Mounting evidence identifies diet quality as a frailty modifying factor. Individuals suffering from metabolic syndrome (MetS) are more likely to be affected by frailty. Therefore, our research sought to explore the relationship of Alternative Healthy Eating Index (AHEI) with frailty risk among patients with MetS.

National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018 were gathered. Frailty Index (FI) was utilized for assessment of frailty status. Weighted multivariate logistic regression model was adopted for investigating the association of AHEI with frailty among patients with MetS. Subgroup analysis, interaction test and restricted cubic spline (RCS) test were also performed in this study.

When the covariates considered were entirely adjusted for, higher AHEI scores exhibited significant association with reduced frailty risk (OR = 0.99,95%CI = 0.981-0.998, P = 0.022). Relative to the frailty risk among participants belonging to the lowest AHEI quartile(Q1), that of individuals in the highest AHEI quartile(Q4) decreased by 32% (OR = 0.68, 95% CI = 0.51-0.92, P = 0.01). Additionally, the negative association of AHEI with frailty persisted for all subgroup analyses, which also indicates the reliability of the relationship.

For patients with MetS, higher AHEI scores reduce the risk of developing frailty. This investigation provides valuable knowledge that could be utilized for treating MetS patients clinically and guiding healthy eating program development.

Akkermansia muciniphila is a promising target for managing obesity and type 2 diabetes (T2D), but human studies are limited. We conducted a 12-week randomized, double-blind, placebo-controlled trial involving 58 participants with overweight or obese T2D, who received A. muciniphila (AKK-WST01) or placebo, along with routine lifestyle guidance. Both groups showed decreases in body weight and glycated hemoglobin (HbA1c), without significant between-group differences. In participants with low baseline A. muciniphila, AKK-WST01 supplementation showed high colonization efficiency and significant reductions in body weight, fat mass, and HbA1c, which were not found in the placebo group. However, AKK-WST01 supplementation showed poor colonization and no significant clinical improvements in participants with high baseline A. muciniphila. These findings were verified in germ-free mice receiving feces with low or high A. muciniphila. Our study indicates that metabolic benefits of A. muciniphila supplementation could depend on its baseline intestinal levels, supporting the potential for gut microbiota-guided probiotic supplementation. (ClinicalTrials.gov number, NCT04797442).

Diabetic nephropathy (DN) is a prevalent complication and serious microvascular of diabetes mellitus. After previous studies, we found that phenylethanol glycosides (CPhGs) derived from Cistanche tubulosa (Schenk) Wight exerts antidiabetic and renoprotective effects. However, the effects of CPhGs on DN remain incompletely understood. The study aimed to examine the effects of CPhGs on DN in rats and explore the underlying mechanism involved. A DN rat model was established by streptozotocin (STZ) combined with a high-fat diet. Reagent kits were used to assess the extent to which CPhGs ameliorate hyperglycemia, insulin resistance (IR), renal dysfunction, kidney oxidative stress, and peripheral inflammation. Histology and immunohistochemical staining were used to detect the changes in renal tissue structure and the expression levels of α-smooth muscle actin (α-SMA) and collagen I. Furthermore, we analyzed the cecal contents of DN rats to investigate the effect of CPhGs on gut microbiota by using 16S rRNA sequencing and broad-spectrum metabolite profiling. The results showed that CPhGs demonstrated a range of advantageous outcomes in DN, encompassing the enhancement of kidney function and alleviation of hyperglycemia, IR, renal injury, oxidative stress, and peripheral inflammatory reactions. In addition, CPhGs regulated the abundance of the [Eubacterium]_coprostanoligenes_group, Oscillospiraceae_UCG-005, etc. to modulate the gut microbiota. CPhGs significantly upregulated the content of vitamin B6 and tyrosyl-tryptophan and downregulated histamine, L-methionine, etc. In summary, the therapeutic efficacy of CPhGs on DN rats may be achieved by modulating the gut microbiota and cecal metabolites to restore the metabolic disorders of vitamin B6, histidine, etc.

