Infusion Of Short-chain Fatty Acids Research Articles

2'-fucosyllactose alone or combined with resistant starch increases circulating short-chain fatty acids in lean men and men with prediabetes and obesity.

Infusion of short-chain fatty acids (SCFA) to the distal colon beneficially affects human substrate and energy metabolism. Here, we hypothesized that the combination of 2'-fucosyllactose (2'-FL) with resistant starch (RS) increases distal colonic SCFA production and improves metabolic parameters. In this randomized, crossover study, 10 lean (BMI 20-24.9 kg/m2) and nine men with prediabetes and overweight/obesity (BMI 25-35 kg/m2) were supplemented with either 2'-FL, 2'-FL+RS, or placebo one day before a clinical investigation day (CID). During the CID, blood samples were collected after a overnight fast and after intake of a liquid high-fat mixed meal to determine plasma SCFA (primary outcomes). Secondary outcomes were fasting and postprandial plasma insulin, glucose, free fatty acid (FFA), glucagon-like peptide-1, and peptide YY concentrations. In addition, fecal SCFA and microbiota composition, energy expenditure and substrate oxidation (indirect calorimetry), and breath hydrogen excretion were determined. In lean men, supplementation with 2'-FL increased postprandial plasma acetate (P = 0.017) and fasting H2 excretion (P = 0.041) compared to placebo. Postprandial plasma butyrate concentration increased after 2'-FL and 2'-FL+RS as compared to placebo (P < 0.05) in lean men and men with prediabetes and overweight/obesity. Additionally, 2'-FL+RS decreased fasting and postprandial plasma FFA concentrations compared to placebo (P < 0.05) in lean men. Supplementation of 2'-FL with/without RS the day before investigation increased systemic butyrate concentrations in lean men as well as in men with prediabetes and obesity, while acetate only increased in lean men. The combination of 2'-FL with RS showed a putatively beneficial metabolic effect by lowering plasma FFA in lean men, indicating a phenotype-specific effect. nr. NCT04795804.

Multi-Omics Reveals the Impact of Exogenous Short-Chain Fatty Acid Infusion on Rumen Homeostasis: Insights into Crosstalk between the Microbiome and the Epithelium in a Goat Model.

Emerging data have underscored the significance of exogenous supplementation of butyrate in the regulation of rumen development and homeostasis. However, the effects of other short-chain fatty acids (SCFAs), such as acetate or propionate, has received comparatively less attention, and the consequences of extensive exogenous SCFA infusion remain largely unknown. In our study, we conducted a comprehensive investigation by infusion of three SCFAs to examine their respective roles in regulating the rumen microbiome, metabolism, and epithelium homeostasis. Data demonstrated that the infusion of sodium acetate (SA) increased rumen index while also promoting SCFA production and absorption through the upregulation of SCFA synthetic enzymes and the mRNA expression of SLC9A1 gene. Moreover, both SA and sodium propionate infusion resulted in an enhanced total antioxidant capacity, an increased concentration of occludin, and higher abundances of specific rumen bacteria, such as "Candidatus Saccharimonas," Christensenellaceae R-7, Butyrivibrio, Rikenellaceae RC9 gut, and Alloprevotella. In addition, sodium butyrate (SB) infusion exhibited positive effects by increasing the width of rumen papilla and the thickness of the stratum basale. SB infusion further enhanced antioxidant capacity and barrier function facilitated by cross talk with Monoglobus and Incertae Sedis. Furthermore, metabolome and transcriptome data revealed distinct metabolic patterns in rumen contents and epithelium, with a particular impact on amino acid and fatty acid metabolism processes. In conclusion, our data provided novel insights into the regulator effects of extensive infusion of the three major SCFAs on rumen fermentation patterns, antioxidant capacity, rumen barrier function, and rumen papilla development, all achieved without inducing rumen epithelial inflammation. IMPORTANCE The consequences of massive exogenous supplementation of SCFAs on rumen microbial fermentation and rumen epithelium health remain an area that requires further exploration. In our study, we sought to investigate the specific impact of administering high doses of exogenous acetate, propionate, and butyrate on rumen homeostasis, with a particular focus on understanding the interaction between the rumen microbiome and epithelium. Importantly, our findings indicated that the massive infusion of these SCFAs did not induce rumen inflammation. Instead, we observed enhancements in antioxidant capacity, strengthening of rumen barrier function, and promotion of rumen papilla development, which were facilitated through interactions with specific rumen bacteria. By addressing existing knowledge gaps and offering critical insights into the regulation of rumen health through SCFA supplementation, our study holds significant implications for enhancing the well-being and productivity of ruminant animals.

