Human Fatty Acid Research Articles

Diet, Microbiome, and Inflammation Predictors of Fecal and Plasma Short-Chain Fatty Acids in Humans

BackgroundGut microbes produce short-chain fatty acids (SCFAs), which are associated with broad health benefits. However, it is not fully known how diet and/or the gut microbiome could be modulated to improve SCFA production. ObjectivesThe objective of this study was to identify dietary, inflammatory, and/or microbiome predictors of SCFAs in a cohort of healthy adults. MethodsSCFAs were measured in fecal and plasma samples from 359 healthy adults in the United States Department of Agriculture Nutritional Phenotyping Study. Habitual and recent diet was assessed using a food frequency questionnaire and automated self-administered 24-h dietary assessment tool dietary recalls. Markers of systemic and gut inflammation were measured in fecal and plasma samples. The gut microbiome was assessed using shotgun metagenomics. Using statistics and machine learning, we determined how the abundance and composition of SCFAs varied with measures of diet, inflammation, and the gut microbiome. ResultsWe show that fecal pH may be a good proxy for fecal SCFA abundance. A higher healthy eating index for a habitual diet was associated with a compositional increase in fecal butyrate relative to acetate and propionate. SCFAs were associated with markers of subclinical gastrointestinal (GI) inflammation. Fecal SCFA abundance was inversely related to plasma lipopolysaccharide-binding protein. When we analyzed hierarchically organized diet and microbiome data with taxonomy-aware algorithms, we observed that diet and microbiome features were far more predictive of fecal SCFA abundances compared to plasma SCFA abundances. The top diet and microbiome predictors of fecal butyrate included potatoes and the thiamine biosynthesis pathway, respectively. ConclusionsThese results suggest that resistant starch in the form of potatoes and microbially produced thiamine provide a substrate and essential cofactor, respectively, for butyrate synthesis. Thiamine may be a rate-limiting nutrient for butyrate production in adults. Overall, these findings illustrate the complex biology underpinning SCFA production in the gut.This trial was registered at clinicaltrials.gov as NCT02367287.

Machine learning predicts the serum PFOA and PFOS levels in pregnant women: Enhancement of fatty acid status on model performance

Human exposure to per- and polyfluoroalkyl substances (PFASs) has received considerable attention, particularly in pregnant women because of their dramatic changes in physiological status and dietary patterns. Predicting internal PFAS exposure in pregnant women, based on external and relevant parameters, has not been investigated. Here, machine learning (ML) models were developed to predict the serum concentrations of PFOA and PFOS in a large population of 588 pregnant participants. Dietary exposure characteristics, demographic parameters, and in particular, serum fatty acid (FA) data were used for the model development. The fitting results showed that the inclusion of FAs as covariates significantly improved the performance of the ML models, with the random forest (RF) model having the best predictive performance for PFOA (R2 = 0.33, MAE = 1.51 ng/mL, and RMSE = 1.89 ng/mL) and PFOS (R2 = 0.12, MAE = 2.65 ng/mL, and RMSE = 3.37 ng/mL). The feature importance analysis revealed that serum FAs greatly affected PFOA concentration in the pregnant women, with saturated FAs being associated with decreased PFOA levels and unsaturated FAs with increased levels. Comparison with one-compartment pharmacokinetic model further demonstrated the advantage of the ML models in predicting PFAS exposure in pregnant women. Our models correlate for the first time blood chemical concentrations with human FA status using ML, introducing a novel perspective on predicting PFAS levels in pregnant women. This study provides valuable insights concerning internal exposure of PFASs generated from external exposure, and contributes to risk assessment and management in pregnant populations.

Salivary fatty acids in humans: a comprehensive literature review.

