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PubMed1995

Influence of intestinal inflammation (IBD) and small and large bowel length on fecal short-chain fatty acids and lactate.

Treatment with short-chain fatty acids (SCFAs) seems promising in ulcerative colitis and changes in colonocyte oxidation of butyrate have been suggested to be of importance for the development of this disease. The influence of small and large bowel length after surgery on SCFAs is only partly known. SCFAs and lactate were measured in consecutive fecal samples from 300 patients with ulcerative colitis (103), Crohn's disease (127), and noninflammatory bowel disease (70); 205 had had surgery, 52 had short bowels (< 200 cm). Lactate (mainly the L-isomer) was elevated in ulcerative colitis patients with pancolitis (mean +/- SEM, 17 +/- 5 mmol/liter) and proctitis (12 +/- 3 mmol/liter) compared with quiescent ulcerative colitis (3 +/- 1 mmol/liter, P < 0.01), and correlated with the index of Truelove (R = 0.52, P < 0.0005). Lactate was also increased in Crohn's colitis (21 +/- 8 mmol/liter), but not in isolated ileitis (4 +/- 2 mmol/liter), compared with quiescent Crohn's disease (7 +/- 2 mmol/liter, P < 0.02), but did not correlate with the activity index (CDAI; R = 0.18, P = 0.12). In contrast to earlier reports, SCFAs (including butyrate) did not correlate with inflammatory activity or localization in either ulcerative colitis or Crohn's disease. The length of the small bowel had no influence on SCFAs and lactate in patients with either no colonic function (ileostomies), or with > 50% and < 50% preserved colorectal length, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2002

Enteral and intraluminal short-chain fatty acids improves ischemic left colonic anastomotic healing in the rat.

BACKGROUND AND AIMS: This study assessed the effect of short-chain fatty acids (SCFAs) on the healing of ischemic colonic anastomosis and compared the enteral and intraluminal (transrectal) forms of SCFAs in the same study. MATERIAL AND METHODS: Left colonic ischemia was induced and a 1-cm left colon resection 2-4 cm above the peritoneal reflection was performed through a midline incision. In all, 160 rats were divided into eight groups: a control group, an ischemia group, a transrectal SCFAs group, an ischemia + transrectal SCFAs group, an enteral guar gum group, an ischemia + enteral guar gum group, an ischemia + enteral sham group, and a control + enteral sham group. The animals in each group were anesthetized again on day 4 or 7 after the operation for in vivo analytic procedures. Wound complications, intestinal obstructions, and anastomotic complications were recorded. Periperitoneal adhesions were graded. The strength of each anastomosis was assessed by measuring its bursting pressure. RESULTS: There were significantly more dense intra-abdominal adhesions in the ischemic group and ischemia + enteral sham group. Five animals in the ischemia group, six in the ischemia + enteral sham group, and one in each of the control and ischemia + transrectal SCFA groups developed anastomotic dehiscence. The median bursting pressures were significantly lower in the ischemic group and in the ischemia + enteral sham group on the 4 day and 7 days. CONCLUSION: Deleterious effects of ischemia on left colonic anastomotic healing were significantly prevented by the administration of either 7 days' pretreatment with enteral guar gum or the intraluminal instillation of SCFAs. There were no significant differences between enteral and intraluminal SCFA groups.

Anastomosis, Surgical↗

PubMed1994

Propionate-initiated changes in intracellular pH in rabbit colonocytes.

