PMID- 36185030
OWN - NLM
STAT- MEDLINE
DCOM- 20221010
LR  - 20221114
IS  - 1879-2618 (Electronic)
IS  - 1388-1981 (Linking)
VI  - 1867
IP  - 12
DP  - 2022 Dec
TI  - Empagliflozin ameliorates type 2 diabetes mellitus-related diabetic nephropathy 
      via altering the gut microbiota.
PG  - 159234
LID - S1388-1981(22)00124-X [pii]
LID - 10.1016/j.bbalip.2022.159234 [doi]
AB  - BACKGROUND: The dysregulation of gut microbiota can be found in patients with 
      type 2 diabetes mellitus (T2DM)-related diabetic nephropathy (DN). Inhibitors of 
      sodium-glucose co-transporter 2 (SGLT2) were reported to affect gut microbiota. 
      This study aimed to identify whether empagliflozin (EMPA) attenuated DN via 
      regulating gut microbiota. MATERIALS AND METHODS: The high-fat diet (HFD) 
      combining streptozocin (STZ) injection was performed to induce DN in mice. The 
      therapeutic effects of EMPA were observed by staining of renal tissues and urine 
      albumin/creatinine ratio (UACR). Mouse feces were collected for 16S rRNA 
      sequencing. Fecal short-chain fatty acids (SCFAs) and fecal and serum 
      lipopolysaccharide (LPS) were determined. An antibiotic-ablated model was 
      established to confirm the role of the gut microbiota in the actions of EMPA. 
      RESULTS: EMPA reduced the elevation of blood glucose and UACR caused by HFD/STZ. 
      It inhibited the thickening of the colonic crypt and restored goblet cells and 
      the expressions of ZO-1 and Occludin. The 16S rRNA sequencing showed that the 
      diversity of gut microbiota was reduced after HFD/STZ treatment, while it was 
      restored after EMPA treatment. The LPS-producing bacteria, Oscillibacter, and the 
      SCFA-producing bacteria, Bateroid and Odoribacter, were changed after EMPA 
      administration. The therapeutic effects of EMPA on ABX-treated mice were reduced. 
      Meanwhile, the level of fecal SCFAs was decreased, while the levels of fecal and 
      serum LPS were elevated, in T2DM mice, and they were negated by the 
      administration of EMPA. CONCLUSION: EMPA ameliorates T2DM-related DN via altering 
      the gut microbiota, especially reducing LPS-producing bacteria and increasing 
      SCFA-producing bacteria.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Deng, Le
AU  - Deng L
AD  - Department of Nephrology, the Second Affiliated Hospital of Nanchang University, 
      Jiangxi 330006, China.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Nephrology, the Second Affiliated Hospital of Nanchang University, 
      Jiangxi 330006, China.
FAU - Xu, Gaosi
AU  - Xu G
AD  - Department of Nephrology, the Second Affiliated Hospital of Nanchang University, 
      Jiangxi 330006, China. Electronic address: sixugao0@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220919
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Biol Lipids
JT  - Biochimica et biophysica acta. Molecular and cell biology of lipids
JID - 101731727
RN  - 0 (Albumins)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Fatty Acids, Volatile)
RN  - 0 (Glucosides)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Occludin)
RN  - 0 (RNA, Ribosomal, 16S)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 5W494URQ81 (Streptozocin)
RN  - 9NEZ333N27 (Sodium)
RN  - AYI8EX34EU (Creatinine)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Albumins/pharmacology
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Bacteria
MH  - Benzhydryl Compounds
MH  - Blood Glucose
MH  - Creatinine/pharmacology
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - *Diabetic Nephropathies/drug therapy
MH  - Fatty Acids, Volatile
MH  - *Gastrointestinal Microbiome
MH  - Glucosides
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Occludin/pharmacology
MH  - RNA, Ribosomal, 16S/genetics
MH  - Sodium/pharmacology
MH  - Sodium-Glucose Transporter 2/pharmacology
MH  - Streptozocin/pharmacology
OTO - NOTNLM
OT  - 16S rRNA sequencing
OT  - Diabetic nephropathy
OT  - Empagliflozin
OT  - Gut microbiota
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/12 06:00
CRDT- 2022/10/03 04:06
PHST- 2022/05/19 00:00 [received]
PHST- 2022/08/22 00:00 [revised]
PHST- 2022/09/04 00:00 [accepted]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/10/03 04:06 [entrez]
AID - S1388-1981(22)00124-X [pii]
AID - 10.1016/j.bbalip.2022.159234 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Dec;1867(12):159234. doi: 
      10.1016/j.bbalip.2022.159234. Epub 2022 Sep 19.