scholarly journals Protein fermentation in the gut; implications for intestinal dysfunction in humans, pigs, and poultry

2018 ◽  
Vol 315 (2) ◽  
pp. G159-G170 ◽  
Author(s):  
Myrthe S. Gilbert ◽  
Noortje Ijssennagger ◽  
Arie K. Kies ◽  
Saskia W. C. van Mil
Keyword(s):  
Fatty Acids ◽  
Dietary Protein ◽  
Protein Intake ◽  
Intestinal Disease ◽  
Gut Health ◽  
Bacterial Strains ◽  
Fermentation Products ◽  
Epithelial Damage ◽  
Production Animals ◽  
Chain Fatty Acids

The amount of dietary protein is associated with intestinal disease in different vertebrate species. In humans, this is exemplified by the association between high-protein intake and fermentation metabolite concentrations in patients with inflammatory bowel disease. In production animals, dietary protein intake is associated with postweaning diarrhea in piglets and with the occurrence of wet litter in poultry. The underlying mechanisms by which dietary protein contributes to intestinal problems remain largely unknown. Fermentation of undigested protein in the hindgut results in formation of fermentation products including short-chain fatty acids, branched-chain fatty acids, ammonia, phenolic and indolic compounds, biogenic amines, hydrogen sulfide, and nitric oxide. Here, we review the mechanisms by which these metabolites may cause intestinal disease. Studies addressing how different metabolites induce epithelial damage rely mainly on cell culture studies and occasionally on mice or rat models. Often, contrasting results were reported. The direct relevance of such studies for human, pig, and poultry gut health is therefore questionable and does not suffice for the development of interventions to improve gut health. We discuss a roadmap to improve our understanding of gut metabolites and microbial species associated with intestinal health in humans and production animals and to determine whether these metabolite/bacterial networks cause epithelial damage. The outcomes of these studies will dictate proof-of-principle studies to eliminate specific metabolites and or bacterial strains and will provide the basis for interventions aiming to improve gut health.

scholarly journals Short chain fatty acids and methylamines produced by gut microbiota as mediators and markers in the circulatory system

2020 ◽  
Vol 245 (2) ◽  
pp. 166-175 ◽  
Author(s):  
Maksymilian Onyszkiewicz ◽  
Kinga Jaworska ◽  
Marcin Ufnal
Keyword(s):  
Fatty Acids ◽  
Cardiovascular Diseases ◽  
Gut Microbiota ◽  
Therapeutic Targets ◽  
Circulatory System ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Bacterial Strains ◽  
Ample Evidence ◽  
Chain Fatty Acids

Ample evidence suggests that gut microbiota-derived products affect the circulatory system functions. For instance, short chain fatty acids, that are the products of dietary fiber bacterial fermentation, have been found to dilate blood vessels and lower blood pressure. Trimethylamine, a gut bacteria metabolite of carnitine and choline, has recently emerged as a potentially toxic molecule for the circulatory system. To enter the bloodstream, microbiota products cross the gut–blood barrier, a multilayer system of the intestinal wall. Notably, experimental and clinical studies show that cardiovascular diseases may compromise function of the gut–blood barrier and increase gut-to-blood penetration of microbiota-derived molecules. Hence, the bacteria products and the gut–blood barrier may be potential diagnostic and therapeutic targets in cardiovascular diseases. In this paper, we review research on the cardiovascular effects of microbiota-produced short chain fatty acids and methylamines. Impact statement Despite a progress in the diagnosis and treatment of cardiovascular diseases, there are still significant gaps in understanding complex mechanisms underlying cardiovascular pathology. Increasing evidence suggests that gut microbiota products such as short chain fatty acids or methylamines may affect the circulatory system in health and disease. Hence, the microbiota-derived molecules are potential diagnostic and therapeutic targets in cardiovascular diseases. Therapeutic options may include administration of selected bacterial strains (probiotics) producing desired metabolites or administration of direct gut microbiota products.

scholarly journals The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection

2009 ◽  
Vol 420 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Nanda Burger-van Paassen ◽  
Audrey Vincent ◽  
Patrycja J. Puiman ◽  
Maria van der Sluis ◽  
Janneke Bouma ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Goblet Cell ◽  
Histone H3 ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Specific Gene ◽  
Mrna Levels ◽  
Fermentation Products ◽  
Muc2 Expression ◽  
Chain Fatty Acids

