Our Science

       Back to 2001, Dr. Xiaofa Qin, the founder of the company, found that digestive pancreatic proteases such as trypsin and chymotrypsin can be inactivated by unconjugated (free) bilirubin but not conjugated bilirubin. More evidences he collected made him to believe that impaired inactivation of digestive proteases by deconjugated bilirubin as the result of reduction in gut bacteria, thus bacterial β-glucuronidase, along with improved hygiene and inhibition by dietary chemicals such as the widely used artificial sweetener saccharin in modern society may have played critical role in the pathogenesis of inflammatory bowel disese (IBD), with the eventual publication of the paper (Qin, X. Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease[J]. Med Hypotheses, 59[2]:159-63, 2002) and establishment of a unified hypothesis on the etiology for IBD including the cause and mechanism of IBD and the relationship between UC and CD (Qin, X. Etiology of inflammatory bowel disease: A unified hypothesis. World J Gastroenterol, 18[15]:1708-22, 2012). 

      The damage by the poorly inactivated digestive proteases in the lower gut may be the primary root cause for IBD, while the damage of the gut barrier (leaky gut) and increased infiltration of bacterial and other toxic components into the blood may have also played critical role in the chronic inflammation and multiple other autoimmune, allergic diseases, metabolic, psychoneurological, cancerous diseases that more and more evidences demonstrated a close association with dysbiosis of gut microbiota, as proposed in some other papers by Dr. Qin (Qin, X. What caused the increase of autoimmune and allergic diseases: a decreased or an increased exposure to luminal microbial components?  World J Gastroenterol, 13[8]:1306-7, 2007) and (Qin X. Changes in complex microecosystem of gut and pathogenesis of diseases in modern society - Impaired inactivation of digestive proteases may be the key event. World J Complex Med 1(1): 38-43, 2015).

Below is a list of our publications, most of them can be found on pubmed. 

76. Qin X. More Epidemiological Studies Warranted to Determine the Cause of Inflammatory Bowel Disease. Inflamm Bowel Dis. 2020 Dec 17:izaa329. doi: 10.1093/ibd/izaa329. Online ahead of print. PMID: 33331632 

75. Qin X. Non-Nutritive Sweeteners May Have a Bell-Shaped Dose Response for Dysbiosis-Related Adverse Effects That Contributed to Discrepancies between Prospective Cohort and Randomized Controlled Studies. J Obes Metab Syndr. 2020 Sep 30;29(3):237-239. doi: 10.7570/jomes20077. PMID: 32908023 Free PMC article. 

74. Qin X. Inhibition of Experimental Colitis by Saccharin in Animals: Should We Dismiss or Raise Concerns Regarding Possible Adverse Effects of Saccharin on Human Gut Microbiota and Health? Inflamm Bowel Dis. 2020 Nov 19;26(12):e159-e160. doi: 10.1093/ibd/izaa180. PMID: 32651958

73. Li X, Liu Y, Wang Y, Li X, Liu X, Guo M, Tan Y, Qin X, Wang X, Jiang M. Sucralose Promotes Colitis-Associated Colorectal Cancer Risk in a Murine Model Along With Changes in Microbiota. Front Oncol. 2020 Jun 3;10:710. doi: 10.3389/fonc.2020.00710. eCollection 2020. PMID: 32582527

72. He Y, Li X, Yu H, Ge Y, Liu Y, Qin X, Jiang M, Wang X. The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice. Front Cell Infect Microbiol. 2019 Nov 15;9:393. doi: 10.3389/fcimb.2019.00393. eCollection 2019. PMID: 31803633 

71. He Y, Li X, Yu H, Ge Y, Liu Y, Qin X, Jiang M, Wang X. The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice. Front Cell Infect Microbiol. 2019 Nov 15;9:393. doi: 10.3389/fcimb.2019.00393. eCollection 2019. PubMed PMID: 31803633; PubMed Central PMCID: PMC6873233.

70. Qin X. Impaired Inactivation of Digestive Proteases in Lower Gut Due to Inhibition of Gut Bacteria by Food Additives Such as Saccharin and Sucralose as Main Cause of Inflammatory Bowel Disease: A Two-Decades-Long Hypothesis Warrants Testing. Inflamm Bowel Dis. 2019 Oct 18;25(11):e141. doi: 10.1093/ibd/izz187. PubMed PMID: 31504530.

