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1
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Ren M, Xia Y, Pan H, Zhou X, Yu M, Ji F. Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways. Hepatol Commun 2025; 9:e0615. [PMID: 39813598 PMCID: PMC11737483 DOI: 10.1097/hc9.0000000000000615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 10/16/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD. METHODS Rats with MASLD were randomly assigned to undergo DJB or sham surgery. Rats were orally administered a broad-spectrum antibiotic cocktail (Abx) or underwent fecal microbiota transplantation to assess the role of gut microbiota in DJB-induced improvement of MASLD. Gut microbiota were profiled by 16S rRNA gene sequencing and metagenomic sequencing, and bile acids (BAs) were analyzed by BA-targeted metabolomics. RESULTS DJB alleviated hepatic steatosis and insulin resistance in rats with diet-induced MASLD. Abx depletion of bacteria abrogated the ameliorating effects of DJB on MASLD. Fecal microbiota transplantation from rats that underwent DJB improved MASLD in high-fat diet-fed recipients by reshaping the gut microbiota, especially by significantly reducing the abundance of Clostridium. This, in turn, suppressed secondary BA biosynthesis and activated the hepatic BA receptor, farnesoid X receptor. Inhibition of farnesoid X receptor attenuated the ameliorative effects of post-DJB microbiota on MASLD. CONCLUSIONS DJB ameliorates MASLD by regulating gut microbiota and BA metabolism through hepatic farnesoid X receptor pathways.
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Affiliation(s)
- Mengting Ren
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Gastroenterology, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yi Xia
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Hanghai Pan
- Department of Gastroenterology, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xinxin Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Mosang Yu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Feng Ji
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Wang L, Li S, Jiang T. Effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy on gut microbiota and glucose metabolism in rats with type 2 diabetes. Front Microbiol 2024; 15:1357749. [PMID: 38863754 PMCID: PMC11165999 DOI: 10.3389/fmicb.2024.1357749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 05/07/2024] [Indexed: 06/13/2024] Open
Abstract
Background Bariatric and metabolic surgery often leads to significant changes in gut microbiota composition, indicating that changes in gut microbiota after bariatric and metabolic surgery might play a role in ameliorating type 2 diabetes (T2D). However, the effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) on gut microbiota in T2D remain unclear. Objectives To investigate the effects of SADI-S on gut microbiota and glucose metabolism in T2D rats. Methods Nineteen T2D rats were randomly divided into the SADI-S group (n = 10) and the sham operation with pair-feeding group (sham-PF, n = 9). Fecal samples were collected to analyze the gut microbiota composition with 16S ribosomal DNA gene sequencing. The fasting blood glucose and glycated hemoglobin were measured to evaluate the effects of SADI-S on glucose metabolism. Results The Chao and ACE index results indicated the richness of the gut microbial community. The ACE and Chao index values were significantly lower in the SADI-S group than in the sham-PF group, indicating that indicating that species richness was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). Shannon and Simpson indices were used to estimate the species diversity of the gut microbiota. Compared with the sham-PF group, the SADI-S group showed significantly lower Shannon index and higher Simpson index values, indicating that the species diversity was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). At the genus level, SADI-S significantly changed the abundances of 33 bacteria, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). SADI-S significantly decreased the fasting blood glucose and glycated hemoglobin levels. The blood glucose level of rats was positively correlated with the relative abundances of 12 bacteria, including Bacteroides, and negatively correlated with the relative abundances of seven bacteria, including Bifidobacterium. Conclusion SADI-S significantly altered the gut microbiota composition of T2D rats, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). The blood glucose level of rats was positively correlated with the abundances of 12 bacteria, including Bacteroides, but negatively correlated with the relative abundance of 7 bacteria, including Bifidobacterium. These alternations in gut microbiota may be the mechanism through which SADI-S improved T2D. More studies should be performed in the future to validate these effects.
