Thursday, December 18, 2014

Fueling C. difficile growth

C. difficile is a spore-forming anaerobe, residing in the human gut. Usually it does not cause any pathology. However, antibiotic use (or over-use), or changes in gut motility can bring up the ugly side of this microbe. There are no vaccines or drugs available for the specific management of C. difficili infection. 

Curiously, in the past few years, several research studies indicated that C. difficile could be controlled by other gut microbes readily available in the healthy humans' feces.

If proven effective in humans, this will open a new chapter in medicine. Our physiology is heavily influenced by gut commensals and their role in human health and disease has just started to be unraveled.

In this respect, two new studies in journal Cell Host and Microbe provided additional clues about potential mechanisms of initiation of C. difficile disease. I will review both of them separately.

One study, led by Justin Sonnenburg at Stanford University of School of Medicine, has examined how fermentation end product, succinate, affect C. difficile growth pattern.

Initially, the authors observed that in germ-free mouse, C. difficile growth was accelerated in the presence of polysaccharide rich-diet and mouse gut flora commensal Bacteriodes Thetaiotaomicron, (Bt).

It is known Bt produces organic acid, succinate, as a fermentation end product. 

Using succinate-transporter mutant C. difficile, the authors confirmed that in vitro culture, WT C. difficile were able to utilize excess succinate for their growth enhancement.

In vivo experiments with succinate supplemented diet validated this observation.

Importantly, the authors showed that Bt-induced growth promotion was not observed with mutant C. difficile.  

To make their observation clinically relevant, the authors conducted the series of experiments with mice treated with antibiotics or gut hyper-motility (diarrhetic) drug.

As predicted, antibiotic treatment specifically increased succinate level.

Similarly, diarrhetic agent mimicked antibiotic's effect.

Finally, the authors showed that changes in gut motility fueled C. difficile growth.  

In summary, these results indicate that changes in gut flora or acceleration of gut motility could lead to specific increase in succinate level that is sensed and utilized by C. difficile for growth enhancement.

David Usharauli

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