69. He Y, Yu H, Ge Y, Li X, Jiang M, Liu Y, Li X, Wang Y, Guo M, Qin X, Wang X. Bacterial β-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease. Biochem Biophys Res Commun. 2019 May 28;513(2):426-433. doi: 10.1016/j.bbrc.2019.03.196. Epub 2019 Apr 6. PubMed PMID: 30967260.

68. Qin X. May Dysbiosis Caused by Dietary Chemicals Such as Sucralose and Saccharin Be More Detrimental to the Gut and Health Than Antibiotics? How? Inflamm Bowel Dis. 2019 Feb 21;25(3):e20. doi: 10.1093/ibd/izy198. PubMed PMID: 29850815.

67. Zheng JD, He Y, Yu HY, Liu YL, Ge YX, Li XT, Li X, Wang Y, Guo MR, Qu YL, Qin XF, Jiang MS, Wang XH. Unconjugated bilirubin alleviates experimental ulcerative colitis by regulating intestinal barrier function and immune inflammation. World J Gastroenterol. 2019 Apr 21;25(15):1865-1878. doi: 10.3748/wjg.v25.i15.1865. PubMed PMID: 31057300; PubMed Central PMCID: PMC6478610.

66. Wang X, Guo J, Liu Y, Yu H, Qin X. Sucralose Increased Susceptibility to Colitis in Rats. Inflamm Bowel Dis. 2019 Jan 10;25(2):e3-e4. doi: 10.1093/ibd/izy196. PubMed PMID: 29846590.

65. Qin X. The Effect of Splenda on Gut Microbiota of Humans Could be Much More Detrimental Than in Animals and Deserves More Extensive Research. Inflamm Bowel Dis. 2019 Jan 10;25(2):e7. doi: 10.1093/ibd/izy181. PubMed PMID: 29771341.

64. Zhou JA, Jiang M, Yang X, Liu Y, Guo J, Zheng J, Qu Y, Song Y, Li R, Qin X, Wang X. Unconjugated bilirubin ameliorates the inflammation and digestive protease increase in TNBS-induced colitis. Mol Med Rep. 2017 Aug;16(2):1779-1784. doi: 10.3892/mmr.2017.6825. Epub 2017 Jun 21. PubMed PMID: 28656252; PubMed Central PMCID: PMC5562003.

63. Qin X. Impaired inactivation of digestive proteases: The possible key factor for the high susceptibility of germ-free and antibiotic-treated animals to gut epithelial injury. World J Gastrointest Pathophysiol. 2017 Feb 15;8(1):1-2. doi: 10.4291/wjgp.v8.i1.1. Review. PubMed PMID: 28251033; PubMed Central PMCID: PMC5311466.

62. Qin X. Inactivation of Digestive Proteases and Degradation of Mucus: The Possible Key Factors That Determined the Different Effects on the Gut by Antibiotics. Inflamm Bowel Dis. 2017 Feb;23(2):E7. doi: 10.1097/MIB.0000000000001015. PubMed PMID: 28079627.

61. Qin X. Damage of the Mucus Layer: The Possible Shared Critical Common Cause for Both Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS). Inflamm Bowel Dis. 2017 Feb;23(2):E11-E12. doi: 10.1097/MIB.0000000000001010. PubMed PMID: 28079624.

60. Qin X. Perinuclear Antineutrophil Cytoplasmic Antibody with a Large Portion Being Anti-β-Glucuronidase, May Have Played a Causative Role in the Pathogenesis of Inflammatory Bowel Disease. Inflamm Bowel Dis. 2016 Nov;22(11):E41-E42. PubMed PMID: 27618502.

59. Qin X. Increased Milk Consumption but Decreased Risk of Crohn's Disease (CD): Critical Evidence Negated Causative Role of Mycobacterium avium Subspecies paratuberculosis (MAP) in CD. Inflamm Bowel Dis. 2016 Sep;22(9):E37-8. doi: 10.1097/MIB.0000000000000892. PubMed PMID: 27542142.

