Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept

Abstract

Background: Antisecretory factor (AF), a 41 kDa cloned and sequenced protein, suppresses intestinal inflammation and hypersecretion in animals. Endogenous AF production can be induced by dietary modifications in several animal species, and this feed has been shown to reduce the incidence of diarrhoeal disease in weaning piglets. The role of AF in intestinal disease in humans is not known.

Aims: To study the effects of hydrothermally processed cereals, optimised for AF induction in animals, added to the diet of patients with longstanding symptoms of inflammatory bowel disease (IBD).

Patients: Fifty three patients with IBD (ulcerative colitis and Crohn's disease) were entered into the study, and 50 completed follow up. The experimental group consisted of 16 females (mean age 50 (SEM 5) years) and 10 males (41 (4) years) and the placebo group of 12 women (41 (4) years old) and 12 men (51 (5) years).

Methods: Patients were randomised to receive either hydrothermally processed cereals (active treatment) or the same amount of ordinary cereals (placebo treatment) for four weeks in a double blind study design. Baseline diet and medications remained unchanged. Bowel symptoms, plasma levels of AF, and colonic biopsies were evaluated before and after treatment.

Results: The active treatment significantly improved subjective ratings of clinical symptoms and increased plasma AF levels compared with placebo. Plasma lipid levels were unaffected.

Conclusion: Hydrothermally processed cereals can induce AF production in human IBD. This increase in endogenous AF activity is associated with clinical improvement. Further studies are warranted to clarify the exact role of AF in human intestinal disease.

Figure 1

Subjective estimation of the effects of the two diets after four weeks of treatment, expressed as percentage improvement of the condition (VAS). Data are mean (SEM). *Significant difference between the active and placebo groups (p<0.05). VAS, visual analogue scale.

Figure 2

Plasma levels of antisecretory factor (AF) in the two groups of patients at the start of the experiment, after four weeks of active or placebo diet, and after eight weeks (that is, four weeks after termination of the diets). Data are mean (SEM). ***Significant difference between groups (p<0.001) at four and eight weeks. NS, not significant.

Figure 3

Biopsies from a healthy large intestine processed to demonstrate immunoreactivity of antisecretory factor (AF). Bars=100 µm. (A) Low magnification showing AF immunoreactivity in the surface epithelium (arrowhead), in crypt cells, and in lymphocyte-like cells (arrows) in the lamina propria. (B) Larger magnification showing the AF positive lymphocyte-like cells (arrows).

Figure 4

Rectal biopsies from patients with ulcerative colitis treated with the active diet. The sections were incubated with an antiserum against antisecretory factor (AF). Bars=100 µm. (A) Patient No 31 before the diet period. (B) Patient No 31 after the diet period. There appears to be more AF positive cells (arrows) in the lamina propria after the diet period. (C) Larger magnification of (B), showing AF positive cells (arrows) in the lamina propria. (D) Patient No 12 before the diet period. There are signs of an acute inflammatory reaction. Many small inflammatory cells show moderate AF immunoreactivity. (E) The same patient after the diet period. In this biopsy there is no acute inflammation. Large AF positive cells (arrows) are evenly distributed within the entire lamina propria.