Search Results (147)

Background: There is an urgent need for novel treatment options for Neisseria gonorrhoeae. Methenamine is an interesting urinary antiseptic with a very low propensity to induce antimicrobial resistance. Methods: We assessed the MICs of methenamine-hippurate for 18 N. gonorrhoeae isolates. We then assessed the in vivo efficacy of methenamine-hippurate against N. gonorrhoeae using the Galleria mellonella infection model. Results: We found that all the gonococcal isolates had a methenamine-hippurate MIC of 300 mg/L. This MIC was not higher in isolates with higher ceftriaxone MICs. No toxicity of methenamine at the doses tested was found, and doses as low as 200 mg/kg were effective in the G. mellonella model. Conclusions: Further studies in mice and humans are required to assess if methenamine-hippurate could be used to treat gonococcal urethritis alone or in combination with other agents such as ceftriaxone. Full article

Dehydration and storage conditions used to preserve dairy cultures in the industry may negatively impact their viability and functionality. This study investigated the effects of freeze-drying and storage on the metabolic activity of Lacticaseibacillus rhamnosus 73 (L73). The strain’s viability after freeze-drying and storage, its metabolic activity in cultured milk, and its performance as a ripening agent in miniature cheeses were evaluated. Neither the freeze-drying process nor the storage conditions negatively affected its viability, as L73 maintained its initially high levels (>10 log cfu mL⁻¹) throughout the storage period. L73 improved the overall quality of the cheeses, as a reduction in hydrophobic peptides (i.e., potential bitter peptides) was evidenced in cheese manufactured with L73. Furthermore, L73 exhibited protective properties, as evidenced by the decreased availability of compounds that could be used as energy sources by adventitious microorganisms (e.g., galactose, hippuric acid) and the increased production of lactic acid in both cultured milk and cheese. Full article

Background: Chronic non-communicable diseases (NCDs) are a major global health challenge, with unhealthy diets contributing significantly to their burden. Metabolomics data offer new possibilities for identifying nutritional biomarkers, as demonstrated in short-term intervention studies. This study investigated associations between habitual dietary intake and urinary metabolites, a not well-studied area. Methods: Data were available from 496 participants of the population-based MEIA study. Linear and median regression models examined associations between habitual dietary intake and metabolites, adjusted for possible confounders. K-means clustering identified urinary metabolite clusters, and multinomial regression models were applied to analyze associations between food intake and metabolite clusters. Results: Using linear regression models, previously reported associations could be replicated, including citrus intake with proline betaine, protein intake with urea, and fiber intake with hippurate. Novel findings include positive associations of poultry intake with taurine, indoxyl sulfate, 1-methylnicotinamide, and trimethylamine-N-oxide. Milk substitutes were positively associated with urinary uracil, pseudouridine, 4-hydroxyhippurate, and 3-hydroxyhippurate, and inversely associated with quinic acid. Dietary fiber intake showed a positive association with 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and a negative association with indoxyl sulfate. We identified sucrose and taurine as key metabolites differentiating metabolite clusters. Multinomial regression analysis confirmed significantly different dietary associations across clusters, particularly for fruits, processed meat, poultry, and alcoholic beverages. Conclusions: This study highlights established and novel food–metabolite associations, demonstrating the potential of urinary metabolomics for use as nutritional biomarkers in individuals from the general population. Full article

