Concentrations Of P-cresol Research Articles

Do high-protein diets have the potential to reduce gut barrier function in a sex-dependent manner?

PurposeImpaired gut barrier function is associated with systemic inflammation and many chronic diseases. Undigested dietary proteins are fermented in the colon by the gut microbiota which produces nitrogenous metabolites shown to reduce barrier function in vitro. With growing evidence of sex-based differences in gut microbiotas, we determined whether there were sex by dietary protein interactions which could differentially impact barrier function via microbiota modification.MethodsFermentation systems were inoculated with faeces from healthy males (n = 5) and females (n = 5) and supplemented with 0.9 g of non-hydrolysed proteins sourced from whey, fish, milk, soya, egg, pea, or mycoprotein. Microbial populations were quantified using fluorescence in situ hybridisation with flow cytometry. Metabolite concentrations were analysed using gas chromatography, solid phase microextraction coupled with gas chromatography-mass spectrometry and ELISA.ResultsIncreased protein availability resulted in increased proteolytic Bacteroides spp (p < 0.01) and Clostridium coccoides (p < 0.01), along with increased phenol (p < 0.01), p-cresol (p < 0.01), indole (p = 0.018) and ammonia (p < 0.01), varying by protein type. Counts of Clostridium cluster IX (p = 0.03) and concentration of p-cresol (p = 0.025) increased in males, while females produced more ammonia (p = 0.02), irrespective of protein type. Further, we observed significant sex-protein interactions affecting bacterial populations and metabolites (p < 0.005).ConclusionsOur findings suggest that protein fermentation by the gut microbiota in vitro is influenced by both protein source and the donor’s sex. Should these results be confirmed through human studies, they could have major implications for developing dietary recommendations tailored by sex to prevent chronic illnesses.

How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule.

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, while PFOA increased in responders. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

Fractal Fractional Derivative Models for Simulating Chemical Degradation in a Bioreactor

A three-differential-equation mathematical model is presented for the degradation of phenol and p-cresol combination in a bioreactor that is continually agitated. The stability analysis of the model’s equilibrium points, as established by the study, is covered. Additionally, we used three alternative kernels to analyze the model with the fractal–fractional derivatives, and we looked into the effects of the fractal size and fractional order. We have developed highly efficient numerical techniques for the concentration of biomass, phenol, and p-cresol. Lastly, numerical simulations are used to illustrate the accuracy of the suggested method.

Characterization of physicochemical properties and flavor profiles of fermented Chinese bamboo shoots (suansun) from Liuzhou and Guilin

Suansun is a traditional fermented vegetable with unique regional characteristics. This study aimed to explore the similarities and differences in the flavors and textures of 16 commercially available suansun from Liuzhou and Guilin. Suansun from two regions exhibited many similarities. The ranges for pH and sugar content in suansun were 3.32–4.37 and 0.02–0.12 g/100g, respectively. Glutamic and alanine were the primary flavor-imparting amino acids found in suansun. A total of 74 volatile compounds were identified. P-cresol and 1-octen-3-ol were found to be the main characteristic odorants of suansun. However, there were also some differences for suansun from two regions. Titratable acidity (0.97–5.10 g/100g) and hardness (59.47–181.39 g) varied with different samples. Notably, the concentration of p-cresol in Liuzhou suansun was higher, resulting in a stronger acidic and pungent flavor. Whereas Guilin suansun contained more alcohols and esters, resulting in a stronger fruity flavor. The comparative analysis of the suansun properties would help to improve the understanding of the flavor spectrum of suansun.

