scholarly journals Faecal microbial metabolites of proteolytic and saccharolytic fermentation in relation to degree of insulin resistance in adult individuals

2021 ◽  
pp. 1-8
Author(s):  
M.A. González Hernández ◽  
E.E. Canfora ◽  
E.E. Blaak
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Metabolic Health ◽  
Model Assessment ◽  
Microbial Metabolites ◽  
Cross Sectional ◽  
Fermentation Products ◽  
Wide Range ◽  
Chain Fatty Acids

The gut microbiota may affect host metabolic health through microbial metabolites. The balance between the production of microbial metabolites by saccharolytic and proteolytic fermentation may be an important determinant of metabolic health. Amongst the best-studied saccharolytic microbial metabolites are the short-chain fatty acids acetate, propionate and butyrate. However, human data on the role of other microbial fermentation by-products in metabolic health are greatly lacking. Therefore, we compared in a cross-sectional study the faecal microbial metabolites (caproate, lactate, valerate, succinate, and the branched-chain fatty acids (BCFA) (isobutyrate, isovalerate)) between insulin sensitive (homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-IR<1.85, IS) and insulin resistant (HOMA-IR>1.85, IR) individuals. Additionally, we assessed the relationships between faecal metabolites and markers of metabolic health including fasting glucose, insulin, free fatty acids, insulin resistance (HOMA-IR) and fasting substrate oxidation in 86 individuals with a wide range of body mass index. Faecal metabolite concentrations did not significantly differ between IS and IR. Furthermore, there were no associations between microbial metabolites and metabolic health markers, except for a slight positive association of isovalerate with carbohydrate oxidation (E%, std β 0.194, P=0.011) and fat oxidation (E%, std β -0.075, P=0.047), also after adjustment for age, sex and BMI. In summary, faecal caproate, lactate, valerate, succinate, and BCFA (isobutyrate, isovalerate) were not different between IR and IS individuals, nor was there any association between these faecal metabolites and parameters of metabolic health. Further human intervention studies are warranted to investigate the role of these microbially-derived fermentation products and their kinetics in metabolic health and insulin sensitivity.

scholarly journals Circulating fatty acid profiles are associated with protein energy wasting in maintenance hemodialysis patients: a cross-sectional study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ban-Hock Khor ◽  
◽  
Sharmela Sahathevan ◽  
Ayesha Sualeheen ◽  
Mohammad Syafiq Md Ali ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Nutritional Status ◽  
Serum Albumin ◽  
Saturated Fatty Acids ◽  
Maintenance Hemodialysis ◽  
Model Assessment ◽  
Cross Sectional ◽  
Markers Of Inflammation

AbstractThe metabolic impact of circulating fatty acids (FAs) in patients requiring hemodialysis (HD) is unknown. We investigated the associations between plasma triglyceride (TG) FAs and markers of inflammation, insulin resistance, nutritional status and body composition. Plasma TG-FAs were measured using gas chromatography in 341 patients on HD (age = 55.2 ± 14.0 years and 54.3% males). Cross-sectional associations of TG-FAs with 13 markers were examined using multivariate linear regression adjusted for potential confounders. Higher levels of TG saturated fatty acids were associated with greater body mass index (BMI, r = 0.230), waist circumference (r = 0.203), triceps skinfold (r = 0.197), fat tissue index (r = 0.150), serum insulin (r = 0.280), and homeostatic model assessment of insulin resistance (r = 0.276), but lower malnutrition inflammation score (MIS, r =  − 0.160). Greater TG monounsaturated fatty acid levels were associated with lower lean tissue index (r =  − 0.197) and serum albumin (r =  − 0.188), but higher MIS (r = 0.176). Higher levels of TG n-3 polyunsaturated fatty acids (PUFAs) were associated with lower MIS (r =  − 0.168) and interleukin-6 concentrations (r =  − 0.115). Higher levels of TG n-6 PUFAs were associated with lower BMI (r =  − 0.149) but greater serum albumin (r = 0.112). In conclusion, TG monounsaturated fatty acids were associated with poor nutritional status, while TG n-3 PUFAs were associated with good nutritional status. On the other hand, TG saturated fatty acids and TG n-6 PUFAs had both favorable and unfavorable associations with nutritional parameters.

