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PubMed1986

Short-chain fatty acids in germfree mice and rats.

The short-chain fatty acids (SCFAs) have been analyzed in small intestinal and cecal content of 10 germfree and six conventional mice from a Norwegian laboratory, in cecal content and serum of five germfree rats and two germfree mice from a Swedish laboratory and in Norwegian and Swedish autoclaved, nonpurified rodor diets. The mean total SCFA concentration was 1020 mumol/kg in cecum and 1010 mumol/kg in small intestine of Norwegian germfree mice; 124,600 mumol/kg in cecum and 6,250 mumol/kg in small intestine of conventional mice; 490 mumol/kg in cecum and 370 mumol/L in serum of Swedish rats; 360 mumol/kg in cecum and 290 mumol/L in serum of Swedish mice; 31.4 mmol/kg in Norwegian and 19.5 mmol/kg in Swedish nonpurified diets. Acetic acid accounted for more than 90% of the total concentration in all samples from germfree animals and diet, but detectable concentrations of propionic, isobutyric, n-butyric, isovaleric and n-valeric acid were also present. Thus, germfree animals have low, but measurable, concentrations of SCFAs in intestinal content compared to conventional animals. Most probably these acids originate mainly from the diet.

Animals↗

PubMed2005

Fructooligosaccharides and fiber partially prevent the alterations in fecal microbiota and short-chain fatty acid concentrations caused by standard enteral formula in healthy humans.

The intestinal microbiota are important during enteral tube feeding because they exert colonization resistance and produce SCFAs. However, the effect of the enteral formula composition on major bacterial groups of the microbiota has not been clearly defined. The aim of this study was to investigate the effect of enteral formulas with and without prebiotic fructooligosaccharides (FOS) and fiber on the fecal microbiota and SCFAs. Healthy subjects (n = 10; 4 men, 6 women) consumed both a standard enteral formula and one containing FOS (5.1 g/L) and fiber (8.9 g/L) as a sole source of nutrition for 14 d in a randomized, double-blind, crossover trial with a 6-wk washout phase. Fecal samples were collected at the start and end of each formula phase, and were analyzed for major bacterial groups and SCFA concentrations using fluorescent in situ hybridization and GLC, respectively. Although there were reductions in total fecal bacteria due to both formula treatments, concentrations were higher after the FOS/fiber formula period compared with the standard formula period (11.2 +/- 0.2 vs. 11.0 +/- 0.2 log(10) cells/g, P = 0.005). The FOS/fiber formula increased bifidobacteria (P = 0.004) and reduced clostridia (P = 0.006). Compared with the standard formula, the FOS/fiber formula resulted in higher concentrations of total SCFA (332.4 +/- 133.8 vs. 220.1 +/- 124.5 micromol/g, P = 0.022), acetate (219.6 +/- 96.3 vs. 136.8 +/- 74.5 micromol/g, P = 0.034) and propionate (58.4 +/- 37.4 vs. 35.6 +/- 25.5 micromol/g, P = 0.02). This study demonstrates that standard enteral formula leads to adverse alterations to the fecal microbiota and SCFA concentrations in healthy subjects, and these alterations are partially prevented by fortification of the formula with FOS and fiber.

Bacteria↗

PubMed2005

Diet and age affect intestinal morphology and large bowel fermentative end-product concentrations in senior and young adult dogs.

The objective of this study was to determine the effects of age and diet on intestinal morphology and large bowel fermentative end-product concentrations in healthy dogs. Small intestinal villus width, height, and area, and small intestinal and colonic crypt depth were measured. Large bowel digesta samples were analyzed for ammonia, SCFAs, and branched-chain fatty acids (BCFAs). SCFAs are considered to be beneficial fermentative end-products in the intestine because they exert trophic effects on intestinal cells. Twelve senior (age = 11.1 y +/- 0.6 at baseline; 6 male, 6 female) and 12 young adult (age = 8 wk old at baseline; 6 male, 6 female) beagles were randomly assigned to 1 of 2 dietary treatments, an animal product-based diet (APB) and a plant product-based diet (PPB). Diets were fed for 12 mo. Jejunal (P = 0.03) and ileal (P = 0.02) villus height, and duodenal (P = 0.04) villus width were greater for dogs consuming the PPB diet. Young dogs had greater (P = 0.04) jejunal villus height, whereas senior dogs had greater (P < 0.001) colonic crypt depth. Ammonia concentrations decreased (P = 0.03) from proximal to distal colon and were higher in dogs consuming APB (P = 0.03). Age and treatment affected butyrate concentrations, with senior dogs (P = 0.04) and dogs consuming APB (P = 0.04) having higher concentrations. Both diet and age affected small and large intestinal morphology, and colonic fermentative end-product concentrations in dogs.

