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It is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the first-line drug for treatment of T2DM unless there are contra-indications. The drug primarily inhibits hepatic gluconeogenesis and increases the sensitivity of target cells (hepatocytes, adipocytes and myocytes) to insulin; however, increasing evidence suggests that it may also influence the gut. As T2DM patients exhibit gut dysbiosis, the intestinal microbiome has gained interest as a key target for metabolic diseases. Interestingly, changes in the gut microbiome were also observed in T2DM patients treated with metformin compared to those who were not. Therefore, the aim of this review is to present the current state of knowledge regarding the association of the gut microbiome with the antihyperglycemic effect of metformin. Numerous studies indicate that the reduction in glucose concentration observed in T2DM patients treated with metformin is due in part to changes in the biodiversity of the gut microbiota. These changes contribute to improved intestinal barrier integrity, increased production of short-chain fatty acids (SCFAs), regulation of bile acid metabolism, and enhanced glucose absorption. Therefore, in addition to the well-recognized reduction of gluconeogenesis, metformin also appears to exert its glucose-lowering effect by influencing gut microbiome biodiversity. However, we are only beginning to understand how metformin acts on specific microorganisms in the intestine, and further research is needed to understand its role in regulating glucose metabolism, including the impact of this remarkable drug on specific microorganisms in the gut. [ABSTRACT FROM AUTHOR]

The failure of the fight against obesity makes us turn to new goals in its treatment. Now, brown adipose tissue has attracted attention as a promising target for the treatment of obesity and associated metabolic disorders such as insulin resistance, dyslipidemia, and glucose tolerance disorders. Meanwhile, the expansion of our knowledge has led to awareness about two rather different subtypes: classic brown and beige (inducible brown) adipose tissue. These subtypes have different origin, differences in the expression of individual genes but also a lot in common. Both tissues are thermogenic, which means that, by increasing energy consumption, they can improve their balance with excess intake. Both tissues are activated in response to specific inducers (cold, beta-adrenergic receptor activation, certain food and drugs), but beige adipose tissue transdifferentiates back into white adipose tissue after the cessation of inducing action, while classic brown adipose tissue persists, but its activity decreases. In this review, we attempted to understand whether there are differences in the effects of different groups of thermogenesis-affecting drugs on these tissues. The analysis showed that this area of research is rather sparse and requires close attention in further studies. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is a major complication of diabetes leading to kidney failure. Methods: This study investigates lipid metabolism profiles of long-standing DKD (LDKD, diabetes duration > 10 years) by integrative analysis of available single-cell RNA sequencing and spatial multi-omics data (focusing on spatial continuity samples) from the Kidney Precision Medicine Project. Results: Two injured cell types, an injured thick ascending limb (iTAL) and an injured proximal tubule (iPT), were identified and significantly elevated in LDKD samples. Both iTAL and iPT exhibit increased lipid metabolic and biosynthetic activities and decreased lipid and fatty acid oxidative processes compared to TAL/PT cells. Notably, compared to PT, iPT shows significant upregulation of specific injury and fibrosis-related genes, including FSHR and BMP7. Meanwhile, comparing iTAL to TAL, inflammatory-related genes such as ANXA3 and IGFBP2 are significantly upregulated. Furthermore, spatial metabolomics analysis reveals regionally distributed clusters in the kidney and notably differentially expressed lipid metabolites, such as triglycerides, glycerophospholipids, and sphingolipids, particularly pronounced in the inner medullary regions. Conclusions: These findings provide an integrative description of the lipid metabolism landscape in LDKD, highlighting injury-associated cellular processes and potential molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background: Lactation is known to improve insulin resistance, but this phenomenon remains poorly understood. Our goal was to evaluate whether subclinical inflammation could mediate the association between breastfeeding (BF) and improvement in glucose metabolism and markers of insulin resistance (MIRs) in the postpartum. Methods: A total of 95 adult women (≥18 years) with a BMI ≥ 25 kg/m2 from the outpatient clinic of the Federal University of São Paulo were followed from early pregnancy until 60 to 180 days postpartum. The patients were divided based on their BF status: BF and non-BF groups. A latent variable termed SubInf was created incorporating inflammation-related biomarkers: adiponectin, E-selectin, branched-chain amino acids, zonulin, copeptin, and lipopolysaccharides. The association of BR with MIRs in the postpartum was evaluated through linear regression analysis, and mediation analysis was performed to evaluate the role of SubInf in this association. Results: The groups were similar regarding gestational diabetes mellitus (GDM) prevalence, pre-gestational BMI, caloric intake, physical activity, and postpartum weight loss. The BF group presented lower levels of triglycerides (TGs), fasting glucose, fasting insulin, TG/HDLcholesterol ratio (TG/HDL), TyG index, and HOMA-IR compared to the non-BF group. A linear regression analysis adjusted for scholarity, parity, pre-gestational BMI, GDM, weight gain during pregnancy, and mode of delivery revealed an inverse association between BF and fasting glucose [−6.30 (−10.71 to −1.89), p = 0.005), HOMA-IR [−0.28 (−0.50 to −0.05), p = 0.017], TyG index [−0.04 (−0.06 to −0.01), p = 0.002], and TG/HDL ratio [−0.23 (−0.46 to −0.01), p = 0.001]. In the mediation analysis, SubInf did not mediate the indirect effect of BF on MIRs. Conclusions: In overweight and obese women, an association between BF and improvement in MIRs in the postpartum was seen, corroborating that BF should be stimulated, especially in these cardiometabolic high-risk women. Subclinical inflammation did not seem to mediate this association. [ABSTRACT FROM AUTHOR]