Desaturase Activity Is Associated With Weight Status and Metabolic Risk Markers in Young Children

2015 ◽  
Vol 100 (10) ◽  
pp. 3760-3769 ◽  
Author(s):  
Maike Wolters ◽  
Heike Schlenz ◽  
Claudia Börnhorst ◽  
Patrizia Risé ◽  
Claudio Galli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Weight Status ◽  
Metabolic Risk ◽  
Model Assessment ◽  
Z Score ◽  
Cross Sectional ◽  
Assessment Index ◽  
Homeostatic Model Assessment ◽  
Z Scores

Context: Activity of delta-9, delta-6, and delta-5 desaturases (D9D, D6D, D5D) are associated with obesity, insulin resistance, and dyslipidemia. Objective: To investigate the association of estimated desaturase activities with weight status, insulin resistance, and dyslipidemia in children, cross-sectionally and longitudinally. Design: The IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort study was used, with examinations at baseline (T0) and after 2 years (T1). Setting and Participants: Children aged 2 to less than 10 years from eight European countries were recruited in kindergartens/primary schools. Children with available data on fatty acids, outcome, and covariate information were included in the analyses. Methods: Whole blood fatty acids were analyzed in 2600 children at baseline. D9D (16:1n-7/16:0), D6D (20:3n-6/18:2n-6), and D5D (20:4n-6/20:3n-6) activities were estimated from product-precursor fatty acids ratios. Body mass index (BMI), Homeostatic Model Assessment index, and high-density lipoprotein cholesterol (HDL), and triglycerides (TG) served as outcomes for weight status, insulin resistance, and dyslipidemia, respectively. Linear and logistic regression and repeated measures models were used to assess the cross-sectional and longitudinal associations between desaturase activity and outcomes. Results: In the cross-sectional analysis, D9D and D6D were positively associated with BMI and TG z-scores and inversely with HDL z-scores. D5D was inversely associated with BMI and TG z-scores (ie, a D5D increase of 1 unit is associated with a BMI z-score decrease of 0.07 and a 28% lower odds ratio for TG ≥75th percentile). Longitudinally, similar associations were found for T0 desaturase activities with BMI and for T0 D6D with HDL at follow-up (T1). Baseline D6D and D5D were positively associated with the change of HDL z-score from T0 to T1, and D6D with the change of Homeostatic Model Assessment index z-score. Conclusion: Desaturase activities are associated with metabolic risk markers already in young children and appear to predict the metabolic risk.

scholarly journals Diagnosing and predicting mixed culture fermentations with unicellular and guild-based metabolic models

2019 ◽  
Author(s):  
Matthew J. Scarborough ◽  
Joshua J. Hamilton ◽  
Elizabeth A. Erb ◽  
Timothy J. Donohue ◽  
Daniel R. Noguera
Keyword(s):  
Fatty Acids ◽  
Microbial Communities ◽  
Organic Substrates ◽  
Fermentation Products ◽  
Organic Mixture ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Metabolic Models ◽  
Chain Fatty Acids

ABSTRACTMulti-species microbial communities determine the fate of materials in the environment and can be harnessed to produce beneficial products from renewable resources. In a recent example, fermentations by microbial communities have produced medium-chain fatty acids (MCFAs). Tools to predict, assess, and improve the performance of these communities, however, are limited. To provide such tools, we constructed two metabolic models of MCFA-producing microbial communities based on available genomic, transcriptomic and metabolomic data. The first model is a unicellular model (iFermCell215), while the second model (iFermGuilds789) separates fermentation activities into functional guilds. Ethanol and lactate are fermentation products known to serve as substrates for MCFA production, while acetate is another common co-metabolite during MCFA production. Simulations with iFermCell215 predict that low molar ratios of acetate-to-ethanol favor MCFA production, whereas the products of lactate and acetate co-utilization are less dependent on the acetate-to-lactate ratio. In simulations of an MCFA-producing community fed a complex organic mixture derived from lignocellulose, iFermGuilds789 predicted that lactate was an extracellular co-metabolite that served as a substrate for butyrate (C4) production. Extracellular hexanoic (C6) and octanoic acids (C8) were predicted by iFermGuilds789 to be from community members that directly metabolize sugars. Modeling results provide several hypotheses that can improve our understanding of microbial roles in a MCFA-producing microbiome and inform strategies to increase MCFA production. Further, these models represent novel tools for exploring the role of mixed microbial communities in carbon recycling in the environment, as well as on beneficial reuse of organic residues.IMPORTANCEMicrobiomes are vital to human health, agriculture, and protecting the environment. Predicting behavior of self-assembled or synthetic microbiomes, however, remains a challenge. In this work, we used unicellular and guild-based metabolic models to investigate production of medium-chain fatty acids by a mixed microbial community that is fed multiple organic substrates. Modeling results provided insights into metabolic pathways of three medium-chain fatty acid-producing guilds and identified potential strategies to increase production of medium-chain fatty acids. This work demonstrates the role of metabolic models in augmenting multi-omic studies to gain greater insights into microbiome behavior.

