Early acidification of stool and urine as a simple noninvasive screening tool for ulcerative colitis activity
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrent inflammation of the colon. The absence of simple, noninvasive, and early biomarkers for disease onset and progression remains a major clinical challenge. This study aimed to evaluate the potential of pH values in biological samples as noninvasive indicators for the early disease-related changes in an experimental rat model of UC. Experimental colitis was induced in rats by administering dextran sulfate sodium, and the results were compared to those of healthy controls. Disease progression was monitored by evaluating disease severity scores and histopathological changes. Throughout the experimental period, stool and urinary pH were measured daily, while colonic and serum pH were assessed post-mortem. As the experiment progressed, the colitic rats exhibited marked weight loss and severe inflammatory changes in the colon. Despite the worsening disease, no significant alterations were observed in colonic or serum pH. In contrast, both stool and urinary pH values significantly decreased during the early phase of experimental colitis. However, these pH fluctuations did not consistently correlate with UC severity. In conclusion, our findings suggest that stool and urinary pH represent promising, noninvasive biomarkers for the early detection and monitoring of disease activity in UC.
- 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
- Sairenji T, Collins KL, Evans DV. An update on inflammatory bowel disease. Prim Care. 2017;44(4):673-692. doi: 10.1016/j.pop.2017.07.010
- Watanabe T, Kitani A, Murray PJ, et al. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol. 2004;5(8):800-808. doi: 10.1038/ni1092
- Massey DC, Parkes M. Genome-wide association scanning highlights two autophagy genes, ATG16L1 and IRGM, as being significantly associated with Crohn’s disease. Autophagy. 2007;3(6):649-651. doi: 10.4161/auto.5075
- Henckaerts L, Figueroa C, Vermeire S, et al. The role of genetics in inflammatory bowel disease. Curr Drug Targets. 2008;9(5):361-368. doi: 10.2174/138945008784221161
- 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
- Kvedaraite E, Lourda M, Ideström M, et al. Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD. Gut. 2016;65(10):1632-1641. doi: 10.1136/gutjnl-2014-309014
- Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-1812. doi: 10.1172/JCI200318921
- Mańkowska-Wierzbicka D, Karczewski J, Poniedziałek B, et al. C-reactive protein as a diagnostic and prognostic factor in inflammatory bowel diseases. Postepy Hig Med Dosw. 2016;70(0):1124-1130. doi: 10.5604/17322693.1223798
- Sipponen T, Kolho KL. Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease. Scand J Gastroenterol. 2015;50(1):74-80. doi: 10.3109/00365521.2014.987809
- Puolanne AM, Kolho KL, Alfthan H, et al. Rapid faecal tests for detecting disease activity in colonic inflammatory bowel disease. Eur J Clin Invest. 2016;46(10):825–832. doi: 10.1111/eci.12660
- Patel A, Panchal H, Dubinsky MC. Fecal calprotectin levels predict histological healing in ulcerative colitis. Inflamm Bowel Dis. 2017;23(9):1600-1604. doi: 10.1097/MIB.0000000000001157
- Cioffi M, De Rosa A, Serao R, et al. Laboratory markers in ulcerative colitis: current insights and future advances. World J Gastrointest Pathophysiol. 2015;6(1):13-22. doi: 10.4291/wjgp.v6.i1.13
- Chen P, Zhou G, Lin J, et al. Serum Biomarkers for Inflammatory Bowel Disease. Front Med. 2020;7:123. doi: 10.3389/fmed.2020.00123
- Almousa AA, Morris M, Fowler S, et al. Elevation of serum pyruvate kinase M2 (PKM2) in IBD and its relationship to IBD indices. Clin Biochem. 2018;53:19-24. doi: 10.1016/j.clinbiochem.2017.12.007
- Shinzaki S, Matsuoka K, Iijima H, et al. Leucine-rich alpha-2 glycoprotein is a serum biomarker of mucosal healing in ulcerative colitis. J Crohns Colitis. 2017;11(1):84-91. doi: 10.1093/ecco-jcc/jjw132
- Simondi D, Mengozzi G, Betteto S, et al. Antiglycan antibodies as serological markers in the differential diagnosis of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(5):645-651. doi: 10.1002/ibd.20368
- Fallingborg J, Christensen LA, Jacobsen BA, et al. Very low intraluminal colonic pH in patients with active ulcerative colitis. Dig Dis Sci. 1993;38(11):1989–1993. doi: 10.1007/BF01297074
- Kaczmarczyk O, Dąbek-Drobny A, Woźniakiewicz M, et al. Fecal levels of lactic, succinic and short-chain fatty acids in patients with ulcerative colitis and Crohn disease: a pilot study. J Clin Med. 2021;10(20):4701. doi: 10.3390/jcm10204701
- Khan I, Ullah N, Zha L, et al. Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome. Pathogens. 2019;8(3):126. doi: 10.3390/pathogens8030126
- Nugent SG, Kumar D, Rampton DS, et al. Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut. 2001;48(4):571-577. doi: 10.1136/gut.48.4.571
- Okada K, Ikemoto M. Carbonic anhydrase III Has Potential as a Biomarker for Experimental Colitis and Functions as an Immune Regulator by Inhibiting Inflammatory Cytokine Secretion. Biology. 2022;11(4):494. doi: 10.3390/biology11040494
- Faramarzpour A, Tehrani AA, Tamaddonfard E, et al. The effects of crocin, mesalazine and their combination in the acetic acid-induced colitis in rats. Vet Res Forum. 2019;10(3):227-234. doi: 10.30466/vrf.2019.35900
- Kühn R, Löhler J, Rennick D, et al. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75(2):263- 274. doi: 10.1016/0092-8674(93)80068-p
- Zhao J, Jin D, Huang M, et al. Glycolysis in the tumor microenvironment: a driver of cancer progression. Front Cell Dev Biol. 2024;12:1416472. doi: 10.3389/fcell.2024.1416472
- Williams KL, Fuller CR, Dieleman LA, et al. Enhanced survival and mucosal repair after dextran sodium sulfate-induced colitis in transgenic mice that overexpress growth hormone. Gastroenterology. 2001;120(4):925-937. doi: 10.1053/gast.2001.22470
- Holtug K, Hove H, Mortensen PB. Stimulation of butyrate absorption in the human rectum in vivo. Scand J Gastroenterol. 1995;30(10):982-988. doi: 10.3109/00365529509096342
- Ricci G, Stabellini G, Bersani G, et al. Ornithine decarboxylase in colonic mucosa from patients with moderate or severe Crohn’s disease and ulcerative colitis. Eur J Gastroenterol Hepatol. 1999;11(8):903-904. doi: 10.1097/00042737-199908000-00016
30. Osuka A, Shimizu K, Ogura H, et al. Prognostic impact of fecal pH in critically ill patients. Crit Care. 2012;16(4):R119. doi: 10.1186/cc11413
