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Obesity Surgery
Published in: Obesity Surgery 5/2019

01-05-2019 | Sleeve Gastrectomy | Original Contributions

TGR5 Protects Against Colitis in Mice, but Vertical Sleeve Gastrectomy Increases Colitis Severity

Authors: Darline Garibay, Karolina E. Zaborska, Michael Shanahan, Qiaonan Zheng, Katie M. Kelly, David C. Montrose, Andrew J. Dannenberg, Andrew D. Miller, Praveen Sethupathy, Bethany P. Cummings

Published in: Obesity Surgery | Issue 5/2019

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Abstract

Background and Aims

Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is the most effective long-term treatment for obesity. However, there are conflicting reports on the effect of bariatric surgery on inflammatory bowel disease (IBD). Bariatric surgery increases bile acid concentrations, which can decrease inflammation by signaling through the bile acid receptor, TGR5. TGR5 signaling protects against chemically induced colitis in mice. VSG increases circulating bile acid concentrations to increase TGR5 signaling, which contributes to improved metabolic regulation after VSG. Therefore, we investigated the effect of VSG on chemically induced colitis development and the role of TGR5 in this context.

Methods

VSG or sham surgery was performed in high fat diet-fed male Tgr5+/+ and Tgr5−/− littermates. Sham-operated mice were food restricted to match their body weight to VSG-operated mice. Colitis was induced with 2.5% dextran sodium sulfate (DSS) in water post-operatively. Body weight, energy intake, fecal scoring, colon histopathology, colonic markers of inflammation, goblet cell counts, and colonic microRNA-21 levels were assessed.

Results

VSG decreased body weight independently of genotype. Consistent with previous work, genetic ablation of TGR5 increased the severity of DSS-induced colitis. Notably, despite the effect of VSG to decrease body weight and increase TGR5 signaling, VSG increased the severity of DSS-induced colitis. VSG-induced increases in colitis were associated with increased colonic expression of TNF-α, IL-6, MCP-1, and microRNA-21.

