Short-chain Fatty Acids In Rats Research Articles

Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs). Propionic acid (PPA) and its related short-chain fatty acids (SCFAs) are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio). SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible environmental agents that can trigger ASDs or ASD-related behaviors and deserve further exploration in basic science, agriculture, and clinical medicine.

4'ガラクトシルラクトースのマウス・ラットの盲腸内フローラおよび短鎖脂肪酸に及ぼす影響

4'ガラクトシルラクトースのマウス・ラットの盲腸内フローラおよび短鎖脂肪酸に及ぼす影響

Determination of Short-chain Fatty Acids in Rat and Human Feces by High-Performance Liquid Chromatography with Electrochemical Detection

A simple method for determining short-chain fatty acids (SCFAs) in rat and human feces was developed using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). A two-channel HPLC-ECD system was fabricated using an ion exclusion column and an electrochemical detector with a glassy carbon working electrode. Aqueous solutions of 0.1 mM HClO(4) and of ethanol containing 2-methyl-1,4-naphthoquinone served as a mobile phase and a quinone solution, respectively. Peak areas for lactic, acetic, propionic, butyric, isovaleric, and valeric acids at a detection potential of -0.9 V vs. an Ag/AgCl electrode showed a linear relationship with the acid amount in the range 0.1 to 40 nmol. Standard acids at 4 nmol were determined ten times with relative standard deviations (RSD) of less than 2.0%. The analytical results of healthy human feces were measured within 35 min. RSD (n = 5) in all SCFAs were less than 2.7%, and recoveries of SCFAs were more than 92%. The present method was characterized by reproducibility with the simple and rapid procedure without derivatization of analytes, and it has the potential for clinical and biomedical applications.

Biochemical Intestinal Parameters in Germ‐free Minipigs and Rats and in Ex‐germ‐free Minipigs and Rats Monoassociated with Escherichia coli

Intestinal contents of newborn and young germ-free minipigs and germ-free rats were investigated for the following biochemical parameters - conversion of cholesterol to coprostanol, degradation of beta-aspartylglycine, level of tryptic activity, formation of urobilinogen and the profile of short-chain fatty acids. Additionally, germ-free minipigs and germ-free rats were monoassociated with non-pathogenic strains of Escherichia coli and were investigated for the same biochemical parameters. The conversion of cholesterol to coprostanol, degradation of beta-aspartylglycine, tryptic activity and the short-chain fatty acid profile were similar to those found in previous studies in germ-free animals. Slightly higher amounts of urobilinogen than in the other species investigated so far were found in samples from germ-free and monoassociated minipigs. Except for the total amount of short-chain fatty acids in rats, monoassociation with E. coli did not alter any of the parameters either in the minipigs or in the rats.

Improvement of Colonic Healing by Preoperative Rectal Irrigation With Short-Chain Fatty Acids in Rats Given Radiotherapy

We investigated the effect of preoperative rectal irrigation with short-chain fatty acids on irradiated colonic anastomosis in rats. Sixty male Wistar rats were divided into four groups. Group I (control group, n = 15) underwent left colon resection and primary anastomosis. Group II (Short-chain fatty acids pretreatment group, n = 15) had short-chain fatty acids rectal irrigation for five days preoperatively. Group III (preoperative radiotherapy group, n = 15) underwent irradiation to the whole pelvis eight and four days before the operation, for a total dose of 20 Gy. Group IV (preoperative radiotherapy group + short-chain fatty acids pretreatment group, n = 15) had rectal irrigation with short-chain fatty acids for five days after the second irradiation. Within each group, animals were anesthetized to assess the clinical, mechanical, histologic, and biochemical parameters of anastomotic healing on either the third or seventh postoperative days. The mean bursting pressure was significantly low in Group III on Day 3 and was significantly high in Group IV on Day 7 (P = 0.001, P = 0.021). The burst occurred at the anastomoses in all animals tested on the third postoperative day, and outside of the anastomoses in all animals tested on the seventh postoperative day. The histologic parameters of anastomotic healing, such as epithelial regeneration and formation of granulation tissue, were significantly improved by use of preoperative rectal irrigation with short-chain fatty acids on Day 7. The amount of total and salt-soluble collagen concentrations significantly increased in Group IV compared with the control group on Day 3 (P = 0.008, P = 0.004). Some mechanical and histologic aspects of colonic anastomotic healing can be adversely affected by preoperative radiotherapy, but rectal irrigation with short-chain fatty acids may improve anastomotic healing.

