The Influence of Diet Change and Oral Metformin on Blood Glucose Regulation and the Fecal Microbiota of Healthy Horses

Simple Summary Horses are susceptible to a condition known as Equine Metabolic Syndrome (EMS), which is somewhat similar to metabolic syndrome and type II diabetes in people, and is characterized by elevated insulin levels and increased susceptibility to other adverse health outcomes. Common treatments, including change to an all-hay diet and a drug called metformin, may provide benefits through modulation of intestinal bacteria, collectively known as the gut microbiota. In the studies reported here, horses undergoing such a diet change, regardless of the presence of metformin, showed a significant expansion in their fecal microbiota of a specific, poorly characterized group of bacteria. Notably, this phylum is distantly related to the bacteria found to expand in the fecal microbiota of mice and humans following metformin administration, suggesting removal from pasture to reduce the caloric intake may exert effects on the equine microbiota similar to those seen in other host species treated with metformin. Abstract Common treatments for Equine Metabolic Syndrome (EMS) and associated conditions include removal from pasture and adoption of an all-hay diet. Pharmacological treatments for EMS include metformin, a biguanide antihyperglycemic agent also administered to people to help improve glucose tolerance and insulin sensitivity. Both treatments may work, at least partially, through the gut microbiota, yet little is known regarding these effects in the equine host. To determine the influence on the fecal microbiota of this diet change and administration of metformin, six healthy horses were removed from pasture and switched to an all-hay diet, with four of those horses also receiving oral metformin for seven days. Control horses (n = 24) remaining on pasture and receiving no metformin were sampled at the beginning and end of one week. All samples were subjected to 16S rRNA sequencing, and horses undergoing the diet change were subjected to an oral sugar test twice, one week apart. Characteristic changes in the microbiota following diet change included the significant expansion of the phylum Kiritimatiellaeota. As Kiritimatiellaeota are related to Verrucomicrobia, found to expand in the microbiota of mice and humans in response to metformin, this taxon may represent the cognate microbes in equine hosts.