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Affiliation(s)
- Lun Wang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shixing Li
- Department of Bariatric and Metabolic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Tao Jiang
- Department of Bariatric and Metabolic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
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3
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Guo H, Ding Q, Huang Y, Guo Z, Ding F, Zhang H, Zheng Z, Zhang X, Weng S. Multi-omics Analysis Reveals the Crucial Mediators of DJB in the Treatment of Type 2 Diabetes. Obes Surg 2023:10.1007/s11695-023-06551-0. [PMID: 37052783 DOI: 10.1007/s11695-023-06551-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 03/01/2023] [Accepted: 03/09/2023] [Indexed: 04/14/2023]
Abstract
PURPOSE Duodenal-jejunal bypass (DJB) has a definite hypoglycemic effect; however, the intrinsic mechanisms remain unclear. The purpose of this study was to determine whether DJB may cause changes in the gut microbiota and metabolite of portal venous blood and to explore the effects of DJB on blood glucose metabolism. METHODS T2DM was induced in rats with a high-fat diet and a low dose of streptozotocin, which were randomly divided into two groups: Sham operation and DJB. RESULTS DJB significantly improved several diabetic parameters. 16S rRNA analyses showed that the compositions of the gut microbiota were significantly different between the two groups. The results of metabolomics showed that DJB could significantly regulate the metabolites, among which diaminopimelic acid and isovaleric acid had a significant down-regulation in the DJB group. Transcriptomic analysis showed that DJB can regulate the expression of hepatic genes related to abnormal glucose metabolism, such as Ltc4s, Alox15, Ggt1, Gpat3, and Cyp2c24. Correlation analyses showed that diaminopimelic acid was positively associated with Allobaculum, Serratia, and Turicibacter. There was a significant correlation between diaminopimelic acid and Gpat3, and its Spearman correlation coefficient was the highest among metabolite-DEG pairs (ρ=0.97). DISCUSSIONS These results suggest an important cue of the relation between the diaminopimelic acid, Gpat3, and gut microbiome in the mechanism by which DJB can improve glucose metabolism.
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Affiliation(s)
- Hailing Guo
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Qingzhu Ding
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Yue Huang
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Zhenyun Guo
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Fadian Ding
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Han Zhang
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Zhou Zheng
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
| | - Xiang Zhang
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China
- National Regional Medical Center, Binhai Campus of the first Affiliated Hospital, Fujian Medical University, Fuzhou, 350200, Fujian, China
| | - Shangeng Weng
- Department of Hepatopancreatobiliary Surgery, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
- Fujian Abdominal Surgery Research Institute, The first Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
- National Regional Medical Center, Binhai Campus of the first Affiliated Hospital, Fujian Medical University, Fuzhou, 350200, Fujian, China.
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4
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Zhan Y, Wen Y, Du LJ, Wang XX, Tang SY, Kong PF, Huang WG, Tang XG. Effects of Maren Pills on the Intestinal Microflora and Short-Chain Fatty Acid Profile in Drug-Induced Slow Transit Constipation Model Rats. Front Pharmacol 2022; 13:804723. [PMID: 35496291 PMCID: PMC9039019 DOI: 10.3389/fphar.2022.804723] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Slow transit constipation (STC) is becoming a common and frequently occurring disease in today’s society, and it is necessary to explore the safe and effective treatment of STC. Method: Our study aimed to investigate whether the laxative effect of Maren pills (MRW) is associated with the regulation of intestinal microflora and intestinal metabolism in the colon. Loperamide hydrochloride-induced STC rats received MRW intragastrically for two consecutive weeks to evaluate the laxative effect of MRW involving the regulation of intestinal microflora, intestinal metabolism, and 5-HT signaling pathway. Intestinal microflora was detected by 16s rDNA sequencing, intestinal metabolism of short-chain fatty acids (SCFAs) was detected by HPLC, and the 5-HT signaling pathway was detected by WB, ELISA, immunofluorescence, and immunohistochemical analysis. Results: Our results revealed that the treatments with MRW increased not only the body weight, 24-h fecal number, 24-h wet fecal weight, 24-h dry fecal weight, fecal water content, and the intestinal propulsion rate but also the colonic goblet cell number, colonic Muc-2 protein expression, and colonic mucus layer thickness in the STC model rats. Moreover, MRW activated the 5-HT pathway by increasing the levels of 5-HT, 5-HIAA, 5-HT4R, CFTR, cAMP, and PKA in the colon tissue of STC rats. The 16S rDNA sequencing results showed that MRW improved the colonic microflora structure in colonic contents of STC rats, mainly by increasing Lactobacillus and decreasing Prevotella. Finally, we found that MRW regulated the SCFA metabolism in the colonic contents of the STC rats, mainly by increasing the contents of acetic acid, propionic acid, and butyric acid; the relative abundance of Lactobacillus was positively correlated with either contents of acetic acid, propionic acid, and butyric acid, and the relative abundance of Clostridium was negatively correlated. Conclusion: Our study further showed that MRW could improve constipation in STC rats, and the mechanism may be by regulating the intestinal microflora structure and improving the metabolism of SCFAs.
