PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “SCFAs”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects.

Faecal excretion of short-chain fatty acids (SCFAs) has been measured by gas chromatography in groups of six or seven healthy subjects before, during, and after they received the antibiotics bacitracin, co-trimoxazol, doxycycline, erythromycin, nalidixic acid, ofloxazin, or vancomycin orally for 6 days. Intake of bacitracin and vancomycin had pronounced effects on faecal SCFAs excretion and reduced median total concentration of SCFAs from 105.4 mmol/kg to 21.8 mmol/kg and from 69.3 mmol/kg to 19.4 mmol/kg, respectively (p less than 0.05). Erythromycin had moderate effects on the faecal SCFAs excretion, whereas small or no changes were seen during intake of co-trimoxazol, doxycycline, nalidixic acid, and ofloxacin. 2-Methylbutyric acid, a SCFA not previously seen in human faeces, was found in the faeces of all subjects (median concentration before intake of antibiotic, 1.3 mmol/kg). Bacitracin, erythromycin, nalidixic acid, and vancomycin were detected in high concentrations in faeces during therapy, whereas trimethoprim, doxycycline, and ofloxacin were found in relatively low concentrations. In conclusion, some, but not all, peroral antimicrobials induce changes in faecal SCFAs, most likely reflecting changes in the colonic ecosystem.

Administration, Oral↗

Short-chain fatty acid release of peptide YY in the isolated rabbit distal colon.

Short-chain fatty acids (SCFAs) form the major ionic fraction of stool, provide the major metabolic substrate for colonic epithelium, and promote mucosal ion transport. Despite this prominent role of SCFAs in metabolism of the colon, their effect on colonic endocrine cell function has not been studied. Consequently, we hypothesized that SCFAs might modulate release of peptide YY (PYY) from colonic type-L endocrine cells. The specific aims of this study were to measure release of PYY from the isolated perfused rabbit distal colon stimulated by intraluminal infusion of 0.9% saline, acetate (10 mM), acetoacetate (10 mM), n-butyrate (1, 3.3, 10, 100 mM), and pyruvate (10 mM). PYY levels were measured by radioimmunoassay in the venous effluent of the rabbit colon. All four SCFAs (10 mM) caused at least a twofold increase in integrated release of PYY from the isolated perfused rabbit colon. Graded concentrations of n-butyrate caused a stepwise release of PYY. This study suggests that SCFAs may modulate the release of colonic PYY in rabbits.

Acetates↗

Oral administration of a product derived from Clostridium butyricum in rats.

Recent studies have suggested that short chain fatty acids (SCFAs) exert a therapeutic effect on some human and experimental animal diseases. Clostridium butyricum produces high levels of SCFAs in the gut lumen. The aim of the present study was to analyze the product derived from Clostridium butyricum in a culture system, and to develop methods to eliminate the odor derived from SCFAs in the product. Clostridium butyricum was incubated in CS medium for 24 h and subsequently in CS broth for 24 h. The suspension of Clostridium butyricum in the broth was centrifugated and the supernatant was analyzed. The results showed this product contained high levels of SCFAs, especially acetic acid and n-butyric acid. Many food materials were tested in order to eliminate the odor derived from SCFAs in the product. Of the food materials tested, yogurt was shown to most effectively eliminate the odor. Using a yogurt base, we prepared a special food additive. Use of the additive completely eliminated the odor of the product derived from Clostridium butyricum. Finally, we administered the product with the additive to Sprague-Dawley rats for 14 days. The rats grew normally for the duration of the experimental period. It is possible that this novel product with the additive exerts therapeutic effects on some gastointestinal disorders.

Acetic Acid↗

Rapid determination of short-chain fatty acids in colonic contents and faeces of humans and rats by acidified water-extraction and direct-injection gas chromatography.