Animal Feed↗

PubMedDate not supplied

Development of five metabolic activities associated with the intestinal microflora of healthy infants.

The establishment of a functionally active intestinal flora was followed in 17 healthy Swedish children from birth up to 6 months of age. Utilizing gas chromatography, spectrophotometry, and gel electrophoresis, feces were analyzed on certain biochemical markers that reflect the action of the intestinal flora in vivo. The establishment of the following five flora-related functions was investigated: production of short chain fatty acids (SCFAs), degradation of mucin, conversion of bilirubin to urobilinogen and of cholesterol to coprostanol, and inactivation of fecal tryptic activity (FTA). Production of SCFAs was the first function to be established, followed by bilirubin conversion and mucin degradation. No child showed conversion of cholesterol. The values of FTA were lower than in adults. This study indicates that the establishment of a functionally active flora is a slow process and that some functions are almost fully established before other functions have started to develop. Environmental factors, such as the diet, seem to be of importance. In general, the functions seem to develop slower in those children receiving breast milk exclusively than in those receiving formula supplements.

Bilirubin↗

PubMed2002

Predominance of caecal injury in a new dextran sulphate sodium treatment in rats: histopathological and fermentative characteristics.

OBJECTIVES: Cyclic administrations of dextran sulphate sodium (DSS) alternating with distilled water usually induce chronic colitis after a few weeks. In order to obtain stable chronic colitis (without recovery or relapse) in a few days, a new continuous DSS treatment was tested and characterized. Short-chain fatty acids (SCFAs), which remain poorly documented in experimental colitis, were also investigated. METHODS: Thirty-six Sprague-Dawley rats were treated with 5% DSS for 7 days (DI) followed by 3% DSS for 7 days (DM) or 14 days (DF). Control rats received only water. Inflammatory injuries in the caecum and the colon were assessed by macroscopic (colon length, caecum weight, damages score) and histological parameters. SCFAs (acetate, propionate, butyrate) were quantified individually in caecal, proximal and distal contents. RESULTS: Macroscopic and histological observations revealed that this continuous DSS treatment induced acute inflammation (DI) followed rapidly by chronic active colitis. The latter was uncommonly predominant in the caecum and the distal colon, and was also associated with some fermentative disturbances. Caecal SCFA concentrations decreased with DSS at DI and DM. The molar ratio of caecal butyrate increased with DSS. Acetate decreased in the colon while propionate increased. CONCLUSION: This new DSS treatment is able to induce in a few days stable chronic inflammation with caecal and distal predominant injuries, and mild fermentative caeco-colonic alterations. This model could contribute to the study of potential anti-inflammatory effects of prebiotics.

Animals↗

PubMed2002

Influence of intestinal anaerobes and organic acids on the growth of enterohaemorrhagic Escherichia coli O157:H7.

A suspension of human faeces (FS) and its anaerobic culture (FC), bacterial metabolic products and organic acids were examined for inhibitory effects on growth and verotoxin 2 (VT2) production of Escherichia coli O157:H7 in vitro. FS and FC showed a marked inhibitory activity to growth and production of VT2 by E. coli O157:H7 under anaerobic conditions. They may have both bacteriostatic and bactericidal effects on E. coli O157. The growth of E. coli O157 was markedly suppressed by acetic, propionic and butyric acids compared with hydrochloric acid and lactic acid at concentrations between 25 mM and 40 mM, being proportional to the pH values. At pH 5.5, 40 mM of short-chain fatty acids (SCFAs) almost completely inhibited the growth of E. coli O157. SCFAs markedly inhibited the growth of E. coli O157 at pH 6.0 rather than pH 7.0. Propionic acid is likely to be more suppressive to E. coli than acetic and butyric acids. The production of VT2 was approximately proportional to the growth of E. coli O157. However, incubation for 24 h in vitro showed that the growth and VT2 production of E. coli O157 decreased but were not completely inhibited at pH 6.5 and 7.0 in a mixture of acetic, propionic and butyric acids at a physiological concentration (110 mM, 60:25:25, respectively, in molar ratio). It is probable that the colonic microflora could contribute to a reduction of E. coli O157:H7 infections via the activation of intestinal fermentation by dietary manipulation or something similar to give pH 6.0 or <6.0 and that factors such as age, chemical therapy and body condition, which have effects on the balance of the intestinal microflora, would be associated with the incidence rates of E. coli O157 infections.