scholarly journals Metatranscriptomic and thermodynamic insights into medium-chain fatty acid production using an anaerobic microbiome

2018 ◽  
Author(s):  
Matthew J. Scarborough ◽  
Christopher E. Lawson ◽  
Joshua J. Hamilton ◽  
Timothy J. Donohue ◽  
Daniel R. Noguera
Keyword(s):  
Fatty Acids ◽  
Metabolic Reconstruction ◽  
Chemical Production ◽  
Fermentation Products ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Coa Transferase ◽  
Pure Cultures ◽  
Chain Fatty Acids

AbstractBiomanufacturing from renewable feedstocks represents a sustainable strategy to offset fossil fuel-based chemical production. One potential biomanufacturing strategy is production of medium chain fatty acids (MCFA) from organic feedstocks using either pure cultures or microbiomes. While the set of microbes in a microbiome can often metabolize more diverse organic materials than a single species, and the role of specific species may be known, knowledge of the carbon and energy flow within and between organisms in MCFA producing microbiomes is only starting to emerge. Here, we integrate metagenomic, metatranscriptomic, and thermodynamic analyses to predict and characterize the metabolic network of an anaerobic microbiome producing MCFA from organic matter derived from lignocellulosic ethanol fermentation conversion residue. A total of 37 high quality (>80% complete, < 10% contamination) metagenome-assembled genomes (MAGs) were recovered from the microbiome and metabolic reconstruction of the 10 most abundant MAGs was performed. Metabolic reconstruction combined with metatranscriptomic analysis predicted that organisms affiliated with Lactobacillus and Coriobacteriaceae degraded carbohydrates and fermented sugars to lactate and acetate. Lachnospiraceae and Eubacteriaceae affiliated organisms were predicted to transform these fermentation products to MCFA. Thermodynamic analyses identified conditions in which H2 is expected to be either produced or consumed, suggesting a potential role of H2 partial pressure on MCFA production. From an integrated systems analysis perspective, we propose that MCFA production could be improved if microbiomes are engineered to use homofermentative instead of heterofermentative Lactobacillus, and if MCFA-producing organisms are engineered to preferentially use a thioesterase instead of a CoA transferase as the terminal enzyme in reverse β-oxidation.ImportanceMixed communities of microbes play important roles in health, the environment, agriculture, and biotechnology. While tapping the combined activity of organisms within microbiomes may allow the utilization of a wider range of substrate over the use of pure cultures for biomanufacturing, harnessing the metabolism of these mixed cultures remains a major challenge. Here, we predict metabolic functions of bacteria in a microbiome that produces medium-chain fatty acids from a renewable feedstock. Our findings lay the foundation to begin addressing how to engineer and control microbiomes for improved biomanufacturing; to build synthetic mixtures of microbes that produce valuable chemicals from renewable resources; and to better understand microbial communities that contribute to health, agriculture, and the environment.

scholarly journals Dynamic Multi-Stage Gastrointestinal Digestion Model Assessment of Microbial Fermentation Products of Collagen Hydrolysates

Proceedings ◽  
2020 ◽  
Vol 61 (1) ◽  
pp. 12
Author(s):  
Christina E. Larder ◽  
Michèle M. Iskandar ◽  
Stan Kubow
Keyword(s):  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Microbial Production ◽  
Microbial Fermentation ◽  
Model Assessment ◽  
Collagen Hydrolysate ◽  
Fecal Matter ◽  
Fermentation Products ◽  
Nitrogenous Compounds ◽  
Chain Fatty Acids