Various research in the past has indicated that the NHHR, which represents the ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI) each act independently as contributors to depression risk. Nonetheless, studies exploring the combination of NHHR with BMI in relation to depression are limited. Consequently, the central aim of this study is investigating the joint and interactive effects of NHHR and BMI on depression risk, as well as the mediating role of NHHR.

Encompassing participants aged 20 years or over, this research incorporated a total of 39,704 individuals from the National Health and Nutrition Examination Survey (NHANES), which covered the period of 2005 to 2023. To analyze the impact of NHHR and its combination with BMI on depression, our analytical approach included multivariate logistic regression, restricted cubic spline modeling, interaction testing and subgroup analyses. Additionally, we studied the joint effects of NHHR and BMI. Finally, we applied a four-way decomposition analysis method to examine the interactions and mediating effects within the aforementioned relationships.

Among all participants in this study, the prevalence of depressive disorder (Patient Health Questionnaire-9 score ≥ 10) was 9.2%. Both the NHHR and BMI were associated with depression, which remained significant even after full adjustment for covariates [NHHR, OR (95% CI): 1.07 (1.04-1.09); BMI, OR (95% CI): 1.02 (1.02-1.03)]. Compared with the reference group, the OR (95% CI) for the highest groups of NHHR, BMI, and their product term NHHR-BMI were 1.41 (1.24-1.61), 1.35 (1.18-1.54), and 1.59 (1.37-1.84), respectively. Participants with NHHR in the fourth quartile and BMI exceeding 30 kg/m², had higher depression risk compared to other participants with NHHR in the first quartile and BMI below 25 kg/m² [OR (95% CI): 1.64 (1.34-2.00)]. Results of the four-way decomposition analyses indicated that NHHR played a mediating role in the association between BMI and depression, with the mediating effect accounting for 17.6%. Similarly, NHHR also mediated 11.0% of the mediating effect between BMI and PHQ-9 score. However, no interaction between NHHR and BMI related to depression was found in the general population. After stratifying by gender, it was found that the mediated interaction between NHHR and BMI had a statistically significant effect on depression and PHQ-9 score in males.

Depression risk is linked to both NHHR and BMI, and NHHR has a significant mediating impact on the association between BMI and depression. Notably, there is a non-negligible mediated interaction effect between BMI and NHHR in male participants. Compared to considering NHHR or BMI individually, participants had a higher risk of depression when the combined terms of the two were in the higher quartiles. These findings suggest that the combined assessment of these two indicators may help deepen the understanding and evaluation of depression, enhance the accuracy of risk stratification, and is worthy of further research.

Background: Short-chain fatty acids (SCFAs), which are produced by the microbial fermentation of undigested carbohydrates, play an important role in the metabolism and physiology of the host. SCFAs are involved in the regulation of maternal metabolism during pregnancy and influence weight gain, glucose metabolism, and metabolic hormones. Methods: In 2017, women who were treated for gestational diabetes mellitus (GDM) at the University Medical Centre Ljubljana were invited to participate in a longitudinal study. A total of 45 women were included in this study and comprehensively phenotyped. During the second and third trimester of pregnancy, the women with GDM provided fecal samples for SCFA analysis. The samples were analyzed by high-performance liquid chromatography for the simultaneous determination of acetate, propionate, and butyrate. Results: SCFA concentrations in feces differed between overweight/obese and normal-weight women with GDM. Acetate and propionate concentrations were significantly higher in pregnant women who were overweight or obese before pregnancy compared to normal-weight women but butyrate concentrations were not. Butyrate was elevated in the third trimester in the group with excessive gestational weight gain. Conclusions: The relationship between SCFAs and obesity is complex, and the association between SCFAs and GDM remains to be clarified. Regardless of the conflicting publications on the role of SCFAs, our study showed that higher acetate and propionate levels were associated with the weight categories of overweight or obesity before pregnancy and higher butyrate levels were associated with excessive gestational weight gain.