Background/Objectives: Recent data indicate the involvement of skeletal muscles in the regulation of metabolism and in the pathogenesis of chronic noncommunicable diseases. The goal of our study was to describe the serum concentrations of myokines in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (HTN) and their correlation with laboratory parameters, blood pressure (BP), and MASLD severity. Methods: A total of 67 patients with MASLD and HTN underwent anthropometric measurements, laboratory tests, and point shear-wave elastography. The serum concentrations of myokines were measured using enzyme-linked immunosorbent assay (ELISA). Results: Patients with detectable serum myonectin concentrations had significantly higher maximum systolic blood pressure (p = 0.022) and higher blood levels of uric acid (p = 0.029). Serum irisin concentration ≥ 6.1 μg/mL was associated with higher FLI values (p = 0.042) and liver stiffness (p = 0.034), as well as with slightly higher waist circumference (p = 0.082) and triglyceride level (p = 0.062). Patients with serum myostatin concentration ≥ 4.98 ng/mL were significantly older (p = 0.033) and had a lower blood albumin level (p = 0.043). Conclusions: In conclusion, the myokine profile in patients with MASLD and HTN correlates both with the severity of MASLD and the parameters characteristic of metabolic health, suggesting the possible contribution of altered irisin, myonectin, and myostatin concentrations to the occurrence of cardiometabolic risks in patients with MASLD. [ABSTRACT FROM AUTHOR]

Background: Shift work has been associated with unhealthy lifestyle habits and a higher prevalence of obesity, which negatively impacts the health of shift workers. The objective of our study was to examine the influence of shift work on obesity, as well as on sociodemographic variables, anthropometric measurements, and lifestyle habits in individuals working this type of schedule. Methods: An observational, cross-sectional, descriptive study involving 53,053 workers from various labour sectors across several Spanish autonomous communities was conducted. It included 31,753 men (17,527 of them working shifts) and 21,300 women (11,281 of them working shifts). The relationship between shift work and obesity was examined, as well as its association with sex, age, social class, education level, smoking, alcohol consumption, sedentary behaviour, and unhealthy diet. Results: Obesity showed higher prevalence and mean values among shift workers across all four formulas used (BMI obesity, WtHR high, CUN BAE obesity, METS-VF high). All variables related to unhealthy lifestyle habits revealed a significantly greater prevalence among shift workers, with high statistical significance (p < 0.001). Age, sex, and social class affected the risk of obesity, with a greater prevalence observed in shift workers compared to non-shift workers (p < 0.001). Men had a higher risk than women, with an OR ranging from 1.17 (1.12–1.21) for BMI obesity to 7.45 (6.71–8.20) for METS-VF high. Conclusions: Shift workers exhibit a higher prevalence of obesity and unhealthy lifestyle habits, with men at greater risk. The variables that most significantly increase the risk of obesity include age, physical inactivity, low adherence to the Mediterranean diet, and alcohol consumption. [ABSTRACT FROM AUTHOR]

Myokines, bioactive peptides released by skeletal muscle, have emerged as crucial regulators of metabolic and protective pathways in peripheral tissues, particularly in combating oxidative stress and inflammation. Their plasma concentration significantly increases following exercise, offering valuable insights into the role of physical activity in preventing sarcopenia and mitigating metabolic diseases, including obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review focuses on discussing the roles of specific myokines in activating intracellular signaling pathways within the liver, which confer protection against steatosis and lipid peroxidation. We detail the mechanism underlying lipid peroxidation and highlight the liver's antioxidant defenses, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are pivotal in reducing ferroptosis. Furthermore, we provide an in-depth analysis of key myokines, including myostatin, brain-derived neurotrophic factor (BDNF), and irisin, among others, and their potential impact on liver function. Finally, we discuss the molecular mechanisms through which these myokines influence oxidate stress and lipid metabolism, emphasizing their capacity to modulate antioxidant responses in the liver. Finally, we underscore the therapeutic potential of exercise as a non-pharmacological intervention to enhance myokine release, thereby preventing the progression of MASD through improved hepatic antioxidant defenses. This review represents a comprehensive perspective on the intersection of exercise, myokine biology, and liver health. [ABSTRACT FROM AUTHOR]

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients' lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1 [ABSTRACT FROM AUTHOR]

Heat stress (HS) has become a common stressor, owing to the increasing frequency of extreme high-temperature weather triggered by global warming, which has seriously affected the reproductive capacity of important livestock such as sheep. However, little is known about whether HS reduces sperm motility by inducing circadian rhythm disorders in rumen microorganisms and metabolites in sheep. In this study, the year-round reproduction of two-year-old Hu rams was selected, and the samples were collected in May and July 2022 at average environmental temperatures between 18.71 °C and 33.58 °C, respectively. The experiment revealed that the mean temperature-humidity index was 86.34 in July, indicating that Hu rams suffered from HS. Our research revealed that HS significantly decreased sperm motility in Hu rams. Microbiome analysis further revealed that HS reshaped the composition and circadian rhythm of rumen microorganisms, leading to the circadian disruption of microorganisms that drive cortisol and testosterone synthesis. Serum indicators further confirmed that HS significantly increased the concentrations of cortisol during the daytime and decreased the testosterone concentration at the highest body temperature. Untargeted metabolomics analysis revealed that the circadian rhythm of rumen fluid metabolites in the HS group was enriched by the cortisol and steroid synthesis pathways. Moreover, HS downregulated metabolites, such as kaempferol and L-tryptophan in rumen fluid and seminal plasma, which are associated with promotion of spermatogenesis and sperm motility; furthermore, these metabolites were found to be strongly positively correlated with Veillonellaceae_UCG_001. Overall, this study revealed the relationship between the HS-induced circadian rhythm disruption of rumen microorganisms and metabolites and sperm motility decline. Our findings provide a new perspective for further interventions in enhancing sheep sperm motility with regard to the circadian time scale. [ABSTRACT FROM AUTHOR]