Microbial metabolites regulate social novelty via CaMKII neurons in the BNST

Social novelty is a cognitive process that is essential for animals to interact strategically with conspecifics based on their prior experiences. The commensal microbiome in the gut modulates social behavior through various routes, including microbe-derived metabolite signaling. Short-chain fatty acids (SCFAs), metabolites derived from bacterial fermentation in the gastrointestinal tract, have been previously shown to impact host behavior. Herein, we demonstrate that the delivery of SCFAs directly into the brain disrupts social novelty through distinct neuronal populations. We are the first to observe that infusion of SCFAs into the lateral ventricle disrupted social novelty in microbiome-depleted mice without affecting brain inflammatory responses. The deficit in social novelty can be recapitulated by activating calcium/calmodulin-dependent protein kinase II (CaMKII)-labeled neurons in the bed nucleus of the stria terminalis (BNST). Conversely, chemogenetic silencing of the CaMKII-labeled neurons and pharmacological inhibition of fatty acid oxidation in the BNST reversed the SCFAs-induced deficit in social novelty. Our findings suggest that microbial metabolites impact social novelty through a distinct neuron population in the BNST.

Exogenous infusion of short-chain fatty acids can improve intestinal functions independently of the gut microbiota.

The present experiment was conducted to investigate the effects of exogenously infused short-chain fatty acids (SCFAs) on the growth development and intestinal functions in a germ-free (GF) pig model. Twelve hysterectomy-derived newborn piglets were reared in six sterile isolators. All piglets were hand-fed Co60-γ-irradiated sterile milk powder for 21 d and then were switched to sterile feed for another 21 d. During the second 21-d period, GF piglets (n = 6) were orally infused with 25 mL/kg sterile saline per day, and SCFA piglets (n = 6) were orally infused with 25 mL/kg SCFAs mixture (acetic, propionic, and butyric acids, 45, 15, and 11 mM, respectively) per day. We observed the concentrations of SCFAs in serum and intestine, and the messenger ribonucleic acid (mRNA) abundance of G-protein-coupled receptor-43 in the ileum was increased (P < 0.05) in the SCFA group. Meanwhile, oral infusion of SCFAs enhanced (P < 0.05) the contents of glucagon-like peptide-2 in the jejunum and serum and tended to increase the villi height in the ileum (P < 0.10). Besides, the activities of lipase, trypsin, sucrase, lactase, Na+-K+-adenosine triphosphatase ([ATPase] P < 0.05), and Ca2+-Mg2+-ATPase (P < 0.10) were stimulated and the mRNA expressions of solute carrier family 7 (SLC7A1) and regeneration protein (REG)-ΙΙΙ γ in the jejunum (P < 0.05) were upregulated in the SCFA group. Additionally, SCFAs infusion downregulated the mRNA abundances of interleukin (IL)-1β and IL-6 in the jejunum, ileum, or colon (P < 0.05) and increased the counts of white blood cell, neutrophils, and lymphocyte in the blood (P < 0.05). Collectively, exogenous infusion of SCFAs might improve intestinal health through promoting intestinal development and absorption function, and enhancing intestinal immune function, and these effects were occur independently of the gut microbiota.

Infusion of short chain fatty acids in the ileum improves the carcass traits, meat quality and lipid metabolism of growing pigs.