Short-chain fatty acids (SCFAs) have attracted much attention recently because of their positive physiological effects. In this work, a rapid and reliable gas chromatographic method for determination of eight SCFAs, in colonic and faecal samples from rats and humans has been developed and validated. The methodology involves extraction of the SCFAs in water before a direct injection procedure on a FFAP capillary column. A stock standard solution containing acetic acid, propionic acid, n-butyric acid, i-butyric acid, n-valeric acid, i-valeric acid, n-caproic acid and n-heptanoic acid was prepared and used. A high linearity (r2 > 0.9990), low quantification limit (2.38-30.14 microm) and high recovery for most acids were obtained. Acidification of faecal samples was found to be crucial for quantitative determination of the SCFAs, and adjustment of pH to 2-3 was regarded as necessary. Glass wool inserted in the glass liner of the injection port proved effective in preventing the contamination of the column by non-volatiles, and 12% formic acid reduced the ghost peak that appeared gradually after several injections. After validation, the methodology was applied on two faecal samples from rats fed diets containing different amount of dietary fibre and one faecal sample from human fed a normal diet to test the accuracy of the developed method.

Adult↗

Inhibition of IL-8 gene expression in Caco-2 cells by compounds which induce histone hyperacetylation.

Ulcerative colitis, an idiopathic inflammatory disease of the colonic mucosa, can be effectively treated by enemas containing short chain fatty acids (SCFA) such as butyrate, propionate, and acetate. The molecular mechanisms that lead to this response have not been well characterized. It is well known that intestinal inflammation leads to an alteration in patterns of epithelial differentiation with an increase in epithelial proliferation and an expansion of cell populations in an undifferentiated state. SCFAs such as butyrate are capable of inhibiting cell proliferation and inducing a differentiated phenotype in vitro. The Caco-2 colon cancer cell line was used to study the effect of SCFAs and the process of cellular differentiation on the expression of the pro-inflammatory cytokine, interleukin 8 (IL-8). SCFAs and trichostatin A, structurally unrelated compounds which both induce histone hyperacetylation, both led to a dose-dependent inhibition of IL-8 gene expression. Furthermore, spontaneous differentiation of Caco-2 cells by growth to a post-confluent state also inhibited the expression of IL-8. A possible mechanism by which SCFAs may be effective in the treatment of ulcerative colitis may be through their ability to increase histone acetylation states and inhibit the production of pro-inflammatory substances by the intestinal epithelium.

Acetylation↗

Fecal short-chain fatty acid concentrations and effect on ileal pouch function.

Random stool samples were obtained from 14 ileal pouch-anal anastomosis (IPAA) patients 43 +/- 5 (mean +/- SEM) months after surgery, and the concentrations of individual short-chain fatty acids (SCFAs) were determined by gas liquid chromatography. Stool frequency was determined from a diary recorded for 15 days prior to stool sampling. The frequency, amplitude, and duration of phasic contractions (PCs) within the pouch following infusion of a physiologic concentration of SCFAs and normal saline randomly into the pouch of six IPAA patients were determined manometrically. The mean total SCFA concentration after IPAA did not differ significantly from normal stools (83 +/- 20 mM after IPAA vs. 97 +/- 10 mM for controls; P > 0.05). In the IPAA patients, regression analysis demonstrated an inverse relationship between stools per day and total SCFA concentration (r = 0.73; P < 0.001). Moreover, no change in frequency (3.0 +/- 0.9 vs. 3.2 +/- 0.8 PCs/30 minutes), amplitude (26 +/- 5 vs. 25 +/- 4 mmHg), or duration (23 +/- 3 vs. 26 +/- 2 seconds) of PCs was found after SCFA infusion compared with saline control (P > 0.1). These findings demonstrate that SCFAs are present in ileal pouch effluent and that stool frequency may be related to fecal SCFA concentration. Also, the normal contractile response of the terminal ileum to SCFAs does not occur in the ileal pouch.

Adult↗

Fecal short-chain fatty acids associated with inflammation in cotton-top tamarin model for idiopathic colitis.

