species. A microbial ecosystem may become particularly dysregulated if keystone species are lost.

Agents other than pathogens can disable the immune response during successive infection. Exposure to toxins, chemicals, pollutants, stress or many other environmental factors can contribute to the successive infection “snowball effect.”

Two implications of successive infection

  • Medicine has often tried to tie certain inflammatory diseases to the presence of one microbial species. However, successive infection allows that the acquisition of multiple pathogens acting together can drive an inflammatory disease process.
  • Many inflammatory diseases are investigated as being either “viral” ,“bacterial”, or “fungal.” However, if pathogens are acquired via successive infection, a mix of different types of pathogens can all contribute to the same disease state. If these different microbes disable immune activity in order to persist, then a bacterial species can aid the survival of a virus or fungus, and vice versa.

Key points

  • Any pathogen capable of slowing immune function creates an environment that makes it easier for other pathogens to also persist in the human body.
  • Under these conditions, a snowball effect can occur; as the human host becomes increasingly immunocompromised, it more easily acquires pathogens over time.
  • If a person becomes immunocompromised to the point where a sufficient number of pathogens drive microbiome dysbiosis, the person may present with the symptoms of an inflammatory disease.
  • Under the above circumstances, the symptoms any one person develops would vary based on the species, location, and virulence of the unique mix of pathogens they have acquired over time.