Judlyn Fernandes

Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans

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.

Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans.

Background: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.Objectives:To compare rectal SCFA absorption, dietary intake and faecal microbial profile in lean (LN) versus overweight and obese (OWO) individuals.Design: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.Results: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).Conclusions: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.

Inulin increases short-term markers for colonic fermentation similarly in healthy and hyperinsulinaemic humans.

Background/Objectives:Colonic fermentation of dietary fibre produces short-chain fatty acids (SCFAs), acetate, propionate and butyrate, which may protect against type 2 diabetes by reducing serum free-fatty acids (FFAs). Since hyperinsulinaemia is associated with insulin resistance and increased diabetes risk, the main objective was to compare markers of colonic fermentation after acute inulin ingestion in subjects with normal (<40 pmol/l, NI) and high (⩾40 pmol/l, HI) plasma insulin.Subjects/Methods:Overnight fasted NI (n=9) and HI (n=9) subjects were studied for 4 h on two separate days after consuming 300 ml drinks containing 75 g glucose (Glucose) or 75 g glucose plus 24 g inulin (Inulin) using a randomized, single-blind, crossover design.Results:Inulin elicited a higher breath hydrogen and methane areas under the curve (AUC), but the increases in SCFA responses were not statistically significant. Mean serum-acetate concentration over the 4-h study period was higher in NI than in HI subjects (44.3±6.9 vs 22.5±3.7 μmol/l, P=0.001). The rate of rebound of FFA was reduced by Inulin, with FFA at 4 h being less after Inulin than Glucose, regardless of insulin status (0.310±0.028 vs 0.432±0.042 mEq/l, P=0.008).Conclusions:This suggests that inulin increases short-term markers for colonic fermentation, but a longer study period may be necessary to observe differences in SCFA production. The reason for the lower serum acetate in HI is unclear but may be due to reduced absorption, increased clearance or decreased endogenous production. This suggests the need to compare acetate kinetics in normal and hyperinsulinaemic subjects.

Intravenous acetate elicits a greater free fatty acid rebound in normal than hyperinsulinaemic humans.

Background/objectives:Colonic fermentation of dietary fiber may improve insulin sensitivity by the metabolic effects of short chain fatty acids (SCFA) in reducing free fatty acids (FFA). The main objectives of this study were to compare peripheral uptake of acetate (AC) in participants with normal (<40 pmol/l, NI) and high (⩾40 pmol/l, HI) plasma insulin, and the ability of AC to reduce FFA in both the groups.Subjects/methods:Overnight fasted NI (n=9) and HI (n=9) participants were given an intravenous (IV) infusion of 140 mmol/l sodium acetate at three different rates over 90 min. The total amount of AC infused was 51.85 mmols.Results:AC clearance in NI participants was not significantly different than that in HI participants (2.11±0.23 vs 2.09±0.24 ml/min). FFA fell in both the groups, but rebounded to a greater extent in NI than HI participants (time × group interaction, P=0.001). Significant correlations between insulin resistance (IR) indices (homeostasis model assessment of insulin resistance (HOMA-IR), Matsuda and insulinogenic index) vs FFA rebound during IV AC infusion were also observed.Conclusions:These findings suggest that AC uptake is similar in both the groups. Participants with lower plasma insulin and lower IR indices had a greater FFA rebound. These results support the hypothesis that increasing AC concentrations in the systemic circulation may reduce lipolysis and plasma FFA concentrations and thus improve insulin sensitivity. More in-depth studies are needed to look at the effects of SCFA on FFA metabolism in insulin-resistant participants.

The acute effects of inulin and resistant starch on postprandial serum short-chain fatty acids and second-meal glycemic response in lean and overweight humans

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.

Interrelationships between age, total dietary fiber intake and breath methane in humans.