This study measured fecal levels of short-chain fatty acids (SCFAs) relative to the severity of colitis in the cotton-top tamarin model of colitis and colon cancer. Severity of colitis was classified as mild, moderate, or severe by subjective scoring of colonic mucosal biopsies and quantification of inflammatory cell infiltrates in the lamina propria. SCFAs were determined by gas chromatography of SCFAs extracted from fresh feces. Tamarins with moderate or severe colitis had significantly reduced levels of fecal SCFAs. The percent dry matter of feces declined significantly in moderate and severe colitis, while total dry matter output per day increased, indicating that moderate and severe colitis in tamarins was associated with diarrhea and increased fecal water loss. In conclusion, this study found colitis in the tamarin model was associated with decreased fecal SCFA levels and progressive inflammation in a pattern similar to human colitis.

Animals↗

Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line.

The expression of GPR41 and 43, which have recently been identified as G-protein-coupled cell-surface receptors for short-chain fatty acids (SCFAs), was detected in a human breast cancer cell line (MCF-7) by RT-PCR. Acetate, propionate and butyrate induced an increase in intracellular Ca2+ in these cells that was not blocked by treatment with pertussis toxin (PTX). SCFAs significantly reduced forskolin-induced cAMP levels in these cells. The phosphorylation of mitogen-activated protein kinase (MAPK) p38 was selectively increased by SCFAs. The downstream substrate heat shock protein 27 (HSP27) was also phosphorylated by SCFAs at Ser-78 and-82, but not-15. Propionate induced elevations in intracellular Ca2+ and the phosphorylation of p38 were inhibited by the silencing of GPR43 using a specific siRNA. These results suggest that GPR41 and 43 mediate SCFA signaling in mammary epithelial cells and thereby play an important role in their stress management.

Acetates↗

Effects of soluble fiber on matrix metalloproteinase-2 activity and healing of colon anastomosis in rats given radiotherapy.

BACKGROUND AND AIMS: Soluble fiber is fermented by colonic microflora yielding short-chain fatty acids (SCFAs) in the colon. We aimed to investigate the effect of oral administration of soluble fiber on healing of anastomosis and matrix metalloproteinase-2 activity in radiotherapy received colonic anastomosis. METHOD: Eighty-four Wistar rats were divided into six groups. All rats were performed a left colonic resection with end-to-end anastomosis. Group I received rat cow. Group II received soluble fiber orally for five consecutive days preoperatively as well as 3rd and 6th days postoperatively. Group III received SCFAs via rectum for five consecutive days preoperatively. Group IV received irradiation to the pelvis at a total dose of 24 Gy on the 10th and 5th days before the operation. Group V was exposed to irradiation like the rats in Group IV and oral treatment like the rats in Group II. Group VI received irradiation like the rats in Group IV and transrectal treatment like the rats in Group III. On the 3rd and 7th postoperative days, all the rats were anesthetized to evaluate the anastomosis healing clinically, histologically and biochemically. RESULTS: Third and 7th day bursting pressures of the rats that were fed with a normal diet and exposed to radiotherapy were significantly decreased (P<0.001). Bursting pressures of Groups V and VI on the 7th day were significantly higher than the control group's bursting pressures (P<0.05). Hydroxyproline levels of Group IV were significantly decreased (P<0.001). Following oral soluble fiber and transrectal administration of SCFAs, these low levels reached to the levels of control radiotherapy group. Matrix metalloproteinase-2 activity of all the rats that were exposed to radiotherapy was higher than the control group (P<0.001). Matrix metalloproteinase-2 enzyme levels in the Groups V and VI were lower than the ones in the Group IV (P<0.001). The histologic parameters of anastomotic healing such as epithelial regeneration, exudate, necrosis, and fibroblast levels were significantly improved by the use of oral soluble fiber and transrectal SCFAs treatment. CONCLUSION: Undesirable effects of preoperative radiotherapy on mechanical, histological and biochemical parameters can be overcome by oral soluble fiber. Oral soluble fiber administration has similar positive effects like the transrectal administration of the SCFA's.

Anastomosis, Surgical↗

Short-chain fatty acids modulate gene expression for vascular endothelial cell adhesion molecules.