A Novel Barley Cultivar (Himalaya 292) with a Specific Gene Mutation in Starch Synthase IIa Raises Large Bowel Starch and Short-Chain Fatty Acids in Rats

Himalaya 292 (Hordeum vulgare, var. himalaya 292) is a novel, hull-less barley cultivar with a single nucleotide change in the gene encoding starch synthase IIa (EC 2.4.1.21). This leads to loss of enzyme activity, resulting in a grain with less total starch and a higher proportion of amylose. These changes, plus higher total and soluble nonstarch polysaccharides (NSP), could increase its resistant starch (RS) content. Accordingly, rats were fed a diet containing stabilized whole-grain barley flours from Himalaya 292 or two commercial varieties (Namoi or Waxiro) or wheat or oat bran at equivalent NSP concentrations for 14 d. There were favorable significant changes in a number of bowel health-related indices. Fecal output by rats fed Himalaya 292 was higher than by those fed Namoi or oat bran, whereas total large bowel digesta mass was higher than in those fed WAXIRO: Cecal starch concentrations and pools were higher in rats fed Himalaya 292 than in all other groups. Fecal and cecal digesta pH was lower in rats fed Himalaya 292 than in all other groups except that fed oat bran. Colonic digesta pH was lower in rats fed Himalaya 292 than in those fed wheat bran or NAMOI: Fecal total SCFA excretion was higher in rats fed Himalaya 292 than in those fed Namoi or oat bran. Although cecal total SCFA pools did not differ among groups, colonic SCFA were higher in rats fed Himalaya 292 than in those fed Namoi or WAXIRO: These data indicate that changes in Himalaya 292 grain composition result in greater RS with consequent alterations in large bowel SCFA and pH when fed to rats.

Feeding resistant starch affects fecal and cecal microflora and short-chain fatty acids in rats.

The effects of different forms of resistant potato starch (RS) on the major microbial population groups and short-chain fatty acids (SCFA) in the cecum and feces of rats were studied over a 5-mo feeding period. Thirty 8-wk-old male Wistar rats, averaging 210 g initial body weight, were adapted for 7 d to a balanced basal diet containing 60% waxy maize starch devoid of any RS. On d 8, three groups of 10 rats each were fed diets containing the following forms of starch: 1) rapidly digestible waxy maize starch (basal diet), 2) a mixture of 83.3% waxy maize starch and 16.7% native granular potato starch (RS 1), or 3) a mixture of 33.3% waxy maize starch and 66.7% modified potato starch (RS 2). The final RS content in RS 1 and RS 2 was 10%. Fecal samples were collected at d 8 and 1, 3, and 5 mo after the start of the experiment. Cecal contents were taken after 5 mo. The colony counts of microbial groups did not vary with time in the control or the RS 1 group (P > .05). Only the number of Bacteroides/fusobacteria decreased between mo 1 and 5 in rats fed RS 1 (P < .05). The RS 2 diet led to a significant increase in total culturable bacteria, lactobacilli, streptococci, and enterobacteria between mo 1 and 5. The RS 1 and RS 2 diets stimulated the growth of bifidobacteria. Cecal numbers of lactobacilli, streptococci, and enterobacteria were higher in rats fed RS 2 than in rats fed RS 1 or control diet (P < .05). Lactobacillus cellobiosus occurred only in rats fed RS 1 or RS 2. Acetate increased in mo 3 compared with d 8 in all groups (P < .05). The fecal and cecal SCFA displayed higher concentrations of acetate and propionate and a higher molar proportion of propionate in RS 2 than in RS 1 or control rats (P < .05). Stimulation of bifidobacteria, lactobacilli, and SCFA may be useful for the suppression of pathogenic organisms in the colon.