Conclusions

While our data demonstrate that TGR5 protects against colitis, they also demonstrate that VSG potentiates chemically induced colitis in mice. These data suggest that individuals undergoing VSG may be at increased risk for developing colitis; however, further study is needed.
Literature
1.
Wehkamp J, Götz M, Herrlinger K, et al. Inflammatory bowel disease: Crohn’s disease and ulcerative colitis. Dtsch Arztebl Int. 2016;113(5):72–82.PubMedPubMedCentral
2.
Biasi F, Leonarduzzi G, Oteiza PI, et al. Inflammatory bowel disease: mechanisms, redox considerations, and therapeutic targets. Antioxid Redox Signal. 2013;19(14):1711–47.CrossRefPubMedPubMedCentral
3.
Singh S, Dulai PS, Zarrinpar A, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017;14(2):110–21.CrossRefPubMed
4.
5.
Nic Suibhne T, Raftery TC, McMahon O, et al. High prevalence of overweight and obesity in adults with Crohn’s disease: associations with disease and lifestyle factors. J Crohn's Colitis. 2013;7(7):e241–8.CrossRef
6.
Winer DA, Luck H, Tsai S, et al. The intestinal immune system in obesity and insulin resistance. Cell Metab. 2016;23(3):413–26.CrossRefPubMed
7.
Pereira SS, Alvarez-Leite JI. Low-grade inflammation, obesity, and diabetes. Curr Obes Rep. 2014;3(4):422–31.CrossRefPubMed
8.
Monteiro R, Azevedo I. Chronic inflammation in obesity and the metabolic syndrome. Mediat Inflamm. 2010;2010(289645):1–10.CrossRef
9.
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.CrossRefPubMed
10.
Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3):339–50. discussion 50-2CrossRefPubMedPubMedCentral
11.
Flores L, Vidal J, Canivell S, et al. Hypertension remission 1 year after bariatric surgery: predictive factors. Surg Obes Relat Dis. 2014;10(4):661–5.CrossRefPubMed
12.
Ahn LB, Huang CS, Forse RA, et al. Crohn's disease after gastric bypass surgery for morbid obesity: is there an association? Inflamm Bowel Dis. 2005;11(6):622–4.CrossRefPubMed
13.
Dodell GB, Albu JB, Attia L, et al. The bariatric surgery patient: lost to follow-up; from morbid obesity to severe malnutrition. Endocr Pract. 2012;18(2):e21–5.CrossRefPubMedPubMedCentral
14.
15.
Aelfers S, Janssen IMC, Aarts EO, et al. Inflammatory bowel disease is not a contraindication for bariatric surgery. Obes Surg. 2018;28(6):1681–7.CrossRefPubMed
16.
Keidar A, Hazan D, Sadot E, et al. The role of bariatric surgery in morbidly obese patients with inflammatory bowel disease. Surg Obes Relat Dis. 2015;11(1):132–6.CrossRefPubMed
17.
Aminian A, Andalib A, Ver MR, et al. Outcomes of bariatric surgery in patients with inflammatory bowel disease. Obes Surg. 2016;26(6):1186–90.CrossRefPubMed
18.
Colombo F, Rizzi A, Ferrari C, et al. Bariatric surgery in patients with inflammatory bowel disease: an accessible path? Report of a case series and review of the literature. J Crohn's Colitis. 2015;9(2):185–90.CrossRef
19.
Braga Neto MB, Gregory M, Ramos GP, et al. De-novo inflammatory bowel disease after bariatric surgery: a large case series. J Crohn's Colitis. 2018;12(4):452–7.CrossRef
20.
Ungaro R, Fausel R, Chang HL, et al. Bariatric surgery is associated with increased risk of new-onset inflammatory bowel disease: case series and national database study. Aliment Pharmacol Ther. 2018;47(8):1126–34.CrossRefPubMed
21.
Beaugerie L, Itzkowitz SH. Cancers complicating inflammatory bowel disease. N Engl J Med. 2015;372(15):1441–52.CrossRefPubMed
22.
Fornaro R, Caratto M, Caratto E, et al. Colorectal cancer in patients with inflammatory bowel disease: the need for a real surveillance program. Clin Colorectal Cancer. 2016;15(3):204–12.CrossRef
23.
Derogar M, Hull MA, Kant P, et al. Increased risk of colorectal cancer after obesity surgery. Ann Surg. 2013;258(6):983–8.CrossRefPubMed
24.
Kant P, Sainsbury A, Reed KR, et al. Rectal epithelial cell mitosis and expression of macrophage migration inhibitory factor are increased 3 years after Roux-en-Y gastric bypass (RYGB) for morbid obesity: implications for long-term neoplastic risk following RYGB. Gut. 2011;60(7):893–901.CrossRefPubMed
25.
Tao W, Konings P, Hull MA, et al. Colorectal cancer prognosis following obesity surgery in a population-based cohort study. Obes Surg. 2017;27(5):1233–9.CrossRefPubMed
26.
Esteban Varela J, Nguyen NT. Laparoscopic sleeve gastrectomy leads the U.S. utilization of bariatric surgery at academic medical centers. Surg Obes Relat Dis. 2015;11(5):987–90.CrossRefPubMed
27.
