Short-chain Fatty Acids Group Research Articles

Fecal short-chain fatty acids and obesity in a community-based Japanese population: The DOSANCO Health Study

In Western populations, fecal concentrations of short-chain fatty acids (SCFAs) are positively correlated with the prevalence of obesity. However, gut microbiota involved in the production of SCFA varies between races. Our purpose was to investigate the associations between fecal SCFAs and the prevalence of obesity in a community-based Japanese population. We classified a total of 568 participants aged ≥18 into four quartiles of fecal concentrations of SCFA subtypes (acetate, butyrate, and propionate) and total SCFAs to compare the prevalence of obesity, defined as a body mass index ≥ 25.0 kg/m2. Using the first quartile SCFA group as a reference, the prevalence ratios of obesity were calculated for each SCFA group through a log-binomial regression model adjusted for major potentially confounding factors including age, sex, exercise habits, total energy intake, and total dietary fiber intake. In the study population, the prevalence of obesity was 35.8%. The prevalence ratios (95% confidence intervals) of obesity in the second, third, and fourth quartile groups of fecal total SCFAs were 1.30 (0.89–1.89), 1.74 (1.23–2.47) and 1.70 (1.19–2.41), respectively, after adjusting for the confounders. Similar positive associations were observed for every subtype. The prevalence ratios (95% confidence intervals) in the fourth quartile groups of fecal acetate, butyrate, and propionate were 1.41 (1.02–1.97), 2.16 (1.49–3.14), and 1.97 (1.35–2.89), respectively, after adjusting for the confounders. In conclusion, our results demonstrated that fecal SCFA concentrations of every subtype were positively associated with the prevalence of obesity in a community-based Japanese population.

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.

The Effects of Short-Chain Fatty Acids on Rat Colonic Hypermotility Induced by Water Avoidance Stress.

PurposeShort-chain fatty acids (SCFAs) have been reported to play an important role in regulating gastrointestinal motility. The aim of this study is to investigate the possible role of SCFAs in water avoidance stress-induced colonic hypermotility.MethodsA rat IBS model was established by water avoidance stress (WAS). Intestinal motility was assessed by fecal pellets expulsion. The fecal SCFA level was detected using gas chromatography-mass spectrometry (GC-MS). Western blotting was performed to assess the expression of SCFAs receptors. To determine the role of SCFAs in gut dysmotility, the rats of the WAS+SCFAS and SCFAs group were administrated with oral SCFAs. The colonic contractile activity was recorded with a RM6240 multichannel physiological signal system.Key ResultsWAS induced gastrointestinal hypermotility and increased defecation in rats. After repeated stress, the fecal SCFAs decreased significantly and the proportion of acetic acid, propionic acid, and butyric acid had changed from Control 2.6:1:1.5 to WAS 2:1:2.3. Protein levels of SCFAs receptors in the colon were promoted by WAS. In addition, oral SCFAs partly inhibited the colonic spontaneous motility both for SCFAs and WAS+SCFAs group in vivo. Meanwhile, we observed acetate had no effect on the contractile amplitudes of muscle strips, but it could slow down contractile frequency in a dose-dependent manner (1–100 mM). Propionate significantly inhibited the motor activity of colonic strips (1–30 mM). Butyrate inhibited the contractile amplitude of CM strips in a dose-dependent manner (1–30 mM), but for LM, it exhibited a stimulating effect at low concentrations of butyrate 1 mM–10 mM and was suppressed at high concentrations of 30 mM butyrate. Total SCFAs increased the contractile amplitude at low concentration (5–50 mM) and inhibited it at high concentration (50–150 mM). All SCFAs slowed down the frequency of colonic activity.ConclusionThe stress-induced colonic hypermotility by WAS could be ameliorated through oral SCFA supplementation. SCFAs may have potential clinical therapeutic use in modulating gut motility.

Oral administration of short chain fatty acids could attenuate fat deposition of pigs.

