The Impact of Bariatric Surgery on Serum Tryptophan-kynurenine Pathway Metabolites

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jan 8

PMID 34996930

Citations 4

Authors

Kai Tai Derek Yeung

Nicholas Penney

Luke Whiley

Hutan Ashrafian

Matthew R Lewis

Sanjay Purkayastha

Ara Darzi

Elaine Holmes

Affiliations

Soon will be listed here.

Abstract

This study aims to explore the immediate effects of bariatric surgery on serum tryptophan-kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway metabolites, type 2 diabetes, and chronic obesity-induced inflammation. This longitudinal study included 20 participants. Half were diagnosed with type 2 diabetes. 11 and 9 underwent RYGB and SG respectively. Blood samples were obtained at pre-operative and 3 months post-operative timepoints. Tryptophan and downstream metabolites of the kynurenine pathway were quantified with an ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionisation method. At 3 months post-operation, RYGB led to significant reductions in tryptophan, kynurenic acid and xanthurenic acid levels when compared to baseline. Significant reductions of the same metabolites after surgery were also observed in individuals with T2D irrespective of surgical procedure. These metabolites were significantly correlated with serum HbA1c levels and BMI. Bariatric surgery, in particular RYGB reduces serum levels of tryptophan and its downstream kynurenine metabolites. These metabolites are associated with T2D and thought to be potentially mechanistic in the systemic processes of obesity induced inflammation leading to insulin resistance. Its reduction after surgery is associated with an improvement in glycaemic control (HbA1c).

Citing Articles

Exploring the serotonin-probiotics-gut health axis: A review of current evidence and potential mechanisms.

Akram N, Faisal Z, Irfan R, Shah Y, Batool S, Zahid T Food Sci Nutr. 2024; 12(2):694-706.

PMID: 38370053 PMC: 10867509. DOI: 10.1002/fsn3.3826.

Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes.

Hernandez N, Lokhnygina Y, Ramaker M, Ilkayeva O, Muehlbauer M, Crawford M J Clin Endocrinol Metab. 2023; 109(4):e1345-e1358.

PMID: 38066593 PMC: 10940256. DOI: 10.1210/clinem/dgad708.

Red Meat Intake, Indole-3-Acetate, and Together Affect Insulin Resistance after Gastric Bypass.

Aguiar Prudencio A, Fonseca D, Machado N, Tepedino Martins Alves J, Sala P, Fernandes G Nutrients. 2023; 15(5).

PMID: 36904185 PMC: 10005351. DOI: 10.3390/nu15051185.

Kynurenine Pathway in Diabetes Mellitus-Novel Pharmacological Target?.

Koziel K, Urbanska E Cells. 2023; 12(3).

PMID: 36766803 PMC: 9913876. DOI: 10.3390/cells12030460.

References

ROSEN D, MAENGWYN-DAVIES G, Becker B, Stone H, FRIEDENWALD J . Xanthurenic acid excretion studies in diabetics with and without retinopathy. Proc Soc Exp Biol Med. 1955; 88(3):321-3. DOI: 10.3181/00379727-88-21576. View

Kotake Y, Ueda T, Mori T, Igaki S, Hattori M . Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA). Acta Vitaminol Enzymol. 1975; 29(1-6):236-9. View

Hubbard T, Murray I, Perdew G . Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation. Drug Metab Dispos. 2015; 43(10):1522-35. PMC: 4576673. DOI: 10.1124/dmd.115.064246. View

Moulton C, Pickup J, Ismail K . The link between depression and diabetes: the search for shared mechanisms. Lancet Diabetes Endocrinol. 2015; 3(6):461-471. DOI: 10.1016/S2213-8587(15)00134-5. View

Mascolo E, Verni F . Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms. Int J Mol Sci. 2020; 21(10). PMC: 7279184. DOI: 10.3390/ijms21103669. View

Jennis M, Cavanaugh C, Leo G, Mabus J, Lenhard J, Hornby P . Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo. Neurogastroenterol Motil. 2017; 30(2). DOI: 10.1111/nmo.13178. View