Short chain fatty acids (SCFA) are the main products of indigestible carbohydrates undergoing bacterial fermentation in the hindgut, which are related to some physiological functions. This study was designed to investigate the effects of SCFA infusion by ileum on the carcass traits, meat quality and lipid metabolism of growing pigs. In a 28-day study, 24 growing barrows fitted with a T-cannula in distal ileum were divided into 4 treatments: 1) Control, 2) antibiotics (AB), 3) AB + 300 mL of SCFA1 solution (ABS1), 4) AB + 300 mL of SCFA2 solution (ABS2). The concentrations of acetate, propionate and butyrate in SCFA1 solution were respectively 61.84, 18.62 and 12.55 mmol/L, and in SCFA2 were respectively 40.08, 15.41 and 9.78 mmol/L. The results showed that the SCFA infusion increased the average daily feed intake and average daily gain of pigs (P < 0.05). Meanwhile, the SCFA treatments increased longissimus dorsi area (P < 0.05) and carcass weight (P = 0.058), decreased the drip loss of longissimus dorsi (P = 0.059), and reduced serum concentrations of triglyceride, total cholesterol and urea nitrogen (P < 0.05). Besides, the SCFA administration inhibited the mRNA expressions of fatty acid synthase (FAS) and acetyl-CoA carboxylase in longissimus dorsi (P < 0.05), the mRNA expression of FAS in the liver (P < 0.05), and the mRNA expression of hormone-sensitive lipase in abdominal fat (P < 0.05). Short chain fatty acid infusion also enhanced the mRNA expression of carnitine palmitoyltransferase-1α in the liver (P < 0.05), the mRNA expressions of peroxisome proliferator activated receptor gamma and lipoprotein lipase in abdominal fat (P < 0.05), and the mRNA expressions of free fatty acid receptor 2, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the colon (P < 0.05). These results suggested that SCFA administration in the ileum could improve the carcass traits and meat quality of growing pigs, which was possibly due to the fact that SCFA modulated lipid metabolism.

Gastric infusion of short-chain fatty acids can improve intestinal barrier function in weaned piglets

BackgroundThe present study was conducted to investigate the effects of gastric infusion of short-chain fatty acids (SCFA) on gut barrier function in a pig model. In this study, 21 DLY barrows with an average initial body weight of (8.31 ± 0.72) kg were randomly allotted into three treatments: (1) control, (2) infusing low SCFA, S1, (3) infusing high SCFA, S2. The experimental period lasted for 7 days.ResultsGastric infusion of SCFA increased the concentrations of SCFA in serum and digesta, and enhanced the mRNA and protein abundances of SCFA receptors in pig intestine (P < 0.05). Moreover, gastric infusion of SCFA led to alteration of intestinal morphology, elevation of intestinal development-related gene abundances, and decrease of apoptotic cell percentage, as well as reduction of pro-apoptosis gene and protein abundances (P < 0.05). Besides, the jejunal SLC7A1 and ileal DMT1 mRNA abundances in the SCFA infusion groups were higher than those in the control group (P < 0.05). Additionally, gastric infusion of SCFA increased the mRNA abundances of Occludin and Claudin-1 in the duodenum and ileum, enhanced Lactobacillus spp counts in the ileal digesta, decreased the mRNA and protein abundances of IL-1β in the colon, and reduced Escherichia coli count in the ileal digesta (P < 0.05).ConclusionsThese data indicated that gastric infusion of SCFA, especially high SCFA concentration, may be beneficial to gut development of piglets via improving gut morphology, decreasing apoptotic cell percentage, and maintaining intestinal barrier function.

Density distribution of free fatty acid receptor 2 (FFA2)-expressing and GLP-1-producing enteroendocrine L cells in human and rat lower intestine, and increased cell numbers after ingestion of fructo-oligosaccharide