Metabolic Syndrome (MS) is a cluster of metabolic abnormalities closely associated with hypertension, diabetes, hyperlipidemia, obesity, etc. Our previous research indicated that fecal microbiota transplantation (FMT) could improve MS, but the factors influencing the efficacy of washed microbiota transplantation (WMT) in treating MS patients remain unclear. The objective of this study is to analyze the influencing factors of WMT in treating MS patients.

The clinical data and influencing factors related to MS patients were collected retrospectively. Not only the changes in body mass index [BMI = weight (kg)/height (m)2], blood glucose, blood lipids, and blood pressure were analyzed, but also the influencing factors of WMT in treating MS patients were carried out based on Logistic Regression. The 16S rRNA gene amplicon sequencing was performed on fecal samples before and after WMT treatment.

A total of 210 patients were included, including 68 patients in the WMT group and 142 patients in the drug treatment (DT) group. WMT had a significant improvement and ASCVD downregulation effect on MS patients, and 42.65% of MS patients removed the label of MS after WMT treatment. Independent influencing factors for treating MS patients through WMT include age < 60 years old, high smoking index, infection, single donor selection, single-course WMT treatment, and having hypertension, diabetes, or obesity. WMT treated MS patients by maintaining the balance of gut microbiota.

WMT has a significant effect in improving MS and downregulating ASCVD risk stratification. The therapeutic effect of WMT on MS patients is closely related to their age, smoking index, infection, chronic disease status, donor type, and WMT courses. Therefore, we can improve the efficacy of WMT by reducing independent influencing factors that affect gut microbiota homeostasis.

A high-fat diet (HFD) is often associated with hepatic lipid metabolism disorders, leading to dysfunction in multiple body systems. Ginsenosides derived from Panax ginseng have been reported to possess potential effects in ameliorating lipid metabolism disorders; however, their underlying mechanisms remain insufficiently explored. This study aims to investigate the bioactivities of ginsenosides in combating lipid metabolism disorders and obesity, with a focus on their mechanisms involving the cholesterol metabolism signaling pathway and gut microbiota. Our results demonstrated that ginsenoside treatment significantly reduced overall body weight, body weight changes, liver weight, and eWAT weight, as well as alleviated hepatic steatosis and dyslipidemia in HFD-fed rats, without affecting food intake. These effects were dose-dependent. Furthermore, 16S rRNA sequencing revealed that ginsenosides significantly increased the relative abundance of Akkermansia muciniphila, Blautia, Eisenbergiella, Clostridium clusters XI, XVIII, and III, while decreasing the relative abundance of Clostridium subcluster XIVa and Dorea. In addition, ginsenoside treatment significantly regulated the expression of hepatic genes and proteins involved in the cholesterol metabolism signaling pathway (FXR, CYP7A1, CYP7B1, CYP27A1, ABCG5, ABCG8, Insig2, and Dhcr7), potentially inhibiting hepatic cholesterol biosynthesis while promoting cholesterol transport to HDL and its excretion via bile and feces. Notably, levels of 7-dehydrocholesterol (7-DHC) and 27-hydroxycholesterol (27-OHC) were reduced, while 5β,6β-epoxycholesterol (5,6β-epoxy) levels were elevated following ginsenoside treatment, indicating significant modulation of oxysterols by ginsenosides. Moreover, bile acid enterohepatic circulation was regulated through the enhancement of hepatic FXR-CYP7A1 signaling and intestinal FXR-FGF15 signaling in HFD-fed rats treated with ginsenosides, which was closely linked to gut microbiota composition. Collectively, our findings suggest that ginsenosides alleviate hepatic lipid metabolism disorders by modulating gut microbiota and the cholesterol metabolism signaling pathway in HFD-fed rats.