Microbial metabolite p-cresol inhibits gut hormone expression and regulates small intestinal transit in mice.

p-cresol is a metabolite produced by microbial metabolism of aromatic amino acid tyrosine. p-cresol and its conjugated forms, p-cresyl sulfate and p-cresyl glucuronide, are uremic toxins that correlate positively with chronic kidney disease and diabetes pathogenesis. However, how p-cresol affects gut hormones is unclear. Here, we expose immortalized GLUTag cells to increasing concentrations of p-cresol and found that p-cresol inhibited Gcg expression and reduced glucagon-like peptide-1 (GLP-1) secretion in vitro. In mice, administration of p-cresol in the drinking water for 2 weeks reduced the transcript levels of Gcg and other gut hormones in the colon; however, it did not affect either fasting or glucose-induced plasma GLP-1 levels. Furthermore, it did not affect glucose tolerance but promoted faster small intestinal transit in mice. Overall, our data suggest that microbial metabolite p-cresol suppresses transcript levels of gut hormones and regulates small intestinal transit in mice.

Metabolomics Differences of the Donor Livers Between In Situ and Ex Situ Conditions During Ischemia-free Liver Transplantation.

Ischemia-free liver transplantation (IFLT) has been innovated to avoid graft ischemia during organ procurement, preservation, and implantation. However, the metabolism activity of the donor livers between in the in situ and ex situ normothermic machine perfusion (NMP) conditions, and between standard criteria donor and extend criteria donor remains unknown. During IFLT, plasma samples were collected both at the portal vein and hepatic vein of the donor livers in situ during procurement and ex situ during NMP. An ultra-high performance liquid chromatography-mass spectrometry was conducted to investigate the common and distinct intraliver metabolite exchange. Profound cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis were found in both in situ and ex situ conditions. However, obvious D-arginine and D-ornithine metabolism, arginine and proline metabolism were only found in the in situ condition. The suppressed activities of the urea cycle pathway during ex situ condition were confirmed in an RNA expression level. In addition, compared with extend criteria donor group, standard criteria donor group had more active intraliver metabolite exchange in metabonomics level. Furthermore, we found that the relative concentration of p-cresol, allocystathionine, L-prolyl-L-proline in the ex situ group was strongly correlated with peak alanine aminotransferase and aspartate aminotransferase at postoperative days 1-7. In the current study, we show the common and distinct metabolism activities during IFLT. These findings might provide insights on how to modify the design of NMP device, improve the perfusate components, and redefine the criteria of graft viability.

Biodegradation of p-cresol by Serratia marcescens strain HL 1 in batch system: Process optimization, growth kinetic study, phytotoxicity and chlorophyll assessment

The batch experiment was performed for biodegradation of p-cresol from synthetic wastewater using an isolated gram-negative bacterial strain (i.e., Serratia marcescens strain HL 1 (EU371058)). Biodegradation rate affecting parameters such as pH (5.0–10), p-cresol concentration (20–100 mg·L−1), and retention time (24–72 h) were optimized. The maximum degradation (86.32 %) of p-cresol was obtained at an initial concentration of 60 mg·L−1, pH of 7.5, and retention time of 48 h. Based on Haldane model, maximum specific growth (μmax) of the cell was 0.2 h−1, and inhabitation constant (KI) of substrate was 76 mg·L−1. FTIR was used to identify the available functional group in biodegraded p-cresol solution. Conclusively, it was observed that a first-order model could accurately predict reaction kinetics. The rate constant values for the first-order was 0.002 L g VSS−1 h−1. Phytotoxicity and chlorophyll were also investigated.

Utilizing Rayleigh light scattering of anthracene nanoparticles for determination of p-cresol in exhaled breath condensate

A simple and sensitive Rayleigh light scattering (RLS) method is developed for the quantification of p-cresol in exhaled breath condensate (EBC). The method is based on an aggregation of anthracene nanoparticles in acidic media after adding the p-cresol which results in a marked enhancement in RLS intensity at 410 nm. The increase of RLS intensity is directly proportional to the p-cresol concentration, and the linearity is obtained in the range of 0.007–0.5 μg mL−1, with the LOD of 0.004 ng mL−1. The relative standard deviations (RSDs, n = 5) for inter-day and intra-day analysis were <6.5 % for investigated concentrations. Finally, the validated method is applied for the analysis of p-cresol in EBC samples taken from patients suffering chronic kidney disease.

