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Am J Physiol Endocrinol Metab 290: E1104-E1108, 2006; doi:10.1152/ajpendo.00557.2005
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Dietary fiber decreases colonic epithelial cell proliferation and protein synthetic rates in human subjects

Viraine Weerasooriya,1 Michael J. Rennie,1,2 Shri Anant,1 David H. Alpers,1 Bruce W. Patterson,1 and Samuel Klein1

1Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri; and 2Graduate Entry Medical School, University of Nottingham, Derby, United Kingdom

Submitted 15 November 2005 ; accepted in final form 14 December 2005


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Although it has been proposed that high fiber consumption can prevent proliferative diseases of the colon, the clinical data to support this hypothesis have been inconsistent. To provide a more robust measure of the effects of fiber on colonic mucosal growth than previous studies, we evaluated both cell proliferation and colonic mucosal protein synthesis in nine healthy volunteers after they consumed a typical Western diet (<20 g fiber/day) or a Western diet supplemented with wheat bran (24 g/day) in a randomized crossover design. Biopsies taken from the sigmoid colon were used to assess mucosal proliferation by determining proliferating cell nuclear antigen (PCNA) in crypt cells and to assess mucosal protein synthetic rate using stable isotopically labeled leucine infusion. Fiber supplementation produced a 12% decrease in labeling index (%crypt cells stained with PCNA) (P < 0.001) and an 11% decrease in mucosal protein fractional synthetic rate (FSR; P < 0.05). Moreover, mucosal protein FSR correlated directly with labeling index (r2 = 0.22, P < 0.05). These data demonstrate that increased wheat bran consumption decreases colonic mucosal proliferation and support the potential importance of dietary fiber in preventing proliferative diseases of the colon.

metabolism; cancer; short-chain fatty acids

MORE THAN 35 YEARS AGO, Burkitt (6) hypothesized that dietary fiber can prevent proliferative diseases of the colon, such as colorectal cancer and polyposis syndromes. However, the effect of fiber intake on colonic disease is unclear because of conflicting results from different cross-sectional epidemiologic studies, longitudinal cohort studies, and randomized controlled trials (30, 14). In addition, data from studies that evaluated colonocyte proliferation, a presumed marker of colorectal polyp and cancer risk, found dietary fiber or its metabolites [i.e., short-chain fatty acids (SCFAs)] increased (7, 8, 19, 23), decreased (1, 10, 17), or did not change proliferation rates (2, 9).

Several factors have been proposed to explain the inconsistent relationship reported between fiber intake and colonic disease, including heterogeneity of dietary fiber, use of inadequate amounts of fiber to affect cellular metabolism, genetic differences in risk of polyps or colon cancer in study subjects, and limitations in the accuracy and precision of techniques used to measure colonocyte proliferation (14, 15, 32). Therefore, additional studies that address the limitations of previous investigations are needed to evaluate the effect of fiber on colon proliferation and metabolism. This issue has considerable physiological and clinical importance because of the notion that a typical Western diet, which contains <15 g/day of nonstarch polysaccharides, is considered inadequate for optimal for colonic health (15, 16).

The purpose of the present study was to determine the effect of supplemental dietary fiber on colonocyte proliferation and mucosal protein metabolism in healthy human subjects who had been consuming a typical Western diet, containing <15 g fiber/day. Subjects were randomized to consume their usual diet or their usual diet plus 24 g/day of wheat bran for 3 wk in a crossover study design. Wheat bran was used as a source of fiber, because it results in high intraluminal concentrations of butyrate, which is the preferred fuel of colonic epithelia. In addition, we used two independent measures to assess cell growth: 1) immunohistochemistry to determine crypt proliferating cell nuclear antigen (PCNA) content, which provides an index of cell proliferation, and 2) stable isotopically labeled tracer infusion to determine mucosal protein synthetic rates (11, 22). We hypothesized that increasing dietary fiber would cause a decrease in rates of mucosal cell proliferation and protein synthesis.


