Chain Fatty Acid Levels Research Articles

Oral Administration of Heat-Treated Lactobacilli Modifies the Murine Microbiome and Reduces Citrobacter Induced Colitis.

Significant evidence supports a relationship between the gut microbiome, inflammation, host response, and health, including the finding that a number of disorders are associated with disruption of the microbiome. In these disorders, a number of dietary interventions (including prebiotics, live probiotics, or heat-killed microbes) have been proposed to be curative or preventative agents. The use of heat-killed microbes has a number of benefits over living organisms, including reduced infection risk in vulnerable individuals, extended shelf life and the potential for use in combination with antimicrobial agents. We previously reported that murine chow supplemented with 5% ADR-159, a heat-treated fermentate generated by two Lactobacillus strains, altered both behavior and the microbiome of male mice. Now we show that ADR-159 fed female mice also display a similar microbiome shift as determined by 16S rDNA analysis. In particular, we observed a reduction of levels of Turicibacter and Clostridium sensu stricto. These subtle changes in the bacterial component of the microbiome were mirrored by changes in the virome. Extended consumption of the ADR-159 diet had no negative effect on general health and lipocalin 2 levels (LCN2; a proxy for inflammation), but we observed increased IL-17f and decreased IL-12α expression in the colon and decreased short chain fatty acid levels in the ADR-159 fed animals. Four weeks into the diet, half of the animals were dosed with Citrobacter to determine the effect of ADR-159 on infection and on pathogen induced colitis. Overall, our results suggest that while the ADR-159 diet does not prevent Citrobacter infection, it had an effect on Citrobacter-induced inflammation. In contrast to animals fed standard chow, ADR-159 fed animals did not show a reduction of small intestine length and increase of colon crypt depth, which occurred in control mice. These microbiological, histological, and immunological results provide evidence to support the impact of heat-treated microorganisms and their metabolites on the murine microbiome and health.

The Effect of Dietary Fiber Intake on Systemic Lupus Erythematosus (SLE) Disease in NZB/W Lupus Mice

Dysbiosis in the gut microbiota has been observed in a various autoimmune disease, including SLE, which could cause a leaky gut, triggering an immune response, and thus worsening autoimmune disease expression. In our current studies, we hypothesized that increasing dietary fiber would create a healthy microbiota environment in the gut, leading to decreased leakiness of the gut and to decreased disease expression in and NZB/NZW female lupus-like mice. NZB/NZW mice were placed on standardized high fiber (HF 30%) or low fiber (LF 0.4%) for 12 weeks beginning at 20 weeks of age. Mice were assessed as they aged for various parameters of disease including proteinuria and anti-dsDNA antibody production. Alteration of the microbiota and short chain fatty acid (SCFA) levels were also assessed. At 36 weeks-of-age, the mice were euthanized, and we assessed occlusion protein expression, splenocyte profiles, and kidney tissue. We found as the mice aged, their body weights, anti-dsDNA antibody levels, and proteinuria were not significantly different between the groups. Similarly, there were no significant differences in SCFA levels. Regarding the microbiota, Chlostridiales bacteria were consistently increased in the HF treated mice compared to the LF treated mice. Furthermore, as the mice aged, disease progression as assessed by - spleen weight, immune cell profiles, proteinuria, dsDNA levels, and kidney pathology, was not different between the HF and LF treated groups. Taken together, these results indicate that in the NZB/W female lupus mouse model, a HF diet may alter the microbiota but does not influence disease progression.

