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Expression and membrane localization of MCT isoforms along the length of the human intestine.

Recent studies from our laboratory and others have demonstrated the involvement of monocarboxylate transporter (MCT)1 in the luminal uptake of short-chain fatty acids (SCFAs) in the human intestine. Functional studies from our laboratory previously demonstrated kinetically distinct SCFA transporters on the apical and basolateral membranes of human colonocytes. Although apical SCFA uptake is mediated by the MCT1 isoform, the molecular identity of the basolateral membrane SCFA transporter(s) and whether this transporter is encoded by another MCT isoform is not known. The present studies were designed to assess the expression and membrane localization of different MCT isoforms in human small intestine and colon. Immunoblotting was performed with the purified apical and basolateral membranes from human intestinal mucosa obtained from organ donor intestine. Immunohistochemistry studies were done on paraffin-embedded sections of human colonic biopsy samples. Immunoblotting studies detected a protein band of approximately 39 kDa for MCT1, predominantly in the apical membranes. The relative abundance of MCT1 mRNA and protein increased along the length of the human intestine. MCT4 (54 kDa) and MCT5 (54 kDa) isoforms showed basolateral localization and were highly expressed in the distal colon. Immunohistochemical studies confirmed that human MCT1 antibody labeling was confined to the apical membranes, whereas MCT5 antibody staining was restricted to the basolateral membranes of the colonocytes. We speculate that distinct MCT isoforms may be involved in SCFA transport across the apical or basolateral membranes in polarized colonic epithelial cells.

Cell Membrane↗

Regulation of butyrate uptake in Caco-2 cells by phorbol 12-myristate 13-acetate.

Butyrate and the other short-chain fatty acids (SCFAs) are the most abundant anions in the colonic lumen. Also, butyrate is the preferred energy source for colonocytes and has been shown to regulate colonic electrolyte and fluid absorption. Previous studies from our group have demonstrated that the HCO(3)(-)/SCFA(-) anion exchange process is one of the major mechanisms of butyrate transport across the purified human colonic apical membrane vesicles and the apical membrane of human colonic adenocarcinoma cell line Caco-2 and have suggested that it is mainly mediated via monocarboxylate transporter-1 (MCT-1) isoform. However, little is known regarding the regulation of SCFA transport by various hormones and signal transduction pathways. Therefore, the present studies were undertaken to examine whether hydrocortisone and phorbol 12-myristate 13-acetate (PMA) are involved in a possible regulation of the butyrate/anion exchange process in Caco-2 cells. The butyrate/anion exchange process was assessed by measuring a pH-driven [(14)C]butyrate uptake in Caco-2 cells. Our results demonstrated that 24-h incubation with PMA (1 microM) significantly increased [(14)C]butyrate uptake compared with incubation with 4alphaPMA (inactive form). In contrast, incubation with hydrocortisone had no significant effect on butyrate uptake in Caco-2 cells compared with vehicle (ethanol) alone. Induction of butyrate uptake by PMA appeared to be via an increase in the maximum velocity (V(max)) of the transport process with no significant changes in the K(m) of the transporter for butyrate. Parallel to the increase in the V(max) of [(14)C]butyrate uptake, the MCT-1 protein level was also increased in response to PMA incubation. Our studies demonstrated that the butyrate/anion exchange was increased in response to PMA treatment along with the induction in the level of MCT-1 expression in Caco-2 cells.

Adenocarcinoma↗

Transport of n-butyrate into human colonic luminal membrane vesicles.

Human colonic short-chain fatty acid (SCFA) absorption is associated with increased luminal pH and HCO3- and enhanced Na+ absorption. Therefore, the mechanism of colonic SCFA transport, its dependence on Na+ and HCO3- and interactions with Cl-/HCO3- and Na+/H+ exchangers were characterized. Luminal membrane vesicles (LMV) isolated by divalent cation precipitation from organ donor colons were used for n-butyrate transport. Uptake of n-butyrate into the human colonic LMV was minimal even in the presence of an inward pH gradient, but an outward HCO3- gradient significantly increased uptake rates. HCO3(-)-stimulated butyrate uptake was saturable with an apparent Michaelis constant of 1.5 +/- 0.2 mM and maximal velocity of 105 +/- 3 nmol.mg protein-1.3 s-1. Intravesicular butyrate resulted in trans-stimulation of n-[1-14C]butyrate uptake. Butyrate uptake was inhibited approximately 25-40% by C2-C5 SCFAs and approximately 40% by niflumic acid. Butyrate uptake was not affected by extravesicular Na+, and 22Na uptake was unaltered by extravesicular butyrate. Butyrate uptake was independent of extra- or intravesicular CI-, and butyrate loading produced no changes in 36Cl uptake. We conclude that the predominant mechanism of n-butyrate transport across the human colonic luminal membrane appears to be via a HCO3-/SCFA antiport system independent of Cl-/HCO3- exchange and Na+ transport.