   MATERIALS AND METHODS
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 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
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Subjects

Nine subjects (4 lean men and 5 lean women, body mass index 22.4 ± 2.3 kg/m2, 25.6 ± 4.9 yr old) participated in this study. All subjects were considered to be healthy after completing a comprehensive medical examination that included a history and physical examination, an electrocardiogram, and standard blood tests. Subjects with a history of existing colonic disease or a family history of colonic disease, including having a first-degree relative with either colon cancer before age 50 yr or a polyposis syndrome, were excluded from this study. In addition, subjects who were normally consuming ≥20 g fiber/day were excluded. The average fiber intake of our subjects was 12.4 ± 3.6 g/day, determined by the Food Frequency Questionnaire (Nutritionist Pro 6 software; First Data Bank, San Bruno, CA).

Written, informed consent was obtained from all subjects before their participation in the study, which was approved by the Human Studies Committee and the General Clinical Research Center (GCRC) Scientific Advisory Committee of Washington University School of Medicine in St. Louis, MO.

Experimental Protocol

Dietary intervention. A randomized, crossover study design was used to evaluate the effect of a normal fiber (subjects' usual diet) and high-fiber diet. Subjects were randomized to one of two groups. Group 1 subjects were given a high-fiber diet, which consisted of their regular diet supplemented with 24 g/day of wheat bran fiber for 3 wk. The fiber supplement was provided as both wheat bran cereal (13 g/day of fiber) and wheat bran muffins (11 g/day of fiber). At the end of the 3-wk, high-fiber diet period, subjects were admitted to the GCRC of Washington University School of Medicine for a colon metabolism study (see below). After the metabolism study was completed, subjects resumed consumption of their normal diet without additional fiber for a 4-wk "washout" period and then continued their usual diet for an additional 3 wk ("normal" fiber period). At the end of the 3-wk regular diet period, subjects were admitted to the GCRC for another colon metabolism study. Subjects randomized to group 2 completed the same protocol, but the order of the high-fiber and normal-fiber diets was reversed.

Dietary compliance was encouraged by weekly phone calls from one member of the research team and by providing each subject with a 1-wk supply of prepackaged daily fiber supplements every week. Dietary compliance was evaluated by a fiber food frequency questionnaire administered before the diets and once during each 3-wk diet period. The subjects were also asked about changes in bowel habits and gastrointestinal symptoms that are often associated with increasing fiber intake (i.e., increased bowel movement frequency, stool changes, or abdominal bloating or cramping).

Colon metabolism study. After completing each 3-wk dietary treatment period, subjects were admitted to the GCRC in the evening before the colon metabolism study. At 1900, subjects consumed a standardized meal containing a total of 12 kcal/kg body wt (55% of total energy from carbohydrates, 30% from fat, and 15% from protein). Subjects randomized to the high-fiber diet consumed their last fiber supplement during this evening meal. After meal consumption, subjects fasted until completion of the metabolism study the next day.

At 0530 the following morning, a catheter was inserted into an antecubital vein to administer stable isotope-labeled amino acid tracers, and a second catheter was inserted into a contralateral hand vein, which was heated to 55°C using a thermostatically controlled box to obtain arterialized blood samples (18). At 0800, a primed continuous infusion of L-[5,5,5-2H3]leucine (Cambridge Isotope Laboratories, Andover, MA) dissolved in 0.9% saline (7.2 µmol/kg priming dose and 0.12 µmol·kg–1·min–1 continuous infusion in 0.9% saline) was started and maintained for 3 h. At 0700, each subject was given a gentle enema, containing 250 ml of 0.9% saline, to help clean the sigmoid colon and rectum.

Blood samples were taken immediately before the tracer infusion to determine baseline substrate concentrations and background tracer-to-tracee ratios (TTR) and at 1, 2, and 3 h during isotope infusion to determine plasma leucine TTR. All blood samples were collected in chilled tubes containing ethylenediaminetetraacetic acid (EDTA) and placed in an ice bath. Plasma was separated by centrifugation within 30 min of collection and stored at –70°C until final analyses were performed.