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Affiliation(s)
- Yu Zhan
- Department of Anorectal, Affiliated Hospital of Integrative Chinese Medicine and Western Medicine of Chengdu University of TCM, Chengdu, China
- Department of Anorectal, Chengdu First People's Hospital, Chengdu, China
| | - Yong Wen
- Department of Anorectal, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Traditional Chinese Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Li-Juan Du
- Department of Anorectal, The Third People's Hospital of Chengdu, Chengdu, China
| | - Xiao-Xiang Wang
- Department of Digestive medicine, Chengdu First People's Hospital, Chengdu, China
| | - Shi-Yu Tang
- Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Peng-Fei Kong
- Department of Anorectal Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Wei-Guo Huang
- Department of Anorectal, Chengdu First People's Hospital, Chengdu, China
| | - Xue-Gui Tang
- Department of Anorectal Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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5
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Tu Y, Bao Y, Zhang P. Metabolic surgery in China: present and future. J Mol Cell Biol 2021; 13:mjab039. [PMID: 34240190 PMCID: PMC8697345 DOI: 10.1093/jmcb/mjab039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 05/27/2021] [Accepted: 06/14/2021] [Indexed: 11/24/2022] Open
Abstract
Obesity and its related complications comprise a serious public health problem worldwide, and obesity is increasing in China. Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications. The pathogenesis of obesity is complex and not yet fully understood. Here, we review the current efficacy and safety of metabolic surgery, as well as recent progress in mechanistic studies and surgical procedures in China. The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.
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Affiliation(s)
- Yinfang Tu
- Department of Endocrinology and Metabolism, Shanghai
Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes
Institute, Shanghai Clinical Center of Diabetes, Shanghai Key Laboratory of
Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic
Disease, Shanghai 200233, China
| | - Yuqian Bao
- Department of Endocrinology and Metabolism, Shanghai
Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes
Institute, Shanghai Clinical Center of Diabetes, Shanghai Key Laboratory of
Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic
Disease, Shanghai 200233, China
- Department of Endocrinology and Metabolism, Jinshan
District Central Hospital of Shanghai Sixth People's
Hospital, Shanghai 201599, China
| | - Pin Zhang
- Department of Bariatric and Metabolic Surgery,
Shanghai Jiao Tong University Affiliated Sixth People’s
Hospital, Shanghai 200233, China
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6
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Gut Microbiota in Patients with Morbid Obesity Before and After Bariatric Surgery: a Ten-Year Review Study (2009-2019). Obes Surg 2020; 31:317-326. [PMID: 33130944 DOI: 10.1007/s11695-020-05074-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 10/14/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023]
Abstract
The changes in the composition and function of gut microbiota affect the metabolic functions (which are mediated by microbial effects) in patients with obesity, resulting in significant physiological regulation in these patients. Most of the studies emphasize that the Western-style diet (high fat and low vegetable consumption) leads to significant changes in the intestinal microbiome in individuals with metabolic syndrome. A deeper understanding of the profiles of gut microbes will contribute to the development of new therapeutic strategies for the management of metabolic syndrome and other metabolic diseases and related disorders. The aim of this review is to evaluate recent experimental evidence outlining the alterations of gut microbiota composition and function in recovery from bariatric surgical operations with an emphasis on sleeve gastrectomy and gastric bypass.