CuO improved energy band of AgO/fibrous SiO2–ZrO2 for optimized simultaneous photocatalytic redox of chromium (VI) and p-cresol using response surface methodology

Ternary CuO/AgO/FSZr photocatalysts were fabricated via the hydrothermal and electrochemical methods with three different CuO loading (1, 3 and 5 wt%), indicated as 1CuO/AgO/FSZr, 3CuO/AgO/FSZr and 5CuO/AgO/FSZr. The photocatalytic reaction was tested towards simultaneous chromium (VI) photoreduction and p-cresol photooxidation and the performance in order as follow: 3CuO/AgO/FSZr > 5CuO/AgO/FSZr > 1CuO/AgO/FSZr > AgO/FSZr > FSZr. CuO/AgO/FSZr photocatalysts showed an improvement in photocatalytic activity compared to AgO/FSZr and FSZr due to the reduction potential of chromium (VI) aligned closer to the conduction band of CuO and provided abundant free active electrons (e−) and holes (h+) with efficient transportation and migration. Interestingly, the 3CuO/AgO/FSZr was established as the best photocatalyst with 98% reduction of chromium (VI) and 83% oxidation of p-cresol simultaneously, owing to its strong corporation between the metal oxides and support and higher total pore volume. The Langmuir-Hinshelwood model were employed for kinetics which followed the pseudo-first-order kinetics model well. Based on the simultaneous photocatalytic mechanism, chromium (VI) and p-cresol were directly reduced and oxidized by e− and h+, respectively. The response surface methodology (RSM) discovered that the quadratic term initial concentration of chromium (VI) is the main significant factor in photocatalytic performance. The optimum parameters for simultaneous photoredox of chromium (VI) and p-cresol predicted from RSM are 9.6 mg L−1 of chromium (VI) concentration, 9.8 mg L−1 of p-cresol concentration and 0.32 g L−1 of catalyst dosage. Under these conditions the error between the predicted and experimental values is only 3.7%. The 3CuO/AgO/FSZr sustained the photocatalytic performance after reused for five cycles and could oxidized various organic pollutants as well as reduced chromium (VI) simultaneously.

Epigallocatechin-3-Gallate Decreases Plasma and Urinary Levels of p-Cresol by Modulating Gut Microbiota in Mice.

p-Cresol (PC), a gut bacterial product of tyrosine catabolism, is recognized as a uremic toxin that has negative biological effects. Lowering the plasma PC level by manipulating the gut bacterial composition represents a promising therapeutic strategy in chronic kidney disease. This study was conducted to reveal whether epigallocatechin-3-gallate (EGCG) decreases plasma PC levels by limiting its bacterial production in a mouse model. The PC concentration in the samples was measured by high-performance liquid chromatography (HPLC) after treatments with sulfatase and β-glucuronidase. The results showed that the addition of EGCG to the diet decreased the plasma and urinary concentrations of PC in a dose-dependent manner, with a statistically significant difference between the control group and the 0.2% EGCG group. However, once EGCG was enzymatically hydrolyzed to epigallocatechin (EGC) and gallic acid, such effects were lost almost completely. The addition of 0.2% EGCG in the diet was accompanied by a decreased abundance of Firmicutes at the phylum level and Clostridiales at the order level, which constitute a large part of PC produced from tyrosine. In conclusion, EGCG, not EGC, reduced plasma and urinary concentrations of PC in mice by suppressing its bacterial production with accompanying alteration of the relative abundance of PC producers.

