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Dean YE, Mohamed MI, Shokri A, Nassar M, Omayer A, Shahid M, Sharif A, Soliman Z, Almadani Y, Yakout A, Guvem AE, Jaiswal U, Hamza A, Zein M, Elnemr MM, Shahabi S, Kermansaravi M, Yang W, Abdelbaki TN. Bariatric Surgery and Remission of Metabolic Syndrome: A Meta-analysis of Randomised Controlled Trials and Prospective Studies. Obes Surg 2025; 35:1337-1349. [PMID: 40000567 DOI: 10.1007/s11695-025-07750-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 12/24/2024] [Accepted: 02/10/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND Studies have discussed the efficacy of bariatric surgery (BS) in remission of individual components of metabolic syndrome (MS). We aimed to analyse the prevalence of MS following BS. METHODS On October 5, 2023, we conducted a literature search on PubMed, Scopus, Web of Science, and Cochrane. RevManv5.4 was used for the analysis. RESULTS MS patients who underwent BS had lower odds of MS within the first year post-BS (OR 0.14, 95%CI 0.12-0.17); patients who had a preoperative BMI < 50 showed a higher reduction in MS post-BS compared with patients who suffered from super obesity (OR 0.12 versus OR 0.17). Older patients (age > 42) had lower odds of MS post-BS compared with younger patients (OR 0.05 versus OR 0.17). There was not a difference in MS prevalence between 1 and 2 years postoperatively (OR 1.07, 95%CI 0.72-1.58). Asians reported the highest reduction in MS post-BS (OR 0.08). MS patients who received medical treatment had three times the odds of having MS compared with patients who underwent BS. Patients who had BS reported a decline in their anti-hypertensives and oral anti-diabetic drugs (OR 0.26, 95%CI 0.15-0.46, OR 0.11, 95%CI 0.07-0.16, respectively). There was not a significant difference in MS prevalence between patients who underwent RYGB and those who had SG (OR 2.16, 95%CI 0.74-6.26). CONCLUSIONS BS is superior to medical treatment in the remission of MS. Age, preoperative BMI, and country of origin affect the rates of MS remission. BS results in a sustainable resolution of MS across 1, 2, and 5 years post-surgery. A tailored approach is warranted to achieve the best outcomes.
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Affiliation(s)
| | | | | | | | - Abu Omayer
- Tbilisi State Medical University, Tbilisi, Georgia
| | | | | | | | | | | | | | | | | | | | | | | | | | - Wah Yang
- First Affiliated Hospital of Jinan University, Guangzhou, China
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Leyaro B, Howie L, McMahon K, Ali A, Carragher R. Weight loss outcomes and associated factors after metabolic bariatric surgery: Analysis of routine clinical data in Scotland. Am J Surg 2025; 241:116151. [PMID: 39719776 DOI: 10.1016/j.amjsurg.2024.116151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/03/2024] [Accepted: 12/16/2024] [Indexed: 12/26/2024]
Abstract
BACKGROUND Bariatric surgery is a cornerstone intervention for individuals with severe obesity, offering substantial and sustainable weight loss. METHODS This retrospective cohort study included 186 patients with obesity and Type2 diabetes who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between 2009 and 2020 at University Hospital Ayr. Optimal clinical response weight loss was defined as excess weight loss (%EWL) ≥50 % or total weight loss (%TWL) ≥20 %. RESULTS At 2-years post-surgery, 43.6 % achieved ≥50 %EWL, and 44.1 % achieved ≥20%TWL, with 31.8 % maintaining this at 5-years. Depending on the definition used, between 11.2 % and 45.9 % of patients experienced recurrent weight gain. BMI had significant positive association with %TWL but negative with %EWL (p < 0.05). RYGB had significantly higher %TWL compared to SG (p < 0.05). CONCLUSION Most patients experienced weight loss which was maintained over time, however recurrent weight gain was noted. Pre-surgery BMI was significantly associated with weight changes.
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Affiliation(s)
- Beatrice Leyaro
- School of Computing, Engineering and Physical Sciences, University of West of Scotland, Scotland, UK; Institute of Public Health: Epidemiology and Biostatistics Department, Kilimanjaro Christian Medical University College, Moshi, Kilimanjaro, Tanzania.
| | - Lyz Howie
- School of Health and Life Sciences, University of the West of Scotland, Scotland, UK
| | - Kevin McMahon
- Department of General & Upper GI Surgery, University Hospital Ayr, Ayr, Scotland, UK
| | - Abdulmajid Ali
- Department of General & Upper GI Surgery, University Hospital Ayr, Ayr, Scotland, UK
| | - Raymond Carragher
- School of Computing, Engineering and Physical Sciences, University of West of Scotland, Scotland, UK
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3
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Chen Z, Zhou J, Zheng X, Xie H, Hao H. Metabolic insights into gut microbiota in the pharmacology of natural medicines. Chin J Nat Med 2025; 23:158-168. [PMID: 39986692 DOI: 10.1016/s1875-5364(25)60820-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/12/2024] [Accepted: 10/24/2024] [Indexed: 02/24/2025]
Abstract
Natural medicines (NMs) demonstrate distinct advantages in the clinical management of chronic diseases. Recent years have seen growing recognition of the gut microbiota's role in the efficacy and synergy of NMs, providing new impetus for elucidating the material basis and mechanisms of NMs and their path toward modernization. A fundamental question that has emerged is how NM-microbiota interactions integrate into the multi-target holistic mechanisms of NMs, the answer to which may also illuminate new avenues for drug discovery. Metabolic regulation via small-molecule metabolites has been increasingly implicated in host-microbe interaction. This review presents an integral metabolic perspective on NMs-microbiota interaction in host health and disease. It highlights the emerging understanding of gut microbiota-related metabolic signals implicated in NM components' local and systemic actions. Additionally, it discusses key issues and prospects related to drug development and the translational study of NMs.
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Affiliation(s)
- Zixin Chen
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Laboratory of Metabolic Regulation and Drug Target Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Junchi Zhou
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Laboratory of Metabolic Regulation and Drug Target Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
| | - Xiao Zheng
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Laboratory of Metabolic Regulation and Drug Target Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
| | - Hao Xie
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Laboratory of Metabolic Regulation and Drug Target Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
| | - Haiping Hao
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Laboratory of Metabolic Regulation and Drug Target Discovery, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
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4
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Rivera-Carranza T, León-Téllez Girón A, Rojano-Rodríguez ME, Romero-Loera LS, Zúñiga-León E. [Metabolic, clinical and body composition changes in Mexican adults undergoing bariatric surgery]. NUTR HOSP 2024; 41:1209-1216. [PMID: 39311005 DOI: 10.20960/nh.05214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024] Open
Abstract
Introduction Background: morbid obesity is a major public health problem that is increasing. Currently, there are a limited number of studies carried out in the Mexican population that describe the effects of bariatric surgery. Objective: to establish in obese people who undergoing weight loss surgery, the metabolic and body composition difference before and after bariatric surgery. Material and methods: an observational, analytical, and longitudinal study was carried out in 50 patients with morbid obesity who underwent laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Body composition and metabolic markers in blood were measured. Differences in the metabolic profile before and after surgery were analyzed in the entire study group and a subanalysis was performed by bariatric surgical technique. It was also determined the percentage of remission of comorbidities. Results: after the intervention, there is a significant decrease in all metabolic and body composition markers, except HDL cholesterol, which showed a tendency to increase without being significant. Women with LRYGB have a greater decrease in fat-free mass. LRYGB decreased the prevalence of fatty liver, gastroesophageal reflux, insulin resistance, and hypercholesterolemia more, while LSG decreased the prevalence of hypertension, osteoarthritis, hypothyroidism, and hypertriglyceridemia more. Conclusion: bariatric surgery induces metabolic changes that could contribute to improving comorbidities associated with obesity. In general, metabolic improvement is greater in LRYGB compared to LSG.
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Affiliation(s)
- Tania Rivera-Carranza
- Colegio de Ciencias y Humanidades. Academia de Nutrición y Salud. Universidad Autónoma de la Ciudad de México
| | | | | | | | - Eduardo Zúñiga-León
- Departamento de Sistemas Biológicos. División de Ciencias Biológicas y de la Salud. Universidad Autónoma Metropolitana. Unidad Xochimilco
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Castelnuovo G, Perez-Diaz-Del-Campo N, Guariglia M, Poggiolini I, Armandi A, Rosso C, Caviglia GP, Bugianesi E. Prebiotics targeting gut-liver axis to treat non-alcoholic fatty liver disease. Minerva Gastroenterol (Torino) 2024; 70:446-453. [PMID: 36892817 DOI: 10.23736/s2724-5985.23.03361-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/10/2023]
Abstract
Non-alcoholic steatohepatitis (NASH) is a high-prevalence, rapidly growing form of non-alcoholic fatty liver disease (NAFLD), which is closely linked to obesity and metabolic disorders. Gut microbiota has been increasingly recognized as a key factor in the onset of NAFLD in recent years. The liver can be strongly influenced by changes in the gut microbiota through the portal vein, giving the gut-liver axis a very important role in understanding the pathophysiology of liver diseases. A healthy intestinal barrier is characterized by selective permeability to nutrients, metabolites, water and bacterial products and its impairment may be a predisposing or aggravating condition for the progression of NAFLD. In most cases, NAFLD patients follow a Western diet pattern, which is closely linked to obesity and associated metabolic diseases, promoting inflammation, structural and behavioral changes in the gut microbiota. In fact, factors such as age, gender, genetic or environmental factors may induce a dysbiotic microbiota that promotes epithelial barrier dysfunction and increased intestinal permeability, favoring the progression of NAFLD. In this context, new dietary approaches, such as prebiotics, are emerging to prevent disease and maintain health. In this review, we reported the role of the gut-liver axis in the pathogenesis of NAFLD and investigated the potential therapeutic effect of prebiotics on the enhancement of intestinal barrier dysfunction, hepatic steatosis and, consequently, the progression of NAFLD.
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Affiliation(s)
| | | | - Marta Guariglia
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Irene Poggiolini
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Angelo Armandi
- Department of Medical Sciences, University of Turin, Turin, Italy
- Metabolic Liver Disease Research Program, First Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Chiara Rosso
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Gian P Caviglia
- Department of Medical Sciences, University of Turin, Turin, Italy -
| | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, Turin, Italy
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
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Fang Y, Qin M, Zheng Q, Wang K, Han X, Yang Q, Sang X, Cao G. Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy. Kidney Int Rep 2024; 9:3116-3133. [PMID: 39534198 PMCID: PMC11551060 DOI: 10.1016/j.ekir.2024.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 07/25/2024] [Accepted: 08/04/2024] [Indexed: 11/16/2024] Open
Abstract
Diabetic nephropathy (DN) is a prevalent microvascular complication that occurs often in individuals with diabetes. It significantly raises the mortality rate of affected patients. Therefore, there is an urgent need to identify therapeutic targets for controlling and preventing the occurrence and development of DN. Bile acids (BAs) are now recognized as intricate metabolic integrators and signaling molecules. The activation of BAs has great promise as a therapeutic approach for preventing DN, renal damage caused by obesity, and nephrosclerosis. The nuclear receptors (NRs), farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR); and the G protein-coupled BA receptor, Takeda G-protein-coupled receptor 5 (TGR5) have important functions in controlling lipid, glucose, and energy metabolism, inflammation, as well as drug metabolism and detoxification. Over the past 10 years, there has been advancement in comprehending the biology and processes of BA receptors in the kidney, as well as in the creation of targeted BA receptor agonists. In this review, we discuss the role of BA receptors, FXR, PXR, VDR, and TGR5 in DN and their role in renal physiology, as well as the development and application of agonists that activate BA receptors for the treatment of kidney diseases.