Acetic Acid↗

PubMed1986

Influence of peroral antibiotics upon the biotransformatory activity of the intestinal microflora in healthy subjects.

The effects of ampicillin, clindamycin or metronidazole, given perorally for 6 days to eighteen healthy volunteers, upon the following intestinal microflora-associated characteristics (MACs) were evaluated: breakdown of mucin, formation of coprostanol, hydrolysis of bilirubin conjugates, formation of urobilinogen, and of some short chain fatty acids (SCFAs), presence of beta-aspartylglycine and inactivation of trypsin. Clindamycin markedly influenced the expression of all characteristics, but trypsin and beta-aspartylglycine, resulting in a pattern very much alike what has been found in germ-free animals. Ampicillin caused a significant reduction in total amount of SCFAs (P less than 0.05) and urobilinogen (P less than 0.05) present in the faecal samples. Metronidazole caused a significant reduction in the formation of coprostanol and the deconjugation of bilirubin (P less than 0.05). We conclude that orally given antibiotics may cause major alterations in several parameters reflecting the normal biotransformatory activity of the intestinal microflora, probably caused by severe disturbances in the intestinal ecosystem.

Administration, Oral↗

PubMed1994

Variations in concentrations of bacterial metabolites, enzyme activities, moisture, pH and bacterial composition between and within individuals in faeces of seven healthy adults.

Variations between and within individuals, and correlations between concentrations of bacterial metabolites, including putrefactive products, ammonia and short chain fatty acids (SCFAs), enzyme activities, moisture and pH, as well as bacterial composition, were studied in faecal samples from seven healthy adults over a period of 7 months. Large variations, both between and within individuals, were observed in concentrations of putrefactive products. Although values for ammonia, SCFAs, enzyme activities, moisture and pH were generally variable, significant person-to-person differences were observed. While ranges of log viable counts of the predominant bacteria such as eubacteria, bifidobacteria and bacteroides in each subject remained between 0.2 and 1.3, those of enterobacteria, streptococci (including enterococci) and lecithinase-negative clostridia varied between 0.4 and 3.0. Levels of bifidobacteria, enterobacteria, streptococci and total aerobic bacteria showed inter-individual variations. Correlations were found among certain of the parameters: moisture correlated negatively with p-cresol (r = -0.707), pH (r = -0.671) and beta-glucosidase activity (GS) (r = -0.608), and positively with acetic acid (r = 0.621), while negative correlations were observed in pH with acetic and butyric acids (r = -0.690 and -0.623, respectively). No significant correlations were found between bacterial compositions, and other faecal factors such as pH, moisture, metabolic enzyme activities and concentrations of putrefactive products.

Adult↗

PubMed2005

Neural and non-neural mediation of propionate-induced contractile responses in the rat distal colon.

Short-chain fatty acids (SCFAs), including propionate, butyrate and acetate, are fermentation products of carbohydrates in the colon. We investigated the contractile effects of SCFAs on the rat distal colon. Mechanical activity of the circular muscle in strip preparations was recorded in vitro. Propionate and butyrate concentration-dependently (10 micromol L(-1)-10 mmol L(-1)) induced rapid, large amplitude phasic contractions (the first phase) followed by tonic contractions (the second phase). Acetate itself had no effect on muscle activity, although preincubation with acetate attenuated both phases of the propionate-induced response. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT4 receptor antagonist SB-204070. The propionate-induced tonic contraction was attenuated by the cyclo-oxygenase inhibitor piroxicam. Antagonists of 5-HT1A, 5-HT2A and 5-HT3 receptors had no effect on the responses. Propionate-induced responses were not observed in mucosa-free preparations. These results suggest that propionate acts on receptors in the mucosa causing the release of 5-HT from enterochromaffin cells. 5-HT acts through 5-HT4 receptors on the endings of intrinsic primary afferent neurones that in turn activate cholinergic motor neurones that contract the circular muscle. Propionate also causes tonic contraction, via prostaglandin release, in the rat distal colon.