Glucagon-like peptide 1 (GLP-1) is a multifunctional hormone in glucose metabolism and intestinal function released by enteroendocrine L-cells. The plasma concentration of GLP-1 is increased by indigestible carbohydrates and luminal infusion of short-chain fatty acids (SCFAs). However, the triggers and modulators of the GLP-1 release remain unclear. We hypothesized that SCFAs produced by bacterial fermentation are involved in enteroendocrine cell proliferation and hormone release through free fatty acid receptor 2 (FFA2, also known as FFAR2 or GPR43) in the large intestine. Fructo-oligosaccharide (Fructo-OS), fermentable indigestible carbohydrate, was used as a source of SCFAs. Rats were fed an indigestible-carbohydrate-free diet (control) or a 5% Fructo-OS-containing diet for 28days. FFA2-, GLP-1-, and 5-hydroxytryptamine (5-HT)-positive enteroendocrine cells were quantified immunohistochemically in the colon, cecum, and terminal ileum. The same analysis was performed in surgical specimens from human lower intestine. The coexpression of FFA2 with GLP-1 was investigated both in rats and humans. Fructo-OS supplementation in rats increased the densities of FFA2-positive enteroendocrine cells in rat proximal colon, by over two-fold, relative to control, in parallel with GLP-1-containing L-cells. The segmental distributions of these cells in human were similar to rats fed the control diet. The FFA2-positive enteroendocrine cells were GLP-1-containing L-cells, but not 5-HT-containing EC cells, in both human and rat colon and terminal ileum. Fermentable indigestible carbohydrate increases the number of FFA2-positive L-cells in the proximal colon. FFA2 activation by SCFAs might be an important trigger for produce and release GLP-1 by enteroendocrine L-cells in the lower intestine.

Effect of Ileal Infusion of Short-Chain Fatty Acids on Pancreatic Prandial Secretion and Gastrointestinal Hormones in Pigs

Nutrients passing the ileum induce mechanisms regulating pancreatic secretion, but the effect of short-chain fatty acids (SCFAs) present in the ileum because of either intestinal fermentation or due to the cecoileal reflux is still unclear. This study investigated the effect of ileal SCFAs on pancreatic secretion and plasma levels of peptide YY, cholecystokinin, motilin, and neurotensin. The pigs were fitted with pancreatic duct, ileal, and jugular vein catheters, and a duodenal T-shaped cannula. Saline, 85.0 or 170.0 mM acetate, 5.0 or 10.0 mM butyrate, 7.5 or 15.0 mM propionate were infused into the ileum during feeding. The ileal infusions of SCFAs did not affect the pancreatic juice outflow and the lipase output. The protein output was lower when 10.0 mM butyrate or 170.0 mM acetate were infused. The trypsin output decreased for most of the SCFA infusions. The alpha-amylase output decreased for the infusion of 10.0 mM butyrate and tended to decrease for 170.0 mM acetate. The infusions did not change gut hormone level. Ileal SCFAs might induce an inhibition of pancreatic enzyme secretion under prandial conditions. Ileal SCFAs do not inhibit pancreatic secretion by a hormonal pathway involving the release of peptide YY, motilin, neurotensin, or cholecystokinin.

Effect of short chain fatty acids infused intraileally on interdigestive exocrine pancreatic secretions in growing pigs

The effect of intraileally infused short chain fatty acids (SCFA) and saline as control on the exocrine pancreatic secretions during the interdigestive phase was studied using three 8-weeks-old piglets. Pigs were surgically fitted with a pancreatic duct catheter, re-entrant duodenal T-cannula for collection and subsequent return of pancreatic juice, and with an infusion T-cannula at the distal ileum. Saline as control, 5.0 and 10.0 mm butyrate, 7.5 and 15.0 mm propionate and 85.0 and 170.0 mm acetate were infused at 2 ml/kg body weight (BW) for 30 min into the ileum of overnight fasted piglets via ileal T-cannula. The calculated volume of infusates was administrated in five equal bolus at 6 min intervals over a period of 30 min. The pancreatic juice was collected 60 and 30 min before and 30, 60, 90 and 120 min after the start of infusion. The trypsin (p = 0.07, p > 0.15 respectively) and protein (p > 0.15, p = 0.05 respectively) outputs immediately decreased after the infusion of acetate at the dose of 85.0 and 170.0 mm, respectively, whereas pancreatic juice outflow (p > 0.15) was not significantly affected when compared with levels 30 min before infusion. After the infusion of butyrate at the dose of 5.0 mm, trypsin (p = 0.01) and protein (p = 0.12) outputs increased immediately whereas pancreatic juice outflow was not affected (p > 0.15) in comparison with levels 30 min before infusion. No significant differences were observed after infusion of butyrate at the dose of 10 mm for the pancreatic juice outflow, trypsin and protein outputs when compared with the level before infusion, although these values were numerically lower immediately after the infusion. The pancreatic juice outflow increased (p = 0.03) after the infusion of propionate at the dose of 7.5 mm and decreased (p = 0.005) immediately after the infusion of propionate at the dose of 15.0 mm when compared with the levels 30 min before the infusions. After the infusion of propionate at the dose of 7.5 or 15.0 mm for the output of protein and trypsin, no significant differences (p > 0.15) were observed when compared with levels 30 min before infusion. In summary, the intraileal infusion of SCFA at different doses exerts a short-term and moderate effect on the interdigestive exocrine pancreatic secretions in pigs.