Abstract In western populations the prevalence of methane producers (MP) is 30–50%. Studies related to dietary intakes of MP are lacking. The aim of this study was to compare dietary intakes in MP and methane nonproducers (MNP). In 122 healthy subjects, breath gases were analysed and 3-day food records were collected to assess the nutrient intakes. The 63 MP were significantly older than the 59 MNP (48.9±2.0 vs 38.3±2.2 y: P

Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans

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.

Kinetic model of acetate metabolism in healthy and hyperinsulinaemic humans

Background/objectives:The short chain fatty acid acetate (AC), may have a role in increasing insulin sensitivity, thus lowering risk for obesity and type 2 diabetes mellitus. It is unclear if AC kinetics is similar in normal (NI) and hyperinsulinaemic (HI) participants. Therefore, we studied AC absorption from the distal colon in participants with normal (<40 pmol/l) and high (⩾40 pmol/l) plasma insulin. This work was a part of a series of studies conceived to compute a kinetic model for AC. Kinetic parameters such as estimates of rate of entry into peripheral blood, hepatic uptake and endogenous/exogenous production were compared in the groups.Subjects/methods:Overnight fasted NI (n=9) and HI (n=8) participants were given rectal infusions containing sodium AC (90 mmol/l). The solutions were retained for 40 min, then voided for AC measurement. Total amount of AC infused was 27 mmols.Results:AC absorption from the distal colon (279±103 vs 322±91 μmol/min, P=0.76) and hepatic uptake of AC (155±101 vs 146±85 μmol/min, P=0.94) were similar in the groups. Endogenous and exogenous AC production was significantly higher in NI than HI participants. Plasma AC was inversely proportional to plasma insulin concentrations in the entire cohort (y=k/x, where k=1813).Conclusions:There was low power to detect differences in AC absorption rate and hepatic AC uptake in NI vs HI. The rate of entry of AC into peripheral blood was similar in NI and HI participants. However, hyperinsulinaemia may alter endogenous and exogenous AC metabolism.

Positive Methane-Producing Status Associated With Increased Serum Cholesterol in Subjects With Impaired Glucose Tolerance

OBJECTIVE To determine if those who produce methane (i.e., have presence of methane in breath) have higher serum cholesterol than those who do not produce methane in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS We measured breath gases and fasting serum total and high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels in 21 subjects with IGT. RESULTS The 11 methane-producers were well matched to the 10 non-methane-producers for age, sex, and body mass index. Methane-producers had higher fasting serum total (6.5 ± 0.3 vs. 5.5 ± 0.2 mmol/l; P < 0.02) and low-density lipoprotein (4.3 ± 0.3 vs. 3.4 ± 0.2 mmol/l; P < 0.05) cholesterol concentrations with no difference in TG or HDL levels. CONCLUSIONS The results suggest that in subjects with IGT, positive methane-producing status may be associated with increased serum cholesterol levels.

METHANE PRODUCING STATUS INCREASES SERUM ACETATE AND LIPIDS IN SUBJECTS WITH IMPAIRED GLUCOSE TOLERANCE

Abstract To determine if methane producers (MP) have a higher post-prandial serum acetate concentrations over a 12-hour period than methane nonproducers (MNP) in subjects with impaired glucose tolerance (IGT), we studied 19 subjects: 11 MP and 8 MNP. Breath gases, hydrogen and methane, fasting serum total and high-density lipoprotein (HDL) cholesterol and triacylglycerol were measured. Plasma glucose and insulin and serum short chain fatty acid concentrations were measured fasting and over a 12-hour period. MP had significantly greater fasting serum total cholesterol (6.5±0.3 vs 5.4±0.3 mmol/L; P = 0.01) and LDL cholesterol (4.2±0.3 vs 3.0±0.4 mmol/L; P = 0.04) concentrations than MNP. No differences in TG or HDL cholesterol concentrations were observed. The mean 5–12 hour incremental area in serum acetate in MP was significantly higher compared to MNP (299.4±37.2 vs 151.3±47.6 μmol/L; P = 0.02). From these results we can conclude that in IGT subjects, a positive methane producing status increases post-prandial serum acetate which may contribute to the increased serum total cholesterol concentration.