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Affecting approximately 25% of the global population, steatotic liver disease (SLD) poses a significant health concern. SLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis and fibrosis with a risk of severe liver complications such as cirrhosis and hepatocellular carcinoma. SLD is associated with obesity, atherogenic dyslipidaemia, and insulin resistance, increasing cardiovascular risks. As such, identifying SLD is vital for cardiovascular disease (CVD) prevention and treatment. Bile acids (BAs) have critical roles in lipid digestion and are signalling molecules regulating glucose and lipid metabolism and influencing gut microbiota balance. BAs have been identified as critical mediators in cardiovascular health, influencing vascular tone, cholesterol homeostasis, and inflammatory responses. The cardio-protective or harmful effects of BAs depend on their concentration and composition in circulation. The effects of certain BAs occur through the activation of a group of receptors, which reduce atherosclerosis and modulate cardiac functions. Thus, manipulating BA receptors could offer new avenues for treating not only liver diseases but also CVDs linked to metabolic dysfunctions. In conclusion, this review discusses the intricate interplay between BAs, metabolic pathways, and hepatic and extrahepatic diseases. We also highlight the necessity for further research to improve our understanding of how modifying BA characteristics affects or ameliorates disease. [ABSTRACT FROM AUTHOR]

Simple Summary: The early detection of pancreatic cancer is critical as it is usually too late for potentially curative surgical resection when obvious symptoms such as jaundice have developed. The pancreas has two main functions in the body, namely, an endocrine role, where it produces insulin to control blood glucose levels; and an exocrine role, where it produces enzymes that aid digestion. Impairment of this latter role is known as pancreatic exocrine insufficiency (PEI). It is an established feature of advanced pancreatic cancer, but it is unclear whether it is present in the early stages when surgery may still be an option. This study used two validated methods of testing pancreatic exocrine function, a breath test and a stool test, to demonstrate that exocrine insufficiency is associated with resectable pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed late, leading to a high mortality rate. Early detection facilitates better treatment options. The aim of this UK-based case–control study was to determine whether two validated tests for pancreatic exocrine insufficiency (PEI), namely, the 13C-mixed triglyceride breath test (13C-MTGBT) and a faecal elastase (FE-1) test, can discriminate between patients with resectable PDAC versus healthy volunteers (HVs) along with a comparison group with chronic pancreatitis (CP). Discrimination between disease states and HVs was tested with receiver operator characteristic (ROC) curves. In total, 59 participants (23 PDAC (16 men), 24 HVs (13 men) and 12 CP (10 men)) were recruited, with a similar age in each population, and a combined median (IQR) age of 66 (57–71). The areas under the ROC curve for discriminating between PDAC and HVs were 0.83 (95% CI: 0.70–0.96) for the 13C-MTGBT, and 0.85 (95% CI: 0.75–0.95) for the FE-1 test. These were similar to CP vs. HV. In conclusion, PEI occurs in resectable PDAC to a similar extent as in CP; further large-scale, prospective studies using these tests in the primary care setting on high-risk groups are warranted. [ABSTRACT FROM AUTHOR]

Phenol-rich foods consumption such as virgin olive oil (VOO) has been shown to have beneficial effects on cardiovascular diseases. The broader biochemical impact of VOO and phenol-enriched OOs remains, however, unclear. A randomized, double-blind, cross-over, controlled trial was performed with thirty-three hypercholesterolemic individuals who ingested for 3-weeks (25 mL/day): (1) an OO enriched with its own olive oil phenolic compounds (PCs) (500 ppm; FOO); (2) an OO enriched with its own olive oil PCs (250 ppm) plus thyme PCs (250 ppm; FOOT); and (3) a VOO with low phenolic content (80 ppm). Serum lipid and glycemic profiles, serum 1H-NMR spectroscopy-based metabolomics, endothelial function, blood pressure, and cardiovascular risk were measured. We combined OPLS-DA with machine learning modelling to identify metabolites discrimination of the treatment groups. Both phenol-enriched OO interventions decreased the levels of glutamine, creatinine, creatine, dimethylamine, and histidine in comparison to VOO one. In addition, FOOT decreased the plasma levels of glycine and DMSO2 compared to VOO, while FOO decreased the circulating alanine concentrations but increased the plasma levels of acetone and 3-HB compared to VOO. Based on these findings, phenol-enriched OOs were shown to result in a favorable shift in the circulating metabolic phenotype, inducing a reduction in metabolites associated with cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Growth failure in infants born preterm is a significant issue, increasing the risk of poorer neurodevelopmental outcomes and metabolic syndrome later in life. During the first 1000 days of life biological systems mature rapidly involving developmental programming, cellular senescence, and metabolic maturation, regulating normal growth and development. However, little is known about metabolic maturation in infants born preterm and the relationship with growth. Objective: To examine the available evidence on urinary markers of metabolic maturation and their relationship with growth in infants born preterm. Eligibility criteria: Studies including in this scoping review using qualitative or quantitative methods to describe urinary markers of metabolic maturation and the relationship with growth in infants born preterm. Results: After a screening process 15 titles were included in this review, from 1998–2021 drawing from China (n = 1), Italy (n = 3), Germany (n = 3), Greece (n = 1), Japan (n = 2), Norway (n = 1), Portugal (n = 1), Spain (n = 2) and USA (n = 1). The included studies examined urinary metabolites in 1131 infants. A content analysis identified 4 overarching themes relating to; (i) metabolic maturation relative to gestational age, (ii) metabolic signature and changes in urinary metabolites over time, (iii) nutrition and (iv) growth. Conclusion: The results of this scoping review suggest there are considerable gaps in our knowledge relating to factors associated with metabolic instability, what constitutes normal maturation of preterm infants, and how the development of reference phenome age z scores for metabolites of interest could improve nutritional and growth outcomes. [ABSTRACT FROM AUTHOR]