Acetates↗

PubMed1999

Regulatory role of cAMP in transport of Na+, Cl- and short-chain fatty acids across sheep ruminal epithelium.

Sodium is absorbed in considerable amounts across the ruminal epithelium, whilst its transport is strongly interrelated with the permeation of chloride and short-chain fatty acids (SCFAs). However, regulation of ruminal Na+, Cl-, and SCFA absorption is hardly understood. The present study was therefore performed to characterize the influence of cAMP on sodium and sodium-coupled transport mechanisms in short-circuited, stripped ruminal epithelia of sheep. Elevation of intracellular cAMP concentrations by theophylline (10 mM) or theophylline in combination with forskolin (0.1 mM) significantly reduced mucosal-to-serosal sodium transport, leading to a reduction of net transport. The theophylline- or theophylline-forskolin-induced reduction of sodium transport was accompanied by a decrease in chloride net transport but revealed no effect on propionate flux. Short-chain fatty acids stimulated Na+ transport but their stimulatory effect was almost completely blocked by theophylline-forskolin. In solutions with and without SCFAs, the inhibitory effect of 1 mM amiloride on sodium transport was strongly reduced after theophylline-forskolin pretreatment of the tissues. Blocking the production of endogenous prostaglandins by addition of indomethacin (10 microM) led to a theophylline-sensitive stimulation of unidirectional and net fluxes of sodium. The findings indicate that apical, amiloride-sensitive Na+-H+ exchange and/or basolateral Na+-K+-ATPase can effectively be blocked by cAMP, leading to a decrease in sodium and chloride transport. In the ruminal epithelium, cAMP is a second messenger of prostaglandins, which are released spontaneously under in vitro conditions.

Animals↗

PubMed1983

Treatment of epileptic patients with valproic acid does not modify plasma and urine short-chain-fatty acids.

The purpose of this study was to evaluate the possible modifications of the plasma and urine short-chain-fatty acid (SCFA) patterns indiced by treatment with valproic acid (VPA). Increased amounts of SCFAs in patients under VPA treatment may explain the presence of VPA-induced hyperammonemia, toxic encephalopathies and rarer Rey-like syndromes recently observed. For this reason we assayed SCFA levels in the plasma and looked for propionic acid in the urine of 10 epileptic patients to whom it was decided to add VPA to their previously unsatisfactory anti-epileptic treatment. This was carried out prior to and during therapy with VPA. 5 of these patients developed toxic encephalopathy with hyperammonemia induced by VPA. Our data show that plasma and urine SCFAs are not modified by VPA treatment. This is so even in patients who have toxic encephalopathy with hyperammonemia indiced by this drug.

Adolescent↗

PubMedDate not supplied

Faecal short-chain fatty acids in breast-fed and bottle-fed infants.

Faecal short-chain fatty acids (SCFAs) were determined in 49 infants on three occasions, i.e. at ages three and six days and two months. At two months, the breast-fed infants had a significantly higher proportion of acetic acid in the SCFA spectra than the bottle-fed infants. The data suggest that the composition of the intestinal microflora in most breast-fed infants is characterized by a high relative content of acetic acid in faecal SCFAs. This may be associated with protection against diarrhoea and respiratory infections in the infant.

Bottle Feeding↗

PubMed1987

Short-chain fatty acids in seven sterile thioglycollate media.

Short-chain fatty acids (SCFAs) were analysed by gas chromatography in 7 sterile fluid thioglycollate media. The total SCFA concentration varied from 250 mumol/l to 1720 mumol/l. Acetic acid (52.0%-91.3% of total SCFA concentration) and n-butyric acid (5.8%-48.0% of total concentration) were the main acids in all sterile media; low concentrations of propionic, isobutyric, isovaleric, and n-valeric acid were present in most media. In studies of bacterial metabolism, or when analyses of SCFAs are used for identification of bacteria, testing of the sterile medium is necessary.

Chromatography, Gas↗

PubMed1992

Segmental differences of short-chain fatty acid transport across guinea-pig large intestine.

