PMID- 31503404
OWN - NLM
STAT- MEDLINE
DCOM- 20201019
LR  - 20210110
IS  - 1753-0407 (Electronic)
IS  - 1753-0393 (Print)
IS  - 1753-0407 (Linking)
VI  - 12
IP  - 3
DP  - 2020 Mar
TI  - Faecalibacterium prausnitzii-derived microbial anti-inflammatory molecule 
      regulates intestinal integrity in diabetes mellitus mice via modulating tight 
      junction protein expression.
PG  - 224-236
LID - 10.1111/1753-0407.12986 [doi]
AB  - BACKGROUND: Impaired intestinal barrier structure and function have been 
      validated as an important pathogenic process in type 2 diabetes mellitus (T2DM). 
      Gut dysbiosis is thought to be the critical factor in diabetic intestinal 
      pathogenesis. As the most abundant commensal bacteria, Faecalibacterium 
      prausnitzii (F. prausnitzii) play important roles in gut homeostasis. The 
      microbial anti-inflammatory molecule (MAM), an F. prausnitzii metabolite, has 
      anti-inflammatory potential in inflammatory bowel disease (IBD). Thus, we aimed 
      to explore the function and mechanism of MAM on the diabetic intestinal 
      epithelium. METHODS: 16S high-throughput sequencing was used to analyze the gut 
      microbiota of db/db mice (T2DM mouse model). We transfected a FLAG-tagged MAM 
      plasmid into human colonic cells to explore the protein-protein interactions and 
      observe cell monolayer permeability. For in vivo experiments, db/db mice were 
      supplemented with recombinant His-tagged MAM protein from E. coli BL21 (DE3). 
      RESULTS: The abundance of F. prausnitzii was downregulated in the gut microbiota 
      of db/db mice. Immunoprecipitation (IP) and mass spectroscopy (MS) analyses 
      revealed that MAM potentially interacts with proteins in the tight junction 
      pathway, including zona occludens 1 (ZO-1). FLAG-tagged MAM plasmid transfection 
      stabilized the cell permeability and increased ZO-1 expression in NCM460, Caco2, 
      and HT-29 cells. The db/db mice supplemented with recombinant His-tagged MAM 
      protein showed restored intestinal barrier function and elevated ZO-1 expression. 
      CONCLUSIONS: Our study shows that MAM from F. prausnitzii can restore the 
      intestinal barrier structure and function in DM conditions via the regulation of 
      the tight junction pathway and ZO-1 expression.
CI  - (c) 2019 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai 
      Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
FAU - Xu, Jihao
AU  - Xu J
AD  - Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, Guangdong, People's Republic of China.
FAU - Liang, Rongrong
AU  - Liang R
AD  - Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, Guangdong, People's Republic of China.
FAU - Zhang, Wang
AU  - Zhang W
AD  - Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, Guangdong, People's Republic of China.
AD  - Department of Gastroenterology, Guangdong Provincial Hospital of Chinese Medicine 
      (2nd Clinical Hospital of Guangzhou University of Chinese Medicine), Guangzhou 
      University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
FAU - Tian, Kuangyi
AU  - Tian K
AD  - Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, Guangdong, People's Republic of China.
FAU - Li, Jieyao
AU  - Li J
AD  - Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, Guangdong, People's Republic of China.
FAU - Chen, Xianming
AU  - Chen X
AD  - Department of Medical Microbiology and Immunology, Creighton University School of 
      Medicine, Omaha, Nebraska.
FAU - Yu, Tao
AU  - Yu T
AUID- ORCID: 0000-0003-4939-8956
AD  - Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, Guangdong, People's Republic of China.
FAU - Chen, Qikui
AU  - Chen Q
AD  - Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, Guangdong, People's Republic of China.
LA  - eng
GR  - 81370475/National Natural Science Foundation of China/
GR  - 2017A030313647/Natural Science Foundation of Guangdong Province/
PT  - Journal Article
DEP - 20191030
PL  - Australia
TA  - J Diabetes
JT  - Journal of diabetes
JID - 101504326
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Tight Junction Proteins)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*metabolism/pharmacology
MH  - Caco-2 Cells
MH  - Diabetes Mellitus, Type 2/genetics/*metabolism
MH  - Dysbiosis/genetics/physiopathology
MH  - Faecalibacterium prausnitzii/*metabolism
MH  - Gastrointestinal Microbiome/drug effects/genetics/physiology
MH  - Gene Expression/drug effects
MH  - HEK293 Cells
MH  - HT29 Cells
MH  - Humans
MH  - Inflammatory Bowel Diseases/genetics/metabolism
MH  - Intestinal Mucosa/drug effects/*metabolism
MH  - Mice
MH  - Permeability/drug effects
MH  - Tight Junction Proteins/genetics/*metabolism
MH  - Tight Junctions/drug effects/*metabolism
PMC - PMC7064962
OTO - NOTNLM
OT  - Faecalibacterium prausnitzii
OT  - diabetes mellitus
OT  - diabetic pathology
OT  - gut microbiota
OT  - intestinal barrier
OT  - 普拉梭菌
OT  - 糖尿病
OT  - 糖尿病病变
OT  - 肠道屏障
OT  - 肠道菌群
EDAT- 2019/09/11 06:00
MHDA- 2020/10/21 06:00
PMCR- 2020/03/11
CRDT- 2019/09/11 06:00
PHST- 2019/06/03 00:00 [received]
PHST- 2019/08/28 00:00 [revised]
PHST- 2019/09/06 00:00 [accepted]
PHST- 2019/09/11 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/09/11 06:00 [entrez]
PHST- 2020/03/11 00:00 [pmc-release]
AID - JDB12986 [pii]
AID - 10.1111/1753-0407.12986 [doi]
PST - ppublish
SO  - J Diabetes. 2020 Mar;12(3):224-236. doi: 10.1111/1753-0407.12986. Epub 2019 Oct 
      30.