Skip to main content
SpringerLink
Log in

Dietary Red Meat Aggravates Dextran Sulfate Sodium-Induced Colitis in Mice Whereas Resistant Starch Attenuates Inflammation

Digestive Diseases and Sciences volume 58, pages 3475–3482 (2013)Cite this article

Abstract

Background

Although a genetic component has been identified as a risk factor for developing inflammatory bowel disease, there is evidence that dietary factors also play a role in the development of this disease.

Aims

The aim of this study was to determine the effects of feeding a red meat diet with and without resistant starch (RS) to mice with dextran sulfate sodium (DSS)-induced colitis.

Methods

Colonic experimental colitis was induced in Balb/c mice using DSS. The severity of colitis was evaluated based on a disease activity index (based on bodyweight loss, stool consistency, rectal bleeding, and overall condition of the animal) and a histological score. Estimations were made of numbers of a range of different bacteria in the treatment pools of cecal digesta using quantitative real-time PCR.

Results

Consumption of a diet high in red meat increased DSS-induced colitis as evidenced by higher disease activity and histopathological scores. Addition of RS to the red meat diet exerted a beneficial effect in acute DSS-induced colitis. Subjective analysis of numbers of a range of bacterial targets suggest changes in the gut microbiota abundance were induced by red meat and RS treatments and these changes could contribute to the reported outcomes.

Conclusions

A dietary intake of red meat aggravates DSS-induced colitis whereas co-consumption of resistant starch reduces the severity of colitis.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

Abbreviations

DSS:

Dextran sulfate sodium

RS:

Resistant starch

RM:

Red meat

IBD:

Inflammatory bowel disease

UC:

Ulcerative colitis

CRC:

Colorectal cancer

SCFA:

Short chain fatty acids

AIN:

American Institute of Nutrition

Hi-maize:

High amylose maize starch

DAI:

Disease activity index

SRB:

Sulfate-reducing bacteria

aps:

Adenosine-5-phosphosulfate reductase gene

References

  1. Molodecky NA, Kaplan GG. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (NY). 2010;6:339–346.

    Google Scholar 

  2. Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev. 2002;15:79–94.

    Article  PubMed  Google Scholar 

  3. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474:307–317.

    Article  PubMed  CAS  Google Scholar 

  4. Lakatos PL. Environmental factors affecting inflammatory bowel disease: have we made progress? Dig Dis. 2009;27:215–225.

    Article  PubMed  Google Scholar 

  5. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004;126:1504–1517.

    Article  PubMed  Google Scholar 

  6. Andersen V, Olsen A, Carbonnel F, et al. Diet and risk of inflammatory bowel disease. Dig Liver Dis. 2012;44:185–194.

    Article  PubMed  CAS  Google Scholar 

  7. Research WCRFAIoC. Food, Nutrition, Physical Activity, and the Prevention of cancer: a Global Perspective; 2007.

  8. Seril DN, Liao J, Yang GY, et al. Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Carcinogenesis. 2003;24:353–362.

    Article  PubMed  CAS  Google Scholar 

  9. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–535.

    Article  PubMed  CAS  Google Scholar 

  10. Lucendo AJ, De Rezende LC. Importance of nutrition in inflammatory bowel disease. World J Gastroenterol. 2009;15:2081–2088.

    Article  PubMed  CAS  Google Scholar 

  11. Bingham SA, Day NE, Luben R, et al. Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study. Lancet. 2003;361:1496–1501.

    Article  PubMed  Google Scholar 

  12. Whitehead RH, Young GP, Bhathal PS. Effects of short chain fatty acids on a new human colon carcinoma cell line (LIM1215). Gut. 1986;27:1457–1463.

    Article  PubMed  CAS  Google Scholar 

  13. Heerdt BG, Houston MA, Augenlicht LH. Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic epithelial cells is linked to mitochondrial function. Cell Growth Differ Mol Biol J Am Assoc Can Res. 1997;8:523–532.

    CAS  Google Scholar 

  14. De Preter V, Arijs I, Windey K, et al. Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway. Inflamm Bowel Dis. 2012;18:1127–1136.

    Article  PubMed  Google Scholar 

  15. Vieira EL, Leonel AJ, Sad AP, et al. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. J Nutr Biochem. 2012;23:430–436.

    Article  PubMed  CAS  Google Scholar 

  16. Morita T, Tanabe H, Sugiyama K, et al. Dietary resistant starch alters the characteristics of colonic mucosa and exerts a protective effect on trinitrobenzene sulfonic acid-induced colitis in rats. Biosci Biotechnol Biochem. 2004;68:2155–2164.

