Speed Round: Jack Gilbert on the Hygiene Hypothesis

Welcome to The Microbiome Coalition's Speed Round series in which we ask key opinion leaders a single question about the latest happenings in the microbiome sphere. We hope you enjoy!  

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In this Speed Round, we feature Jack Gilbert, Faculty Director of the Microbiome Center and Professor of Surgery at the University of Chicago. 

TMBC: Is the hygiene hypothesis dead and replaced by the old friends hypothesis, or are they flip sides of a coin, part of a continuum, or something else entirely?

Gilbert: Definitions are important here. As I understand it the hygiene hypothesis stipulates that reduced exposure to microbial sources may be detrimental for our health, where as the old friends hypothesis states that our physiology and immunology evolved to adapt to the burden of parasites and microbes that would otherwise be pathogenic. Both of these definitions are woefully incomplete and hide a rich vein of complexity. The primary reason why the hygiene hypothesis and the (microbial) old friends hypothesis are incorrect in their existing proposition is that microbes are hugely varied; there is more diversity in one of the phyla of the bacteria than in the entirely kingdom of the animals and plants combined. So just stating that it is exposure to microbes generally that needs to be enriched misses the point that some bugs need to be avoided, and others need to be allowed to have contact with our immune system. 

Secondly, these hypotheses don't delineate between exposure and colonization. Many microbial exposures appear to elicit beneficial effect even when the bacteria or viruses are dead. This would suggest that immune stimulation is the key outcome that elicits a beneficial effect upon exposure, not colonization. However, our body has a microbial community and ecology associated with it, and as such some microbes have colonized us. Of course the immune system is very good at controlling and managing that colonization (like a good gardener), but essentially some microbes seem very well adapted to the peculiarities of our gut or mouth for example. So one might assume that these colonizers are some how important for our immune homeostasis, i.e. the immune system is expecting to see them. But why it overreacts in their absence it still not fully understood.

In our work on the Amish and Hutterite exposure it appears that dead bugs are fine for immune stimulatory protection, and that the immune stimulation leads to increased macrophage activity, which clears out aged neutrophils that are significantly more pro inflammatory than younger neutrophils. So essentially stimulus reduces systemic inflammation. But these children may also be acquiring pathogens or opportunistic bacteria from their environment as well, and these could have negative consequences. We know that infections can result in immune symbiosis and cause the onset of some conditions, such as asthma. So, as in all things, balance is needed. Just saying we need more exposure if not appropriate. We need to control our exposure where possible, and practice common sense to ensure appropriate exposure and yet reduced interaction with pathogens that can wreak havoc.