Kinetics investigation of phenolic pollutant degradation via Serratia marcescens ABHI 001 and its application in wastewater treatment

In the present work, kinetic study has been conducted in order to effectively eliminate the p-cresol from wastewater employing isolated bacterial strain Serratia marcescens ABHI001 under batch shake flasks in the concentration varying from 50 to 500 mg/L. Further, effects of various parameters including p-cresol concentration, inoculum dosage, temperature, pH and agitation have been investigated. It was found that 10% v/v inoculum of 24 h age, was effective in degrading p-cresol. Beside this, it was noticed that the concentration of P-cresol above 100 mg/L exhibited an inhibitory effect. The maximum specific growth rate (μmax) was obtained to be 0.360 h−1 for 100 mgL−1 concentration. Further, the experimental results were well fitted with Halden's and Andrew's models and kinetic parameters μmax, KS and Ki in case of Haldane model were calculated to be 0.9697 h−1, 88.07 mgL−1 and 219.9 mgL−1, respectively whereas the corresponding values in case of Andrews's constants were 0.6917 h−1, 62.83 mgL−1 and 307.4 mgL−1, respectively. The yield coefficient for the growth on p-cresol was found to be 0.82.

Indole and p-cresol in feces of healthy subjects: Concentration, kinetics, and correlation with microbiome.

Indole and p-cresol are precursors of the most important uremic toxins, generated from the fermentation of amino acids tryptophan and tyrosine by the proteolytic community of intestinal bacteria. The present study focused on the relationship between the microbiome composition, the fecal levels of indole and p-cresol, and their kinetics of generation/degradation in fecal cultures. The concentration of indole and p-cresol, the volatilome, the dry weight, and the amount of ammonium and carbohydrates were analyzed in the feces of 10 healthy adults. Indole and p-cresol widely differed among samples, laying in the range of 1.0-19.5μg/g and 1.2-173.4μg/g, respectively. Higher fecal levels of indole and p-cresol were associated with lower carbohydrates and higher ammonium levels, that are markers of a more pronounced intestinal proteolytic metabolism. Positive relationship was observed also with the dry/wet weight ratio, indicator of prolonged intestinal retention of feces. p-cresol and indole presented a statistically significant negative correlation with OTUs of uncultured Bacteroidetes and Firmicutes, the former belonging to Bacteroides and the latter to the families Butyricicoccaceae (genus Butyricicoccus), Monoglobaceae (genus Monoglobus), Lachnospiraceae (genera Faecalibacterium, Roseburia, and Eubacterium ventriosum group). The kinetics of formation and/or degradation of indole and p-cresol was investigated in fecal slurries, supplemented with the precursor amino acids tryptophan and tyrosine in strict anaerobiosis. The presence of the precursors bursted indole production but had a lower effect on the rate of p-cresol formation. On the other hand, supplementation with indole reduced the net rate of formation. The taxa that positively correlated with fecal levels of uremic toxins presented a positive correlation also with p-cresol generation rate in biotransformation experiments. Moreover other bacterial groups were positively correlated with generation rate of p-cresol and indole, further expanding the range of taxa associated to production of p-cresol (Bacteroides, Alistipes, Eubacterium xylanophylum, and Barnesiella) and indole (e.g., Bacteroides, Ruminococcus torques, Balutia, Dialister, Butyricicoccus). The information herein presented contributes to disclose the relationships between microbiota composition and the production of uremic toxins, that could provide the basis for probiotic intervention on the gut microbiota, aimed to prevent the onset, hamper the progression, and alleviate the impact of nephropaties.

In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells.

Eryptosis is the stress-induced RBC (red blood cell) death mechanism. It is known that eryptosis is largely influenced by plasma and blood composition, and that it is accelerated in patients affected by chronic kidney disease (CKD). The aim of this study is to evaluate the eryptosis rate in healthy RBCs treated with different concentration of IL-6, IL-1β, urea and p-cresol, comparable to plasmatic level of CKD patients, at different time points. We exposed healthy RBCs to increasing concentrations of IL-6, IL-1β, urea and p-cresol. Morphological markers of eryptosis (cell membrane scrambling, cell shrinkage and PS exposure at RBC surface) were evaluated by flow cytometric analyses. The cytotoxic effect of cytokines and uremic toxins were analyzed in vitro on healthy RBCs at 4, 8 and 24 h. Morphology of treated RBCs was dramatically deranged, and the average cell volume was significantly higher in RBCs exposed to higher concentration of all molecules (all, p < 0.001). Furthermore, healthy RBCs incubated with each molecules demonstrated a significant increase in eryptosis. Cytofluorimetric analysis of eryptosis highlighted significantly higher cell death rate in RBCs incubated with a higher concentration of both cytokines compared with RBCs incubated with a lower concentration (all, p < 0.05). In conclusion, our data show that cytokines and uremic toxins have a harmful effect on RBCs viability and trigger eryptosis. Further studies are necessary to validate these results in vivo and to associate abnormal eryptosis with cytokine levels in CKD patients. The eryptosis pathway could, moreover, become a new promising target for anemia management in CKD patients.