58. Li R, Zheng J, Jiang M, Liu Y, Qin X, Wang X. Increased Digestive Proteases and Decreased β-Glucuronidase in Feces of Rats Treated with Sucralose and Saccharin-Another Critical Evidence That These Dietary Chemicals May Be Important Causative Factors for Inflammatory Bowel Disease. Inflamm Bowel Dis. 2016 Aug;22(8):E29-30. doi: 10.1097/MIB.0000000000000859. PubMed PMID: 27416049.

57. Qin X. How Sugar and Soft Drinks Are Related to Inflammatory Bowel Disease? Inflamm Bowel Dis. 2016 Jun;22(6):E18-9. doi: 10.1097/MIB.0000000000000774. PubMed PMID: 27057687.

56. Qin X. Is Colonic Crohn's Disease More Closely Related to Ulcerative Colitis or Crohn's Disease by Nature? Inflamm Bowel Dis. 2016 May;22(5):E15. doi: 10.1097/MIB.0000000000000777. PubMed PMID: 26978729.

55. Qin X. Can Crohn’s disease really be caused by Mycobacterium avium subspecies paratuberculosis? – With my alternative theory that reduction in commensal gut bacteria and resultant impaired inactivation of digestive proteases as the primary cause. Int J Clin Med Microbiol 1: 109, 2016.

54. Qin X. Inactivation of pancreatic digestive proteases by deconjugated bilirubin from the liver: A critical mechanism for gut protection. Journal of Gastroenterology, Pancreatology & Liver Disorders 3(1): 1-2, 2016.

53. Qin X. Impaired inactivation of digestive proteases and increased degradation of mucus: the possible primary cause of translocation of native commensal colonic bacteria and inflammation by antibiotics. J Clin Pathol Microbes 1(1): 1- 2, 2016.

52. Qin X. The Possible Link Between Artificial Sweeteners Such as Saccharin and Sucralose and Inflammatory Bowel Disease Deserves Further Study. Inflamm Bowel Dis. 2016 Jun;22(6):E17. doi: 10.1097/MIB.0000000000000760. PubMed PMID: 26978727.

51. Qin X. Food Additives Should Not Be Ruled Out as the Possible Causative Factors of Inflammatory Bowel Disease in Korea. Inflamm Bowel Dis. 2016 Jan;22(1):E1. doi: 10.1097/MIB.0000000000000668. PubMed PMID: 26566247.

50. Qin X. How to Explain the Dramatic Increase Around 2000 but Recent Leveling Off of Inflammatory Bowel Disease in Korea? Inflamm Bowel Dis. 2015 Aug;21(8):E16-7. doi: 10.1097/MIB.0000000000000491. PubMed PMID: 26111209.

49. Qin X. Can inflammatory bowel disease really be solved by the multiple –omics and meta-omics analyses? Immunol Lett. 2015 Jun;165(2):107-8. doi: 10.1016/j.imlet.2015.03.007. Epub 2015 Mar 28. PubMed PMID: 25827759.

48. Zhou K, Jiang M, Qin X, Wang X. Role of bilirubin in digestive proteases inactivation in the lower intestine. Dig Liver Dis. 2015 May;47(5):438-9. doi: 10.1016/j.dld.2015.01.158. Epub 2015 Feb 7. PubMed PMID: 25732433.

47. Qin X. The close relationship between mucosal healing and prognoses of inflammatory bowel disease may have just reflected the root mechanism of the disease. J Clin Gastroenterol Treat 1：002, 2015.

46. Qin X. Changes in complex microecosystem of gut and pathogenesis of diseases in modern society - Impaired inactivation of digestive proteases may be the key event. World J Complex Med 1(1): 38-43, 2015.

45. Qin X. How to explain recent multiple reports on the decline of inflammatory bowel disease in Canada. Can J Gastroenterol Hepatol. 2014 Dec;28(11):620. PubMed PMID: 25575113; PubMed Central PMCID: PMC4277177.

