Shuhei Takauji1,2, Hiroaki Konishi3, Mikihiro Fujiya4,5, Nobuhiro Ueno2, Hiroki Tanaka6, Hiroki Sato2, Shotaro Isozaki2, Shin Kashima2, Kentaro Moriichi2, Yusuke Mizukami7, Toshikatsu Okumura8. 1. Department of Emergency Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan. 2. Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan. 3. Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan. 4. Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan. fjym@asahikawa-med.ac.jp. 5. Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan. fjym@asahikawa-med.ac.jp. 6. Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan. 7. Cancer Genetics, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan. 8. Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1, Midorigaoka Higashi, Asahikawa, 078-8510, Japan.
Abstract
BACKGROUND: We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. AIMS: We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. METHODS: Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. RESULTS: The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. CONCLUSIONS: Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.
BACKGROUND: We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. AIMS: We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. METHODS:Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. RESULTS: The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. CONCLUSIONS:Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.
Authors: Tommaso Schepis; Sara S De Lucia; Enrico C Nista; Vittoria Manilla; Giulia Pignataro; Veronica Ojetti; Andrea Piccioni; Antonio Gasbarrini; Francesco Franceschi; Marcello Candelli Journal: J Clin Med Date: 2021-12-17 Impact factor: 4.241