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Affiliation(s)
- Yuanyuan Fang
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Minjing Qin
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qitong Zheng
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Kuilong Wang
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xin Han
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiao Yang
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xia'nan Sang
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
| | - Gang Cao
- School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China
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Wang B, Han D, Hu X, Chen J, Liu Y, Wu J. Exploring the role of a novel postbiotic bile acid: Interplay with gut microbiota, modulation of the farnesoid X receptor, and prospects for clinical translation. Microbiol Res 2024; 287:127865. [PMID: 39121702 DOI: 10.1016/j.micres.2024.127865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 08/01/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024]
Abstract
The gut microbiota, mainly resides in the colon, possesses a remarkable ability to metabolize different substrates to create bioactive substances, including short-chain fatty acids, indole-3-propionic acid, and secondary bile acids. In the liver, bile acids are synthesized from cholesterol and then undergo modification by the gut microbiota. Beyond those reclaimed by the enterohepatic circulation, small percentage of bile acids escaped reabsorption, entering the systemic circulation to bind to several receptors, such as farnesoid X receptor (FXR), thereby exert their biological effects. Gut microbiota interplays with bile acids by affecting their synthesis and determining the production of secondary bile acids. Reciprocally, bile acids shape out the structure of gut microbiota. The interplay of bile acids and FXR is involved in the development of multisystemic conditions, encompassing metabolic diseases, hepatobiliary diseases, immune associated disorders. In the review, we aim to provide a thorough review of the intricate crosstalk between the gut microbiota and bile acids, the physiological roles of bile acids and FXR in mammals' health and disease, and the clinical translational considerations of gut microbiota-bile acids-FXR in the treatment of the diseases.
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Affiliation(s)
- Beibei Wang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Dong Han
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Xinyue Hu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Jing Chen
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Yuwei Liu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Jing Wu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China.
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8
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Komorniak N, Pawlus J, Gaweł K, Hawryłkowicz V, Stachowska E. Cholelithiasis, Gut Microbiota and Bile Acids after Bariatric Surgery-Can Cholelithiasis Be Prevented by Modulating the Microbiota? A Literature Review. Nutrients 2024; 16:2551. [PMID: 39125429 PMCID: PMC11314327 DOI: 10.3390/nu16152551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 07/28/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Cholelithiasis is one of the more common complications following bariatric surgery. This may be related to the rapid weight loss during this period, although the exact mechanism of gallstone formation after bariatric surgery has not been fully elucidated. METHODS The present literature review focuses on risk factors, prevention options and the impact of the gut microbiota on the development of gallbladder stones after bariatric surgery. RESULTS A potential risk factor for the development of cholelithiasis after bariatric surgery may be changes in the composition of the intestinal microbiota and bile acids. One of the bile acids-ursodeoxycholic acid-is considered to reduce the concentration of mucin proteins and thus contribute to reducing the formation of cholesterol crystals in patients with cholelithiasis. Additionally, it reduces the risk of both asymptomatic and symptomatic gallstones after bariatric surgery. Patients who developed gallstones after bariatric surgery had a higher abundance of Ruminococcus gnavus and those who did not develop cholelithiasis had a higher abundance of Lactobacillaceae and Enterobacteriaceae. CONCLUSION The exact mechanism of gallstone formation after bariatric surgery has not yet been clarified. Research suggests that the intestinal microbiota and bile acids may have an important role in this.
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Affiliation(s)
- Natalia Komorniak
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (V.H.); (E.S.)
| | - Jan Pawlus
- Department of General Mini-Invasive and Gastroenterological Surgery, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland;
| | - Katarzyna Gaweł
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland;
| | - Viktoria Hawryłkowicz
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (V.H.); (E.S.)
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (V.H.); (E.S.)
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9
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Wang R, Mijiti S, Xu Q, Liu Y, Deng C, Huang J, Yasheng A, Tian Y, Cao Y, Su Y. The Potential Mechanism of Remission in Type 2 Diabetes Mellitus After Vertical Sleeve Gastrectomy. Obes Surg 2024; 34:3071-3083. [PMID: 38951388 DOI: 10.1007/s11695-024-07378-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 06/13/2024] [Accepted: 06/19/2024] [Indexed: 07/03/2024]
Abstract
In recent years, there has been a gradual increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), with bariatric surgery remaining the most effective treatment strategy for these conditions. Vertical sleeve gastrectomy (VSG) has emerged as the most popular surgical procedure for bariatric/metabolic surgeries, effectively promoting weight loss and improving or curing T2DM. The alterations in the gastrointestinal tract following VSG may improve insulin secretion and resistance by increasing incretin secretion (especially GLP-1), modifying the gut microbiota composition, and through mechanisms dependent on weight loss. This review focuses on the potential mechanisms through which the enhanced action of incretin and metabolic changes in the digestive system after VSG may contribute to the remission of T2DM.
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Affiliation(s)
- Rongfei Wang
- Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No.57 Mei Hua East Road, Xiang Zhou District, Zhuhai, 519000, Guangdong, China
| | - Salamu Mijiti
- Department of General Surgery, The First People's Hospital of Kashi, Autonomous Region, Kashi, 844000, Xinjiang Uygur, China
| | - Qilin Xu
- Department of General Surgery, The First People's Hospital of Kashi, Autonomous Region, Kashi, 844000, Xinjiang Uygur, China
| | - Yile Liu
- Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No.57 Mei Hua East Road, Xiang Zhou District, Zhuhai, 519000, Guangdong, China
| | - Chaolun Deng
- Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No.57 Mei Hua East Road, Xiang Zhou District, Zhuhai, 519000, Guangdong, China
| | - Jiangtao Huang
- Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No.57 Mei Hua East Road, Xiang Zhou District, Zhuhai, 519000, Guangdong, China
| | - Abudoukeyimu Yasheng
- Department of General Surgery, The First People's Hospital of Kashi, Autonomous Region, Kashi, 844000, Xinjiang Uygur, China
| | - Yunping Tian
- Department of General Surgery, The First People's Hospital of Kashi, Autonomous Region, Kashi, 844000, Xinjiang Uygur, China.
| | - Yanlong Cao
- Department of General Surgery, The First People's Hospital of Kashi, Autonomous Region, Kashi, 844000, Xinjiang Uygur, China.
| | - Yonghui Su
- Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, No.57 Mei Hua East Road, Xiang Zhou District, Zhuhai, 519000, Guangdong, China.
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10
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Wahlström A, Aydin Ö, Olsson LM, Sjöland W, Henricsson M, Lundqvist A, Marschall HU, Franken R, van de Laar A, Gerdes V, Meijnikman AS, Hofsø D, Groen AK, Hjelmesæth J, Nieuwdorp M, Bäckhed F. Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetes. EBioMedicine 2024; 106:105265. [PMID: 39096744 PMCID: PMC11345581 DOI: 10.1016/j.ebiom.2024.105265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 07/17/2024] [Accepted: 07/21/2024] [Indexed: 08/05/2024] Open
Abstract
BACKGROUND Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. METHODS In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. FINDINGS We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. INTERPRETATION Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission. FUNDING Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw.
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Affiliation(s)
- Annika Wahlström
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
| | - Ömrüm Aydin
- Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands
| | - Lisa M Olsson
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
| | - Wilhelm Sjöland
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
| | - Marcus Henricsson
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
| | - Annika Lundqvist
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
| | - Hanns-Ulrich Marschall
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden
| | - Rutger Franken
- Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands
| | | | - Victor Gerdes
- Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
| | - Abraham S Meijnikman
- Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
| | - Dag Hofsø
- Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, Tønsberg, Norway
| | - Albert K Groen
- Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
| | - Jøran Hjelmesæth
- Department of Endocrinology, Obesity and Nutrition, Vestfold Hospital Trust, Tønsberg, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Institute of Clinical Medicine, University of Oslo, Norway
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands; Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands
| | - Fredrik Bäckhed
- Wallenberg Laboratory and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden.
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11
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Faramia J, Choi BSY, Brunelle L, Marette A, Drapeau V, Tremblay A, Picard F. Effects of Lacticaseibacillus rhamnosus HA-114 probiotic supplementation on circulating IGFBP-2 levels during a calorie-restricted diet in overweight humans. J Clin Transl Endocrinol 2024; 36:100357. [PMID: 38948244 PMCID: PMC11211884 DOI: 10.1016/j.jcte.2024.100357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 05/07/2024] [Accepted: 06/10/2024] [Indexed: 07/02/2024] Open
Abstract
Background and aim Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic Lacticaseibacillus rhamnosus HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of L. rhamnosus HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors. Methods Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (-500 kcal/day), in combination with probiotic L. rhamnosus HA-114 or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors. Results On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters. Conclusion Probiotic supplementation with L. rhamnosus HA-114 did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.
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Affiliation(s)
- Justine Faramia
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada
- Faculty of Pharmacy, Université Laval, Québec, QC, Canada
| | - Béatrice S.-Y. Choi
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada
- Centre Nutrition, santé et société (NUTRISS) and Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, Canada
| | - Lucie Brunelle
- Department of Kinesiology, PEPS, Université Laval, QC, Canada
| | - André Marette
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada
- Centre Nutrition, santé et société (NUTRISS) and Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, Canada
- Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada
| | - Vicky Drapeau
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada
- Centre Nutrition, santé et société (NUTRISS) and Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, Canada
- Department of Physical Education, Faculty of Education, Université Laval, QC, Canada
| | - Angelo Tremblay
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada
- Centre Nutrition, santé et société (NUTRISS) and Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, Canada
- Department of Kinesiology, PEPS, Université Laval, QC, Canada
| | - Frédéric Picard
- Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval, Québec, QC, Canada
- Faculty of Pharmacy, Université Laval, Québec, QC, Canada
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12
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Yun C, Yan S, Liao B, Ding Y, Qi X, Zhao M, Wang K, Zhuo Y, Nie Q, Ye C, Xia P, Ma M, Li R, Jiang C, Qiao J, Pang Y. The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice. Nat Metab 2024; 6:947-962. [PMID: 38769396 DOI: 10.1038/s42255-024-01041-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 04/02/2024] [Indexed: 05/22/2024]
Abstract
Polycystic ovary syndrome (PCOS), an endocrine disorder afflicting 6-20% of women of reproductive age globally, has been linked to alterations in the gut microbiome. We previously showed that in PCOS, elevation of Bacteroides vulgatus in the gut microbiome was associated with altered bile acid metabolism. Here we show that B. vulgatus also induces a PCOS-like phenotype in female mice via an alternate mechanism independent of bile acids. We find that B. vulgatus contributes to PCOS-like symptoms through its metabolite agmatine, which is derived from arginine by arginine decarboxylase. Mechanistically, agmatine activates the farnesoid X receptor (FXR) pathway to subsequently inhibit glucagon-like peptide-1 (GLP-1) secretion by L cells, which leads to insulin resistance and ovarian dysfunction. Critically, the GLP-1 receptor agonist liraglutide and the arginine decarboxylase inhibitor difluoromethylarginine ameliorate ovarian dysfunction in a PCOS-like mouse model. These findings reveal that agmatine-FXR-GLP-1 signalling contributes to ovarian dysfunction, presenting a potential therapeutic target for PCOS management.
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Affiliation(s)
- Chuyu Yun
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
- Institute of Advanced Clinical Medicine, Peking University, Beijing, China
| | - Sen Yan
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
- Institute of Advanced Clinical Medicine, Peking University, Beijing, China
| | - Baoying Liao
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Yong Ding
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Xinyu Qi
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
- Institute of Advanced Clinical Medicine, Peking University, Beijing, China
- Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Min Zhao
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Kai Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Yingying Zhuo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Qixing Nie
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Chuan Ye
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Pengyan Xia
- Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Research on Major Immunology-related Diseases, Peking University, Beijing, China
| | - Ming Ma
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Rong Li
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
- Institute of Advanced Clinical Medicine, Peking University, Beijing, China.
- Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China.
| | - Changtao Jiang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
- Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Research on Major Immunology-related Diseases, Peking University, Beijing, China.
- Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.
| | - Jie Qiao
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
- Institute of Advanced Clinical Medicine, Peking University, Beijing, China.
- Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China.
| | - Yanli Pang
- State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
- Institute of Advanced Clinical Medicine, Peking University, Beijing, China.
- Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China.