Adrenal Insufficiency by Adrenoleukodystrophy

The X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disorder due to mutations in the ABCD1 gene. Objective: To report a case of a 19-year-old man with adrenal insufficiency due to adrenoleukodystrophy. Method: Case report and literature review. Result: A previously healthy 19-year-old male patient was admitted to the emergency room with nausea and vomiting for 5 days, who progressed to abdominal pain, severe asthenia, and fever (38.5°C). He referred progressive darkening of the skin, oral mucosa, tongue and nail bed of the hands and feet, observed in the last 6 years. Emergency laboratory evaluation showed severe hyponatremia and hyperkalemia, which, together with decreased plasma cortisol, directed the investigation to causes of adrenal insufficiency. High ACTH (Adrenocorticotropic hormone) and very long chain fatty acid levels closed the diagnosis. Discussion: ALD is characterized by progressive demyelination in the central and peripheral nervous system and adrenal insufficiency consequence to the accumulation of very long chain fatty acids (VLCFA) in the adrenal. The overall incidence of ALD is 1:17,000. Adrenal insufficiency may be the first symptom of ALD in boys and adults. The diagnosis is based on the measurement of VLCFA plasma levels. Allogeneic bone marrow transplantation is the only treatment that provides a permanent cure when the procedure is performed at an early stage of brain demyelination, i.e. when patients are asymptomatic, although brain magnetic resonance imaging (MRI) is abnormal. Treatment of Addison’s disease is obligatory, but does not change the course of neurological symptoms.

The Effect of Cigarette and Alcohol on Intestinal Flora: A Population-Based Cross-Sectional Study

Background: Human intestinal flora is affected by the exogenous microenvironment. This study aims to figure out the effect of cigarette and alcohol drinking on gut microbiota in health adults. Methods: 170 health subjects were enrolled and divided into four groups including none smokers and drinkers (group A), smokers (group B), drinkers (group C), and smokers and drinkers (group D). Fecal samples were collected and sequenced by 16S rRNA to analyze the microbial composition and KEGG predicted functional pathways. Short chain fatty acids (SCFAs) levels in feces were determined by gas chromatography. Findings: We observed lower diversity and evenness indicated by Simpson and Heip indexes in smokers or drinkers when compared as control group A (p<0.05). The smokers only group had lower diversity and evenness compared with group C and group D (p＜0.01 and p＜0.05, respectively). The overall bacterial profiles had no difference among different groups. Smokers only (group B) or both smokers and drinkers (group D) showed significant increase of phylum Bacteroidetes, as well as higher Bacteroidetes: Firmicutes ratio by nearly 3- and 2- fold change respectively compared with group A(p<0.05). In contrast, the abundance of ‘beneficial’ bacteria, including butyric-producing bacteria Ruminococcaceae_UCG-005, Flavonifractor and Bacillus was significantly decreased in smoker or drinker populations, especially in smokers. We found that immunity-related, bacterial metabolism and disease-associated pathways were more abundant in group smoker or drinker populations. There is no difference in SCFAs among all groups. Interpretation: Human intestinal flora was affected by cigarette and alcohol, especially by cigarette in microbial diversity and composition. Our results indicated that the intestinal flora played potential role in cigarette/alcohol-related diseases. However, when two factors considered, the effect on the intestinal flora and diseases maybe counteract by each other. Funding Statement: This work was supported by the Public Welfare Technology Application Research Plan of Zhejiang Province for Laboratory Animals (2017C37149), Science and Technology Plan of Medicine and Health of Zhejiang Province (2018KY474), Natural Science Foundation of Zhejiang Province (LY18H160011). Declaration of Interests: All authors claim that there is no competing interest between them. Ethics Approval Statement: This study was conducted under the guide of Ethics Committee of Sir Run Run Shaw Hospital and the China Association for Clinical Research.

Effects of stachyose on intestinal microbiota and immunity in mice infected with enterotoxigenic Escherichia coli

Abstract Enterotoxigenic Escherichia coli (ETEC) is an important pathogen causing diarrhea in humans. Finding natural, safe and effective functional ingredients to replace antibiotics is an important direction for preventing and treating E. coli infection and protecting intestinal health. However, it is unknown whether stachyose promotes the proliferation of probiotics and thus inhibits ETEC infection. Here, we investigated whether stachyose improves the gut microbiota of ETEC-infected mice and induces effects in early postnatal life. Stachyose promoted the proliferation of A. muciniphila and Bifidobacterium, increased short chain fatty acids (SCFAs) levels, increased the expression of tight junction proteins (occludin and ZO-1), increased SIgA and albumin levels, and reduced the level of lipopolysaccharide (LPS), IL-1, 6, 17 and TNF-α. After antibiotic-induced ablation, the resistance of the intestinal microbiota of the ETEC-infected mice to bacteria was significantly reduced, and the level of inflammation was increased, the SIgA and albumin levels decreased significantly, showed the intestinal microbiota plays an important role in maintaining immune resistance. Stachyose enabled partial microbiota recovery and protection after ETEC infection.

