Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans.
ABSTRACT: Short-chain fatty acids (SCFA) are produced by colonic microbiota from dietary carbohydrates and proteins that reach the colon. It has been suggested that SCFA may promote obesity via increased colonic energy availability. Recent studies suggest obese humans have higher faecal SCFA than lean, but it is unclear whether this difference is due to increased SCFA production or reduced absorption.To compare rectal SCFA absorption, dietary intake and faecal microbial profile in lean (LN) versus overweight and obese (OWO) individuals.Eleven LN and eleven OWO individuals completed a 3-day diet record, provided a fresh faecal sample and had SCFA absorption measured using the rectal dialysis bag method. The procedures were repeated after 2 weeks.Age-adjusted faecal SCFA concentration was significantly higher in OWO than LN individuals (81.3±7.4 vs 64.1±10.4?mmol?kg(-1), P=0.023). SCFA absorption (24.4±0.8% vs 24.7±1.2%, respectively, P=0.787) and dietary intakes were similar between the groups, except for a higher fat intake in OWO individuals. However, fat intake did not correlate with SCFAs or bacterial abundance. OWO individuals had higher relative Firmicutes abundance (83.1±4.1 vs 69.5±5.8%, respectively, P=0.008) and a higher Firmicutes:Bacteriodetes ratio (P=0.023) than LN individuals. There was a positive correlation between Firmicutes and faecal SCFA within the whole group (r=0.507, P=0.044), with a stronger correlation after adjusting for available carbohydrate (r=0.615, P=0.005).The higher faecal SCFA in OWO individuals is not because of differences in SCFA absorption or diet. Our results are consistent with the hypothesis that OWO individuals produce more colonic SCFA than LN individuals because of differences in colonic microbiota. However, further studies are needed to prove this.
Project description:BACKGROUND/OBJECTIVES: High dietary fibre intakes may protect against obesity by influencing colonic fermentation and the colonic microbiota. Though, recent studies suggest that increased colonic fermentation contributes to adiposity. Diet influences the composition of the gut microbiota. Previous research has not evaluated dietary intakes, body mass index (BMI), faecal microbiota and short chain fatty acid (SCFA) in the same cohort. Our objectives were to compare dietary intakes, faecal SCFA concentrations and gut microbial profiles in healthy lean (LN, BMI?25) and overweight or obese (OWOB, BMI>25) participants. DESIGN: We collected demographic information, 3-day diet records, physical activity questionnaires and breath and faecal samples from 94 participants of whom 52 were LN and 42 OWOB. RESULTS: Dietary intakes and physical activity levels did not differ significantly between groups. OWOB participants had higher faecal acetate (P=0.05), propionate (P=0.03), butyrate (P=0.05), valerate (P=0.03) and total short chain fatty acid (SCFA; P=0.02) concentrations than LN. No significant differences in Firmicutes to Bacteroides/Prevotella (F:B) ratio was observed between groups. However, in the entire cohort, Bacteroides/Prevotella counts were negatively correlated with faecal total SCFA (r=-0.32, P=0.002) and F:B ratio was positively correlated with faecal total SCFA (r=0.42, P<0.0001). Principal component analysis identified distinct gut microbiota and SCFA-F:B ratio components, which together accounted for 59% of the variation. F:B ratio loaded with the SCFA and not with the microbiota suggesting that SCFA and F:B ratio vary together and may be interrelated. CONCLUSIONS: The results support the hypothesis that colonic fermentation patterns may be altered, leading to different faecal SCFA concentrations in OWOB compared with LN humans. More in-depth studies looking at the metabolic fate of SCFA produced in LN and OWOB participants are needed in order to determine the role of SCFA in obesity.
Project description:BACKGROUND/OBJECTIVES:Colonic fermentation of dietary fiber to short-chain fatty acids (SCFA) may protect against obesity and diabetes, but excess production of colonic SCFA has been implicated in the promotion of obesity. We aimed to compare the effects of two fermentable fibers on postprandial SCFA and second-meal glycemic response in healthy overweight or obese (OWO) vs lean (LN) participants. SUBJECTS/METHODS:Using a randomized crossover design, 13 OWO and 12 LN overnight fasted participants were studied for 6?h on three separate days after consuming 300?ml water containing 75?g glucose (GLU) as control or with 24?g inulin (IN) or 28?g resistant starch (RS). A standard lunch was served 4?h after the test drink. RESULTS:Within the entire group, compared with control, IN significantly increased serum SCFA (P<0.001) but had no effect on free-fatty acids (FFA) or second-meal glucose and insulin responses. In contrast, RS had no significant effect on SCFA but reduced FFA rebound (P<0.001) and second-meal glucose (P=0.002) and insulin responses (P=0.024). OWO had similar postprandial serum SCFA and glucose concentrations but significantly greater insulin and FFA than LN. However, the effects of IN and RS on SCFA, glucose, insulin and FFA responses were similar in LN and OWO. CONCLUSIONS:RS has favorable second-meal effects, likely related to changes in FFA rather than SCFA concentrations. However, a longer study may be needed to demonstrate an effect of RS on SCFA. We found no evidence that acute increases in SCFA after IN reduce glycemic responses in humans, and we were unable to detect a significant difference in SCFA responses between OWO vs LN subjects.