BACKGROUND/AIMS: Because regulation of intracellular pH (pHi) is critical to basic cell functions, most cells have evolved mechanisms to closely regulate intracellular acid-base balance. Short-chain fatty acids (SCFAs), the predominant luminal anion in the colon, acidify the cell interior in several cell systems, but their effect on their "natural target," the colonocytes, has not been examined thoroughly. METHODS: We monitored the pHi response to a model SCFA, propionate, in isolated cells and epithelial sheets from rabbit proximal colon loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and -6)carboxyfluorescein. RESULTS: SCFAs induced a characteristic pHi response curve in colonocytes: an immediate acidification and a recovery phase returning to baseline in 100-200 seconds. Acidification was altered by increasing concentrations of SCFAs, by increasing SCFA chain length, extracellular osmolarity, and intracellular pH, and finally, Na+ removal. The recovery phase was slowed by amiloride and 4-alpha-OH cinnamate, an inhibitor of proton-monocarboxylate cotransport. CONCLUSIONS: Physiological concentrations of SCFAs have profound effects on intracellular pH. Simple diffusion of the SCFA may not explain the complexities of propionate-induced protonated acidification; the pH recovery phase may involve multiple processes including Na(+)-H+ exchange and H(+)-SCFA cotransport. Luminal constituents such as SCFAs may have significant effects on the intracellular pH and function of colonocytes.

Acid-Base Equilibrium↗

PubMed1993

Short chain fatty acid-induced hyperventilation is due to PGF2-alpha.

While studying the significance of the short chain fatty acids (SCFAs) in the pathogenesis of hyperventilation, we have found that experimental rabbits injected with SCFA sodium salt (4 mmol/kg b.wt) develop hyperventilation 20 min later. This hyperventilation results in a decrease of PCO2 in the arterial blood from 32.05 +/- 1.18 to 24.55 +/- 0.83 (p < 0.001). The SCFAs also bring about pronounced mixed alkalosis. The prostaglandin F2-alpha (PGF2-alpha) in both the arterial and venous blood of rabbits increased significantly after treatment with SCFAs salts. If the rabbits are pretreated with indomethacin (10 mg/kg), the SCFAs do not cause hyperventilation. Therefore we can conclude, that the SCFAs bring about hyperventilation through an increase in the PGF2-alpha synthesis.

Alkalosis↗

PubMed2005

Structure-dependent and receptor-independent increase in osmotic fragility of rat erythrocytes by short-chain fatty acids.

We examined short-chain fatty acids (SCFAs) with 1 (C1) to 5 (C5) carbon atoms for osmotic fragility (OF) in isolated red blood cells (RBCs) in rats. The RBCs were used as prototypical plasma membrane model. The dense packed RBC was incubated in a phosphate-NaCl buffer solution containing each SCFA at 0 to 100 mM. The RBC suspensions were transferred into the OF test tubes containing NaCl from 0.2 to 0.9%. The hemoglobin concentration was determined and the EC50 in hemolysis was calculated. The OF in RBCs was dose-dependently increased by exposure to SCFAs, except for C1, with an increasing number of carbon atoms. Branched-chain fatty acids (isomers of C4 and C5) have a smaller effect on OF than straight-chain fatty acids (C4 and C5). The SCFA-induced increases in OF were not affected by pretreatment of RBCs with trypsin. The response of the RBC membrane to SCFAs depends on their concentration, carbon chain length and chain structure (straight or branched). The SCFAs probably disturb the lipid bilayer of the RBC membrane and result in a decrease in osmotic resistance. The plasma membrane in rat RBCs could respond to the structure of the SCFAs in detail by using the OF as an indicator.

Animals↗

PubMed2005

Effects of total enteral nutrition supplemented with a multi-fibre mix on faecal short-chain fatty acids and microbiota.