Background: Respiratory pathologies, such as COVID-19 and bronchitis, pose significant challenges for high-level athletes, particularly during demanding altitude training camps. Metabolomics offers a promising approach for early detection of such pathologies, potentially minimizing their impact on performance. This study investigates the metabolic differences between athletes with and without respiratory illnesses during an altitude training camp using urine samples and multivariate analysis. Methods: Twenty-seven elite rowers (15 males, 12 females) participated in a 12-day altitude training camp at 1850 m. Urine samples were collected daily, with nine athletes developing respiratory pathologies (8 COVID-19, 1 bronchitis). Nuclear Magnetic Resonance spectroscopy was used to analyze the samples, followed by data processing with Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), allowing to use Variable Importance in Projection (VIP) scores to identify key metabolites contributing to group separation. Results: The PLS-DA model for respiratory illness showed good performance (R² = 0.89, Q² = 0.35, p < 0.05). Models for altitude training achieved higher predictive power (Q² = 0.51 and 0.72, respectively). Metabolites kynurenine, N-methylnicotinamide, pyroglutamate, propionate, N-formyltryptophan, tryptophan and glucose were significantly highlighted in case of respiratory illness while trigonelline, 3-hydroxyphenylacetate, glutamate, creatine, citrate, urea, o-hydroxyhippurate, creatinine, hippurate and alanine were correlated to effort in altitude. This distinction confirms that respiratory illness induces a unique metabolic profile, clearly separable from hypoxia and training-induced adaptations. Conclusions: This study highlights the utility of metabolomics in identifying biomarkers of respiratory pathologies in athletes during altitude training, offering the potential for improved monitoring and intervention strategies. These findings could enhance athlete health management, reducing the impact of illness on performance during critical training periods. Further research with larger cohorts is warranted to confirm these results and explore targeted interventions. Full article

Background/Objectives: Assessing nutrient intake is essential for understanding body homeostasis and diet–health interactions. Traditional methods, such as dietary questionnaires and quality indices, are limited by subjectivity and variability in food composition tables. Metabolomic markers, like urinary hippuric acid, provide an objective means to estimate food and nutrient intake, helping to link dietary patterns with metabolic outputs and health outcomes. This study uniquely evaluates urinary hippuric acid as a putative biomarker of nut intake, expanding the previously known role as a fruit intake marker, and investigates sex-related differences in the excretion. Methods: Using Nuclear Magnetic Resonance (NMR) spectroscopy, 34 urinary metabolites from 138 participants (69.7% women) in the Dietary Deal project were analyzed. Metabolite concentrations were categorized by median adherence to the EAT-Lancet score (≤p50 or >p50). A validated Food Frequency Questionnaire (FFQ) assessed dietary and energy intake. Correlation analyses linked metabolites to the 14 EAT-Lancet food groups, and a linear regression adjusted model examined associations between urinary hippuric acid and fruit/nut consumption, with sensitivity analysis for sex. Results: The EAT-Lancet index, stratified by median adherence, effectively distinguished between high and low dietary intake of fruits (p = 0.012) and nuts (p < 0.001). Urinary hippuric acid concentrations were found to be influenced by sex (p = 0.020), with females showing a 44.7% higher mean concentration. Overall, urinary hippuric acid levels were positively associated with FFQ-estimated nut consumption (p = 0.049), providing the first evidence of potential suitability as a nut intake biomarker. Conclusions: Hippuric acid emerges as a promising dietary biomarker for assessing nut intake in healthy populations. This study provides novel insights that extend the application of hippuric acid to dietary nut assessment and emphasizes the importance of a sex-specific interpretation for precision nutrition purposes using NMR technology. Full article

Background/Objectives: FimH adhesin, located at the tips of type 1 pili in Escherichia coli (E. coli), plays a crucial role in bacterial adhesion to the surface urothelial cells—a key step in the pathogenesis of urinary tract infections (UTIs). Given the rising concern over antimicrobial resistance (AMR), and considering that E. coli is one of the pathogens with the largest AMR burdens on a global scale, alternative strategies targeting bacterial adhesion are gaining increasing attention. Products that contain D-mannose and cranberry-derived phenolic compounds have shown promise in preventing E. coli colonization and infection. The aim of this study was to investigate the antiadhesive effects of cranberry-related phenolic compounds on FimH-mediated E. coli adhesion using a cellular hemagglutination inhibition assay, as well as to assess the synergistic effects of mannose and phenolic compounds on biofilm formation. Methods: A range of phenolic acids (benzoic, chlorogenic, hippuric, p-coumaric, ferulic and caffeic), resveratrol, (+)-catechin and procyanidin A, as well as a Vaccinium macrocarpon extract, were evaluated for their ability to inhibit FimH-mediated adhesion. A binocular microscope was used to observe agglutination, and we also evaluated the biofilm inhibition potential of the phenolic compounds in the presence of D-mannose. Results: Our results demonstrated that these compounds significantly reduced hemagglutination, with benzoic acid, chlorogenic acid, caffeic acid and resveratrol exhibiting strong inhibitory effects at concentrations as low as 0.25 mM. Furthermore, the addition of 1 mM solutions of these phenolic compounds to D-mannose resulted in a twofold reduction in the inhibition titer, suggesting synergistic interactions. In addition to their antiadhesive properties, the tested phenolic compounds contributed slightly to the inhibition of FimH-mediated biofilm formation, further supporting their potential roles in UTI prevention. Conclusions: These findings highlight the potential of cranberry-derived phenolics as natural antiadhesive agents against E. coli and warrant further investigation into their mechanisms of action and possible applications in infection control. Full article

