Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis

Abstract

Background/aim: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a single center intervention study. Primary endpoints were the risk parameters cell proliferation and glutathione S-transferase (GST) detoxification capacity in the pouch mucosa; secondary endpoints were the short chain fatty acid (SCFA) contents, pH, and cytotoxicity of fecal water.

Methods: Before the start and at the end of each 4-week intervention period, six biopsies of the pouch were taken and feces was collected during 24 h. Cell proliferation and GST enzyme activity was assessed in the biopsies and pH, SCFA contents, and cytotoxicity were assessed in the fecal water fraction. The three interventions (sulindac, inulin/VSL#3, sulindac/inulin/VSL#3) were compared with the Mann-Whitney U test.

Results: Cell proliferation was lower after sulindac or VSL#3/inulin, the combination treatment with sulindac/inulin/VSL#3 showed the opposite. GST enzyme activity was increased after sulindac or VSL#3/inulin, the combination treatment showed the opposite effect. However, no significance was reached in all these measures. Cytotoxicity, pH, and SCFA content of fecal water showed no differences at all among the three treatment groups.

Conclusion: Our study revealed non-significant decreased cell proliferation and increased detoxification capacity after treatment with sulindac or VSL#3/inulin; however, combining both regimens did not show an additional effect.

Fig. 1

Study design

Fig. 2

For each patient, the difference in cell proliferation at the end of the intervention period, minus cell proliferation at start, was calculated. Median differences (solid line in each bar) in cell proliferation are given for each intervention group. Bars represent 25% and 75% percentiles, and the minimum and maximum differences are also indicated (T bar). Number of patients involved are: sulindac, n = 7, VSL#3 + inulin, n = 9, sulindac + VSL#3 + inulin (combi), n = 14, P value (Kruskal–Wallis) = 0.13

Fig. 3

For each patient, the difference in GST enzyme activity at the end of the intervention period, minus GST enzyme activity at start, was calculated. Median differences (solid line in each bar) in GST enzyme activity are given for each intervention group. Bars represent 25% and 75% percentiles, and the minimum and maximum differences are also indicated (T bar). Number of patients involved are: sulindac, n = 7, VSL#3 + inulin, n = 9, sulindac + VSL#3 + inulin (combi), n = 15, P value (Kruskal–Wallis) = 0.16

Fig. 4

For each patient, the difference in cytotoxicity of fecal water at the end of the intervention period, minus cytotoxicity at start, was calculated. Median differences (solid line in each bar) in cytotoxicity are given for each intervention group. Bars represent 25% and 75% percentiles, and the minimum and maximum differences are also indicated (T bar). Number of patients involved are: sulindac, n = 7, VSL#3 + inulin, n = 9, sulindac + VSL#3 + inulin (combi), n = 15, P value (Kruskal–Wallis) = 0.19

Fig. 5

For each patient, the difference in total SCFA concentrations in fecal water at the end of the intervention period, minus total SCFA concentrations at start, was calculated. Median differences (solid line in each bar) in total SCFA concentrations in fecal water are given for each intervention group. Bars represent 25% and 75% percentiles, and the minimum and maximum differences are also indicated (T bar). Number of patients involved are: sulindac, n = 7, VSL#3 + inulin, n = 9, sulindac + VSL#3 + inulin (combi), n = 15, P value (Kruskal–Wallis) = 0.98

Fig. 6

For each patient, the difference in fecal pH at the end of the intervention period, minus fecal pH at start, was calculated. Median differences (solid line in each bar) in fecal pH are given for each intervention group. Bars represent 25% and 75% percentiles, and the minimum and maximum differences are also indicated (T bar). Number of patients involved are: sulindac, n = 7, VSL#3 + inulin, n = 9, sulindac + VSL#3 + inulin (combi), n = 15, P value (Kruskal–Wallis) = 0.64