OBJECTIVE: Leukocyte infiltration into the intestinal wall is central to the pathogenesis of tissue injury that occurs in patients with a variety of inflammatory bowel diseases. Migration of leukocytes from the intestinal circulation into bowel tissues is mediated by chemotactic substances and adhesion molecules (i.e., intercellular adhesion molecule-1 [ICAM-1] and E-selectin) on the surface of endothelial cells lining blood vessels. Short-chain fatty acids (SCFAs) derived from dietary fiber decrease inflammatory responses in colon cells. However, the effect of SCFAs on vascular adhesion molecules is unknown. We investigated the effects of SCFAs on vascular endothelial cell adhesion molecule expression. METHODS: We assessed the effect of physiologically relevant concentrations of butyrate on expression of ICAM-1 protein and mRNA in cultures of human umbilical vein endothelial cells. We also assessed the effect of butyrate on levels of HLA-DR, E-selectin, vascular cell adhesion molecule-1, and endoglin. In additional experiments, we evaluated the effect of butyrate on ICAM-1 mRNA stability and the effect of valerate, isobutyrate, and propionate on ICAM-1 expression. The effect of butyrate on ICAM-1 expression was compared with that of trichostatin A, a specific inhibitor of histone deacetylase. Data were evaluated with Student's t tests or Tukey's multiple comparison tests, with P < 0.05 considered statistically significant. RESULTS: Butyrate concentrations of 2.5 to 5 mM significantly increased endothelial expressions of ICAM-1 protein and mRNA. The effect of butyrate (5 mM) on ICAM-1 expression was time dependent, with significant increases in levels occurring after 16 h of incubation. Butyrate (5 mM) also increased expression of E-selectin but not of HLA-DR, vascular cell adhesion molecule-1, or endoglin. Isobutyrate had little effect on ICAM-1 expression, whereas valerate and propionate significantly increased expression of ICAM-1 but were weaker stimulants compared with butyrate. Butyrate (5 mM) did not alter stability of ICAM-1 mRNA. The effect of butyrate (5 mM) was comparable to that of trichostatin A. The stimulatory effect of butyrate on ICAM-1 expression was reversed after 48 h of butyrate withdrawal. CONCLUSIONS: Butyrate increases vascular endothelial expressions of ICAM-1 and E-selectin. We speculate that butyrate-induced effects on vascular adhesion molecules modulate gut inflammation. The role of SCFAs and fiber in the pathogenesis and modulation of gut inflammation in vivo requires further study.

Butyrates↗

Both wheat (Triticum aestivum) bran arabinoxylans and gut flora-mediated fermentation products protect human colon cells from genotoxic activities of 4-hydroxynonenal and hydrogen peroxide.

Dietary fibers are fermented by the gut flora to yield short chain fatty acids (SCFAs), which inhibit the growth of tumor cells, induce glutathione S-transferases (GSTs), and protect cells from the genotoxic activity of 4-hydroxynonenal (HNE). Here, we investigated effects of wheat bran-derived arabinoxylans and fermentation products on these parameters of chemoprevention. Newly isolated water extractable (WeAx) and alkali extractable arabinoxylans (AeAx) were fermented under anaerobic conditions with human feces. Resulting fermentation supernatants (FSs) were analyzed for SCFAs and used to treat HT29 colon cancer cells. Cell growth, cytotoxicity, antigenotoxicity against hydrogen peroxide (H2O2) or HNE, and GST activity were determined. Nonfermented WeAx decreased H2O2-induced DNA damage by 64%, thus demonstrating chemoprotective properties by this nonfermented wheat bran fiber. The fermentation of WeAx and AeAx resulted in 3-fold increases of SCFA, but all FSs (including the control without arabinoxylans) inhibited the growth of the HT29 cells, reduced the genotoxicity of HNE, and enhanced the activity of GSTs (FS WeAx, 2-fold; FS AeAx, 1.7-fold; and control FS, 1.4-fold), which detoxify HNE. Thus, increases in SCFAs were not reflected by enhanced functional effects. The conclusion is that fermentation mixtures contain modulatory compounds that arise from the feces and might add to the effectiveness of SCFAs.

Aldehydes↗

Colonic fermentation and proximal gastric tone in humans.