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Jamialahamdi T, Gadde KM, Nguyen NT, Kroh M, Sukhorukov VN, Almahmeed W, Al-Rasadi K, Sahebkar A. Improvement of Triglyceride-Glucose Index Following Bariatric Surgery: a Systematic Review and Meta-analysis. Obes Surg 2024; 34:741-750. [PMID: 38102370 DOI: 10.1007/s11695-023-06992-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 12/07/2023] [Accepted: 12/11/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND Bariatric surgery is an effective intervention for the management of severe obesity and its associated comorbidities, including metabolic abnormalities. This meta-analysis aimed to evaluate the impact of bariatric surgery on the triglyceride-glucose (TyG) index, a novel marker of insulin resistance and metabolic syndrome. METHODS A systematic search was conducted in Embase, PubMed, Web of Science, and Scopus. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V4 software. The overall effect size was determined by a random-effects meta-analysis and the leave-one-out approach. RESULTS A total of 9 trials including 1620 individuals confirmed a significant reduction in TyG following bariatric surgery (weighted mean difference (WMD) - 0.770, 95% CI - 1.006, - 0.534, p < 0.001). In a sub-analysis according to the type of bariatric surgery there was a significant reduction in TyG index for Roux-en-Y gastric bypass (WMD - 0.775, 95% CI - 1.000, - 0.550, p < 0.001), and sleeve gastrectomy (WMD - 0.920, 95% CI - 1.368, - 0.473, p < 0.001). In a sub-analysis according to the follow-up duration there was similarly a significant reduction in TyG index for both < 12 months (WMD - 1.645, 95% CI - 2.123, - 1.167, p < 0.001), and ≥ 12 months follow-up (WMD - 0.954, 95% CI - 1.606, - 0.303, p < 0.001). CONCLUSION The results of this meta-analysis demonstrated a significant reduction in the TyG index following bariatric surgery, indicating improved insulin sensitivity and metabolic health. These findings highlight the potential of bariatric surgery as a valuable therapeutic option for individuals with obesity and its metabolic consequences.
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Affiliation(s)
- Tannaz Jamialahamdi
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kishore M Gadde
- Department of Surgery, University of California Irvine Medical Center, Orange, CA, USA
| | - Ninh T Nguyen
- Department of Surgery, University of California Irvine Medical Center, Orange, CA, USA
| | - Matthew Kroh
- Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Vasily N Sukhorukov
- Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow, 125315, Russia
| | - Wael Almahmeed
- Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | | | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Zhu Z, Xu Y, Xia Y, Jia X, Chen Y, Liu Y, Zhang L, Chai H, Sun L. Review on chronic metabolic diseases surrounding bile acids and gut microbiota: What we have explored so far. Life Sci 2024; 336:122304. [PMID: 38016578 DOI: 10.1016/j.lfs.2023.122304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/22/2023] [Accepted: 11/23/2023] [Indexed: 11/30/2023]
Abstract
Bile acid, the final product of cholesterol breakdown, functions as a complex regulator and signaling factor in human metabolism. Chronic metabolic diseases pose significant medical challenges. Growing research underscores bile acids' capacity to enhance metabolism via diverse pathways, regulating disorders and offering treatment potential. Numerous bile-acid-triggered pathways have become treatment targets. This review outlines bile acid synthesis, its role as a signal in chronic metabolic diseases, and highlights its interaction with gut microbiota in different metabolic conditions. Exploring host-bacteria-bile acid links emerges as a valuable future research direction with clinical implications.
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Affiliation(s)
- Zhenzheng Zhu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuemiao Xu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuwei Xia
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinru Jia
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yixin Chen
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuyue Liu
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Leyin Zhang
- Department of Medical Oncology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Hui Chai
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Leitao Sun
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China; Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
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15
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Di Ciaula A, Bonfrate L, Khalil M, Portincasa P. The interaction of bile acids and gut inflammation influences the pathogenesis of inflammatory bowel disease. Intern Emerg Med 2023; 18:2181-2197. [PMID: 37515676 PMCID: PMC10635993 DOI: 10.1007/s11739-023-03343-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 06/08/2023] [Indexed: 07/31/2023]
Abstract
Bile acids (BA) are amphipathic molecules originating from cholesterol in the liver and from microbiota-driven biotransformation in the colon. In the gut, BA play a key role in fat digestion and absorption and act as potent signaling molecules on the nuclear farnesoid X receptor (FXR) and membrane-associated G protein-coupled BA receptor-1 (GPBAR-1). BA are, therefore, involved in the maintenance of gut barrier integrity, gene expression, metabolic homeostasis, and microbiota profile and function. Disturbed BA homeostasis can activate pro-inflammatory pathways in the gut, while inflammatory bowel diseases (IBD) can induce gut dysbiosis and qualitative and/or quantitative changes of the BA pool. These factors contribute to impaired repair capacity of the mucosal barrier, due to chronic inflammation. A better understanding of BA-dependent mechanisms paves the way to innovative therapeutic tools by administering hydrophilic BA and FXR agonists and manipulating gut microbiota with probiotics and prebiotics. We discuss the translational value of pathophysiological and therapeutic evidence linking BA homeostasis to gut inflammation in IBD.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy.
| | - Mohamad Khalil
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri" and Division Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University "Aldo Moro" Medical School, Policlinico Hospital, Piazza G. Cesare 11, 70124, Bari, Italy
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Leyderman M, Wilmore JR, Shope T, Cooney RN, Urao N. Impact of intestinal microenvironments in obesity and bariatric surgery on shaping macrophages. IMMUNOMETABOLISM (COBHAM, SURREY) 2023; 5:e00033. [PMID: 38037591 PMCID: PMC10683977 DOI: 10.1097/in9.0000000000000033] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 10/26/2023] [Indexed: 12/02/2023]
Abstract
Obesity is associated with alterations in tissue composition, systemic cellular metabolism, and low-grade chronic inflammation. Macrophages are heterogenous innate immune cells ubiquitously localized throughout the body and are key components of tissue homeostasis, inflammation, wound healing, and various disease states. Macrophages are highly plastic and can switch their phenotypic polarization and change function in response to their local environments. Here, we discuss how obesity alters the intestinal microenvironment and potential key factors that can influence intestinal macrophages as well as macrophages in other organs, including adipose tissue and hematopoietic organs. As bariatric surgery can induce metabolic adaptation systemically, we discuss the potential mechanisms through which bariatric surgery reshapes macrophages in obesity.
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Affiliation(s)
- Michael Leyderman
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Joel R. Wilmore
- Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY, USA
- Sepsis Interdisciplinary Research Center, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Timothy Shope
- Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Robert N. Cooney
- Sepsis Interdisciplinary Research Center, State University of New York Upstate Medical University, Syracuse, NY, USA
- Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Norifumi Urao
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY, USA
- Sepsis Interdisciplinary Research Center, State University of New York Upstate Medical University, Syracuse, NY, USA
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17
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Stefura T, Rusinek J, Zając M, Zapała B, Gosiewski T, Sroka-Oleksiak A, Salamon D, Pędziwiatr M, Major P. Duodenal microbiota and weight-loss following sleeve gastrectomy and Roux-en-Y gastric bypass - a pilot study. BMC Surg 2023; 23:173. [PMID: 37365522 PMCID: PMC10291748 DOI: 10.1186/s12893-023-02076-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 06/13/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Bariatric surgery is the most effective method of morbid obesity treatment. Microbiota has many functions in human body and many of them remain to be unknown. The aim of this study was to establish if the composition of duodenal microbiota influences success rate of bariatric surgery. METHODS It was a prospective cohort study. The data concerning demographics and comorbidities was collected perioperatively. The duodenal biopsies were collected prior to surgery with the gastroscope. Then DNA analysis was conducted. The data connected to the operation outcomes was gathered after 6 and 12 months after surgery. RESULTS Overall, 32 patients were included and divided into two groups (successful - group 1 and unsuccessful - group 0) based on percentage excess weight loss after 6 months were created. The Total Actual Abundance was higher in group 0. In group 0 there was a significantly higher amount of Roseburia and Arthrobacter (p = 0.024, p = 0.027, respectively). Genus LDA effect size analysis showed Prevotella, Megasphaera and Pseudorhodobacter in group 1 to be significant. Whereas abundance of Roseburia and Arthrobacter were significant in group 0. CONCLUSIONS Duodenal microbiota composition may be a prognostic factor for the success of the bariatric surgery but further research on the larger group is needed.
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Affiliation(s)
- Tomasz Stefura
- Department of Medical Education, Jagiellonian University Medical College, Krakow, Poland
| | - Jakub Rusinek
- Students' Scientific Group at 2nd Department of General Surgery, Jagiellonian University, Medical College, Krakow, Poland
| | - Maciej Zając
- Students' Scientific Group at 2nd Department of General Surgery, Jagiellonian University, Medical College, Krakow, Poland
| | - Barbara Zapała
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
| | - Tomasz Gosiewski
- Department of Microbiology, Jagiellonian University Medical College, Krakow, Poland
| | | | - Dominika Salamon
- Department of Microbiology, Jagiellonian University Medical College, Krakow, Poland
| | - Michał Pędziwiatr
- 2nd Department of General Surgery, Jagiellonian University Medical College, Kopernika 21 St, 31-501, Kraków, Poland
| | - Piotr Major
- 2nd Department of General Surgery, Jagiellonian University Medical College, Kopernika 21 St, 31-501, Kraków, Poland.
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Majait S, Nieuwdorp M, Kemper M, Soeters M. The Black Box Orchestra of Gut Bacteria and Bile Acids: Who Is the Conductor? Int J Mol Sci 2023; 24:ijms24031816. [PMID: 36768140 PMCID: PMC9916144 DOI: 10.3390/ijms24031816] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 01/11/2023] [Accepted: 01/14/2023] [Indexed: 01/18/2023] Open
Abstract
Over the past decades the potential role of the gut microbiome and bile acids in type 2 diabetes mellitus (T2DM) has been revealed, with a special reference to low bacterial alpha diversity. Certain bile acid effects on gut bacteria concern cytotoxicity, or in the case of the microbiome, bacteriotoxicity. Reciprocally, the gut microbiome plays a key role in regulating the bile acid pool by influencing the conversion and (de)conjugation of primary bile acids into secondary bile acids. Three main groups of bacterial enzymes responsible for the conversion of bile acids are bile salt hydrolases (BSHs), hydroxysteroid dehydrogenases (HSDHs) and enzymes encoded in the bile acid inducible (Bai) operon genes. Interventions such as probiotics, antibiotics and fecal microbiome transplantation can impact bile acids levels. Further evidence of the reciprocal interaction between gut microbiota and bile acids comes from a multitude of nutritional interventions including macronutrients, fibers, prebiotics, specific individual products or diets. Finally, anatomical changes after bariatric surgery are important because of their metabolic effects. The heterogeneity of studies, diseases, bacterial species and (epi)genetic influences such as nutrition may challenge establishing specific and detailed interventions that aim to tackle the gut microbiome and bile acids.
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Affiliation(s)
- Soumia Majait
- Department of Pharmacy and Clinical Pharmacy, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
| | - Marleen Kemper
- Department of Pharmacy and Clinical Pharmacy, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
| | - Maarten Soeters
- Department of Endocrinology and Metabolism, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
- Correspondence:
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Livzan MA, Mozgovoi SI, Gaus OV, Bordin DS, Kononov AV. Diagnostic Principles for Chronic Gastritis Associated with Duodenogastric Reflux. Diagnostics (Basel) 2023; 13:186. [DOI: https:/doi.org/10.3390/diagnostics13020186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2023] Open
Abstract
This article systematizes available data from the literature on biliary gastritis (BG) in order to increase the awareness of specialists about the latest possibilities for diagnosing the disease. BG occurs as a result of pathological duodenogastric reflux. In patients with a preserved duodenogastric junction, the dominant factor is represented by motor disorders of the upper digestive tract (primary biliary gastritis), while in patients recovering from surgical interventions it is represented by structural changes (secondary biliary gastritis). Progressive BG can lead to atrophy of the gastric mucosa, intestinal metaplasia, epithelial dysplasia, and eventually to gastric cancer. Diagnostic methods for BG are carried out to identify risk factors, exclude alarm symptoms and identify persistent motor disorders and pathological reflux (24 h pH-impedancemetry, hepatobiliary scintigraphy, 24 h monitoring of bilirubin content in the reflux using a Bilitec 2000 photometer), as well as to diagnose gastritis itself (esophagogastroduodenoscopy, morphological gastrobiopsy examination). The diagnosis of BG should be based on a multidisciplinary approach that combines a thorough analysis of a patient’s complaints, an anamnesis of the disease, and the results of endoscopic and histological research methods.