A metabolomic investigation of splanchnic metabolism using 1H NMR spectroscopy of bovine blood plasma

This is the first study introducing an NMR-based metabolomic approach to elucidate metabolism in the portal-drained viscera and liver. High-resolution 1H NMR spectroscopy was performed on blood plasma obtained from the mesenteric artery, the hepatic portal vein and the hepatic vein of steers before and after interruminal infusion of short-chain fatty acids (SCFA). Partial least squares regression discriminant analysis (PLS-DA) on 1H NMR spectra obtained for arterial and portal plasma samples revealed increases in the intensities of spectral regions that could mostly be assigned to the methyl group of propionate, β-hydroxybutyrate as well as acetate in portal plasma samples compared with arterial plasma samples. PLS-DA on portal and hepatic plasma samples showed decreases in the intensities of spectral regions corresponding to the regions where methyl and methylene groups of n-butyrate, propionate, iso-butyrate, valerate, iso-valerate as well as lactate are reported to have chemical shifts. In addition, spectral differences likely to reflect a hepatic excretion of β-hydroxybutyrate and glucose were observed between portal and hepatic samples. All findings were supported by traditional biochemical analyses. Consequently, the present study clearly demonstrated the great potential of the NMR-based metabolomic approach for elucidating splanchnic metabolism. In addition, prediction of metabolite concentrations from the 1H NMR spectra obtained on plasma samples was investigated using PLS, which in relation to use 1H NMR spectra quantitatively revealed promising results with R-values in the region of 0.87–0.98.

Effects of short-chain fatty acids and lactic acids on survival of Oesophagostomum dentatum in pigs

The direct influence of intracaecal infusion of short-chain fatty acids (SCFA) and lactic acids (LA) on already established Oesophagostomum dentatum infection in cannulated pigs was investigated. We tested the hypothesis that the previously discovered anti-parasitic effect of inulin is mediated through its metabolic products SCFA and LA by infusing into cannulated pigs these compounds in amounts approximating to those produced in the pigs large intestine and caecum during the metabolism of inulin. The experiment comprised of 18 pigs—2 groups of 9 pigs in each. The normal diet used in the experiment was based on barley flour with insoluble fibre from oat husk with added soybean meal, vitamins and minerals. After 2 weeks of adaptation to the diet all the pigs were inoculated with 6000 infective larvae of O. dentatum. Six weeks later, surgery on all pigs was performed to install cannulas into caeci. At 7 weeks post-infection (p.i.) the SCFA and LA infusion was initiated in Group 1 (experimental) pigs; at the same time pigs in Group 2 (controls) were infused with saline. At week 10 p.i., all pigs were killed and their worm burdens determined. SCFA and LA infused pigs exhibited markedly reduced fecal egg counts and worm recoveries (98 and 92% reduction, respectively, compared to saline controls). The results from this study demonstrate that SCFA and LA have a significant negative influence on established O. dentatum infection in growing pigs. The results also show that the type of dietary carbohydrates fed and its intestinal degradation can yield metabolic by products that profoundly influence helminth survival.