BACKGROUND & AIMS: Some carbohydrates escape small intestinal absorption, and their presence in the ileum can affect proximal gut motility. Carbohydrates reaching the colon can inhibit gastric and pancreatic secretions. The hypothesis of this study was that colonic fermentation products of carbohydrates (short-chain fatty acids [SCFAs]) affect proximal gut motility and especially gastric tone. METHODS: Healthy volunteers were studied after oral administration of 20 g lactulose (n = 6) and intracolonic infusions of 20 g lactose (n = 7) and SCFAs (54 mmol/180 mL and 90 mmol/180 mL, respectively). Gastric tone (electronic barostat) and H2 concentrations in exhaled air were simultaneously monitored, and peripheral intestinal peptide levels were measured by specific radioimmunoassays. RESULTS: After oral lactulose administration (but not after saline), a significant decrease in gastric tone was observed, which rapidly followed the increase in H2 concentrations. Gastric tone also decreased after intracolonic infusions of both lactose and SCFAs; the most marked effect occurred after the highest SCFA dose. No significant changes in the level of plasma oxyntomodulin-like immunoreactivity and glucagon-like peptide 1 were found, whereas the level of peptide YY increased significantly over time, but not differently after saline and test solutions. CONCLUSIONS: Colonic fermentation of undigestible carbohydrates can inhibit gastric tone, and SCFAs may be responsible for this colonic brake. The role of intestinal peptides, if any, was not identified.

Adult↗

Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.

BACKGROUND & AIMS: Because short-chain fatty acids (SCFAs) and heat shock proteins (hsps) confer protection to intestinal epithelia cells (IECs), we studied whether SCFAs modulate IEC hsp expression. METHODS: Hsp 25, hsp72, and hsc73 protein expression in rat intestinal tissues and IEC-18 cells were determined by Western blot and immunohistochemistry. Cell survival under conditions of oxidant stress (monochloramine) was determined using (51)Cr release in hsp25 cDNA anti-sense and sense-transfected cells expressing minimal and increased hsp25, respectively. RESULTS: Butyrate induces a time- and concentration-dependent increase in hsp25, but not hsp72 or hsc73, protein expression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, including the poorly metabolized isobutyate, also induced selective expression of hsp25. Butyrate treatment significantly improved the ability of IEC-18 cells to withstand oxidant (monochloramine) injury. This effect could be blocked in cells in which hsp25 induction by butyrate was blocked by stable hsp25 antisense transfection. Additionally, hsp25-transfected overexpressing IEC-18 cells showed increased resistance to monochloramine. In vivo, increasing dietary fiber increased colonic, but not proximal, ileal hsp25 while having no effect on hsp72 or hsc73 expression. CONCLUSIONS: SCFAs, the predominant anions of colonic fluid derived from bacterial flora metabolism of luminal carbohydrates, protect IECs against oxidant injury, an effect mediated in part by cell-specific hsp25 induction.

3T3 Cells↗

Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation.

Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are produced at high concentration by bacteria in the gut and subsequently released in the bloodstream. Basal acetate concentrations in the blood (about 100 microm) can further increase to millimolar concentrations following alcohol intake. It was known previously that SCFAs can activate leukocytes, particularly neutrophils. In the present work, we have identified two previously orphan G protein-coupled receptors, GPR41 and GPR43, as receptors for SCFAs. Propionate was the most potent agonist for both GPR41 and GPR43. Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41. The two receptors were coupled to inositol 1,4,5-trisphosphate formation, intracellular Ca2+ release, ERK1/2 activation, and inhibition of cAMP accumulation. They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxin-sensitive Gi/o family, whereas GPR43 displayed a dual coupling through Gi/o and Pertussis toxin-insensitive Gq protein families. The broad expression profile of GPR41 in a number of tissues does not allow us to infer clear hypotheses regarding its biological functions. In contrast, the highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection. The pharmacology of GPR43 matches indeed the effects of SCFAs on neutrophils, in terms of intracellular Ca2+ release and chemotaxis. Such a neutrophil-specific SCFA receptor is potentially involved in the development of a variety of diseases characterized by either excessive or inefficient neutrophil recruitment and activation, such as inflammatory bowel diseases or alcoholism-associated immune depression. GPR43 might therefore constitute a target allowing us to modulate immune responses in these pathological situations.

