So, yesterday, we spoke about one new avenue to developing new antibiotics. Today, we will talk about what happens when we take antibiotics.
We ingest these antibiotics which often find their way to our intestines. And, that means our gut microbes (yes, there is a cornucopia of bacteria that thrive in our intestines) are put out of whack. It’s not atypical for many of us to develop diarrhea after a course of antibiotics, since we’ve reduced the ability of these intestinal flora to effect critical functions in our body. (It’s also why I always recommend those who are undergoing antibiotic therapy to have at least one yoghurt serving each day- the kind that contains bacteria.)
But, gut microbes are also critical for the functioning of our immune function. And, when these gut microbes are lost, a patient may develop what is called Vancomycin-resistant Enterococcus faecium (VRE). Because the opportunistic pathogen was able to develop an infection in our guts. And, this infection is one that often comes when we are being treated for something else in hospitals. (This infection is an example of why some folks require fecal transplants.)
Drs. M.C. Abt, C.G. Buffie, B. Susac, S. Becattini, R.A. Carter, I. Leiner, J.W. Keith, and E.G. Pamer (all of Memorial Sloan Kettering Cancer Center; Abt and Pamer are the senior authors) along with Dr. D. Artis (Cornell Medical) and L.C. Osborne (UBC, Vancouver, British Columbia) published some very interesting results in Science Translational Medicine.
What made it interesting? Their idea is to enhance the gut immune system by adding another infection- one of a norovirus. This norovirus attacks the VRE, which reduces its population in our guts.
Normally, our gut bacteria induce our immune system to produce antimicrobial proteins. But, because of antibiotic administration- that system is attenuated- because the drugs affect our gut bacteria- and VRE (which may or may not have been present in our guts already) are free to run rampant. Leaving us with an infection that is most resistant to treatment.
But, the murine norovirus seems to be able to turn on our intestinal defenses. Once injected (inoculated), gene coding for TLR7 (Toll-like Receptor 7), which is critical to antiviral and antibacterial immunity, is elevated. And, there is at least partial resistance to VRE overpopulation.
Unfortunately, not quite enough. Resiquimod (R848), a synthetic ligand that mimics single-strand RNA and binds to TLR7, was effective in reducing VRE levels in mice. It’s also possible IL22 (interleukin 22) may yield similar results.
But, as is true with antibiotics, there always is another side to the equation. There are harmful effects when we stimulate TLR7- and we don’t know what many of those long-term effects may be.
