Why Antibiotics Cause Diarrhea

A well-known and widely-experienced side effect of antibiotic use is diarrhea. Antibiotics disturb the uneasy bacterial truce that exists within the gut, promoting the growth and proliferation of pathogenic bacteria, like the colitis-causing Clostridium difficile and Salmonella, the villain in many a food poisoning and a normal resident of the human gut, albeit in relatively small, safe concentrations.

The mechanisms behind gut flora disturbances are poorly understood. We can see their effects well enough, but gut microbial interactions are murky, highly-complicated territory. Understanding them better will go a long way toward generally doing antibiotics better and with more care. And, needless to say, given the slow-moving antibiotic doomsday approaching, this understanding is sorely needed.

To that end, molecular biologist Franziska Faber and colleagues at the University of California at Davis have discovered a critical if not exactly heartening piece in the gut puzzle. In a paper published Wednesday in Nature, they describe a mechanism by which the antibiotic streptomycin, a very old drug commonly used to treat tuberculosis, promotes the generation of sugars in the gut, which in turn feed Salmonella (Salmonella typhimurium). This bonus food source can be enough to tip the balance in favor of the harmful bacteria, leading to a bonus bacterial infection.

"Antibiotic-mediated disruption of the microbial food web can give rise to microbiota-liberated sugars in the gut that promote the growth of S. Typhimurium and C. difficile," explains an accompanying Nature commentary by Stanford microbiologists Thibault Sana and Denise Monack. "Moreover, antibiotics also increase expression of a host enzyme called inducible nitric oxide synthase (iNOS), but the link between iNOS and enhanced S. Typhimurium growth in the gut had not been previously established."

What the current paper shows (using mouse models) is that iNOS-dependent oxidization of the sugars glucose and galactose leads to the generation of related varieties of sugars that can be metabolized by S. Typhimurium. Faber and co. were further able to characterize the genes expressed by S. Typhimurium in metabolizing these sugars, finding that they're "switched on" by the presence of hydrogen, a byproduct of fermentation in the gut. Similar genes were found in gut party crashers E. coli and K. oxytoca.

These are all members of the bacterial family Enterobacteriaceae, which has recently developed resistance to broad-spectrum antibiotics known as carbapenems.

Monack and Sana continue:

According to a report released last month from the Review on Antimicrobial Resistance, antibiotic resistance will claim 10 million lives annually by 2050, handily overtaking current annual deaths from cancer. We're not winning, clearly, and every new antibiotic complication makes winning seem less and less attainable. At the very least, new knowledge can help us not help the other side win.