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7
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Role of Gut Microbiome and Microbial Metabolites in Alleviating Insulin Resistance After Bariatric Surgery. Obes Surg 2020; 31:327-336. [PMID: 32974816 DOI: 10.1007/s11695-020-04974-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 09/05/2020] [Accepted: 09/11/2020] [Indexed: 02/07/2023]
Abstract
Insulin resistance (IR) is the most common pathophysiological change in patients with type 2 diabetes mellitus (T2DM). Several recent studies have suggested that the gut microbiome and microbial metabolites are involved in the pathogenesis of IR. Bariatric surgery, as an effective treatment for T2DM, can markedly alleviate IR through mechanisms that have not been elucidated. In this review, we summarize the current evidence on the changes in the gut microbiome and microbial metabolites (including lipopolysaccharide, short-chain fatty acids, branched-chain amino acids, aromatic amino acids, bile acids, methylamines, and indole derivatives) after bariatric surgery. Additionally, we discuss the mechanisms that correlate the changes in microbial metabolites with the postoperative alleviation of IR. Furthermore, we discuss the prospect of bariatric surgery as a treatment for T2DM.
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8
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Yu X, Wu Z, Song Z, Zhang H, Zhan J, Yu H, Huang H, Yang B, Xie L, Dai X, Zhao W, Yu J, Wu L. Single-Anastomosis Duodenal Jejunal Bypass Improve Glucose Metabolism by Regulating Gut Microbiota and Short-Chain Fatty Acids in Goto-Kakisaki Rats. Front Microbiol 2020; 11:273. [PMID: 32153548 PMCID: PMC7047167 DOI: 10.3389/fmicb.2020.00273] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 02/06/2020] [Indexed: 12/13/2022] Open
Abstract
In recent years, bariatric surgery has emerged as a promising treatment for type 2 diabetes. Bariatric surgery is known to cause alterations in the relative abundance and composition of gut microbiota, which may lead to alterations in the levels of Short-Chain Fatty Acids (SCFAs) that are produced during fermentation by gut microbes. However, little is known about the mechanism of improved glucose metabolism mediated by gut microbiota following bariatric surgery. The aim of our study was to explore whether changes in gut microbiota and in fecal SCFA could be detected following single-anastomosis duodenal jejunal bypass (DJB-sa) surgery, a type of bariatric surgery, and whether these alterations might be related to the improvement of glucose metabolism. To this end, we performed DJB-sa or SHAM surgery on Goto-Kakisaki (GK) rats. We then compared the glucose metabolism as well as changes in gut microbiota and SCFAs levels between both groups. Our results showed that DJB-sa surgery was associated with a significant decrease in fasting blood glucose (FBG), intraperitoneal glucose tolerance test (IPGTT), and fasting serum insulin (FSI). And, DJB-sa led to a change in the composition of gut microbiota including an increase in the relative abundance of SCFA-producing bacteria (Bifidobacterium and Subdoligranulum). Moreover, the levels of six SCFAs in feces, as well as the intestinal expression of SCFA receptors including G-protein-coupled receptor 41 (GPR41), G-protein-coupled receptor 43 (GPR43), and G-protein-coupled receptor 109A (GPR109A), and the expression of Glucagon-like peptide-1 (GLP-1) displayed a significant increase following DJB-sa compared with the Sham group. Thus, the gut microbiota may contribute to the improvement of glucose metabolism in type 2 diabetes following DJB-sa. In conclusion, our study shows that DJB-sa improves glucose metabolism by modulating gut microbiota and by increasing short-chain fatty acid production.
