Treating C. difficile without antibiotics

Scanning electron micgrograph of individual C. difficile bacilli cultured from a stool sample of an infected individual.

Scanning electron micgrograph of individual C. difficile bacilli cultured from a stool sample of an infected individual.

I recently had the pleasure of hearing a talk by Professor Xinhua Chen from the Beth Israel Deaconess Medical Center about various ways to treat C. difficile infections without antibiotics.  As we know, antibiotics are often successful in treating C. diff infections. However, 30% of all treated infections result in a relapse, likely due to the fact that these antibiotics kill commensal  bacteria which are needed to keep C. diff populations low.  In addition, Dr. Chen discussed how other bacteria can act as a 'sink' for the C. diff. toxins, which, when they bind to other bacteria, do not harm humans.  Therefore Dr. Chen is investigating methods that can prevent acute infection to buy time for commensal bacteria to reestablish themselves in the host.

Host inflammatory response is often the danger in C. Diff infections, and his lab has shown two drugs that help mitigate this response.  The first is a molecule called vascular endothelial growth factor (VEGF) that prevents the toxins from entering the vasculature, which is a cause of inflammation.  The second is by increasing the amount of lipotechoic acid (LTA) in the gut.  LTA is a major component of gram-positive bacteria that can bind to the toxins, much like commensal bacteria can, to prevent infection.  

In addition, Dr. Chen discussed an experiment based on fecal microbiota transfers (FMT).  His group bought two groups of mice, one which had high gut microbiome diversity and one with low gut microbiome diversity.  The mice with high microbiome diversity survived C. Diff infections while those with low microbiome diversity were killed by C. Diff.  When these mice were co-housed their microbiome diversity converged to a diversity that was somewhere between the two.  These mice all died with C. Diff. infection.  Dr. Chen though, was able to isolate one bacteria from the mice with high microbiome diversity, that when given to the mice with low microbiome diversity prevented C. Diff. infection.  His studies are still underway.

On a final note, Dr. Chen was against FMTs.  He thought there was too much 'hype' surrounding them, and that clinicians 'need to be cautious'.  He also discussed the work of Seres Health that has made an oral microbiome drug for C. Diff that includes only spore forming bacteria.   Some of the work came from a PLoS ONE article authored by Chen, but most of what he discussed has yet to be published.


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