The combination of wheat peptides and fucoidan protects against chronic superficial gastritis and alters gut microbiota: a double-blinded, placebo-controlled study.

Chronic gastritis is observed in almost half world population. Traditional medications against chronic gastritis might produce adverse effects, so alternative nutritional strategies are needed to prevent the aggravation of gastric mucosal damage. The aim of this study is to evaluate the protective effect of the combination of wheat peptides and fucoidan (WPF) on adults diagnosed with chronic superficial gastritis in a randomized, double-blind, placebo-controlled clinical trial. Participants were randomized to receive WPF (N = 53) or placebo (N = 53) once daily for 45days. Pathological grading of gastric mucosal damage was scored using gastroscopy. Fecal samples were collected for the determination of calprotectin, short chain fatty acids (SCFA) levels and metagenomics analysis. Questionnaires for self-reported gastrointestinal discomforts, life quality and food frequency were collected throughout the study. WPF intervention reduced gastric mucosal damage in 70% subjects (P < 0.001). Significantly less stomach pain (P < 0.001), belching (P = 0.028), bloating (P < 0.001), acid reflux (P < 0.001), loss of appetite (P = 0.021), increased food intake (P = 0.020), and promoted life quality (P = 0.014) were reported in the WPF group. WPF intervention significantly decreased fecal calprotectin level (P = 0.003) while slightly increased fecal SCFAs level (P = 0.092). In addition, we found altered microbiota composition post-intervention with increased Bifidobacterium pseudocatenulatum (P = 0.032), Eubacterium siraeum (P = 0.036), Bacteroides intestinalis (P = 0.024) and decreased Prevotella copri (P = 0.055). WPF intervention could be utilized as a nutritional alternative to mitigate the progression of chronic gastritis. Furthermore, WPF played an important role in altering gut microbial profile and SCFA production, which might benefit the lower gastrointestinal tract.

Production and faecal fermentation of pentose oligomers of hemicellulose: Study of variables influencing bioprocess efficiency

Almond shell, a by-product obtained from the nut industry, was valorised into low degree of polymerisation xylooligosaccharides using alkaline pretreatment and enzymatic hydrolysis. The effect of particle size on hemicellulose recovery upon pretreatment was studied using 1 and 2 M NaOH. It was observed that particle size significantly influences hemicellulose recovery, as particles below 120 µm resulted in near complete recovery at 2 M NaOH. Enzymatic hydrolysis of hemicellulose was optimised using response surface methodology, to obtain efficient xylooligosaccharides production at low enzyme dose and high substrate concentration. For higher XOS yield, an enzyme dose of 10 U and substrate concentration <2% was optimal. The in-vitro human faecal fermentation study revealed no significant difference in gas and short chain fatty acid level among substrates evaluated. It was observed that short chain oligosaccharides produce higher level of acetate than medium chain oligosaccharides.

Fermented Soybean Dregs by Neurospora crassa: a Traditional Prebiotic Food.

Soybean dregs fermented by Neurospora crassa is a typical traditional food in Gannan district of China. In this study, in vitro imitated gut fermentation was carried out to evaluate whether the oligosaccharides from this fermented soybean dregs had potential prebiotic properties. 11.91% of oligosaccharides were extracted from the fermented soybean dregs at the optimized condition which of 1:25 for ratio of soybean dregs (g) to 50% ethanol (ml), 90min of extracted duration at 70°C for twice. The soybean dreg oligosaccharides (SBOS) were progressively purified with Sevag method and on columns filled with AB-8 macroporous resin, and then identified as cellobiose by HPLC-ESI-MS and FT-IR. Oligosaccharides of soybean dregs with 800mg/L significantly decreased pH value (p < 0.05) and ammonia N concentration (p < 0.05), and increased short chain fatty acid (SCFA) level (p < 0.05) in imitated gut fermentation compared with control group. It was shown that this fermented soybean dregs could be a potential prebiotic food.