Portal recovery of short-chain fatty acids infused into the temporarily-isolated and washed reticulo-rumen of sheep

The present study was undertaken to study the metabolism of short-chain fatty acids (SCFA) by the reticulo-ruminal epithelium and the portal-drained viscera (PDV) under in vivo conditions with no interference from the metabolism of the rumen microbes. The technique of temporary isolation of the reticulo-rumen was applied to wethers implanted with catheters in a mesenteric artery, the hepatic portal vein and the right ruminal vein. Portal blood flow was measured by downstream dilution of p-aminohippuric acid; the PDV uptake of arterial acetate, as well as the whole-body irreversible loss rate (ILR) of acetate, was estimated by [2-(13)C]acetate infusion into the right ruminal vein. The sheep were maintained with a bicarbonate-buffered solution of SCFA in the reticulo-rumen along with continuous intraruminal infusion of SCFA for 4 h. The portal appearance of SCFA of non-reticulo-ruminal origin was estimated before and after the infusion protocol. Of the acetate absorbed by the sheep, 89 (SE 5), 109 (SE 7) and 101 (SE 7)% was recovered as portal net appearance of acetate, portal net appearance of acetate corrected for PDV uptake of arterial acetate and increase in the ILR of acetate respectively. Of the propionate, isobutyrate, butyrate, isovalerate and valerate absorbed by the sheep, 95 (SE 7), 102 (SE 9), 23 (SE 3), 48 (SE 5) and 32 (SE 4)% respectively was recovered as portal net appearance. In contrast to current concepts, the present study showed that the reticulo-ruminal epithelium metabolizes none (or only a small proportion) of the acetate and propionate absorbed from the rumen. This observation could lead to the more efficient use of results obtained with multi-catheterized animals to quantify the net metabolite output of the rumen microbes.

Modulation by colonic fermentation of LES function in humans.

Colonic fermentation of carbohydrate has been shown to influence gastric and intestinal motility. Our aim was to investigate the effects of colonic infusion of lactose and short-chain fatty acids (SCFAs) on lower esophageal sphincter (LES) function in humans. LES pressure (LESP), transient relaxations of LES (TLESRs), and esophageal pH were monitored over 6 h on 4 different days in 7 healthy volunteers. After 1 h of baseline recording, the effects of different colonic infusions (270 ml of isotonic or hypertonic saline, 30 g lactose, or 135 mmol SCFAs) were tested in fasting conditions and after a standard meal. Peptide YY (PYY) and oxyntomodulin (OLI) were also measured in plasma. Both lactose and SCFA infusions increased the number of TLESRs as well as the proportion of TLESRs associated with acid reflux episodes, but saline solutions did not. The postprandial fall of LESP was enhanced by previous SCFA infusion. Plasma PYY and OLI increased similarly after all colonic infusions. Colonic fermentation of lactose markedly affected LES function, and this effect was reproduced by SCFA infusion. Whether the mechanisms of this feedback phenomenon are of hormonal nature, neural nature, or both remains to be determined.

A ação dos ácidos graxos de cadeia curta na cicatrização de anastomoses colônicas: estudo experimental em ratos

Os ácidos graxos de cadeia curta (AGCC) derivam da fermentação das fibras ingeridas na dieta e atuam como substrato das células da mucosa colônica. O presente estudo tem como objetivo avaliar a ação dos AGCC na cicatrização do cólon. Utilizaram-se 16 ratos fêmea divididos em 2 grupos de 8 animais. No grupo controle (HC) os animais foram submetidos à cirurgia de Hartmann e infusão pós-operatória de solução salina isotônica via retal por 7 dias. No grupo experimento (HA) a solução salina foi substituída por solução isosmolar contendo AGCC. Nos animais do grupo controle, a pressão média de ruptura do segmento distal do cólon foi de 128,37 mmHg, sendo este valor de 137,25 mmHg no grupo experimento (p=0,5693). A avaliação histológica em hematoxilina-eosina foi semelhante nos dois grupos estudados. A densitometria do colágeno demonstrou concentração significativamente maior de colágeno maduro (tipo I) no grupo experimento, quando comparado com o grupo controle (p=0,0094). O colágeno total também foi mais encontrado no grupo experimento, comparado-se com o grupo controle (p=0,0371). Conclui-se que os ratos submetidos à infusão intraluminal de AGCC têm maior concentração de colágeno maduro e total na linha de sutura do coto retal, quando comparados com o grupo controle.

