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PubMed1998

Short-chain fatty acid-supplemented total parenteral nutrition alters intestinal structure, glucose transporter 2 (GLUT2) mRNA and protein, and proglucagon mRNA abundance in normal rats.

Intestinal adaptation is a complex physiologic process that is not completely understood. Intravenous short-chain fatty acids (SCFAs) enhance intestinal adaptation after 80% enterectomy in rats. The purpose of this study was to examine rapid responses to SCFA-supplemented total parenteral nutrition (TPN) in the normal small intestine. After jugular catheterization, 31 Sprague-Dawley rats (weighing 258 +/- 3 g) were randomly assigned to receive standard TPN or an isoenergetic, isonitrogenous TPN solution supplemented with SCFAs (TPN+SCFA). Intestinal samples were obtained after 24 or 72 h of nutrient infusion. TPN+SCFA for 24 h increased (P < 0.05) the ileal RNA concentration (microg RNA/mg ileum) whereas TPN+SCFA for 72 h increased (P < 0.05) the ileal DNA concentration (microg DNA/mg ileum) and decreased (P < 0.05) the ileal protein concentration (microg protein/mg ileum). Ileal proglucagon mRNA abundance was elevated (P < 0.05) after 24 h of TPN+SCFA infusion and returned to levels seen with control TPN by 72 h. Glucose transporter 2 (GLUT2) mRNA was significantly higher (P < 0.05) in the TPN+SCFA groups at both time points when compared with control TPN groups. Ileal GLUT2 protein abundance in the 72-h TPN+SCFA group was significantly higher (P < 0.05) than that of all other groups. Sodium-glucose cotransporter (SGLT-1) mRNA and protein abundance and uptake of D-fructose and D-glucose did not differ between groups. Jejunal uptake of L-glucose and lauric acid was significantly higher (P < 0.05) after 72 h of TPN+SCFA than after 24 h, whereas the 24- and 72-h TPN groups did not differ. In summary, SCFAs led to rapid changes in ileal proglucagon and glucose transporter expression in rats receiving TPN and provide insights into therapeutic management of individuals with short bowel syndrome or intestinal malabsorption syndromes.

Animal Nutritional Physiological Phenomena↗

PubMed2002

Do colonic short-chain fatty acids contribute to the long-term adaptation of blood lipids in subjects with type 2 diabetes consuming a high-fiber diet?

BACKGROUND: We recently obtained evidence of long-term adaptation of blood lipids to changes in intakes of carbohydrate and fiber in subjects with type 2 diabetes. OBJECTIVE: We determined the effect of increased carbohydrate and fiber intakes on serum short-chain fatty acids (SCFAs) and the relation between changes in serum acetate and changes in blood lipids. DESIGN: Subjects with type 2 diabetes (n = 62) were randomly assigned to receive approximately 10% of energy from low-fiber breakfast cereal (LF diet), high-fiber breakfast cereal (HF diet), or monounsaturated fatty acids (MUFA diet) for 6 mo. RESULTS: Carbohydrate intakes were higher in the LF and HF groups than in the MUFA group (54% compared with 43%), and more fiber was consumed by the HF group (approximately 50 g/d) than by the LF or MUFA group (approximately 23 g/d). Fasting serum SCFAs did not change significantly over the first 3 mo. Between 3 and 6 mo, serum acetate tended (NS) to decrease in the LF group (from 69 +/- 4 to 59 +/- 5 micromol/L) and increase in the HF group (from 100 +/- 18 to 107 +/- 17 micromol/L), with no significant change in the MUFA group. Serum butyrate did not change significantly in the LF or MUFA group but increased in the HF group (from 2.5 +/- 0.5 to 3.1 +/- 0.6 micromol/L; P < 0.001). Changes in serum acetate from 0 to 3 mo were not related to changes in lipids. However, changes in serum acetate from 3 to 6 mo were positively related to changes in the ratio of total to HDL cholesterol (P = 0.041) and in fasting (P = 0.013) and postprandial (P = 0.016) triacylglycerols. CONCLUSIONS: In subjects with type 2 diabetes, changes in serum SCFAs in response to changes in carbohydrate and fiber intakes took many months to occur, and the changes in serum acetate were significantly related to the long-term adaptive changes in blood lipids.

Acetates↗

PubMed2001

Butyrate and propionate downregulate ERK phosphorylation in HT-29 colon carcinoma cells prior to differentiation.

