This letter, published in 1999, is not now available on the website of the Pharmaceutical Journal. Only those later than 2000 can be accessed online. The letter has relevance to current interest in the gut microbiome and is published here with permission of the Pharmaceutical Journal.
Ulcerative colitis
More pieces for the jigsaw please
From Dr Mary Griffiths, MRPharmS, MIBiol
SIR,�The report on the treatment of ulcerative colitis with E coli (PJ, August 28, p303) was another piece in the intriguing jigsaw of what produces the condition and its relapses. The mechanisms of inflammation and treatment and prevention of the damage to the inner surface of the colon by anti-inflammatory, steroid and immunosuppressant preparations are well documented. Dietary changes have little effect on ulcerative colitis, except for omitting milk in some patients. Sometimes, stressful, emotional events are linked with the onset of the disease and episodic symptoms and there may be a hereditary link.
Just suppose that the appendix is not a useless relic of evolution but a culture vessel and inoculating system to deliver actively growing organisms into the caecum. These are added to the chyme, which spurts from the ileocaecal valve, and to the residues of digestion of previous meals which are moved on more slowly when they reach the colon. The segmentation and pendulum movements of the first part of the colon mix its contents and there is fermentation and a rapid increase in the number of micro-organisms.
Why the body encourages this symbiosis is perhaps answered by the question of how does the body get rid of digestive enzymes before they are concentrated in faeces and give rise to self-harm? These enzymes are not normally reabsorbed in any quantity. The capacity of the system can perhaps be exceeded, for example, when single high doses of pancreatic enzymes given for cystic fibrosis damage the ascending colon. The diarrhoea caused by antibiotics is attributed to the ascent of resistant organisms such as Candida albicans, but a lower number of organisms to deal with digestive residues could also be involved. Appendectomy can result in more frequent colon upsets and a higher risk of certain cancers. In active ulcerative colitis, the colon walls are smooth and tubular and reduced segmentation means less effective mixing of its contents. E coli organisms surviving digestion could supplement the reduced numbers for the deactivation of digestive residues. Short-chain fatty acids normally produced by caecum fermentation have a beneficial effect in ulcerative colitis and the protection of mucous lining from enzyme action has explained the effectiveness of bismuth enemas.
I remember reading somewhere that there is an excess of acetylcholinesterase in ulcerative colitis which could be either a cause or effect of the lack of colon mixing movements and might be genetically determined; certainly, sympathetic stimulation would compound such an effect. Lack of movement causes toxic megacolon, which can be relieved by neostigmine injection. Nicotine stimulates acetylcholine release from postsynaptic neurones in the “gut brain” in the colon wall and would increase segmentation and caecum mixing. This explains why ulcerative colitis is less common in smokers, can relapse if smoking is stopped and symptoms can be reduced by nicotine patches.
Does anyone know of any other pieces of this jigsaw? Have any other anticholinesterase or cholinergic drugs ever been tried in ulcerative colitis to increase colon mixing? Do more readily available probiotics, eg, Lactobacillus species have any benefits? Are there any differences in enzyme activity in the faeces of patients when the disease is active or in remission. Many articles are not specific about which type of colon movement is involved in diseases and treatments, and ulcerative colitis is not always considered separately from Crohn’s disease.
Any comments on this speculative jigsaw puzzle would be appreciated.
Mary Griffiths
Macclesfield, Cheshire
Tags: Appendix, Bacteria, Enzymes, Microbiome, Ulcerative colitis