BACKGROUND AND AIMS: Impaired bowel function is frequent in tube-fed patients, and diarrhoea is associated with decreased faecal short-chain fatty acids (SCFAs) concentrations. The aim of this study was to compare the effects of a multi-fibre-enriched formula (15 g/l) and a fibre-free isoenergetic and isonitrogenous formula on faecal SCFAs and microbiota in long-term enteral nutrition (EN) patients. METHODS: Fifteen patients [11M/4F, aged 53 (40-73)] on total EN for 43 (1-310) months for dysphagia received a fibre-free formula for 7 days, followed in a random order by either the multi-fibre-enriched formula for 14 days and then the fibre-free formula for 14 days or vice versa. Stool samples were taken at the end of each period for measurement of SCFAs levels and different groups of bacteria. Results were compared with non-parametric tests. RESULTS: After the multi fibre EN, there was a significant median increase in total faecal SCFAs (+84%), butyrate (+20%) and acetate (+147%) compared with baseline. A significant increase in the total number of bacteria as determined with the molecular method was found after the multi-fibre EN period compared with the fibre-free EN period. There were no concomitant changes in the dominant groups of intestinal bacteria. CONCLUSION: In long-term EN patients, a polymeric enteral formula supplemented with a mixture of six fibres increases faecal SCFAs and total number of bacteria, which may contribute to an improved bowel function.

Adult↗

PubMed1988

Short-chain fatty acids stimulate ileal motility in humans.

We tested the hypothesis that short-chain fatty acids (SCFAs) and distention would stimulate ileal motility in humans. Intraluminal pressures in the ileocolonic region were recorded in 18 healthy human volunteers after instillation of boluses of SCFAs, air, and saline. Ileal motility was stimulated more often by SCFAs than by similar volumes of air or saline. Although increasing volumes of distention evoked greater numbers of contractions, this phenomenon was not apparent after repeated stimulation, suggesting that the "mechanoreceptor" in the human ileum has a refractory period. Symptoms of abdominal pain, cramps, and an urge to defecate may have resulted from instillation of SCFAs, even at small volumes. The motility stimulated in the ileum by SCFAs was not associated with systemic release of gastrointestinal regulatory peptides and was not affected by naloxone or indomethacin. Short-chain fatty acids, which can be considered as "markers" of colonic contents, might be associated with the motor response to coloileal reflux in humans.

Adult↗

PubMed1998

Short-chain fatty acids have polarized effects on sodium transport and intracellular pH in rabbit proximal colon.

BACKGROUND & AIMS: Short-chain fatty acids (SCFAs) stimulate colonic Na+ absorption, presumably by acidification of colonocytes and activation of apical Na+/H+ exchangers. It is unclear whether this effect depends on SCFA gradients across the colonic epithelium, and, if so, why. The aim of this study was to determine (1) whether SCFAs added unilaterally to either the apical or basolateral border of the cell have similar effects on intracellular pH (pHi); (2) whether SCFA gradients alter Na+ transport and; (3) what regulatory factors are involved in gradient-induced Na+ transport. METHODS: pHi was measured in intact epithelial rabbit proximal colon using the pH-sensitive indicator 2',7'-bis(carboxyethyl)-5-(6)-carboxyfluorescein, and Na+ transport was measured under short-circuit conditions. RESULTS: Apical and basolateral SCFAs had equivalent effects on decreasing pHi, but the recovery toward baseline was more vigorous after apical SCFAs. Gradients of both propionate and lactate (50 mmol/L [mucosal], 0 mmol/L [serosal]) stimulated electroneutral Na+ absorption, which was inhibited by bicarbonate, mucosal 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid, and Cl- removal. However, it was not blocked by amiloride. The differential response to a series of pharmacological agents showed that gradient-stimulated transport is distinct from epinephrine-stimulated electroneutral Na+ absorption. CONCLUSIONS: A physiological gradient of SCFAs across the colonic epithelium elicits polarized effects on both pHi and Na+ absorption that may be important determinants of colonic fluid transport.

Amiloride↗

PubMed1998

Effects of short-chain fatty acids on primary urothelial cells in culture: implications for intravesical use in enterocystoplasties.