Project description:BACKGROUND:Colonic fermentation of dietary fibre to short-chain fatty acids (SCFA) influences appetite hormone secretion in animals, but SCFA production is excessive in obese animals. This suggests there may be resistance to the effect of SCFA on appetite hormones in obesity. OBJECTIVES:To determine the effects of inulin (IN) and resistant starch (RS) on postprandial SCFA, and gut hormone (glucagon-like peptide (GLP-1), peptide-tyrosine-tyrosine (PYY) and ghrelin) responses in healthy overweight/obese (OWO) vs lean (LN) humans. SUBJECTS/METHODS:Overnight-fasted participants (13 OWO and 12 LN) consumed 300?ml water containing 75?g glucose (GLU) as control or 75?g GLU plus 24?g IN, or 28.2?g RS using a randomised, single-blind, cross-over design. Blood for appetite hormones and SCFA was collected at intervals over 6?h. A standard lunch was served 4?h after the test drink. RESULTS:Relative to GLU, IN, but not RS, significantly increased SCFA areas under the curve (AUC) from 4-6?h (AUC4-6). Neither IN nor RS affected GLP-1 or PYY-AUC4-6. Although neither IN nor RS reduced ghrelin-AUC4-6 compared with GLU, ghrelin at 6?h after IN was significantly lower than that after GLU (P<0.05). After IN, relative to GLU, the changes in SCFA-AUC4-6 were negatively related to the changes in ghrelin-AUC4-6 (P=0.017). SCFA and hormone responses did not differ significantly between LN and OWO. CONCLUSIONS:Acute increases in colonic SCFA do not affect GLP-1 or PYY responses in LN or OWO subjects, but may reduce ghrelin. The results do not support the hypothesis that SCFA acutely stimulate PYY and GLP-1 secretion; however, a longer adaptation to increased colonic fermentation or a larger sample size may yield different results.
Project description:BACKGROUND: Populations at low risk of colonic cancer consume large amounts of fibre and starch and pass acid, bulky stools. One short chain fatty acid (SCFA), butyrate, is the colon's main energy source and inhibits malignant transformation in vitro. AIM: To test the hypothesis that altering colonic transit rate alters colonic pH and the SCFA content of the stools. PATIENTS: Thirteen healthy adults recruited by advertisement. METHODS: Volunteers consumed, in turn, wheat bran, senna and loperamide, each for nine days with a two week washout period between study periods, dietary intake being unchanged. Before, and in the last four days of each intervention, whole gut transit time (WGTT), defaecation frequency, stool form, stool beta-glucuronidase activity, stool pH, stool SCFA concentrations and intracolonic pH (using a radiotelemetry capsule for continuous monitoring) were assessed. RESULTS: WGTT decreased, stool, output and frequency increased with wheat bran and senna, vice versa with loperamide. The pH was similar in the distal colon and stool. Distal colonic pH fell with wheat bran and senna and tended to increase with loperamide. Faecal SCFA concentrations, including butyrate, increased with senna and fell with loperamide. With wheat bran the changes were non-significant, possibly because of the short duration of the study. Baseline WGTT correlated with faecal SCFA concentration (r = -0.511, p = 0.001), with faecal butyrate (r = -0.577, p < 0.001) and with distal colonic pH (r = 0.359, p = 0.029). CONCLUSION: Bowel transit rate is a determinant of stool SCFA concentration including butyrate and distal colonic pH. This may explain the inter-relations between colonic cancer, dietary fibre intake, stool output, and stool pH.