Flexible sigmoidoscopy was performed at 1, 2, and 3 h during isotope infusion to obtain mucosal biopsies from the distal sigmoid colon (15–20 cm proximal to the anal verge) to determine mucosal protein fractional synthetic rate (FSR) and crypt proliferation. Four biopsies, containing a total of ~30 mg of mucosal tissue, were obtained during each procedure. Biopsy specimens were gently rinsed in 0.9% saline to remove any blood and fecal material and were placed in formalin or immediately frozen in liquid nitrogen. Frozen samples were stored at –70°C until subsequent processing.

Sample Analyses

Assessment of leucine TTR. Plasma leucine TTRs were determined as previously described (24). Plasma samples were deproteinized with ice-cold pure acetone and lipids extracted with hexane. The aqueous fraction was dried using a SpeedVac centrifugal concentrator (Savant Instruments, Farmingdale, NY). A tert-butyldimethylsilyl (t-BDMS) derivative was prepared, and TTR was measured by electron impact (EI) ionization gas chromatography-mass spectrometry (GC-MS; MSD 5973 system with capillary column; Hewlett-Packard, Palo Alto, CA). Ions at mass-to-charge ratios (m/z) 200 and 203 were monitored, representing unlabeled and labeled leucine, respectively.

Intracellular free leucine and protein-bound leucine TTRs were determined as previously described (24). Mucosal biopsies specimens were treated with trichloroacetic acid (Sigma, St. Louis, MO) and ground with a tissue homogenizer in a conical microcentrifuge tube. Intracellular free amino acids were recovered by cation exchange column chromatography (Dowex AG 50W-X8; Bio-Rad Laboratories, Hercules, CA) and dried in a Speed-Vac centrifugal concentrator. The protein precipitate was hydrolyzed in 6 N HCl (at 110°C for 24 h), and free amino acids were recovered by cation exchange column chromatography (Dowex AG 50W-X8; Bio-Rad Laboratories) and dried by Speed-Vac centrifugation.

Tissue free amino acids and protein hydrolysates were converted to t-BDMS derivatives, and [2H3]leucine TTR was measured by EI ionization GC-MS on a Hewlett Packard 5973 MSD system with a capillary column. Ions at m/z 200 and 203 were used to measure intracellular free leucine TTR, and ions at m/z 202 and 203 were used to measure the low TTR in protein-bound leucine (25, 29). All TTR measurements were made using appropriate standards of [2H3]leucine of known TTR.

Mucosal protein synthesis. The FSR of mucosal protein was calculated by dividing the rate of increase of leucine labeling in mucosal protein between 1 and 3 h of tracer infusion by the average mucosal intracellular free leucine TTR during this time period (25).

Immunohistochemistry for PCNA. Paraffin-embedded tissue sections (4 µm) were deparaffinized and brought through descending alcohols to distilled water. Antigen retrieval was performed by heating in a solution of Antigen Decloaker (Biocare Medical, Walnut Creek, CA) in a pressure cooker at 15 psi for 3 min. After blocking of nonspecific binding with avidin-biotin (SP-2001; Vector Labs, Burlingame, CA) and protein (X0909; Dako, Carpenteria, CA) -blocking reagents, the slides were incubated with a rabbit anti-PCNA antibody (1:800 dilution, catalog no. sc-7907; Santa Cruz Biotechnology, Santa Cruz, CA) followed by a biotinylated goat anti-mouse IgG (1:2,000 dilution, catalog no. NEF-813; NEN Life Science, Boston, MA). Endogenous peroxidase activity was quenched by incubating the slides in 3% hydrogen peroxide for 5 min. The slides were then incubated with streptavidin-conjugated horseradish peroxidase (1:1,000, catalog no. P0397; Dako). Tyramide amplification was performed with NEL700A (NEN Life Science). 3,3-Diaminobenzidine (catalog no. D-9015; Sigma) was used as a chromogen to demonstrate the presence of PCNA, and sections were counterstained with Harris hematoxylin. Negative control tissues were prepared in the same manner as that described above, except for the omission of primary antibodies and the substitution of an isotype-matched but irrelevant antibody. Two different samples were examined for each subject at each time point.