Acetates↗

Transfer of energy substrates across the ruminal epithelium: implications and limitations.

The ruminal epithelium has an enormous capacity for the absorption of short-chain fatty acids (SCFAs). This not only delivers metabolic energy to the animal but is also an essential regulatory mechanism that stabilizes the intraruminal milieu. The epithelium itself, however, is endangered by the influx of SCFAs because the intracellular pH (pHi) may drop to a lethal level. To prevent severe cytosolic acidosis, the ruminal epithelium is able to extrude (or buffer) protons by various mechanisms: (i) a Na+/H+ exchanger, (ii) a bicarbonate importing system and (iii) an H+/monocarboxylate cotransporter (MCT). Besides pHi regulation, the MCT also provides the animal with ketone bodies derived from the intraepithelial breakdown of SCFAs. Ketone bodies, in turn, can serve as an energy source for extrahepatic tissues. In addition to SCFA uptake, glucose absorption has recently been identified as a potential way of eliminating acidogenic substrates from the rumen. At least with respect to SCFAs, absorption rates can be elevated when adapting animals to energy-rich diets. Although they are very effective under physiological conditions, the absorptive and regulatory mechanisms of the ruminal epithelium also have their limits. An increased number of protons during the state of ruminal acidosis can be eliminated neither from the lumen nor the cytosol, thus worsening dysfermentation and finally leading to functional and morphological alterations of the epithelial lining.

Absorption↗

Faecal short-chain fatty acids in patients with antibiotic-associated diarrhoea, before and after faecal enema treatment.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) may range from mild disturbances to severe pseudomembranous colitis. Many antibiotics affect several intestinal microflora-associated characteristics, such as short-chain fatty acid (SCFA) pattern. In the present study we investigated SCFAs in 31 patients on admittance to the hospital for severe AAD. Nine patients were followed up more extensively after they had received an enema containing faecal microflora from a healthy person on a Western diet. METHODS: Faecal SCFAs were determined by gas chromatography. The enema was characterized before use. RESULTS: AAD patients showed significant disturbances in faecal SCFA pattern. Clinically, most enema-treated patients recovered within days and had no relapses within 18 months. CONCLUSIONS: Intestinal microflora showed great disturbances, and the amounts of SCFAs were reduced, although the diarrhoea was not related to total amount SCFAs. Administration of a faecal enema resulted in the clinical recovery of most patients with severe diarrhoea within 4 days.

Adult↗

Colonic health: fermentation and short chain fatty acids.

Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.

Carbohydrate Metabolism↗

Fecal short-chain fatty acids in children with inflammatory bowel disease.

Nutrition of colonic epithelial cells (colonocytes) is maintained by luminal short-chain fatty acids (SCFAs), chiefly by n-butyrate. The importance of SCFAs for the maintenance of colonic epithelium has been demonstrated in animal models of colitis produced by rectal instillation of an inhibitor of SCFA oxidation and in patients with diversion colitis in whom a segment of colonic epithelium was deprived of contact with luminal SCFAs. We measured fecal SCFAs and lactate in children with ulcerative colitis (UC; n = 17) and with Crohn's disease with ileocolonic involvement (CD; n = 22) and age-matched controls (n = 12) by a vacuum-distillation, gas chromatographic method. Fecal SCFA concentrations were correlated with scores of clinical disease activity. Patients with UC and CD had a decrease in the fecal concentration of acetate (p < 0.05) and an increase in n-butyrate (p < 0.01) compared with controls. No significant changes in fecal lactate were seen. A comparison of inactive- or mild-UC patients with moderate or severe-UC patients yielded major differences in SCFA concentrations with n-butyrate increased in inactive and mild UC well above control values and total SCFA and acetate decreased in moderate and severe UC below control levels. Raised concentrations of fecal n-butyrate may reflect impaired utilization of this SCFA in the colon of patients with mild UC and Crohn's disease with colonic involvement. Whether this defect is primary or secondary to inhibitors in the colonic lumen, due to impaired transport of n-butyrate into the cell or defective metabolism within the cell, or specific to inflammatory bowel disease remains to be explored.

Adolescent↗