Fatty acids (FAs) exert diverse biological functions in humans, influencing physiological responses and, ultimately, health and disease risk. The analysis of FAs in human samples has significant implications and attracts interest in diagnostics and research. The standard method for assessing FA profiles involves the collection of blood samples, which can be inconvenient, invasive, and potentially painful, particularly for young individuals outside hospital settings. Saliva emerged as a promising alternative for evaluating FA profiles in both clinical and research settings. However, to the best of our knowledge, an updated synthesis of the related evidence is unavailable. This comprehensive review aims to summarize data on FA analysis and highlight the potential of the use of salivary FAs as a biomarker in health and disease. Over the past decade, there has been a growing interest in studying salivary FAs in chronic diseases, and more recently, researchers have explored the prognostic value of FAs in acute conditions to check the availability of a non-invasive sampling methodology. A deeper understanding of salivary FAs could have relevant implications both for healthy individuals and patients, particularly in elucidating the correlation between the dietary lipidic content and salivary FA level, Finally, it is crucial to address the standardization of the methods as the sampling, processing, and analysis of saliva are heterogeneous among studies, and limited correlation between blood FAs and salivary FAs is available.

Comparison of comprehensive fatty acid profile from different regions in Chinese human milk project (CHMP) study

In this study, we aimed to detect the comprehensive fatty acid (FA) profile in human milk, including total fatty acids (total FAs), Sn-2 fatty acids (Sn-2 FAs), and phospholipid fatty acids (PLFAs), and further analyzed the influence of the sampling regions on human milk FA profile. The results showed that oleic acid (C18:1n9c), palmitic acid (C16:0), and linoleic acid (C18:2n6c) were the main FA species in total FAs, and Sn-2 C16:0 was the dominant Sn-2 FA species. Moreover, the PLFAs were mainly comprised of PL C16:0, PL stearic acid (PL C18:0), PL C18:1n9c, and PL C18:2n6c. Furthermore, FAs showed geographical differences, such as the highest content of linolenic acid (C18:3n3) and docosahexaenoic acid (C22:6n3) of total FAs was observed in Lanzhou and Weihai, respectively. Therefore, these results provide more FA data for the Chinese human milk database, and further enrich the theoretical information for the development of infant formula.

Intraintestinal fermentation of fructo- and galacto-oligosaccharides and the fate of short-chain fatty acids in humans

Consumption of fructo- (FOS) and galacto-oligosaccharides (GOS) has health benefits which have been linked in part to short-chain fatty acids (SCFA) production by the gut microbiota. However, detailed knowledge of this process in the human intestine is lacking. We aimed to determine the acute fermentation kinetics of a FOS:GOS mixture in healthy males using a naso-intestinal catheter for sampling directly in the ileum or colon. We studied the fate of SCFA as substrates for glucose and lipid metabolism by the host after infusion of 13C-SCFA. In the human distal ileum, no fermentation of FOS:GOS, nor SCFA production, or bacterial cross-feeding was observed. The relative composition of intestinal microbiota changed rapidly during the test day, which demonstrates the relevance of postprandial intestinal sampling to track acute responses of the microbial community toward interventions. SCFA were vividly taken up and metabolized by the host as shown by incorporation of 13C in various host metabolites.

Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma

Palmitic acid (PA) is the most common fatty acid in humans and mediates palmitoylation through its conversion into palmitoyl coenzyme A. Although palmitoylation affects many proteins, its pathophysiological functions are only partially understood. Here we demonstrate that PA acts as a molecular checkpoint of lipid reprogramming in HepG2 and Hep3B cells. The zinc finger DHHC-type palmitoyltransferase 23 (ZDHHC23) mediates the palmitoylation of plant homeodomain finger protein 2 (PHF2), subsequently enhancing ubiquitin-dependent degradation of PHF2. This study also reveals that PHF2 functions as a tumor suppressor by acting as an E3 ubiquitin ligase of sterol regulatory element-binding protein 1c (SREBP1c), a master transcription factor of lipogenesis. PHF2 directly destabilizes SREBP1c and reduces SREBP1c-dependent lipogenesis. Notably, SREBP1c increases free fatty acids in hepatocellular carcinoma (HCC) cells, and the consequent PA induction triggers the PHF2/SREBP1c axis. Since PA seems central to activating this axis, we suggest that levels of dietary PA should be carefully monitored in patients with HCC.