Short chain fatty acids (SCFAs) are the main products of indigestible carbohydrates that are fermented by microbiota in the hindgut. This study was designed to investigate the effects of oral SCFAs administration on the lipid metabolism of weaned pigs. A total of 21 barrows were randomly allocated into three groups, including control group (orally infused with 200 mL physiological saline per day), low dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 20.04 mM, propionic acid 7.71 mM and butyric acid 4.89 mM per day), and high dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 40.08 mM, propionic acid 15.42 mM and butyric acid 9.78 mM per day). The results showed that the average daily feed intake of SCFAs groups were lower than that of control group (P<0.05). Oral administration of SCFAs decreased the concentrations of triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol and insulin (P<0.05), and increased the leptin concentration in serum (P<0.05). The total fat, as well as TC and TG levels in liver, was decreased by oral SCFAs administration (P<0.05). In addition, SCFAs down-regulated the mRNA expressions of fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (P<0.05), and enhanced the mRNA expression of carnitine palmitoyltransferase-1α (CPT-1α) in liver (P<0.05). SCFAs also decreased FAS, acetyl-CoA carboxylase (ACC) and peroxisome proliferator activated receptor σ mRNA expressions in longissimus dorsi (P<0.05). And in abdominal fat, SCFAs reduced FAS and ACC mRNA expressions (P<0.05), and increased CPT-1α mRNA expression (P<0.05). These results suggested that oral administration of SCFAs could attenuate fat deposition in weaned pigs via reducing lipogenesis and enhancing lipolysis of different tissues.

Changes throughout lactation in phenotypic and genetic correlations between methane emissions and milk fatty acid contents predicted from milk mid-infrared spectra

The aim of this study was to estimate phenotypic and genetic correlations between methane production (Mp) and milk fatty acid contents of first-parity Walloon Holstein cows throughout lactation. Calibration equations predicting daily Mp (g/d) and milk fatty acid contents (g/100 dL of milk) were applied on milk mid-infrared spectra related to Walloon milk recording. A total of 241,236 predictions of Mp and milk fatty acids were used. These data were collected between 5 and 305 d in milk in 33,555 first-parity Holstein cows from 626 herds. Pedigree data included 109,975 animals. Bivariate (i.e., Mp and a fatty acid trait) random regression test-day models were developed to estimate phenotypic and genetic parameters of Mp and milk fatty acids. Individual short-chain fatty acids (SCFA) and groups of saturated fatty acids, SCFA, and medium-chain fatty acids showed positive phenotypic and genetic correlations with Mp (from 0.10 to 0.16 and from 0.23 to 0.30 for phenotypic and genetic correlations, respectively), whereas individual long-chain fatty acids (LCFA), and groups of LCFA, monounsaturated fatty acids, and unsaturated fatty acids showed null to positive phenotypic and genetic correlations with Mp (from −0.03 to 0.13 and from −0.02 to 0.32 for phenotypic and genetic correlations, respectively). However, these correlations changed throughout lactation. First, de novo individual and group fatty acids (i.e., C4:0, C6:0, C8:0, C10:0, C12:0, C14:0, SCFA group) showed low phenotypic or genetic correlations (or both) in early lactation and higher at the end of lactation. In contrast, phenotypic and genetic correlations between Mp and C16:0, which could be de novo synthetized or derived from blood lipids, were more stable during lactation. This fatty acid is the most abundant fatty acid of the saturated fatty acid and medium-chain fatty acid groups of which correlations with Mp showed the same pattern across lactation. Phenotypic and genetic correlations between Mp and C17:0 and C18:0 were low in early lactation and increased afterward. Phenotypic and genetic correlations between Mp and C18:1 cis-9 originating from the blood lipids were negative in early lactation and increased afterward to become null from 18 wk until the end of lactation. Correlations between Mp and groups of LCFA, monounsaturated fatty acids, and unsaturated fatty acids showed a similar or intermediate pattern across lactation compared with fatty acids that compose them. Finally, these results indicate that correlations between Mp and milk fatty acids vary following lactation stage of the cow, a fact still often ignored when trying to predict Mp from milk fatty acid profile.

Glutamine alone or combined with short-chain fatty acids fails to enhance gut adaptation after massive enterectomy in rats&lt;A NAME="volta1"&gt;&lt;/A&gt;

To investigate the effect of oral glutamine alone or combined with short chain fatty acids (SCFA) in the intestinal adaptation of rats submitted to an massive enterectomy. After receiving 70% small bowel resection, 30 Wistar rats were randomized to received either standard rat chow (control group, n=10) or the same diet supplemented with 3,05% of glutamine alone (glutamine group, n=10) or combined with a solution containing SCFA (glutamine+SCFA group, n=10). Animals were killed on the 14th postoperative day. Mucosal weight, crypt depth, villus height, wall width, and the mucosal content of DNA, were assessed in basal conditions (resected gut specimen) and compared to the small bowel specimen collected on the postoperative day 14, at both jejunum and ileum sites. All groups presented similar pattern in weight evolution. In all groups, both the morphological findings and the DNA content were significantly higher at the end of the experiment than in basal conditions, at both the jejunum and ileum. Except for the jejunum wall width that was higher in control group (808+/-95 micro) than in the other two groups (glutamine = 649+/-88 micro and glutamine+SCFA = 656+/-92; p<0.01), there was no difference among them in all variables at both intestinal sites after 14 days. All groups presented adaptation of the intestinal mucosa in the remnant gut. Glutamine combined or not with short chain fatty acids fails to influence the adaptive response of the small bowel.