Effect of Dietary Corn Oil, Butter and Beef Tallow on the Cecal Microflora and Short-Chain Fatty Acids in Rats

Effect of Dietary Corn Oil, Butter and Beef Tallow on the Cecal Microflora and Short-Chain Fatty Acids in Rats

Determination of portal short-chain fatty acids in rats fed various dietary fibers by capillary gas chromatography.

A simple, rapid and sensitive capillary gas chromatographic method was investigated to measure portal short-chain fatty acids (SCFAs). A 20-microliters sample of portal plasma was denatured with sulfosalicylic acid and then extracted with diethyl ether before the removal of protein precipitate. The resultant extract was concentrated by a transfer to 50 microliters of 0.2 M NaOH, thus avoiding tedious further concentration steps. This reduced the sample volume to one-fourth. Since the ratio of acetic acid, a major SCFA, to other acids varies widely, ranging from 10-fold to 100-fold, acrylic and methacrylic acids were used as internal standards to simultaneously measure SCFAs having a carbon number of 2-6. As a result, good recovery (90.38-103.17%) and reproducibility (coefficient of variation 0.83-8.85%) were observed over a wide range. Furthermore, portal SCFAs in rats fed various dietary fibers were determined by the present method. We showed that the amounts not only of the major acids such as acetic acid and propionic acid, but also of the minor fermented products such as n-valeric acid and n-caproic acid, could be significantly changed by dietary manipulation. Thus, the present method is simple and reliable, and requires only a small amount of sample.

Effects of high dietary cellulose on the large intestinal microflora and short-chain fatty acids in rats

Wistar rats fed diets containing different contents of cellulose or 5% transgalactosylated oligosaccharides (TOS) for 7 weeks were examined for faecal microflora and caecal short-chain fatty acids. High (15 %) cellulose diet showed remarkable increases in concentrations of faecal bifidobacteria and caecal butyrate with a reduced concentration of propionate as compared with the other diets. TOS-fed rats showed strikingly increased concentrations of bifidobacteria and acetate. A comparison of pH values between the caecal contents and faeces suggested more fermentation of cellulose in the distal than proximal part of the large bowel of rats

Erratum to : Effects of 4'-Galactosyllactose on the Cecal Microflora and Short-Chain Fatty Acids in Rats and Mice

Erratum to : Effects of 4'-Galactosyllactose on the Cecal Microflora and Short-Chain Fatty Acids in Rats and Mice

The effect of dietary mannitol on the caecal microflora and short-chain fatty acids in rats

Wistar rats fed 5%-mannitol diet showed significant decreases of viridans streptococci and bifidobacteria, and a remarkable increase of butyric acid concentration and a decrease of acetic acid in the caecal contents compared with the sucrose and basal diet groups. Stocky fusiform bacteria were increased in concentration in the rats on mannitol compared with the other groups.

An increase in cerebral benzodiazepine receptors induced by a subacute administration of ammonia, mercaptans and short-chain fatty acids in rats.

1. In the search to identify peripheral toxins which could be responsible for the supersensitivity of brain benzodiazepine receptors in experimental models of hepatic encephalopathy, [3H]diazepam-binding studies have been performed on brain tissues of normal rats treated with ammonium chloride, dimethyldisulphide and octanoic acid administered alone or in combination. 2. The subacute administration of the three toxins in combination induced a 30% increase in the number of benzodiazepine recognition sites. The administration of these toxins alone or in combination showed that this increase was mainly linked to the synergistic action of dimethyldisulphide or octanoic acid with ammonia, since dimethyldisulphide plus octanoic acid was ineffective. 3. These observations seem to reinforce the suggestion that these three toxins are able to induce neurochemical derangements similar to those described in experimental hepatic encephalopathy.