The presence of inflammatory changes and mucopus production in an enterocystoplasty may be similar to the condition of diversion colitis and starvation diarrhea caused by a lack of luminal short-chain fatty acids (SCFAs). We postulate a therapeutic role for intravesical SCFA. Because this treatment will also contact the urothelium, we have assessed the effect on cellular proliferation by utilizing primary urothelial cells in culture. Primary urothelial cells were grown from biopsy samples of normal urothelium obtained intraoperatively. A cocktail of SCFA used in the treatment of diversion colitis was incubated with these cells for time intervals ranging from 30 minutes to 72 hours at drug concentrations ranging from 0.04 to 20 mmol/L butyrate equivalent (BE). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the residual viable biomass to assess growth inhibition. These experiments were repeated on cells grown on matrigel substrate. The human urothelial cancer line RT112 was likewise exposed to SCFAs to assess selectivity between primary and transformed cells. Primary urothelial cells in culture undergo growth inhibition when exposed to SCFAs. The concentration of SCFAs required to reduce the general biomass by 50% or more (IC> or =50) was 20 mmol/L BE when exposure was for 2 hours or less. When drug exposure was prolonged for 72 hours, the IC> or =50 was 2.5 mmol/L BE. Cells grown on matrigel had their growth similarly inhibited. The IC > or = 50 for the RT112 cell line was 2.5 mmol/L BE after 72 hours of drug incubation. Primary urothelial cells in culture undergo a time- and dose-dependent growth inhibition when exposed to SCFAs. This inhibition is particularly apparent at the higher doses similar to those in use in clinical practice. Cells grown on a matrigel substrate suffer growth attenuation similar to that affecting cells grown on polystyrene plates. In vivo assessment in a rodent intravesical model is advisable before considering instillations in patients.

Cell Division↗

PubMed1996

Induction of glutathione-S-transferase-pi by short-chain fatty acids in the intestinal cell line Caco-2.

Glutathione S-transferases (GSTs) are a multigene family of detoxification and metabolizing enzymes that have been linked with the susceptibility of tissues to environmental carcinogens. In addition to their role as the main energy source in the colonic mucosa, short-chain fatty acids (SCFAs) have been found to act as potent antiproliferative and differentiating agents in various cancer cell lines. The objective of this study was to evaluate the effects of SCFAs on the induction of GSTpi in the intestine as a possible new anticarcinogenic mechanism of SCFAs. Studies were performed in Caco-2 cells, a cell line resembling functionally normal enterocytes. Cells, cultured in DMEM supplemented with 10% fetal calf serum, were studied from day 0 dpc (days post confluence) until 21 dpc and culture. SCFAs (acetate, propionate, butyrate) were added to give a final concentration of 5 mmol L(-1). At 0, 3, 6, 9, 15, and 21 dpc, protein, lactate dehydrogenase (LDH), alkaline phosphatase (AP) and GSTpi were measured. Butyrate supplementation significantly (P < or = 0.01) increased GSTpi levels compared with controls in a concentration-dependent manner. The effect was detectable within 3 dpc with a maximum at 15 dpc. In contrast to butyrate, the other SCFAs tested had no (acetate) or little effect (propionate). In conclusion, the data suggest that the anticancer effect of butyrate in part may be based on the induction of GSTpi activity, resulting in an enhanced detoxification capacity of the gut.

Butyrates↗

PubMed2004

A novel bifunctionality: PAT1 and PAT2 mediate electrogenic proton/amino acid and electroneutral proton/fatty acid symport.

Recently, the PAT family of proton-dependent amino acid transporters has been identified as a novel class of mammalian amino acid symporters. PAT1 and PAT2 members mediate electrogenic uptake of small, neutral amino acids and derivatives by cotransport of protons. Analysis of the structural requirements for substrate recognition by PAT1 identified that a free amino group in a substrate is not essential for recognition. We therefore hypothesized that PAT1 and its ortholog PAT2 may also be able to recognize and transport the homologous short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. We examined in Xenopus laevis oocytes whether the SCFAs interact with the transporter by employing flux studies, electrophysiology and intracellular pH recordings. SCFAs did not induce positive inward currents but inhibited glycine-induced transport currents. PAT-mediated uptake of radiolabeled proline was also dose-dependently reduced by SCFA and could be described by first order competition kinetics with apparent Ki-values for butyrate of 6.0 +/- 0.7 and 7.6 +/- 1.3 mM for PAT1 and PAT2, respectively. Acetate as well as propionate uptake was significantly enhanced in oocytes expressing PAT1 or PAT2. An electroneutral H+/SCFA symport mode was demonstrated by recording intracellular pH changes under voltage clamp conditions with rate constants for the initial intracellular acidification in the presence of SCFAs significantly increased in PAT-expressing oocytes. In conclusion, our data demonstrate that the PAT1 and PAT2 proteins are capable to transport selected SCFAs in an electroneutral and the homologous amino acids in an electrogenic mode and are therefore a paradigm for bifunctional solute carriers.