Bacterial communities and volatile organic compounds in traditional fermented salt-free bamboo shoots

Fermented bamboo shoot is a traditional salt-free fermented vegetable product, which has been widely used as cooking ingredient in southern China. This paper intends to evaluate the changes of bacterial diversity and volatile organic compounds (VOCs) in bamboo shoots during fermentation. FT-IR spectra confirmed the significant original difference in transmittance between fresh and fermented bamboo shoots. Four VOCs in fresh bamboo shoots, namely α-gurjunene, p-cresol, methoxyphenyloxime, hexanal, were retained after fermentation. At the same time, new VOCs, namely β-cedrene, ethyl caprylate, 1-nonanal, 4-methylanisole, (z)-2-heptenal, acetic acid, valeraldehyde, 1-hexanol, ethyl palmitate were produced. Among them, the concentration of p-cresol was the highest among all VOCs. At the phylum level, proteobacteria was the dominant bacterial biota in fresh bamboo shoots (GC-0 group). Firmicutes became the dominant bacterial biota in fermented samples. At the genus level, bacterial groups in fresh bamboo shoots were dominated by Oxyphotobacteria (unclassified) and Lactobacillus. With the progress of fermentation, Lactobacillus increased continuously and finally became the dominant bacterial biota. Weissella appeared in the early stage of fermentation, but began to decline to less than 0.1% in the later stage. Lactobacillus became increasingly abundant during fermentation, and there was a significant positive correlation between Lactobacillus and valeraldehyde, 1-hexanol, ethyl palmitate, propyl acetate, 2-methoxy-4-methylphenol. These results suggest that the aroma quality of fermented bamboo shoots may be seriously affected by the bacterial biota in traditional fermented bamboo shoots. To sum up, this study provides a comprehensive and in-depth correlation between bacterial community and VOCs in fermented bamboo shoots.

Determination of p-cresol levels in smoked meat products using QuEChERS method and gas chromatography-mass spectrometry

p-Cresol is known as an environmental chemical contaminant that has toxic effects on humans. However, the presence of p-cresol in smoked foods has been seen as a flavor constituent. The present study had as objective to optimize and validate the QuEChERS method for the determination of p-cresol in beef hamburger, which was chosen as a representative matrix for six smoked meat products. The analysis was performed by gas chromatography coupled with mass spectrometry (GC-MS). The method showed limit of quantification (LOQ) of 40 µg kg−1, linearity between 40 and 200 µg kg−1, recovery higher than 70% and relative standard deviation lower than 14%. The proposed method was applied to six different smoked foods and the p-cresol concentration ranged from 148 to 872 µg kg−1 and only the turkey breast pate showed a concentration lower than the LOQ. The descending order of p-cresol level in smoked samples was: sausage > shredded tuna > salami > turkey breast > hamburger > turkey breast pate. In three analyzed samples, the results showed that the p-cresol migrates from the surface to the food inner. Finally, the proposed method was simple and efficient to quantify high levels of this contaminant in smoked foods and it could be a useful tool for the monitoring food safety and quality.