SCFAs (short-chain fatty acids), fermentation products of bacteria, influence epithelial-specific gene expression. We hypothesize that SCFAs affect goblet-cell-specific mucin MUC2 expression and thereby alter epithelial protection. In the present study, our aim was to investigate the mechanisms that regulate butyrate-mediated effects on MUC2 synthesis. Human goblet cell-like LS174T cells were treated with SCFAs, after which MUC2 mRNA levels and stability, and MUC2 protein expression were analysed. SCFA-responsive regions and cis-elements within the MUC2 promoter were identified by transfection and gel-shift assays. The effects of butyrate on histone H3/H4 status at the MUC2 promoter were established by chromatin immunoprecipitation. Butyrate (at 1 mM), as well as propionate, induced an increase in MUC2 mRNA levels. MUC2 mRNA levels returned to basal levels after incubation with 5–15 mM butyrate. Interestingly, this decrease was not due to loss of RNA stability. In contrast, at concentrations of 5–15 mM propionate, MUC2 mRNA levels remained increased. Promoter-regulation studies revealed an active butyrate-responsive region at −947/−371 within the MUC2 promoter. In this region we identified an active AP1 (c-Fos/c-Jun) cis-element at −818/−808 that mediates butyrate-induced activation of the promoter. Finally, MUC2 regulation by butyrate at 10–15 mM was associated with increased acetylation of histone H3 and H4 and methylation of H3 at the MUC2 promoter. In conclusion, 1 mM butyrate and 1–15 mM propionate increase MUC2 expression. The effects of butyrate on MUC2 mRNA are mediated via AP-1 and acetylation/methylation of histones at the MUC2 promoter.

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.

Short-chain fatty acids and acidic pH upregulate UT-B, GPR41, and GPR4 in rumen epithelial cells of goats

2015 ◽  
Vol 308 (4) ◽  
pp. R283-R293 ◽  
Author(s):  
Zhongyan Lu ◽  
Hongbing Gui ◽  
Lei Yao ◽  
Lei Yan ◽  
Holger Martens ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Acidic Ph ◽  
Fermentation Products ◽  
Plasma Urea ◽  
Protein Levels ◽  
Rumen Epithelium ◽  
Chain Fatty Acids

Currently, the mechanism(s) responsible for the regulation of urea transporter B (UT-B) expression levels in the epithelium of the rumen remain unclear. We hypothesized that rumen fermentation products affect ruminal UT-B expression. Therefore, the effects of short-chain fatty acids (SCFA), pH, ammonia, and urea on mRNA and protein levels of UT-B were assayed in primary rumen epithelial cell cultures and in rumen epithelium obtained from intact goats. In vitro, SCFA and acidic pH were found to synergetically stimulate both mRNA and protein expression of UT-B, whereas NH4Cl decreased mRNA and protein levels of UT-B at pH 6.8. Treatment with urea increased both levels at pH 7.4. When goats received a diet rich in nitrogen (N) and nonfiber carbohydrates (NFC), their rumen epithelium had higher levels of UT-B, and the rumen contained higher concentrations of SCFA and NH3-N with a lower pH. An increase in plasma urea-N concentration was also observed compared with the plasma of the goats that received a diet low in N and NFC. In a second feeding trial, goats that received a NFC-rich, but isonitrogenous, diet had higher mRNA and protein levels of UT-B, and higher levels of G protein-coupled receptor (GPR) 41 and GPR4, in their rumen epithelium. The ruminal concentrations of SCFA and NH3-N also increased, while a lower pH was detected. In contrast, the serum urea-N concentrations remained unchanged. These data indicate that ruminal SCFA and pH are key factors, via GPR4 and GPR41, in the dietary regulation of UT-B expression, and they have priority over changes in plasma urea.

scholarly journals Effect of dark sweet cherry powder consumption on the gut microbiota, short-chain fatty acids, and biomarkers of gut health in obese db/db mice

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4195 ◽  
Author(s):  
Jose F. Garcia-Mazcorro ◽  
Nara N. Lage ◽  
Susanne Mertens-Talcott ◽  
Stephen Talcott ◽  
Boon Chew ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Standard Diet ◽  
Gut Health ◽  
Microbial Composition ◽  
Unifrac Distance ◽  
Colonic Microbiota ◽  
Chain Fatty Acids