44. Qin X, Deitch EA. Dissolution of lipids from mucus: a possible mechanism for prompt disruption of gut barrier function by alcohol. Toxicol Lett. 2015 Jan 22;232(2):356-62. doi: 10.1016/j.toxlet.2014.11.027. Epub 2014 Nov 25. PubMed PMID: 25445722; PubMed Central PMCID: PMC4291284.

43. Qin X. May bacterial or pancreatic proteases play a critical role in inflammatory bowel disease? World J Gastroenterol. 2014 Sep 21;20(35):12709-10. doi: 10.3748/wjg.v20.i35.12709. PubMed PMID: 25253982; PubMed Central PMCID: PMC4168115.

42. Qin X. May artificial sweeteners not sugar be the culprit of dramatic increase of inflammatory bowel disease in China? Chin Med J (Engl). 2014;127(17):3196-7. PubMed PMID: 25189972.

41. Qin X. Why pediatric inflammatory bowel disease (IBD) in Sweden shared similar trend of change as general population IBD in Denmark but not pediatric IBD in Norway? Scand J Gastroenterol. 2014 Oct;49(10):1268-9. doi: 10.3109/00365521.2014.946086. Epub 2014 Aug 6. PubMed PMID: 25099193.

40. Zhou K, Jiang M, Liu Y, Qu Y, Shi G, Yang X, Qin X, Wang X. Effect of bile pigments on the compromised gut barrier function in a rat model of bile duct ligation. PLoS One. 2014 Jun 3;9(6):e98905. doi: 10.1371/journal.pone.0098905. eCollection 2014. PubMed PMID: 24892651; PubMed Central PMCID: PMC4044053.

39. Qin X. What might be the cause for the emerging inflammatory bowel disease in Saudi outpatients? Saudi J Gastroenterol. 2014 Jan-Feb;20(1):75. doi: 10.4103/1319-3767.126329. PubMed PMID: 24496163; PubMed Central PMCID: PMC3952426.

38. Qin X. Comment on: paediatric inflammatory bowel disease in a multiracial Asian country. Singapore Med J. 2013 Dec;54(12):716. PubMed PMID: 24356761.

37. Qin X. When and how was the new round of increase in inflammatory bowel disease in the United States started? J Clin Gastroenterol. 2014 Jul;48(6):564-5. doi: 10.1097/MCG.0000000000000031. PubMed PMID: 24231936.

36. Qin X. Is the gap between the developed and developing countries in the incidence of inflammatory bowel disease disappearing? Gastroenterology. 2013 Oct;145(4):912. doi: 10.1053/j.gastro.2013.07.052. Epub 2013 Aug 22. PubMed PMID: 23973855.

35. Qin X. How NOD2 and autophagy may be related to Crohn's disease? A view shifted from live microbes to luminal bacterial debris. J Crohns Colitis. 2014 Jan;8(1):88. doi: 10.1016/j.crohns.2013.07.013. Epub 2013 Aug 19. PubMed PMID: 23969121.

34. Qin X. Does the association with NOD2, autophagy and some pathogens really mean Crohn's disease is caused by uncontrolled infection? J Crohns Colitis. 2014 Jan;8(1):87. doi: 10.1016/j.crohns.2013.07.010. Epub 2013 Aug 13. PubMed PMID: 23953237.

33. Qin X. Why is damage limited to the mucosa in ulcerative colitis but transmural in Crohn's disease? World J Gastrointest Pathophysiol. 2013 Aug 15;4(3):63-4. doi: 10.4291/wjgp.v4.i3.63. PubMed PMID: 23946890; PubMed Central PMCID: PMC3740262.

32. Qin X. How to explain the discordant change of ulcerative colitis and Crohn disease in adjacent or even the same regions and time periods. J Pediatr Gastroenterol Nutr. 2013 Nov;57(5):e30. doi: 10.1097/MPG.0b013e3182a504e8. PubMed PMID: 23863324.

31. Qin X. Have genome-wide association studies or knockout mice more reflected the true nature of inflammatory bowel disease? J Crohns Colitis. 2013 Jun;7(5):419-20. doi: 10.1016/j.crohns.2013.01.013. Epub 2013 Feb 9. PubMed PMID: 23403038.

