Heinrich Kasper

Effect of Short-Chain Fatty Acids on the Human Colonic Mucosa in Vitro

Fermentable dietary fiber components are known to stimulate colonic crypt proliferation. As these compounds are rapidly degraded to short-chain fatty acids (SCFAs) by the anaerobic microflora, the hypothesis was tested that this trophic effect of fiber may be mediated by SCFAs. Biopsies were taken from normal cecal mucosa of 45 individuals during routine colonoscopy. They were incubated for 3 hours with sodium salts of SCFAs at physiological concentrations (three SCFAs = acetate 60 mmol/L + propionate 25 mmol/L + butyrate 10 mmol/L; acetate 60 mmol/L; propionate 25 mmol/L; butyrate 10 mmol/L) or equimolar NaCl (control). Cell proliferation was measured autoradiographically by subsequent pulse labeling with [3H]thymidine (1 hour). The labeling index (number of labeled cells divided by the total number of cells) was computed for the crypt as a whole and for five equal crypt compartments (compartment 1 = crypt base, compartment 5 = crypt surface). Cecal crypt proliferation was raised significantly in all incubation experiments with SCFAs. Butyrate (10 mmol/L, increase + 89%) and propionate (25 mmol/L, + 70%) were as effective in stimulating proliferation as the combination of three SCFAs (+103%), although the effect of acetate (+31%) was minor. Increasing the butyrate concentration to 25 mmol/L or 60 mmol/L did not result in a further increase of cell labeling. SCFAs stimulated proliferation in the basal three crypt compartments only. An expansion of the proliferative zone to compartments 4 and 5 was not observed. SCFAs, especially butyrate and propionate, are luminal trophic factors for the cecal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Starch Malabsorption on Colonic Function and Metabolism in Humans

To study the impact of starch on colonic function and metabolism, 12 healthy volunteers consumed a controlled diet rich in starch for two 4-wk periods. In one of the study periods they received the glucosidase inhibitor acarbose (BAY g 5421) and placebo in the other. Stool wet weight increased by 68%, stool dry weight by 57%, fecal water content by 73%, and the mean transit time by 30% on acarbose. Breath hydrogen was significantly higher on acarbose, indicating stimulated carbohydrate fermentation in the colon. Fecal bacterial mass (+78%), total stool nitrogen (+53%), bacterial nitrogen (+200%), and stool fat (+56%) were higher in the acarbose than in the control period. The stimulation of fermentation in the human large intestine may be important in colonic and possibly other diseases.

Addition of dietary fiber to liquid formula diets: the pros and cons.

Dietary fiber defined as nonstarch polysaccharides (NSP) has been added to liquid formula diets in order to approach a more physiological state of nutrition. There are interesting experimental data supporting a role for fiber in artificial enteral feeding: NSP components have been shown to increase fecal bacterial mass, to favor colonic sodium and water absorption, to stimulate colonic crypt proliferation and to delay small intestinal glucose absorption. The number of controlled studies testing the effects of fiber added to liquid formulas is, however, small. Thus, there is no firm basis for the routine use of fiber-enriched formulas although these products are commercially available and in widespread clinical use. Research in this important field of digestive physiology is encouraged as many experimental data are in favor of supplementing formula diets with fiber.

histological changes in the colonic mucosa following irrigation with short-chain fatty acids

Objectives: Short‐chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. Design: A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n‐butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed. Results: Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. Conclusion: SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

Faecal Fat Excretion, Diarrhea, and Subjective Complaints with Highly Dosed Oral Fat Intake

Healthy subjects received a diet with a constant content of protein, fat, minerals and vitamins. To this diet were added increasing amounts of fat in the form of corn oil and olive oil up to a maximum

MISSING ANTI-PROLIFERATIVE EFFECT OF FISH OIL ON RECTAL EPITHELIUM IN HEALTHY VOLUNTEERS CONSUMING A HIGH-FAT DIET: POTENTIAL ROLE OF THE N-3

Several studies have indicated dietary fish oil (FO) as a protective agent in colon carcinogenesis. Rectal cell proliferation as an intermediate biomarker of cancer risk was shown to be reduced by dietary FO in patients with adenomatous polyps and healthy subjects consuming a low-fat diet. Because the synthesis of prostaglandins (PG) which seem to be involved in this process is dependent on the ratio of n-3:n-6 fatty acids in the diet, the present study was designed to investigate whether this FO effect is also detectable in volunteers eating a high-fat diet (50% of energy) with a low n-3:n-6 ratio of 0.25. Twelve healthy volunteers received in addition to a controlled basal diet either FO (4.4 g n-3 fatty acids/day) or corn oil supplements (double-blind, crossover) for two 4-week periods. No significant differences between the two study periods were found for rectal cell proliferation as assessed by bromodeoxyuridine immunohistochemistry and ornithine decarboxylase activity, as well as for mucosal PGE2 release and mucosal membrane fatty acid composition. The results emphasize the importance of dietary n-3:n-6 ratio in determining the effects of FO on rectal cell proliferation.

