Short-chain Fatty Acids Mixture Research Articles

Short-chain fatty acids induce cell cycle inhibitors in colonocytes

Background & Aims: We tested the hypothesis that short-chain organic acids in the colon derived from dietary pectin, wheat bran, and oat bran are protective against the development of colon cancer because they induce transforming growth factor (TGF)-β1, which in turn inhibits cell growth by inducing cyclin-directed kinase (cdk) inhibitors. Methods: U4 human colon carcinoma cells differentiate into water- and salt-transporting columnar enterocytes and therefore model normal colonocytes. The composition and kinase activity of cdk/cyclin complexes were determined by immunoprecipitation and Western blotting studies in U4 cells treated in vitro with short-chain fatty acid (SCFA) mixtures that mimic the digestion products of wheat bran, oat bran, pectin, and cellulose (as control), which is largely unfermentable. Results: Induction of the cdk inhibitors p21cip1 and p27kip1 by fiber-mimicking SCFA mixtures occurs much more rapidly and is many-fold greater than their induction by TGF-β1. The SCFA mixtures most effective in causing growth inhibition and cdk inhibitor production mimicked those from wheat bran > oat bran > pectin. Conclusions: cdk inhibitor induction by SCFA mixtures is not mediated by TGF-β1. The SCFA mixture mimicking digested wheat bran fiber was the most effective of all mixtures tested in inhibiting cell growth through induction of cdk inhibitors. GASTROENTEROLOGY 1998;114:940-946

Short chain fatty acid mixtures mimicking fiber digests induce CDK inhibitors

Short chain fatty acid mixtures mimicking fiber digests induce CDK inhibitors

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

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. 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. 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. SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

Effects of short-chain fatty acids on electrophysiological properties and permeability characteristics of sheep ( Ovis aries) abomasal mucosa

Transepithelial potential differences (PD), electrical conductances (g t) and mannitol fluxes were measured in sheep abomasal epithelia incubated in vitro with either short-chain fatty acids (SCFA) or with lactic acid. In contrast to lactic acid a SCFA mixture, or acetic acid alone, drastically reduced both PD and G, within minutes. Transepithelial mannitol fluxes were significantly reduced by SCFA during 60 min of incubation but increased greatly during incubation over two consecutive flux periods of 60 min. Lactic acid had no such effect. It is suggested that SCFA may overload pH and volume regulative systems of the abomasal epithelial cells resulting in cell swelling and reduced transepithelial rheogenic transport.

Effect of Short‐Chain Fatty Acids on Colonic Function and Structure

Short-chain fatty acids (SCFA), fermentation products of fiber, are believed to play a role in intestinal adaptation. Although the administration of fiber or the infusion of SCFA has been shown to cause colonic growth, studies have been done primarily in enterally fed animals. In addition, the effects of SCFA on absorptive function have not been determined. Adult male rats were maintained on total parenteral nutrition (TPN) and, in addition, received either 150 mmol/L of saline or 150 mmol/L of SCFA mixture (60:25:15, acetate:propionate:butyrate) into the proximal colon. One week later, the in vivo absorption of water, electrolytes, and 20 mmol/L of butyrate was measured. After the rats were killed, parameters of colonic mass were determined. SCFA infusion into the colon had no significant effect on absorptive function. However, significantly greater mucosal height (p less than .01) and mucosal DNA (p less than .05), were observed. Although SCFA has a modest effect on colonic structure, they do not influence absorptive function in TPN rats.

Human exposure to putative pheromones and changes in aspects of social behaviour

Student volunteers (38 of each sex) were exposed unknowingly overnight to the vapour of pheromonally active substance and compared with controls. The substances were either 5α-16-androsten-3α-ol (androstenol, occuring in human underarm sweat, and known to be pheromonally active in pig and man), or a mixture of short-chain fatty acids (occurring in human vaginal fluid, and known to be sexually attractive to the male rhesus monkey). The following morning, the subjects provided information about their social exchanges since rising, by recording on a standardized test diagram the number, depth, duration and direction of initiation, of all verbal exchanges with other individuals. Irrespective of treatment, males returned significantly higher scores than did females for all exchanges and also for some exchanges initiated by other males. Neither exposure to androstenol nor to the fatty acids had any significant effects on any of the scores of males interacting with either sex, nor on any scores of females with other females. However, exposure of females to androstenol, but not to the fatty acids, resulted in significantly higher scores of exchanges with males, in terms of all parameters for all exchanges. Findings are considered in relation to the origin and maintenance across species of pheromonal communication: evolutionary conservation is seen in terms of the utilization of substances that have provided the means of controlling the social milieu.