Statistical Analyses

The statistical significance of differences in study endpoints between high-fiber and regular-fiber diets was assessed by using a two-tailed Student's t-test for paired samples. A P value of ≤0.05 was considered statistically significant. All data are expressed as means ± SD.


   RESULTS
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Mucosal Proliferation

Increased dietary fiber intake decreased the rate of colonic crypt proliferation (Fig. 1). The fraction of crypt cells that were positively stained for PCNA decreased from 57 ± 3% cells per crypt after subjects consumed their usual-fiber diet to 50 ± 3% cells per crypt after they consumed the high-fiber diet (P < 0.001), representing a 12% decrease during the high-fiber diet.


Figure 1
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  		Fig. 1. Percentage of proliferating cell nuclear antigen-positive cells per crypt in colonic mucosa after subjects consumed a normal-fiber or a high-fiber diet. Dashed lines represent mean values for each diet group. *High-fiber diet value significantly different from normal-fiber diet value, P < 0.001.

 
Mucosal Protein Kinetics

Plasma leucine and intracellular mucosal free leucine TTRs were constant, whereas mucosal protein leucine TTR increased linearly between 1 and 3 h of isotope infusion. Colonic mucosal protein FSR decreased from 2.14 ± 0.24%/h after subjects consumed the regular-fiber diet to 1.81 ± 0.30%/h after subjects consumed the high-fiber diet (P < 0.05; Fig. 2), representing a 15% decrease during the high-fiber diet.


Figure 2
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  		Fig. 2. Colonic mucosal protein fractional synthetic rate (FSR) after subjects consumed a normal-fiber or a high-fiber diet. Dashed lines represent mean values for each diet group. *High-fiber diet value significantly different from normal-fiber diet value, P < 0.05.

 
The mean TTR of intracellular and mucosal protein [2H3]leucine was 0.033 and 0.0018, respectively, averaged over all time points across all studies; the average coefficient of variation for replicate TTR measurements was 0.54 and 1.1%, respectively. The standard error associated with measuring the mucosal protein slope and the intracellular leucine TTR over 3 time points within each study averaged 9.8 and 6.0%, respectively, over all studies. These measurements of variability were not significantly different between diets.

Relationship Between Cell Proliferation and Mucosal FSR

Cell proliferation, assessed by PCNA labeling, correlated directly with mucosal protein FSR, assessed by using isotopicaly labeled tracer infusion, during both regular-fiber and high-fiber diet periods (r2 = 0.22, P < 0.05; Fig. 3).


Figure 3
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  		Fig. 3. Top: relationship between the fraction of proliferating cells per crypt and colon mucosal protein FSR after subjects consumed a normal-fiber ({circ}) and a high-fiber diet (bullet) (n = 18, r2 = 0.22, P < 0.05). Bottom: relationship between the change in fraction of proliferating cells per crypt and percent change in colon mucosal protein FSR when subjects consumed a high-fiber diet compared with a normal-fiber diet ({blacksquare}) (n = 9, r2 = 0.28, P < 0.05).

 

   DISCUSSION
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Since Burkitt proposed his novel "fiber hypothesis" more than 35 years ago (6), it has been generally accepted that inadequate fiber content of a typical Western diet increases the risk of proliferative diseases of the colon, such as polyps and cancer (30). However, the results from studies evaluating the effect of dietary fiber or SCFA administration on colorectal neoplasia or colonocyte proliferation are not conclusive because of inconsistent results from different studies (1, 4, 9, 21, 22, 30). This is the first study to evaluate the effect of dietary fiber on colonic mucosal proliferation and protein metabolism in healthy human subjects. Two independent methods were used to assess mucosal growth to cross-validate any observed effects. Our results demonstrate that dietary supplementation with wheat bran decreases both epithelial cell proliferation and mucosal protein synthetic rate. It is likely that the observed decline in cellular protein synthesis was due to the decrease in the rate of cell proliferation, which requires the production of new proteins during the generation and differentiation of new crypt epithelia. Therefore, these data support the notion that dietary fiber supplementation can decrease the risk of developing colonic polyps and cancer by a direct effect on cell proliferation.

