Prevalence of inhibitory LPS within gut microflora could underlie hygiene hypothesis

This week prestigious journal Cell published seminal microbiome study that could explain hygiene hypothesis that suggests that "microbial cleanliness" in developed countries predisposes individuals to immunopathologies such as allergy, multiple sclerosis and other autoimmune diseases. 

This study found that gut microflora in babies from Finland and Estonia, but not from Russian Karelia, are enriched in gut bacteria with inhibitory LPS that failed to properly "educate" newborns innate immune system thus predisposing them to higher incidence of immunopathologies.

The first finding was that microbiota in babies from Finland, but not from Russian Karelia, were enriched in Bacteroides. Now this fact by itself isn't too surprising. 

The second finding was that lipid A component of LPS from these Bacteroides [unlike lipid A component of LPS from E. coli] species were non-stimulatory in TLR4 assay. In fact, molecular analysis showed that Bacteroides harbored tetra- and penta-acylated lipid A structures, as opposed to the hexa-acylated lipid A seen in E. coli. Such structural modification converted Bacteroides lipid A into totally non-stimulatory ligand.

In fact, Bacteroides derived lipid A was inhibitory when combined with stimulatory, E.coli derived lipid A [LPS tolerance assay, where primary exposure to E. coli LPS makes responding cell refractory to secondary exposure].

Finally, third finding was that presence of non-stimulatory lipid A had immunological consequences since it failed to reduce incidence of diabetes in NOD mice [whereas lipid A from E. coli could, as expected].  

In summary, this important study has provided one of the first definite molecular evidence underlying hygiene hypothesis and suggested the path for its prevention.

David Usharauli