Cherries are fruits containing fiber and bioactive compounds (e.g., polyphenolics) with the potential of helping patients with diabetes and weight disorders, a phenomenon likely related to changes in the complex host-microbiota milieu. The objective of this study was to investigate the effect of cherry supplementation on the gut bacterial composition, concentrations of caecal short-chain fatty acids (SCFAs) and biomarkers of gut health using an in vivo model of obesity. Obese diabetic (db/db) mice received a supplemented diet with 10% cherry powder (supplemented mice, n = 12) for 12 weeks; obese (n = 10) and lean (n = 10) mice served as controls and received a standard diet without cherry. High-throughput sequencing of the 16S rRNA gene and quantitative real-time PCR (qPCR) were used to analyze the gut microbiota; SCFAs and biomarkers of gut health were also measured using standard techniques. According to 16S sequencing, supplemented mice harbored a distinct colonic microbiota characterized by a higher abundance of mucin-degraders (i.e., Akkermansia) and fiber-degraders (the S24-7 family) as well as lower abundances of Lactobacillus and Enterobacteriaceae. Overall this particular cherry-associated colonic microbiota did not resemble the microbiota in obese or lean controls based on the analysis of weighted and unweighted UniFrac distance metrics. qPCR confirmed some of the results observed in sequencing, thus supporting the notion that cherry supplementation can change the colonic microbiota. Moreover, the SCFAs detected in supplemented mice (caproate, methyl butyrate, propionate, acetate and valerate) exceeded those concentrations detected in obese and lean controls except for butyrate. Despite the changes in microbial composition and SCFAs, most of the assessed biomarkers of inflammation, oxidative stress, and intestinal health in colon tissues and mucosal cells were similar in all obese mice with and without supplementation. This paper shows that dietary supplementation with cherry powder for 12 weeks affects the microbiota and the concentrations of SCFAs in the lower intestinal tract of obese db/db diabetic mice. These effects occurred in absence of differences in most biomarkers of inflammation and other parameters of gut health. Our study prompts more research into the potential clinical implications of cherry consumption as a dietary supplement in diabetic and obese human patients.

scholarly journals FiberGrowth Pipeline: A Framework Toward Predicting Fiber-Specific Growth From Human Gut Bacteroidetes Genomes

2021 ◽  
Vol 12 ◽  
Author(s):  
Bénédicte Colnet ◽  
Christian M. K. Sieber ◽  
Fanny Perraudeau ◽  
Marion Leclerc
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
False Positive Rate ◽  
Short Chain Fatty Acids ◽  
Glycoside Hydrolases ◽  
Short Chain ◽  
Bacterial Strains ◽  
Positive Rate ◽  
Chain Fatty Acids

Dietary fibers impact gut colonic health, through the production of short-chain fatty acids. A low-fiber diet has been linked to lower bacterial diversity, obesity, type 2 diabetes, and promotion of mucosal pathogens. Glycoside hydrolases (GHs) are important enzymes involved in the bacterial catabolism of fiber into short-chain fatty acids. However, the GH involved in glycan breakdown (adhesion, hydrolysis, and fermentation) are organized in polysaccharide utilization loci (PUL) with complex modularity. Our goal was to explore how the capacity of strains, from the Bacteroidetes phylum, to grow on fiber could be predicted from their genome sequences. We designed an in silico pipeline called FiberGrowth and independently validated it for seven different fibers, on 28 genomes from Bacteroidetes-type strains. To do so, we compared the existing GH annotation tools and built PUL models by using published growth and gene expression data. FiberGrowth’s prediction performance in terms of true positive rate (TPR) and false positive rate (FPR) strongly depended on available data and fiber: arabinoxylan (TPR: 0.89 and FPR: 0), inulin (0.95 and 0.33), heparin (0.8 and 0.22) laminarin (0.38 and 0.17), levan (0.3 and 0.06), mucus (0.13 and 0.38), and starch (0.73 and 0.41). Being able to better predict fiber breakdown by bacterial strains would help to understand their impact on human nutrition and health. Assuming further gene expression experiment along with discoveries on structural analysis, we hope computational tools like FiberGrowth will help researchers prioritize and design in vitro experiments.

scholarly journals Determination and Comparison of Short-Chain Fatty Acids in Serum and Colon Content Samples: Alzheimer’s Disease Rat as a Case Study

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5739
Author(s):  
Lin-Xiu Guo ◽  
Yue Tong ◽  
Jue Wang ◽  
Guo Yin ◽  
Hou-Shuang Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Whole Body ◽  
Serum Samples ◽  
Fermentation Products ◽  
Chain Fatty Acids

Short-chain fatty acids (SCFAs) are the main microbial fermentation products from dietary fibers in the colon, and it has been speculated that they play a key role in keeping healthy in the whole-body. However, differences in SCFAs concentration in the serum and colon samples had attracted little attention. In this study, we have optimized the extract and analysis methods for the determination of ten SCFAs in both serum and colon content samples. Methanol and acetonitrile were chosen for extraction of SCFAs from serum and colon content samples, respectively. Biological samples were collected from Alzheimer’s disease rats treated by extract of Schisandra chinensis (Turcz.) Baill (SC-extract) were taken as research objects. The results showed that, the relative peak intensities of SCFAs in the colon content from all groups were quite similar, and the trend was identical in the serum samples. Compared with the values in humans, the ratio of ten SCFAs in rat’s colon was similar, while the percent of acetate in rat’s serum was significantly higher. For therapy of Alzheimer’s disease (AD), SC-extract decreased the concentration of butyrate, 3-Methyvalerate, and caproate in the serum samples towards the trend of normal rats. This study may help our understanding of how SCFAs are transported across colonic epithelium in healthy and diseased organisms.