We have characterized the effects of different short-chain fatty acids (SCFAs) on cell growth and differentiation as well as the phosphorylation state of ERK1 and 2 in the human colon adenocarcinoma cell line HT-29. Of the five SCFAs tested, only butyrate and propionate impaired cellular proliferation. Moreover, butyrate and propionate specifically resulted in a decrease in ERK1 and 2 phosphorylation at 3 and 6 hours post-treatment, suggesting a correlation between the ability of these SCFAs to inhibit cellular proliferation and decrease ERK phosphorylation. Notably, the decrease in ERK phosphorylation was observed prior to the induction of the differentiation markers alkaline phosphatase (AP) and carcinoembryonic antigen (CEA) by butyrate and propionate from days 6 to 18 post-treatment. In the case of butyrate- and propionate-induced differentiation, ERK phosphorylation is a marker and may play a role in the proliferation and/or differentiation states of this cell line.

Alkaline Phosphatase↗

PubMed2005

Short-chain fatty acid induces intestinal mucosal injury in newborn rats and down-regulates intestinal trefoil factor gene expression in vivo and in vitro.

BACKGROUND: Luminal administration of short-chain fatty acids (SCFAs) induces dose-dependent intestinal mucosal injury in newborn rats. However, the mechanism underlying the injurious effects of SCFAs on intestinal mucosa in neonates is unclear. Intestinal trefoil factor (ITF) is a factor important for the maintenance and repair of the intestinal mucosal barrier. Regulation of ITF gene expression by SCFAs may be involved as one of the mechanisms. OBJECTIVES: To examine the effect of butyrate-induced colonic injury on ITF gene expression in vivo and to determine the molecular mechanisms underlying the butyrate regulation of ITF gene expression in vitro. METHODS: Whole-section colonic tissues from 9- to 10-day-old Sprague-Dawley rats that have received butyric acid at two different concentrations (150 mmol/L and 300 mmol/L) and for different time periods were processed for total RNA extraction and Northern blot analysis. Littermates that received normal saline or lactic acid at 300 mmol/L served as controls. The effect of butyrate on ITF gene expression was also examined in vitro with human colonic epithelial LS 174T cells. To further define ITF gene regulation by butyrate, transient transfection assays were performed on a 930 bp human ITF promoter-luciferase reporter gene plasmid in LS174T cells with or without the presence of butyrate. RESULTS: Concurrent with mucosal injury, butyric acid inhibited ITF gene expression in colonic tissues of newborn rats as well as in intestinal epithelial cells in a dose- and time-dependent manner. Furthermore, butyrate reduced ITF promoter report gene activity in transfected LS174T cell, suggesting that butyric acid regulation of ITF gene is by way of a specific ITF promoter. CONCLUSIONS: Butyric acid induced-intestinal mucosal injury in newborn rats is associated with down-regulation of ITF gene expression. The changes in ITF gene expression in vivo may play a role in the pathogenesis of SCFA-induced intestinal mucosal injury.

Animals↗

PubMed2004

Inhibition of Clostridium difficile strains by intestinal Lactobacillus species.

Indigenous intestinal microflora (including lactobacilli) has an important role in protection against Clostridium difficile infection. To assess in vitro interaction between lactobacilli and C. difficile, antagonistic activity of 50 intestinal Lactobacillus spp. strains against 23 pathogenic C. difficile strains was determined. Phenotypic properties of C. difficile strains [production of short-chain fatty acids (SCFAs) and toxin A, and antimicrobial susceptibility] and lactobacilli (production of SCFAs and H(2)O(2)) were investigated. Five lactobacilli (Lactobacillus paracasei and Lactobacillus plantarum species) were antagonistic to all C. difficile strains, 18 were antagonistic to some C. difficile strains and 27 showed no antagonistic activity. This antagonistic activity was strain-specific and seemed to correlate with H(2)O(2) and lactic acid production. C. difficile strains that were more sensitive to lactobacilli (n = 9) usually produced higher toxin levels and more SCFAs, and were more resistant to antibiotics, than strains that were resistant to lactobacilli (n = 14). Compatibility of C. difficile strain properties (resistance to lactobacilli or antibiotics) with intestinal microecological conditions (e.g. presence of antagonistic lactobacilli, concentration of antibiotics) may determine expression of disease.

Anti-Bacterial Agents↗

PubMed2005

Birth-related increase in intracolonic hydrogen gas and nitric oxide as indicator of host-microbial interactions.