Obesity and metabolic disorders, such as metabolic syndrome (MetS) facilitate the development of neurodegenerative diseases and cognitive decline. Persistent neuroinflammation plays an important role in this process. Pleiotrophin (PTN) is a cytokine that regulates energy metabolism and high-fat diet (HFD)-induced neuroinflammation, suggesting that PTN could play an important role in the connection between obesity and brain alterations, including cognitive decline. To test this hypothesis, we used an HFD-induced obesity model in Ptn genetically deficient mice (Ptn-/-). First, we confirmed that Ptn deletion prevents HFD-induced obesity. Our findings demonstrate that feeding wild-type (Ptn+/+) mice with HFD for 6 months results in short- and long-term memory loss in the novel object recognition task. Surprisingly, we did not observe any sign of cognitive impairment in Ptn-/- mice fed with HFD. In addition, we observed that HFD induced microglial responses, astrocyte depletion, and perineuronal nets (PNNs) alterations in Ptn+/+ mice, while these effects of HFD were mostly prevented in Ptn-/- mice. These results show a crucial role of PTN in metabolic responses and brain alterations induced by HFD and suggest the PTN signalling pathway as a promising therapeutic target for brain disorders associated with MetS.

Attention Deficit Hyperactivity Disorder (ADHD) is a clinically common neurodevelopmental disorder of the brain. In addition to genetic factors, an imbalance in gut flora may also play a role in the development of ADHD. Currently, it is critical to investigate the function of gut flora and related metabolites, which may form the fundamental basis of bidirectional cross-linking between the brain and the gut, in addition to focusing on the changed gut flora in ADHD. This study aimed to investigate the possible relationship between changes in gut flora and metabolites and ADHD by analyzing metagenome and untargeted metabolomics of fecal samples from ADHD patients. Specifically, we attempted to identify key metabolites and the metabolic pathways they are involved in, as well as analyze in detail the structure and composition of the gut flora of ADHD patients. In order to further investigate the relationship between gut flora and ADHD symptoms, some behavioral studies were conducted following the transplantation of gut flora from ADHD patients into rats. The results of the metagenome analysis revealed several distinct strains, including Bacteroides cellulosilyticus, which could be important for diagnosing ADHD. Additionally, the ADHD group showed modifications in several metabolic pathways and metabolites, including the nicotinamide and nicotinic acid metabolic pathways and the metabolite nicotinamide in this pathway. The behavioral results demonstrated that rats with ADHD gut flora transplants displayed increased locomotor activity and interest, indicating that the onset of behaviors such as ADHD could be facilitated by the flora associated with ADHD. This research verified the alterations in gut flora and metabolism observed in ADHD patients and provided a list of metabolites and flora that were significantly altered in ADHD. Simultaneously, our findings revealed that modifications to the microbiome could potentially trigger behavioral changes in animals, providing an experimental basis for comprehending the function and influence of gut flora on ADHD. These results might provide new perspectives for the development of novel treatment strategies.

The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed "nutritional programming." Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.

Polycystic ovary syndrome (PCOS) is a common gynecological condition affecting individuals of reproductive age and is linked to the gut microbiome. This study aimed to identify the hotspots and research trends within the domain of the gut microbiome in PCOS through bibliometric analysis.

Utilizing bibliometric techniques, we examined the literature on the gut microbiome in PCOS from the Web of Science Core Collection spanning the period from 2012 to 2023. Analytical tools such as CiteSpace, VOSviewer, and Bibliometric R packages were employed to evaluate various metrics, including countries/regions, institutions, authors, co-cited authors, authors' H-index, journals, co-references, and keywords.