Adipose tissue is composed of adipocytes, stromal vascular fraction, nerves, surrounding immune cells, and the extracellular matrix. Under various physiological or pathological conditions, adipose tissue shifts cellular composition, lipid storage, and organelle dynamics to respond to the stress; this remodeling is called "adipose tissue plasticity". Adipose tissue plasticity includes changes in the size, species, number, lipid storage capacity, and differentiation function of adipocytes, as well as alterations in the distribution and cellular composition of adipose tissue. This plasticity has a major role in growth, obesity, organismal protection, and internal environmental homeostasis. Moreover, certain thresholds exist for this plasticity with significant individualized differences. Here, we comprehensively elaborate on the specific connotation of adipose tissue plasticity and the relationship between this plasticity and the development of many diseases. Meanwhile, we summarize possible strategies for treating obesity in response to adipose tissue plasticity, intending to provide new insights into the dynamic changes in adipose tissue and contribute new ideas to relevant clinical problems. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5–67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant global health issue. The condition is closely linked to metabolic dysfunctions such as obesity and type 2 diabetes. The gut–liver axis, a bidirectional communication pathway between the liver and the gut, plays a crucial role in the pathogenesis of NAFLD. This review delves into the mechanisms underlying the gut–liver axis, exploring the influence of gut microbiota, intestinal permeability, and inflammatory pathways. This review also explores the potential therapeutic strategies centered on modulating gut microbiota such as fecal microbiota transplantation; phage therapy; and the use of specific probiotics, prebiotics, and postbiotics in managing NAFLD. By understanding these interactions, we can better comprehend the development and advancement of NAFLD and identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders. [ABSTRACT FROM AUTHOR]

Cardiovascular comorbidities owing to hormonal excess or deficiency are the main cause of mortality in patients with pituitary disorders. In patients with Cushing's Disease, there is an increased prevalence of cardiovascular diseases and/or risk factors including visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia, hypercoagulability as well as structural and functional changes in the heart, like cardiac hypertrophy and left ventricle (LV) dysfunction. Notably, these demonstrate limited reversibility even after remission. Furthermore, patients with acromegaly may manifest insulin resistance but also structural and functional heart changes, also known as "acromegalic cardiomyopathy". Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism as well as endothelial dysfunction. Hypopituitarism and conventional hormonal replacement therapy may also contribute to an unhealthy metabolic status, which promotes atherosclerosis and may lead to premature mortality. This review discusses the literature on cardiovascular risk in patients with pituitary disorders to increase physician awareness regarding this aspect of management in patients with pituitary disorders. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) implies different conditions where insulin resistance constitutes a major hallmark of the disease. The disease incurs a high risk for the development of cardiovascular complications, and takes its toll in regard to the gut–liver axis (pancreas, primary liver and colorectal)-associated immunity. The modulation of immunometabolic responses by immunonutritional factors (IFs) has emerged as a key determinant of the gut–liver axis' metabolic and immune health. IFs from plant seeds have shown in vitro and pre-clinical effectiveness primarily in dealing with various immunometabolic and inflammatory diseases. Only recently have immunonutritional studies established the engagement of innate intestinal immunity to effectively control immune alterations in inflamed livers preceding the major features of the MetS. However, integrative analyses and the demonstration of causality between IFs and specific gut–liver axis-associated immunometabolic imbalances for the MetS remain ill-defined in the field. Herein, a better understanding of the IFs with a significant role in the MetS, as well as within the dynamic interplay in the functional differentiation of innate immune key effectors (i.e., monocytes/macrophages), worsening or improving the disease, could be of crucial relevance. The development of an adequate intermediary phenotype of these cells can significantly contribute to maintaining the function of Tregs and innate lymphoid cells for the prevention and treatment of MetS and associated comorbidities. [ABSTRACT FROM AUTHOR]

Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. Epigenetics, which involves the regulation of host gene expression without changing the nucleotide sequence, provides an exact direction for us to understand how the environment, lifestyle factors, and other risk factors contribute to obesity. DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. In this review, we examined recent advancements in research, focusing on the involvement of intestinal microbiota and DNA methylation in the etiology and progression of obesity, as well as potential interactions between the two factors, providing novel perspectives and avenues for further elucidating the pathogenesis, prevention, and treatment of obesity. [ABSTRACT FROM AUTHOR]

A very low calorie ketogenic diet (VLCKD) impacts host metabolism in people marked by an excess of visceral adiposity, and it affects the microbiota composition in terms of taxa presence and relative abundances. As a matter of fact, there is little available literature dealing with microbiota differences in obese patients marked by altered intestinal permeability. With the aim of inspecting consortium members and their related metabolic pathways, we inspected the microbial community profile, together with the set of volatile organic compounds (VOCs) from untargeted fecal and urine metabolomics, in a cohort made of obese patients, stratified based on both normal and altered intestinal permeability, before and after VLCKD administration. Based on the taxa relative abundances, we predicted microbiota-derived metabolic pathways whose variations were explained in light of our cohort symptom picture. A totally different number of statistically significant pathways marked samples with altered permeability, reflecting an important shift in microbiota taxa. A combined analysis of taxa, metabolic pathways, and metabolomic compounds delineates a set of markers that is useful in describing obesity dysfunctions and comorbidities. [ABSTRACT FROM AUTHOR]

According to the World Health Organization, ischemic stroke is the second leading cause of death in the world. Frequently, it is caused by brachiocephalic artery (BCA) atherosclerosis. Timely detection of atherosclerosis and its unstable course can allow for a timely response to potentially dangerous changes and reduce the risk of vascular complications. Omics technologies allow us to identify new biomarkers that we can use in diagnosing diseases. This research included 90 blood plasma samples. The study group comprised 52 patients with severe atherosclerotic lesions BCA, and the control group comprised 38 patients with no BCA atherosclerosis. Targeted and panoramic lipidomic profiling of their blood plasma was carried out. There was a statistically significant difference (p < 0.05) in the values of the indices saturated fatty acids (FAs), unsaturated FAs, monounsaturated FAs, omega-3, and omega-6. Based on the results on the blood plasma lipidome, we formed models that have a fairly good ability to determine atherosclerotic lesions of the brachiocephalic arteries, as well as a model for identifying unstable atherosclerotic plaques. According only to the panoramic lipidome data, divided into groups according to stable and unstable atherosclerotic plaques, a significant difference was taken into account: p value < 0.05 and abs (fold change) > 2. Unfortunately, we did not observe significant differences according to the established plasma panoramic lipidome criteria between patients with stable and unstable plaques. Omics technologies allow us to obtain data about any changes in the body. According to our data, statistically significant differences in lipidomic profiling were obtained when comparing groups with or without BCA atherosclerosis. [ABSTRACT FROM AUTHOR]

Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this alteration plays a role in NAFLD pathogenesis. We investigated whether prebiotic administration affects liver fat content and/or liver-related and metabolic parameters. Patients with NAFLD and metabolic syndrome (age: 50 ± 11; 79% men) were randomized to receive either 16 g/day of prebiotic (ITFs—inulin-type fructans) (n = 8) or placebo (maltodextrin) (n = 11) for 12 weeks. Patients were instructed to maintain a stable weight throughout the study. Liver fat content (measured by H1MRS), fecal microbiota, and metabolic, inflammatory, and liver parameters were determined before and after intervention. Fecal samples from patients who received the prebiotic had an increased content of Bifidobacterium (p = 0.025), which was not observed with the placebo. However, the baseline and end-of-study liver fat contents did not change significantly in the prebiotic and placebo groups, neither did the liver function tests' metabolic and inflammatory mediators, including fibroblast growth factor-19 and lipopolysaccharide-binding protein. Body weight remained stable in both groups. These findings suggest that prebiotic treatment without weight reduction is insufficient to improve NAFLD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide. Numerous studies conducted recently have demonstrated a connection between the dysbiosis of the development of NAFLD and gut microbiota. Rebuilding a healthy gut ecology has been proposed as a strategy involving the use of probiotics. The purpose of this work is to investigate and compare the function of probiotics Akkermansia muciniphila (A. muciniphila) and VSL#3 in NAFLD mice. Rodent NAFLD was modeled using a methionine choline-deficient diet (MCD) with/without oral probiotic delivery. Subsequently, qPCR, histological staining, and liver function tests were conducted. Mass spectrometry-based analysis and 16S rDNA gene sequencing were used to investigate the liver metabolome and gut microbiota. We found that while both A. muciniphila and VSL#3 reduced hepatic fat content, A. muciniphila outperformed VSL#3. Furthermore, probiotic treatment restored the β diversity of the gut flora and A. muciniphila decreased the abundance of pathogenic bacteria such as Ileibacterium valens. These probiotics altered the metabolism in MCD mice, especially the glycerophospholipid metabolism. In conclusion, our findings distinguished the role of A. muciniphila and VSL#3 in NAFLD and indicated that oral-gavage probiotics remodel gut microbiota and improve metabolism, raising the possibility of using probiotics in the cure of NAFLD. [ABSTRACT FROM AUTHOR]

Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, and is a strong pyrogen. Obesity is a chronic, low-grade inflammatory condition, and LPS are thought to trigger and exacerbate it. The gut flora is the largest source of LPS in the body, and it is increasingly believed that altered intestinal microorganisms can play an essential role in the pathology of different diseases. Today, the complex axis linking gut flora to inflammatory states and adiposity has not been well elucidated. This review summarises the evidence for an interconnection between LPS, obesity, and gut flora, further expanding our understanding of LPS as a mediator of low-grade inflammatory disease and contributing to lessening the effects of obesity and related metabolic disorders. As well as providing targets associated with LPS, obesity, and gut flora, it is hoped that interventions that combine targets with gut flora address the individual differences in gut flora treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). In this narrative review, we summarize the roles of gut barrier dysfunction and gut microbiota in NAFLD, including their physiological functions, assessment methods, related mechanisms, and therapeutic approaches for the prevention and treatment of NAFLD. Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular carcinoma (HCC), posing significant health risks. As a multisystem disease, NAFLD is closely associated with systemic insulin resistance, central obesity, and metabolic disorders, which contribute to its pathogenesis and the development of extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain extrahepatic cancers. Recent evidence highlights the indispensable roles of intestinal barrier dysfunction and gut microbiota in the onset and progression of NAFLD/NASH. This review provides a comprehensive insight into the role of intestinal barrier dysfunction and gut microbiota in NAFLD, including intestinal barrier function and assessment, inflammatory factors, TLR4 signaling, and the gut–liver axis. Finally, we conclude with a discussion on the potential therapeutic strategies targeting gut permeability and gut microbiota in individuals with NAFLD/NASH, such as interventions with medications/probiotics, fecal transplantation (FMT), and modifications in lifestyle, including exercise and diet. [ABSTRACT FROM AUTHOR]

Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut–liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut–liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

A strong correlation between the occurrence of various pathological conditions and intestinal dysbiosis is supported by a range of strong evidence. Vice versa, many pathologies have been shown, in turn, to be responsible for alterations in the gut microbiota, a condition that can worsen illness outcomes and response to therapies. For these reasons, great efforts have been made, and studies are still ongoing, to elucidate the mechanisms underlying gut microbiota alterations and to search for pharmacologic or other strategies that can effectively restore the gut microbiota. In this narrative review, we examined the most significant literature on the role of some milk bioactive compounds, such as milk oligosaccharides and whey proteins, in modulating the composition of the gut microbiota and the underlying mechanisms of action, with the aim of investigating the impact of the microbiota changes mediated by these milk bioactive molecules on human health, and their potential use as therapeutics to treat or adjuvate the treatment of gut dysbiosis and associated pathologies. [ABSTRACT FROM AUTHOR]

The sense of smell plays an important role in influencing the eating habits of individuals and consequently, their body weight, and its impairment has been associated with modified eating behaviors and malnutrition problems. The inter-individual variability of olfactory function depends on several factors, including genetic and physiological ones. In this study, we evaluated the role of the Kv1.3 channel genotype and age, as well as their mutual relationships, on the olfactory function and BMI of individuals divided into young, adult and elderly groups. We assessed olfactory performance in 112 healthy individuals (young n = 39, adult n = 36, elderly n = 37) based on their TDI olfactory score obtained through the Sniffin' Sticks test and their BMI. Participants were genotyped for the rs2821557 polymorphism of the human gene encoding Kv1.3 channels, the minor C allele of which was associated with a decreased sense of smell and higher BMIs compared to the major T allele. The results show that TT homozygous subjects obtained higher TDI olfactory scores and showed lower BMIs than CC homozygous subjects, in all age groups considered. Furthermore, the positive effect of the T allele on olfactory function and BMI decreased with increasing age. The contribution of the genetic factor is less evident with advancing age, while the importance of the age factor is compensated for by genetics. These results show that genetic and physiological factors such as age act to balance each other. [ABSTRACT FROM AUTHOR]