Short-chain fatty acids improve clinical, pathologic, and microbiologic features of experimental shigellosis.

Because of the metabolic and antibacterial actions of short-chain fatty acids (SCFA), their roles in modifying the clinicopathologic features of shigellosis were evaluated in a rabbit model of shigellosis. Acute colitis was induced in adult rabbits by intracolonic administration of Shigella flexneri 2a. After 24 h, rabbits were given 6-h colonic infusions of SCFA (acetate, propionate, n-butyrate; 60:30:40 mM) or SCFA-free solution (control); groups of rabbits were killed in batches of 2 or 3 animals at 24, 48, 72, and 96 h after treatment, for histologic and bacteriologic assessment. SCFA significantly reduced fecal blood and mucus and improved clinical symptoms. Histologically, SCFA significantly (P<.01) reduced mucosal congestion, cellular infiltration, and necrotic changes. SCFA also significantly (P<.05) reduced the number of shigellae in the colon. No such improvements occurred in the control group. SCFA may be useful agents in improving clinicopathologic features of shigellosis and should be clinically evaluated.

Ileal Short-Chain Fatty Acids Inhibit Transpyloric Flow in Pigs

Background: Short-chain fatty acids (SCFA) found in the ileum after caecoileal reflux might trigger a physiologic ileal brake similar to that induced by ileal nutrient infusion. This study evaluates gastric emptying and motility after ileal administration of SCFA. Methods: In eight conscious pigs gastric emptying was evaluated by double dilution (liquids) and direct measurement of duodenal effluent (liquids and solids) during ileal infusions of SCFA and isotonic and hypertonic saline. Antropyloroduodenal manometry and flow were recorded concurrently. Results: Ileal SCFA significantly delayed gastric emptying of liquids and solids. During SCFA infusion the emptying pattern of liquids was less pulsatile, and flow pulses had a smaller stroke volume than during isotonic saline. The antroduodenal pressure gradient was decreased, whereas pyloric tone was increased. A reduced number of antral pressure waves occurred together with an increased frequency of isolated pyloric pressure waves. Conclusions: Ileal SCFA infusion delays gastric emptying of liquid and solid as a consequence of a decreased antral and increased pyloric motility.

Stimulation of Epithelial Cell Proliferation of Isolated Distal Colon of Rats by Continuous Colonic Infusion of Ammonia or Short-Chain Fatty Acids Is Nonadditive

Dietary fibers accelerate colonic epithelial cell proliferation at least in part by modulating bacterial metabolism in the large intestine. Ammonia and short-chain fatty acids (SCFA) are major metabolites of hindgut bacteria and are believed to affect epithelial cell kinetics of the colon. However, the effect of luminal ammonia itself and the possible interaction of ammonia with SCFA on colonic epithelial cell proliferation have not yet been studied. The colon of rats was surgically isolated and continuously administered infusates with saline, ammonia, SCFA or both into the isolated colon for 7 d in a two-way factorial design. On d 7, vincrystine sulfate was administered intravenously to cause metaphase arrest. The activity of epithelial cell proliferation in the distal colon was estimated by using a stathmokinetic method and by histologic examination. The crypt size was significantly larger in rats given infusates containing SCFA than in rats given infusates without SCFA. Infusion of ammonia or SCFA significantly stimulated colonic epithelial cell proliferation compared with the saline infusion. Infusion of both ammonia and SCFA resulted in accumulated mitoses per crypt that did not differ from the other three infusions although the value tended to be lower than when SCFA alone were infused. Thus, stimulation of epithelial cell proliferation by ammonia and SCFA is not additive, and the interaction between them should be considered when the effects of dietary fibers on gut epithelial proliferation are investigated.