Proteins, peptides and amino acids (AAs) that bypass upper gastrointestinal (GI) digestion can be fermented in the colonic regions. This could lead to microbial production of health promoting short-chain fatty acids (SCFAs). Nitrogenous compounds can also be fermented to generate potentially harmful branched chain fatty acids (BCFAs). As collagen hydrolysate (CH) supplements contain a high peptide content, we evaluated whether peptides that undergo intestinal CH digestion and microbial fermentation can generate SCFAs and BCFAs. Two bovine-sourced CH formulations (CH-GL and CH-OPT) underwent digestive processes and microbial fermentation for 24 h in a dynamic GI digestion model containing human fecal matter. After 24 h, CH-OPT showed a significant (p < 0.05) increase in SCFAs (propionic, butyric and valeric acids) in the ascending colonic vessel with no changes observed with CH-GL. Only CH-OPT showed a significant (p < 0.05) increase in BCFAs, also noted in the ascending colon. No significant (p < 0.05) changes to SCFAs and BCFAs were observed in the transverse and descending colons for both CHs. These findings demonstrate that CHs can induce microbial production of SCFAs and BCFAs although this appears to depend on the CH tested. More studies are needed to determine the physiological significance of these microbial metabolites from intake of CH supplements.

scholarly journals Metatranscriptomic and Thermodynamic Insights into Medium-Chain Fatty Acid Production Using an Anaerobic Microbiome

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Matthew J. Scarborough ◽  
Christopher E. Lawson ◽  
Joshua J. Hamilton ◽  
Timothy J. Donohue ◽  
Daniel R. Noguera
Keyword(s):  
Fatty Acids ◽  
Metabolic Reconstruction ◽  
Chemical Production ◽  
Fermentation Products ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Coa Transferase ◽  
Pure Cultures ◽  
Chain Fatty Acids

ABSTRACTBiomanufacturing from renewable feedstocks can offset fossil fuel-based chemical production. One potential biomanufacturing strategy is production of medium-chain fatty acids (MCFA) from organic feedstocks using either pure cultures or microbiomes. While the set of microbes in a microbiome can often metabolize organic materials of greater diversity than a single species can and while the role of specific species may be known, knowledge of the carbon and energy flow within and between organisms in MCFA-producing microbiomes is only now starting to emerge. Here, we integrated metagenomic, metatranscriptomic, and thermodynamic analyses to predict and characterize the metabolic network of an anaerobic microbiome producing MCFA from organic matter derived from lignocellulosic ethanol fermentation conversion residue. A total of 37 high-quality (>80% complete, <10% contamination) metagenome-assembled genomes (MAGs) were recovered from the microbiome, and metabolic reconstruction of the 10 most abundant MAGs was performed. Metabolic reconstruction combined with metatranscriptomic analysis predicted that organisms affiliated withLactobacillusandCoriobacteriaceaewould degrade carbohydrates and ferment sugars to lactate and acetate.Lachnospiraceae- andEubacteriaceae-affiliated organisms were predicted to transform these fermentation products to MCFA. Thermodynamic analyses identified conditions under which H2is expected to be either produced or consumed, suggesting a potential role of H2partial pressure in MCFA production. From an integrated systems analysis perspective, we propose that MCFA production could be improved if microbiomes were engineered to use homofermentative instead of heterofermentativeLactobacillusand if MCFA-producing organisms were engineered to preferentially use a thioesterase instead of a coenzyme A (CoA) transferase as the terminal enzyme in reverse β-oxidation.IMPORTANCEMixed communities of microbes play important roles in health, the environment, agriculture, and biotechnology. While tapping the combined activities of organisms within microbiomes may allow the utilization of a wider range of substrates in preference to the use of pure cultures for biomanufacturing, harnessing the metabolism of these mixed cultures remains a major challenge. Here, we predicted metabolic functions of bacteria in a microbiome that produces medium-chain fatty acids from a renewable feedstock. Our findings lay the foundation for efforts to begin addressing how to engineer and control microbiomes for improved biomanufacturing, how to build synthetic mixtures of microbes that produce valuable chemicals from renewable resources, and how to better understand the microbial communities that contribute to health, agriculture, and the environment.

scholarly journals Decreased activity of desaturase 5 in association with obesity and insulin resistance aggravates declining long-chainn-3 fatty acid status in Cree undergoing dietary transition