A total of 191 publications were identified in the field of gut microbiome in PCOS, with an increase in annual publications from 2018 to 2023. People's Republic of China was the most productive country, followed by the United States of America (USA), India. Shanghai Jiao Tong University, Fudan University, and Beijing University of Chinese Medicine were the top three most publications institutions. Thackray VG was identified as the most prolific author, holding the highest H-index, while Liu R received the highest total number of citations. The journal "Frontiers in Endocrinology" published the most articles in this domain. The most frequently co-cited reference was authored by Qi XY. The analysis of keyword burst detection identified "bile acids" (2021-2023) as the leading frontier keyword. Additionally, "gut dysbiosis," "phenotypes," "adolescents," "metabolomics," "metabolites," "fecal microbiota transplantation," and "IL-22" have emerged as the primary keywords reflecting recent research trends.

This bibliometric analysis explores how the gut microbiome influences endocrine and metabolic disorders related to PCOS, emphasizing its role in the development of PCOS and treatments targeting the gut microbiome. The findings serve as a valuable resource for researchers, enabling them to identify critical hotspots and emerging areas of investigation in this field.

Polysaccharide extracted from Grifola frondosa (GFP) was selected in this study. After preliminary separation, four factions were collected, named GFP-F1, GFP-F2, GFP-F3 and GFP-F4. GPF-F2 was further separated into two fractions, namely GFP-N1 and GFP-N2. The molecular weight of GFP-N1 and GFP-N2 was 3.323×103 kDa and 10.8 kDa, respectively. GFP-N1 was composed of glucose and galactose and 1 → 3, 1 → 4, and 1 → 6 glycosidic bonds. GFP-N2 was composed of glucose, galactose and mannose and 1 → 2, 1 → 3, 1 → 4, and 1 → 6 glycosidic bonds. GFP could significantly relieve the insulin resistance induced by HFD. GFP significantly alleviated gut microbiota disturbance caused by HFD and increased the production of short-chain fatty acids, and further reduced the expression of LPS/TLR4 inflammatory pathway. GFP significantly reduced the oxidative stress induced by HFD, increased the expression of the Nrf2/ARE signaling pathway. These results indicated that GFP could be developed as a potential ingredient for the management of insulin resistance.

Indole-3-carbinol (I3C) is a compound derived from Cruciferous vegetables. We aim to ascertain whether I3C mediates the relations between mouse gut microbiota, intestinal barrier function, and metabolism to treat obesity in mice.

The experimental analyses focused on the changes in lipid distribution, inflammatory cytokines, glucose tolerance, gut microbiota composition, and serum metabolomics of 60 C57BL/6N mice.

The experimental results demonstrated that I3C reduced body weight, hepatic steatosis, and systemic inflammation and improved insulin resistance in mice on a high-fat diet (HFD). Furthermore, I3C remarkably enhanced the enrichment of probiotics Akkermansia and Ligilactobacillus as well as SCFA-producing bacteria (Eubacterium, Lactococcus, and Coprococcus), while reducing the abundance of Eisenbergiella and Rikenellaceae_RC9_gut_group. Also, I3C notably up-regulated the levels of Claudin4, Occludin, and ZO-1 proteins and modulated the metabolism of argininosuccinic acid and galactose.

The aforementioned findings suggest that I3C exerts a significant anti-obesity effect in mice by regulating abnormal gut microbiome, enhancing intestinal barrier function, and improving metabolic disorders.

Intestinal remnant chylomicrons (CMs) are involved in cardiovascular residual risk and the atherogenic process. Microsomal triglyceride transfer protein (MTTP) catalyzes the assembly of lipids to apolipoprotein B48, generating CMs. Dysbiosis could alter this behavior. This study investigated the chemical composition of CMs and their associations with intestinal MTTP and gut fat depots in a diet-induced dysbiosis animal model.

