The propionic acid and butyric acid in serum but not in feces are increased in patients with diarrhea-predominant irritable bowel syndrome.
ABSTRACT: BACKGROUND:Short-chain fatty acids (SCFAs) alteration have been reported in irritable bowel syndrome (IBS), but the results are conflicting. Our study aims to explore the alteration of SCFAs in patients with diarrhea-predominant IBS (IBS-D) and their potential role in the occurrence and development of IBS. METHODS:We recruited patients with IBS-D defined by Rome IV criteria and age-and-gender matched healthy controls (HCs). A headspace solid-phase microextraction gas chromatography-mass spectrometric (HS-SPME-GC-MS) method was developed for the analysis of acetic, propionic and butyric acid in feces and serum. RESULTS:Compared with HCs, the levels of the serum propionate (2.957?±?0.157 vs 2.843?±?0.098?mmol/L, P?=?0.012) and butyrate (2.798?±?0.126 vs 2.697?±?0.077?mmol/L, P?=?0.012) were significantly higher in IBS-D group. No significant differences were found among two groups with regard to the concentration of fecal acetate (4.953?±?1.065 vs 4.774?±?1.465?mg/g, P?=?0.679), propionate (6.342?±?1.005 vs 6.282?±?1.077?mg/g, P?=?0.868) and butyrate (2.984?±?0.512 vs 3.071?±?0.447?mg/g, P?=?0.607). CONCLUSIONS:Metabolites of gut microbiota, the propionic and butyric acid, are increased in patients with IBS-D in serum but not in feces. It suggests that propionic and butyric acid might be associated with the occurrence and development of IBS.
Project description:BACKGROUND:Recent studies indicate that gut microbiota disorders potentially contribute to the pathogenesis of irritable bowel syndrome (IBS), which can be partly reflected by fecal short-chain fatty acids (SCFAs) generated from gut microbiota. Previous studies on SCFA alterations in patients with IBS have yielded conflicting results. No prior systematic review has been conducted on the alterations in fecal SCFAs in IBS patients. AIMS:We performed a meta-analysis to explore and clarify alterations in fecal SCFAs in IBS patients. METHODS:Case-control studies, randomized controlled trials (RCTs), and self-controlled studies were identified through electronic database searches. The standardized mean difference (SMD) with 95% confidence interval (CI) in fecal SCFA levels between different groups was calculated. RESULTS:The proportion of fecal propionate in patients with IBS was significantly higher than in healthy controls (HCs) (SMD = 0.44, 95% CI = 0.12, 0.76). A subgroup analysis showed that the concentration of fecal propionate (SMD = -0.91, 95% CI = -1.41, -0.41) and butyrate (SMD = -0.53, 95% CI = -1.01, -0.04) in patients with constipation-predominant IBS (IBS-C) was significantly lower than that in HCs, and the concentration of fecal butyrate in patients with diarrhea-predominant IBS (IBS-D) was higher than that in HCs (SMD = 0.34, 95% CI = 0.00, 0.67). Finally, we found that restricted diets correlated with fecal butyrate reduction in IBS (SMD = -0.26, 95% CI = -0.51, -0.01). CONCLUSIONS:In terms of fecal SCFAs, there were differences between patients with IBS and HCs. In IBS-C patients, propionate and butyrate were reduced, whereas butyrate was increased in IBS-D patients in comparison to HCs. Propionate and butyrate could be used as biomarkers for IBS diagnosis.
Project description:<h4>Background</h4>Short-chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT.<h4>Methods</h4>This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30-g (superdonor feces), and 60-g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS-SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography.<h4>Key results</h4>The fecal butyric acid level was significantly increased after FMT in both the 30-g and 60-g groups (both P ? 0.001). In the 60-g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30-g and 60-g FMT groups were significantly inversely correlated with IBS-SSS and FAS scores (P = 0.001, r = -0.3 and P = 0.0001. r=- 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT.<h4>Conclusion and inferences</h4>FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini?caltr?ials.gov (NCT03822299).