Analysis of omega-3 and omega-6 polyunsaturated fatty acid metabolism by compound-specific isotope analysis in humans

Natural variations in the 13C:12C ratio (carbon-13 isotopic abundance [δ13C]) of the food supply have been used to determine the dietary origin and metabolism of fatty acids, especially in the n-3 PUFA biosynthesis pathway. However, n-6 PUFA metabolism following linoleic acid (LNA) intake remains under investigation. Here, we sought to use natural variations in the δ13C signature of dietary oils and fatty fish to analyze n-3 and n-6 PUFA metabolism following dietary changes in LNA and eicosapentaenoic acid (EPA) + DHA in adult humans. Participants with migraine (aged 38.6 ± 2.3 years, 93% female, body mass index of 27.0 ± 1.1 kg/m2) were randomly assigned to one of three dietary groups for 16 weeks: 1) low omega-3, high omega-6 (H6), 2) high omega-3, high omega-6 (H3H6), or 3) high omega-3, low omega-6 (H3). Blood was collected at baseline, 4, 10, and 16 weeks. Plasma PUFA concentrations and δ13C were determined. The H6 intervention exhibited increases in plasma LNA δ13C signature over time; meanwhile, plasma LNA concentrations were unchanged. No changes in plasma arachidonic acid δ13C or concentration were observed. Participants on the H3H6 and H3 interventions demonstrated increases in plasma EPA and DHA concentration over time. Plasma δ13C-EPA increased in total lipids of the H3 group and phospholipids of the H3H6 group compared with baseline. Compound-specific isotope analysis supports a tracer-free technique that can track metabolism of dietary fatty acids in humans, provided that the isotopic signature of the dietary source is sufficiently different from plasma δ13C.

Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation.

Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.

Lifestyle Factors Associated with Circulating Very Long-Chain Saturated Fatty Acids in Humans: A Systematic Review of Observational Studies.

Recent observational studies have documented inverse associations of circulating very long-chain saturated fatty acids (VLCSFAs), namely arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), with cardiometabolic outcomes. In addition to their endogenous production, it has been suggested that dietary intake or an overall healthier lifestyle may influence VLCSFA concentrations; however, a systematic review of the modifiable lifestyle contributors to circulating VLCSFAs is lacking. Therefore, this review aimed to systematically assess the effects of diet, physical activity, and smoking on circulating VLCSFAs. Following registration on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42021233550), a systematic search of observational studies was conducted in MEDLINE, EMBASE, and The Cochrane databases up to February 2022. A total of 12 studies consisting of mostly cross-sectional analyses were included in this review. The majority of the studies documented the associations of dietary intake with total plasma or red blood cell VLCSFAs, in which a range of macronutrients and food groups were examined. Two cross-sectional analyses showed a consistent positive association between total fat and peanut intake with 22:0 and 24:0 and an inverse association between alcohol intake and 20:0 and 22:0. Furthermore, a moderate positive association between physical activity and 22:0 and 24:0 was observed. Lastly, there were conflicting results on the effects of smoking on VLCSFA. Although most studies had a low risk of bias; the findings of this review are limited by the bi-variate analyses presented in the majority of the included studies, therefore, the impact of confounding is unclear. In conclusion, although the current observational literature examining lifestyle determinants of VLCSFAs is limited, existing evidence suggests that circulating 22:0 and 24:0 may be influenced by higher total and saturated fat consumption and nut intake.

α-linolenic acid interconversion is sufficient as a source of longer chain ω-3 polyunsaturated fatty acids in humans: An opinion.

α-linolenic acid (αLNA) conversion into the functionally important ω-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), has been regarded as inadequate for meeting nutritional requirements for these PUFA. This view is based on findings of small αLNA supplementation trials and stable isotope tracer studies that have been interpreted as indicating human capacity for EPA and, in particular, DHA synthesis is limited. The purpose of this review is to re-evaluate this interpretation. Markedly differing study designs, inconsistent findings and lack of trial replication preclude robust consensus regarding the nutritional adequacy of αLNA as a source of EPC and DHA. The conclusion that αLNA conversion in humans is constrained is inaccurate because it presupposes the existence of an unspecified, higher level of metabolic activity. Since capacity for EPA and DHA synthesis is the product of evolution it may be argued that the levels of EPA and DHA it maintains are nutritionally appropriate. Dietary and supra-dietary EPA plus DHA intakes confer health benefits. Paradoxically, such health benefits are also found amongst vegetarians who do not consume EPA and DHA, and for whom αLNA conversion is the primary source of ω-3 PUFA. Since there are no reported adverse effects on health or cognitive development of diets that exclude EPA and DHA, their synthesis from αLNA appears to be nutritionally adequate. This is consistent with the dietary essentiality of αLNA and has implications for developing sustainable nutritional recommendations for ω-3 PUFA.