Project description:PURPOSE:To investigate whether age influences colonic polyphenol metabolism. METHODS:Healthy participants, younger (n = 8; 23-43 years) and older (n = 13; 51-76 years), followed a 3-day low-polyphenol diet (LPD) and a 3-day high-polyphenol diet (HPD). Urinary phenolic acids (PA), short chain fatty acids (SCFA), pH and gas were monitored, alongside selected colonic bacteria. Human faecal in vitro fermentations of rutin with or without raftiline were used to evaluate the gut microbiota capacity in a subset of both groups. RESULTS:Total urinary PA were higher in the older group after HPD compared to the younger group (1.5-fold; p = 0.04), with no difference between groups in terms of a change between diets (Δ high-low diet). While 17 PA were detected in all younger participants after HPD, a narrower range (n = 8 to 16 PA) was detected in most (n = 9/13) older participants, with lower level of benzoic acid (19-fold; p = 0.03), vanillic acid (4.5-fold; p = 0.04) but higher hippuric acid (2.7-fold; p = 0.03). Faecal SCFA concentration did not change after HPD within group, with similar differential excretion (Δ high-low diet) between groups. There were no differences between groups for faecal pH, total, faecal bacteria including Flavonifractor plautii, bifidobacteria, and bacteroides. In human in vitro faecal fermentations, seven PAs were detected in both groups after 24 h of rutin fermentation, with no quantitative and modest qualitative differences between groups. Total SCFA in faecal fermentation did not differ between groups, except for butyric acid (twofold higher in the older group; p = 0.009) when rutin was fermented with raftiline over 24 h. CONCLUSIONS:Urinary phenolic acids were less diverse in older participants despite limited difference in functional capacity of in vitro faecal fermentations.
Project description:Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans.To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake.Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0-61 wt% (IPE-0-IPE-61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). Propionate release was determined using (13) C-labelled IPE variants.In vitro, IPE-27-IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE-27 led to greater (13) C recovery in breath CO2 than IPE-54 (64.9 vs. 24.9%, P = 0.001). IPE-27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from inulin control.IPE-27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short-chain fatty acid esters provide a novel tool for probing the diet-gut microbiome-host metabolism axis in humans.
Project description:In some studies, high intake of dietary fibre has been associated with a lower risk of colorectal cancer. The present study aimed to compare physiological effects of three legume kernel fibres and citrus fibre on blood lipids (primary outcome: LDL cholesterol) and colonic health.Ninety-two subjects were recruited for the double-blind, controlled crossover trial. Seventy-eight participants were randomly divided into three groups. Following run-in, half the volunteers from each group consumed 25 g/d of a legume fibre, comprising blue lupin fibre, white lupin fibre, and soya fibre for two weeks. The other half received the same amount of citrus fibre (active comparator). The intervention was crossed within each group after two weeks wash-out. At the end of run-in and intervention, a quantitative faeces collection took place and fasting blood samples were drawn. Repeated measures ANOVA with the general linear model were applied to evaluate changes following interventions.Seventy-six subjects completed the study. Dietary fibre intake during all interventions was approximately twice the fibre intake at run-in. The lupin fibre supplementations increased daily faecal dry matter and faecal weight compared to run-in, representing an increase of 1.76 g faeces/g additional dietary fibre contributed by blue lupin and of 1.64 g faeces/g by white lupin, respectively. Both lupin interventions led to a significantly enhanced formation of short-chain fatty acids, and blue lupin fibre to a decrease in faecal pH compared to run-in (0.27 units, P <?0.01). Further, blue lupin increased primary bile acids-excretion (P?=?0.02). All legume fibres reduced faecal concentrations of total and secondary bile acids (blue lupin: 16% white lupin: 24% soya: 16%). Blood lipids were not influenced by any intervention. No serious adverse effects were observed.The tested fibre preparations do not affect lipid metabolism through bile acid-binding in normocholesterolaemic subjects. However, particularly blue lupin kernel fibre improve colonic function and have beneficial effects on putative risk factors for colorectal cancer such as faecal mass, transit time, SCFA, faecal pH, and secondary bile acid concentration. Therefore, enhancing dietary fibre intake through blue lupin up to about 50 g/d can be recommended.NCT01036308.
