High-dose taurine exacerbates ulcerative colitis via macrophage activation
While taurine is generally considered beneficial, excessive intake may be harmful under certain conditions. In this study, we examined the effects of dietary taurine on Wistar rats with ulcerative colitis (UC)—a chronic inflammatory disease—induced with 3% dextran sulfate sodium (DSS). Normal rats fed a 10% taurine diet served as the control group, and UC model rats were assigned to the DSS group (standard diet) or taurine-supplemented diets containing 1%, 5%, or 10% taurine (the 1 TAU, 5 TAU, or 10 TAU group). In parallel, primary peritoneal macrophages were stimulated with lipopolysaccharide (LPS) and/or taurine in vitro. Control rats gained more weight than all DSS-exposed groups and showed no colonic atrophy or increased inflammatory scores. Among DSS-exposed rats, the 10 TAU group was associated with the greatest body weight loss and the highest disease activity index, whereas colon length did not differ significantly on day 20. Histology revealed epithelial injury and inflammatory infiltration in DSS-exposed groups, with the most pronounced damage in the DSS and 10 TAU groups and comparatively milder injury in the 1 TAU and 5 TAU groups. Serum TNF-α was significantly elevated in the 5 TAU group and showed an increasing trend in the 10 TAU group. In vitro, taurine enhanced macrophage activation in an LPS-stimulated context. Overall, very high dietary taurine (10% w/w) was associated with pathological exacerbation and greater histopathologic severity, while 5% taurine showed intermediate, outcome-dependent effects rather than a uniform dose response.
- Marks DJ, Segal AW. Innate immunity in inflammatory bowel disease: a disease hypothesis. J Pathol. 2008;214(2):260-266. doi: 10.1002/path.2291
- Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54. doi: 10.1053/j.gastro.2011.10.001
- Sartor RB. Mechanisms of disease: Pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(7):390–407. doi: 10.1038/ncpgasthep0528
- Zhang Y, Xun, L, Qiao R, et al. Advances in research on the role of high carbohydrate diet in the process of inflammatory bowel disease (IBD). Front Immunol. 2024;15:1478374. doi: 10.3389/fimmu.2024.1478374
- Chicco F, Magrì S, Cingolani A, et al. Multidimensional Impact of Mediterranean Diet on IBD Patients. Inflamm Bowel Dis. 2021;27(1):1–9. doi: 10.1093/ibd/izaa097
- Stipanuk MH. Role of the liver in regulation of body cysteine and taurine levels: a brief review. Neurochem Res. 2004;29(1):105-110. doi: 10.1023/b:nere.0000010438.40376.c9.
- Laidlaw SA, Grosvenor M, Kopple JD. The taurine content of common foodstuffs. JPEN J Parenter Enteral Nutr. 1990;14(2):183-188. doi: 10.1177/0148607190014002183.
- Schuller-Levis GB, Park E. Taurine: new implications for an old amino acid. FEMS Microbiol Lett. 2003;226(2):195-202. doi: 10.1016/S0378-1097(03)00611-6.
- El Idrissi A, Okeke E, Yan X, et al. Taurine regulation of blood pressure and vasoactivity. Adv Exp Med Biol. 2013;775:407-425. doi: 10.1007/978-1-4614-6130-2_31.
- Pasin F, Porro E, Frattini F, et al. Thrombocytopenia induced by a taurine-containing energy drink: an adverse reaction to herbal medicine. Ital J Med. 2014;8(4):259-261. doi: 10.4081/itjm.2014.466
- Zheng J, Zhang J, Zhou Y, et al. Taurine Alleviates Experimental Colitis by Enhancing Intestinal Barrier Function and Inhibiting Inflammatory Response through TLR4/NF-κB Signaling. J Agric Food Chem. 2024;72(21):12119-12129. doi: 10.1021/acs.jafc.4c00662
- Frascatani R, Mattogno A, Iannucci A, et al. Reduced Taurine Serum Levels in Inflammatory Bowel Disease. Nutrients. 2024;16(11):1593. doi: 10.3390/nu16111593.
- Camargo RL, Batista TM, Ribeiro RA, et al. Effects of taurine supplementation upon food intake and central insulin signaling in malnourished mice fed on a high-fat diet. Adv Exp Med Biol. 2013;776:93-103. doi: 10.1007/978-1-4614-6093-0_10
- Dawson R, Jr Liu S, Eppler B. Effects of dietary taurine supplementation or deprivation in aged male Fischer 344 rats. Mech Ageing Dev. 1999;107(1):73-91. doi: 10.1016/s0047-6374(98)00138-9.
- Okada K, Matsuo K, Amada M, et al. Excessive glucose and fructose intake aggravates the pathogenesis of rat experimental colitis. Gastrointest Disord. 2023;5(4):474-486. doi: 10.3390/gidisord5040039
- Batbold D, Shinoda M, Honda K, et al. Macrophages in trigeminal ganglion contribute to ectopic mechanical hypersensitivity following inferior alveolar nerve injury in rats. J Neuroinflammation. 2017;14(1):249. doi: 10.1186/s12974-017-1022-3
- Cooper HS, Murthy SN, Shah RS, et al. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1933;69(2):238-249.