Psychological stress exposure is well recognized to exacerbate inflammatory bowel disease (IBD) but the mechanisms involved remain poorly understood. In this study, chronic T cell-mediated colitis was induced by adoptively transferring CD4+CD45RBhigh splenic T cells from C57BL/6 WT donor mice into Rag1tm1Mom mice. Two weeks after T cell transfer, mice were exposed to a prolonged restraint stressor (RST) for 8 h per day for 6 consecutive days. The colitis phenotype was assessed via histopathology and semi-quantitative rt-PCR at humane endpoints or 10 weeks post-T-cell transfer. Mice that received the T cell transplant developed chronic colitis marked by increases in colonic histopathology and inflammatory cytokines. Colonic histopathology was greater in males than females regardless of RST exposure but RST exposure increased histopathology scores in females such that they reached scores observed in the males. This pattern was consistent with cytokine gene expression and protein levels in the colon (especially for IFN-γ, IL-17A, and TNF-α). Serum cytokine levels were not strongly affected by exposure to the stressor. Using a murine model of chronic T cell-mediated colitis, this study demonstrates that biological sex strongly influences colonic inflammation and exposure to chronic stress has a more pronounced effect in females than in males. [ABSTRACT FROM AUTHOR]

Dysbiosis, generally defined as the disruption to gut microbiota composition or function, is observed in most diseases, including allergies, cancer, metabolic diseases, neurological disorders and diseases associated with autoimmunity. Dysbiosis is commonly associated with reduced levels of beneficial gut microbiota-derived metabolites such as short-chain fatty acids (SCFA) and indoles. Supplementation with these beneficial metabolites, or interventions to increase their microbial production, has been shown to ameliorate a variety of inflammatory diseases. Conversely, the production of gut 'dysbiotic' metabolites or by-products by the gut microbiota may contribute to disease development. This review summarizes the various 'dysbiotic' gut-derived products observed in cardiovascular diseases, cancer, inflammatory bowel disease, metabolic diseases including non-alcoholic steatohepatitis and autoimmune disorders such as multiple sclerosis. The increased production of dysbiotic gut microbial products, including trimethylamine, hydrogen sulphide, products of amino acid metabolism such as p-Cresyl sulphate and phenylacetic acid, and secondary bile acids such as deoxycholic acid, is commonly observed across multiple diseases. The simultaneous increased production of dysbiotic metabolites with the impaired production of beneficial metabolites, commonly associated with a modern lifestyle, may partially explain the high prevalence of inflammatory diseases in western countries. [ABSTRACT FROM AUTHOR]

Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut–liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut–liver interplay into clinical practice as an additional tool to fight CLD and its complications. [ABSTRACT FROM AUTHOR]

The aim of this systematic review was to synthesise the impact of the COVID-19 pandemic on binge eating disorder (BED) the new onset and course. Inclusion criteria: original articles and BED diagnosis; and the main outcomes: relationships between the COVID-19 pandemic and the new onset/clinical changes in BED, and specific results for BED. Exclusion criteria: mixed/inaccurate diagnoses and articles not written in English. We searched four databases and one registry until 5 May 2023. The quality appraisal was conducted using the Effective Public Health Practice Project (EPHPP) tool. Twelve studies with 4326 participants were included. All studies were observational with nine cross-sectional and three longitudinal. Four of the included studies investigated new-onset BED, while eight examined the BED clinical course of patients with a previous diagnosis. With the exception of one study, the available literature indicates both an increase in BED diagnoses and a clinical worsening during COVID-19. Major limitations include study quality (weak-to-moderate) and high heterogeneity in terms of pandemic phase, population, geographical areas, and psychometric tools. Our findings indicate that BED patients are particularly vulnerable to events characterised by social distancing and over-worry, and should be, therefore, carefully monitored. Further studies are needed to corroborate our findings, implement preventive strategies, and promote personalised treatments. PROSPERO registration number: CRD42023434106 [ABSTRACT FROM AUTHOR]

With the increasing prevalence of energy metabolism disorders such as diabetes, cardiovascular disease, obesity, and anorexia, the regulation of feeding has become the focus of global attention. The gastrointestinal tract is not only the site of food digestion and absorption but also contains a variety of appetite-regulating signals such as gut-brain peptides, short-chain fatty acids (SCFAs), bile acids (BAs), bacterial proteins, and cellular components produced by gut microbes. While the central nervous system (CNS), as the core of appetite regulation, can receive and integrate these appetite signals and send instructions to downstream effector organs to promote or inhibit the body's feeding behaviour. This review will focus on the gut-brain axis mechanism of feeding behaviour, discussing how the peripheral appetite signal is sensed by the CNS via the gut-brain axis and the role of the central "first order neural nuclei" in the process of appetite regulation. Here, elucidation of the gut-brain axis mechanism of feeding regulation may provide new strategies for future production practises and the treatment of diseases such as anorexia and obesity. [ABSTRACT FROM AUTHOR]

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is recognized as the most prevalent chronic liver disease globally. However, its pathogenesis remains incompletely understood. Recent advancements in the gut-liver axis offer novel insights into the development of MAFLD. Polysaccharides, primarily derived from fungal and algal sources, abundantly exist in the human diet and exert beneficial effects on glycometabolism, lipid metabolism, inflammation, immune modulation, oxidative stress, and the release of MAFLD. Numerous studies have demonstrated that these bioactivities of polysaccharides are associated with their prebiotic properties, including the ability to modulate the gut microbiome profile, maintain gut barrier integrity, regulate metabolites produced by gut microbiota such as lipopolysaccharide (LPS), short-chain fatty acids (SCFAs), and bile acids (BAs), and contribute to intestinal homeostasis. This narrative review aims to present a comprehensive summary of the current understanding of the protective effects of polysaccharides on MAFLD through their interactions with the gut microbiota and its metabolites. Specifically, we highlight the potential molecular mechanisms underlying the prebiotic effects of polysaccharides, which may give new avenues for the prevention and treatment of MAFLD. [ABSTRACT FROM AUTHOR]