BACKGROUND: Bacterial colonization of the intestine early in life might have implications for allergy development. We studied early host-bacterial interactions in the gut by simultaneous measurements of hydrogen gas (H(2)) and faecal short chain fatty acid pattern (SCFAs), i.e. bacterial products, as well as of nitric oxide (NO), a marker of mucosal immune activation. METHODS: A novel minimally invasive technique was used for repeated measurements of luminal colonic H(2) and NO in 32 healthy newborn infants delivered vaginally or by Caesarean section. Luminal gas was sampled and analysed at five occasions: immediately after birth, day 1, days 3-5, 1 and 5-6 months after birth. RESULTS: Colonic H(2), NO and faecal SCFAs were undetectable at birth. The H(2) and SCFAs appeared within 24 h and continued to increase during the 6 months follow-up. Nitric oxide remained very low until 3-5 days after birth at which time it markedly increased. In some apparently healthy infants NO transiently reached levels similar to those seen in adults with inflammatory bowel disease. CONCLUSION: Intracolonic measurements of H(2) and NO may be useful to monitor the developmental colonization process as well as mucosal responses.

Aging↗

PubMed2005

Colonic short-chain fatty acids inhibit encystation of Entamoeba invadens.

Entamoeba parasites multiply as trophozoites in the layer of mucus that overlies the colonic epithelium. In response to stimuli that are not understood, trophozoites stop multiplying and differentiate into cysts that are released to infect another host. In the colon, Entamoeba trophozoites are exposed to the large variety of biochemicals that are carried into or are produced within this organ. The normal bacterial population of the colon releases large amounts of short-chain fatty acids (SCFAs). These compounds have effects on the growth, differentiation and repair of the colonic epithelium that correlate with de-creased activity of a Class I/II histone deacetylase (HDAC). We found that the formation of cysts, but not the growth of trophozoite-stage Entamoeba invadens parasites, was inhibited by physiologic concentrations of SCFAs. Variable levels of cyst formation did occur if SCFA concentrations were lowered. Specific inhibitors of Class I/II-type HDACs also prevented encystation, and trophozoites exposed to these compounds had increased levels of acetylation of histone H4 and other nuclear proteins. These results suggest that production of the infectious cyst stage of Entamoeba parasites is regulated in part by the levels of SCFAs made by the bacterial population of the colon.

Amino Acid Sequence↗

PubMed2005

Gut microflora associated characteristics in children with celiac disease.

OBJECTIVES: The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls. METHODS: The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. RESULTS: There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups. CONCLUSIONS: This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient.

Biomarkers↗

PubMed2005

Alteration of the fatty acid profile of Streptomyces coelicolor by replacement of the initiation enzyme 3-ketoacyl acyl carrier protein synthase III (FabH).

The first elongation step of fatty acid biosynthesis by a type II dissociated fatty acid synthases is catalyzed by 3-ketoacyl-acyl carrier protein (ACP) synthase III (KASIII, FabH). This enzyme, encoded by the fabH gene, catalyzes a decarboxylative condensation between an acyl coenzyme A (CoA) primer and malonyl-ACP. In organisms such as Escherichia coli, which generate only straight-chain fatty acids (SCFAs), FabH has a substrate preference for acetyl-CoA. In streptomycetes and other organisms which produce a mixture of both SCFAs and branched-chain fatty acids (BCFAs), FabH has been shown to utilize straight- and branched-chain acyl-CoA substrates. We report herein the generation of a Streptomyces coelicolor mutant (YL/ecFabH) in which the chromosomal copy of the fabH gene has been replaced and the essential process of fatty acid biosynthesis is initiated by plasmid-based expression of the E. coli FabH (bearing only 35% amino acid identity to the Streptomyces enzyme). The YL/ecFabH mutant produces predominantly SCFAs (86%). In contrast, BCFAs predominate (approximately 70%) in both the S. coelicolor parental strain and S. coelicolor YL/sgFabH (a deltafabH mutant carrying a plasmid expressing the Streptomyces glaucescens FabH). These results provide the first unequivocal evidence that the substrate specificity of FabH observed in vitro is a determinant of the fatty acid made in an organism. The YL/ecFabH strain grows significantly slower on both solid and liquid media. The levels of FabH activity in cell extracts of YL/ecFabH were also significantly lower than those in cell extracts of YL/sgFabH, suggesting that a decreased rate of fatty acid synthesis may account for the observed decreased growth rate. The production of low levels of BCFAs in YL/ecFabH suggests either that the E. coli FabH is more tolerant of different acyl-CoAs substrates than previously thought or that there is an additional pathway for initiation of BCFA biosynthesis in Streptomyces coelicolor.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

PubMed1993

Effects of feeding premature infants with Lactobacillus GG on gut fermentation.

