Abstract
Measurements of luminal pH in the normal gastrointestinal tract have shown a progressive increase in pH from the duodenum to the terminal ileum, a decrease in the caecum, and then a slow rise along the colon to the rectum. Some data in patients with ulcerative colitis suggest a substantial reduction below normal values in the right colon, while limited results in Crohn's disease have been contradictory.
Determinants of luminal pH in the colon include mucosal bicarbonate and lactate production, bacterial fermentation of carbohydrates and mucosal absorption of short chain fatty acids, and possibly intestinal transit. Alterations in these factors, as a result of mucosal disease and changes in diet, are likely to explain abnormal pH measurements in inflammatory bowel disease (IBD).
It is conceivable that reduced intracolonic pH in active ulcerative colitis impairs bioavailability of 5-aminosalicylic acid from pH dependent release formulations (Asacol, Salofalk) and those requiring cleavage by bacterial azo reductase (sulphasalazine, olsalazine, balsalazide), but further pharmacokinetic studies are needed to confirm this possibility. Reports that balsalazide and olsalazine may be more efficacious in active and quiescent ulcerative colitis, respectively, than Asacol suggest that low pH may be a more critical factor in patients taking directly pH dependent release than azo bonded preparations. Reduced intracolonic pH also needs to be considered in the development of pH dependent colonic release formulations of budesonide and azathioprine for use in ulcerative and Crohn's colitis.
This paper reviews methods for measuring gut pH, its changes in IBD, and how these may influence current and future therapies.
Under normal physiological conditions, the pH value from the stomach to the intestine basically showed an increasing trend, specifically, acidic stomach (pH 1.5 to 3.5), duodenum (pH 6), terminal ileum (pH 7.4), terminal cecum (pH 6), and colon (pH 6.7) (Chambin et al., 2006). However, in patients with IBD, there was a significant change in the pH of the colon, which was significantly more acidic (pH 2.3–5.5) than that of normal colon. Changes in pH may be mainly due to differences in mucosal lactate and bicarbonate production, mucosal absorption of short-chain fatty acids (SCFAs), bacterial fermentation of carbohydrates, and intestinal transport between the diseased and normal intestines (Nugent, 2001). The pH-responsive systems based on the characteristics of pH in different parts of the gastrointestinal tract have been applied to the research of colon-targeted DNSs. However, DNSs based on pH difference had low colon-targeted delivery efficiency due to changes in the pH environment in the colon of patients with IBD, which affected the aggregation of drugs in the diseased regions.
In particular, this review presents the distribution of pH in the human body, its role and clinical significance, and various factors that affect intestinal and fecal pH, including the gut microbiota and its metabolites.
According to this report, the average pH value of the small intestinal tract is 6.1 in the duodenum, which is in direct contact with the stomach, rising to 7.1 in the middle part of the small intestine and reaching 7.5 in the distal part of the small intestine (Figure 1). The pH of the intestinal lumen increases to approximately 6.5 in the proximal small bowel and to approximately 7.5 near the ileum in the distal small bowel. Thereafter, it temporarily reduces to approximately 6.0 near the cecum at the entrance of the large intestine and then increases toward the rectum, where it reaches to around 7.0 near the exit of the large intestine.