title: Intestinal microbial dysbiosis and colonic epithelial cell hyperproliferation by dietary α-mangostin is independent of mouse strain.
abstract: Beverages and supplements prepared from mangosteen fruit are claimed to support gut health and immunity, despite the absence of supporting evidence from clinical trials. We recently reported that α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, altered the intestinal microbiome, promoted dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study was to determine whether induction of dysbiosis by dietary α-MG is limited to the C57BL/6J strain or represents a more generic response to chronic intake of the xanthone on the gut microbiota of mice. C3H, Balb/c, Nude FoxN1nu, and C57BL/6J mice, each demonstrating unique microbiomes, were fed standard diet or diet containing 0.1% α-MG for four weeks. Dietary α-MG significantly altered the cecal and colonic microbiota in all four strains of mice, promoting a reduction in generally assumed beneficial bacterial groups while increasing the abundance of pathogenic bacteria. Consumption of α-MG was associated with reduced abundance of Firmicutes and increased abundance of Proteobacteria. The abundance of Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae was reduced in α-MG-fed mice, while that of Enterobacteriaceae and Enterococcaceae was increased. Dietary α-MG also was associated with increased proliferation of colonic epithelial cells, infiltration of immune cells, infiltration of immune cells and increased fluid content in stool. These results suggest that ingestion of pharmacologic doses of xanthones in mangosteen-containing supplements may adversely alter the gut microbiota and should be used with caution.
authors.affiliation: Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Gutierrez-Orozco.1@osu.edu.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Gutierrez-Orozco
authors.affiliation: Food Innovation Center, The Ohio State University, Columbus, OH 43210, USA. Jennifer.Thomas-Ahner@osumc.edu.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Thomas-Ahner
authors.affiliation: Food Innovation Center, The Ohio State University, Columbus, OH 43210, USA. Galley.2@osu.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Galley
authors.affiliation: Food Innovation Center, The Ohio State University, Columbus, OH 43210, USA. Michael.Bailey@osumc.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bailey
authors.affiliation: Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Steven.Clinton@osumc.edu.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
authors.affiliation: Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. Gregory.Lesinski@osumc.edu.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Lesinski
authors.affiliation: Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA. failla.3@osu.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Failla
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000187:drug effects / Q000382:microbiology*; D019587:Dietary Supplements; D064806:Dysbiosis / Q000139:chemically induced*; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005638:Fruit / Q000737:chemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D064307:Microbiota / Q000187:drug effects*; D044004:Xanthones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein; D044004:Xanthones; C021053:mangostin