In the US, Clostridioides difficile (C. difficile) infection (CDI) is the eighth leading cause for hospital readmission and seventh for mortality among all gastrointestinal (GI) disorders [1]. C. difficile is an anaerobic, Gram-positive, spore-forming bacterium that is transmitted by oral ingestion of spores. Once intestinal microbiota is disrupted by antibiotic use, C. difficile spores can germinate and grow into vegetative cells, which in turn secrete toxins [2]. C. difficile toxins A (TcdA) and B (TcdB) are the main virulence factors involved in CDI [[3], [4], [5]].

In humans, CDI has been shown to promote long-term GI symptoms after resolution of infection including irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), functional diarrhea, dyspepsia and constipation [6]. IBS and constipation were the most common GI complications in patients post-CDI [6].

The enteric nervous system (ENS), which is formed by enteric glia and neuron, is composed of two major plexuses: submucosal (Meissner's) and myenteric (Auerbach's). The submucosal plexuses is situated on the submucosa layer closely to circular muscle layer, while the myenteric plexus is located between the circular and longitudinal muscle layers [7]. ENS plays a crucial role in regulating important GI functions such as permeability, secretion and intestinal motility [7]. Previously, we showed that CDI causes changes in the ENS, including loss of enteric neurons and reactive gliosis in the acute phase of the disease [3,4,8].

While there is evidence supporting changes in ENS components during the acute phase of CDI in preclinical models, there is limited data on how CDI could impact GI function after resolution of active disease. Here, we performed a retrospective study to investigate GI dysfunction post-CDI in humans and used a murine preclinical model of CDI to track GI dysfunction post-acute infection.