Gut microbes and immunity: The hygiene hypothesis, peak antibiotics, and the post-Pasteurian Age

“Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that, in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma compared to specific pathogen-free (SPF) mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal—but not adult—GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.”

That’s the abtract from the paper “Gut Microbes Keep Rare Immune Cells in Line” (I think subscription is required, sorry).

There have been a good series of papers and studies into the “hygiene hypothesis” – that exposure to microbes early in life are actually important for the proper evolution of the immune system. This paper is one more example of that – these researchers were able to show what happened to the immune cells in the but of mice that never acquire bacteria, acquire bacteria only as adults, or acquire bacteria as pups.

I sometimes think of the 1850s-1990s as the Pasteurian Age – we were controlling bacteria to create a sterile world based on germ theory, aseptic techniques, public policies, and, of course, antibiotics. Alas, in the past 20 years, we’ve come to the realizations that we’ve reached (to joke a bit here) “peak antibiotics”, and that the only bugs to survive our clean homes and hospitals and antibiotics were Superbugs.

Now, in the past 5-10 years, I feel we are entering a post-Pasteurian Age, where we are gaining a deeper respect for the bacteria and fungi that share our world (and bodies) and that we are slowly thinking of how we can balance the sterile world we want and the microbe-filled world we need.

Great time to be a practical microbiologist, don’t you think?