Effects of short chain fatty acids and K on absorption of Mg and other cations by the colon and caecum

The influence of short chain fatty acids (SCFA) on Mg, Na, and water absorption was studied in the rat distal colon and caecum using an in vivo luminal perfusion technique. The effect of SCFA on K absorption by the distal colon and the effect of K on Mg absorption by the distal colon and caecum were also investigated. Butyrate (60 mmol/l) or a mixture of SCFA (60 mmol/l acetate, 20 mmol/l propionate, 10 mmol/l butyrate) stimulated Mg and K absorption by the distal colon, while Na and water absorption was not affected. The effect on Mg absorption was pH-dependent. In the caecum, butyrate enhanced Na and water absorption, but not Mg absorption. Acetate (60 mmol/l) did not influence electrolyte absorption by either intestinal segment. K (30 mmol/l) inhibited Mg absorption by the distal colon, but not by the caecum. It is concluded from these findings that SCFA deriving from fermentation of carbohydrates in the large intestine stimulate Mg, K, and Na absorption by delivering protons to Mg++/H+, K+/H+ and Na+/H+ exchangers located in the apical membrane of the epithelium. K seems to inhibit Mg absorption in the colon by affecting a mechanism which does not respond to SCFA.

A relationship between the molar proportion of propionic acid and the clearance rate of the liquid phase in the rumen of the sheep

1. Four rumen-cannulated sheep were given a forage mixture (F) of chopped hay-ground, pelleted, dried grass (92:8, w/w) and two concentrate mixtures (C and S) of ground barley-ground hay-flaked maize (46:24:30 and 56:24:20, by wt respectively) in twenty-four hourly meals each day. Each of the diets was offered in successive periods of 16 d to give a feeding sequence F-S-C-S for one pair of sheep and C-S-F-S for the other pair. 2. The average composition (mol/100 mol) of the mixture of short-chain fatty acids, acetic, propionic and butyric, in the rumen was respectively 70-1, 18-5 and 7-5 with diet F, and 55-8, 24-8 and 13-6 with diet C. With diet S, the pattern of fermentation varied both between animals and in the same animal for different periods having either 'high' (28-39 mol/100 mol) or 'low' (16-21 mol/100 mol) proportions of propionic acid. On average when diet S followed diet F there was less propionic acid in the fermentation mixture than when diet S followed diet C (59-3 acetic, 22-2 propionic and 14-1 butyric as compared with 52-7, 29-4 and 13-1 respectively) but this trend was not significant and there was evidence of interactions between the feeding sequences and the individual sheep. 3. The mean concentrations of ammonia, sodium, potassium and chloride were similar for all diets but the pH and concentrations of calcium, magnesium and phosphorus tended to be higher and the buffering capacity lower for diet F than for diets C or S. In animals receiving diet S there was no relationship between the concentrations of minerals, the pH or buffering capacity and the pattern of fermentation except for ammonia, the concentration of which was high when the molar proportion of propionic acid was low. 4. Rumen volume, outflow rate and clearance rate, determined using polyethylene glycol, were higher for diet F than for diets C and S but within each diet, particularly for diet S, values varied considerably between sheep and between periods. 5. There was evidence of an interrelationship between the molar proportion of propionic acid in the fermentation products and the clearance rate, which indicated that the clearance rate may be an important factor influencing the pattern of fermentation in the rumen.

The effect of exposure to two odorous compounds (pheromones) on an assessment of people test

Publisher Summary This chapter focuses on the effect of exposure to two odorous compounds (pheromones) on an assessment of people test. Work is carried out on the effect of exposing people, for a short period of time, to a mixture of short-chain fatty acids and to androstenol. A test was designed that required participants to express favorable or unfavorable opinions about the suitability of a number of applicants, of both sexes, for a position of responsibility. The results show that women exposed to the presence of the fatty acids and the androstenol are not affected in their assessments of applicants of their own sex, but that exposure is accompanied by a change in their assessment of male applicants. Males were little affected by the compounds, but there was some evidence to suggest that they reacted differently when assessing men and women. In addition, the chapter also describes the effect of epinephrine on liver 5-nucleotidase.

The voluntary intake of acetate by dairy cows given ammonium salts of short-chain fatty acids in their drinking water

A solution of ammonium salts of a mixture of short-chain fatty acids (mainly acetic acid) was added to the sole source of drinking water of 10 lactating Jersey cows. There was considerable variation in the concentration of salts tolerated without depression in water intake. Some animals refused solution offered at a concentration of 0·5% (w/w) whereas one animal accepted solution at a concentration of 8% (w/w) and had a mean daily intake of salts equivalent to 836 g acetic acid.2. Adjustment of the pH of the drinking solution to 6·5–7·5 increased the tolerance to the salts solution of animals which showed a low tolerance to the unadjusted solution. A mean daily intake equivalent to 480 g acetic acid was achieved without a significant depression of water intake. Replacement of 50 % of the ammonium ions by calcium increased the intake of salts by some cows but two out of eight refused the solution at a concentration of 0·5% (w/w).3. The addition of saccharine, vanilla or aniseed to a solution of the ammonium salts gave little or no improvement in acetate intake but sodium cyclamate, ethyl acetate or molasses reduced the variability between animals in their tolerance to the solution and increased the mean intake of salts. With an addition of molasses, which gave the most marked response, there was a mean daily intake of salts equivalent to 495±26 g acetic acid.