The mechanism(s) responsible for the effect that we observed of wheat bran supplementation on colonic mucosal proliferation and protein synthesis is not known, but it is presumably related to bacterial metabolism of undigested carbohydrate. Ingesting wheat bran increases the production of SCFAs in the colon by bacterial fermentation. Moreover, wheat bran preferentially produces butyrate, which is the primary fuel for colonocytes (27). Butyrate decreases growth of most human colon cancer cell lines by inhibiting cell proliferation, enhancing differentiation, and increasing apoptosis (10, 12). Incubating human colon cancer cells with SCFAs inhibits NF-{kappa}B activation, modulates the expression of cell cycle-regulating proteins, and induces apoptosis (3). In addition, fermentation of dietary fiber by human gut flora produces other growth inhibitors, which enhance the antiproliferative effects of butyrate and prevent chemoresistance in HT29 cells (5). Therefore, it seems likely that butyrate and other product(s) of fiber fermentation account for the effect on cell proliferation in human colon.

We used two independent markers to evaluate cell growth and proliferation to help ensure the reliability of our results. Most studies that evaluated the effect of fiber on colonic mucosa used the thymidine labeling technique to assess cell proliferation. This approach requires fresh tissue and only labels the S phase of the cell cycle (28). In the present study, we evaluated cell proliferation by staining colonic tissue for PCNA, which has the advantages of labeling all phases of the cell cycle, and by using fixed, rather than fresh, tissue (22). In addition, this approach is associated with minimal interobserver variability (20, 22, 31). We also evaluated the rate of protein synthesis in colonic tissue by using stable isotopically labeled tracer infusion to provide an additional and independent marker of cellular metabolism that is associated with proliferation. Several previous studies have used isotope tracer infusions to determine colorectal mucosal protein synthetic rate in human subjects during different physiological (e.g., glucagon infusion) and clinical (inflammatory bowel disease, colorectal cancer) conditions (11, 13, 26). However, the present study is the first to use this technique to evaluate the effect of dietary fiber on colonic protein metabolism. Our data demonstrate that the rate of mucosal protein synthesis is directly correlated with cell proliferation, which strengthens the validity of our conclusions regarding dietary fiber.

We attempted to address some of the limitations of previous clinical dietary fiber studies by implementing certain study design features. First, we evaluated supplementation with only one type of fiber (wheat bran) to avoid the confounding influence of different fiber types. Second, we tried to ensure dietary compliance by providing the fiber source, frequent phone and personal contacts, and monitoring intake with diet records. Third, we used a randomized crossover design to minimize the effect of intersubject variability. Fourth, we used two independent methods for assessing cell proliferation, as already noted. Fifth, we conducted this study in normal human subjects to eliminate the potential influence of proliferative disease on our study endpoints.

In conclusion, the results from the present study demonstrate that dietary fiber can induce physiologically important effects on the trophic properties of the colon in healthy volunteers. Therefore, it is likely that the products of fiber fermentation affect the proliferative zone of normal human colonic mucosa. These findings support the hypothesis that adding wheat bran to a Western diet can have protective effects against developing colon polyps and cancer.


   GRANTS
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
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REFERENCES
 
This study was supported by National Institutes of Health Grants DK-37948, RR-00954 (Biomedical Mass Spectrometry Resource), RR-00036 (General Clinical Research Center), and DK-56341 (Clinical Nutrition Research Unit).


   ACKNOWLEDGMENTS
 
We thank the nursing staff of the General Clinical Research Center for their help in performing the studies, Freida Custodio and Junyoung Kwon for technical assistance, and the study subjects for their participation.