Project description:There have been mixed results regarding the relationship among short chain fatty acids (SCFAs), microbiota, and obesity in human studies. We selected studies that provided data on SCFA levels or fecal microbiota abundance in obese and nonobese individuals and then combined the published estimates using a random-effects meta-analysis. Obese individuals had significantly higher fecal concentrations of acetate (SMD (standardized mean differences) = 0.87, 95% CI (confidence interva) = 0.24-1.50, I2 (I-squared) = 88.5), propionate (SMD = 0.86, 95% CI = 0.35-1.36, I2 = 82.3%), and butyrate (SMD = 0.78, 95% CI = 0.29-1.27, I2 = 81.7%) than nonobese controls. The subgroup analyses showed no evidence of heterogeneity among obese individuals with a BMI >30 kg/m2 (I2 = 0.0%). At the phylum level, the abundance of fecal microbiota was reduced in obese compared to nonobese individuals, but the difference was not statistically significant (Bacteroidetes phylum, SMD = -0.36, 95% CI = -0.73-0.01; Firmicutes phylum, SMD = -0.10, 95% CI = -0.31-0.10). The currently available human case-control studies show that obesity is associated with high levels of SCFA but not gut microbiota richness at the phylum level. Additional well-designed studies with a considerable sample size are needed to clarify whether this association is causal, but it is also necessary to identify additional contributors to SCFA production, absorption, and excretion in humans.
Project description:As raw sorghum is not able to influence considerable colonic fermentation despite its higher resistant starch (RS) content, our study aimed to investigate the effects of frozen autoclaved sorghum on colonic fermentation. Fischer 344 rats were fed frozen cooked refined (S-Rf) and whole (S-Wh) sorghum diets and were compared against ?-corn starch (CON) and high amylose starch (HAS) fed rats for zoometric parameters, cecal biochemical and microbiological parameters. Sorghum fed rats exhibited significantly lower feed intake and visceral adipose tissue mass compared to CON. Bacterial alpha diversity was significantly higher in the sorghum fed rats compared to HAS and the two sorghum fed groups clustered together, separately from HAS and CON in the beta diversity plot. Serum non-High Density Lipoprotein cholesterol and total cholesterol in S-Rf group were significantly lower compared to CON, while total fecal bile excretion was also significantly higher in the two sorghum fed groups. Lower visceral adiposity was correlated with lower feed intake, RS content ingested and cecal short chain fatty acid (SCFA) contents. Thus, higher RS inflow to the colon via frozen autoclaved sorghum might have influenced colonic fermentation of RS and the resultant SCFA might have influenced lower adiposity as manifested by the lower body weight gain.
Project description:BACKGROUND:In recent years, high phosphate intakes were discussed critically. In the small intestine, a part of the ingested phosphate and calcium precipitates to amorphous calcium phosphate (ACP), which in turn can precipitate other intestinal substances, thus leading to a beneficial modulation of the intestinal environment. Therefore, we analysed faecal samples obtained from a human intervention study regarding gut-related parameters. METHODS:Sixty-two healthy subjects (men, n =?30; women, n =?32) completed the double-blind, placebo-controlled and parallel designed study (mean age: 29?±?7 years; mean BMI: 24?±?3 kg/m2). Supplements were monosodium phosphate and calcium carbonate. During the first 2 weeks, all groups consumed a placebo sherbet powder, and afterwards a sherbet powder for 8 weeks according to the intervention group: P1000/Ca0 (1000 mg/d phosphorus), P1000/Ca500 (1000 mg/d phosphorus and 500 mg/d calcium) and P1000/Ca1000 (1000 mg/d phosphorus and 1000 mg/d calcium). After the placebo period and after 8 weeks of intervention faecal collections took place. We determined in faeces: short-chain fatty acids (SCFA) and fat as well as the composition of the microbiome (subgroup) and cyto- and genotoxicity of faecal water (FW). By questionnaire evaluation we examined tolerability of the used phosphorus supplement. RESULTS:Faecal fat concentrations did not change significantly due to the interventions. Concentrations of faecal total SCFA and acetate were significantly higher after 8 weeks of P1000/Ca500 supplementation compared to the P1000/Ca0 supplementation. In men, faecal total SCFA and acetate concentrations were significantly higher after 8 weeks in the P1000/Ca1000 group compared to the P1000/Ca0 one. None of the interventions markedly affected cyto- and genotoxic activity of FW. Men of the P1000/Ca1000 intervention had a significantly different gut microbial community compared to the men of the P1000/Ca0 and P1000/Ca500 ones. The genus Clostridium XVIII was significantly more abundant in men of the P1000/Ca1000 intervention group compared to the other groups. Supplementations did not cause increased intestinal distress. CONCLUSIONS:The used high phosphorus diet did not influence cyto- and genotoxicity of FW and the concentrations of faecal fat independent of calcium intake. Our study provides first hints for a potential phosphorus-induced modulation of the gut community and the faecal total SCFA content. TRIAL REGISTRATION:The trial is registered at ClinicalTrials.gov as NCT02095392 .