Unidirectional fluxes of short-chain fatty acids (SCFAs) were measured under short-circuit current conditions across guinea-pig caecum, proximal and distal colon. Fluxes increased linearly with concentration. In the caecum with equal concentrations on both sides of the mucosa the serosal-to-mucosal (sm) fluxes were nearly twice the mucosal-to-serosal (ms) fluxes for all SCFAs; in the distal colon ms fluxes were always higher than sm fluxes. Thus, in the caecum the net effect was secretion while in the distal colon net absorption occurred. In caecum, ms fluxes decreased with chain length while sm fluxes were similar for the three fatty acids, acetic, propionic and butyric acid. In the distal colon both unidirectional fluxes increased with chain length. Fluxes across the mucosa of the proximal colon were intermediate to those in caecum and distal colon. A paracellular transport of short-chain fatty acids is not present. The results indicate that other processes are involved in transcellular transport of SCFA besides non-ionic diffusion.

Acetates↗

PubMed1994

Effects of short chain fatty acids on gut morphology and function.

Short chain fatty acids (SCFAs) are the products of colonic bacterial degradation of unabsorbed starch and non-starch polysaccharide (fibre). They are important anions in the colonic lumen, affecting both colonocyte morphology and function. The three main acids (acetate, propionate, and butyrate) stimulate colonic sodium and fluid absorption and exert proliferative effects on the colonocyte. Experimental animal studies have shown that they promote adaptive responses to small intestinal resection and colonic anastomosis. Acetate increases colonic blood flow and enhances ileal motility. Butyrate has been shown to be the preferred energy substrate for the colonocyte and to be a potent differentiating agent in cell culture. Butyrate may also have a role in preventing certain types of colitis. A diet low in resistant starch and fibre, which will result in a low production of SCFAs in the colon, may explain the high occurrence of colonic disorders seen in the Western civilization.

Cell Differentiation↗

PubMed1995

Colonic short chain fatty acids mediate jejunal growth by increasing gastrin.

Colonic infusion of short chain fatty acids (SCFAs) is trophic to rat jejunum and is associated with raised jejunal gastrin concentration. This study examined the hypothesis that the jejunal trophic effects of colonic SCFAs are mediated in part by gastrin. Forty six adult rats underwent caecectomy to reduce endogenous production of SCFA, ileocolonic anastomosis, and placement of a colonic infusion catheter. SCFA (70 mM acetate, 35 mM propionate, 20 mM butyrate) or saline were continuously infused into the colon for seven days. Rats received either a gastrin receptor blocker (L-365,260) or a control solution and animals were killed on day 8. SCFA infused into the colon acted systemically to significantly improve jejunal structure and increase jejunal gastrin concentrations. Gastrin receptor blockade abolished effects of SCFA on jejunal DNA, protein, crypt cell proliferation, and gastrin. Gastrin blockade did not reduce SCFA induced augmentation of villous height or crypt depth. It is concluded that the jejunal trophic effects of colonically infused SCFA are mediated in part by gastrin.

Animals↗

PubMed1996

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic fermentation. Considering the effects of some fermentation products on intestinal morphology and function, these variations may be relevant to the pathogenesis of colorectal diseases.

Adult↗

PubMed1998

The influence of a preserved colon on the absorption of medium chain fat in patients with small bowel resection.

BACKGROUND: Medium chain C8-C10 triglycerides (MCTs) improve fat absorption in short bowel patients. Effects on overall energy absorption remain unknown. AIMS: To determine whether MCTs and medium chain fatty acids (MCFAs) are absorbed in the colon like the short chain fatty acids (SCFAs) or are lost in faeces similarly to long chain fatty acids (LCFAs). METHODS: Nine small bowel resected patients without and 10 with a colon in continuity excreted 2-6 MJ/day and were randomised and crossed over between two high fat diets (10 MJ/day, 50% as fat), based on either long chain triglycerides (LCT) alone or equal quantities of LCT and MCT. RESULTS: Patients with a colon absorbed C8-C10 fatty acids considerably better than patients without a colon at similar and extreme levels of LCFA malabsorption; the colonic impact on absorption of C14-18 fatty acids was negligible. MCT redoubled fat (MCT+LCT) absorption from 23% to 58% in patients with a colon, and increased overall bomb calorimetric energy absorption from 46% to 58%. The increase in fat absorption from 37% to 46% in patients without a colon did not improve overall energy absorption because malabsorption of carbohydrate and protein increased. CONCLUSION: In small bowel resected patients, the colon seems to serve as a digestive organ for medium chain fat, probably absorbed as MCFAs, perhaps because like the SCFAs, they are water soluble. Only patients with a colon gained from MCT treatment.

Adult↗