Aloin, a component of the aloe vera plant leaf, induces pathological changes and modulates the composition of microbiota in the large intestines of F344/N Male Rats

In a previous study, the oral administration of an Aloe vera whole leaf extract induced dose-related mucosal and goblet cell hyperplasia in the rat colon after 13 weeks and colon cancer after 2 years. The primary goal of this study was to determine whether or not the administration of aloin, a component of the Aloe vera plant leaf, would replicate the pathophysiological effects that were observed in rats in the previous study with an Aloe vera whole leaf extract. Groups of 10 male F344/N rats were administered aloin at 0, 6.95, 13.9, 27.8, 55.7, 111, 223, and 446 mg/kg drinking water for 13 weeks. At the end of study, rat feces were collected, and the composition of fecal bacteria was investigated by next generation sequencing of the PCRamplified V3/V4 region of the 16S rRNA gene. At necropsy, blood was collected by cardiac puncture and organs and sections of the large intestine were collected for histopathology. Aloin induced dose-related increased incidences and severities of mucosal and goblet cell hyperplasia that extended from the cecum to the rectum, with increased incidences and severities detected at aloin doses≥55.7 mg/kg drinking water. Analysis of the 16S rRNA metagenomics sequencing data revealed marked shifts in the structure of the gut microbiota in aloin-treated rats at each taxonomic rank. This study highlights the similarities in effects observed for aloin and the Aloe vera whole leaf extract, and points to a potential mechanism of action to explain the observed pathological changes via modulation of the gut microbiota composition.