The study aimed to find out whether gut colonisation of premature babies with a probiotic, Lactobacillus GG, modified enteric carbohydrate fermentation. Twenty preterm infants were randomised to receive Lactobacillus GG 10(8) colony forming units twice a day for two weeks or to a control group. Faecal short chain fatty acids (SCFAs), ethanol, and urinary 2,3-butanediol, were measured in parallel with microbiological studies. Lactobacillus GG colonised nine babies. From 1-28 days of age faecal SCFAs did not differ significantly from controls. Median and ranges were (treated and controls, respectively): acetic acid: 173 (trace-799), 166 (trace-700); propionic acid: 44 (trace-169), 37 (11-229); butyric acid: 31 (5-107), 37 (2-118) mumol/g dry weight. Ethanol was detected in more faecal samples from treated babies (65% v 37%), and at higher concentration (6.3 (trace-40) v 3.3 (0.6-8.8; one 229) mumol/g). 2,3-Butanediol was found in 66% of urine samples from treated babies and 58% from controls. On 83% of these occasions Klebsiella sp, Enterobacter sp, or Serratia sp were cultured from faeces. Lactobacillus GG had no obvious adverse effects on nutritionally important SCFAs. The small increase in ethanol excretion is unlikely to have clinical significance.

Anti-Bacterial Agents↗

PubMed1992

Effect of the dietary fibre content of lifelong diet on colonic cellular proliferation in the rat.

The effect of the fibre content of lifelong (18 months) diets on proximal and distal colonic cellular proliferation and short chain fatty acid (SCFA) content was investigated in 40 rats. Rats were fed a low fibre diet (17 g/kg non-starch polysaccharides NSP) or the stock diet (133 g/kg NSP). The higher fibre fed rats had increased caecal and colonic total contents (p < 0.001) and SCFAs than the low fibre fed rats (caecal SCFAs: higher fibre rats 96.4 (6.8) mumol/g wet weight v low fibre 22.7 (3.0): p < 0.001, colonic SCFAs: higher fibre 52.3 (3.1) mumol/g wet weight v low fibre 6.9 (2.2) mumol/g wet weight: p < 0.001). Cellular proliferation was increased in the proximal colon (bromodeoxyuridine labelling index, higher fibre 9.3 v low fibre 8.4 p < 0.05; flow cytometry, % cells in S phase higher fibre diet 7.9 v low fibre 6.9; p < 0.01) and there was a shift of proliferating cells to a higher region in each crypt. There was no significant difference in the percentage of cells in S phase in the distal colon of rats in both diet groups. The proliferative zone, however, was expanded in the distal colon of the higher fibre diet fed rats. This study indicates that long term higher fibre intake in rats is associated with a modest increase in cellular proliferation in the proximal colon but not the distal colon.

Animals↗

PubMed1987

Short-chain fatty acid transport and its effects on ion transport by rabbit cecum.

Short-chain fatty acid (SCFA) metabolism and transport were examined in vitro across isolated rabbit cecal epithelia whose primary function is absorption of these solutes. This study shows that although there was some low-level metabolism of SCFAs to ketone bodies by the isolated cecum, a significantly higher oxygen consumption was sustained for a longer time period by tissues incubated in glucose-containing salines. The cecum supported a significant net secretory flux of acetate (J net Ac- = -1.13 +/- 0.13 mu eq X cm-2 X h-1) and propionate (J net Pr- = -0.61 +/- 0.14 mu eq X cm-2 X h-1). This study also shows that glucose significantly enhanced short-circuit current (Isc), tissue conductance (Gt), and sodium transport across this tissue. Neither Ac- nor Pr- enhanced net sodium flux (J net Ac-) but Pr- significantly reduced net chloride flux (J net Cl-), whereas Ac- had no effect. The increase in Isc and Gt observed in the presence of SCFAs was attributable to the presence of SCFA in the serosal bathing solution alone. To explain the latter finding and the unexpected finding of SCFA secretion, the existence of an electrogenic anion (HCO3-) secretory pathway is postulated. It is suggested that this system can accommodate SCFAs in vitro and that it is a Na+-dependent system located on the basolateral membrane of the cecal cell.

Animals↗

PubMed1992

Effect of short-chain fatty acids on contractile activity and fluid flow in rat colon in vitro.