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Affiliation(s)
- Maria A. Livzan
- Department of Faculty Therapy and Gastroenterology, Omsk State Medical University, 644099 Omsk, Russia
| | - Sergei I. Mozgovoi
- Department of Pathological Anatomy, Omsk State Medical University, 644099 Omsk, Russia
| | - Olga V. Gaus
- Department of Faculty Therapy and Gastroenterology, Omsk State Medical University, 644099 Omsk, Russia
| | - Dmitry S. Bordin
- A.S. Loginov Moscow Clinical Scientific Center, Department of Pathology of the Pancreas, Biliary Tract and Upper Digestive Tract, 111123 Moscow, Russia
- Department of Propaedeutics of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
- Department of General Medical Practice and Family Medicine, Tver State Medical University, 170100 Tver, Russia
| | - Alexei V. Kononov
- Department of Pathological Anatomy, Omsk State Medical University, 644099 Omsk, Russia
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20
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Livzan MA, Mozgovoi SI, Gaus OV, Bordin DS, Kononov AV. Diagnostic Principles for Chronic Gastritis Associated with Duodenogastric Reflux. Diagnostics (Basel) 2023; 13:186. [PMID: 36672996 PMCID: PMC9858268 DOI: 10.3390/diagnostics13020186] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 12/30/2022] [Accepted: 01/02/2023] [Indexed: 01/06/2023] Open
Abstract
This article systematizes available data from the literature on biliary gastritis (BG) in order to increase the awareness of specialists about the latest possibilities for diagnosing the disease. BG occurs as a result of pathological duodenogastric reflux. In patients with a preserved duodenogastric junction, the dominant factor is represented by motor disorders of the upper digestive tract (primary biliary gastritis), while in patients recovering from surgical interventions it is represented by structural changes (secondary biliary gastritis). Progressive BG can lead to atrophy of the gastric mucosa, intestinal metaplasia, epithelial dysplasia, and eventually to gastric cancer. Diagnostic methods for BG are carried out to identify risk factors, exclude alarm symptoms and identify persistent motor disorders and pathological reflux (24 h pH-impedancemetry, hepatobiliary scintigraphy, 24 h monitoring of bilirubin content in the reflux using a Bilitec 2000 photometer), as well as to diagnose gastritis itself (esophagogastroduodenoscopy, morphological gastrobiopsy examination). The diagnosis of BG should be based on a multidisciplinary approach that combines a thorough analysis of a patient's complaints, an anamnesis of the disease, and the results of endoscopic and histological research methods.
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Affiliation(s)
- Maria A. Livzan
- Department of Faculty Therapy and Gastroenterology, Omsk State Medical University, 644099 Omsk, Russia
| | - Sergei I. Mozgovoi
- Department of Pathological Anatomy, Omsk State Medical University, 644099 Omsk, Russia
| | - Olga V. Gaus
- Department of Faculty Therapy and Gastroenterology, Omsk State Medical University, 644099 Omsk, Russia
| | - Dmitry S. Bordin
- A.S. Loginov Moscow Clinical Scientific Center, Department of Pathology of the Pancreas, Biliary Tract and Upper Digestive Tract, 111123 Moscow, Russia
- Department of Propaedeutics of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
- Department of General Medical Practice and Family Medicine, Tver State Medical University, 170100 Tver, Russia
| | - Alexei V. Kononov
- Department of Pathological Anatomy, Omsk State Medical University, 644099 Omsk, Russia
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21
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Ruze R, Liu T, Zou X, Song J, Chen Y, Xu R, Yin X, Xu Q. Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. Front Endocrinol (Lausanne) 2023; 14:1161521. [PMID: 37152942 PMCID: PMC10161731 DOI: 10.3389/fendo.2023.1161521] [Citation(s) in RCA: 255] [Impact Index Per Article: 127.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 04/06/2023] [Indexed: 05/09/2023] Open
Abstract
The prevalence of obesity and diabetes mellitus (DM) has been consistently increasing worldwide. Sharing powerful genetic and environmental features in their pathogenesis, obesity amplifies the impact of genetic susceptibility and environmental factors on DM. The ectopic expansion of adipose tissue and excessive accumulation of certain nutrients and metabolites sabotage the metabolic balance via insulin resistance, dysfunctional autophagy, and microbiome-gut-brain axis, further exacerbating the dysregulation of immunometabolism through low-grade systemic inflammation, leading to an accelerated loss of functional β-cells and gradual elevation of blood glucose. Given these intricate connections, most available treatments of obesity and type 2 DM (T2DM) have a mutual effect on each other. For example, anti-obesity drugs can be anti-diabetic to some extent, and some anti-diabetic medicines, in contrast, have been shown to increase body weight, such as insulin. Meanwhile, surgical procedures, especially bariatric surgery, are more effective for both obesity and T2DM. Besides guaranteeing the availability and accessibility of all the available diagnostic and therapeutic tools, more clinical and experimental investigations on the pathogenesis of these two diseases are warranted to improve the efficacy and safety of the available and newly developed treatments.
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Affiliation(s)
- Rexiati Ruze
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tiantong Liu
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- School of Medicine, Tsinghua University, Beijing, China
| | - Xi Zou
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianlu Song
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ruiyuan Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinpeng Yin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qiang Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China
- *Correspondence: Qiang Xu,
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22
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Di Ciaula A, Bonfrate L, Baj J, Khalil M, Garruti G, Stellaard F, Wang HH, Wang DQH, Portincasa P. Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling. Nutrients 2022; 14:4950. [PMID: 36500979 PMCID: PMC9738051 DOI: 10.3390/nu14234950] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/18/2022] [Accepted: 11/20/2022] [Indexed: 11/23/2022] Open
Abstract
Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In the small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, and lipid-soluble vitamins. Primary BA escaping the active ileal re-absorption undergo the microbiota-dependent biotransformation to secondary BA in the colon, and passive diffusion into the portal vein towards the liver. BA also act as signaling molecules able to play a systemic role in a variety of metabolic functions, mainly through the activation of nuclear and membrane-associated receptors in the intestine, gallbladder, and liver. BA homeostasis is tightly controlled by a complex interplay with the nuclear receptor farnesoid X receptor (FXR), the enterokine hormone fibroblast growth factor 15 (FGF15) or the human ortholog FGF19 (FGF19). Circulating FGF19 to the FGFR4/β-Klotho receptor causes smooth muscle relaxation and refilling of the gallbladder. In the liver the binding activates the FXR-small heterodimer partner (SHP) pathway. This step suppresses the unnecessary BA synthesis and promotes the continuous enterohepatic circulation of BAs. Besides BA homeostasis, the BA-FXR-FGF19 axis governs several metabolic processes, hepatic protein, and glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted in cholestasis, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Thus, targeting FXR activity can represent a novel therapeutic approach for the prevention and the treatment of liver and metabolic diseases.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari “Aldo Moro” Medical School, 70124 Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari “Aldo Moro” Medical School, 70124 Bari, Italy
| | - Jacek Baj
- Department of Anatomy, Medical University of Lublin, 20-059 Lublin, Poland
| | - Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari “Aldo Moro” Medical School, 70124 Bari, Italy
| | - Gabriella Garruti
- Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari “Aldo Moro” Medical School, 70124 Bari, Italy
| | - Frans Stellaard
- Institute of Clinical Chemistry and Clinical Pharmacology, Venusberg-Campus 1, University Hospital Bonn, 53127 Bonn, Germany
| | - Helen H. Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - David Q.-H. Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari “Aldo Moro” Medical School, 70124 Bari, Italy
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23
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Roessler J, Leistner DM, Landmesser U, Haghikia A. Modulatory role of gut microbiota in cholesterol and glucose metabolism: Potential implications for atherosclerotic cardiovascular disease Atherosclerosis. Atherosclerosis 2022; 359:1-12. [PMID: 36126379 DOI: 10.1016/j.atherosclerosis.2022.08.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/12/2022] [Accepted: 08/31/2022] [Indexed: 11/02/2022]
Abstract
Accumulating evidence suggests an important role of gut microbiota in physiological processes of host metabolism as well as cardiometabolic disease. Recent advances in metagenomic and metabolomic research have led to discoveries of novel pathways in which intestinal microbial metabolism of dietary nutrients is linked to metabolic profiles and cardiovascular disease risk. A number of metaorganismal circuits have been identified by microbiota transplantation studies and experimental models using germ-free rodents. Many of these pathways involve gut microbiota-related bioactive metabolites that impact host metabolism, in particular lipid and glucose homeostasis, partly via specific host receptors. In this review, we summarize the current knowledge of how the gut microbiome can impact cardiometabolic phenotypes and provide an overview of recent advances of gut microbiome research. Finally, the potential of modulating intestinal microbiota composition and/or targeting microbiota-related pathways for novel preventive and therapeutic strategies in cardiometabolic and cardiovascular diseases will be discussed.
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Affiliation(s)
- Johann Roessler
- Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - David M Leistner
- Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; DZHK (German Center of Cardiovascular Research), Partner Site Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Ulf Landmesser
- Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; DZHK (German Center of Cardiovascular Research), Partner Site Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Arash Haghikia
- Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; DZHK (German Center of Cardiovascular Research), Partner Site Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
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24
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Martínez-López YE, Esquivel-Hernández DA, Sánchez-Castañeda JP, Neri-Rosario D, Guardado-Mendoza R, Resendis-Antonio O. Type 2 diabetes, gut microbiome, and systems biology: A novel perspective for a new era. Gut Microbes 2022; 14:2111952. [PMID: 36004400 PMCID: PMC9423831 DOI: 10.1080/19490976.2022.2111952] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The association between the physio-pathological variables of type 2 diabetes (T2D) and gut microbiota composition suggests a new avenue to track the disease and improve the outcomes of pharmacological and non-pharmacological treatments. This enterprise requires new strategies to elucidate the metabolic disturbances occurring in the gut microbiome as the disease progresses. To this end, physiological knowledge and systems biology pave the way for characterizing microbiota and identifying strategies in a move toward healthy compositions. Here, we dissect the recent associations between gut microbiota and T2D. In addition, we discuss recent advances in how drugs, diet, and exercise modulate the microbiome to favor healthy stages. Finally, we present computational approaches for disentangling the metabolic activity underlying host-microbiota codependence. Altogether, we envision that the combination of physiology and computational modeling of microbiota metabolism will drive us to optimize the diagnosis and treatment of T2D patients in a personalized way.