Biological Transport↗

Application of the colon-simulation technique for studying the effects of Saccharomyces boulardii on basic parameters of porcine cecal microbial metabolism disturbed by clindamycin.

AIMS: The present study analyzed the effects of Saccharomyces boulardii on the biochemical parameters of microbial hindgut metabolism disturbed by clindamycin. METHODS: The experiments were carried out under in vitro conditions using the semicontinuous colon-simulation technique. This technique is standardized for quantitatively measuring parameters of microbial hindgut metabolism. The fluid and particle phase of pig hindgut contents were used for the in vitro incubations. The 5-day control period was followed by clindamycin exposure alone (312.5 mg/day for 5 days) or by a combined treatment of clindamycin and S. boulardii (400 mg/day for 5 days). RESULTS: Clindamycin resulted in significant decreases in production rates of short-chain fatty acids (SCFAs) which were associated with substantial changes in molar SCFA proportions at the expense of butyrate. These effects could at least partly be compensated for by S. boulardii, in particular by enhancements of acetate and propionate fermentation to control levels. In contrast, butyrate fermentation could not be reconstituted. In a second experiment the potential use of S. boulardii as a substrate for hindgut microbial metabolism was studied by comparing living and autoclaved yeast. Propionate and butyrate fermentation rates were unaffected whereas acetate fermentation tended to be higher in the presence of living yeast. CONCLUSIONS: S. boulardii can be effective to compensate for changes in microbial fermentation in response to antibiotic treatment. Despite the lack of statistical significance it might be concluded that the increase in fermentation end products can only partly be explained by the utilization of the yeast as a substrate for microbial metabolism.

Analysis of Variance↗

Effects of guar gum and cellulose on cecal enzyme activity and cecal short-chain fatty acids in young and aged mice.

The effects of cellulose or guar gum on cecal enzyme activity and cecal short-chain fatty acids (SCFAs) in young and aged mice were studied. Male Crj:CD-1 (ICR) mice were fed an MF diet for 4 (young mice) or 23 months (aged mice). The MF diet was then replaced with a semisynthetic diet supplemented with 5% guar gum or 5% cellulose. The mice were fed the guar gum or cellulose diet for 3 weeks. There was no significant difference in cecal content between the two diet groups. There were no significant differences in total short-chain fatty acid production between the young mice fed the cellulose and those fed the guar gum diet, and between the aged mice fed the cellulose and guar gum diet. There were significant differences in cecal enzyme activity between the young mice fed the cellulose and those fed the guar gum diet. Beta-glucuronidase activity was significantly higher in the young mice fed the guar gum diet than in those fed the cellulose diet. There were also significant differences in cecal enzyme activity between the aged mice fed the cellulose diet and those fed the guar gum diet. Beta-glucuronidase activity was significantly higher in the aged mice fed the guar gum diet than in these fed the cellulose diet. Beta-glucosidase activity was significantly lower in the aged mice fed the guar gum diet than in those fed the cellulose diet. The effect of cellulose on the microflora between the young and aged mice might be different from the effect of guar gum. The degree of adaptation to the diet of microflora in young and aged mice fed the cellulose diet might differ from that in those fed the guar gum diet. The higher enzyme activities of microflora in aged animals compared to young animals, might have some relation with the incidence of colon cancer in aged animals.

Aging↗

Diet, length of gestation, and fecal short chain fatty acids in healthy premature neonates.