    Article  PubMed  CAS  Google Scholar 

  17. Okayasu I, Hatakeyama S, Yamada M, et al. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98:694–702.

    PubMed  CAS  Google Scholar 

  18. Le Leu RK, Hu Y, Brown IL, et al. Effect of high amylose maize starches on colonic fermentation and apoptotic response to DNA-damage in the colon of rats. Nutr Metab (Lond). 2009;6:11.

    Article  Google Scholar 

  19. Birkett AM, Jones GP, de Silva AM, et al. Dietary intake and faecal excretion of carbohydrate by Australians: importance of achieving stool weights greater than 150 g to improve faecal markers relevant to colon cancer risk. Eur J Clin Nutr. 1997;51:625–632.

    Article  PubMed  CAS  Google Scholar 

  20. Bellomonte G, Costantini A, Giammarioli S. Comparison of modified automatic Dumas method and the traditional Kjeldahl method for nitrogen determination in infant food. J Assoc Off Anal Chem. 1987;70:227–229.

    PubMed  CAS  Google Scholar 

  21. Folch J, Lees M. Sloane Stanley GH: a simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226:497–509.

    PubMed  CAS  Google Scholar 

  22. Cooper HS, Murthy SN, Shah RS, et al. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993;69:238–249.

    PubMed  CAS  Google Scholar 

  23. Yazbeck R, Sulda ML, Howarth GS, et al. Dipeptidyl peptidase expression during experimental colitis in mice. Inflamm Bowel Dis. 2010;16:1340–1351.

    Article  PubMed  Google Scholar 

  24. Yu Z, Morrison M. Improved extraction of PCR-quality community DNA from digesta and fecal samples. Biotechniques. 2004;36:808–812.

    PubMed  CAS  Google Scholar 

  25. Wang L, Christophersen CT, Sorich MJ, et al. Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Appl Environ Microbiol. 2011;77:6718–6721.

    Article  PubMed  CAS  Google Scholar 

  26. Christophersen CT, Morrison M, Conlon MA. Overestimation of the abundance of sulfate-reducing bacteria in human feces by quantitative PCR targeting the Desulfovibrio 16S rRNA gene. Appl Environ Microbiol. 2011;77:3544–3546.

    Article  PubMed  CAS  Google Scholar 

  27. Clarke JM, Topping DL, Christophersen CT, et al. Butyrate esterified to starch is released in the human gastrointestinal tract. Am J Clin Nutr. 2011;94:1276–1283.

    Article  PubMed  CAS  Google Scholar 

  28. Mondot S, Kang S, Furet JP, et al. Highlighting new phylogenetic specificities of Crohn’s disease microbiota. Inflamm Bowel Dis. 2011;17:185–192.

    Article  PubMed  CAS  Google Scholar 

  29. Png CW, Linden SK, Gilshenan KS, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105:2420–2428.

    Article  PubMed  CAS  Google Scholar 

  30. Bartosch S, Fite A, Macfarlane GT, et al. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Appl Environ Microbiol. 2004;70:3575–3581.

    Article  PubMed  CAS  Google Scholar 

  31. Shoda R, Matsueda K, Yamato S, et al. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr. 1996;63:741–745.

    PubMed  CAS  Google Scholar 

  32. Jantchou P, Morois S, Clavel-Chapelon F, et al. Animal protein intake and risk of inflammatory bowel disease: the E3 N prospective study. Am J Gastroenterol. 2010;105:2195–2201.

    Article  PubMed  CAS  Google Scholar 

  33. Maconi G, Ardizzone S, Cucino C, et al. Pre-illness changes in dietary habits and diet as a risk factor for inflammatory bowel disease: a case-control study. World J Gastroenterol. 2010;16:4297–4304.

    Article  PubMed  Google Scholar 

  34. Le Leu RK, Young GP. Fermentation of starch and protein in the colon: implications for genomic instability. Cancer Biol Ther. 2007;6:259–260.

    Article  PubMed  Google Scholar 

  35. Cummings JH, Hill MJ, Bone ES, et al. The effect of meat protein and dietary fiber on colonic function and metabolism. II. Bacterial metabolites in feces and urine. Am J Clin Nutr. 1979;32:2094–2101.

    PubMed  CAS  Google Scholar 

  36. Geypens B, Claus D, Evenepoel P, et al. Influence of dietary protein supplements on the formation of bacterial metabolites in the colon. Gut. 1997;41:70–76.