McGavigan AK, Garibay D, Henseler ZM, et al. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut. 2017;66:226–34.CrossRefPubMed
28.
Patti ME, Houten SM, Bianco AC, et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring). 2009;17(9):1671–7.CrossRef
29.
Steinert RE, Peterli R, Keller S, et al. Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Obesity (Silver Spring). 2013;21(12):E660–8.CrossRef
30.
Guo C, Qi H, Yu Y, et al. The G-protein-coupled bile acid receptor Gpbar1 (TGR5) inhibits gastric inflammation through antagonizing NF-κB signaling pathway. Front Pharmacol. 2015;6:287.CrossRefPubMedPubMedCentral
31.
Fiorucci S, Cipriani S, Mencarelli A, et al. Counter-regulatory role of bile acid activated receptors in immunity and inflammation. Curr Mol Med. 2010;10(6):579–95.PubMed
32.
Cipriani S, Mencarelli A, Chini MG, Distrutti E, Renga B, Bifulco G, Baldelli F, Donini A, Fiorucci S. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One. 2011;6(10):e25637.
33.
Ding L, Sousa KM, Jin L, et al. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology. 2016;64(3):760–73.CrossRefPubMedPubMedCentral
34.
Garibay D, McGavigan AK, Lee SA, et al. Beta-cell glucagon-like peptide-1 receptor contributes to improved glucose tolerance after vertical sleeve gastrectomy. Endocrinology. 2016;157(9):3405–9.CrossRefPubMedPubMedCentral
35.
Viennois E, Chen F, Laroui H, et al. Dextran sodium sulfate inhibits the activities of both polymerase and reverse transcriptase: lithium chloride purification, a rapid and efficient technique to purify RNA. BMC Res Notes. 2013;6:360.CrossRefPubMedPubMedCentral
36.
Ludwig K, Fassan M, Mescoli C, et al. PDCD4/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis. Virchows Arch. 2013;462(1):57–63.CrossRefPubMed
37.
Peck BC, Weiser M, Lee SE, et al. MicroRNAs classify different disease behavior phenotypes of Crohn’s disease and may have prognostic utility. Inflamm Bowel Dis. 2015;21(9):2178–87.CrossRefPubMedPubMedCentral
38.
Shi C, Liang Y, Yang J, et al. MicroRNA-21 knockout improve the survival rate in DSS induced fatal colitis through protecting against inflammation and tissue injury. PLoS One. 2013;8(6):e66814.CrossRefPubMedPubMedCentral
39.
Yang Y, Ma Y, Shi C, et al. Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB. Biochem Biophys Res Commun. 2013;434(4):746–52.CrossRefPubMed
40.
Ando Y, Mazzurana L, Forkel M, et al. Downregulation of MicroRNA-21 in colonic CD3+ T cells in UC remission. Inflamm Bowel Dis. 2016;22(12):2788–93.CrossRefPubMed
41.
Biagioli M, Carino A. The bile acid receptor GPBAR1 regulates the M1/M2 phenotype of intestinal macrophages and activation of GPBAR1 rescues mice from murine colitis. J Immunol. 2017;199(2):718–33.CrossRefPubMed
42.
43.
Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015;12(12):720–7.CrossRefPubMed
44.
Li S, Vinci A, Behnsen J, et al. Bariatric surgery attenuates colitis in an obese murine model. Surg Obes Relat Dis. 2017;13(4):661–8.CrossRefPubMed
45.
Cummings BP, Bettaieb A, Graham JL, et al. Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats. Dis Model Mech. 2013;6(2):443–56.CrossRefPubMed
46.
47.
Liou AP, Paziuk M, Luevano Jr JM, et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):178ra41.CrossRefPubMedPubMedCentral
48.
49.
50.
Tremaroli V, Karlsson F, Werling M, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22(2):228–38.CrossRefPubMedPubMedCentral
51.
Lupp C, Robertson ML, Wickham ME, et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe. 2007;2(3):204.CrossRef
52.
Benjamin JL, Hedin CR, Koutsoumpas A, et al. Smokers with active Crohn’s disease have a clinically relevant dysbiosis of the gastrointestinal microbiota. Inflamm Bowel Dis. 2012;18(6):1092–100.CrossRefPubMed
53.
Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780–5.CrossRefPubMedPubMedCentral
54.
Shi C, Yang Y, Xia Y, et al. Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer. Gut. 2016;65(9):1470–81.CrossRefPubMed
Metadata
Title
TGR5 Protects Against Colitis in Mice, but Vertical Sleeve Gastrectomy Increases Colitis Severity
Authors
Darline Garibay
Karolina E. Zaborska
Michael Shanahan
Qiaonan Zheng
Katie M. Kelly
David C. Montrose
Andrew J. Dannenberg
Andrew D. Miller
Praveen Sethupathy
Bethany P. Cummings
Publication date
01-05-2019
Publisher
Springer US
Published in
Obesity Surgery / Issue 5/2019
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-019-03707-9

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