Male Wistar rats were fed either a standard diet (control, n=10) or a high-fat high-sucrose diet (HFSD, n=10) for 14 weeks. Measurements included serum glucose, lipid-lipoprotein profile, free fatty acids (FFAs), lipopolysaccharide (LPS) and the Firmicutes/Bacteroidetes (F/B) ratio in stool samples, via real-time quantitative polymerase chain reaction. Lipid content in isolated CMs (ultracentrifugation d <0.95 g/mL) was assessed, and MTTP, cell intestinal fat content (CIF), histology, apoB mRNA and tight junction (TJ) proteins were analyzed, in intestinal tissue.

Compared to control, HFSD rats showed higher levels of LPS, triglycerides (TGs), non-high-density lipoprotein cholesterol (HDL-C) levels, TG/HDL-C ratio, FFAs, and the F/B ratio. HFSD CMs showed increased TG and phospholipids. TJ proteins levels were lower in the HFSD group, while histological scores showed no differences. CIF was increased in the HFSD group. No significant differences in apoB mRNA were found. MTTP expression was higher in the HFSD group, and directly correlated with CM-TG and inversely correlated with CIF.

Our findings imply that gut TG content may constitute an important determinant of the secretion of TG-rich CMs, promoted by MTTP, with increased atherogenic potential.

The prenatal period is a critical developmental juncture with enduring effects on offspring health trajectories. An individual's gut microbiome is associated with health and developmental outcomes across the lifespan. Prenatal stress can disrupt an infant's microbiome, thereby increasing susceptibility to adverse outcomes. This cross-species systematic review investigates whether maternal prenatal stress affects the offspring's gut microbiome. The study analyzes 19 empirical, peer-reviewed research articles, including humans, rodents, and non-human primates, that included prenatal stress as a primary independent variable and offspring gut microbiome characteristics as an outcome variable. Prenatal stress appeared to correlate with differences in beta diversity and specific microbial taxa, but not alpha diversity. Prenatal stress is positively correlated with Proteobacteria, Bacteroidaceae, Lachnospiraceae, Prevotellaceae, Bacteroides, and Serratia. Negative correlations were observed for Actinobacteria, Enterobacteriaceae, Streptococcaceae, Bifidobacteria, Eggerthella, Parabacteroides, and Streptococcus. Evidence for the direction of association between prenatal stress and Lactobacillus was mixed. The synthesis of findings was limited by differences in study design, operationalization and timing of prenatal stress, timing of infant microbiome sampling, and microbiome analysis methods.

Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood. Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile. Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota-BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.

The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction.

This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis.

In view of recent evidence that the gut-brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut-brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut-brain axis homeostasis towards local and systemic pro-inflammatory responses.

As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field.

Dysregulation of energy metabolism, including hyperglycemia, insulin resistance and fatty liver have been reported in a substantial proportion of lean children. However, non-obese murine models recapitulating these features are lacking to study the mechanisms underlying the development of metabolic dysregulations in lean children. Here, we develop a model of diet-induced metabolic dysfunction without obesity in juvenile mice by feeding male and female mice a diet reflecting Western nutritional intake combined with protein restriction (mWD) during 5 weeks after weaning. mWD-fed mice (35% fat, 8% protein) do not exhibit significant weight gain and have moderate increase in adiposity compared to control mice (16% fat, 20% protein). After 3 weeks of mWD, juvenile mice have impaired glucose metabolism including hyperglycemia, insulin resistance and glucose intolerance. mWD also triggers hepatic metabolism alterations, as shown by the development of simple liver steatosis. Both male and female mice fed with mWD displayed metabolic dysregulation, which a probiotic treatment with Lactiplantibacillus plantarum WJL failed to improve. Overall, mWD-fed mice appear to be a good preclinical model to study the development of diet-induced metabolic dysfunction without obesity in juveniles.

