Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation

Background. Disturbances in bowel function in chronic constipation could result in changes in the colonic flora and lead to disordered immunity and to decreased resistance to pathogenic flora. Aim. To investigate systemic immunity, the faecal flora and intestinal permeability in patients with chronic constipation, under basal conditions and following therapy with the laxative Bisacodyl. Methods. Intestinal permeability, faecal flora analysis, T- and B-lymphocyte numbers, T-cell subpopulations, lymphocyte proliferation, phagocytosis, intracellular killing of Staphylococcus aureus by neutrophils, as well as circulating levels of immunoglobulins, immune complexes and antibacterial antibodies were assessed in 57 patients with functional constipation. In 12 patients with severely delayed transit, investigations were repeated following therapy with Bisacodyl. Results. Ovalbumin concentrations, in serum, were higher in constipated patients (28.2 +/- 4.1 ng/ml versus 1.0 +/- 0.4 ng/ml, p < 0.05). Elevated counts of CD3+, CD4+, CD25+ cells, increased spontaneous proliferation of lymphocytes, elevated titres of antibodies to Escherichia coli and S. aureus, diminished counts of CD72+ B cells, diminished lymphocyte proliferation under phytohemagglutinin (PHA) stimulation and a diminished phagocytic index for both neutrophils and monocytes were found in the constipated patients. Concentrations of Bifidobacterium and Lactobacillus were significantly lower in constipated patients; potentially pathogenic bacteria and/or fungi were increased. Therapy with Bisacodyl resulted in normalisation of the faecal flora, a reduction in ovalbumin concentration and return towards normal for certain immunologic parameters. Conclusion. Constipation is associated with striking changes in the faecal flora, intestinal permeability and the systemic immune response. Relief of constipation tends to normalise these findings suggesting that these changes are secondary to, rather than a cause of, constipation. (C) 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.