Project description:Enterometabolic disturbances may cause meal-related symptoms. We performed a functional evaluation of the intestinal microflora in patients with unexplained, self-reported food hypersensitivity by measuring fecal short-chain fatty acids (SCFAs).Thirty-five consecutive patients with self-reported food hypersensitivity and 15 healthy volunteers of similar age, gender, and body mass index collected all feces for 72 hours. Fecal concentrations of acetic, propionic, n-butyric, i-butyric, n-valeric, i-valeric, n-caproic, and i-caproic acids were analyzed by gas-liquid chromatography. Concentrations and excretions (output) of SCFAs in patients and controls were compared and related to gastrointestinal symptoms.Despite nonsignificant differences between patients and controls for both total and individual SCFA concentrations and excretions, n-butyric acid comprised a higher (P = 0.035) and acetic acid a lower (P = 0.012) proportion of total SCFA in patients compared to controls. There were no significant correlations between symptom scores and concentrations or excretions of individual or total SCFAs, but the proportion of n-butyric acid was significantly higher in patients with severe symptoms compared to patients with moderate symptoms (P = 0.016).The results indicate an enterometabolic disturbance in patients with self-reported food hypersensitivity. Higher proportions of n-butyric acid may be related to abdominal symptom generation, but may also protect against organic bowel disease. Further studies are needed to clarify these aspects.
Project description:1. Sheep fed at a constant rate were infused intraruminally with [1-(14)C]-acetate, -propionate or -butyrate during 5hr. periods. 2. Volatile fatty acids were estimated in the rumen contents and steady-state conditions were obtained. 3. Of the butyric acid carbon 60% was in equilibrium with 20% of the acetic acid carbon, and 2-3g.atoms of carbon were interconverted/day. 4. Little interconversion took place between propionic acid, acetic acid or butyric acid. 5. The net production rates for acetic acid, propionic acid and butyric acid were 3.7, 1.0 and 0.7moles/day respectively. 6. The production of volatile fatty acids accounted for 80% of the animal's energy expenditure.
Project description:Short chain fatty acids (SCFAs) play an important role in the maintenance of colonic homeostasis, and their depletion has been reported in various gastrointestinal disorders. Inflammatory colorectal polyps (ICRPs) are a recently recognized disease specific to miniature dachshunds (MDs), and fecal dysbiosis with a reduction of SCFA-producing bacteria has been reported with this disease. Therefore, this study was performed based on the hypothesis that a reduced SCFA concentration associates with the development of ICRPs. We recruited 11 ICRP-affected MDs and 25 control MDs. Their fecal SCFA concentrations and bacterial proportions were quantified using high performance liquid chromatography and quantitative real-time PCR, respectively. The feces of ICRP-affected MDs contained lower amounts of propionic acid and lower proportions of Bifidobacterium than the feces of control MDs. Furthermore, fecal proportions of Bifidobacterium, Firmicutes and Lactobacillus exhibited significant positive correlations with fecal concentrations of total SCFAs and/or propionic acid; fecal Escherichia coli proportions correlated negatively with fecal concentrations of total SCFAs, as well as acetic, propionic and butyric acid. This result indicates an association between fecal dysbiosis and fecal SCFA concentrations; these phenomena may contribute to ICRP pathogenesis in MDs. Potential therapeutic targeting of the reduced propionic acid concentration using probiotics, prebiotics or SCFA enemas merits further study.
Project description:Candida albicans is the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemic C. albicans infections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to prevent C. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization of C. albicans. Our results indicate that cefoperazone-treated mice susceptible to C. albicans infection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, using in vivo concentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development of C. albicans in vitro. Collectively, results from this study suggest that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization of C. albicans.
Project description:Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism. Mice were infused in cecum with stably-labelled isotopes of the three main short chain fatty acids or control solution. After 6 hrs, livers were removed and pooled RNA samples were subjected to gene expression profiling.
