Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair

Simonato, Manuela; Fochi, Igor; Vedovelli, Luca; Giambelluca, Sonia; Carollo, Cristiana; Padalino, Massimo A.; Carnielli, Virgilio P.; Cogo, Paola

doi:10.1007/s11306-019-1605-3

Cited by 19 publications

(23 citation statements)

References 36 publications

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“…Raw data were acquired by Xcalibur 4.1 software and processed by Compound Discoverer 3.1 software (Thermo Fisher Scientific, Waltham, MA, USA) for peak detection, peak alignment, and peak integration. The processing procedures were modified from a previous method [ 23 ]. The multivariate statistical analysis including principle component analysis (PCA) and partial least-squares-latent structure discriminate analysis (PLS-DA) were performed in SIMCA-P 13.0 (Umetrics AB, Umea, Vasterbotten, Sweden) [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host–Microbe Interplay

et al. 2021

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Intimate metabolic host–microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology.

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Section: Methodsmentioning

confidence: 99%

Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host–Microbe Interplay

et al. 2021

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“…Tryptophan is mostly metabolized through the kynurenine pathway (90%); the 3% is converted into serotonin (5-OH-tryptamine) and the remaining quote undergoes intestinal microbiota degradation with production of indole and its derivatives ( 124 ).…”

Section: Discussionmentioning

confidence: 99%

“…Tryptophan and kynurenine could pass the blood-brain barrier and determine anti-inflammatory, immunosuppressive and antioxidant functions with neuroprotective actions ( 124 ).…”

Section: Discussionmentioning

confidence: 99%

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Early Urinary Metabolomics in Patent Ductus Arteriosus Anticipates the Fate: Preliminary Data

et al. 2020

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Introduction: In premature neonates, the persistence of hemodynamically significant ductus arteriosus (hsPDA) can be associated with short- and long-term consequences, impairing their outcome. The correct strategy of management for such condition is under debate, especially regarding contraindications and/or side effects. In recent years, metabolomics was applied to several perinatal, pediatric, and adult conditions to investigate potential biomarkers of disease, which have become useful for early diagnosis and/or therapeutic management.Aim of the Study: The main purpose of our exploratory study was to asses, through 1H-NMR metabolomics analysis of urinary samples at birth, possible metabolic pathways differentiating, with a significant predictive power, those preterm neonates who will subsequently develop hsPDA and neonates of comparable gestational age (GA) who will undergo spontaneous ductal closure or the persistence of an irrelevant PDA (no-hsPDA). Moreover, we investigated potential prenatal or perinatal clinical factors potentially influencing the development of hsPDA.Materials and Methods: We enrolled n = 35 preterm neonates with GA between 24 and 32 weeks; urinary samples were collected within the first 12 h of life. Patients were closely monitored regarding intensive care, respiratory support, fluid balance and administered drugs; an echocardiogram was performed at 48–72 h.Results: Our results reported a significant correlation between lower GA at birth and the development of hsPDA. Moreover, neonates with GA ≤ 30w developing hsPDA were characterized by lower Apgar scores at 1′ and 5′, higher rates of perinatal asphyxia, higher need of delivery room resuscitation and subsequent surfactant administration. Interestingly, metabolomics analysis at birth detected a clear separation between the 1H-NMR urinary spectra of subjects GA ≤ 30w not developing hsPDA (n = 19) and those of subjects born at GA ≤ 30w in which hsPDA was confirmed at 48–72 h of life (n = 5).Conclusions: This is the first study applying metabolomics to investigate the PDA condition. Although preliminary and conducted on a limited sample, our results reveal that metabolomics could be a promising tool in the early identification of hsPDA, potentially superior to the clinical or laboratory predictive tools explored to date and even to the clinical observations and correlations in our sample, through the detection of specific urinary metabolites.

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“…First, the raw data are acquired by Xcalibur 4.1 software (Thermo Fisher Scientific, Waltham, MA, USA), and initial data processing, including peak detection and peak alignment, was performed in Compound Discoverer 3.1 software (Thermo Fisher Scientific, Waltham, MA, USA) as described previously [ 39 ]. Then, the partial least-squares-latent structure discriminates analysis (PLS-DA) models were built for multivariate statistical analysis using SIMCA-P 13.0 (Umetrics AB, Umea, Sweden) and metabolites with variable importance in the project (VIP) values of more than 1 were selected as differential metabolites [ 40 ].…”

Section: Methodsmentioning

confidence: 99%

Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Han

Zheng

et al. 2021

Nutrients

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Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

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Urinary metabolomics reveals kynurenine pathway perturbation in newborns with transposition of great arteries after surgical repair

Cited by 19 publications

References 36 publications

Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host–Microbe Interplay

Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host–Microbe Interplay

Early Urinary Metabolomics in Patent Ductus Arteriosus Anticipates the Fate: Preliminary Data

Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

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