Fluoroquinolones (FQs) are a class of antibiotics intended to be prescribed for life-threatening infections. However, they are often administered for less severe infections, which they are not meant to treat. In addition, studies suggest that FQs can lead to severe long-lasting complications described as Fluoroquinolone Associated Disability (FQAD). Some of these permanent issues affect the central nervous system, cardiac, and musculoskeletal systems among others. Gastrointestinal issues have also been considered a possible side effect due to how FQs may negatively modulate the vagus nerve, which plays a major role in digestion and regulation of satiety. Indeed, the inhibitory neurotransmitter GABA regulates the motor portion of the vagus nerve, and FQs act as a selective inhibitor of GABAA receptors. This blockade of GABAA receptors is believed to contribute to the GI issues that seem to arise after taking FQs.
To measure possible changes in digestion, Sprague Dawley rats were treated daily for 14 consecutive days with either 0.3ml of 0.9% saline (CTL n=6) or 20mg/kg of ciprofloxacin (CPX) via oral gavage. On experiment day (day 14 or 28; n=6 for both), rats were administered phenol red dye, sacrificed, and the stomach, proximal, middle, and distal small intestine were harvested to measure dye recovery via spectrophotometry as a measure of gastrointestinal transit. Results showed that both male and female rats in the 28 day group had significantly less dye recovered from their stomach compared to the 14 day and CTL group, with female rats being disproportionately affected compared to males (Plt;0.05). This data provides strong evidence that FQs lead to permanent acceleration in digestive patterns. Further experiments will analyze how the phenotype of enteric motor neurons, as well as the phenotype of neurons within the Dorsal Motor Nucleus of the vagus in the medulla oblongata, is affected by this drug. This will contribute to determining the mechanism underlying the observed digestion change in rats treated with ciprofloxacin.
This study received support from the Biology Department at Bucknell University