30. Qin X. Etiology of inflammatory bowel disease: a unified hypothesis. World J Gastroenterol. 2012 Apr 21;18(15):1708-22. doi: 10.3748/wjg.v18.i15.1708. Review. PubMed PMID: 22553395; PubMed Central PMCID: PMC3332284.

29. Qin X. Food additives: possible cause for recent remarkable increase of inflammatory bowel disease in children. J Pediatr Gastroenterol Nutr. 2012 Apr;54(4):564. doi: 10.1097/MPG.0b013e3182464b0e. PubMed PMID: 22450042.

28. Qin X. What made Canada become a country with the highest incidence of inflammatory bowel disease: could sucralose be the culprit? Can J Gastroenterol. 2011 Sep;25(9):511. PubMed PMID: 21912763; PubMed Central PMCID: PMC3202359.

27. Qin X. What caused the recent worldwide increase of inflammatory bowel disease: should sucralose be added as a suspect? Inflamm Bowel Dis. 2011 Oct;17(10):E139. doi: 10.1002/ibd.21823. Epub 2011 Jul 7. PubMed PMID: 21739539.

26. Qin X. The effect of dietary chemicals on gut bacteria and IBD demands further study. J Crohns Colitis. 2011 Apr;5(2):175. doi: 10.1016/j.crohns.2011.01.007. Epub 2011 Feb 18. PubMed PMID: 21453893.

25. Qin X. How can we really reduce the morbidity of inflammatory bowel disease - Research on genes and cytokines, or find out the causative factors in the environment? J Crohns Colitis. 2009 Dec;3(4):315. doi: 10.1016/j.crohns.2009.09.001. Epub 2009 Oct 8. PubMed PMID: 21172295.

24. Qin X, Sheth SU, Sharpe SM, Dong W, Lu Q, Xu D, Deitch EA. The mucus layer is critical in protecting against ischemia-reperfusion-mediated gut injury and in the restitution of gut barrier function. Shock. 2011 Mar;35(3):275-81. doi: 10.1097/SHK.0b013e3181f6aaf1. PubMed PMID: 20856173; PubMed Central PMCID: PMC3261620.

23. Sharpe SM, Qin X, Lu Q, Feketeova E, Palange DC, Dong W, Sheth SU, Lee MA, Reino D, Xu DZ, Deitch EA. Loss of the intestinal mucus layer in the normal rat causes gut injury but not toxic mesenteric lymph nor lung injury. Shock. 2010 Nov;34(5):475-81. doi: 10.1097/SHK.0b013e3181dc3ff5. PubMed PMID: 20220565; PubMed Central PMCID: PMC2923274.

22. Sheth SU, Lu Q, Twelker K, Sharpe SM, Qin X, Reino DC, Lee MA, Xu DZ, Deitch EA. Intestinal mucus layer preservation in female rats attenuates gut injury after trauma-hemorrhagic shock. J Trauma. 2010 Feb;68(2):279-88. doi: 10.1097/TA.0b013e3181caa6bd. PubMed PMID: 20154538; PubMed Central PMCID: PMC3024717.

21. Qin X. Can meat and protein really increase, while vegetables and fruits decrease the risk of inflammatory bowel disease? How? J Crohns Colitis. 2009 Jun;3(2):136. doi: 10.1016/j.crohns.2009.02.001. Epub 2009 Mar 3. PubMed PMID: 21172259.

20. Qin X. Inactivation of Digestive Proteases by Deconjugated Bilirubin and the Physiological Significance of Fasting Hyperbilirubinemia. Gastroenterology Res. 2009 Feb;2(1):62. Epub 2009 Jan 20. PubMed PMID: 27956956; PubMed Central PMCID: PMC5139891.

19. Qin X. Impaired inactivation of digestive proteases: a factor that may have confounded the efficacy of antibiotics aimed at reducing the exposure to luminal bacteria and their components. Am J Gastroenterol. 2008 Nov;103(11):2955-6. doi: 10.1111/j.1572-0241.2008.02094_17.x. PubMed PMID: 19032485.

18. Qin XF. Bilirubin would be the indispensable component for some of the most important therapeutic effects of Calculus Bovis (Niuhuang). Chin Med J (Engl). 2008 Mar 5;121(5):480. PubMed PMID: 18364128.