The energy value of short-chain fatty acids infused into the caecum of pigs.

The present work was undertaken to study the energy value of a mixture of acetic, propionic and butyric acids (0.682:0.226:0.092) infused intracaecally in growing pigs. A basal diet low in fibre (42 g NSP/kg DM) was given at below the requirement for maximum weight gain. In six 2-week periods, N and energy balance measurements in eight growing pigs were carried out with and without infusion of short-chain fatty acids (SCFA). Heat production was measured using open-circuit chambers and the concentration of SCFA in faeces was determined. Less than 1% of the infused SCFA was excreted in faeces illustrating the capacity of the hind-gut to absorb and metabolize SCFA. Infusion of SCFA did not affect the digestibility of nutrients and energy. However, N retention increased demonstrating that SCFA are an energy source for protein gain when pigs are fed at below the requirement of energy. Increased CH4 production together with an increased excretion of branched-chain fatty acids in faeces suggested that there was a higher microbial activity in the hind-gut during infusion. The partial utilization of the infused energy in SCFA was 0.821. A small proportion of the infused energy in SCFA was retained in protein (0.099) and a considerable amount was retained as fat (0.722).

Effects of Short-Chain Fatty Acids on Gastrointestinal Motility

Besides their action on gut morphology and function, short-chain fatty acids (SCFAs), produced by bacterial fermentation of carbohydrates in the colon, influence gastrointestinal motility. As they are not present in the stomach and proximal small intestine, SCFAs do not directly affect motility of these segments. However, caecal infusion of SCFAs as well as colonic fermentation of lactulose induce a relaxation of the proximal stomach in humans, indicating that SCFAs can affect motility at a distance from their site of production. Moreover, this suggests that SCFAs may be involved in the so-called ‘ileocolonic brake’, i.e. the inhibition of gastric emptying by nutrients reaching the ileo-colonic junction. In the terminal ileum, where their concentration may increase following a colo-ileal reflux, SCFAs stimulate contractions and shorten ileal emptying, which may protect ileal mucosa against the potentially harmful effects of the reflux of colonic contents. Although SCFAs are produced and concentrated in the colon, their action on motility of this organ is not clearly understood and may depend on concentration, molecular structure of the acids, responsiveness of the colonic segments and animal species. The mechanisms of action of SCFAs on gastrointestinal motility are not completely elucidated. They may involve systemic humoral and neural pathways as well as local reflexes and myogenic responses.

Effect of fiber and its fermentation on colonic adaptation after cecal resection in the rat.

The role of fiber in postresection adaptation is poorly understood. We examined the significance of short-chain fatty acids produced by intracolonic fiber fermentation during colonic adaptation. Rats underwent one of three surgeries: control laparotomy, cecal resection, or cecal resection with placement of perfusion catheter. Rats of each surgical group were randomly assigned to receive treatment regimens of standard fiber diet (with or without fermentation-suppressing antibiotics), fiber-free diet, or diet plus intracolonic perfusion of short-chain fatty acids. Adaptation parameters of mucosal weight, mucosal DNA and protein content, water absorption, and butyrate absorption were measured. Compared with controls, postresection rats that were fed fiber had 65% greater basal and 112% greater butyrate-stimulated water absorption as well as 140% greater butyrate absorption. Fiber-fed rats exhibited significantly greater colonic weight and colonic mucosal protein after cecal resection. These changes were absent in postresection rats fed a fiber-free diet. Inhibition of fermentation by neomycin and metronidazole added to a standard fiber diet also prevented postresection adaptation. All adaptive changes were restored when the cecal-resection rats that were fed the fiber diet with antibiotics received an intracolonic infusion of short-chain fatty acids. Adaptation did not occur when short-chain fatty acids were infused into colons of postresection rats that were fed a fiber-free diet. Cecal resection leads to significant functional and structural changes in the adapting residual colon. Fermentation of dietary fiber by colonic flora to short-chain fatty acids is necessary, but it alone is not sufficient to mediate adaptation.