Bacteria, biodiversity, and allergies.

You may not have heard of gammaproteobacteria, but I'm sure the names salmonella, escherichia coli, pests and cholera do ring a bell. They are all caused by bacteria that belong to the gammaproteobacteria family. Hanski et al. took small skin samples from 118 Finnish adolescents and found a variety of bacteria, the most represented being Actinobacteria, Bacilli, Clostridia, Betaproteobacteria, Alphaproteobacteria, and Gammaproteobacteria.

"Ew," you're probably thinking. Well. . . think again.

On an average human there are an estimated 10^12 bacteria that make their home in the outer layers of our epidermis and in our hair follicles. And yes, you've guessed it: these guys are very much needed. In their study [1], Hanski et al. correlated the lack of biodiversity in skin microbiota with allergic disposition. The study subjects were from different size towns and villages, offering a diverse range of exposure to bacteria. To analyze the skin microbiota, they took DNA samples from the epidermis on the inside of the arm. To test allergy predisposition they measured IgE antibody levels after exposure to a mixture of common inhalant allergens, and used a cutoff point to define atopic individuals (the ones that showed a predisposition toward allergic hypersensitivity). A side note: IgE antibodies are responsible for the over-stimulation of mast cells and basophils that trigger allergic reactions. Atopic individuals can have up to ten times the normal IgE levels, though that doesn't exclude individuals with normal IgE levels from having an allergic reaction.

In order to test their hypothesis, Hanski et al. did a principal component analysis in which they compared the number of bacteria genera found in the skin samples with land use in the immediate surrounding (whether agricultural, , forest, built area, etc. within 3 km of the subject's home).

"The PC1_env of the land use types was significantly (P = 0.0033) related to PC2_bac, indicating that the generic diversity of proteo-bacteria was higher on the skin of individuals living in an environment with more forest and agricultural land compared with those living in built areas and near water bodies."

PC1 and PC2 in the above are the first and second principal components. Next, the researchers repeated a similar principal component analysis to attest the correlation between diversity in skin microbiota and atopy. One thing to ask when carrying this kind of analyses is whether the atopic subjects in the study are evenly distributed across agricultural and urban areas. If the distribution is skewed (for example, if most atopic subjects live in the city and only a few in agricultural areas), this could clearly skew the results. The researchers checked this and found no correlation between atopy and spatial distribution. they also checked for other possible confounders (other factors that might skew the analysis) such as passive smoking and pets, but none were significantly correlated with atopy.

"Atopic individuals had highly significantly (P = 0.0003) lower generic diversity of gammaproteobacteria on the skin compared with healthy individuals."

Furthermore, the researchers found "one significant correlation, between the relative abundance of gammaproteobacteria and IL-10 expression in healthy individuals (P = 0.015)." IL-10 are anti-inflammatory cytokines (protein molecules).

Overall, an interesting paper, as it reinforces the hypothesis that by limiting the exposures to our immune system we are somehow altering our ability to build appropriate responses to the environment. We are indeed seeing a decline in biodiversity of the environment we live in and at the same time witnessing an increasing prevalence of allergies. I do wonder about the number of subjects (118) versus the high number of tests the researchers conducted. And I also wonder whether the researchers tried a logistic regression fit as an alternative to the principal component analysis.

Hanski, I., von Hertzen, L., Fyhrquist, N., Koskinen, K., Torppa, K., Laatikainen, T., Karisola, P., Auvinen, P., Paulin, L., Makela, M., Vartiainen, E., Kosunen, T., Alenius, H., & Haahtela, T. (2012). Environmental biodiversity, human microbiota, and allergy are interrelated Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1205624109