17. Qin X. What caused the extra high incidence of inflammatory bowel disease in the industrialized countries in the West: lack of some nutrients or increased intake of some harmful agents? Inflamm Bowel Dis. 2009 Feb;15(2):319. doi: 10.1002/ibd.20606. PubMed PMID: 18668675.

16. Qin X. Gut microbiota: a new aspect that should be taken into more consideration when assessing the toxicity of chemicals or the adverse effects and efficacy of drugs. Regul Toxicol Pharmacol. 2008 Jul;51(2):251. doi: 10.1016/j.yrtph.2008.04.004. Epub 2008 May 19. PubMed PMID: 18490094.

15. Qin X. With the great complexity unveiling, can we still decipher the interaction between gut flora and the host in inflammatory bowel disease to find out the mechanism and cause? How? Inflamm Bowel Dis. 2008 Nov;14(11):1607-8. doi: 10.1002/ibd.20474. PubMed PMID: 18421753.

14. Qin X. Has Crohn's disease really occurred anywhere in the digestive tract? Inflamm Bowel Dis. 2008 Oct;14(10):1461-2. doi: 10.1002/ibd.20451. PubMed PMID: 18383523.

13. Qin X. Reduced production of digestive proteases and the efficacy of enteral and parenteral nutrition on inflammatory bowel disease. Inflamm Bowel Dis. 2008 Jun;14(6):871. doi: 10.1002/ibd.20366. PubMed PMID: 18200511.

12. Qin X. Inactivation of digestive proteases by deconjugated bilirubin: the possible evolutionary driving force for bilirubin or biliverdin predominance in animals. Gut. 2007 Nov;56(11):1641-2. PubMed PMID: 17938442; PubMed Central PMCID: PMC2095646.

11. Qin X. Synergic effect of bacterial glycosidases and digestive proteases on mucus degradation and the reduced risk of inflammatory bowel disease-like gut damage in both germ-free and poor hygiene conditions. Inflamm Bowel Dis. 2008 Jan;14(1):145-6. PubMed PMID: 17924564.

10. Qin X. Inactivation of digestive proteases: another mechanism that probiotics may have conferred a protection. Am J Gastroenterol. 2007 Sep;102(9):2109. PubMed PMID: 17727445.

9. Qin X, Caputo FJ, Xu DZ, Deitch EA. Hydrophobicity of mucosal surface and its relationship to gut barrier function. Shock. 2008 Mar;29(3):372-6. PubMed PMID: 17693944.

8. Qin X. What is human inflammatory bowel disease (IBD) more like: Johne's disease in cattle or IBD in dogs and cats? Inflamm Bowel Dis. 2008 Jan;14(1):138. PubMed PMID: 17680652.

7. Qin X. Inhibition of gut bacteria by dietary chemicals and the hygiene hypothesis. Ann Allergy Asthma Immunol. 2007 Jun;98(6):602. PubMed PMID: 17601281.

6. Qin X. High incidence of inflammatory bowel disease with improved hygiene and failure to get human-like IBD in laboratory animals. World J Gastroenterol. 2007 Jun 21;13(23):3271. PubMed PMID: 17589913; PubMed Central PMCID: PMC4436620.

5. Qin X. Primary sclerosing cholangitis and inflammatory bowel disease: where is the link? Am J Gastroenterol. 2007 Jun;102(6):1332-3. PubMed PMID: 17531026.

4. Qin X. Inactivation of digestive proteases: another aspect of gut bacteria that should be taken into more consideration. World J Gastroenterol. 2007 Apr 28;13(16):2390-1. PubMed PMID: 17511046; PubMed Central PMCID: PMC4147156.

3. Qin X. What caused the increase of autoimmune and allergic diseases: a decreased or an increased exposure to luminal microbial components? World J Gastroenterol. 2007 Feb 28;13(8):1306-7. PubMed PMID: 17451223; PubMed Central PMCID: PMC4147017.

2. Qin X. Is the incidence of inflammatory bowel disease in the developed countries increasing again? Is that surprising? Inflamm Bowel Dis. 2007 Jun;13(6):804-5.

1. Qin, X. Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease. Med Hypotheses 59: 159-163, 2002.