Skip to main content
Erschienen in: Obesity Surgery 12/2019

30.07.2019 | Original Contributions

Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Attenuate Pro-inflammatory Small Intestinal Cytokine Signatures

verfasst von: Renuka Subramaniam, Hassan Aliakbarian, Hina Y. Bhutta, David A. Harris, Ali Tavakkoli, Eric G. Sheu

Erschienen in: Obesity Surgery | Ausgabe 12/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Bariatric surgery rapidly induces improvements in type 2 diabetes (T2D) in concert with reduction in systemic markers of inflammation. The impact of bariatric surgery on local intestinal immunity is not known. We hypothesize that sleeve gastrectomy (SG) and gastric bypass (RYGB) surgeries resolve obesity-induced intestinal inflammation, thereby promoting T2D resolution.

Methods

SG and RYGB, or control surgery was performed in SD rats (n = 4–6/group). Key cytokines involved in insulin resistance (TNF-α, IFN-γ), inflammasome activation (IL-1β, IL-18), inflammation resolution (IL-10, IL-33), and Th17 cell responses (IL-17, IL-23) were measured by qPCR in mucosal scrapings of jejunum at 4 weeks post-surgery. Intestinal cytokine expressions were correlated with weight change, systemic and portal glucose, and insulin levels in response to an enteral glucose load.

Results

SG downregulated IL-17 and IL-23 in both proximal and distal jejunum, and IFN-γ was reduced only in distal jejunum (p < 0.05). Jejunal IL-17 and IL-23 expression correlated positively with weight changes after SG (0.93 and 0.98, respectively; p < 0.05). Changes in IFN-γ correlated strongly with insulin levels in portal and systemic circulation (0.99 and 0.95, respectively, p < 0.05). As with SG, IFN-γ, IL-17, and IL-23 were significantly reduced by RYGB. RYGB also reduced TNF-α and IL-18 and increased IL-33 levels (p < 0.05).