Recurrent urinary tract infection (rUTI) is a significant public health problem in women. General measures to prevent recurrence include behavioral changes and increased fluid intake, cranberry ingest, use of methenamine hippurate, antibiotic prophylaxis, D-mannose, probiotics, or vaccines. We conducted a literature review of the latest updates on preventing rUTI in December 2024. The search concluded with 27 articles that fulfilled our inclusion criteria. Our review demonstrated that behavioral changes such as correct genital hygiene, avoiding postponing micturition or defecation, urinating after sexual intercourse, and ingesting 1.5–2 L of water could prevent rUTI. The ingestion of cranberries reduces the risk of symptomatic, culture-verified urinary tract infections in women with rUTIs. Methenamine hippurate is an alternative to antibiotics to avoid rUTI. Estrogen reduces rUTI in women with hypoestrogenism. Limited evidence supports using D-mannose, probiotics, and vaccines to prevent rUTI. In conclusion, after successful treatment of the acute episode, preventative measures are needed to reduce rUTI frequency and morbidity according to each patient’s characteristics and preferences. Full article

Background: The mixed type of irritable bowel syndrome (IBS-M) is characterized by recurrent constipation and diarrhea. The cause of the variability of these symptoms is not sufficiently understood. The aim of this study was to perform metagenomic and metabolic assessment of the gut microbiome in constipation and diarrheal period of IBS-M. Methods: This study included 30 women, aged 28–47 years old, with the symptoms which aligned with those of IBS-M, according to the Rome IV Criteria. Results: In both periods of the disease, the dysbiosis index (DI), the Shannon diversity index (SDI), the hydrogen–methane and ammonia breath tests, as well as the selected bacterial metabolites (-p-hydroxyphenyl acetic acid (HPA), 3-indoxyl sulfate (Indican, 3-IS)), and hippuric acid (A) in urine, were determined. The dysbiosis index (DI) in the period of constipation was 3.73 ± 0.90 points, and in the diarrheal period it did not change significantly 3.93 ± 0.75 points (p > 0.05). During the diarrheal period, the diversity of bacteria increases from 2.16 ± 0.59 to 2.74 ± 0.50 points on the Shannon dietary index (p < 0.001). The gut microbiome profile also changed, especially during the diarrheal period where an abundance of Bifidobacterium spp. and Lactobacillus spp. decreased significantly. In addition, during this period, the levels of hydrogen and ammonia in breath air increased, while the methane level decreased. The differences also concern the results of urinary metabolites, especially related to hippuric acid and indican. During the diarrheal period, the levels of hydrogen and ammonia ions increased, while the methane level decreased. The differences also concern the results of urinary metabolites, especially related to hippuric acid and indican. Conclusions: In patients with IBS-M, periodic changes in the profile and metabolism of the gut microbiome occur, which coexist with recurrent symptoms such as constipation and diarrhea. Full article