A unique polysaccharide from Hericium erinaceus mycelium ameliorates acetic acid-induced ulcerative colitis rats by modulating the composition of the gut microbiota, short chain fatty acids levels and GPR41/43 respectors

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa. Risk of colorectal cancer in ulcerative colitis is increased in patients with long-standing disease compared with the general population. Hericium erinaceus (HE) has been used in traditional folk medicine and medicinal cuisine in China, Korea and Japan with anti-gastritis and anti-ulcerative colitis activities. EP-1, a purified unique polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for anti- ulcerative colitis activity by using a cell model for identification. In this study, our data shows that EP-1 was effective in relieving the symptoms of acetic acid induced UC rats. Based on the Illumina MiSeq platform, 16S rRNA sequencing of the rat colonic contents indicated that the intestinal flora structure remarkably changed in the model rats and the tendency was alleviated to a certain degree by EP-1. The further results showed that in the acetic acid induced UC rats EP-1 modulated the gut microbiota community and increased short chain fatty acids (SCFAs). And immunoblot analyses showed that after treated by EP-1, GPR41 and GPR43 were significantly suppressed expression in colonic tissues of the UC rats. In the meanwhile, EP-1 also showed its antioxidant, anti-inflammatory and enhancing immune activities. Thus, the polysaccharide purified from HE showed potential for anti-UC activity and the complementary and alternative medicine (CAM) herb therapy.

Ganoderma lucidum polysaccharide improves rat DSS-induced colitis by altering cecal microbiota and gene expression of colonic epithelial cells

BackgroundThe effects of β-glucan on colitis mice are contradictory in previous reports. As a result, it is still unclear whether there is an anti-colitis effect in Ganoderma lucidum polysaccharide (GLP), which is mainly composed of β-glucan. Moreover, the association between GLP function and gut microbiota remains to be elucidated.ObjectiveThis study aimed to investigate whether GLP consumption improved rat dextran sodium sulfate (DSS)-induced colitis by regulating gut microbiota and altering colonic epithelial expression.DesignThe disease activity index (DAI) scores and the cecal short chain fatty acid (SCFA) levels of DSS-induced colitis rats fed with a GLP diet (Group GLP, n = 6) and a control diet (Group Con, n = 6) were investigated and analyzed. Moreover, the profiles of gut microbiota and colonic epithelial expression were analyzed using metagenomics and transcriptomics.ResultsGLP consumption significantly lowered animal DAI scores by producing more SCFAs by increasing SCFA-producing bacteria such as Ruminococcus_1 and reducing pathogens such as Escherichia-Shigella in both the small intestine and cecum of rat. Moreover, GLP consumption regulated 11 genes, including six upregulated (Ccl5, Cd3e, Cd8a, Il21r, Lck, and Trbv) and five downregulated (Ccl3, Gro, Il11, Mhc2, and Ptgs) genes enriched in six inflammation-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, resulting in enhancement of immunity and reduction of inflammatory response and colonic cancer risk.ConclusionsGLP consumption alleviated DSS-induced colitis and may have potential for ulcerative colitis relief.

Cream Cheese-Derived Lactococcus chungangensis CAU 28 Modulates the Gut Microbiota and Alleviates Atopic Dermatitis in BALB/c Mice

Atopic dermatitis (AD) has a drastic impact on human health owing to complex skin, gut microbiota, and immune responses. Some lactic acid bacteria (LAB) are effective in ameliorating AD; however, the alleviative effects of dairy products derived from these LAB remain unclear. In this study, the efficacies of Lactococcus chungangensis CAU 28 (CAU 28) cream cheese and L. chungangensis CAU 28 dry cells were evaluated for treating AD in an AD mouse model. Overall, CAU 28 cream cheese administration was more effective against AD than L. chungangensis CAU 28 dry cells. Faeces from CAU 28 cream cheese-administered mice had increased short chain fatty acid, butyrate, acetate, and lactic acid levels, as well as butyrate-producing bacteria, including Akkermansia, Bacteroides, Lactobacillus, and Ruminococcus. Furthermore, oral CAU 28 cream cheese administration resulted in regulatory T cell (Treg)-mediated suppression of T helper type 2 (Th2) immune responses in serum and mRNA expression levels in the ileum. Oral CAU 28 cream cheese further reduced IgE levels, in addition to eosinophil and mast cell numbers. Therefore, CAU 28 cream cheese administration induced a coordinated immune response involving short-chain fatty acids and gut microbiota, indicating its potential for use as a supplement for AD mitigation.