Periodontal disease is a complex and progressive chronic inflammatory condition that leads to the loss of alveolar bone and teeth. It has been associated with various systemic diseases, including diabetes mellitus and obesity, among others. Some of these conditions are part of the metabolic syndrome cluster, a group of interconnected systemic diseases that significantly raise the risk of cardiovascular diseases, diabetes mellitus, and stroke. The metabolic syndrome cluster encompasses central obesity, dyslipidemia, insulin resistance, and hypertension. In this review, our objective is to investigate the correlation between periodontal disease and the components and outcomes of the metabolic syndrome cluster. By doing so, we aim to gain insights into the fundamental mechanisms that link each systemic condition with the metabolic syndrome. This deeper understanding of the interplay between these conditions and periodontal disease can pave the way for more effective treatments that take into account the broader impact of managing periodontal disease on the comprehensive treatment of systemic diseases, and vice versa. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can lead to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observe that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy for liver diseases. [ABSTRACT FROM AUTHOR]

Adipose tissue (AT) secretes pro- and anti-inflammatory cytokines involved in AT homeostasis, including tumor necrosis factor-α (TNFα) and irisin. The functionality of AT is based on a regulated equilibrium between adipogenesis and extracellular matrix (ECM) remodeling. We investigated the contributions of adipose progenitors (ASCs) and adipocytes (AMCs) to TNFα-induced ECM remodeling and a possible implication of irisin in AT impairment in obesity. ASCs and AMCs were exposed to TNFα treatment and nuclear factor–kappa (NF-kB) pathway was investigated: Tissue Inhibitor of Metalloproteinase (TIMP-1), Twist Family Transcription Factor 1 (TWIST-1), and peroxisome proliferator-activated receptor-γ (PPARγ) expression levels were analyzed. The proteolytic activity of matrix metalloproteinases (MMPs) -2 and -9 was analyzed by zymography, and the irisin protein content was measured by ELISA. In inflamed AMCs, a TIMP-1/TWIST-1 imbalance leads to a drop in PPARγ. Adipogenesis and lipid storage ability impairment come with local tissue remodeling due to MMP-9 overactivation. In vitro and ex vivo measurements confirm positive correlations among inflammation, adipose secreting irisin levels, and circulating irisin levels in patients with visceral obesity. Our findings identify the NF-kB downstream effectors as molecular initiators of AT dysfunction and suggest irisin as a possible AT damage and obesity predictive factor. [ABSTRACT FROM AUTHOR]

The experimental details reported in preclinical fecal microbiota transplantation (FMT) protocols are highly inconsistent, variable, and/or incomplete. We therefore evaluated FMT from a human donor to antibiotic-induced microbial-depleted mice by exploring the effects of six techniques based on antibiotic (AB) or antibiotic + antimycotic (AB + T) gut decontamination, different administration routes, and different dosing intervals on the gut microbial population, assessed using 16S and 18S sequencing. In addition, we explored the effectiveness of FMT in terms of inflammation, physiological, and behavioral outcomes. Our results showed that intrarectal FMT at low dosing intervals better preserved the donor's gut bacterial community at genus level. Furthermore, we showed a lower abundance of several genera of fungi in animals treated with AB + T. In addition, we observed that AB + T gut decontamination followed by per os FMT, once every 3 days, affected behavioral parameters when compared to other FMT techniques. Accordingly, the same FMT groups that showed an association with some of the behavioral tests were also related to specific gut fungal genera, suggesting a possible mediation. Our findings may be useful for optimizing the practice of FMT and also in terms of donor microbiota preservation. This information may help to improve the reproducibility and reliability of FMT studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Parathyroid-hormone-related protein (PTHrP) is a protein hormone of 139, 141, or 173 amino acids, which may be cleaved into smaller bioactive forms, comprising amino terminus, mid-region, and carboxy terminus peptides, active as key controllers of viability, proliferation, and differentiation in diverse normal and pathological cell and tissue model systems via the reprogramming of gene expression and intracellular signalization. Within the large number of data available in the literature on this matter, the objective of this review is to review selected studies that report the detection of molecular markers of exposure to PTHrP, either as full-length protein or as discrete peptides, in peculiar normal or non-neoplastic biological contexts. In particular, the data presented relate to adipose, bone, dental, cartilaginous, and skin tissues, as well as intestinal, renal, hepatic, pulmonary, and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis-, and diabetes-related changes, as demonstrated by molecular profiling, briefly recapitulating the biological implications of the specific gene and/or pathway activation or inactivation. Parathyroid-hormone-related protein (PTHrP) is encoded by the PTHLH gene which, via alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141, and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, mid-region (containing a nuclear/nucleolar targeting signal), and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation, and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated, or nontumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous, and skin tissues, as well as intestinal, renal, hepatic, pulmonary, and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis-, and diabetes-related changes as diseased states. When reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination are also briefly described. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests worldwide, with an estimated prevalence ranging between 19–46% in the general population. Of note, NAFLD is also expected to become a leading cause of end-stage liver disease in the next decades. Given the high prevalence and severity of NAFLD, especially in high-risk populations (i.e., patients with type-2 diabetes mellitus and/or obesity), there is a major interest in early detection of the disease in primary care. Nevertheless, substantial uncertainties still surround the development of a screening policy for NAFLD, such as limitations in currently used non-invasive markers of fibrosis, cost-effectiveness and the absence of a licensed treatment. In this review, we summarise current knowledge and try to identify the limitations surrounding the screening policy for NAFLD in primary care. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent cause of chronic liver disease (CLD). Currently, the only therapeutic recommendation available is a lifestyle change. However, adherence to this approach is often difficult to guarantee. Alteration of the microbiota and an increase in intestinal permeability seem to be key in the development and progression of NAFLD. Therefore, the manipulation of microbiota seems to provide a promising therapeutic strategy. One way to do so is through faecal microbiota transplantation (FMT). Here, we summarize the key aspects of FMT, detail its current indications and highlight the most recent advances in NAFLD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with the pathological accumulation of lipids inside hepatocytes. Untreated NAFL can progress to non-alcoholic hepatitis (NASH), followed by fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The common denominator of the above-mentioned metabolic disorders seems to be insulin resistance, which occurs in NAFLD patients. Obesity is the greatest risk factor for lipid accumulation inside hepatocytes, but a part of the NAFLD patient population has a normal body weight according to the BMI index. Obese people with or without NAFLD have a higher incidence of small intestinal bacterial overgrowth (SIBO), and those suffering from NAFLD show increased intestinal permeability, including a more frequent presence of bacterial overgrowth in the small intestine (SIBO). The health consequences of SIBO are primarily malabsorption disorders (vitamin B12, iron, choline, fats, carbohydrates and proteins) and bile salt deconjugation. Undetected and untreated SIBO may lead to nutrient and/or energy malnutrition, thus directly impairing liver function (e.g., folic acid and choline deficiency). However, whether SIBO contributes to liver dysfunction, decreased intestinal barrier integrity, increased inflammation, endotoxemia and bacterial translocation is not yet clear. In this review, we focus on gut–liver axis and discuss critical points, novel insights and the role of nutrition, lifestyle, pre- and probiotics, medication and supplements in the therapy and prevention of both SIBO and NAFLD. [ABSTRACT FROM AUTHOR]