Indonesian freshwater fisheries’ oil for health and nutrition applications: a narrative review

The consumption and production of freshwater fish in Indonesia have recently increased significantly, especially in the food sector. This is for health purposes due to the dietary content, including freshwater fish protein. Fish is not only a source of protein but also a considerable supply of polyunsaturated fatty acids (PUFAs) and is essential. Using fish oils has caught a growing interest due to an increased understanding of the possible health benefits of omega-3 fatty acids in humans. This review provided thoughts on progress in the research of Indonesia’s freshwater fisheries’ oil potential. Here, fish oil's potential was addressed through its outstanding biochemical features and its potential as an antiinflammatory, cardiovascular, cancer, and autoimmune disorder agent. Generally, nutritional properties, their possible application in food production, and therapeutic and socioeconomic significance are considered. Indonesian freshwater aquaculture fisheries and inland capture fisheries have the potential for refined fish oil production. The top freshwater fisheries include aquaculture (Oreochromis niloticus, Clarias, Cyprinus carpio, Pangasius, and Osphronemus goramy) and inland capture fisheries (Channa striata, Oreochromis niloticus, Trichogaster, Hemibagrus capitulum, and Pangasius). Indonesian fish oil is rich in omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, and can potentially be developed into drugs and food supplements

A convenient route to mono-trans polyunsaturated free fatty acids

Trans unsaturated fatty acids in humans may be originated both from dietary supplementation and from an endogenous free-radical-catalyzed cis−trans isomerization of fatty acid residues in naturally occurring cis lipids. The latter process affords geometrical isomers and the polyunsaturated fatty acid mono-trans isomers were demonstrated to be connected with stress conditions in living organisms. Synthesis of mono-trans polyunsaturated fatty acid is useful for analytical and biological research, and in this case, the availability of free fatty acids is needed as well as the possibility of mg scale of the synthetic protocol. Herein, we report a simple synthetic route to mono-trans isomers of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, which includes thiyl radical-catalyzed isomerization reaction of polyunsaturated fatty acid methyl esters and fraction isolation of mono-trans mixture isomers followed by optimization of hydrolysis condition to free fatty acids and purification of each mono-trans polyunsaturated fatty acid. Our approach to mono-trans polyunsaturated fatty acids as free acids can reach the mg scale, thus fostering more applications to biochemical and biological studies.

Alpha-linolenic acid inhibits IgE-mediated anaphylaxis by inhibiting Lyn kinase and suppressing mast cell activation

Excessive reactions to allergens can induce systemic, life-threatening physiological dysfunction (anaphylaxis) in humans. The surface of mast cells expresses high-affinity IgE receptors that play a vital role during anaphylaxis. Alpha-linolenic acid (ALA) is an essential non-toxic fatty acid in humans. Since it has been reported having potential to regulate pro-inflammatory reactions, we postulated that ALA could inhibit anaphylaxis by down-regulating Lyn kinase phosphorylation. We found that local and systematic inflammation induced by albumin from chicken egg white (OVA) were attenuated by ALA in vivo. Furthermore, ALA inhibited IgE-mediated Ca2+ mobilization, degranulation, and cytokine release in Laboratory of Allergic Disease 2 (LAD2) cells. The western blot results showed that ALA down-regulate the FcεRI/Lyn/Syk signaling pathway by suppressing Lyn kinase activity. Therefore, ALA could serve as a therapeutic drug candidate for preventing IgE-mediated anaphylaxis.