Conclusions

RYGB and SG reduce expression of pro-inflammatory cytokines IL-17, IL-23, and IFN-γ in the jejunum. RYGB showed attenuation of additional pro-inflammatory cytokines and enhanced expression of IL-33. Post-surgical changes in intestinal IL-17, IL-23, and IFN-γ correlate strongly with changes in weight and glucose-triggered insulin responses.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med. 2017;376:641–51.CrossRef Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med. 2017;376:641–51.CrossRef
2.
Zurück zum Zitat Wallenius V, Dirinck E, Fändriks L, et al. Glycemic control after sleeve gastrectomy and Roux-en-Y gastric bypass in obese subjects with type 2 diabetes mellitus. Obes Surg. 2017;28:1461–72.CrossRef Wallenius V, Dirinck E, Fändriks L, et al. Glycemic control after sleeve gastrectomy and Roux-en-Y gastric bypass in obese subjects with type 2 diabetes mellitus. Obes Surg. 2017;28:1461–72.CrossRef
3.
Zurück zum Zitat Heshmati K, Harris DA, Aliakbarian H, et al. Comparison of early type 2 diabetes improvement after gastric bypass and sleeve gastrectomy: medication cessation at discharge predicts 1-year outcomes. SOARD.2019; S1550–7289(18)31259-0. Heshmati K, Harris DA, Aliakbarian H, et al. Comparison of early type 2 diabetes improvement after gastric bypass and sleeve gastrectomy: medication cessation at discharge predicts 1-year outcomes. SOARD.2019; S1550–7289(18)31259-0.
4.
Zurück zum Zitat Yarmush ML, D'Alessandro M, Saeidi N. Regulation of energy homeostasis after gastric bypass surgery. Annu Rev Biomed Eng. 2017;19:459–84.CrossRef Yarmush ML, D'Alessandro M, Saeidi N. Regulation of energy homeostasis after gastric bypass surgery. Annu Rev Biomed Eng. 2017;19:459–84.CrossRef
5.
Zurück zum Zitat Murphy R, Tsai P, Jüllig M, et al. Differential changes in gut microbiota after gastric bypass and sleeve gastrectomy bariatric surgery vary according to diabetes remission. Obes Surg. 2017;27:917–25.CrossRef Murphy R, Tsai P, Jüllig M, et al. Differential changes in gut microbiota after gastric bypass and sleeve gastrectomy bariatric surgery vary according to diabetes remission. Obes Surg. 2017;27:917–25.CrossRef
6.
Zurück zum Zitat Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18:363–74.CrossRef Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012;18:363–74.CrossRef
7.
Zurück zum Zitat Delzenne NM, Cani PD. Gut microbiota and the pathogenesis of insulin resistance. Curr Diab Rep. 2011;11:154–9.CrossRef Delzenne NM, Cani PD. Gut microbiota and the pathogenesis of insulin resistance. Curr Diab Rep. 2011;11:154–9.CrossRef
8.
Zurück zum Zitat De Wit NJ, Bosch-Vermeulen H, de Groot PJ, et al. The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice. BMC Med Genomics. 2008;1:14.CrossRef De Wit NJ, Bosch-Vermeulen H, de Groot PJ, et al. The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice. BMC Med Genomics. 2008;1:14.CrossRef
9.
Zurück zum Zitat Ding S, Chi MM, Scull BP, et al. High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One. 2010;5:e12191.CrossRef Ding S, Chi MM, Scull BP, et al. High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One. 2010;5:e12191.CrossRef
10.
Zurück zum Zitat Spagnuolo MI, Cicalese MP, Caiazzo MA, et al. Relationship between severe obesity and gut inflammation in children: what’s next? Ital J Pediatr. 2010;36:66.CrossRef Spagnuolo MI, Cicalese MP, Caiazzo MA, et al. Relationship between severe obesity and gut inflammation in children: what’s next? Ital J Pediatr. 2010;36:66.CrossRef
11.
Zurück zum Zitat Febbraio MA. Role of interleukins in obesity: implications for metabolic disease. Trends Endocrinol Metab. 2014;25:312–9.CrossRef Febbraio MA. Role of interleukins in obesity: implications for metabolic disease. Trends Endocrinol Metab. 2014;25:312–9.CrossRef
12.
Zurück zum Zitat Winer DA, Luck H, Tsai S, et al. The intestinal immune system in obesity and insulin resistance. Cell Metab. 2016;23:413–26.CrossRef Winer DA, Luck H, Tsai S, et al. The intestinal immune system in obesity and insulin resistance. Cell Metab. 2016;23:413–26.CrossRef
13.
Zurück zum Zitat Rao SR. Inflammatory markers and bariatric surgery: a meta-analysis. Inflamm Res. 2012;61:789–807.CrossRef Rao SR. Inflammatory markers and bariatric surgery: a meta-analysis. Inflamm Res. 2012;61:789–807.CrossRef
14.
Zurück zum Zitat Illán-Gómez F, Gonzálvez-Ortega M, Orea-Soler I, et al. Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery. Obes Surg. 2012;22:950–5.CrossRef Illán-Gómez F, Gonzálvez-Ortega M, Orea-Soler I, et al. Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery. Obes Surg. 2012;22:950–5.CrossRef
15.
Zurück zum Zitat Poitou C, Perret C, Mathieu F, et al. Bariatric surgery induces disruption in inflammatory signaling pathways mediated by immune cells in adipose tissue: a RNA-Seq study. PLoS One. 2015;10:e0125718.CrossRef Poitou C, Perret C, Mathieu F, et al. Bariatric surgery induces disruption in inflammatory signaling pathways mediated by immune cells in adipose tissue: a RNA-Seq study. PLoS One. 2015;10:e0125718.CrossRef
16.
Zurück zum Zitat Roberts HM, Grant MM, Hubber N, et al. Impact of bariatric surgical intervention on peripheral blood neutrophil (PBN) function in obesity. Obes Surg. 2017;6:1611–21. Roberts HM, Grant MM, Hubber N, et al. Impact of bariatric surgical intervention on peripheral blood neutrophil (PBN) function in obesity. Obes Surg. 2017;6:1611–21.
17.