Project description:BACKGROUND:Treatment with the α-glucosidase inhibitor acarbose increases median lifespan by approximately 20% in male mice and 5% in females. This longevity extension differs from dietary restriction based on a number of features, including the relatively small effects on weight and the sex-specificity of the lifespan effect. By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites. RESULTS:Microbial communities and the concentrations of SCFAs in the feces of mice treated with acarbose were notably different from those of control mice. At all three study sites, the bloom of a single bacterial taxon was the most obvious response to acarbose treatment. The blooming populations were classified to the largely uncultured Bacteroidales family Muribaculaceae and were the same taxonomic unit at two of the three sites. Propionate concentrations in feces were consistently elevated in treated mice, while the concentrations of acetate and butyrate reflected a dependence on study site. Across all samples, Muribaculaceae abundance was strongly correlated with propionate and community composition was an important predictor of SCFA concentrations. Cox proportional hazards regression showed that the fecal concentrations of acetate, butyrate, and propionate were, together, predictive of mouse longevity even while controlling for sex, site, and acarbose. CONCLUSION:We observed a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the responses illustrate the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, testing causal roles of SCFAs in the observed effects of acarbose.
Project description:Short chain fatty acids (SCFAs), such as acetate, butyrate and propionate, are products of microbial macronutrients fermentation that distribute systemically and are believed to modulate host immune responses. Recent data have indicated that certain SCFAs, such as butyrate and propionate, directly modulate human dendritic cell (DC) function. Given the role of DCs in initiating and shaping the adaptive immune response, we now explore how SCFAs affect the activation of antigen-specific CD8+ T cells stimulated with autologous, MART1 peptide-pulsed DC. We show that butyrate reduces the frequency of peptide-specific CD8+ T cells and, together with propionate, inhibit the activity of those cells. On the contrary, acetate does not affect them. Importantly, butyrate and propionate inhibit the production of IL-12 and IL-23 in the DCs and exogenous IL-12 fully restores the activation of the MART-1-specific CD8+ T cells, whereas IL-23 has no effect. In conclusion, these results point to a pivotal role of butyrate and propionate in modulating CD8+ T cell activation via the inhibition of IL-12 secretion from DCs. These findings reveal a novel mechanism whereby bacterial fermentation products may modulate CD8+ T cell function with possible implications in anti-cancer immunotherapy.
Project description:BACKGROUND:Actinomyces oris is an early colonizer and has two types of fimbriae on its cell surface, type 1 fimbriae (FimP and FimQ) and type 2 fimbriae (FimA and FimB), which contribute to the attachment and coaggregation with other bacteria and the formation of biofilm on the tooth surface, respectively. Short-chain fatty acids (SCFAs) are metabolic products of oral bacteria including A. oris and regulate pH in dental plaques. To clarify the relationship between SCFAs and fimbrillins, effects of SCFAs on the initial attachment and colonization (INAC) assay using A. oris wild type and fimbriae mutants was investigated. INAC assays using A. oris MG1 strain cells were performed with SCFAs (acetic, butyric, propionic, valeric and lactic acids) or a mixture of them on human saliva-coated 6-well plates incubated in TSB with 0.25% sucrose for 1?h. The INAC was assessed by staining live and dead cells that were visualized with a confocal microscope. RESULTS:Among the SCFAs, acetic, butyric and propionic acids and a mixture of acetic, butyric and propionic acids induced the type 1 and type 2 fimbriae-dependent and independent INAC by live A. oris, but these cells did not interact with streptococci. The main effects might be dependent on the levels of the non-ionized acid forms of the SCFAs in acidic stress conditions. GroEL was also found to be a contributor to the FimA-independent INAC by live A. oris cells stimulated with non-ionized acid. CONCLUSION:SCFAs affect the INAC-associated activities of the A. oris fimbrillins and non-fimbrillins during ionized and non-ionized acid formations in the form of co-culturing with other bacteria in the dental plaque but not impact the interaction of A. oris with streptococci.