The homeoviscous adaptation to dietary lipids (HADL) model explains controversies over saturated fat, cholesterol, and cardiovascular disease risk

SFAs play the leading role in 1 of the greatest controversies in nutrition science. Relative to PUFAs, SFAs generally increase circulating concentrations of LDL cholesterol, a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the purpose of regulatory mechanisms that control the diet-induced lipoprotein cholesterol dynamics is rarely discussed in the context of human adaptive biology. We argue that better mechanistic explanations can help resolve lingering controversies, with the potential to redefine aspects of research, clinical practice, dietary advice, public health management, and food policy. In this paper we propose a novel model, the homeoviscous adaptation to dietary lipids (HADL) model, which explains changes in lipoprotein cholesterol as adaptive homeostatic adjustments that serve to maintain cell membrane fluidity and hence optimal cell function. Due to the highly variable intake of fatty acids in humans and other omnivore species, we propose that circulating lipoproteins serve as a buffer to enable the rapid redistribution of cholesterol molecules between specific cells and tissues that is necessary with changes in dietary fatty acid supply. Hence, circulating levels of LDL cholesterol may change for nonpathological reasons. Accordingly, an SFA-induced raise in LDL cholesterol in healthy individuals could represent a normal rather than a pathologic response. These regulatory mechanisms may become disrupted secondarily to pathogenic processes in association with insulin resistance and the presence of other ASCVD risk factors, as supported by evidence showing diverging lipoprotein responses in healthy individuals as opposed to those with metabolic disorders such as insulin resistance and obesity. Corresponding with the model, we suggest alternative contributing factors to the association between elevated LDL cholesterol concentrations and ASCVD, involving dietary factors beyond SFAs, such as an increased endotoxin load from diet-gut microbiome interactions and subsequent chronic low-grade inflammation that interferes with fine-tuned signaling pathways.

Quantification of Fatty Acids and their Regioisomeric Distribution in Triacylglycerols from Porcine and Bovine Sources Using 13 C NMR Spectroscopy.

The uptake of specific fatty acids in humans is dependent on their position on the glycerol backbone. There is a great interest in methods that can access this information fast and accurately. By way of high-resolution NMR, we have analyzed TAG extracted from pig and beef tissues and obtained quantitative data for the composition and regioisomeric distribution of all major unsaturated fatty acids usually found in these source materials, using a combination of manual integration and deconvolution of 13 C NMR spectra. In addition, we have developed a method for determining composition and regioisomeric distribution of the two main saturated fatty acids found in pork (16:0, 18:0). The results are discussed in relation to species-specific genetic characteristics of fatty acid and TAG biosynthesis. The developed method could support decisions related to breeding for desired fatty acid profiles, and stimulate further methodology developments using high field NMR.

Autocrine C-peptide protects INS1 β cells against palmitic acid-induced oxidative stress in peroxisomes by inducing catalase.

AimsC‐peptide, produced by pancreatic β cells and co‐secreted in the bloodstream with insulin, has antioxidant properties in glucose‐ and hydrogen peroxide (H2O2)‐exposed INS1 β cells. Palmitic acid, the most physiologically abundant long‐chain free fatty acid in humans, is metabolized in peroxisomes of β cells accumulating H2O2 that can lead to oxidative stress. Here, we tested the hypothesis that C‐peptide protects β cells from palmitic acid‐induced stress by lowering peroxisomal H2O2.Materials and methodsWe exposed INS1 β cells to palmitic acid and C‐peptide in the setting of increasing glucose concentration and tested for changes in parameters of stress and death. To study the ability of C‐peptide to lower peroxisomal H2O2, we engineered an INS1 β cell line stably expressing the peroxisomal‐targeted H2O2 sensor HyPer, whose fluorescence increases with cellular H2O2. An INS1 β cell line stably expressing a live‐cell fluorescent catalase reporter was used to detect changes in catalase gene expression.ResultsC‐peptide protects INS1 β cells from the combined effect of palmitic acid and glucose by reducing peroxisomal H2O2 to baseline levels and increasing expression of catalase.ConclusionsIn conditions of glucolipotoxicity, C‐peptide increases catalase expression and reduces peroxisomal oxidative stress and death of INS1 β cells. Maintenance of C‐peptide secretion is a pro‐survival requisite for β cells in adverse conditions. Loss of C‐peptide secretion would render β cells more vulnerable to stress and death leading to secretory dysfunction and diabetes.