Cross-talk between the immune system and the brain is essential to neuronal development, neuronal excitability, neuroplasticity, and neurotransmission. Gut microbiota are essential to immune system development and immune function; hence, it is essential to consider more broadly the microbiota-immune-brain axis in neurodevelopment. The gut, brain, and microbial metabolomes obtained from C57Bl/6 and T-cell-deficient mice across four developmental timepoints (postnatal day 17, 24, 28, and 84) were studied by 1H NMR spectroscopy. 16S rRNA gene sequencing was performed on cecal and fecal samples. In the absence of T-cells, the developmental trajectory of the gut microbiota and of the host's metabolic profile was altered. The novel insights from this work include (1) the requirement of functional T-cells for the normal trajectory of microbiotal development and the metabolic maturation of the supra-organism, (2) the potential role for Muribaculaceae taxa in modulating the cecal availability of metabolites previously implicated with a role in the gut-brain axis in T-cell deficient mice, and (3) the impact of T-cell-deficiency on central levels of neuroactive metabolites. [ABSTRACT FROM AUTHOR]

The response of a coeliac and a healthy gut microbiota to the green algae Chlorella pyrenoidosa was evaluated using an in vitro continuous, pH controlled, gut model system, which simulated the human colon. The effect of C. pyrenoidosa on the microbial structure was determined by 16S rRNA gene sequencing and inferred metagenomics, whereas the metabolic activitywas determined by1H-nuclear magnetic resonancespectroscopic analysis. The addition of C. pyrenoidosa significantly increased the abundance of the genera Prevotella, Ruminococcus and Faecalibacterium in the healthy donor, while an increase in Faecalibacterium, Bifidobacterium and Megasphaera and a decrease in Enterobacteriaceae were observed in the coeliac donor. C. pyrenoidosa also altered several microbial pathways including those involved in short-chain fatty acid (SCFA) production. At the metabolic level, a significant increase from baseline was seen in butyrate and propionate (p < 0.0001) in the healthy donor, especially in vessels 2 and 3. While acetate was significantly higher in the healthy donor at baseline in vessel 3 (p < 0.001) compared to the coeliac donor, this was markedly decreased after in vitro fermentation with C. pyrenoidosa. This is the first in vitro fermentation study of C. pyrenoidosa and human gut microbiota, however, further in vivo studies are needed to prove its efficacy. [ABSTRACT FROM AUTHOR]

The gut microbiome is recognized to exert a wide-ranging influence on host health and disease, including brain development and behavior. Commensal bacteria can produce bioactive molecules that enter the circulation and impact host physiology and homeostasis. However, little is known about the potential for these metabolites to cross the blood–brain barrier and enter the developing brain under normal physiological conditions. In this study, we used a liquid chromatography–mass spectrometry-based metabolomic approach to characterize the developmental profiles of microbial-derived metabolites in the forebrains of mice across three key postnatal developmental stages, co-occurring with the maturation of the gut microbiota. We demonstrate that direct metabolites of the gut microbiome (e.g., imidazole propionate) or products of the combinatorial metabolism between the microbiome and host (e.g., 3-indoxyl-sulfate, trimethylamine-N-oxide, and phenylacetylglycine) are present in the forebrains of mice as early as the neonatal period and remain into adulthood. These findings demonstrate that microbial-associated molecules can cross the BBB either in their detected form or as precursor molecules that undergo further processing in the brain. These chemical messengers are able to bind receptors known to be expressed in the brain. Alterations in the gut microbiome may therefore influence neurodevelopmental trajectories via the regulation of these microbial-associated metabolites. [ABSTRACT FROM AUTHOR]

Bovine mycotoxicosis is a disorder caused by the ingestion of fungal toxins. It is associated with chronic signs, such as reduced growth rate and milk yield, and causes significant economic cost to the dairy industry. The mycotoxins deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) are commonly found in grain fed to cattle. Patulin (PA) is a common grass silage contaminant but is also found in grain. The effects of these mycotoxins on cellular function at low concentrations are not well understood. Using Madin–Darby bovine kidney cells we evaluated the cellular response to these mycotoxins, measuring cytotoxicity, de novo protein synthesis, cell proliferation, cell cycle analysis, and also metabolic profiling by 1H NMR spectroscopy. DON, ZEN, and PA induced cytotoxicity, and PA and FB1 induced a decrease in metabolic activity in surviving cells. DON was the only mycotoxin found to have a significant effect on the metabolic profile, with exposed cells showing increased cellular amino acids, lactate, 2-oxoglutarate, 3-hydroxybutyrate, and UDP-N-acetylglucosamine and decreased β-alanine, choline, creatine, taurine, and myo-inositol. Cells exposed to DON also showed reductions in protein synthesis. DON has previously been documented as being a ribotoxin; the results here suggest that exposure of bovine cells to DON causes a decrease in protein synthesis with corresponding cellular accumulation of precursors. Cell proliferation was also arrested without causing apoptosis. It is likely that exposure triggers hypoxic, hypertonic, and ribotoxic responses in bovine cells, and that these responses contribute to reduced productivity in exposed cattle. [ABSTRACT FROM AUTHOR]