The effect of short-chain fatty acids (SCFAs) on the contractile activity and fluid output of the large bowel of the rat was studied using an isolated segment of cecum and colon, mounted in vitro. The rate of contractile activity per minute in the proximal, mid, and distal regions of the colon was depressed by luminal infusion of associated SCFAs either as a mixture (acetic, propionic, and butyric) or individually (100 mM/pH = 4.1, in each case). Dose responses were observed for the individual fatty acids, with the 100 mM solutions eliciting a more prominent reduction in colonic motor activity than that induced by 10 mM. Neither the Na salt of the fatty acids nor an acidified Krebs solution (pH = 4.1) inhibited contractile activity or fluid output. No reduction in the rate of contractile activity was observed in the cecum with any test solutions, except 100 mM butyric acid. The data suggest that SCFAs inhibit smooth muscle contractility and resultant fluid transit.

Animals↗

PubMed1997

Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model.

Control of paracellular permeability in the colonic epithelium is fundamental to its functional competence. This study examines the relationship between physiologically relevant short-chain fatty acids (SCFAs) and paracellular permeability using the Caco-2 cell line model. Butyrate induced a concentration-dependent, reversible increase in transepithelial resistance (TER) that was maximal after 72 h. Butyrate (2 mM) increased TER by 299 +/- 69% (mean +/- SE; n = 5; P < 0.05; t-test) and reduced mannitol flux to 52 +/- 11% (P < 0.05) of control. The effect of butyrate was dependent on protein synthesis and gene transcription but not dependent on its oxidation or activation of adenosine 3',5'-cyclic monophosphate. The other SCFAs, propionate and acetate, also induced a concentration-dependent increase in TER. The effect of butyrate paralleled changes in cellular differentiation, because alkaline phosphatase activity, carcinoembryonic antigen expression, and dome formation were increased. Furthermore, other differentiating agents (dimethyl sulfoxide and retinoic acid) also increased TER. Thus SCFAs reduce paracellular permeability in the Caco-2 cell line, possibly by promotion of a more differentiated phenotype. If such an effect occurs in vivo, it may have ramifications for the biology and pathobiology of colonic mucosa.

Acetic Acid↗

PubMed2003

Effects of the soluble fibre pectin on intestinal cell proliferation, fecal short chain fatty acid production and microbial population.

AIM: Although pectin, a dietary fibre, has been suggested to possess some trophic effects on the intestine, the mechanisms involved remain unclear. This study aimed to evaluate the effects of pectin on rat intestinal cell proliferation and the intraluminal environment. METHODS: Control and pectin-fed rats were given a fibre-free elemental diet (ED) and an ED containing 2.5% pectin, respectively. On the 15th day, the length, weight and number of Ki-67-positive cells from each intestinal segment, and the short chain fatty acids (SCFAs) and microbial population in the caecum were measured. Plasma glucagon-like peptide-2 (GLP-2) concentration and GLP-2 receptor (GLP-2R) mRNA levels in the epithelium were also determined. RESULTS: Pectin supplementation resulted in significant increases in the length, weight, and number of Ki-67-positive cells in the ileum, caecum and colon. Although pectin supplementation did not affect the caecal microbial flora that produced SCFAs, the caecal SCFA content was significantly increased. Pectin supplementation also induced an increase in the plasma GLP-2 concentration, but did not affect the GLP-2R mRNA levels in the small intestine. CONCLUSIONS: The increases in the caecal SCFAs and plasma GLP-2 levels induced by pectin supplementation may cause mucosal proliferation in the lower intestinal tract.

Animals↗

PubMedDate not supplied

Apparent fiber digestibility and fecal short-chain fatty acid concentrations with ingestion of two types of dietary fiber.

Short-chain fatty acids (SCFAs) are products of dietary fiber fermentation. As such, fiber digestibility is thought to be related to SCFA production. The effects of two concentrations of cereal fiber as wheat bran (WB) and vegetable fiber (VF) on fiber digestibility were examined in 34 free-living volunteers. Five diets consisting of a fiber-free liquid nutrition supplement and quick breads containing either (1) 0 g of fiber, (2) 10 g of WB, (3) 30 g of WB, (4) 10 g of VF, or (5) 30 g of VF were consumed in random order. Apparent digestibility of neutral detergent fiber (NDF) was determined. Colonic fluid, collected by in vivo dialysis in 9 subjects, was analyzed for SCFAs by gas chromatography. Digestibility of NDF was greater with WB than with VF ingestion in those 9 subjects, but digestibility was not different with ingestion of both fibers when all 34 subjects were considered. No effect of intake level was seen with either WB or VF. Fiber ingestion increased acetate, propionate, and butyrate concentrations above those on the 0 g of fiber diet (43%, 31%, and 90%, respectively; p < .0001). Propionate and butyrate concentrations were greater on WB than VF (p < .01); acetate concentrations were similar with both fibers. No correlation between NDF digestibility and SCFA concentrations was observed. Despite differences in origin, chemistry, particle size, and subject transit time, the WB and VF were similar in NDF fermentability. Molar ratios of specific SCFAs were influenced by type of fiber ingested.