Amino Acid Transport Systems↗

PubMed1997

Bacterial metabolites sodium butyrate and propionate inhibit epithelial cell growth in vitro.

The structural and functional barrier preventing the free advancement of microbial plaque subgingivally along the tooth surface is formed by the junctional epithelial (JE) cells directly attached to the tooth (DAT cells). The mechanism leading to degeneration of the DAT cells is not known. In the present study we examined the possible role of short chain fatty acids (SCFAs) on epithelial cells by making use of 2 epithelial cell cultures (HaCaT and ERM) and an explant culture model of human JE. The SCFAs butyrate and propionate were used in concentrations found in human plaque and gingival crevicular fluid (0.25-16.0 mM). The SCFAs had no effect on primary cell adhesion nor on the epithelial attachment apparatus (EAA). By contrast, even 0.25 mM of butyrate significantly retarded epithelial cell growth. Similar effects with propionate were first observed at concentrations higher than 1.0 mM. The retardation of epithelial cell growth was found to be due to inhibition of cell division. Furthermore, after butyrate treatment dense accumulations of intermediate filaments and cytoplasmic vacuolization were characteristically seen in cells adjacent to cells of normal appearance. This suggests that some cells of the growing epithelial cell population are more sensitive to the SCFAs than others, and agrees with previous reports on the DAT cells of periodontally-involved teeth in vivo. The results suggest that SCFAs are microbial factors that play a role in the initiation and progression of periodontal pocket formation by impairing epithelial cell function rather than having a direct effect on the EAA.

Analysis of Variance↗

PubMed1994

Chemical specificity of short-chain fatty acids in stimulating insulin and glucagon secretion in sheep.

The chemical specificity and structural requirements of short-chain fatty acids (SCFAs) in stimulating pancreatic endocrine responses was investigated in conscious sheep. Normal SCFAs with one to eight carbons were injected intravenously at seven doses of 39-2,500 mumol/kg body wt. The isomers or derivatives of SCFAs were administered at 625 mumol/kg body wt. Analysis of dose-response curves showed that n-butyric acid (4 carbons in the molecule) was most effective for both insulin and glucagon secretion among the normal SCFAs tested. In addition, one carboxylic group was absolutely required, since hormone secretion was significantly reduced or abolished with compounds in which the carboxylic element was replaced by other groups and with dicarboxylic acids. The form of the hydrocarbon chain (branched, cyclic, or benzoic ring) also affected hormone secretory activity. Most of the compounds that replaced hydrogen in the hydrocarbon chain by other groups at various positions reduced or abolished the hormone secretory effect obtained by n-butyric acid. In conclusion, a monocarboxylic acid with several numbers of hydrocarbons was required for insulin or glucagon secretion. These results suggest that the pancreatic endocrine system can recognize the chemical structure of SCFAs in detail and induce hormone secretion in sheep.

Animals↗

PubMed2006

The peristaltic reflex induced by short-chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF.