scholarly journals Stool pH and Short/Branched Chain Fatty Acids in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (P11-076-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Car Reen Kok ◽  
Bradford Brabec ◽  
Maciej Chichlowski ◽  
Cheryl Harris ◽  
Nancy Moore ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Amino Acid ◽  
Human Milk ◽  
Dietary Protein ◽  
Fused Silica ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Mother’S Own Milk ◽  
Different Sources ◽  
Chain Fatty Acids

Abstract Objectives Infant feeding influences early development of the gut microbiome, colonization pattern, and community structure. Metabolites, including short- and branched-chain fatty acids (S/BCFA) (e.g., butyrate, propionate), produced by colonic bacteria serve as signaling molecules, influence immunity, and reduce luminal pH in the gastrointestinal environment. The objective of this study was to evaluate stool S/BCFA and pH in infants fed with different sources of dietary protein. Methods In this multicenter, double-blind, controlled, parallel-group, pilot study, healthy term infants were randomized to receive one of two infant formulas (IF): amino-acid based (AAF; n = 25) or extensively hydrolyzed cow's milk protein (EHF; n = 28) from Baseline (1-7 days of age) up to 60 days of age. A human milk reference group (HM; n = 25) received mother's own milk over the same period. Diethyl ether extractions of S/BCFA from stool samples (Baseline, Day 30, and Day 60) were quantified by gas chromatography (Clarus 580; PerkinElmer) using a fused silica capillary column (Nukol 30m × 0.25mm id × 0.25μm film). Mean stool S/BCFA (μmol/g) and pH were analyzed by repeated measures analysis of variance (ANOVA). Results Complete stool data (all study time points) were available for 49 participants. Stool pH (∼6) was similar among groups at Baseline with no significant changes for HM and EHF groups through Day 60. The AAF group was significantly higher at Days 30 and 60 (Figure 1). Total SCFA were similar for all groups through Day 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group (P = 0.026) and was significantly higher vs HM at Days 30 and 60 (P = 0.0009 and 0.0004 respectively). Butyrate was significantly higher for AAF vs HM at Day 60 only (P = 0.038). Propionate was significantly higher for EHF and AAF at Day 30 (P = 0.0009 and < 0.0001 respectively) and AAF only at Day 60 (P = 0.005) vs HM. Total and individual BCFA increased for AAF and EHF groups vs HM through Day 60. Conclusions Distinct patterns of pH and microbial metabolites were demonstrated for infants receiving mother's own milk compared to amino acid-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites. Funding Sources Mead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs

scholarly journals Combined Buckwheat d-Fagomine and Fish Omega-3 PUFAs Stabilize the Populations of Gut Prevotella and Bacteroides While Reducing Weight Gain in Rats

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2606 ◽  
Author(s):  
Mercè Hereu ◽  
Sara Ramos-Romero ◽  
Roser Marín-Valls ◽  
Susana Amézqueta ◽  
Bernat Miralles-Pérez ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Weight Gain ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Omega 3 ◽  
Sprague Dawley ◽  
Bacterial Strains ◽  
Pufa Supplementation ◽  
Sprague Dawley Rats ◽  
Chain Fatty Acids

Some functional food components may help maintain homeostasis by promoting balanced gut microbiota. Here, we explore the possible complementary effects of d-fagomine and ω-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA 1:1) on putatively beneficial gut bacterial strains. Male Sprague–Dawley rats were supplemented with d-fagomine, ω-3 PUFAs, or both, for 23 weeks. Bacterial subgroups were evaluated in fecal DNA by quantitative real-time polymerase chain reaction (qRT-PCR) and short-chain fatty acids were determined by gas chromatography. We found that the populations of the genus Prevotella remained stable over time in animals supplemented with d-fagomine, independently of ω-3 PUFA supplementation. Animals in these groups gained less weight than controls and rats given only ω-3 PUFAs. d-Fagomine supplementation together with ω-3 PUFAs maintained the relative populations of Bacteroides. ω-3 PUFAs alone or combined with d-fagomine reduced the amount of acetic acid and total short-chain fatty acids in feces. The plasma levels of pro-inflammatory arachidonic acid derived metabolites, triglycerides and cholesterol were lower in both groups supplemented with ω-3 PUFAs. The d-fagomine and ω-3 PUFAs combination provided the functional benefits of each supplement. Notably, it helped stabilize populations of Prevotella in the rat intestinal tract while reducing weight gain and providing the anti-inflammatory and cardiovascular benefits of ω-3 PUFAs.

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