Short-chain fatty acid-supplemented total parenteral nutrition enhances functional adaptation to intestinal resection in rats

BACKGROUND & AIMS: Intestinal adaptation is a complex physiological process that is not completely understood. Total parenteral nutrition (TPN) induces intestinal atrophy that is prevented by the systemic administration of short-chain fatty acids (SCFAs) as measured by morphological indices (i.e., mucosal weight and mucosal DNA, RNA, and protein concentration). The aim of this study was to examine the effect of SCFA-supplemented TPN on functional markers of intestinal adaptation.METHODS: Forty-eight male Sprague-Dawley rats underwent an 80% jejunoileal resection and jugular catheterization. Rats received standard TPN or an isoenergetic, isonitrogenous TPN supplemented with SCFA (TPN + SCFA). Animals were further randomized to receive nutrient solutions for 3 or 7 days.RESULTS: Ileal uptakes of D-glucose were higher (P < 0.05) in both TPN + SCFA groups. Expression of glucose transporter (GLUT)2 messenger RNA (mRNA) was higher (P < 0.007) in the TPN + SCFA group at day 3. Expression of sodium-dependent glucose transporter 1 tended to be higher in both TPN + SCFA groups (P = 0.1). Na+,K+-adenosine triphosphatase mRNA was significantly more abundant in the TPN groups. GLUT5 and sucrase-isomaltase mRNA abundance did not differ between groups.CONCLUSIONS: Intravenous SCFAs facilitate intestinal adaptation after resection by increasing basolateral intestinal nutrient transport. The addition of SCFAs to current TPN formulations may be warranted to improve functional characteristics of the gastrointestinal tract.(Gastroenterology 1997 Mar;112(3):792-802)

Treatment of diversion colitis by short-chain fatty acids

Diminished production of short-chain fatty acids (SCFA) by altered flora has been suggested in the pathogenesis of diversion colitis (DC). We evaluated prospectively the effectiveness of SCFA irrigation in 13 patients with excluded colon (eight males, five females; mean age, 48 years). The causes of diversion were inflammatory bowel disease (n = 4), colonic cancer (n = 2), sigmoid diverticulitis with perforation (n = 3), ischiorectal abscess (n = 2), and miscellaneous (n = 2). Patients were given, twice a day for 14 days in a double-blind manner, a 60-ml enema containing either SCFA (acetate: 60 mmol/liter; propionate: 30 mmol/liter; and N-butyrate: 40 mmol/liter) (Group 1; n = 7) or isotonic NaCl (Group 2; n = 6). Endoscopy with biopsies was performed before starting the trial (D1) and 14 days later (D14). On D1 all patients had endoscopic and histologic findings suggestive of DC. No endoscopic or histologic changes were observed on D14 in either group. We conclude that endoscopic and histologic lesions of DC were not improved by SCFA irrigation during the 14 days.

Stimulation of Intestinal Mucosal Growth with Intracolonic Infusion of Short‐Chain Fatty Acids

Dietary fiber, which stimulates intestinal mucosal growth, is fermented by anaerobic bacteria in the rat hindgut to the short-chain fatty acids (SCFA) acetate, propionate, and butyrate. Butyrate is the preferred oxidative fuel of the colonocyte in vitro, and the provision of preferred intestinal fuels has been shown to stimulate mucosal proliferation in vivo. This study determined whether chronic colonic infusion of butyrate or a combination of SCFA would stimulate intestinal mucosal growth in an animal deprived of its normal source of SCFA, fiber fermentation in the cecum. Adult male Sprague-Dawley rats were fed a fat- and fiber-free elemental liquid diet and underwent cecectomy, ileocolic anastomosis, and insertion of a proximal colonic infusion catheter. Rats were then assigned to receive either a continuous infusion of butyrate (20 mM, 40 mM, or 150 mM), SCFA (70 mM acetate + 35 mM propionate + 20 mM butyrate), or saline, or to receive no infusion. A seventh group underwent proximal colonic transection and reanastomosis. After 7 days, jejunal, ileal, and proximal colonic segments were analyzed for mucosal weight, protein, RNA, and DNA. In the colon, the 40-mM butyrate infusion resulted in significant elevations in all mucosal parameters relative to all three control groups, saline infusion, no infusion, and transection. Both the 20-mM butyrate and the SCFA groups showed increased colonic mucosal DNA compared to controls. In the jejunum and ileum, mucosal DNA content was significantly greater in the SCFA group than in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)