Structural Basis for the Utilization of Host Fatty Acids by Bacterial Fatty Acid Binding Proteins

The Fatty acid kinase (Fak) system is a two‐protein system allowing Gram‐positive pathogens to incorporate exogenous fatty acids (FA) for membrane phospholipid synthesis. Exogenous FA bind to a FA binding protein, FakB, are phosphorylated by a kinase, FakA, and used to construct the membrane. Phosphorylated FA can also be interconverted to acyl‐acyl carrier protein, via the phosphate acyltransferase PlsX, and be elongated by the fatty acid synthase type II (FASII) system. We used a combination of cellular labeling experiments, genetics, and biochemistry to characterize two FakBs of Staphylococcus aureus and three FakBs of Streptococcus pneumoniae. FakBs have structure‐specific FA binding selectivity unlike mammalian FA binding proteins. Both bacteria use one FakB (FakB1) to exclusively bind saturates and use a second FakB (FakB2) to bind monounsaturates. The additional FakB in S. pneumoniae (FakB3) binds polyunsaturates, specifically linoleate which is an abundant human FA. High‐resolution crystal structures of five FakBs show nearly identical tertiary structures allowing all FakBs to interact with other proteins involved in lipid metabolism. FakBs differ in the shape and volume of their interior FA binding pockets resulting in FA selectivity. FakB1s have a highly tailored pocket and exclude unsaturates. The FA binding pockets of FakB2s are tailored to bind monounsaturates and have a kinked tunnel to match the conformation of the cis double bond. The S. pneumoniae‐specific FakB3 has an expanded acyl chain pocket allowing polyunsaturates to bind. FakB2s and FakB3 cannot completely exclude the binding of saturates because flexible saturated acyl chains fit into both kinked and expanded binding pockets. A lipidomic workflow was used to determine the impact of the two FakBs on the structure of the S. aureus membrane phosphatidylglycerol in a thigh infection model. Wild type S. aureus incorporated saturated and unsaturated host FA into the 1‐position of phosphatidylglycerol, whereas the fakB1 mutant was deficient in saturated FA utilization and the fakB2 mutant did not incorporate unsaturated FA. Mutagenesis, X‐ray crystallography, and NMR show that FakBs bind to anionic membranes using surface lysine residues. The membrane‐bound FA exchanges into FakB after two helices near the FA binding pocket shift outward. This mobile “flap” exposes the FA binding pocket and allows the carboxyl end of the FA to hydrogen bond to polar residues in the pocket. This work reveals the structural basis for the physiological functions of bacterial FA binding proteins in the acquisition of specific host fatty acids at the infection site.Support or Funding InformationThis work was supported by National Institutes of Health grant GM034496, Cancer Center Support Grant CA21765 and the American Lebanese Syrian Associated Charities. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W‐31‐109‐Eng‐38.Model for the function of FakB proteins in S. pneumoniae. Host fatty acids (FA) are incorporated into bacterial phospholipid membranes by binding to FakB. Distinct FakBs bind either saturated FA (SFA), monounsaturated FA (MUFA), or polyunsaturated FA (PUFA). FA are then phosphorylated by a kinase, FakA, and work in concert with the S. pneumoniae FASII machinery to produce substrates for acyltransferases (PlsX, PlsY) which acylate a G3P backbone and form phospholipids.Figure 1

Effects of oats on gastrointestinal health as assessed by in vitro, animal, and human studies.

Oats are uniquely nutritious, owing to their composition of bioactive compounds, lipids, and β-glucan. Scientific research has established that oats can improve diet quality, reduce cholesterol, regulate satiety, and protect against carcinogenesis in the colon; however, determining the effects of oats on gastrointestinal health and the gut microbiome is a newer, evolving area of research. To better understand the effects of oats on gastrointestinal health in humans, a literature review with predefined search criteria was conducted using the PubMed database and keywords for common gastrointestinal health outcomes. Moreover, to examine the gastrointestinal effects of oats across the scientific spectrum, a similar search strategy was executed to identify animal studies. In vitro studies were identified from the reference lists of human and animal studies. A total of 8 human studies, 19 animal studies, and 5 in vitro studies met the inclusion criteria for this review. The evidence in humans shows beneficial effects of oats on gastrointestinal health, with supportive evidence provided by in vitro and animal studies. The effective dose of oats varies by type, although an amount providing 2.5 to 2.9g of β-glucan per day was shown to decrease fecal pH and alter fecal bacteria. For oat bran, 40 to 100g/d was shown to increase fecal bacterial mass and short-chain fatty acids in humans. Differences in study design, methodology, and type of oats tested make valid comparisons difficult. The identification of best practices for the design of oat studies should be a priority in future research, as the findings will be useful for determining how oats influence specific indices of gastrointestinal health, including the composition of the human gut microbiome.