Zurück zum Zitat Schernthaner GH, Kopp HP, Kriwanek S, et al. Effect of massive weight loss induced by bariatric surgery on serum levels of interleukin-18 and monocyte-chemoattractant-protein-1 in morbid obesity. Obes Surg. 2006;16:709–15.CrossRef Schernthaner GH, Kopp HP, Kriwanek S, et al. Effect of massive weight loss induced by bariatric surgery on serum levels of interleukin-18 and monocyte-chemoattractant-protein-1 in morbid obesity. Obes Surg. 2006;16:709–15.CrossRef
18.
Zurück zum Zitat Mallipedhi A, Prior SL, Barry JD, et al. Changes in inflammatory markers after sleeve gastrectomy in patients with impaired glucose homeostasis and type 2 diabetes. Surg Obes Relat Dis. 2014;10:1123–8.CrossRef Mallipedhi A, Prior SL, Barry JD, et al. Changes in inflammatory markers after sleeve gastrectomy in patients with impaired glucose homeostasis and type 2 diabetes. Surg Obes Relat Dis. 2014;10:1123–8.CrossRef
19.
Zurück zum Zitat Greer RL, Morgun A, Shulzhenko N. Bridging immunity and lipid metabolism by gut microbiota. J Allergy Clin Immunol. 2013;132:253–62.CrossRef Greer RL, Morgun A, Shulzhenko N. Bridging immunity and lipid metabolism by gut microbiota. J Allergy Clin Immunol. 2013;132:253–62.CrossRef
20.
Zurück zum Zitat Rodrigues RR, Greer RL, Dong X, et al. Antibiotic- induced alterations in gut microbiota are associated with changes in glucose metabolism in healthy mice. Front Microbiol. 2017;8:2306.CrossRef Rodrigues RR, Greer RL, Dong X, et al. Antibiotic- induced alterations in gut microbiota are associated with changes in glucose metabolism in healthy mice. Front Microbiol. 2017;8:2306.CrossRef
21.
Zurück zum Zitat Winer DA, Winer S, Dranse HJ, et al. Immunologic impact of the intestine in metabolic disease. J Clin Invest. 2017;127:33–42.CrossRef Winer DA, Winer S, Dranse HJ, et al. Immunologic impact of the intestine in metabolic disease. J Clin Invest. 2017;127:33–42.CrossRef
22.
Zurück zum Zitat Cani PD. Severe obesity and gut microbiota: does bariatric surgery really reset the system? Gut. 2019;68:5–6.CrossRef Cani PD. Severe obesity and gut microbiota: does bariatric surgery really reset the system? Gut. 2019;68:5–6.CrossRef
23.
Zurück zum Zitat Bhutta HY, Deelman TE, le Roux CW, et al. Intestinal sweet-sensing pathways and metabolic changes after Roux-en-Y gastric bypass surgery. Am J Physiol Gastrointest Liver Physiol. 2014;307:G588–93.CrossRef Bhutta HY, Deelman TE, le Roux CW, et al. Intestinal sweet-sensing pathways and metabolic changes after Roux-en-Y gastric bypass surgery. Am J Physiol Gastrointest Liver Physiol. 2014;307:G588–93.CrossRef
24.
Zurück zum Zitat Sumarac-Dumanovic M1, Stevanovic D, Ljubic A, et al. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes. 2009;33(1):151–6.CrossRef Sumarac-Dumanovic M1, Stevanovic D, Ljubic A, et al. Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes. 2009;33(1):151–6.CrossRef
25.
Zurück zum Zitat Fatima N, Faisal SM, Zubair S, et al. Emerging role of interleukins IL-23/IL-17 axis and biochemical markers in the pathogenesis of type 2 diabetes: association with age and gender in human subjects. Int J Biol Macromol. 2017;105:1279–88.CrossRef Fatima N, Faisal SM, Zubair S, et al. Emerging role of interleukins IL-23/IL-17 axis and biochemical markers in the pathogenesis of type 2 diabetes: association with age and gender in human subjects. Int J Biol Macromol. 2017;105:1279–88.CrossRef
26.
Zurück zum Zitat Ip B, Cilfone NA, Belkina AC, et al. Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production. Obesity. 2016;24:102–12.CrossRef Ip B, Cilfone NA, Belkina AC, et al. Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production. Obesity. 2016;24:102–12.CrossRef
27.
Zurück zum Zitat DeFuria J, Belkina AC, Jagannathan-Bogdan M, et al. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. PNAS. 2013;110:5133–8.CrossRef DeFuria J, Belkina AC, Jagannathan-Bogdan M, et al. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. PNAS. 2013;110:5133–8.CrossRef
28.
Zurück zum Zitat Luck H, Tsai S, Chung J, et al. Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metab. 2015;21:527–42.CrossRef Luck H, Tsai S, Chung J, et al. Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metab. 2015;21:527–42.CrossRef
29.
Zurück zum Zitat McLaughlin T, Ackerman SE, Shen L, et al. Role of innate and adaptive immunity in obesity-associated metabolic disease. J Clin Invest. 2017;127:5–13.CrossRef McLaughlin T, Ackerman SE, Shen L, et al. Role of innate and adaptive immunity in obesity-associated metabolic disease. J Clin Invest. 2017;127:5–13.CrossRef
30.
Zurück zum Zitat Ben-Zvi D, Meoli L, Abidi WM, et al. Time-dependent molecular responses differ between gastric bypass and dieting but are conserved across species. Cell Metab. 2018;28:1–14.CrossRef Ben-Zvi D, Meoli L, Abidi WM, et al. Time-dependent molecular responses differ between gastric bypass and dieting but are conserved across species. Cell Metab. 2018;28:1–14.CrossRef
Metadaten
Titel
Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Attenuate Pro-inflammatory Small Intestinal Cytokine Signatures
verfasst von
Renuka Subramaniam
Hassan Aliakbarian
Hina Y. Bhutta
David A. Harris
Ali Tavakkoli
Eric G. Sheu
Publikationsdatum
30.07.2019
Verlag
Springer US
Erschienen in
Obesity Surgery / Ausgabe 12/2019
Print ISSN: 0960-8923
Elektronische ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-019-04059-0

Weitere Artikel der Ausgabe 12/2019

Obesity Surgery 12/2019 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.