Short-chain fatty acids (SCFAs) accelerate colonic transit. This study examined whether this action was mediated by activation of the peristaltic reflex. SCFAs (acetate, butyrate, or propionate) were applied to the central compartment of a three-compartment flat-sheet preparation of the rat middle to distal colon. The release of serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and CGRP was measured in all three compartments. Ascending contraction and descending relaxation were measured in the orad and caudad compartments. The addition of SCFAs at physiological to supraphysiological concentrations (0.5-100 mM) to the central compartment elicited concentration-dependent ascending contraction and descending relaxation (EC50 approximately 5 mM). At this concentration, SCFAs induced an 8- to 11-fold increase in 5-HT release and a 2- to 3-fold increase in CGRP release in the central compartment only. They had no effect on BDNF release. CGRP release was inhibited by a 5-HT4 but not a 5-HT3 receptor antagonist. Ascending contraction and descending relaxation were also inhibited by 5-HT4 and by CGRP receptor antagonists added to the central compartment. 5-HT and CGRP release, as well as ascending contraction and descending relaxation induced by mechanical stimulation of the mucosa (2-8 strokes), were significantly augmented by 1 mM acetate. Acetate (1 mM) also doubled propulsive velocity in isolated whole segments of the guinea pig colon. In conclusion, chemical stimulation of the mucosa by SCFAs triggers a peristaltic reflex mediated by the release of 5-HT from mucosal cells and activation of 5-HT4 receptors on sensory CGRP-containing nerve terminals. This SCFA-induced peristaltic pathway augments the peristaltic reflex elicited by mechanical stimulation of the mucosa.

Acetic Acid↗

PubMed2004

Stereospecific regulation of tyrosine hydroxylase and proenkephalin genes by short-chain fatty acids in rat PC12 cells.

Circulating short-chain fatty acids (SCFAs) are primarily derived from bacterial fermentation of carbohydrates in the colon where they function as physiologic modulators of epithelial cell maturation. Butyrate has been shown to induce tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis, and enkephalin neuropeptide gene transcription, suggesting a role in perinatal sympathoadrenal stress-adaptation. We sought to determine whether there were SCFA structural requirements for this effect. Nine biologically relevant SCFAs and butyrate derivatives were tested in an in vitro model (PC12, rat pheochromocytoma cells) for their ability to regulate neurotransmitter-related gene expression. Our results revealed that among all the studied SCFAs, only propionate and butyrate increased tyrosine hydroxylase and proenkephalin mRNA levels. The functional activity was selective to the carbon atom chain length and associated with the presence of an ethyl moiety in the carbon atom backbone chain. Modifications or absence of this domain affected the gene induction response, suggesting a receptor-mediated mechanism(s). Moreover, propionate, butyrate, and the drug 4-phenylbutyrate were each shown to regulate transmitter genes via at least three independent mechanisms: histone hyperacetylation, cAMP signaling, or peroxisome proliferator-activated receptor gamma-mediated pathways. Thus, the biologic impact of SCFAs on catecholaminergic and opioid systems depend on the activation of SCFA-specific, dose-specific, and gene-specific molecular mechanisms. We speculate that 1) circulating levels of SCFAs may influence sympathoadrenal transmitter biosynthesis and hence whole animal stress-adaptive responsiveness after birth, and 2) the adverse effects of antibiotics on delayed acquisition of postnatal gut flora may affect this apparent evolutionary advantage of gut colonization.

Acetylation↗

PubMed2006

Evaluation of the effects of short-chain fatty acids and extracellular pH on bovine neutrophil function in vitro.