BACKGROUND: Excretion of fecal short-chain fatty acids (SCFAs) may indicate changes in colonic or colonocyte metabolism. The aim of this study was to detect the influence of gestational age and feeding practices on SCFA concentrations and profiles in healthy preterm infants. METHODS: A total of 198 fecal samples (28 infants) were collected from 8 to 21 days of age from 3 groups of preterm infants born at 33 to 37 weeks of gestation and fed either breast milk (group I) or Nutramigen, a lactose-free formula (group II), and extremely preterm infants born before 33 weeks of gestation and fed breast milk (group III). Total SCFA concentrations and SCFA profiles were analyzed using a gas chromographic (GC) procedure. RESULTS: Total fecal SCFA excretion did not differ significantly between group I (mean, 24.0 micromol/g; range, 1.3 to 118.8 micromol/g) and group II (mean, 23.0 micromol/g; range, 3.0 to 73.3 micromol/g). Conversely, differences occurred between SCFA profiles and became significant after day 17. The main differences were a significant increase in the butyric acid concentration (12% versus 30%) with group II. Compared with group I, fecal SCFA concentrations were 3.2-fold lower (7.4 micromol/g; range, 0.3 to 37.4 micromol/g) in group III with no significant changes in the profiles. CONCLUSIONS: Fecal SCFA excretion may vary in absence of any digestive disease. During this study, in terms of gestational age, total SCFA concentrations were significantly lower in extremely premature infants compared with infants born less premature, despite their known higher deficiency in intestinal lactase activity. In terms of diet, the absence of lactose did not lead to a decrease in colonic fermentation and induced changes in SCFA patterns. These new baseline data may offer clues to further development of milk formulas.

Age Factors↗

Fecal short-chain fatty acids predict digestive disorders in premature infants.

BACKGROUND: Excretion of fecal short-chain volatile fatty acids (SCFAs) may indicate changes in colonic or colonocyte metabolism. The aim of this study was to detect the existence of an average fecal SCFA profile and to define which changes were associated with clinical events that occurred during the survey period. METHODS: SCFA profiles of 185 stool samples collected from 46 fed preterm neonates (mean birth weight, 1920 g; mean gestational age, 32.8 weeks) were evaluated and their association with digestive disorders or therapy was explored. RESULTS: Total SCFA concentration increased from 0 to 80 micromol/g feces wet weight over the first 20 days of life. A basic SCFA profile revealed the existence of a highly sensitive period between the second and the third week of life. In the absence of any digestive problem (n = 15), the butyric acid (C4) ratio increased from 7% to 24%. Phototherapy (n = 13) enhanced the SCFA concentration but decreased the ratios of C4 and minor acids. Digestive disorders reported included abdominal distention (n = 6) or bleeding (n = 8). Only in the case of bleeding was the SCFA profile changed by an enhancement of C4 by >50%. Antibiotic therapy (n = 3) suppressed SCFA production. CONCLUSIONS: This study supports a hypothesis that changes in the SCFA profile could offer a noninvasive method to anticipate functional modifications of the gastrointestinal tract before the first clinical signs of pathologic events, including necrotizing enterocolitis.

Anti-Bacterial Agents↗

Recent advances: parenteral nutrition support.

Even though there is an abundance of research related to the clinical and physiologic effects of parenteral nutrition and specific nutritional substrates, few new products have been released for clinical use. This review illustrates some of the directions being taken in the future development of parenteral nutrition products and some new perspectives related to the current effects (or lack of effects) of TPN. When considering the individual effects of specific nutrient substrates (arginine, glutamine, LCTs, MCTs, SCFAs) as reviewed here, it becomes apparent that the infusion of parenteral nutrition has the potential to produce a variety of metabolic responses that could be both beneficial and harmful. These effects depend on the type and quantity of substance infused as well as the disease and clinical condition of the patient. This also is true for those substances (GH, IGF-1) being evaluated to direct the effects of TPN infusions in a manner that improves protein accretion and supports the immunologic response of the body. At best, these investigations are producing a great amount of new and more specific information about the metabolic response to illness and the effects of TPN and individual substrate on that response.

Arginine↗

Short-chain fatty acid derivatives induce fetal globin expression and erythropoiesis in vivo.