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Affiliation(s)
- Xiang Yu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Zhuangwei Wu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Zhigao Song
- Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hongbin Zhang
- Department of Medical Experimental, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China
| | - Junfang Zhan
- Health Management Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Hao Yu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Hongyan Huang
- Department of Metabolic Surgery, UDM Medical Group, Guangzhou, China.,Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
| | - Baolin Yang
- Department of Metabolic Surgery, UDM Medical Group, Guangzhou, China.,Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
| | - Lang Xie
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaojiang Dai
- Department of Metabolic Surgery, UDM Medical Group, Guangzhou, China.,Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
| | - Weiguo Zhao
- Department of Metabolic Surgery, UDM Medical Group, Guangzhou, China.,Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
| | - Jinlong Yu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Liangping Wu
- Department of Metabolic Surgery, UDM Medical Group, Guangzhou, China.,Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China
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9
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Adeshirlarijaney A, Zou J, Tran HQ, Chassaing B, Gewirtz AT. Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota. Am J Physiol Endocrinol Metab 2019; 317:E1121-E1130. [PMID: 31573841 PMCID: PMC6962505 DOI: 10.1152/ajpendo.00245.2019] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 09/10/2019] [Accepted: 09/25/2019] [Indexed: 12/29/2022]
Abstract
Metformin beneficially impacts several aspects of metabolic syndrome including dysglycemia, obesity, and liver dysfunction, thus making it a widely used frontline treatment for early-stage type 2 diabetes, which is associated with these disorders. Several mechanisms of action for metformin have been proposed, including that it acts as an anti-inflammatory agent, possibly as a result of its impact on intestinal microbiota. In accord with this possibility, we observed herein that, in mice with diet-induced metabolic syndrome, metformin impacts the gut microbiota by preventing its encroachment upon the host, a feature of metabolic syndrome in mice and humans. However, the ability of metformin to beneficially impact metabolic syndrome in mice was not markedly altered by reduction or elimination of gut microbiota, achieved by the use of antibiotics or germfree mice. Although reducing or eliminating microbiota by itself suppressed diet-induced dysglycemia, other features of metabolic syndrome including obesity, hepatic steatosis, and low-grade inflammation remained suppressed by metformin in the presence or absence of gut microbiota. These results support a role for anti-inflammatory activity of metformin, irrespective of gut microbiota, in driving some of the beneficial impacts of this drug on metabolic syndrome.
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Affiliation(s)
| | - Jun Zou
- Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia
| | - Hao Q Tran
- Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia
| | - Benoit Chassaing
- Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia
- Neuroscience Institute, Georgia State University, Atlanta, Georgia
| | - Andrew T Gewirtz
- Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia
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10
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Souteiro P, Belo S, Magalhães D, Pedro J, Neves JS, Oliveira SC, Freitas P, Varela A, Carvalho D. Long-term diabetes outcomes after bariatric surgery-managing medication withdrawl. Int J Obes (Lond) 2019; 43:2217-2224. [PMID: 30696933 DOI: 10.1038/s41366-019-0320-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 12/20/2018] [Accepted: 01/04/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND/OBJECTIVES Bariatric surgery leads to type 2 diabetes mellitus (T2DM) remission, but recurrence can ensue afterwards. However, literature provides heterogenous remission/recurrence criteria and there is no consensus on long-term T2DM management after surgery. We aim to assess T2DM remission/recurrence rates using standardized criteria and to identify relapse predictors. We also intend to analyze the management of residual T2DM and the impact of maintaining/withdrawing metformin in avoiding future relapse. SUBJECTS/METHODS We investigated a cohort of 110 obese patients with T2DM who underwent bariatric surgery and were followed for 5 years (Y0-Y5). Patients who ever attained remission were accounted for cumulate remission, while prevalent remission was considered for individuals who were on remission in a specific visit. RESULTS A complete prevalent remission of 47.3% was reached at Y1 and it remained stable till Y5 (46.4-48.2%). Complete cumulative rate was of 57.3% at Y5. Five-year T2DM recurrence rate was 15.9% and it was associated with higher pre-operative HbA1c levels (β = 1.06; p < 0.05) and a milder excess body weight loss (EBWL) (β = 0.49; p < 0.05). Glucose-lowering agents were fully stopped in 51.4% of the patients till Y1 and in 16.2% of them afterwards. Medication withdrawal was mainly attempted in patients with a lower baseline HbA1c (β = 0.54; p < 0.01) and higher first-year EBWL (β = 1.04; p < 0.01). Patients that kept metformin after reaching a HbA1c in the complete remission range (<6.0%) did not have greater odds of avoiding relapse in the next visit (OR = 0.33; p = 0.08). CONCLUSIONS Baseline HbA1c and EBWL were the main variables driving both T2DM relapse after bariatric surgery and the attempt to withdrawal anti-diabetic medication. In our population keeping metformin once an HbA1c < 6.0% is achieved did not seem to diminish relapse but further studies on this matter are needed.
