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Free Fatty Acids Profiles Are Related to Gut Microbiota Signatures and Short-Chain Fatty Acids.

ABSTRACT: A growing body of evidence highlights the relevance of free fatty acids (FFA) for human health, and their role in the cross talk between the metabolic status and immune system. Altered serum FFA profiles are related to several metabolic conditions, although the underlying mechanisms remain unclear. Recent studies have highlighted the link between gut microbiota and host metabolism. However, although most of the studies have focused on different clinical conditions, evidence on the role of these mediators in healthy populations is lacking. Therefore, we have addressed the analysis of the relationship among gut microbial populations, short-chain fatty acid (SCFA) production, FFA levels, and immune mediators (IFNγ, IL-6, and MCP-1) in 101 human adults from the general Spanish population. Levels of selected microbial groups, representing the major phylogenetic types present in the human intestinal microbiota, were determined by quantitative PCR. Our results showed that the intestinal abundance of Akkermansia was the main predictor of total FFA serum levels, displaying a negative association with total FFA and the pro-inflammatory cytokine IL-6. Similarly, an altered FFA profile, identified by cluster analysis, was related to imbalanced levels of Akkermansia and Lactobacillus as well as increased fecal SCFA, enhanced IL-6 serum levels, and higher prevalence of subclinical metabolic alterations. Although no differences in nutritional intakes were observed, divergent patterns in the associations between nutrient intakes with intestinal microbial populations and SCFA were denoted. Overall, these findings provide new insights on the gut microbiota-host lipid metabolism axis and its potential relevance for human health, where FFA and SCFA seem to play an important role.

SUBMITTER: Rodriguez-Carrio J

PROVIDER: S-EPMC5522850 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:BackgroundPrevious studies found the dysbiosis of intestinal microbiota in diabetic kidney disease (DKD), especially the decreased SCFA-producing bacteria. We aimed to investigate the concentration of the stool and serum short-chain fatty acids (SCFAs), gut microbiota-derived metabolites, in individuals with DKD and reveal the correlations between SCFAs and renal function.MethodsA total of 30 participants with DKD, 30 participants with type 2 diabetes mellitus (DM), and 30 normal controls (NC) in HwaMei Hospital were recruited from 1/1/2018 to 12/31/2019. Participants with DKD were divided into low estimated glomerular filtration rate (eGFR)(eGFR<60ml/min, n=14) and high eGFR (eGFR≥60ml/min, n=16) subgroups. Stool and serum were measured for SCFAs with gas chromatograph-mass spectrometry.ResultsThe DKD group showed markedly lower levels of fecal acetate, propionate, and butyrate versus NC (p<0.001, p<0.001, p=0.018, respectively) [1027.32(784.21-1357.90)]vs[2064.59(1561.82-2637.44)]μg/g,[929.53(493.65-1344.26)]vs[1684.57(1110.54-2324.69)]μg/g,[851.39(409.57-1611.65)] vs[1440.74(1004.15-2594.73)]μg/g, respectively, and the lowest fecal total SCFAs concentration among the groups. DKD group also had a lower serum caproate concentration than that with diabetes (p=0.020)[0.57(0.47-0.61)]vs[0.65(0.53-0.79)]μmol/L. In the univariate regression analysis, fecal and serum acetate correlated with eGFR (OR=1.013, p=0.072; OR=1.017, p=0.032). The correlation between serum total SCFAs and eGFR showed statistical significance (OR=1.019, p=0.024) unadjusted and a borderline significance (OR=1.024, p=0.063) when adjusted for Hb and LDL. The decrease in serum acetate and total SCFAs were found of borderline significant difference in both subgroups (p=0.055, p=0.050).ConclusionThis study provides evidence that in individuals with DKD, serum and fecal SCFAs levels (fecal level in particular) were lowered, and there was a negative correlation between SCFAs and renal function.

Project description:Postural orthostatic tachycardia syndrome (POTS) is a devastating chronic form of orthostatic intolerance associated with excessive heart rate increase without hypotension during upright posture. POTS patients exhibit increased circulating norepinephrine levels with exaggerated sympathetic nervous system response upon standing. Emerging evidence suggests a role for the gut microbiome in cardiovascular disorders. However, the etiology of POTS and whether the gut microbiome plays a role are not fully elucidated. We assessed whether the gut microbiome and fecal short-chain fatty acids were different in POTS patients (N = 25) compared to healthy control (N = 23) women. Patients underwent hemodynamic measurements while supine and upon standing. Fecal samples were collected and analyzed using shotgun sequencing and Liquid Chromatography-High Resolution Mass Spectrometry and dietary habits were measured with a fitness application. We found that POTS patients in the standing position had higher circulating norepinephrine and epinephrine levels and increased heart rate. There were no differences in diet composition between groups. Of note dietary salt intake was also similar despite the fact that these patients are advised to consume a high salt diet. Alpha and beta diversity were similar between groups. We observed no differences in bacteria at the phylum levels or Firmicutes to Bacteroidetes ratio. We found no significant differences at the genus level, but observed trends in certain bacteria. Lachnoclostridium genus were higher in POTS when compared to the control group. On the other hand, Coprococcus and Coprobacter, were lower in POTS patients compared to controls. Although our KEGG metabolic pathways indicated differences related to short-chain fatty acids (SCFAs), we found that both POTS patients and healthy controls had similar levels of SCFAs. These results suggest POTs per se may have limited effects on gut microbiota composition and derived SCFAs. Further studies are needed to assess the role of the alterations observed at the genus level.

Project description:Background/objectivesHigh 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.DesignWe 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.ResultsDietary 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.ConclusionsThe 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.

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Free Fatty Acids Profiles Are Related to Gut Microbiota Signatures and Short-Chain Fatty Acids.

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