    Article  PubMed  CAS  Google Scholar 

  37. Glei M, Klenow S, Sauer J, et al. Hemoglobin and hemin induce DNA damage in human colon tumor cells HT29 clone 19A and in primary human colonocytes. Mutat Res. 2006;594:162–171.

    Article  PubMed  CAS  Google Scholar 

  38. Sesink AL, Termont DS, Kleibeuker JH, et al. Red meat and colon cancer: the cytotoxic and hyperproliferative effects of dietary heme. Cancer Res. 1999;59:5704–5709.

    PubMed  CAS  Google Scholar 

  39. Toden S, Bird AR, Topping DL, et al. Resistant starch prevents colonic DNA damage induced by high dietary cooked red meat or casein in rats. Cancer Biol Ther. 2006;5:267–272.

    Article  PubMed  CAS  Google Scholar 

  40. Winter J, Nyskohus L, Young GP, et al. Inhibition by resistant starch of red meat-induced promutagenic adducts in mouse colon. Cancer Prev Res (Phila). 2011;4:1920–1928.

    Article  CAS  Google Scholar 

  41. Englyst HN, Kingman SM, Cummings JH. Classification and measurement of nutritionally important starch fractions. Eur J Clin Nutr. 1992;46:S33–S50.

    PubMed  Google Scholar 

  42. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001;81:1031–1064.

    PubMed  CAS  Google Scholar 

  43. Andoh A, Tsujikawa T, Fujiyama Y. Role of dietary fiber and short-chain fatty acids in the colon. Curr Pharm Des. 2003;9:347–358.

    Article  PubMed  CAS  Google Scholar 

  44. Flint HJ. The impact of nutrition on the human microbiome. Nutr Rev. 2012;70:S10–S13.

    Article  PubMed  Google Scholar 

  45. Le Leu RK, Hu Y, Brown IL, et al. Synbiotic intervention of Bifidobacterium lactis and resistant starch protects against colorectal cancer development in rats. Carcinogenesis. 2010;31:246–251.

    Article  PubMed  Google Scholar 

  46. Le Leu RK, Brown IL, Hu Y, et al. Effect of dietary resistant starch and protein on colonic fermentation and intestinal tumourigenesis in rats. Carcinogenesis. 2007;28:240–245.

    Article  PubMed  Google Scholar 

  47. Toden S, Bird AR, Topping DL, et al. High red meat diets induce greater numbers of colonic DNA double-strand breaks than white meat in rats: attenuation by high-amylose maize starch. Carcinogenesis. 2007;28:2355–2362.

    Article  PubMed  CAS  Google Scholar 

  48. Cummings JH, Macfarlane GT. Role of intestinal bacteria in nutrient metabolism. JPEN. 1997;21:357–365.

    Article  CAS  Google Scholar 

  49. Manichanh C, Rigottier-Gois L, Bonnaud E, et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut. 2006;55:205–211.

    Article  PubMed  CAS  Google Scholar 

  50. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohns disease patients. PNAS. 2008;105:16731–16736.

    Article  PubMed  CAS  Google Scholar 

  51. Sokol H, Seksik P, Furet JP, et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15:1183–1189.

    Article  PubMed  CAS  Google Scholar 

  52. Toden S, Bird AR, Topping DL, et al. Dose-dependent reduction of dietary protein-induced colonocyte DNA damage by resistant starch in rats correlates more highly with caecal butyrate than with other short chain fatty acids. Cancer Biol Ther. 2007;6:253–258.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Health and Medical Research Council (grant ID 535079) and CSIRO Preventative Health National Research Flagship.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Preventative Health National Research Flagship, CSIRO, and CSIRO Animal, Food and Health Sciences, Adelaide, SA, Australia

    Richard K. Le Leu & Michael A. Conlon

  2. Flinders Centre for Innovation in Cancer, Flinders University of South Australia, Bedford Park, SA, Australia

    Richard K. Le Leu, Graeme P. Young, Ying Hu & Jean Winter

Authors
  1. Richard K. Le Leu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Graeme P. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jean Winter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael A. Conlon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard K. Le Leu.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Le Leu, R.K., Young, G.P., Hu, Y. et al. Dietary Red Meat Aggravates Dextran Sulfate Sodium-Induced Colitis in Mice Whereas Resistant Starch Attenuates Inflammation. Dig Dis Sci 58, 3475–3482 (2013). https://doi.org/10.1007/s10620-013-2844-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-013-2844-1

Keywords

search

Navigation