   FOOTNOTES
 

Address for reprint requests and other correspondence: S. Klein, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8031, St. Louis, MO 63110

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
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 RESULTS
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  1. Alberts DS, Einspahr J, Rees-McGee S, Ramanujam P, Buller MK, Clark L, Ritenbaugh C, Atwood J, Pethigal P, Earnest D, Villar H, Phelps J, Lipkin M, Wargovich M, and Meyskens FL Jr. Effects of dietary wheat bran fiber on rectal epithelial cell proliferation in patients with resection for colorectal cancers. J Natl Cancer Inst 82: 1280–1285, 1990.[Abstract/Free Full Text]
  2. Alberts DS, Einspahr J, Ritenbaugh C, Aickin M, Rees-McGee S, Atwood J, Emerson S, Mason-Liddil N, Bettinger L, Patel J, Bellapravalu S, Ramanujam PS, Phelps J, and Clark L. The effect of wheat bran fiber and calcium supplementation on rectal mucosal proliferation rates in patients with resected adenomatous colorectal polyps. Cancer Epidemiol Biomarkers Prev 6: 161–169, 1997.[Abstract]
  3. Andoh A, Tsujikawa T, and Fujiyama Y. Role of dietary fiber and short-chain fatty acids in the colon. Curr Pharm Des 9: 47–58, 2003.
  4. Anti M, Marra G, Percesepe A, Armelao F, and Gasbarrini G. Reliability of rectal epithelial kinetic patterns as an intermediate biomarker of colon cancer. J Cell Biochem Suppl 19: 68–75, 1994.[Medline]
  5. Beyer-Sehlmeyer G, Glei M, Hartmann E, Hughes R, Persin C, Bohm V, Rowland I, Schubert R, Jahreis G, and Pool-Zobel BL. Butyrate is only one of several growth inhibitors produced during gut flora-mediated fermentation of dietary fibre sources. Br J Nutr 90: 1057–1070, 2003.[CrossRef][Web of Science][Medline]
  6. Burkitt DP. Related disease, related cause? Lancet 2: 1229–1231, 1969.[CrossRef][Web of Science][Medline]
  7. Folino M, Mcintyre A, and Young GP. Dietary fibers differ in their effects on large bowel epithelial proliferation and fecal fermentation-dependent events in rats. J Nutr 125: 1521–1528, 1995.[Abstract/Free Full Text]
  8. Frankel WL, Zhang W, Singh A, Klurfeld DM, Don S, Sakata T, Modlin I, and Rombeau JL. Mediation of the trophic effects of short-chain fatty acids on the rat jejunum and colon. Gastroenterology 106: 375–380, 1994.[Web of Science][Medline]
  9. Gregoire R, Yeung KS, Stadler J, Stern HS, Kashtan H, Neil G, and Bruce WR. Effect of high-fat and low-fiber meals on the cell proliferation activity of colorectal mucosa. Nutr Cancer 15: 21–26, 1991.[Web of Science][Medline]
  10. Hague A, Manning AM, Hanlon KA, Huschtscha LI, Hart D, and Paraskeva C. Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: implications for the possible role of dietary fibre in the prevention of large-bowel cancer. Int J Cancer 55: 498–505, 1993.[Web of Science][Medline]
  11. Hartl WH, Demmelmair H, Jauch KW, Koletzko B, and Schildberg FW. Effect of glucagon on protein synthesis in human rectal cancer in situ. Ann Surg 227: 390–397, 1998.[CrossRef][Web of Science][Medline]
  12. Heerdt BG, Houston AM, and Augenlicht LH. Potentiation by specific short chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines. Cancer Res 54: 3288–3294, 1994.[Abstract/Free Full Text]
  13. Heys SD, Park KG, McNurlan MA, Keenan RA, Miller JD, Eremin O, and Garlick PJ. Protein synthesis rates in colon and liver: stimulation by gastrointestinal pathologies. Gut 33: 976–981, 1992.[Abstract/Free Full Text]
  14. Hill M. Dietary fibre and colon cancer: where do we go from here? Proc Nutr Soc 62: 63–65, 2003.[CrossRef][Web of Science][Medline]