Adult↗

PubMedDate not supplied

Luminal short-chain fatty acids and postresection intestinal adaptation.

BACKGROUND: Short-chain fatty acids (SCFAs) reportedly have a trophic effect on the small intestine. However, it is unclear if this is a local or primarily systemic effect. Loss of the ileocolonic junction (ICJ) may result in increased SCFAs and bacteria in the small intestine from colonic reflux. Our aim was to evaluate the effect of bypass of the ICJ on intestinal SCFA content and postresection adaptation. METHODS: Thirty dogs were studied: transection control (TC, n = 10), distal resection of 50% intestine (DR, n = 10), and distal resection with bypass of ICJ (DRBP, n = 10). Animals were killed at 4 and 12 weeks. Luminal SCFAs and bacteria and adaptation of the small intestine were evaluated. RESULTS: Caloric intake was significantly less in the two resected groups (67 +/- 3 DR and 63 +/- 3, DRBP vs 78 +/- 5 kcal/kg/d TC, p < .05). Body weight and albumin levels were decreased at 12 weeks but were similar between the resected groups (81% +/- 3% and 74% +/- 6% initial and 1.9 +/- 0.1 and 2.1 +/- 0.2 g/dL, DR and DRBP, respectively). Steatorrhea was present for 12 weeks after resection and was greater after DRBP (14.2% +/- 3.8% vs 8.6% +/- 1.9% at 4 weeks and 13.6% +/- 2.5% vs 6.7% +/- 0.6% at 12 weeks, p < .05). Bypassed animals had elevated intraluminal SCFA content (3126 +/- 1094 vs 1791 +/- 538 DR and 1600 +/- 446 micrograms/mL TC, p < .05) and anaerobic bacterial counts (100% vs 50% and 44%, respectively). Tissue inflammation and myeloperoxidase activity were similar. Small intestinal length (174 +/- 10 and 180 +/- 10 cm) and circumference (5.2 +/- 0.4 and 5.2 +/- 0.3 cm) increased to a similar extent in both resected groups at 12 weeks. Thickness of mucosa (1939 +/- 162 vs 1662 +/- 162 microns) and muscle (865 +/- 45 vs 978 +/- 79 microns) layers were similar after DR and DRBP. CONCLUSION: (1) Bypass of the ICJ after distal resection results in increased growth of anaerobic bacteria and luminal SCFA and is associated with more marked steatorrhea. (2) Bypass of the ICJ does not influence structural adaptation of the small intestine. (3) These findings do not support a local trophic effect for SCFA.

Adaptation, Physiological↗

PubMedDate not supplied

Short-chain fatty acids increase proglucagon and ornithine decarboxylase messenger RNAs after intestinal resection in rats.

BACKGROUND: Intestinal adaptation is a complex physiological process that is not completely understood. Systemic administration of short-chain fatty acids (SCFAs) has been shown to facilitate adaptation to small bowel resection; however the mechanisms underlying this phenomena are unknown. METHODS: Forty-six male Sprague-Dawley rats underwent an 80% jejunoileal resection and jugular catheterization. After surgery, rats were randomly assigned to receive standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous TPN supplemented with SCFAs. On day 3 or 7 after surgery, ileal samples were removed for determination of mucosal wet weight, DNA, RNA, and protein concentrations. Total cellular RNA was extracted for use in Northern blot analysis to quantify proglucagon and ornithine decarboxylase messenger RNAs (mRNAs). RESULTS: Total, mucosal, and submucosal weights were increased (p < .05) in the SCFA group both 3 and 7 days after surgery. Ileal DNA and RNA concentrations were increased (p < .05) in the SCFA group at both time points; however ileal protein concentration did not differ between groups until 7 days after resection. Levels of proglucagon and ornithine decarboxylase messenger RNAs were higher (p < .05) in the SCFA group at both time points. CONCLUSION: The upregulation of proglucagon and ornithine decarboxylase gene expression may be the mechanism by which SCFAs facilitate intestinal adaptation.

Adaptation, Physiological↗