OBJECTIVE: To investigate the effects of short-chain fatty acids (SCFAs) and pH on neutrophil oxidative burst, phagocytosis, and morphology after exposure to acetate, propionate, butyrate, or succinate at pH 5.5 and 6.7. SAMPLE POPULATION: Neutrophils isolated from bovine blood samples and Porphyromonas levii, Prevotella spp, and Bacteroides fragilis isolated from lesions of cattle with acute interdigital phlegmon (foot rot). PROCEDURES: Bacteria were cultured in strictly anaerobic conditions. Bacterial SCFA production was measured with high-performance liquid chromatography. Neutrophils were isolated, stimulated with phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan (OZ), and incubated with dihydroethidium or dichlorofluorescein diacetate to measure production of O(2)and H(2)O(2), respectively. Phagocytosis was assessed after exposure to serum-opsonized bacteria. Cellular morphology was assessed with differential staining. RESULTS: All bacteria produced at least 3 of the 4 SCFAs. Production of both O(2) and H(2)O(2) was markedly curtailed in PMA-stimulated neutrophils exposed to SCFA at pH 5.5, compared with production at pH 6.7. Succinate caused a significant dose-dependent decrease in O(2) production at pH 6.7 in OZ-stimulated neutrophils. Monoprotic SCFAs elicited a significant increase in H(2)O(2) production in OZ-stimulated neutrophils at pH 6.7 but a significant decrease at pH 5.5. Monoprotic SCFAs significantly increased phagocytosis at pH 6.7 but decreased phagocytic activity at pH 5.5. Cellular necrosis was observed in cells exposed to SCFAs at pH 5.5. CONCLUSIONS AND CLINICAL RELEVANCE: Establishment and persistence of anaerobic bacteria in cattle with foot rot infection may result in part from neutrophil dysfunction secondary to the effects of bacterially secreted SCFA in acidotic microenvironments.

Analysis of Variance↗

PubMed1985

Short-chain fatty acids in the small-bowel bacterial overgrowth syndrome.

The short-chain fatty acids (SCFAs) have been measured by gas chromatography in fasting jejunal secretions, saliva, and feces from 8 patients with the small-bowel bacterial overgrowth syndrome (BO) and 9 control patients; in jejunal secretions and saliva from 6 healthy subjects; and in feces from 20 healthy subjects. The concentrations of SCFAs (median (range), mumol/l) in jejunal secretions of BO patients were as follows: total, 990 (210-12,370); acetic acid, 650 (170-6770); propionic acid, 110 (16-3070); isobutyric acid, 26 (1-310); n-butyric acid, 90 (12-1340); isovaleric acid, 35 (2-680); n-valeric acid, 7 (3-200). In BO patients the total concentration of SCFAs in jejunal secretions was approximately four times higher than in control patients (p less than 0.01) and in healthy subjects (p less than 0.025). The relative distribution of the acids resembled the distribution found in feces more than that of saliva or the normal jejunal secretions. These findings indicate that patients with BO have a colon-like flora in the small intestine and that the main part of the SCFAs in the jejunal secretions of these patients is produced by the altered microbial flora in the jejunum. Combined with other tests, analyses of intestinal SCFAs may prove to be valuable in the diagnosis of small-bowel bacterial overgrowth.

Adult↗

PubMed1985

Short-chain fatty acids in intestinal content of germfree mice monocontaminated with Escherichia coli or Clostridium difficile.

The short-chain fatty acids (SCFAs) have been analysed in coecal and small-intestinal content of conventional (CONV) and germfree (GF) mice, in germfree mice monocontaminated with Escherichia coli (MEC) or Clostridium difficile (MCD), and in germfree mice conventionalized by the visitor technique (EXG). The total concentrations of SCFAs in coecal content, measured by gas chromatography, were (mean (SD), mmol/kg): CONV, 125.2 (32.9); GF, 1.02 (0.39); MEC, 6.88 (0.76); MCD, 4.50 (0.12); and EXG, 115.6 (17.4). The concentrations of SCFAs were 3- to 25-fold higher in the coecum than in the small intestine in CONV, MEC, and EXG mice (p less than 0.05). The fermentation patterns (that is, the relative composition of the acids) of E. coli and Cl. difficile were distinctively different under defined in vitro conditions and similar to those found in intestinal content of monocontaminated animals. Combined gas chromatography and mass spectrometry showed that Cl. difficile produced an unusual metabolite, 2-methylbutyric acid, in vitro and in vivo. The findings indicate that the fermentation patterns are closely related to the bacteria. Variations in the bacterial flora may be more important in determining the concentrations and patterns of SCFAs in intestinal content than variations in the intake of substrate for SCFAs formation as dietary fibre.

Animals↗