The production of urinary phenols by gut bacteria and their possible ce:role in the causation of large bowel cancer

Abstract

Epidemiological evidence is presented to relate the amount of dietary meat to the risk of large bowel cancer; it has been suggested that this may be due to the production of cocarcinogenic volatile phenols by intestinal bacteria from tyrosine. This paper describes preliminary experiments to test this suggestion. In vitro, aerobic bacteria tended to produce phenol from tyrosine while anaerobic bacteria produced p-cresol. Urine from 10 normal healthy persons contained a mean of 9.8 mg phenol/day and 51.8 mg p-cresol/day. Results from studies on patients with ileostomy, colostomy, and diverticular disease indicated that p-cresol is largely produced by the anaerobic flora of the left colon while phenol was produced in the ileum (when colonized) and cecum. In patients with familial polyposis the activity of the aerobic flora was apparently normal but there was greatly reduced amounts of p-cresol produced. The amounts of urinary volatile phenols in six patients with newly diagnosed large bowel cancer were not different from the normal values, indicating that cocarcinogenic phenols were unlikely to be a major cause of the disease.

Hypothesis: Phenol and hydroquinone derived mainly from diet and gastrointestinal flora activity are causal factors in leukemia

“…54 Patients with diverticular disease or polyposis with ileorectal anastamosis appeared to have elevated urinary phenol levels (about 2-fold) relative to normal individuals. The most noticeable increase in phenol levels was observed among patients with Crohn's disease, which is a common type of inflammatory bowel disease ( Figure 2).…”

“…High background concentrations of phenol, hydroquinone, catechol and 1,2,4-benzenetriol have been measured in the blood, urine and intestines of presumably unexposed humans [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] and in the blood and urine of rodents. [63][64][65] Representing measurements of hundreds of individuals in total, these studies showed that mean urinary phenol and hydroquinone levels were about 10 p.p.m.…”

“…The urinary concentrations of phenol and hydroquinone varied widely (ie 5-to 25-fold) within a given population. [49][50][51] Some studies have reported differences in phenol levels between sexes, 54 whereas others have not. 48 Variability of phenol levels among individuals appears to be greater than the difference among males and females.…”

“…The other important factors affecting reported phenol values are variation in sampling and adjustment for gravity and creatinine. Phenol levels are typically reported as a concentration, mass per mass creatinine, or total mass excreted in 24 h. Data from Refs 47,50,51,54,57,58,75,107,108. flora. Below we discuss these sources and also describe additional host and environmental factors that affect the variability of the background levels of the phenolic compounds.…”

“…Endogenous bacterial strains that convert tyrosine to phenol include the obligate anaerobes, Bacteroides fragilis, Peptostreptococcus asaccharolyticus, and the facultative anaerobes, Escherichia coli, Proteus sp., Staphylococcus faecalis and Staphylococcus albus (Figure 3). 54,62,85 Studies of human colonic contents in sudden death victims in the UK showed that anaerobic bacteria outnumber facultative microorganisms in the human gut by two to three orders of magnitude with Bacteroides fragilis being the most numerous 86 (Figure 3). However, the composition of intestinal bacteria varies considerably among different populations, particularly in Western vs other non-industrialized societies.…”