Arachidonic Acid Kills Staphylococcus aureus through a Lipid Peroxidation Mechanism.

Staphylococcus aureus infects every niche of the human host. In response to microbial infection, vertebrates have an arsenal of antimicrobial compounds that inhibit bacterial growth or kill bacterial cells. One class of antimicrobial compounds consists of polyunsaturated fatty acids, which are highly abundant in eukaryotes and encountered by S. aureus at the host-pathogen interface. Arachidonic acid (AA) is one of the most abundant polyunsaturated fatty acids in vertebrates and is released in large amounts during the oxidative burst. Most of the released AA is converted to bioactive signaling molecules, but, independently of its role in inflammatory signaling, AA is toxic to S. aureus Here, we report that AA kills S. aureus through a lipid peroxidation mechanism whereby AA is oxidized to reactive electrophiles that modify S. aureus macromolecules, eliciting toxicity. This process is rescued by cotreatment with antioxidants as well as in a S. aureus strain genetically inactivated for lcpA (USA300 ΔlcpA mutant) that produces lower levels of reactive oxygen species. However, resistance to AA stress in the USA300 ΔlcpA mutant comes at a cost, making the mutant more susceptible to β-lactam antibiotics and attenuated for pathogenesis in a murine infection model compared to the parental methicillin-resistant S. aureus (MRSA) strain, indicating that resistance to AA toxicity increases susceptibility to other stressors encountered during infection. This report defines the mechanism by which AA is toxic to S. aureus and identifies lipid peroxidation as a pathway that can be modulated for the development of future therapeutics to treat S. aureus infections.IMPORTANCE Despite the ability of the human immune system to generate a plethora of molecules to control Staphylococcus aureus infections, S. aureus is among the pathogens with the greatest impact on human health. One class of host molecules toxic to S. aureus consists of polyunsaturated fatty acids. Here, we investigated the antibacterial properties of arachidonic acid, one of the most abundant polyunsaturated fatty acids in humans, and discovered that the mechanism of toxicity against S. aureus proceeds through lipid peroxidation. A better understanding of the molecular mechanisms by which the immune system kills S. aureus, and by which S. aureus avoids host killing, will enable the optimal design of therapeutics that complement the ability of the vertebrate immune response to eliminate S. aureus infections.

Nuclear magnetic resonance screening of changes in fatty acid and cholesterol content of ovine milk induced by ensiled olive cake inclusion in Chios sheep diets

Lipid supplementation of dairy ewe diets has been shown to introduce changes in the fatty acid (FA) profile and cholesterol content of milk. In the present study sheep were fed diets including ensiled olive cake (OC), a conserved by-product of olive oil production, and the lipid content of their milk was assessed in lyophilized samples with nuclear magnetic resonance (NMR) technique. Thirty lactating Chios ewes were allocated into three groups of ten animals fed isonitrogenous and isoenergetic diets which differed in the quantity of ensiled OC inclusion: G0, G500 and G1000 groups with 0, 500, 1000 g (on fresh weight basis) of ensiled OC inclusion per ewe, per day, respectively. Fat percentage, FA profile and cholesterol content were determined in milk samples collected after a 4-week feeding period. Results indicated that saturated FA were reduced by 7.2% and 11.3% in milk samples from the G500 and G1000 groups, respectively. Ensiled OC increased unsaturated FA content by 26.3% and 41.4% and monounsaturated FA content of milk by 30.3% and 45.6% in the G500 and G1000 groups, respectively. Furthermore, the inclusion of 1000 g ensiled OC significantly increased the content of beneficial for human health FA such as conjugated linoleic acids (CLA isomers: 9-cis, 11-trans CLA; 9-trans, 11-cis CLA and 10-trans, 12-cis CLA) by 47.2% and linoleic acid by 14.4% compared to control group. However, any rate of ensiled OC inclusion in the diets of ewes had no effect on milk cholesterol content or milk fat percentage. Overall, the present work provides novel experimental data with NMR fingerprinting of the lyophilized milk lipid fraction, and suggests the use of ensiled OC in sheep rations since it induces desirable changes in ovine milk lipids.