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Affiliation(s)
- Yoscelina Estrella Martínez-López
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Programa de Doctorado en Ciencias Médicas, Odontológicas y de la Salud, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México,Metabolic Research Laboratory, Department of Medicine and Nutrition. University of Guanajuato. León, Guanajuato, México
| | | | - Jean Paul Sánchez-Castañeda
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México
| | - Daniel Neri-Rosario
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Programa de Maestría en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México
| | - Rodolfo Guardado-Mendoza
- Metabolic Research Laboratory, Department of Medicine and Nutrition. University of Guanajuato. León, Guanajuato, México,Research Department, Hospital Regional de Alta Especialidad del Bajío. León, Guanajuato, México,Rodolfo Guardado-Mendoza Metabolic Research Laboratory, Department of Medicine and Nutrition. University of Guanajuato. León, Guanajuato, México
| | - Osbaldo Resendis-Antonio
- Human Systems Biology Laboratory. Instituto Nacional de Medicina Genómica (INMEGEN). México City, México,Coordinación de la Investigación Científica – Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México (UNAM). Ciudad de México, México,CONTACT Osbaldo Resendis-Antonio Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México (UNAM), Periferico Sur 4809, Arenal Tepepan, Tlalpan, 14610 Ciudad de México, CDMX
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25
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Copranaerobaculum intestinale gen. nov., sp. nov., a novel anaerobic bacterium isolated from human faeces. Int J Syst Evol Microbiol 2022; 72. [DOI: 10.1099/ijsem.0.005373] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
A novel obligate anaerobic organism, designated DONG20-135T, was isolated from human faeces collected in Beijing, PR China. Cells were Gram-stain-negative, rod-shaped, non-motile and non-spore-forming. Growth occurred at 25‒45 °C (optimum, 30‒35 °C), a pH range of 6–9 (optimum, pH 8) and in the presence of 0‒3.5 % (w/v) NaCl (optimum, 0.5‒1.5 %). The major fatty acids were C16 : 0, C18 : 1
ω9c and C10 : 0, the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, four glycolipids, six aminolipids, three aminophospholipids and four unidentified lipids. No respiratory quinones were detected. The cell-wall peptidoglycan of the strain was A1γ type, containing meso-diaminopimelic acid. The 16S rRNA gene sequences shared a lower identity (<92.7 % similarity) with the described species. The phylogenetic tree based on 16S rRNA gene sequences and the protein-concatamer tree showed that strain DONG20-135T formed a distinct lineage within the family
Erysipelotrichaceae
. The genomic DNA G + C content was 42.2 mol%. Based on the results of phenotypic, chemotaxonomic and genomic analyses, strain DONG20-135T represents a novel genus of the family
Erysipelotrichaceae
, for which the name Copranaerobaculum intestinale gen. nov., sp. nov. is proposed (=KCTC 15868T=CGMCC 1.17357T).
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26
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He Q, Liu L, Wei J, Jiang J, Rong Z, Chen X, Zhao J, Jiang K. Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review. Cell Death Dis 2022; 8:158. [PMID: 35379788 PMCID: PMC8979943 DOI: 10.1038/s41420-022-00962-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 12/13/2022]
Abstract
Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.
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Affiliation(s)
- Qijin He
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Limin Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Jingge Wei
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Jiaying Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Zheng Rong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
| | - Jingwen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
| | - Kui Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
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27
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Camastra S, Palumbo M, Santini F. Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation. Eat Weight Disord 2022; 27:449-461. [PMID: 33895917 PMCID: PMC8933374 DOI: 10.1007/s40519-021-01194-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 04/10/2021] [Indexed: 01/19/2023] Open
Abstract
Bariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB-less after SG-bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review.
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Affiliation(s)
- Stefania Camastra
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy. .,Interdepartmental Research Center "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
| | - Maria Palumbo
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy
| | - Ferruccio Santini
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.,Interdepartmental Research Center "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy
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28
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Stefura T, Zapała B, Gosiewski T, Skomarovska O, Pędziwiatr M, Major P. Changes in the Composition of Oral and Intestinal Microbiota After Sleeve Gastrectomy and Roux-En-Y Gastric Bypass and Their Impact on Outcomes of Bariatric Surgery. Obes Surg 2022; 32:1439-1450. [PMID: 35188608 PMCID: PMC8986729 DOI: 10.1007/s11695-022-05954-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/31/2022] [Accepted: 02/03/2022] [Indexed: 01/14/2023]
Abstract
Background We aimed to assess the changes in composition of bacterial microbiota at two levels of the digestive tract: oral cavity and large intestine in patients 6 months after bariatric surgery. Methods This was a prospective cohort study including patients undergoing bariatric surgery. Before surgery and 6 months after the procedure, oral swabs were obtained and stool samples were provided. Our endpoint was the analysis of the differences in compositions of oral and fecal microbiota prior and after the surgical treatment of obesity. Results Bacteria from phylum Bacteroidetes seemed to increase in abundance in both the oral cavity and the large intestine 6 months after surgery among patients undergoing bariatric surgery. The subgroup analysis we conducted based on the volume of weight-loss revealed that patients achieving at least 50% of excess weight loss present similar results to the entire study group. Patients with less favorable outcomes presented an increase in the population of bacteria from phylum Fusobacteria and a decrease of phylum Firmicutes in oral cavity. Conclusion Intestinal microbiota among these patients underwent similar changes in composition to the rest of the study group. Bariatric surgery introduces a significant change in composition of oral and intestinal microbiota. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1007/s11695-022-05954-9.
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Affiliation(s)
- Tomasz Stefura
- 2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2 st, 30-688 Cracow, Poland
| | - Barbara Zapała
- Department of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, 31-501 Cracow, Poland
| | - Tomasz Gosiewski
- Department of Microbiology, Division of Molecular Medical Microbiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Cracow, Poland
| | - Oksana Skomarovska
- 2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2 st, 30-688 Cracow, Poland
| | - Michał Pędziwiatr
- 2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2 st, 30-688 Cracow, Poland
- Centre for Research, Training and Innovation in Surgery (CERTAIN Surgery), 30-688 Cracow, Poland
| | - Piotr Major
- 2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2 st, 30-688 Cracow, Poland
- Centre for Research, Training and Innovation in Surgery (CERTAIN Surgery), 30-688 Cracow, Poland
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Intestinal transit rhythm and associated factors during the COVID-19 pandemic: a pilot study. Clin Nutr ESPEN 2022; 48:220-226. [PMID: 35331495 PMCID: PMC8849827 DOI: 10.1016/j.clnesp.2022.02.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 02/09/2022] [Accepted: 02/13/2022] [Indexed: 11/20/2022]
Abstract
Background & aims Social distancing may lead to changes in lifestyle, such as the reduction in physical exercise practice, dietary changes, weight alterations, as well as intestinal rhythm. Our study aimed to investigate the intestinal transit rhythm of adults during social distancing due to the COVID-19 pandemic, in association with sociodemographic variables, physical activity, nutritional status, frequency of food intake, and water intake. Methods Our cross-sectional study comprised an online questionnaire that was shared by the internet concerning demographic information (sex and age); physical activity; anthropometric data (reported weight and height); dietary habits information (food frequency of simple high-carbohydrates foods, whole food, and processed foods; water intake; intestinal transit rhythm). The survey was conducted from April and July 2020. Statistical analysis was performed using Pearson's chi-square test (χ2) or Fisher's exact test, considering p < 0.05. Results During social distancing, 72.5% of the respondents presented an adequate intestinal transit rhythm, and 27.5% had inadequate intestinal transit rhythm (19.0% slow and 8.5% rapid intestinal transit rhythm). Intestinal transit rhythm differs between sex, with women presenting significantly higher odds for altered bowel rhythm, compared to men (OR (95% CI) = 2.324 (1.027–5.257); p = 0.043). Also, results showed that individuals who frequently ingest simple high carb foods have high prevalence of slow intestinal transit rhythm (63%, p = 0.032). Conclusion In this study, we found a higher prevalence of adequate intestinal transit during social distancing due to the COVID-19 pandemic. Women had significantly higher odds for altered bowel rhythm, compared to men. Frequent consumption of simple carbohydrates was associated with a higher prevalence of slow intestinal transit rhythm.
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Bandopadhyay P, Ganguly D. Gut dysbiosis and metabolic diseases. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2022; 191:153-174. [DOI: 10.1016/bs.pmbts.2022.06.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Zhang M, Hu R, Huang Y, Zhou F, Li F, Liu Z, Geng Y, Dong H, Ma W, Song K, Song Y. Present and Future: Crosstalks Between Polycystic Ovary Syndrome and Gut Metabolites Relating to Gut Microbiota. Front Endocrinol (Lausanne) 2022; 13:933110. [PMID: 35928893 PMCID: PMC9343597 DOI: 10.3389/fendo.2022.933110] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 06/20/2022] [Indexed: 11/30/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common disease, affecting 8%-13% of the females of reproductive age, thereby compromising their fertility and long-term health. However, the pathogenesis of PCOS is still unclear. It is not only a reproductive endocrine disease, dominated by hyperandrogenemia, but also is accompanied by different degrees of metabolic abnormalities and insulin resistance. With a deeper understanding of its pathogenesis, more small metabolic molecules, such as bile acids, amino acids, and short-chain fatty acids, have been reported to be involved in the pathological process of PCOS. Recently, the critical role of gut microbiota in metabolism has been focused on. The gut microbiota-related metabolic pathways can significantly affect inflammation levels, insulin signaling, glucose metabolism, lipid metabolism, and hormonal secretions. Although the abnormalities in gut microbiota and metabolites might not be the initial factors of PCOS, they may have a significant role in the pathological process of PCOS. The dysbiosis of gut microbiota and disturbance of gut metabolites can affect the progression of PCOS. Meanwhile, PCOS itself can adversely affect the function of gut, thereby contributing to the aggravation of the disease. Inhibiting this vicious cycle might alleviate the symptoms of PCOS. However, the role of gut microbiota in PCOS has not been fully explored yet. This review aims to summarize the potential effects and modulative mechanisms of the gut metabolites on PCOS and suggests its potential intervention targets, thus providing more possible treatment options for PCOS in the future.
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Affiliation(s)
- Mingmin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Runan Hu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanjing Huang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fanru Zhou
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fan Li
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhuo Liu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuli Geng
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haoxu Dong
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenwen Ma
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kunkun Song
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yufan Song
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Yufan Song,
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Getahun D, Fassett MJ, Jacobsen SJ, Sacks DA, Murali SB, Peltier MR, Mulugeta W, Chiu VY, Wing DA, Coleman KJ. Perinatal outcomes after bariatric surgery. Am J Obstet Gynecol 2022; 226:121.e1-121.e16. [PMID: 34216568 DOI: 10.1016/j.ajog.2021.06.087] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/03/2021] [Accepted: 06/25/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Bariatric surgery is a widely used treatment option for obesity that often provides long-term weight control and health benefits. Although a growing number of women are becoming pregnant after bariatric surgery, only a few population-based studies have assessed the impact thereof on perinatal outcomes. OBJECTIVE This study aimed to examine the association between bariatric surgery and adverse perinatal outcomes in pregnant women and to examine whether the risk for adverse perinatal outcomes is modified by the postsurgery weight, gestational weight gain, type of bariatric surgery, timing of pregnancy after bariatric surgery, and maternal comorbidities. STUDY DESIGN A retrospective cohort study was performed with the use of the Bariatric Surgery Registry and hospital inpatient and outpatient physician encounter records. The International Classification of Diseases, Ninth and Tenth Revision codes from hospitalizations during pregnancy and infant birth records were used to ascertain the outcomes of interest. Women eligible for BS who delivered at ≥20 weeks of gestation (n=20,213) at Kaiser Permanente Southern California hospitals (January 1, 2007 to December 31, 2018) were included in the study. Adjusted odds ratios were derived from logistic regression models with inverse probability of treatment weighting to adjust for confounding using propensity scores. RESULTS Bariatric surgery was associated with a reduction in the risks for gestational diabetes (adjusted odds ratio, 0.60; 95% confidence interval, 0.53-0.69; P<.001), preeclampsia (adjusted odds ratio, 0.53; 95% confidence interval, 0.46-0.61; P<.001), chorioamnionitis (adjusted odds ratio, 0.45; 95% confidence interval, 0.32-0.63; P<.001), cesarean delivery (adjusted odds ratio, 0.65; 95% confidence interval, 0.59-0.72; P<.001), large for gestational age neonate (adjusted odds ratio, 0.23; 95% confidence interval, 0.19-0.29; P<.001), macrosomia (adjusted odds ratio, 0.24; 95% confidence interval, 0.19-0.30; P<.001), and neonatal intensive care unit admission (adjusted odds ratio, 0.70; 95% confidence interval, 0.61-0.81; P<.001). However, bariatric surgery was also associated with a significantly increased risk for small for gestational age neonates (adjusted odds ratio, 2.46; 95% confidence interval, 2.16-2.79; P<.001). The risk for the adverse outcomes is independent of the time interval between the surgery and subsequent pregnancy. CONCLUSION These data suggest that there are many pregnancy outcome benefits for women with severe obesity who undergo bariatric surgery; however, women who have undergone bariatric surgery before pregnancy should be monitored closely to reduce the risk for small for gestational age neonates and postpartum hemorrhage.