Correlation of inflammatory biomarkers with the diversity of Bacteroidaceae, Bifidobacteriaceae, Prevotellaceae and Lactobacillaceae families in the intestinal microbiota of patients with end stage renal disease

PurposeSerum levels of inflammatory cytokines and uremic toxins, and their inter-correlations with the diversity of Bacteroidaceae, Bifidobacteriaceae, Prevotellaceae and Lactobacillaceae families in intestinal microbiota were investigated in patients with end stage renal disease (ESRD). MethodsStool and blood samples from 20 ESRD patients on maintenance hemodialysis were collected. DNA genome of the bacterial composition of the stool samples was extracted and evaluated by the sequencing analysis of 16S rRNA genes. Serum levels of inflammatory cytokines and uremic toxins were then analyzed. ResultsThe mean serum concentrations of TNF-α, IL-6, indoxyl sulfate (IS) and p-cresol (PC) were 305.99 ​± ​12.03 ​ng/L, 159.95 ​± ​64.22 ​ng/L, 36.76 ​± ​5.09 ​μg/mL and 0.39 ​± ​0.15 ​μg/mL, respectively. The most significant positive correlation was observed between Prevotellaceae family and total antioxidant capacity (TAC), Lactobacilli species and CRP and PC, as well as Scardovia wiggsiae and IS (p ​< ​0.001). A negative correlation was also found between Bacteroides clarus and PC. Patients with ESRD on maintenance hemodialysis had elevated levels of PC and IS and increased levels of the inflammatory markers. The most positive correlation was found between microbiota and CRP and PC, while the most negative one was between microbiota and IL-1 and TAC. ConclusionsThe abundance and diversity of Bacteroidaceae, Bifidobacteriaceae, Prevotellaceae and Lactobacillaceae families and their correlations with clinical parameters could provide benefits in the ESRD patients but they could not promote the symptoms.

Substitution of Refined Conventional Wheat Flour with Wheat High in Resistant Starch Modulates the Intestinal Microbiota and Fecal Metabolites in Healthy Adults: A Randomized, Controlled Trial

BackgroundResistant starch (RS) confers many health benefits, mostly through the microbial production of SCFAs, but foods containing appreciable RS are limited. High-amylose wheat (HAW) is high in RS and lowers the glycemic response of foods, but whether it can improve gastrointestinal health measures is unknown. ObjectivesThe objective of this study was to determine whether daily consumption of HAW food products improved markers of gastrointestinal health in healthy men and women compared with similar foods made from conventional wheat. MethodsEighty healthy adults (47 women and 33 men) were enrolled in a 4-arm parallel, randomized-controlled, double-blind trial. After a 2-wk low–dietary fiber run-in period, they were randomly allocated to 1 of 4 treatment groups: low-amylose wheat (LAW)–refined (LAW-R), LAW–wholemeal (LAW-W), HAW–refined (HAW-R), and HAW–wholemeal (HAW-W) and consumed the assigned test bread (160 g/d) and biscuits (75 g/d) for 4 wk. Fecal biochemical markers were measured at baseline and 4 wk. Microbial abundance and diversity were quantified using 16S ribosomal RNA sequencing and perceived gut comfort by a semiquantitative questionnaire completed at baseline, 2 wk, and 4 wk. ResultsHAW showed similar effects on fecal output and excretion of total SCFA compared with LAW, but changes were observed in secondary measures for the refined treatment groups. At 4 wk, the HAW-R group had 38% higher fecal butyrate excretion than the LAW-R group (P < 0.05), and higher fecal SCFA-producing bacteria, Roseburia inulinivorans (P < 0.001), than at baseline. In comparison with baseline, LAW-R increased fecal p-cresol concentration, and fecal abundance of a p-cresol-producing bacterium, Clostridium from the Peptostreptococcaceae family, but both were reduced by HAW-R. Amylose level did not affect measures of fecal consistency or adversely affecting digestive comfort. ConclusionsIncreasing RS intake of healthy adults by substituting refined conventional wheat with refined HAW modulates fecal metabolites and microbes associated with gastrointestinal health.This trial was registered at anzctr.org.au as ACTRN12618001060235.

Clostridioides difficile Infection Dysregulates Brain Dopamine Metabolism.