Orally bioactive compounds that induce gamma globin gene expression at tolerable doses are needed for optimal treatment of the beta-hemoglobinopathies. Short-chain fatty acids (SCFAs) of 2 to 6 carbons in length induce gamma globin expression in animal models, and butyrate, phenylbutyrate, and valproate induce gamma globin in human patients. The usefulness of these compounds, however, is limited by requirements for large doses because of their rapid metabolism and their tendency to inhibit cell proliferation, which limits the pool of erythroid progenitors in which gamma globin can be induced. Selected short-chain fatty acid derivatives (SCFADs) were recently found to induce gamma globin and to stimulate the proliferation of hematopoietic cells in vitro. These SCFADs are now evaluated in vivo in nonanemic transgenic mice containing the human beta globin gene locus and in anemic phlebotomized baboons. In mice treated with a SCFAD once daily for 5 days, gamma globin mRNA increased 2-fold, reticulocytes increased 3- to 7-fold, and hematocrit levels increased by 27%. Administration of 3 SCFADs in anemic baboons increased F-reticulocytes 2- to 15-fold over baseline and increased total hemoglobin levels by 1 to 2 g/dL per week despite ongoing significant daily phlebotomy. Pharmacokinetic studies demonstrated 90% oral bioavailability of 2 SCFADs, and targeted plasma levels were maintained for several hours after single oral doses equivalent to 10% to 20% of doses required for butyrate. These findings identify SCFADs that stimulate gamma globin gene expression and erythropoiesis in vivo, activities that are synergistically beneficial for treatment of the beta hemoglobinopathies and useful for the oral treatment of other anemias.

Anemia↗

Bifidobacterium infantis strains with and without a combination of oligofructose and inulin (OFI) attenuate inflammation in DSS-induced colitis in rats.

BACKGROUND: Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. METHODS: Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1beta, TNF-alpha, IL-10 and TGF-beta) and malondialdehyde (MDA). RESULTS: OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1beta decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. CONCLUSION: Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations.

Animals↗

Effects of difructose anhydride III (DFA III) administration on rat intestinal microbiota.

The effects of difructose anhydride III (di-D-fructofuranose-1,2':2,3'-dianhydride; DFA III) administration (3% DFA III for 4 weeks) on rat intestinal microbiota were examined using denaturing gradient gel electrophoresis (DGGE). According to DGGE profiles, the number of bacteria related to Bacteroides acidofaciens and uncultured bacteria within the Clostridium lituseburense group decreased, while that of bacteria related to Bacteroides vulgatus, Bacteroides uniformis and Ruminococcus productus increased in DFA III-fed rat cecum. In the cecal contents of DFA III-fed rats, a lowering of pH and an increase in short chain fatty acids (SCFAs), especially acetic acid, were observed. The DFA III-assimilating bacterium, Ruminococcus sp. M-1, was isolated from the cecal contents of DFA III-fed rats. The strain had 98% similarity with R. productus ATCC 27340T (L76595), and mainly produced acetic acid. These results confirmed that the bacteria harmful to host health were not increased by DFA III administration. Moreover, DFA III stimulated the growth of Ruminococcus sp. M-1 producing acetic acid, which may alter the intestinal microbiota towards a healthier composition. It is expected that DFA III would be a new candidate as a prebiotic.

Administration, Oral↗

Effect of deaerated water on serum biochemical values and on the cecum concentration of short-chain fatty acids in the rat.

The effects of drinking deaerated water on serum biochemical values, and on the concentrations of short-chain fatty acids (SCFAs) derived from bacterial fermentation in the colon were examined in rats. Drinking deaerated water decreased the levels of serum alkaline phosphatase (SAP) and serum urea nitrogen (SUN), and increased the serum potassium (SK) and serum phosphorus (SP) levels. Although the concentration of propionic acid in the cecum was decreased by drinking deaerated water, the concentrations of isobutyric, valeric, and isovaleric acid in the cecum were increased.

Alkaline Phosphatase↗

Five-week intake of short-chain fructo-oligosaccharides increases intestinal absorption and status of magnesium in postmenopausal women.