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Affiliation(s)
- Pedro Souteiro
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal. .,Faculty of Medicine of University of Porto, Porto, Portugal. .,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
| | - Sandra Belo
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Multidisciplinary Group for Surgical Management of Obesity, Centro Hospitalar São João, Porto, Portugal
| | - Daniela Magalhães
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Faculty of Medicine of University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
| | - Jorge Pedro
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Faculty of Medicine of University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
| | - João Sérgio Neves
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Faculty of Medicine of University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
| | - Sofia Castro Oliveira
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Faculty of Medicine of University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
| | - Paula Freitas
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Faculty of Medicine of University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.,Multidisciplinary Group for Surgical Management of Obesity, Centro Hospitalar São João, Porto, Portugal
| | - Ana Varela
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Faculty of Medicine of University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.,Multidisciplinary Group for Surgical Management of Obesity, Centro Hospitalar São João, Porto, Portugal
| | - Davide Carvalho
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal.,Faculty of Medicine of University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
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Akalestou E, Genser L, Villa F, Christakis I, Chokshi S, Williams R, Rubino F. Establishing a successful rat model of duodenal- jejunal bypass: A detailed guide. Lab Anim 2018; 53:362-371. [PMID: 30227760 DOI: 10.1177/0023677218797370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Gastric bypass surgery, an operation that restricts the stomach and bypasses the duodenum and part of the jejunum, results in major improvement or remission of type 2 diabetes. Duodenual-jejunal bypass was developed by one of the authors (FR) as an experimental, stomach-sparing variant of gastric bypass surgery to investigate weight-independent mechanisms of surgical control of diabetes. Duodenual-jejunal bypass has been shown to improve various aspects of glucose homeostasis in rodents and in humans, thus providing an experimental model for investigating mechanisms of action of surgery and elusive aspects of gastrointestinal physiology. Performing duodenual-jejunal bypass in rodents, however, is associated with a steep learning curve. Here we report our experience with duodenual-jejunal bypass and provide practical tips for successful surgery in rats. Duodenual-jejunal bypass was performed on 50 lean rats as part of a study aimed at investigating the effect of the procedure on the physiologic mechanisms of glucose homeostasis. During the study, we have progressively refined details of anatomic exposure, technical aspects of duodeno-jejunostomy and peri-operative care. We analysed the role of such refinements in improving operative time and post-operative mortality. We found that refinement of exposure methods of the gastro-duodenal junction aimed at minimizing tension on small visceral vasculature, technical aspects of duodeno-jejunal anastomosis and peri-operative management played a major role in improving the survival rate and operative time. Overall, an experimental model of duodenual-jejunal bypass was successfully reproduced. Based on this experience, we describe here what we believe are the most important technical tips to reduce the learning curve for the procedure.