Gut Microbiota Features in Young Children With Autism Spectrum Disorders.

Proliferation and/or depletion of clusters of specific bacteria regulate intestinal functions and may interfere with neuro-immune communication and behavior in patients with autism spectrum disorder (ASD). Consistently, qualitative and quantitative alteration of bacterial metabolites may functionally affect ASD pathophysiology. Up to date, age-restricted cohort studies, that may potentially help to identify specific microbial signatures in ASD, are lacking. We investigated the gut microbiota (GM) structure and fecal short chain fatty acids (SCFAs) levels in a cohort of young children (2–4 years of age) with ASD, with respect to age-matched neurotypical healthy controls. Strong increase of Bacteroidetes and Proteobacteria and decrease of Actinobacteria was observed in these patients. Among the 91 OTUs whose relative abundance was altered in ASD patients, we observed a striking depletion of Bifidobacterium longum, one of the dominant bacteria in infant GM and, conversely, an increase of Faecalibacterium prausnitzii, a late colonizer of healthy human gut and a major butyrate producer. High levels of F. prausnitzii were associated to increase of fecal butyrate levels within normal range, and over representation of KEGG functions related to butyrate production in ASD patients. Here we report unbalance of GM structure with a shift in colonization by gut beneficial bacterial species in ASD patients as off early childhood.

Natural history of a cohort of ABCD1 variant female carriers.

The therapeutic scenario of X-linked adrenoleukodystrophy (X-ALD) is rapidly changing. Whereas the disease is well characterized in men, the condition remains to be fully clarified in women carrying ATP binding cassette subfamily D member 1 (ABCD1) variants. Specifically, data on clinical progression are needed, in order to recommend any appropriate management. The objective of this study was to outline the natural history of a cohort of untreated ABCD1 heterozygous female carriers. Longitudinal data from a single-center population of 60 carriers were retrospectively reviewed. Demographics, anthropometrics, serum very long chain fatty acid (VLCFA) levels, clinical parameters and the Adult ALD Clinical Score (AACS) were collected from every recorded visit in a 7-year period and analyzed to define the phenotype modifications, to determine factors associated with clinical features, and to estimate the annual progression rate and the subsequent sample size for interventional trials. Thirty-two patients were eligible for the study, and 59.4% were symptomatic at baseline. Clinical severity worsens with age which increases risk of symptom onset, the cut-off of 41years being crucial for phenoconversion. VLCFA levels were not predictive and did not change over time. Symptomatic carriers were followed up for 3.45±2.1years. The AACS increased at an annual rate of 0.24 points. The estimated sample size for 30% reduction in annual progression at 80% power was 272. This study provides data on the natural disease progression of untreated ABCD1 heterozygous female carriers, demonstrating the relevance of aging. The estimated annual increase of the AACS will be useful for future interventional studies.

Preparation, characterization and improvement in intestinal function of polysaccharide fractions from okra

The purpose of this study was to investigate the effect of okra polysaccharides with similar molecular weight on intestinal ecology. After extraction, ethanol precipitation, deproteinization and purification, two polysaccharide fractions, named as water-extracted polysaccharides (WEP) and alkaline-extracted polysaccharides (AEP), were obtained. According to the results of high performance liquid chromatography, AEP contained mannose, rhamnose, galacturonic acid and galactose, while WEP was composed of galactose, rhamnose, fructose, arabinose, glucose, galacturonic acid and mannose. The compositions of intestinal microbiota were affected by the change of daily substrates. Meanwhile, the concentration of ammonia and gastrointestinal transit time decreased, the total short chain fatty acid (SCFA) levels, moisture of caecum content increased. These findings suggested that the effect of okra polysaccharides on intestinal microbiota was achieved by the output of detrimental compounds and the supply of nutrients. Besides, AEP supported a more pivotal role in manipulating gut microbiota than WEP.

