Antibiotics benefit pathogen growth by disrupting oxygen levels, fiber processing in the gut

Antibiotics benefit pathogen growth by disrupting oxygen levels, fiber processing in the gut

Antibiotics are essential for fighting bacterial infection, but, paradoxically, they can also make the body more prone to infection and diarrhea.

Exactly how the resident "good" microbes in the gut protect against pathogens, such asSalmonella, and how antibiotic treatments foster growth of disease-causing microbes have been poorly understood.

But research in a mouse model by the researchers from UC Davis Health System, has identified the chain of events that occur within the gut lumen after antibiotic treatment that allow "bad" bugs to flourish.

The process begins with antibiotics depleting "good" bacteria in the gut, including those that breakdown fiber from vegetables to create butyrate, an essential organic acid that cells lining the large intestine need as an energy source to absorb water. The reduced ability to metabolize fiber prevents these cells from consuming oxygen, increasing oxygen levels in the gut lumen that favor the growth of Salmonella.

"Unlike Clostridia and other beneficial microbes in the gut, which grow anaerobically, or in the complete absence of oxygen, Salmonella flourished in the newly created oxygen-rich micro environment after antibiotic treatment," author said. "In essence, antibiotics enabled pathogens in the gut to breathe."

Clostridia depletion and aerobic Salmonella expansion were also observed in the absence of streptomycin treatment in genetically resistant mice but proceeded with slower kinetics and required the presence of functional Salmonella type III secretion systems. The Salmonella cytochrome bd-II oxidase synergized with nitrate reductases to drive luminal expansion, and both were required for fecal-oral transmission.

Other research has linked low levels of butyrate-producing microbes with inflammatory bowel disease, but additional research is needed to determine if these findings are limited to butyrate and growth of Salmonella or if similar mechanisms underlie interactions that influence human health.