title: Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.
abstract: The life span of intestinal epithelial cells (IECs) is short (3-5 days), and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen-free (SPF) mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs) as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs.
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Jung-Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Kotani
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Konno
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Jajar
authors.initials: J
authors.lastname: Setiawan
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Imada
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Usui
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hatano
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002725:Chloroform / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry* / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013559:Symbiosis
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D050796:STAT3 Transcription Factor; D002725:Chloroform; D019893:Ribosomal Protein S6 Kinases; D048049:Extracellular Signal-Regulated MAP Kinases