2009 ◽  
Vol 102 (6) ◽  
pp. 888-894 ◽  
Author(s):  
Yuan E. Zhou ◽  
Stan Kubow ◽  
Eric Dewailly ◽  
Pierre Julien ◽  
Grace M. Egeland
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fasting Blood Glucose ◽  
Age Groups ◽  
Erythrocyte Membranes ◽  
Model Assessment ◽  
Anthropometric Measures ◽  
Cross Sectional ◽  
Age Related ◽  
Dietary Transition

Emerging evidence shows that desaturase 5 (Δ5), the key regulator in the synthesis of highly unsaturated long-chain fatty acids (HUFA), is modulated by factors including adiposity, diet and insulin resistance. We explored the association of these factors in a cross-sectional study within a high-risk Cree population. Anthropometric measures and fasting blood glucose and insulin were analysed. Δ5 was estimated as the 20 : 4n-6:20 : 3n-6 ratio in erythrocyte membranes. The setting of the present study was the Mistissini community in the Cree Territory of Québec, Canada with ninety-eight female and sixty-eight male subjects aged 20–88 years. Obesity (BMI ≥ 30 kg/m2) was prevalent across age groups. Δ5 was inversely associated with BMI (Spearman's correlation coefficient (rs) − 0·175;P = 0·03) and positively associated with age (rs0·593;P < 0·0001), which was driven by age-related increases in dietary intake ofn-3 fatty acids and decreases in 20 : 3n-6. Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely associated with Δ5 in age-adjusted linear regression analyses in normoglycaemic individuals (β − 2·110 (se0·566);P < 0·001), whereas no association was observed among glucose-intolerant individuals (interaction termP = 0·03). In contrast, there were no significant interactions indicating differences in the slope for each of the adiposity measures in their associations with Δ5. The present study indicates that the dietary transition of reduced consumption of fish among younger Cree may compound the effects of obesity and emerging insulin resistance which, in turn, could reduce bioavailability of HUFAn-3 (through reduced Δ5 activity). Also, the study suggests that disease progression is an important consideration when evaluating correlates of Δ5 activity in observational studies.

scholarly journals The Effect of Fortified Dadih (Fermented Buffalo Milk) with Vitamin D3 on Caecum Short Chain Fatty Acids (SCFA) Concentration and HOMA-IR of T2DM-Rats

2021 ◽  
Vol 9 (2) ◽  
pp. 500-510
Author(s):  
Rita Arni ◽  
Gemala Anjani ◽  
Kis Djamiatun
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Vitamin D3 ◽  
Fasting Blood Glucose ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Control Group ◽  
Model Assessment ◽  
Post Intervention ◽  
Chain Fatty Acids

The prevalence of T2DM continues to increase along the years. Probiotics and vitamin D have antidiabetic effects and a synergism between them is evident. Fermented milk such as dadih is a great source of probiotics, specifically lactic acid bacteria (LAB). Probiotics are involved in the formation of short-chain fatty acids (SCFA) which can increase insulin production and improve Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The objective of this study was to investigate the effect of vitamin D3-fortified dadih on caecum SCFA concentration and HOMA-IR of T2DM-induced Wistar rats. A total of thirty rats were randomly split into five-groups: four diabetic groups (C2, T1, T2, and T3) and one healthy control group (C1). Intervention groups were either given vitamin D3 (T1), unfortified dadih (T2), or vitamin D3-enriched dadih (T3). Concentration of SCFA, glucose, and insulin were measured by gas chromatography, GOD-POD, and ELISA, respectively. T3 group showed significantly lower fasting blood glucose and higher insulin than T1 or T2 at post-intervention. The HOMA-IR index at the end of intervention indicated that T3 was significantly different from T1. Total caecum SCFA and butyrate concentrations were significantly higher in T3 than T1 or T2. The HOMA-IR had an inverse correlation with total caecum SCFA (r=-0.600, p=0.001) and butyrate concentration (r= -0.692, p=0.000). The decreased insulin resistance might be partially attributed to total caecum SCFA and butyrate concentrations. In conclusion, vitamin D3-fortified dadih had better efficacy in improving glycemic status, insulin, and SCFA concentration, leading to improved insulin resistance in T2DM rats.

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