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Yue W, Huang X, Zhang W, Li S, Liu X, Zhao Y, Shu J, Liu T, Li W, Liu S. Metabolic Surgery on Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2022; 13:848947. [PMID: 35360056 PMCID: PMC8961297 DOI: 10.3389/fendo.2022.848947] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 02/09/2022] [Indexed: 11/13/2022] Open
Abstract
UNLABELLED Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease that is closely related to obesity. Metabolic surgery ameliorates a series of clinical manifestations and related comorbidities of PCOS. However, the overall efficacy of metabolic surgery on PCOS remains uncertain. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of metabolic surgery on obese patients with PCOS. A systematic literature search for relevant studies was conducted on PubMed, Embase, Web of Science, and the Cochrane Library from inception to June 2021. Data extraction and quality evaluation were performed by three researchers, and RevMan 5.4 software was used to conduct the meta-analysis. A total of 14 studies involving 501 obese patients with PCOS were included. Incidence of PCOS in obese women ranged from 5.5% to 63.5% among the included studies. The results showed the incidence of abnormal menstruation decreased from 81% to 15% (OR=0.03, 95% confidence interval (CI): 0.01-0.08), while the incidence of hirsutism dropped from 71% to 38% (OR=0.21, 95% CI: 0.06-0.74). Serum total testosterone and free testosterone levels decreased by 25.92 ng/dL (MD = -25.92, 95% CI: -28.90- -22.93) and 2.28 ng/dL (SMD = -2.28, 95% CI: -3.67- -0.89), respectively. Sex hormone-binding globulin (SHBG) levels increased by 26.46 nmol/L (MD = 26.46, 95% CI: 12.97-39.95). Serum anti-Mullerian hormone (AMH) levels decreased by 1.29 ng/mL (MD = -1.29, 95% CI: -1.92- -0.66). Small sample size studies revealed that pregnancy rates ranged from 95.2% to 100% postoperatively. Metabolic surgery contributed to marked improvement of abnormal menstruation, hirsutism, and levels of free testosterone, total testosterone, SHBG, and AMH in patients with PCOS. Our findings indicate that patients with PCOS are expected to benefit from metabolic surgery, and could help potentially improve their reproductive outcomes. Metabolic surgery could thus be a new viable option for the clinical treatment of PCOS. SYSTEMATIC REVIEW REGISTRATION PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021251524.
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Affiliation(s)
- Wenwen Yue
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xin Huang
- Division of Bariatric and Metabolic Surgery, Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Wenjing Zhang
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shumin Li
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
| | - Xu Liu
- School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yian Zhao
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jiaxin Shu
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Teng Liu
- Division of Bariatric and Metabolic Surgery, Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Weihua Li
- Operating Theater, Qilu Hospital of Shandong University, Jinan, China
- *Correspondence: Shaozhuang Liu, ; Weihua Li,
| | - Shaozhuang Liu
- Division of Bariatric and Metabolic Surgery, Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
- *Correspondence: Shaozhuang Liu, ; Weihua Li,
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Portincasa P, Bonfrate L, Khalil M, Angelis MD, Calabrese FM, D’Amato M, Wang DQH, Di Ciaula A. Intestinal Barrier and Permeability in Health, Obesity and NAFLD. Biomedicines 2021; 10:83. [PMID: 35052763 PMCID: PMC8773010 DOI: 10.3390/biomedicines10010083] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/20/2021] [Accepted: 12/28/2021] [Indexed: 02/07/2023] Open
Abstract
The largest surface of the human body exposed to the external environment is the gut. At this level, the intestinal barrier includes luminal microbes, the mucin layer, gastrointestinal motility and secretion, enterocytes, immune cells, gut vascular barrier, and liver barrier. A healthy intestinal barrier is characterized by the selective permeability of nutrients, metabolites, water, and bacterial products, and processes are governed by cellular, neural, immune, and hormonal factors. Disrupted gut permeability (leaky gut syndrome) can represent a predisposing or aggravating condition in obesity and the metabolically associated liver steatosis (nonalcoholic fatty liver disease, NAFLD). In what follows, we describe the morphological-functional features of the intestinal barrier, the role of major modifiers of the intestinal barrier, and discuss the recent evidence pointing to the key role of intestinal permeability in obesity/NAFLD.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
| | - Leonilde Bonfrate
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
| | - Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (M.D.A.); (F.M.C.)
| | - Maria De Angelis
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (M.D.A.); (F.M.C.)
| | - Francesco Maria Calabrese
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (M.D.A.); (F.M.C.)
| | - Mauro D’Amato
- Gastrointestinal Genetics Lab, CIC bioGUNE-BRTA, 48160 Derio, Spain;
- Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain
| | - David Q.-H. Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, New York, NY 10461, USA;
| | - Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
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Dreyfuss JM, Yuchi Y, Dong X, Efthymiou V, Pan H, Simonson DC, Vernon A, Halperin F, Aryal P, Konkar A, Sebastian Y, Higgs BW, Grimsby J, Rondinone CM, Kasif S, Kahn BB, Foster K, Seeley R, Goldfine A, Djordjilović V, Patti ME. High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control. Nat Commun 2021; 12:6951. [PMID: 34845204 PMCID: PMC8630169 DOI: 10.1038/s41467-021-27289-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 11/11/2021] [Indexed: 12/13/2022] Open
Abstract
To improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR's mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling.Trial Registration: Clinicaltrials.gov NCT01073020.
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Affiliation(s)
- Jonathan M Dreyfuss
- Bioinformatics and Biostatistics Core, Research Division, Joslin Diabetes Center, Boston, MA, USA
- Biomedical Engineering, Boston University, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Yixing Yuchi
- Harvard Medical School, Boston, MA, USA
- Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA
- Vertex Pharmaceuticals, Boston, MA, USA
| | - Xuehong Dong
- Harvard Medical School, Boston, MA, USA
- Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Endocrinology, Diabetes & Metabolism, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Vissarion Efthymiou
- Harvard Medical School, Boston, MA, USA
- Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA
| | - Hui Pan
- Bioinformatics and Biostatistics Core, Research Division, Joslin Diabetes Center, Boston, MA, USA
- Biomedical Engineering, Boston University, Boston, MA, USA
| | - Donald C Simonson
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Ashley Vernon
- Harvard Medical School, Boston, MA, USA
- Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA
| | - Florencia Halperin
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Form Health, Boston, MA, USA
| | - Pratik Aryal
- Harvard Medical School, Boston, MA, USA
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Anish Konkar
- MedImmune, Gaithersburg, MD, USA
- Eli Lilly and Company, Indianapolis, IN, USA
| | | | | | - Joseph Grimsby
- MedImmune, Gaithersburg, MD, USA
- AstraZeneca, Gaithersburg, MD, USA
| | | | - Simon Kasif
- Biomedical Engineering, Boston University, Boston, MA, USA
| | - Barbara B Kahn
- Harvard Medical School, Boston, MA, USA
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Kathleen Foster
- Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA
| | - Randy Seeley
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Allison Goldfine
- Harvard Medical School, Boston, MA, USA
- Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
- Novartis Institute for Biomedical Research, Cambridge, MA, USA
| | - Vera Djordjilović
- Department of Economics, Ca' Foscari University of Venice, Venice, Italy
| | - Mary Elizabeth Patti
- Harvard Medical School, Boston, MA, USA.
- Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Boston, MA, USA.
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Hegazy WAH, Rajab AAH, Abu Lila AS, Abbas HA. Anti-diabetics and antimicrobials: Harmony of mutual interplay. World J Diabetes 2021; 12:1832-1855. [PMID: 34888011 PMCID: PMC8613656 DOI: 10.4239/wjd.v12.i11.1832] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/26/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes is one of the four major non-communicable diseases, and appointed by the world health organization as the seventh leading cause of death worldwide. The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes. The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes, assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation. On a parallel basis, microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment, all of which can be reversed by antimicrobial treatment. Standing at the crossroads between diabetes, immunity and infection, we aim in this review at projecting the interplay between immunity and diabetes, shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents. Furthermore, we focused on the anti-diabetic drugs that can confer antimicrobial or anti-virulence activities.
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Affiliation(s)
- Wael A H Hegazy
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
| | - Azza A H Rajab
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
| | - Amr S Abu Lila
- Department of Pharmaceutics, Zagazig University, Faculty of Pharmacy, Zagzig 44519, Egypt
- Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
| | - Hisham A Abbas
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
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Microbiome Changes after Type 2 Diabetes Treatment: A Systematic Review. ACTA ACUST UNITED AC 2021; 57:medicina57101084. [PMID: 34684121 PMCID: PMC8540512 DOI: 10.3390/medicina57101084] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 12/12/2022]
Abstract
Background and objectives: Although the role of the gut microbiome in type 2 diabetes (T2D) pathophysiology is evident, current systematic reviews and meta-analyses analyzing T2D treatment mainly focus on metabolic outcomes. The objective of this study is to evaluate the microbiome and metabolic changes after different types of treatment in T2D patients. Materials and Methods: A systematic search of PubMed, Wiley online library, Science Direct, and Cochrane library electronic databases was performed. Randomized controlled clinical trials published in the last five years that included T2D subjects and evaluated the composition of the gut microbiome alongside metabolic outcomes before and after conventional or alternative glucose lowering therapy were selected. Microbiome changes were evaluated alongside metabolic outcomes in terms of bacteria taxonomic hierarchy, intestinal flora biodiversity, and applied intervention. Results: A total of 16 eligible studies involving 1301 participants were reviewed. Four trials investigated oral glucose-lowering treatment, three studies implemented bariatric surgery, and the rest analyzed probiotic, prebiotic, or synbiotic effects. The most common alterations were increased abundance of Firmicutes and Proteobacteria parallel to improved glycemic control. Bariatric surgery, especially Roux-en-Y gastric bypass, led to the highest variety of changed bacteria phyla. Lower diversity post-treatment was the most significant biodiversity result, which was present with improved glycemic control. Conclusions: Anti-diabetic treatment induced the growth of depleted bacteria. A gut microbiome similar to healthy individuals was achieved during some trials. Further research must explore the most effective strategies to promote beneficial bacteria, lower diversity, and eventually reach a non-T2D microbiome.
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Li Y, Wang S, Hu Y, Cheng J, Cheng X, Cheng P, Cui Z. Dietary bile acid supplementation reveals beneficial effects on intestinal healthy status of tongue sole (Cynoglossus semiliaevis). FISH & SHELLFISH IMMUNOLOGY 2021; 116:52-60. [PMID: 34216786 DOI: 10.1016/j.fsi.2021.06.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/27/2021] [Accepted: 06/29/2021] [Indexed: 06/13/2023]
Abstract
The aim of this study was to investigate the effects of dietary bile acids (BAs) on intestinal healthy status of tongue sole in terms of immunity, antioxidant status, digestive ability, mucosal barrier-related genes expression and microbiota. Three experimental diets were prepared with BA levels at 0 mg/kg (CT), 300 mg/kg (BA1) and 900 mg/kg (BA2) in a commercial basal diet. Each diet was fed to three replicates with 120 fish (10.87 ± 0.32 g) in each tank. After an 8-week feeding trial, growth parameters were significantly enhanced in both BAs supplementary groups (P < 0.05), and compared with CT group, survival rate in BA2 group was significantly improved (P < 0.05). Intestinal lysozyme activity and contents of immunoglobulin M and complement 3 were significantly increased in both BAs supplementary groups (P < 0.05), suggesting an enhancement effect on the non-specific immune response. BAs inclusion also significantly improved intestinal antioxidant capabilities by increasing antioxidase activities and decreasing malondialdehyde levels. In addition, compared with CT group, intestinal digestive ability was substantially enhanced as indicated by the significantly increased lipase activity in BA2 group (P < 0.05) and significantly increased amylase activity in BA1 and BA2 groups (P < 0.05). Coincidentally, BAs inclusion significantly upregulated the relative expression of intestinal mucosal barrier-related genes (P < 0.05). Further, dietary BAs distinctly remodeled intestinal microbiota by decreased the abundance of some potential pathogenic bacteria. In conclusion, dietary BAs supplementation is an effective way to improve the intestinal healthy status of tongue sole.
