The microbial diversity hypothesis suggests that the diversity and turnover of bacterial species in the gut mucosa and other areas around the body are key factors in the regulation of the immune system. This is in contrast to the historical belief that the body showed stable colonization with certain microbial species.
It was proposed as an extension of or alternative to the hygiene hypothesis, following the emergence of several factors that could not be explained by the original hypothesis.
Shortcomings of the Hygiene Hypothesis
The hygiene hypothesis, as initially proposed by Strachan in 1989, traced the supposed reduction in exposure to microbes during childhood to the rise in the incidence of allergic and autoimmune disease.
However, this theory is unable to explain several factors about the epidemiology of allergic disease including:
- Why allergic asthma is on the rise in American cities classed as 'unhygienic'.
- Why migrant children in some large European cities have a lower incidence of allergic disease despite sharing many common characteristics as to the environment.
- Why infection by airborne viruses does not seem to protect from allergic sensitization.
- Why research has not shown congruent findings to support the link between certain viral infections and allergic diseases in diverse populations.
- The inefficiency of probiotics in the prevention and treatment of allergic diseases.
As a result of these factors, there is a need to reconsider the basis of the hygiene hypothesis and identify particular microbial agents that may play a protective role in the prevention of allergic diseases.
Microbial Diversity
The microbial diversity, also known as the “high turnover and diversity hypothesis”, was first proposed by Paolo Matricardi, and later refined by von Herzen.
It suggests that a high turnover of bacteria at the mucosal level, located in the lymphoid tissue of the nasal tubes, bronchi and gut, is the predominant state of the normal body. This is in contrast to the supposed static colonization by particular species. This wide and changing variety of bacteria causes the presentation of many strong antigens to the immune system, resulting in its incessant stimulation. This is thought to have a protective effect against atopic and allergic diseases.
Some research has supported this notion, although the sample size was small and further studies are required to validate the hypothesis. It remains unclear if the protective effect is brought about by diversity alone, or by a diverse population which encompasses particular organisms that are necessary for the development of the immune system.
The embryonic immune system has been compared to a computer that is equipped with programs but lacks significant data. As individuals progress through gestation and infancy, they are naturally exposed to a number of diverse organisms to fill up their database of organisms that can be recognized by the immune system. This allows them to identify known and harmful agents, and to exhibit an allergic response as deemed necessary.
Allergic Disease
The microbial diversity hypothesis is of particular interest in that it seems likely that a lack of diversity may be linked to an increased incidence of allergic disease. Specific life stages are considered to be the most important points in regards to the development of allergies. These include:
- Early development.
- Later part of pregnancy.
- The first days and months of infancy.
For this reason, it is essential that microbial exposure is maintained over an extended period of time that covers these critical life stages.
In fact, there is some research to suggest that being born vaginally has a protective effect against the development of allergic disease. It is postulated that this may be linked to the passage of natural flora that are passed from mother to infant during birthing. In contrast, infants delivered by Caesarean section are more likely to be affected by allergies. However, breastfeeding has long been proved to help reduce the risk of allergies for all babies, regardless of the mode of delivery.
Beyond birth and through the early years of childhood, the effect of microbial exposure required for optimal outcomes remains unknown.
References
Further Reading
Delabeling penicillin allergy to improve syphilis care