Bombesin Prevents the Atrophy of Peyer's Patches and the Dysfunction of M Cells in Rabbits Receiving Long-Term Parenteral Nutrition

Abstract

Background: Long-term parenteral nutrition (PN) induces atrophy of the gut-associated lymphoid tissue (GALT). We examined whether bombesin could ameliorate this atrophy of Peyer's patches and the down-regulation of particle transport by M cells, which was also observed in rabbits undergoing PN. Methods: Adult female rabbits were randomized into 6 groups to receive chow ad libitum, chow + bombesin, PN, or PN + bombesin (20μ g/kg, subcutaneously every 8 hours) for 2 or 4 weeks. At the end of each nutrition period, a laparotomy was performed under anesthesia and a suspension of 1 × 10¹⁰/mL of 0.5-μm fluorescent microspheres was injected into the lumen of intestinal segments containing Peyer's patches and incubated for 2 hours. After the incubation, segments were harvested and prepared for light microscopy, immunohistochemistry, fluorescent microscopy, and electron microscopy. Results: Long-term PN reduced the size of ileal Peyer's patches, the number of microspheres that was taken up into the follicle-associated epithelium of lymphoid nodules, and the area of Peyer's patch surface occupied by M cells. The number of intraepithelial lymphocytes within the follicle-associated epithelium near the perifollicular crypts of Peyer's patches was also reduced by long-term PN. These consequences were dramatically ameliorated by treatment with bombesin. No ultrastructural alteration of the M cells of Peyer's patches was found in the chow, the PN, or the PN + bombesin groups. Conclusions: Bombesin prevents PN-induced atrophy of GALT, reduction of M cell numbers, and decrease in particulate transport by M cells during long-term PN. Bombesin may modulate the genesis of and particulate transport by M cells through stimulation of lymphoid cells in Peyer's patch epithelium near perifollicular crypts, where M cells and other constituents of lymphoid follicle epithelium are generated, thereby preserving mucosal immunity.

Bombesin could prevent the atrophy of Peyer’s patches and the decrease in number of and particle transport by M cells of Peyer’s patches in rabbits under long-term parenteral nutrition (PN). These findings suggest that neuropeptides such as bombesin may be of therapeutic use not only in reducing sepsis but also in preventing atrophy of intestinal mucosa and gut-associated lymphoid tissue in patients receiving PN.