Effects of Deoxycholic Acid and Butyrate on Mucosal Prostaglandin E2 Release and Cell Proliferation in the Human Sigmoid Colon

BACKGROUND A high-fat, low-fiber diet resulting in increased excretion of fecal secondary bile acids is regarded as a major risk factor for colon cancer. Incubation of human colonic biopsies with the secondary bile acid deoxycholic acid (DCA) leads to hyperproliferation with expansion of the proliferative zone, ie, a biomarker of increased cancer risk. Antiproliferative effects on various colon cancer cell lines, however, were reported for butyrate (BUT), a fermentation product of dietary fiber. METHODS In the following in vitro study we incubated biopsies from the normal sigmoid colon of 12 patients (age 55.8 +/- 3.6 years) with 5 microM DCA or a combination of 5 microM DCA plus 10 mM BUT (DCA/BUT) and determined epithelial proliferation by bromodeoxyuridine immunohistochemistry. As a possible mediator for the DCA effects on colonic cell proliferation, mucosal prostaglandin E2 (PGE2) release into the incubation medium was measured by 125I-PGE2 radioimmunoassay. RESULTS Incubation with DCA alone revealed a significantly higher labeling index for the whole crypt (.17 vs .11, p < .01) and for the upper 40% of the crypt (.05 vs .01, p < .01) compared with DCA/BUT. Mucosal PGE2 release during DCA/BUT incubation showed a trend toward lower values compared with DCA incubation (357.07 vs 434.29 pg/mg per hour; p = .07). CONCLUSION The results indicate a normalization of DCA-induced hyperproliferation of colonic epithelium by butyrate that is not clearly mediated by PGE2. Considering that nutrition affects the luminal concentrations of DCA and butyrate, our findings may have implications for colonic carcinogenesis.

In Vitro Fermentation of High-Amylose Cornstarch by a Mixed Population of Colonic Bacteria

BACKGROUND Malabsorbed starch is probably the most important substrate for bacterial fermentation in the human large intestine. Fermentability of starch may depend on the composition of the colonic flora and its adaptation to the substrate supply. METHODS Ten healthy volunteers were fed a controlled diet containing either 7.0 to 8.3 or 50.7 to 59.7 g/d of resistant starch (Hylon VII) for 4 weeks. At the end of each diet period, fecal starch concentrations were measured. Fecal samples were incubated in 48-hour batch cultures containing 10 g/L Hylon VII or digestible Lintners starch. Bacterial breakdown of starch and short-chain fatty acid concentrations were measured at 0, 3, 6, 12, 24, and 48 hours. RESULTS Fecal starch concentrations were higher during the Hylon VII period (35.7 +/- 16 vs 8.9 +/- 3.3 mg/g). Starch was fermented rapidly and completely in vitro in all but two subjects. Fermentability of resistant starch was comparable to that of digestible starch. No differences were found between the dietary periods. Fermentation of resistant starch produced higher rates of n-butyrate. Two subjects had substantially higher fecal starch concentrations. In vitro starch breakdown in these subjects was slow and incomplete. CONCLUSIONS Fermentation of resistant starch by the colonic microflora was rapid and complete in 8 of 10 subjects. No adaptation of the fermentation capacity was observed after 4 weeks of dietary resistant starch supplementation. Fermentation of resistant starch increased the proportion of n-butyrate in vitro. In two subjects, fecal starch concentrations were substantially higher than in the other subjects and in vitro starch fermentation was slow and incomplete.

Effect of a single oat bran cereal breakfast on serum cholesterol, lipoproteins, and apolipoproteins in patients with hyperlipoproteinemia type IIa.

Serum cholesterol-lowering effects of oat bran-enriched diets have been indicated in several studies in which oat bran was given several times a day. Concomitant changes in the daily diet, ie, a diminished energy intake or changes in the composition of fats in the diet, also have been reported and used to explain the hypocholesterolemic effect of oats. The present study was designed to replace only the conventional continental breakfast by a single oat bran cereal muesli containing 60 g of oat bran and to measure the effects of this dietetic modification on serum lipids in 13 patients with hypercholesterolemia type IIa. Compared with a 3-week baseline period, total serum cholesterol (7.38 +/- 0.35 mmol/L, mean +/- SEM) was reduced by 10.9, 8.4, and 9.7% in the first, second, and third week of oat bran ingestion (p < .01). High-density lipoprotein and low-density lipoprotein cholesterol as well as apolipoprotein A1 decreased to the same extent (8 to 11%; p < .05) during the oat bran period, whereas a pronounced reduction of 25.8% was seen for apolipoprotein B100 (p < .01), which is a major component of low-density lipoprotein. Dietary data obtained by 3-day food records at baseline, oat bran, and follow-up period did not show any differences between the study periods except for dietary fiber, which was increased from 21.9 g/day to 42.4 g/day (p < .002) during the test period because of the daily oat bran intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Untersuchungen zur Frage der Vitaminresorption im Dickdarm

ZusammenfassungMittels einer Methode, die es gestattet, beliebig oft Lösungen in das Caecum der Ratte zu injizieren, wurde untersucht, ob der Dickdarm in der Lage ist, Thiamin, Pantothensäure, Vitamin A undΒ-Carotin zu resorbieren. Für alle untersuchten Substanzen konnte eine Resorption nachgewiesen werden. Bei Vitamin A wurde weiterhin der Einfluß verschiedener Lösungsformen, bei Vitamin A undΒ-Carotin der Einfluß gleichzeitiger Gaben eines schwerresorbierbaren Sulfonamids auf die Resorption ermittelt.