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Affiliation(s)
- Yangzhen Li
- Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Shengpeng Wang
- Dezhou Key Laboratory for Applied Bile Acid Research, Shandong Longchang Animal Health Product CO., Ltd., Dezhou 251100, China.
| | - Yuanri Hu
- Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Jiayu Cheng
- Engineering and Technology Center for Flatfish Aquaculture of Tangshan, Tangshan Weizhuo Aquaculture Co., Ltd., Tangshan 063202, China
| | - Xiangming Cheng
- Engineering and Technology Center for Flatfish Aquaculture of Tangshan, Tangshan Weizhuo Aquaculture Co., Ltd., Tangshan 063202, China
| | - Peng Cheng
- Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
| | - Zhongkai Cui
- Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
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Duan L, An X, Zhang Y, Jin D, Zhao S, Zhou R, Duan Y, Zhang Y, Liu X, Lian F. Gut microbiota as the critical correlation of polycystic ovary syndrome and type 2 diabetes mellitus. Biomed Pharmacother 2021; 142:112094. [PMID: 34449321 DOI: 10.1016/j.biopha.2021.112094] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 08/05/2021] [Accepted: 08/20/2021] [Indexed: 12/16/2022] Open
Abstract
Gut microbiota forms a symbiotic relationship with the host and maintains the ecological balance of the internal and external environment of the human body. However, dysbiosis of the gut microbiota and immune deficiency, as well as environmental changes, can destroy the host-microbial balance, leading to the occurrence of a variety of diseases, such as polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), and obesity. Meanwhile, diseases can also affect gut microbiota, forming a vicious cycle. The role of the intestinal microbiota in different diseases have been proven by several studies; however, as a common target of PCOS and T2DM, there are few reports on the treatment of different diseases through the regulation of intestinal microbiota as the critical correlation. This review analyzed the common mechanisms of intestinal microbiota in PCOS and T2DM, including the dysbiosis of gut microbiota, endotoxemia, short-chain fatty acids, biotransformation of bile acids, and synthesis of amino acid in regulating insulin resistance, obesity, chronic inflammation, and mitochondrial dysfunction. The possible therapeutic effects of probiotics and/or prebiotics, fecal microbiota transplantation, bariatric surgery, dietary intervention, drug treatment, and other treatments targeted at regulating intestinal microbiota were also elucidated.
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Affiliation(s)
- Liyun Duan
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Xuedong An
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yuehong Zhang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - De Jin
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Shenghui Zhao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; Beijing University of Chinese Medicine, Beijing 100029, China
| | - Rongrong Zhou
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yingying Duan
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yuqing Zhang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Xinmin Liu
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
| | - Fengmei Lian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
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Grøndahl MFG, Johannesen J, Kristensen K, Knop FK. Treatment of type 2 diabetes in children: what are the specific considerations? Expert Opin Pharmacother 2021; 22:2127-2141. [PMID: 34420454 DOI: 10.1080/14656566.2021.1954160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: The number of individuals under 18 years of age with type 2 diabetes is increasing at an alarming rate worldwide. These patients are often characterized by obesity and they often experience a more rapid disease progression than adults with type 2 diabetes. Thus, focus on prevention and management of complications and comorbidities is imperative. With emphasis on weight loss and optimal glycemic control, treatment includes lifestyle changes and pharmacotherapy, which in this patient group is limited to metformin, liraglutide and insulin. In selected cases, bariatric surgery is indicated.Areas covered: This perspective article provides an overview of the literature covering pathophysiology, diagnosis, characteristics and treatment of pediatric type 2 diabetes, and outlines the gaps in our knowledge where further research is needed. The paper draws on both mechanistic studies, large scale intervention trials, epidemiological studies and international consensus statements.Expert opinion: Type 2 diabetes in pediatric patients is an increasing health care problem, and the current treatment strategies do not successfully meet the many challenges and obstacles in this patient group. Treatments must be early, intensive, multifaceted and durable. Also, prevention of obesity and type 2 diabetes in at-risk children should be addressed and prioritized on all levels.
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Affiliation(s)
- Magnus F G Grøndahl
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jesper Johannesen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Pediatrics, Copenhagen University Hospital, Herlev and Gentofte, Denmark
| | - Kurt Kristensen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Steno Diabetes Center Aarhus - Children and Adolescence, Aarhus University, Aarhus, Denmark
| | - Filip K Knop
- Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Steno Diabetes Center Copenhagen, Gentofte, Denmark.,Novo Nordisk Foundation for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Zhang C, Yang M. The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:3740. [PMID: 34359642 PMCID: PMC8345138 DOI: 10.3390/cancers13153740] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/22/2021] [Accepted: 07/24/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.
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Affiliation(s)
- Chunye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA;
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65211, USA
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Mueller A, Palilla S, Carter J. Optimal Surgical Treatment for Type 2 Diabetes: Sleeve Gastrectomy or Gastric Bypass? Adv Surg 2021; 55:1-8. [PMID: 34389085 DOI: 10.1016/j.yasu.2021.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Amanda Mueller
- Department of Surgery, University of California - San Francisco, 513 Parnassus Avenue, HSW1601, San Francisco, CA 94143, USA
| | - Sarah Palilla
- Department of Surgery, University of California - San Francisco, 513 Parnassus Avenue, HSW1601, San Francisco, CA 94143, USA
| | - Jonathan Carter
- Department of Surgery, University of California - San Francisco, 513 Parnassus Avenue, HSW1601, San Francisco, CA 94143, USA.
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Sauter ER, Heckman-Stoddard B. Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research. Cancers (Basel) 2021; 13:cancers13133183. [PMID: 34202319 PMCID: PMC8268861 DOI: 10.3390/cancers13133183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 06/22/2021] [Indexed: 12/19/2022] Open
Abstract
Simple Summary Metabolic (bariatric) surgery (MBS) provides the greatest maximum and sustained weight loss among individuals who are morbidly obese. It is more effective than lifestyle interventions in improving or eliminating type 2 diabetes mellitus (T2DM) and in decreasing cardiovascular (CV) risk. Preclinical studies have been conducted to investigate the mechanisms by which MBS leads to the benefits in T2DM and CV risk. In this review, we describe the emerging evidence that MBS may also impact cancer risk and mortality, and whom may benefit most. We describe the long term involvement and commitment of the National Institutes of Health in obesity research in general and MBS in particular. We outline the need for additional research to understand the mechanism(s) by which MBS may influence cancer, since these mechanism(s) are currently unknown. Abstract Metabolic (bariatric) surgery (MBS) is recommended for individuals with a BMI > 40 kg/m2 or those with a BMI 35–40 kg/m2 who have one or more obesity related comorbidities. MBS leads to greater initial and sustained weight loss than nonsurgical weight loss approaches. MBS provides dramatic improvement in metabolic function, associated with a reduction in type 2 diabetes mellitus and cardiovascular risk. While the number of MBS procedures performed in the U.S. and worldwide continues to increase, they are still only performed on one percent of the affected population. MBS also appears to reduce the risk of certain obesity related cancers, although which cancers are favorably impacted vary by study, who benefits most is uncertain, and the mechanism(s) driving this risk reduction are mostly speculative. The goal of this manuscript is to highlight (1) emerging evidence that MBS influences cancer risk, and that the potential benefit appears to vary based on cancer, gender, surgical procedure, and likely other variables; (2) the role of the NIH in MBS research in T2DM and CV risk for many years, and more recently in cancer; and (3) the opportunity for research to understand the mechanism(s) by which MBS influences cancer. There is evidence that women benefit more from MBS than men, that MBS may actually increase the risk of colorectal cancer in both women and men, and there is speculation that the benefit in cancer risk reduction may vary according to which MBS procedure an individual undergoes. Herein, we review what is currently known, the historical role of government, especially the National Institutes of Health (NIH), in driving this research, and provide suggestions that we believe could lead to a better understanding of whether and how MBS impacts cancer risk, which cancers are impacted either favorably or unfavorably, the role of the NIH and other research agencies, and key questions to address that will help us to move the science forward.
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Berkovskaya MA, Sych YP, Gurova OY, Fadeev VV. Significance of intestinal microbiota in implementing metabolic effects of bariatric surgery. RUSSIAN OPEN MEDICAL JOURNAL 2021. [DOI: 10.15275/rusomj.2021.0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Bariatric surgery is among successful methods of obesity treatment, with effects going beyond weight reduction alone, but rather involving improved glucose tolerance, along with control or remission of the type 2 diabetes mellitus. The precise mechanisms causing metabolic effects of bariatric surgery are not fully elucidated, even though substantial evidence suggest that they include changes in the gut microbiota, bile acid homeostasis, and the close interactions of these factors.
Intestinal microflora is directly involved in the energy metabolism of a host human. Obesity and type 2 diabetes mellitus are associated with certain changes in the species composition and diversity of intestinal microflora, which are considered important factors in the development and progression of these ailments. Bariatric surgery leads to significant and persistent changes in the composition of the intestinal microbiota, often bringing it closer to the characteristics of the microbiota of an average person with a normal weight. An important role in implementing the metabolic effects of bariatric surgery, primarily in the improvement of glucose metabolism, belongs to postoperative changes in homeostasis of bile acids. These changes imply close metabolism. Moreover, changes in the bile acid metabolism after bariatric surgery affect the microbiota of the host. Further study of these relationships would clarify the mechanisms underlying metabolic surgery, make it more predictable, targeted and controlled, as well as open new therapeutic targets in the treatment of obesity and associated conditions.
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Affiliation(s)
| | - Yulia P. Sych
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Olesya Yu. Gurova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Valentin V. Fadeev
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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Type 2 diabetes mellitus status in obese patients following sleeve gastrectomy or one anastomosis gastric bypass. Sci Rep 2021; 11:4421. [PMID: 33627710 PMCID: PMC7904834 DOI: 10.1038/s41598-021-83807-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 02/08/2021] [Indexed: 02/06/2023] Open
Abstract
This study aims to compare sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB) in terms of remission of type 2 diabetes mellitus (T2DM) in obese patients. All T2DM patients were followed-up for at least 36 months. The primary outcome was remission of T2DM. Secondary endpoints included weight reduction and the procedure’s impact on quality of life. In total, 53/1177 morbidly obese patients who underwent SG (Group A, n = 28) or OAGB (Group B, n = 25) had T2DM. Preoperatively, the mean Body Mass Index (BMI) values were 52.2 ± 8.5 kg/m2 and 52.9 ± 10.9 kg/m2 for Group A and Group B, respectively. Six patients in Group A were insulin dependent, while 8 were insulin dependent in Group B. After 36 months, diabetes remission was achieved by only 10 patients (35.7%) in Group A. However, in Group B, 22 patients (88%) remained off antidiabetic agents (p < 0.0001), with ΔHbA1c (%) reaching 1.4 ± 1.5% in Group A and 2.7 ± 2.1% in Group B (p = 0.02). Excess weight loss% (%EWL) was again significantly different between the two groups (MA = 79.8 ± 14.5%, MB = 93.3 ± 16.0%, p = 0.003). OAGB is more effective in improving glycaemic control and %EWL, with almost immediate resolution of diabetes, as well as long-term weight loss.