Diet is currently considered one of the most important adjustable determinants of human health. The gut microbiota, the collection of microorganisms that inhabit (mainly) the distal bowel, has recently been shown to ensure critical physiological functions, such as immune, metabolic and neuropsychiatric. Many of these biological effects result from the production of bacterial metabolites that may target host cells, tissues and organs. In line with this rationale, epigenetics has brought new insights to our understanding of how environmental factors influence gene expression and, interestingly, gut microbiota metabolites have recently been proposed as novel and significant inducers of epigenetic modifications. Efforts have been dedicated to unveil how the production of specific metabolites influences the activity of epigenetic writers and erasers in order to establish a mechanistic link between gut microbiota, epigenetic modifications and health. Recent data is now evidencing how specific microbial metabolites shape the epigenetic landscape of eukaryotic cells, paving new avenues for innovative therapeutic strategies relying on diet-driven microbiota: epigenetic interactions. Herein is discussed the impact of diet on gut microbiota and the molecular mechanisms underlying microbiota–host interactions, highlighting the influence of diet on microbiota metabolome and how this may induce epigenetic modifications in host cells. Furthermore, it is hypothesized that epigenetics may be a key process transducing the effects of diet on gut microbiota with consequences for health and disease. Accordingly, innovating strategies of disease prevention based on a "precision diet", a personalized dietary planning according to specific epigenetic targets, are discussed. [ABSTRACT FROM AUTHOR]

Aims: Scientists have recently discovered a link between the circulating microbiome and homeostasis, as well as the pathogenesis of a number of metabolic diseases. It has been demonstrated that low-grade chronic inflammation is one of the primary mechanisms that has long been implicated in the risk of cardio-metabolic disease (CMDs) and its progression. Currently, the dysbiosis of circulating bacteria is considered as a key regulator for chronic inflammation in CMDs, which is why we have conducted this systemic review focused on circulating bacterial dysbiosis. Methods: A systemic review of clinical and research-based studies was conducted via PubMed, Scopus, Medline, and Web of Science. Literature was considered for risk of bias and patterns of intervention effects. A randomized effect model was used to evaluate the dysbiosis of circulating microbiota and clinical outcomes. We conducted a meta-analysis considering the circulating bacteria in both healthy people and people with cardio-metabolic disorders, in reports published mainly from 2008 to 2022, according to the PRISMA guidelines. Results: We searched 627 studies and, after completing the risk of bias and selection, 31 studies comprising of 11,132 human samples were considered. This meta-analysis found that dysbiosis of phyla Proteobacteria, Firmicutes, and Bacteroidetes was associated with metabolic diseases. Conclusions: In most instances, metabolic diseases are linked to higher diversity and elevated bacterial DNA levels. Bacteroides abundance was higher in healthy people than with metabolic disorders. However, more rigorous studies are required to determine the role of bacterial dysbiosis in cardio-metabolic diseases. Understanding the relationship between dysbiosis and cardio-metabolic diseases, we can use the bacteria as therapeutics for the reversal of dysbiosis and targets for therapeutics use in cardio-metabolic diseases. In the future, circulating bacterial signatures can be used as biomarkers for the early detection of metabolic diseases. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a lipid metabolism disorder associated with the loss of the physiological homeostasis that ensures safe levels of lipids in the organism. This metabolic disorder can trigger pathological conditions such as atherosclerosis and cardiovascular diseases. In this regard, statins currently represent the main pharmacological therapy, but their contraindications and side effects limit their use. This is stimulating the search for new therapeutic strategies. In this work, we investigated in HepG2 cells the hypolipidemic potential of a picrocrocin-enriched fraction, analyzed by high-resolution 1H NMR and obtained from a saffron extract, the stigmas of Crocus sativus L., a precious spice that has already displayed interesting biological properties. Spectrophotometric assays, as well as expression level of the main enzymes involved in lipid metabolism, have highlighted the interesting hypolipidemic effects of this natural compound; they seem to be exerted through a non-statin-like mechanism. Overall, this work provides new insights into the metabolic effects of picrocrocin, thus confirming the biological potential of saffron and paving the way for in vivo studies that could validate this spice or its phytocomplexes as useful adjuvants in balancing blood lipid homeostasis. [ABSTRACT FROM AUTHOR]