Background/Objectives: Diabetes mellitus is often accompanied by mental health complications, including anxiety, depression, and cognitive decline. Recent research suggested that capsaicin, the active component of chili peppers, may influence mental health. This study aimed to determine the effect of dietary capsaicin on mental disorders in a type 1 diabetes (T1D) mouse model, while also exploring the potential involvement of the microbiota-gut-brain axis. Methods: We induced T1D in mice using streptozotocin (STZ) and administered a diet supplemented with 0.005% capsaicin for five weeks. Behavioral assessments, including the open field test (OFT), tail suspension test (TST), forced swimming test (FST), elevated plus maze (EPM) test, and Morris water maze (MWM) test, were conducted to evaluate depressive and anxiety-like behaviors as well as cognitive function. Targeted and untargeted metabolomics analyses were performed to assess neurotransmitter levels in the hippocampus and serum metabolites, while 16S rRNA sequencing was utilized to analyze gut microbiota composition. Intestinal barriers were determined using western blot detection of the tight junction proteins ZO-1 and occludin. Results: Dietary capsaicin exacerbated anxiety and depressive-like behaviors along with cognitive declines in T1D mice. Capsaicin reduced gut microbiota diversity and levels of beneficial bacteria, while broad-spectrum antibiotic treatment further intensified anxiety and depression behaviors. Metabolomic analysis indicated that capsaicin disrupted metabolic pathways related to tryptophan and phenylalanine, leading to decreased neuroprotective metabolites, such as kynurenic acid, hippurate, and butyric acid. Additionally, capsaicin diminished the expression of ZO-1 and occludin, indicating increased intestinal permeability. Conclusions: Dietary capsaicin aggravates gut microbiota and metabolic disturbances in diabetic mice, thereby worsening anxiety, depression, and cognitive decline. Full article

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m² vs. 55.8 mL/min/1.73 m², p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R² of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = −0.250 and p = 0.04, citric acid with r = −0.296 and p = 0.014, formic acid with r = −0.349 and p = 0.004, and glycine with r = −0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites. Full article

The objective of this study was to investigate the regulatory effects of a high-fiber content feed on the productive performance, meat quality, and fat acid composition. A total of 18 120-day-old Yushan pigs with similar initial body weight were randomly allotted into high-concentrate diet (high energy, HE) and high-fiber diet (low energy, LE) treatments for the determination of regulatory effects on productive performance, meat quality, and fatty acid content. Further, blood metabolomic, gut microbiota, and liver energy-related gene expression measurements were used to investigate the underlying mechanisms. Results showed that the LE treatment significantly increased ADFI while decreasing carcass weight, fat percentage, and IMF. Metabolomic results showed that the high-fiber treatment significantly down-regulated metabolites that participated in lipid metabolism such as cyclic ADP-ribose and hippuric acid, while up-regulated metabolites were mainly enriched in nitrogen metabolism such as DL-arginine and propionylcarnitine (p < 0.05). Microbial results showed relative abundances of Lactobacillus and Bifidobacterium are significantly proliferated in the high-fiber feeding treatments (p < 0.05). Transcriptomic results showed that genes mainly enriched into the lipid metabolism are significantly up-regulated under the high-fiber dietary treatment (p < 0.05). Conclusion: higher dietary fiber significantly reduced dietary energy provision, effectively decreased the backfat and abdominal fat content of Yushan pigs through proliferating intestinal fiber-degradable bacteria, and up-regulating the hepatic lipolysis-related gene expression. Full article

The objectives of this review are to investigate how benzoic acid can mitigate the negative effects of weaning stress, improve the intestinal microbiota, intestinal health, and growth of nursery pigs, determine the optimal dose level of benzoic acid for the growth rate in nursery pigs, and compare the efficacy of benzoic acid and other acids in pig feeds. After weaning, pigs are exposed to less lactose and solid feed with high acid-binding capacity at infrequent intervals, causing an increase in digesta pH, reducing protein digestion, and increasing ammonia-producing bacteria in the stomach. Benzoic acid supplementation has improved the intestinal health and growth of nursery pigs through its antimicrobial properties and pH reduction in the digesta. The positive modulation of luminal microbiota in the small intestine of pigs by benzoic acid improves intestinal morphology and enhances nutrient utilization, especially nitrogen, of nursery pigs. Benzoic acid supplementation of up to 1% in feeds also increases hippuric acid contents in the urine of nursery pigs, decreasing urinary pH, which is related to ammonia emission and barn conditions in intensive pig production. Supported by the beneficial impacts of benzoic acid, the growth performance of nursery pigs was also improved. However, excessive benzoic acid (over 2.5% up to 5%) in feeds reduces the growth performance of nursery pigs. Thus, this review conducted a meta-analysis of the results from 16 papers to determine the optimal dose level of benzoic acid for body weight gain of nursery pigs, which was found to be 0.60%. The efficacy of benzoic acid was similar to that of other organic acids, including citric acid, fumaric acid, formic acid, and formate salts. Collectively, benzoic acid supplementation can positively modulate the luminal and mucosal microbiota in the small intestine, increase nutrient utilization and intestinal health, decrease urinary pH, and improve the growth performance of nursery pigs. Full article