McTigue K, Wellman R, Nauman E, Anau J, Coley R, Odor A . Comparing the 5-Year Diabetes Outcomes of Sleeve Gastrectomy and Gastric Bypass: The National Patient-Centered Clinical Research Network (PCORNet) Bariatric Study. JAMA Surg. 2020; 155(5):e200087. PMC: 7057171. DOI: 10.1001/jamasurg.2020.0087. View

Meyramov G, Korchin V, Kocheryzkina N . Diabetogenic activity of xanturenic acid determined by its chelating properties?. Transplant Proc. 1998; 30(6):2682-4. DOI: 10.1016/s0041-1345(98)00788-x. View

Badawy A . Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention. Egypt J Basic Clin Pharmacol. 2019; 9. PMC: 6520243. DOI: 10.32527/2019/101415. View

10.

Favennec M, Hennart B, Caiazzo R, Leloire A, Yengo L, Verbanck M . The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation. Obesity (Silver Spring). 2015; 23(10):2066-74. DOI: 10.1002/oby.21199. View

11.

Schrocksnadel K, Wirleitner B, Winkler C, Fuchs D . Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta. 2005; 364(1-2):82-90. DOI: 10.1016/j.cca.2005.06.013. View

12.

Lu C, Chang Y, Lee Y, Kuo C, Chang H, Huang C . Increased risk for major depressive disorder in severely obese patients after bariatric surgery - a 12-year nationwide cohort study. Ann Med. 2018; 50(7):605-612. DOI: 10.1080/07853890.2018.1511917. View

13.

Cervenka I, Agudelo L, Ruas J . Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health. Science. 2017; 357(6349). DOI: 10.1126/science.aaf9794. View

14.

Kotake Y . Xanthurenic acid, an abnormal metabolite of tryptophan and the diabetic symptoms caused in albino rats by its production. J Vitaminol (Kyoto). 1955; 1(2):73-87. DOI: 10.5925/jnsv1954.1.2_73. View

15.

Favennec M, Hennart B, Verbanck M, Pigeyre M, Caiazzo R, Raverdy V . Post-Bariatric Surgery Changes in Quinolinic and Xanthurenic Acid Concentrations Are Associated with Glucose Homeostasis. PLoS One. 2016; 11(6):e0158051. PMC: 4915629. DOI: 10.1371/journal.pone.0158051. View

16.

Keszthelyi D, Troost F, Jonkers D, Kruimel J, Leue C, Masclee A . Decreased levels of kynurenic acid in the intestinal mucosa of IBS patients: relation to serotonin and psychological state. J Psychosom Res. 2013; 74(6):501-4. DOI: 10.1016/j.jpsychores.2013.01.008. View

17.

Aminian A . Bariatric procedure selection in patients with type 2 diabetes: choice between Roux-en-Y gastric bypass or sleeve gastrectomy. Surg Obes Relat Dis. 2020; 16(2):332-339. DOI: 10.1016/j.soard.2019.11.013. View

18.

Raatz S, Johnson L, Caliquary A, King W, Kalarchian M, Devlin M . Reported nutrient intake over 7 years after Roux-en-Y gastric bypass in the Longitudinal Assessment of Bariatric Surgery-3 (LABS-3) psychosocial study. Surg Obes Relat Dis. 2020; 16(8):1022-1029. PMC: 7423730. DOI: 10.1016/j.soard.2020.04.007. View

19.

Wallenius V, Alaraj A, Bjornfot N, Orrenius B, Kyleback A, Bjorklund P . Sleeve gastrectomy and Roux-en-Y gastric bypass in the treatment of type 2 diabetes. Two-year results from a Swedish multicenter randomized controlled trial. Surg Obes Relat Dis. 2020; 16(8):1035-1044. DOI: 10.1016/j.soard.2020.04.033. View

20.

Cussotto S, Delgado I, Anesi A, Dexpert S, Aubert A, Beau C . Tryptophan Metabolic Pathways Are Altered in Obesity and Are Associated With Systemic Inflammation. Front Immunol. 2020; 11:557. PMC: 7174689. DOI: 10.3389/fimmu.2020.00557. View