Effects of antibiotics on colonic neurons of the myenteric plexus in wild Peromyscus mice

Abstract

A community of trillions of commensal bacteria inhabit the gastrointestinal tract, collectively known as the intestinal microbiota. The gut microbes are essential for the development and functioning of the enteric nervous system. Approximately two-thirds of the cell bodies of all enteric neurons are gathered in the myenteric plexus, an intricate network of neurons and glial cells that primarily regulate gut neuromuscular activity. Studies in laboratory mice have observed that antibiotic treatment leads to a reduction in microbial abundance and diversity within the intestine, and these findings are correlated with enteric nervous system structural abnormalities. Specifically, antibiotic-treated mice have an abnormal myenteric plexus, which is characterized by a reduction in myenteric neuron numbers and ganglia area. However, it is unknown whether these effects occur in wild Peromyscus mice that are exposed to a natural bacterial flora. The goal of this study was to evaluate the effects of antibiotic exposure on the colonic neurons of the myenteric plexus in wild Peromyscus mice. Thirty-two wild-caught adult male Peromyscus mice were divided into control and antibiotic-treated groups. Whole mount preparations of longitudinal muscle with adherent myenteric plexus were prepared and alterations in colonic neuron and ganglia numbers were assessed by immunohistochemistry analysis. Antibiotic-treatment reduced the total number of colonic enteric neurons/mm2 and the total number of ganglia per myenteric plexus. Our results suggest that antibiotic-induced microbial dysbiosis affects the colonic neurons and ganglia of wild Peromyscus mice similarly to laboratory mice. We showed that the antibiotic-driven changes in neuronal density and ganglia arrangement are inducible in wild Peromyscus species that are exposed to real world bacteria.