- Williams KL, Fuller CR, Dieleman LA, et al. Enhanced survival and mucosal repair after dextran sodium sulfateinduced colitis in transgenic mice that overexpress growth hormone. Gastroenterology. 2001;120(4):925-937. doi: 10.1053/gast.2001.22470
- Matsuo K, Ikemoto M, Okada K. Intraperitoneal Administration of S100A8 Ameliorates Experimental Acute Colitis in Rats. Biology. 2024;13(11):916. doi: 10.3390/biology13110916
- Yoshino T, Nakase H, Honzawa Y, et al. Immunosuppressive effects of tacrolimus on macrophages ameliorate experimental colitis. Inflamm Bowel Dis. 2010;16(12):2022-2033. doi: 10.1002/ibd.21318
- European Food Safety Authority (EFSA). Scientific Opinion on the safety and efficacy of taurine as a feed additive for all animal species. EFSA J. 2012;10(6):2736. doi: 10.2903/j.efsa.2012.2736
- Yang C, Merlin D. Unveiling Colitis: A Journey through the Dextran Sodium Sulfate-induced Model. Inflamm Bowel Dis. 2024;30(5):844-853. doi: 10.1093/ibd/izad312.
- Shimizu M, Zhao Z, Ishimoto Y, et al. Dietary taurine attenuates dextran sulfate sodium (DSS)-induced experimental colitis in mice. Adv Exp Med Biol. 2010;643:265-271. doi: 10.1007/978-0-387-75681-3_27.
- Perez-Hernandez E, Pastrana-Carballo JJ, Gomez-Chavez F, et al. A Key Metabolic Regulator of Bone and Cartilage Health. Endocrinol Metab. 2022;37(4):559-574. doi: 10.3803/EnM.2022.1443
- Perše M, Cerar A. Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol. 2012;2012:718617. doi: 10.1155/2012/718617
- Adamkova P, Hradicka P, Kupcova Skalnikova H, et al. Dextran Sulphate Sodium Acute Colitis Rat Model: A Suitable Tool for Advancing Our Understanding of Immune and Microbial Mechanisms in the Pathogenesis of Inflammatory Bowel Disease. Vet Sci. 2022;9(5):238. doi: 10.3390/vetsci9050238
- Hassan AM, Jain P, Reichmann F, et al. Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice. Front Behav Neurosci. 2014;8:386. doi: 10.3389/fnbeh.2014.00386
- Hamdani G, Gabet Y, Rachmilewitz D, et al. Dextran sodium sulfate-induced colitis causes rapid bone loss in mice. Bone. 2008;43(5):945-950. doi: 10.1016/j.bone.2008.06.018
- Wang Z, Ohata Y, Watanabe Y, et al. Taurine Improves Lipid Metabolism and Increases Resistance to Oxidative Stress. J Nutr Sci Vitaminol. 2020;66(4):347-356. doi: 10.3177/jnsv.66.347
- Song Q, Kobayashi S, Kataoka Y, et al. Direct Molecular Action of Taurine on Hepatic Gene Expression Associated with the Amelioration of Hypercholesterolemia in Rats. Antioxidants. 2024;13(8):990. doi: 10.3390/antiox13080990
- Curran CP, Marczinski CA. Taurine, caffeine, and energy drinks: Reviewing the risks to the adolescent brain. Birth Defects Res. 2017;109(20):1640-1648. doi: 10.1002/bdr2.1177
- Candelli M, Franza L, Pignataro G, et al. Interaction between lipopolysaccharide and gut microbiota in inflammatory bowel diseases. Int J Mol Sci. 2021;22(12):6242. doi: 10.3390/ijms22126242
- Gupte R, Christian S, Keselman P, et al. Evaluation of taurine neuroprotection in aged rats with traumatic brain injury. Brain Imaging Behav. 2019;13(2):461-471. doi: 10.1007/s11682-018-9865-5
- Piccioni A, Covino M, Zanza C, et al. Energy drinks: a narrative review of their physiological and pathological effects. Intern Med J. 2021;51(5):636-646. doi: 10.1111/imj.14881
- Orecchioni M, Ghosheh Y, Pramod AB, et al. Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Front Immunol. 2019;10:1084. doi: 10.3389/fimmu.2019.01084
- Meng L, Lu C, Wu B, et al. Taurine Antagonizes Macrophages M1 Polarization by Mitophagy-Glycolysis Switch Blockage via Dragging SAM-PP2Ac Transmethylation. Front Immunol. 2021;12:648913. doi: 10.3389/fimmu.2021.648913
- Prideaux M, Kitase Y, Kimble M, et al. Taurine, an osteocyte metabolite, protects against oxidative stress-induced cell death and decreases inhibitors of the Wnt/β-catenin signaling pathway. Bone. 2020;137:115374. doi: 10.1016/j.bone.2020.115374
- Qian W, Li M, Yu L, et al. Effects of Taurine on Gut Microbiota Homeostasis: An Evaluation Based on Two Models of Gut Dysbiosis. Biomedicines. 2023;11(4):1048. doi: 10.3390/biomedicines11041048
- Duszka K. Versatile Triad Alliance: Bile Acid, Taurine and Microbiota. Cells. 2022;11(15):2337. doi: 10.3390/cells11152337.
- Cui C, Song H, Han Y, et al. Gut microbiota-associated taurine metabolism dysregulation in a mouse model of Parkinson’s disease. mSphere. 2023;8(6):e0043123. doi: 10.1128/msphere.00431-23
- Sasaki K, Sasaki D, Okai N, et al. Taurine does not affect the composition, diversity, or metabolism of human colonic microbiota simulated in a single-batch fermentation system. PLoS One. 2017;12(7):e0180991. doi: 10.1371/journal.pone.0180991
- Mendes LF, Gaspar VM, Conde TA, et al. Flavonoidmediated immunomodulation of human macrophages involves key metabolites and metabolic pathways. Sci Rep. 2019;9(1):14906. doi: 10.1038/s41598-019-51113-z