From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn\u2019s disease

Crohn’s disease (CD) is associated with an ecological imbalance of the intestinal microbiota, consisting of hundreds of species. The underlying complexity as well as individual differences between patients contributes to the difficulty to define a standardized treatment. Computational modeling can systematically investigate metabolic interactions between gut microbes to unravel mechanistic insights. In this study, we integrated metagenomic data of CD patients and healthy controls with genome-scale metabolic models into personalized in silico microbiotas. We predicted short chain fatty acid (SFCA) levels for patients and controls, which were overall congruent with experimental findings. As an emergent property, low concentrations of SCFA were predicted for CD patients and the SCFA signatures were unique to each patient. Consequently, we suggest personalized dietary treatments that could improve each patient’s SCFA levels. The underlying modeling approach could aid clinical practice to find dietary treatment and guide recovery by rationally proposing food aliments.

Metabolomic changes in human adipose tissue derived products following non-enzymatic microfacturing.

In this study, we evaluated the metabolomic profiling of cryopreserved Lipogems® tissue products and the initial lipoaspirates before microfracturing, to determine altered metabolites that could result from the non-enzymatic processing or the cryopreservation method. Human Lipoaspirate samples (n=10) were divided in two aliquots, of which one was non-processed and the other was processed by Lipogems® device. Non-processed lipoaspirates and Lipogems® processed tissues were stored at -80°C fresh frozen (N=3 per group) or in the presence of 0.5 M dimethyl sulfoxide (DMSO) (N=7 per group). A global non-targeted metabolic profile on these samples was performed. Differences were observed in carbohydrate and nucleotide metabolism. These alterations translated in long chain and polyunsaturated fatty acid levels and amino acid metabolites showed divergent trends. When Lipogems® and Lipoaspirate tissue products were cryopreserved with DMSO, amino acids tended to increase in Lipogems® product. However, in the absence of DMSO aminoacids and their catabolites, tended to decrease in Lipogems® fat tissue product. Microfractured human adipose tissue has been shown to provide a more effective source of adult stromal cells compared to the initial lipoaspirated tissue material. These could be, according to our findings, due to the changes in the metabolic profile of lipoaspirate tissues products.

Peroxisomal Disorders: Experience from a Genetic Center in North India

AbstractDiagnosis of peroxisomal disorders (PDs) is often delayed because of unfamiliarity with the characteristic features of PDs and their genetic heterogeneity. Aim of this study was to describe clinical profiles of six children with PDs. This is a retrospective study involving six children with PDs. The patients included three males, one female, and a fetus. Three patients were diagnosed with Zellweger's syndrome, two with rhizomelic chondrodysplasia punctata, and one with X-linked adrenoleukodystrophy. These diagnoses were established based on clinical, radiological, and biochemical features (elevated very long chain fatty acids levels). Parents of all cases have been provided genetic counseling and advised of prenatal diagnosis. Diagnosis of PDs requires knowledge of characteristic clinicoradiological features, and clinical confirmation is possible with simple imaging and biochemical investigations. Molecular diagnosis is possible for selected cases.

Impaired Insulin‐like Growth Factor‐1 function in X‐linked Adrenoleukodystrophy patients

IntroductionX‐linked Adrenoleukodystrophy (X‐ALD), a common peroxisomal disorder is characterized by elevated very long chain fatty acids (VLCFA) levels in tissues and body fluids of patients. X‐ALD patients present with adrenal insufficiency, demyelination and progressive mental retardation and IGF‐1 has been reported to alleviate demyelination and neurodegeneration in an animal model of X‐ALD. We examined the effect of VLCFA on IGF‐1 function in human skin fibroblasts.MethodsHuman skin fibroblasts grown from skin explants were cultured in growth medium. Cell cultures were treated with varying concentrations of IGF‐1 and/or VLCFA (Lignoceric acid; C24:0, hexadecanoic acid; C26:0 ) for 24–72 hrs. DNA synthesis into cultured fibroblasts was measured and total RNA was extracted for RT‐PCR analysis of IGF‐1 receptor and GAPDH. Cell homogenates were prepared for western blotting and protein measurements. Levels of IGF‐1 and VLCFA were measured in blood samples of 10 patients with confirmed diagnosis of X‐ALD.ResultsBoth VLCFAs used in this study significantly (p &lt;0.01) reduced the IGF‐1–induced DNA synthesis in cultured skin fibroblasts. Lignoceric acid as well as hexadecanoic acid markedly reduced the gene expression of IGF‐1 receptor. IGF‐1 receptor protein was also significantly reduced following 48 hrs of treatment with VLCFAs. X‐ALD patients were observed to have significantly lower levels of plasma IGF‐1 as compared to healthy controls.ConclusionsThis study suggests that abnormally elevated VLCFA in X‐ALD patients might impair IGF‐1 function through downregulation of IGF‐1 receptor thereby providing a new insight into molecular mechanisms of X‐ALD pathogenesis.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Mutual Interaction of Phenolic Compounds and Microbiota: Metabolism of Complex Phenolic Apigenin-C- and Kaempferol-O-Derivatives by Human Fecal Samples.