Fermentable carbohydrates have been shown to be nondigestible by human enzymes in the small intestine but are fermented extensively in the large bowel to short-chain fatty acids (SCFAs), which can increase mineral absorption. It has been shown that feeding such carbohydrates including short-chain fructo-oligosaccharides (sc-FOSs) increases intestinal magnesium (Mg) absorption in animals, but their beneficial impact on Mg absorption in humans still remains to be established. Therefore, this work aimed to investigate the effect of moderate daily doses of sc-FOSs (10 g/day) on the intestinal absorption and status of Mg in postmenopausal women without hormone replacement therapy (HRT). Eleven healthy postmenopausal women aged 59 +/- 6 years (mean +/- SD) received for 5 weeks sc-FOS or sucrose (placebo) treatments according to a randomized, double-blind, crossover design separated by a washout period of at least 3 weeks. Subjects ingested 87.5 mg of stable isotope 25Mg together with a fecal marker. Subsequently, feces were collected for 5-7 days. An inductively coupled plasma mass spectrometer (ICP/MS) was used for 25Mg stable isotope measurements in feces, urine, and blood. Mg levels were assessed also at the beginning and at the end of each treatment in plasma, erythrocytes, and urine. These measurements allowed for the determination of net intestinal Mg absorption and Mg status. The results show that the addition of 10 g sc-FOS to the diet increased Mg absorption by 12.3%, from 30.2 +/- 5.0% (placebo treatment) to 33.9 +/- 7.2% (sc-FOS treatment; mean +/- SD; p < 0.02). This increase in intestinal Mg absorption was accompanied by an increase in plasma 25Mg level and led to a higher urinary 25Mg excretion. This is the first time that such an effect is shown in humans. The overall conclusion of this work is that the ingestion of moderate doses of sc-FOS did improve intestinal Mg absorption and status in postmenopausal women. Because of the important role of Mg in many cellular functions, such Mg absorption improvement may be particularly interesting when the dietary intake of Mg is limited.

Aged↗

The influence of ispaghula husk and lactulose on the in vivo and the in vitro production capacity of short-chain fatty acids in humans.

To evaluate factors influencing the short-chain fatty acid (SCFA) concentrations in stools, three different experiments were performed: faecal concentrations of SCFA at defecation were determined by gas liquid chromatography in nine healthy volunteers on a free diet. SCFAs were 114 +/- 15.0 mmol/l (means +/- SD). The coefficient of variation (CV) of the assay was 4-15%, the intraindividual CV 12-33%, and the interindividual CV 11-29%. On incubation of faeces at 37 degrees C concentrations of SCFA doubled in 6 h and rose fourfold in 72 h. In three volunteers the experiments were extended by adding ispaghula husk or lactulose to the diet for two 14-day periods each; no change in faecal SCFA concentrations was seen, either at defecation or after incubation. When ispaghula husk or lactulose was added to faeces in an in vitro incubation system, the concentrations of SCFA were five times higher than those of controls. We conclude that instant handling of faeces is essential for determinations of SCFA concentrations to obtain interpretable and comparable results; that determination of total SCFA output is of limited value; that addition of fibre to the diet does not influence faecal SCFA concentrations; and that the capacity for SCFA production in faeces is large provided a sufficient amount of substrate is available.

Adult↗

Short-chain fatty acids and other intestinal microflora-associated characteristics in faeces of patients with severe B-cell immunodeficiency.

The intestinal microflora of 18 patients with severe B-cell immunodeficiency was studied by determination of short-chain fatty acids (SCFAs) and other intestinal microflora-associated characteristics in the faeces. Glucose-hydrogen (H2) breath test was also performed. The results were within normal values in most of the patients, indicating no major pathologic changes in the intestinal bacterial microflora. These findings do not indicate any important role of the mucosa-associated B-cell system in the regulation of the composition and metabolic activity of the intestinal microflora.

Adolescent↗

Plasma cholesterol reduction by defatted soy ontjom (fermented with Neurospora intermedia) in rats fed a cholesterol-free diet.