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Affiliation(s)
- Elina Akalestou
- 1 Division of Diabetes and Nutritional Sciences, King's College London, UK.,2 Institute of Hepatology London, Foundation for Liver Research, London, UK.,3 Division of Transplantation, Immunology and Mucosal Biology, Faculty of Life Sciences and Medicine, King's College London, UK
| | - Laurent Genser
- 1 Division of Diabetes and Nutritional Sciences, King's College London, UK.,4 Department of Surgery, King's College Hospital NHS Foundation Trust, London, UK
| | - Francesco Villa
- 1 Division of Diabetes and Nutritional Sciences, King's College London, UK.,4 Department of Surgery, King's College Hospital NHS Foundation Trust, London, UK
| | - Ioannis Christakis
- 4 Department of Surgery, King's College Hospital NHS Foundation Trust, London, UK
| | - Shilpa Chokshi
- 2 Institute of Hepatology London, Foundation for Liver Research, London, UK.,3 Division of Transplantation, Immunology and Mucosal Biology, Faculty of Life Sciences and Medicine, King's College London, UK
| | - Roger Williams
- 2 Institute of Hepatology London, Foundation for Liver Research, London, UK.,3 Division of Transplantation, Immunology and Mucosal Biology, Faculty of Life Sciences and Medicine, King's College London, UK
| | - Francesco Rubino
- 1 Division of Diabetes and Nutritional Sciences, King's College London, UK.,4 Department of Surgery, King's College Hospital NHS Foundation Trust, London, UK
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Abstract
PURPOSE OF REVIEW Metabolic surgery is recommended for the treatment of type 2 diabetes for its potent ability to improve glycemic control. However, the mechanisms underlying the beneficial effects of metabolic surgery are still under investigation. We provide an updated review of recent studies into the molecular underpinnings of metabolic surgery, focusing in on what is known about the role of gut microbiota. Over the last 7 years several reports have been published on the topic, however the field is expanding rapidly. RECENT FINDINGS Studies have now linked the regulation of glucose and lipid metabolism, neuronal and intestinal adaptations, and hormonal and nutrient signaling pathways to gut microbiota. Given that the composition of gut microbiota is altered by metabolic surgery, investigating the potential mechanism and outcomes of this change are now a priority to the field. SUMMARY As evidence for a role for microbiota builds, we expect future patients may receive microbe-based therapeutics to improve surgical outcomes and perhaps one day preclude the need for surgical therapies all together. In this review and perspective, we evaluate the current state of the field and its future.
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Affiliation(s)
- Bailey C. E. Peck
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Randy J. Seeley
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
- Correspondence should be addressed to: Randy J. Seeley, Department of Surgery, University of Michigan, 2800 Plymouth Road, NCRC Building 26-343N, Ann Arbor, MI 48109, USA; Phone: +1 (734) 615-2880;
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Liu T, Zhong MW, Liu Y, Sun D, Wei M, Huang X, Cheng YG, Wu QZ, Wu D, Zhang XQ, Wang KX, Hu SY, Liu SZ. Diabetes recurrence after metabolic surgeries correlates with re-impaired insulin sensitivity rather than beta-cell function. World J Gastroenterol 2017; 23:3468-3479. [PMID: 28596682 PMCID: PMC5442082 DOI: 10.3748/wjg.v23.i19.3468] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 04/25/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB).
METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet (HFD) and streptozotocin (STZ). HFD was used to induce diabetes recurrence at 4 wk postoperatively. Body weight, oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), insulin signaling [IR, insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3-kinase and AKT in liver and skeletal muscle], oral glucose stimulated insulin secretion, beta-cell morphology (mass, apoptosis and insulin secretion), glucagon-like peptide (GLP)-1, PYY and ghrelin were compared among SG rats with common low-fat diet (SG-LFD), SG with HFD (SG-HFD), DJB rats with LFD (DJB-LFD), DJB with HFD (DJB-HFD) and sham-operation with LFD (Sham) at targeted postoperative times.
RESULTS SG and DJB resulted in significant improvement in glucose tolerance, lower HOMA-IR, up-regulated hepatic and muscular insulin signaling, higher levels of oral glucose-stimulated insulin secretion, bigger beta-cell mass, higher immunofluorescence intensity of insulin, fewer transferase-mediated dUTP-biotin 3’ nick end-labeling (TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group. The improvement in glucose tolerance was reversed at 12 wk postoperatively. Compared with the SG-LFD and DJB-LFD groups, the SG-HFD and DJB-HFD groups showed higher HOMA-IR, down-regulated hepatic and muscular insulin signaling, and more TUNEL-positive beta cells. No significant difference was detected between HFD and LFD groups for body weight, glucose-stimulated insulin secretion, beta-cell mass, immunofluorescence intensity of insulin, and postprandial GLP-1 and PYY levels. Fasting serum ghrelin decreased in SG groups, and there was no difference between HFD-SG and LFD-SG groups.
CONCLUSION HFD reverses the improvement in glucose homeostasis after SG and DJB. Diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.
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