ABSTRACTGastrointestinal illnesses and dysbiosis are among the most common comorbidities reported in patients with neurodevelopmental disorders. The manuscript reports that C. difficile infection (CDI), predisposed by antibiotic-induced gut dysbiosis, causes significant alterations in dopamine metabolism in major dopaminergic brain regions in mice (P < 0.05). In addition, C. difficile infected mice exhibited significantly reduced dopamine beta-hydroxylase (DBH) activity compared to controls (P < 0.01). Moreover, a significantly increased serum concentration of p-cresol, a DBH inhibiting gut metabolite produced by C. difficile, was also observed in C. difficile infected mice (P < 0.05). Therefore, this study suggests a potential mechanistic link between CDI and alterations in the brain dopaminergic axis. Such alterations may plausibly influence the precipitation and aggravation of dopamine dysmetabolism-associated neurologic diseases in infected patients.IMPORTANCE The gut-brain axis is thought to play a significant role in the development and manifestation of neurologic diseases. This study reports significant alterations in the brain dopamine metabolism in mice infected with C. difficile, an important pathogen that overgrows in the gut after prolonged antibiotic therapy. Such alterations in specific brain regions may have an effect on the precipitation or manifestation of neurodevelopmental disorders in humans.

Why Do High-Risk Patients Develop or Not Develop Coronary Artery Disease? Metabolic Insights from the CAPIRE Study.

Traditional cardiovascular (CV) risk factors (RFs) and coronary artery disease (CAD) do not always show a direct correlation. We investigated the metabolic differences in a cohort of patients with a high CV risk profile who developed, or did not develop, among those enrolled in the Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation (CAPIRE) study. We studied 112 subjects with a high CV risk profile, subdividing them according to the presence (CAD/High-RFs) or absence of CAD (No-CAD/High-RFs), assessed by computed tomography angiography. The metabolic differences between the two groups were identified by gas chromatography-mass spectrometry. Characteristic patterns and specific metabolites emerged for each of the two phenotypic groups: high concentrations of pyruvic acid, pipecolic acid, p-cresol, 3-aminoisobutyric acid, isoleucine, glyceric acid, lactic acid, sucrose, phosphoric acid, trimethylamine-N-oxide, 3-hydroxy-3-methylglutaric acid, erythritol, 3-hydroxybutyric acid, glucose, leucine, and glutamic acid; and low concentrations of cholesterol, hypoxanthine, glycerol-3-P, and cysteine in the CAD/High-RFs group vs the No-CAD/High-RFs group. Our results show the existence of different metabolic profiles between patients who develop CAD and those who do not, despite comparable high CV risk profiles. A specific cluster of metabolites, rather than a single marker, appears to be able to identify novel predisposing or protective mechanisms towards CAD beyond classic CVRFs.

Urinary organic acids spectra in children with altered gut microbiota composition and autistic spectrum disorder

Introduction: Alteration of human gut microbiota is described in a number of neuro-developmental and cognitive disorders including autistic spectrum disorder (ASD). Along with the changes in the gut microbiota, children with ASD are also reported to have changes in urinary organic acid spectra implying these metabolites as potential biomarkers for gastrointestinal dysbiosis. Aim: Identify urinary metabolites that would indicate specific changes in the gut microbiota and could be useful as biomarkers. Methods: The study group consisted of 44 children with ASD. Urinary organic acids spectra and composition of gut microbiota were analysed. Results: Any significant deviation in quantified metabolites compared to the reference values were not confirmed. The main variations were detected in concentration of p-cresol and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), but we cannot confirm the presence of HPHPA in urine as a biomarker for Clostridium sp. overgrowth in the gut. The acquired results indicate higher relative abundance of Firmicutes phylum alone may be attributed to increased concentration of p-cresol in urine. Decreased Bacteroidetes/Firmicutes ratio was found in the group with the presence of HPHPA in urine. Conclusions: Metabolites of human urine can be used as biomarkers for alterations of gut microbiota with caution, guided treatment should be administrated only based on gut microbiota analysis results or in combination with urinary organic acid results, but not solely based on organic acid biomarkers.