Human colonic bacteria have an important impact on the biotransformation of flavonoid glycosides and their conversion can result in the formation of bioactive compounds. However, information about the microbial conversion of complex glycosylated flavonoids and the impact on the gut microbiota are still limited. In this study, in vitro fermentations with selected flavonoid O- and C-glycosides and three different fecal samples were performed. As a result, all flavonoid glycosides were metabolized via their aglycones yielding smaller substances. Main metabolites were 3-(4-hydroxyphenyl)propionic acid, 3-phenylpropionic acid, and phenylacetic acid. Differences in the metabolite formation due to different time courses between the donors were determined. Therefore, from all fermentations, the ones with a specific donor were always slower resulting in a lower number of metabolites compared to the others. For example, tiliroside was totally degraded from 0 h (105 ± 13.2 μM) within the first 24 h, while in the fermentations with fecal samples from other donors, tiliroside (107 ± 52.7 μM at 0 h) was not detected after 7 h anymore. In general, fermentation rates of C-glycosides were slower compared to the fermentation rates of O-glycosides. The O-glycoside tiliroside was degraded within 4 h while the gut microbiota converted the C-glycoside vitexin within 13 h. However, significant changes (p < 0.05) in the microbiota composition and short chain fatty acid levels as products of carbohydrate fermentation were not detected between incubations with different phenolic compounds. Therefore, microbiota diversity was not affected and a significant prebiotic effect of phenolic compounds cannot be assigned to flavonoid glycosides in food-relevant concentrations.

Barley β-glucan increases fecal bile acid excretion and short chain fatty acid levels in mildly hypercholesterolemic individuals.

The cholesterol-lowering effect of barley β-glucan has been proposed to be the result of a pleiotropic effect, which involves several biological mechanisms such as gut fermentation, inhibition of intestinal cholesterol absorption and increased bile acid excretion and its synthesis. However, one of the recent studies from our laboratory indicated that increased bile acid excretion and subsequent increase in its synthesis, but not the inhibition of cholesterol absorption or synthesis might be responsible for the cholesterol-lowering effect of barley β-glucan. Accordingly, the primary objective of the present study was to investigate the concentration of bile acids (BA), neutral sterols (NS) and short chain fatty acids (SCFA) excreted through the feces by mildly hypercholesterolemic subjects who consumed diets containing barley β-glucan with varying molecular weights (MW) and concentrations. In a controlled, four phase, crossover trial, 30 mildly hypercholesterolemic but otherwise healthy subjects were randomly assigned to receive breakfast containing 3 g high MW (HMW), 5 g low MW (LMW), 3 g LMW barley β-glucan or a control diet for 5 weeks. The concentrations of BA, NS and SCFA in the feces were measured at the end of each treatment phase. Compared to the other treatment groups, 3 g day-1 HMW barley β-glucan consumption resulted in increased lithocholic acid (LCA) excretion (P < 0.001) but not LMW β-glucan, even at the high dose of 5 g day-1. Increased fermentability of fibre was also evident from a significant increase in fecal total SCFA concentrations in response to the 3 g HMW β-glucan diet compared to the 3 g LMW barley β-glucan and control diet (P = 0.0015). In summary, the current results validate our previous report on the role of fecal bile acid excretion in cholesterol lowering through the consumption of barley β-glucan. In addition, increased SCFA concentrations indicate that an increase in β-glucan molecular weight promotes hindgut fermentation, which might also be playing a role in attenuating cholesterol levels.