To popularize defatted soy ontjom (DSB-ontjom, soy product fermented with Neurospora intermedia) as a new food, I examined the plasma cholesterol-reducing effects of DSB-ontjom and DSB in rats fed cholesterol-free diets and compared the efficiencies of these effects. DSB-ontjom greatly reduced the plasma cholesterol level and increased fecal steroid excretion as compared to DSB. DSB-ontjom was rich in pepsin-resistant protein having a high bile acid binding capacity and was abundant in isoflavone-aglycones, especially daizein. The dietary fiber (DF) of DSB-ontjom stimulated the production of short-chain fatty acids (SCFAs) by intestinal microflora. The effect of DSB-ontjom on plasma cholesterol reduction was attributed to the collaborative effects of pepsin-resistant-protein, isoflavone-aglycones and SCFA-producing DF in DSB-ontjom.

Animals↗

Metabolic Engineering of Probiotic Saccharomyces boulardii Enables Intestinal 3-Hydroxybutyrate Delivery and Alters Short-Chain Fatty Acid Profiles in Mice.

3-Hydroxybutyric acid (3-HB) is a bioactive ketone body involved in the regulation of intestinal inflammation and metabolic homeostasis. Although engineered bacterial probiotics have been developed for localized 3-HB delivery, their susceptibility to antibacterial antibiotics may limit their use during concurrent antibiotic treatment. The probiotic yeast Saccharomyces boulardii offers an alternative host for intestinal 3-HB delivery because of its compatibility with antibacterial antibiotics and the availability of well-established genetic engineering tools. Here, we engineered S. boulardii for 3-HB production using Cas9-mediated genome editing. A heterologous 3-HB biosynthetic pathway was introduced into S. boulardii MYA-797, and endogenous acetyl-CoA and ethanol metabolism was subsequently rewired by overexpressing ACS1, deleting ADH1, and overexpressing ADH7. The optimized strain, SbDY02, produced 1.7 g/L 3-HB under microaerobic conditions. Oral administration of SbDY02 to C57BL/6J mice increased fecal 3-HB and short-chain fatty acid (SCFA) concentrations by 1.89-fold and 1.68-fold, respectively, compared with mice receiving the parental strain. Repeated administration also increased fecal acetate and circulating total SCFAs, butyrate, and propionate. In human colonic epithelial cells, purified 3-HB attenuated lipopolysaccharide-induced p38 MAPK phosphorylation, supporting its direct activity toward inflammation-associated epithelial signaling. To our knowledge, this study provides the first demonstration of a 3-HB-producing probiotic yeast and links central metabolic engineering of S. boulardii with increased 3-HB availability, altered SCFA profiles, and a host-relevant epithelial response.

3-hydroxybutyrate↗

Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition.

AIM: Diarrhea is a significant problem in patients on total enteral nutrition (TEN) and may involve changes in intestinal short chain fatty acids or microflora. Recent studies suggest that the probiotic yeast Saccharomyces boulardii (Sb) may decrease its incidence. The aim of this study was to assess the effects of Sb on fecal flora and short-chain fatty acids (SCFA) in patients on long-term TEN. METHODS: Ten patients (3 females, 7 males, 59+/-5.5 years), on TEN for a median of 13 mo (1-125), and 15 healthy volunteers (4 females, 11 males, 32+/-2.0 years) received Sb (0.5 g bid PO) for 6 d. Two stool samples were taken before, on the last 2 d and 9-10 d after treatment, for SCFA measurement and for culture and bacterial identification. Values (mean+/-SE) were compared using sign tests and ANOVA. RESULTS: Fecal butyrate levels were lower in patients (10.1+/-2.9 mmol/kg) than in controls (19.2+/-3.9, P = 0.02). Treatment with Sb increased total fecal SCFA levels in patients (150.2+/-27.2 vs 107.5+/-18.2 mmol/kg, P = 0.02) but not in controls (129.0+/-28.6 vs 113.0+/-15.2 mmol/kg, NS). At the end of treatment with Sb, patients had higher fecal butyrate (16.0+/-4.4 vs 10.1 [2.9] mmol/kg, P = 0.004). Total SCFAs remained high 9 d after treatment was discontinued. Before the treatment, the anaerobe to aerobe ratio was lower in patients compared to controls (2.4+/-2.3 vs 69.8+/-1.8, P = 0.003). There were no significant changes in the fecal flora of TEN patients. CONCLUSION: Sb-induced increase of fecal SCFA concentrations (especially butyrate) may explain the preventive effects of this yeast on TEN-induced diarrhea.

Diarrhea↗