We here characterize changes in metabolite patterns in glioblastoma patients undergoing surgery and concurrent chemoradiation using machine learning (ML) algorithms to characterize metabolic changes during different stages of the treatment protocol. We examined 105 plasma specimens (before surgery, 2 days after surgical resection, before starting concurrent chemoradiation, and immediately after chemoradiation) from 36 patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma. Untargeted GC-TOF mass spectrometry-based metabolomics was used given its superiority in identifying and quantitating small metabolites; this yielded 157 structurally identified metabolites. Using Multinomial Logistic Regression (MLR) and GradientBoostingClassifier (GB Classifier), ML models classified specimens based on metabolic changes. The classification performance of these models was evaluated using performance metrics and area under the curve (AUC) scores. Comparing post-radiation to pre-radiation showed increased levels of 15 metabolites: glycine, serine, threonine, oxoproline, 6-deoxyglucose, gluconic acid, glycerol-alpha-phosphate, ethanolamine, propyleneglycol, triethanolamine, xylitol, succinic acid, arachidonic acid, linoleic acid, and fumaric acid. After chemoradiation, a significant decrease was detected in 3-aminopiperidine 2,6-dione. An MLR classification of the treatment phases was performed with 78% accuracy and 75% precision (AUC = 0.89). The alternative GB Classifier algorithm achieved 75% accuracy and 77% precision (AUC = 0.91). Finally, we investigated specific patterns for metabolite changes in highly correlated metabolites. We identified metabolites with characteristic changing patterns between pre-surgery and post-surgery and post-radiation samples. To the best of our knowledge, this is the first study to describe blood metabolic signatures using ML algorithms during different treatment phases in patients with glioblastoma. A larger study is needed to validate the results and the potential application of this algorithm for the characterization of treatment responses. [ABSTRACT FROM AUTHOR]

The novel term metabolic dysfunction-associated fatty liver disease (MAFLD), which has been proposed to describe the major cause of hepatic disease, pinpoints the coexistence of multiple metabolic disturbances and liver steatosis, giving rise to different phenotypic manifestations. Within the psychoneuroendocrineimmunological (PNEI) network that regulates body–mind interactions, the stress response plays a pervasive role by affecting metabolic, hormonal, immune, and behavioral balance. In this perspective, we focus on chronic psychosocial stress and high levels of cortisol to highlight their role in MAFLD pathogenesis and worsening. From a PNEI perspective, considering the stress response as a therapeutic target in MAFLD allows for simultaneously influencing multiple pathways in the development of MAFLD, including dysmetabolism, inflammation, feeding behaviors, gut–liver axis, and dysbiosis, with the hope of better outcomes. [ABSTRACT FROM AUTHOR]

The study of the effects of the COVID-19 pandemic on individuals who attended mental health services is needed to identify the specific vulnerabilities associated to this challenging period. Despite several analyses reporting the worsening of eating disorders symptomatology after the beginning of the pandemic, characterizations of adult inpatients with eating disorders are still lacking. We conducted a retrospective analysis to assess whether adult individuals who underwent hospitalization in a specialized eating disorders unit in the two years after the beginning of the COVID-19 pandemic differed in clinical presentation, psychopathological measures, and treatment outcomes from inpatients hospitalized in the two years before. In the comparison between the two groups, the individuals who began treatment after the start of the pandemic presented with more physical hyperactivity and more severe psychopathological scores in most of the areas investigated, with differences in eating symptoms still evident at discharge. Notably, body-related symptoms (i.e., body shape concerns, body checking, body avoidance) were associated with the pandemic, and also for inpatients with extreme anorexia nervosa. This retrospective analysis does not allow us to separate the impact of COVID-19 from other potentially relevant co-occurring factors; however, these findings help in understanding how the pandemic could have affected individuals that needed specialized intensive treatment. [ABSTRACT FROM AUTHOR]

The first COVID-19 confinement has led to changes in the population's behaviour. However, little has been analysed about the changes in eating behaviour beyond the decrease in adherence to healthy dietary patterns. The aim of the CoV-Eat project was to identify factors related to each of the following eating behaviours (EB): cognitive restraints (CR), uncontrolled eating (UE), and emotional eating (EE) in adults from Spanish-speaking countries. Participants completed an anonymous online survey. EB was assessed using the Three-Factor Eating Questionnaire and the scores were classified into tertiles. Socio-demographic characteristics and lifestyle habits including physical activity, sleep quality, screen use, smoking consumption, and relationship with food were also collected. A total of 9849 participants from 21 countries were included in this study. The median of CR, UE, and EE behaviours was 15, 24, and 9, respectively. We observed that higher age, days of confinement, number of times leaving home in the last week, changes in sleep quality, and their relationship with food were negatively associated with CR, EE, and UE, while being a man was positively associated with an increased in all these EBs. A higher household income was negatively associated with a higher score of CR, and a higher education level (>primary) was positively associated with a medium score of EE. Lower physical activity was a factor negatively associated with a medium score of EE and UE. Higher screen use showed the same negative association for a medium score of EE and UE and a high score of CR. In addition, higher tobacco consumption was found to be a protective factor against having a medium or high score of CR and EE. In conclusion, some sociodemographic characteristics and lifestyle changes may be important factors for EB and should be considered in emergency situations such as confinement to prevent risky eating behaviour. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disorder that is implicated in dysregulations in multiple biological pathways, orchestrated by interactions between genetic predisposition, metabolic syndromes and environmental factors. The limited knowledge of its pathogenesis is one of the bottlenecks in the development of prognostic and therapeutic options for MAFLD. Moreover, the extent to which metabolic pathways are altered due to ongoing hepatic steatosis, inflammation and fibrosis and subsequent liver damage remains unclear. To uncover potential MAFLD pathogenesis in humans, we employed an untargeted nuclear magnetic resonance (NMR) spectroscopy- and high-resolution mass spectrometry (HRMS)-based multiplatform approach combined with a computational multiblock omics framework to characterize the plasma metabolomes and lipidomes of obese patients without (n = 19) or with liver biopsy confirmed MAFLD (n = 63). Metabolite features associated with MAFLD were identified using a metabolome-wide association study pipeline that tested for the relationships between feature responses and MAFLD. A metabolic pathway enrichment analysis revealed 16 pathways associated with MAFLD and highlighted pathway changes, including amino acid metabolism, bile acid metabolism, carnitine shuttle, fatty acid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and steroid metabolism. These results suggested that there were alterations in energy metabolism, specifically amino acid and lipid metabolism, and pointed to the pathways being implicated in alerted liver function, mitochondrial dysfunctions and immune system disorders, which have previously been linked to MAFLD in human and animal studies. Together, this study revealed specific metabolic alterations associated with MAFLD and supported the idea that MAFLD is fundamentally a metabolism-related disorder, thereby providing new perspectives for diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]