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Ke Z, Li F, Gao Y, Tan D, Sun F, Zhou X, Chen J, Lin X, Zhu Z, Tong W. The Use of Visceral Adiposity Index to Predict Diabetes Remission in Low BMI Chinese Patients After Bariatric Surgery. Obes Surg 2021; 31:805-812. [PMID: 33063158 DOI: 10.1007/s11695-020-05034-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 10/01/2020] [Accepted: 10/06/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Visceral Adiposity Index (VAI) is considered to be a reliable indicator for evaluation of visceral adipose dysfunction and cardiovascular disease risk. However, no previous studies have reported the VAI variation after bariatric surgery and the predictive effect of preoperative VAI on diabetes remission. The aim of this study is to evaluate whether preoperative VAI is useful to predict diabetes remission in low BMI Chinese patients after bariatric surgery. METHODS Eighty-seven type 2 diabetes mellitus patients with BMI < 35 kg/m2 underwent bariatric surgery from May 2010 to March 2018 in our hospital. VAI, glycolipid metabolic parameters, and anthropometric variables were measured before and 4 years after surgery. Complete remission was defined as follows: HbA1c < 6%, FPG < 5.6 mmol/L, achieved without anti-diabetic medication. Analysis included using binary logistic regression to identify predictors and ROC curves to determine clinically useful cutoff values. RESULTS Seventy-four patients (85.1%) underwent Roux-en-Y gastric bypass (RYGB), while the remaining 13 patients (14.9%) underwent sleeve gastrectomy (SG). Patients' weight, glycemic control, and lipid profiles were improved significantly after surgery (p < 0.05). Complete remission of T2DM was found in 35 patients (40.2%) 1 year after surgery. VAI decreased from baseline 4.41 to 1.74 in 3 months after surgery (p < 0.05) and showed a downward trend over the period from 6 months to 4 years. Patients with complete remission had a significantly shorter duration of diabetes, lower HbA1c level, and higher VAI, in comparison to those without remission. Binary logistics regression and ROC curves analysis confirm that VAI, HbA1c, and duration of diabetes can predict diabetes remission after bariatric surgery, and the VAI of 4.46 is a useful threshold for predicting surgical efficacy. CONCLUSION VAI is a significant predictor of diabetes remission for lower BMI patients with T2DM following bariatric surgery in China. The VAI of 4.46 is a useful threshold for predicting surgical efficacy. Multi-center and larger prospective studies are needed to confirm our findings.
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Affiliation(s)
- Zhigang Ke
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Fan Li
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Yu Gao
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Dewen Tan
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, China
| | - Fang Sun
- Department of Hypertension and Endocrinology, Daping Hospital, Army Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing, 400042, China
| | - Xunmei Zhou
- Department of Hypertension and Endocrinology, Daping Hospital, Army Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing, 400042, China
| | - Jing Chen
- Department of Hypertension and Endocrinology, Daping Hospital, Army Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing, 400042, China
| | - Xia Lin
- Department of General Surgery, Chongqing Three Goreges Central Hospital, Wanzhou, Chongqing, 404000, China
| | - Zhiming Zhu
- Department of Hypertension and Endocrinology, Daping Hospital, Army Medical University, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Chongqing, 400042, China
| | - Weidong Tong
- Department of General Surgery, Daping Hospital, Army Medical University, Chongqing, 400042, China.
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Stefura T, Zapała B, Gosiewski T, Krzysztofik M, Skomarovska O, Major P. Relationship between bariatric surgery outcomes and the preoperative gastrointestinal microbiota: a cohort study. Surg Obes Relat Dis 2021; 17:889-899. [PMID: 33619006 DOI: 10.1016/j.soard.2021.01.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 12/02/2020] [Accepted: 01/06/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND The composition of the gastrointestinal microbiota is associated with obesity. We hypothesized that the gut microbiota influences the outcomes of bariatric surgery. OBJECTIVES We aimed to analyze using oral swabs and stool samples the microbiota of patients with morbid obesity who were undergoing laparoscopic sleeve gastrectomy (SG). SETTING A university hospital in Poland. METHODS This prospective cohort study was conducted between November 2018 and June 2019. Participants underwent SG or no surgery (controls). Results were then analyzed as a group 1 (surgical participants who achieved a percentage of excess weight loss [%EWL] >50%), group 2 (surgical participants who achieved a %EWL <50%), and group 3 (nonsurgical controls). %EWL was measured 6 months following surgery. Before surgery, oral swabs were obtained and stool samples were provided. The endpoint was the composition of the gut microbiota. RESULTS Group 1 comprised 19 participants, group 2 comprised 11 participants, and group 3 comprised 16 participants. No participants were lost to follow-up during the study. Participants in group 1 had an oral microbiota that was enriched in the phyla Proteobacteria, and Bacteroidetes. Their intestinal microbiota was enriched in the Proteobacteria. In contrast, the oral microbiota of group 2 was enriched in the Actinobacteria and the intestinal microbiota was enriched in the phyla Bacteroidetes and Firmicutes. CONCLUSIONS The compositions of the microbiota of the oral cavity and large intestine are related to the weight loss achieved following SG.
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Affiliation(s)
- Tomasz Stefura
- 2nd Department of General Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Barbara Zapała
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
| | - Tomasz Gosiewski
- Department of Microbiology, Jagiellonian University Medical College, Krakow, Poland
| | - Marta Krzysztofik
- 2nd Department of General Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Oksana Skomarovska
- 2nd Department of General Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Piotr Major
- 2nd Department of General Surgery, Jagiellonian University Medical College, Krakow, Poland; Centre for Research, Training and Innovation in Surgery, Krakow, Poland.
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Guimarães M, Pereira SS, Monteiro MP. From Entero-Endocrine Cell Biology to Surgical Interventional Therapies for Type 2 Diabetes. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1307:273-297. [PMID: 32016913 DOI: 10.1007/5584_2020_480] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The physiological roles of the enteroendocrine system in relation to energy and glucose homeostasis regulation have been extensively studied in the past few decades. Considerable advances were made that enabled to disclose the potential use of gastro-intestinal (GI) hormones to target obesity and type 2 diabetes (T2D). The recognition of the clinical relevance of these discoveries has led the pharmaceutical industry to design several hormone analogues to either to mitigate physiological defects or target pharmacologically T2D.Amongst several advances, a major breakthrough in the field was the unexpected observation that enteroendocrine system modulation to T2D target could be achieved by surgically induced anatomical rearrangement of the GI tract. These findings resulted from the widespread use of bariatric surgery procedures for obesity treatment, which despite initially devised to induce weight loss by limiting the systemic availably of nutrients, are now well recognized to influence GI hormone dynamics in a manner that is highly dependent on the type of anatomical rearrangement produced.This chapter will focus on enteroendocrine system related mechanisms leading to improved glycemic control in T2D after bariatric surgery interventions.
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Affiliation(s)
- Marta Guimarães
- Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.,Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.,Department of General Surgery, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal
| | - Sofia S Pereira
- Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.,Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.,Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Porto, Portugal.,Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal
| | - Mariana P Monteiro
- Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal. .,Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
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Chaudhari SN, Luo JN, Harris DA, Aliakbarian H, Yao L, Paik D, Subramaniam R, Adhikari AA, Vernon AH, Kiliç A, Weiss ST, Huh JR, Sheu EG, Devlin AS. A microbial metabolite remodels the gut-liver axis following bariatric surgery. Cell Host Microbe 2021; 29:408-424.e7. [PMID: 33434516 DOI: 10.1016/j.chom.2020.12.004] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 10/15/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023]
Abstract
Bariatric surgery is the most effective treatment for type 2 diabetes and is associated with changes in gut metabolites. Previous work uncovered a gut-restricted TGR5 agonist with anti-diabetic properties-cholic acid-7-sulfate (CA7S)-that is elevated following sleeve gastrectomy (SG). Here, we elucidate a microbiome-dependent pathway by which SG increases CA7S production. We show that a microbial metabolite, lithocholic acid (LCA), is increased in murine portal veins post-SG and by activating the vitamin D receptor, induces hepatic mSult2A1/hSULT2A expression to drive CA7S production. An SG-induced shift in the microbiome increases gut expression of the bile acid transporters Asbt and Ostα, which in turn facilitate selective transport of LCA across the gut epithelium. Cecal microbiota transplant from SG animals is sufficient to recreate the pathway in germ-free (GF) animals. Activation of this gut-liver pathway leads to CA7S synthesis and GLP-1 secretion, causally connecting a microbial metabolite with the improvement of diabetic phenotypes.
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Affiliation(s)
- Snehal N Chaudhari
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
| | - James N Luo
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - David A Harris
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Hassan Aliakbarian
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Lina Yao
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Donggi Paik
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Renuka Subramaniam
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Arijit A Adhikari
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Ashley H Vernon
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Ayse Kiliç
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
| | - Scott T Weiss
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Program in Molecular Integrative Physiological Sciences, Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MA 02115, USA
| | - Jun R Huh
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Eric G Sheu
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
| | - A Sloan Devlin
- Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
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Woźniewska P, Diemieszczyk I, Groth D, Szczerbiński Ł, Choromańska B, Błachnio-Zabielska A, Krętowski A, Hady HR. The influence of patient's age on metabolic and bariatric results of laparoscopic sleeve gastrectomy in 2-year observation. BMC Surg 2020; 20:323. [PMID: 33298009 PMCID: PMC7727122 DOI: 10.1186/s12893-020-00989-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 11/29/2020] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND The incidence of obesity has been constantly growing and bariatric procedures are considered to be the most effective treatment solution for morbidly obese patients. The results of laparoscopic sleeve gastrectomy (LSG) may differ depending on patient's age, gender, preoperative body mass index (BMI) and physical activity. METHODS The aim of this study was to evaluate age-related differences in the outcome of LSG in terms of weight loss parameters, lipid and carbohydrate profile. The retrospective analysis of 555 patients who had undergone LSG was performed to compare the metabolic outcomes of surgery in individuals < 45 and ≥ 45 years old. Evaluation of weight loss parameters along with selected laboratory data was performed to demonstrate the results of LSG in 2 years follow-up. RESULTS Overall, 238 males and 317 females (43%/57%) with median age of 43 years and median preoperative BMI of 46.41 (42.06-51.02) kg/m2 were analyzed. Patients in both groups presented significant weight loss at 24 months after the surgery with comparable percentage of total weight loss (40.95% in < 45 years old group and 40.44% in ≥ 45 years old group). The percentage of excess weight loss (78.52% vs. 74.53%) and percentage of excess BMI loss (91.95% vs. 88.01%) were higher in patients < 45 years old. However, the differences were not statistically significant (p = 0.662, p = 0.788 respectively). Patients under 45 years old experienced faster decrease in fasting glucose level that was observed after only 3 months (109 mg/dl to 95 mg/dl in < 45 years old group vs. 103.5 mg/dl to 99.5 mg/dl in ≥ 45 years old group, p < 0.001). Both groups presented improvement of lipid parameters during the observation. However, patients < 45 years old achieved lower values of LDL at 3 and 12 months follow-up (115 mg/dl vs. 126 mg/dl, p = 0.010; 114.8 mg/dl vs. 122 mg/dl, p = 0.002). Younger group of patients also showed superior improvement of triglycerides level. CONCLUSIONS LSG results in significant weight loss in all patients regardless age. In turn, superior and faster improvement in lipid and carbohydrate profile is achieved in patients under 45 years old.
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Affiliation(s)
- Paulina Woźniewska
- 1St Department of General and Endocrine Surgery, Medical University of Bialystok, ul. Marii Skłodowskiej-Curie 24A, 15-276, Bialystok, Poland.
| | - Inna Diemieszczyk
- 1St Department of General and Endocrine Surgery, Medical University of Bialystok, ul. Marii Skłodowskiej-Curie 24A, 15-276, Bialystok, Poland
| | - Dawid Groth
- Eastern Center of the Burns Treatment and Reconstructive Surgery, Independent Public Health Care Center in Łeczna, Łęczna, Poland
| | - Łukasz Szczerbiński
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Barbara Choromańska
- 1St Department of General and Endocrine Surgery, Medical University of Bialystok, ul. Marii Skłodowskiej-Curie 24A, 15-276, Bialystok, Poland
| | | | - Adam Krętowski
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Hady Razak Hady
- 1St Department of General and Endocrine Surgery, Medical University of Bialystok, ul. Marii Skłodowskiej-Curie 24A, 15-276, Bialystok, Poland
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