Gestational diabetes mellitus (GDM) triggers alterations in the maternal microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. We investigated maternal microbiome-metabolomic changes, including over 600 metabolites from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n = 18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n = 16, 40% carbohydrate/45% fat/15% protein). All meals were provided. Diets were eucaloric, and fiber content was similar. CHOICE was associated with increases in trimethylamine N-oxide, indoxyl sulfate, and several triglycerides, while CONV was associated with hippuric acid, betaine, and indole propionic acid, suggestive of a healthier metabolome. Conversely, the microbiome of CHOICE participants was enriched with carbohydrate metabolizing genes and beneficial taxa such as Bifidobacterium adolescentis, while CONV was associated with inflammatory pathways including antimicrobial resistance and lipopolysaccharide biosynthesis. We also identified latent metabolic groups not associated with diet: a metabolome associated with less of a decrease in fasting glucose, and another associated with relatively higher fasting triglycerides. Our results suggest that GDM diets produce specific microbial and metabolic responses during pregnancy, while host factors also play a role in triglycerides and glucose metabolism. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing health concern due to its increasing prevalence worldwide. Metabolic homeostasis encompasses the stable internal conditions vital for efficient metabolism. This equilibrium extends to the intestinal microbiota, whose metabolic activities profoundly influence overall metabolic balance and organ health. The metabolites derived from the gut microbiota metabolism can be defined as microbiota-related co-metabolites. They serve as mediators between the gut microbiota and the host, influencing various physiological processes. The recent redefinition of the term MASLD has highlighted the metabolic dysfunction that characterize the disease. Metabolic dysfunction encompasses a spectrum of abnormalities, including impaired glucose regulation, dyslipidemia, mitochondrial dysfunction, inflammation, and accumulation of toxic byproducts. In addition, MASLD progression has been linked to dysregulation in the gut microbiota and associated co-metabolites. Short-chain fatty acids (SCFAs), hippurate, indole derivatives, branched-chain amino acids (BCAAs), and bile acids (BAs) are among the key co-metabolites implicated in MASLD progression. In this review, we will unravel the relationship between the microbiota-related metabolites which have been associated with MASLD and that could play an important role for developing effective therapeutic interventions for MASLD and related metabolic disorders. Full article

This study was conducted to elucidate the intestinal damage induced by the IPEC-J2 cell culture-passaged PDCoV. The results showed that PDCoV disrupted the intestinal structure and increased intestinal permeability, causing abnormalities in mucosal pathology. Additionally, PDCoV induced an imbalance in the intestinal flora and disturbed its stability. Microbial community profiling revealed bacterial enrichment (e.g., Proteobacteria) and reduction (e.g., Firmicutes and Bacteroidetes) in the PDCoV-inoculated piglet model. In addition, metabolomics analysis indicated that 82 named differential metabolites were successfully quantified, including 37 up-regulated and 45 down-regulated metabolites. Chenodeoxycholic acid, sphingosine, and oleanolic aldehyde levels were reduced in PDCoV-inoculated piglets, while phenylacetylglycine and geranylgeranyl-PP levels were elevated. Correlation analysis indicated a negative correlation between Escherichia-Shigella and choline, succinic acid, creatine, phenyllactate, and hippuric acid. Meanwhile, Escherichia-Shigella was positively correlated with acetylcholine, L-Glutamicacid, and N-Acetylmuramate. Roseburia, Lachnospiraceae_UCG-010, Blautia, and Limosilactobacillus were negatively and positively correlated with sphingosine, respectively. These data suggested PDCoV-inoculated piglets exhibited significant taxonomic perturbations in the gut microbiome, which may result in a significantly altered metabolomic profile. Full article