  15. Hill MJ. Cereals, cereal fibre and colorectal cancer risk: a review of the epidemiological literature. Eur J Cancer Prev 6: 219–225, 1997.[Web of Science][Medline]
  16. IOM (Institute of Medicine). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academy, 2002.
  17. Jenab M and Thompson LU. Phytic acid in wheat bran affects colon morphology, cell differentiation and apoptosis. Carcinogenesis 21: 1547–1552, 2000.[Abstract/Free Full Text]
  18. Jensen M and Heiling V. Heated hand vein blood is satisfactory for measurements during free fatty acid kinetic studies. Metabolism 40: 406–409, 1991.[CrossRef][Web of Science][Medline]
  19. Jin L. Effects of dietary fiber on intestinal growth, cell proliferation, and morphology in growing pigs. J Anim Sci 72: 2270–2278, 1995.
  20. Kallay E, Pietschmann P, Toyokuni S, Bajna E, Hahn P, Mazzucco K, Bieglmayer C, Kato S, and Cross HS. Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage. Carcinogenesis 22: 1429–1435, 2001.[Abstract/Free Full Text]
  21. Lupton JR. Microbial degradation products influence colon cancer risk: the butyrate controversy. J Nutr 134: 479–482, 2004.[Abstract/Free Full Text]
  22. Macrae FA, Kilias D, Selbie L, Abbott M, Sharpe K, and Young GP. Effect of cereal fibre source and processing on rectal epithelial cell proliferation. Gut 41: 239–244, 1997.[Abstract/Free Full Text]
  23. Mccullough JS, Ratcliffe B, Mandir N, Carr KE, and Goodlad RA. Dietary fibre and intestinal microflora: effects on intestinal morphometry and crypt branching. Gut 42: 799–806, 1998.[Abstract/Free Full Text]
  24. Patterson BW, Horowitz JF, Wu G, Watford M, Coppack SW, and Klein S. Regional muscle and adipose tissue amino acid metabolism in lean and obese women. Am J Physiol Endocrinol Metab 282: E931–E936, 2002.[Abstract/Free Full Text]
  25. Patterson BW, Zhang XJ, Chen Y, Klein S, and Wolfe RR. Measurement of very low stable isotope enrichments by gas chromatography/mass spectrometry: application to measurement of muscle protein synthesis. Metabolism 46: 943–948, 1997.[CrossRef][Web of Science][Medline]
  26. Rittler P, Demmelmair H, Koletzko B, Jauch KW, and Hartl WH. Effect of tumor removal on mucosal protein synthesis in patients with colorectal cancer. Am J Physiol Endocrinol Metab 284: E1018–E1021, 2003.[Abstract/Free Full Text]
  27. Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 83: 424–429, 1982.[Web of Science][Medline]
  28. Schipper DL, Wagenmans MJ, Peters WH, and Wagener DJ. Significance of cell proliferation in gastric cancer. Eur J Cancer 34: 781–790, 1998.[CrossRef][Web of Science][Medline]
  29. Schwenk WF, Berg PJ, Beaufrere B, Miles JM, and Haymond MW. Use of t-butyldimethylsilylation in the gas chromatographic/mass spectrometric analysis of physiologic compounds found in plasma using electron-impact ionization. Anal Biochem 141: 101–109, 1984.[CrossRef][Web of Science][Medline]
  30. Sengupta S, Tjandra JJ, and Gibson PR. Dietary fiber and colorectal neoplasia. Dis Colon Rectum 44: 1016–1033, 2001.[CrossRef][Web of Science][Medline]
  31. Steinbrecher KA, Wowk SA, Rudolph JA, Witte DP, and Cohen MB. Targeted inactivation of the mouse guanylin gene results in altered dynamics of colonic epithelial proliferation. Am J Pathol 161: 2169–2178, 2002.[Abstract/Free Full Text]
  32. Whiteley LO and Klurfeld DM. Are dietary fiber-induced alterations in colonic epithelial cell proliferation predictive of fiber's effect on colon cancer? Nutr Cancer 36: 131–149, 2000.[CrossRef][Web of Science][Medline]



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