Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Aug 28;18(32):4278-87.
doi: 10.3748/wjg.v18.i32.4278.

Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis

Rodrigo Goulart Pacheco  1 , Christiano Costa Esposito, Lucas C M Müller, Morgana T L Castelo-Branco, Leonardo Pereira Quintella, Vera Lucia A Chagas, Heitor Siffert P de Souza, Alberto Schanaider
Affiliations

Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis

Rodrigo Goulart Pacheco et al. World J Gastroenterol. .

Abstract

Aim: To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.

Methods: Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine, butyrate, or saline. Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure. Follow-up colonoscopy was performed every 4 wk for 12 wk. The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β, tumor necrosis factor-alpha, and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.

Results: Colonoscopies of the diverted segment showed mucosa with hyperemia, increased number of vessels, bleeding and mucus discharge. Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic (P < 0.02) and histological scores (P < 0.01) and restored the densities of collagen fibers in tissue (P = 0.015; P = 0.001), the number of goblet cells (P = 0.021; P = 0.029), and the rate of apoptosis within the epithelium (P = 0.043; P = 0.011) to normal values. The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.

Conclusion: The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

Keywords: Butyrate; Cytokines; Diversion colitis; Glutamine; Short-chain fatty acids.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Steps of the surgical procedure. A: Isolation of the distal colon exposing the vascular arcade; B: Section of distal colon; C: Confection of colostomy; D: Completion of colostomy.
Figure 2
Figure 2
Endoscopic images of the diverted segments of the colon treated with different protocols at 4 wk, before treatment, and at 8 wk, the peak of inflammation in this experimental model. Diversion colitis is characterized by the presence of a fragile mucosa, hyperemia, spontaneous bleeding, and increased number of vessels and mucous secretion (at 8 wk). Colonoscopic images were semi-quantitatively analyzed with an endoscopic score. Animals treated with either glutamine or butyrate showed significantly reduced colonoscopic scores compared to animals without any treatment at 8 and 12 wk. Significant differences are noted (n = 6 in each group).
Figure 3
Figure 3
Hematoxylin-eosin-stained slides of diverted colon samples obtained at 8 wk. A, B: Images were captured at ×100 and ×400 magnifications, respectively. Diversion colitis is characterized by a predominantly mononuclear cell infiltration, hyperemia, vasodilatation, and associated atrophic changes; C, D: Glutamine-treated animals show a slightly inflamed colon; E, F: Butyrate-treated animals show an almost normal colon (n = 6 in each group). Bars represent 50 μm.
Figure 4
Figure 4
Quantitative analysis of goblet cells using periodic acid-schiff-stained slides of diverted colon samples obtained at 8 wk. Images show a significant reduction in the number of goblet cells in slides from animals with placebo-treated (A) colitis compared to (B) glutamine-treated, butyrate-treated(C) and control animals (D). Images were captured at ×100 magnification. In the slides, bars represent 50 μm. In the graph (E), horizontal bars represent medians, boxes represent the 25th and 75th percentiles, and vertical bars represent ranges. Significant differences are noted (n = 6 in each group).
Figure 5
Figure 5
Quantitative analysis of collagen fiber deposition in picric acid-stained slidesand apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells of diverted colon samples obtained at 8 wk. Images show a significant increase of collagen density in slides from animals with placebo-treated (A) colitis compared to (B) glutamine-treated, butyrate-treated (C) and control animals (D). Images were captured at ×100 magnification. In the slides, bars represent 50 μm. In the graph (E), horizontal bars represent medians, boxes represent the 25th and 75th percentiles, and vertical bars represent ranges. Significant differences are noted (n = 6 in each group).
Figure 6
Figure 6
Quantitative analysis of apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells of diverted colon samples obtained at 8 wk. Images show a significant reduction in the number of apoptotic cells in slides from animals with placebo-treated (A) colitis compared to (B) glutamine-treated, butyrate-treated (C) and control animals (D). Images were captured at ×100 magnification. In the slides, bars represent 50 μm. In the graph (G), horizontal bars represent medians, boxes represent the 25th and 75th percentiles, and vertical bars represent ranges. Significant differences are noted (n = 6 in each group).
Figure 7
Figure 7
Cytokine production by the colonic mucosa of the diverted segment, obtained at 8 wk. Cytokines in 24 h organ cultures were measured by enzyme-linked immunosorbent assay and presented in pg/mL of culture supernatant, normalized to the protein content of tissues. A: High levels of tumor necrosis factor-α (TNF-α) measured in saline-treated colitis were restored to normal values following treatment with glutamine or butyrate; B, C: The high levels of interleukin (IL)-1β and of transforming growth factor beta (TGF-β) detected in supernatants of saline-treated colitis decreased significantly after treatment with butyrate. Horizontal bars represent medians, boxes represent the 25th and 75th percentiles, and vertical bars represent ranges. Significant differences are noted (n = 6 in each group).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Glotzer DJ, Glick ME, Goldman H. Proctitis and colitis following diversion of the fecal stream. Gastroenterology. 1981;80:438–441. - PubMed
    1. Ma CK, Gottlieb C, Haas PA. Diversion colitis: a clinicopathologic study of 21 cases. Hum Pathol. 1990;21:429–436. - PubMed
    1. Ona FV, Boger JN. Rectal bleeding due to diversion colitis. Am J Gastroenterol. 1985;80:40–41. - PubMed
    1. Lusk LB, Reichen J, Levine JS. Aphthous ulceration in diversion colitis. Clinical implications. Gastroenterology. 1984;87:1171–1173. - PubMed
    1. Whelan RL, Abramson D, Kim DS, Hashmi HF. Diversion colitis. A prospective study. Surg Endosc. 1994;8:19–24. - PubMed

Publication types

MeSH terms