Direct and indirect evidence suggests that endometrial receptivity may play a crucial role in the reduced fertility rate of women with polycystic ovary syndrome (PCOS). Various pharmacological and non-pharmacological strategies with potential effects on endometrial receptivity in patients with PCOS have been proposed. The aim of this study was to summarize the rationale and the clinical and experimental evidence of interventions tested for improving endometrial receptivity in infertile patients with PCOS. A systematic review was conducted by consulting electronic databases. All interventions with a potential influence on endometrial receptivity in infertile patients with PCOS were evaluated, and their main biological mechanisms were analysed. In total, 24 interventions related to endometrial receptivity were identified. Notwithstanding a strong biological rationale, no intervention aimed at improving endometrial receptivity in women with PCOS is supported by an adequate body of evidence, limiting their use in clinical practice. Further high-quality research is needed in this field to limit potentially ineffective and unsafe add-on treatments in infertile patients with PCOS.

Gallstone disease (GSD), nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and metabolic syndrome (MetS) are common medical disorders worldwide. This study aimed to ascertain how NAFLD, MAFLD, MetS, and other factors affect the development of GSD, and how the GSD-associated factors influence patient recovery after laparoscopic cholecystectomy (LC).

We included 200 patients who were diagnosed with GSD and underwent LC between January 2017 and February 2022. A total of 200 subjects without GSD and "non-calculous causes" during the same period were also included as controls. We compared the metabolic disorder differences between GSD patients and controls. Furthermore, we sub-grouped patients based on the comorbidities of preoperative NAFLD, MAFLD, and MetS, and compared the impacts of these comorbidities on short-term post-LC functional recovery of the patients.

The prevalence of NAFLD and MetS were higher in GSD patients (P < 0.05). Based on multivariate logistic regression analysis, hyperglycemia [odds ratio (OR) = 2.2, 95% confidence interval (CI): 1.4-3.4, P = 0.001] and low high-density lipoprotein cholesterol (HDL-C) level (OR = 1.8, 95% CI: 1.1-3.1, P = 0.048) were linked to GSD. NAFLD and MetS linked to liver enzymes after LC (P < 0.05). MetS also linked to the levels of inflammatory indicators after LC (P < 0.05). The obesity, hyperlipidemia, low HDL-C level, and hyperglycemia linked to liver enzymes after LC (P < 0.05). Hyperlipidemia, low HDL-C level, and hypertension linked to inflammation after LC (P < 0.05).

The prevalence of GSD may be linked to NAFLD and MetS. Hyperglycemia and low HDL-C level were independent risk factors of GSD.

Edible fungi polysaccharides (EFPs) and gut microbiota (GM) play an important role in lipid metabolism. The structure of GM is complex and can be dynamically affected by the diet. EFPs can be used as dietary intervention to improve lipid metabolism directly, or by regulate the GM to participate in the host lipid metabolism by a complex mechanism. In this paper, we reviewed that EFPs regulate the balance of GM by increasing the number of beneficial bacteria and decreasing the number of harmful bacteria in the intestinal tract. The metabolites of GM are mainly bile acids (BAs), short-chain fatty acids (SCFAs), and lipopolysaccharides (LPS). EFPs can promote the synthesis of BAs and increase the content of SCFAs that produced by GM fermented EFPs, but reduce the content of LPS to regulate lipid metabolism. This review provides a valuable reference for further elucidation of the relationship between EFPs-GM-lipid metabolism and EFPs targeted regulation of GM to improve public health.

Pidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the "Pidan" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied.

This study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics.

The IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT.

PDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified_f__Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine.

Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota-including bacteria, viruses, fungi, and parasites-in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the "hygiene hypothesis" suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.

To prevent infection, the experience of the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has led to recognition of the importance of not only vaccines but also the strengthening of mucosal barriers by secretory immunoglobulin A (IgA). Strong mucosal barrier provided by IgA is also possible to prevent allergies and chronic inflammatory conditions in the intestinal tract, since it can protect foreign enemies or antigens at the first line of defense before their invasion. Therefore, it is important to understand the role of IgA antibodies secreted by the mucosa of the body. In this section, we discuss the role of mucosal IgA antibodies in relation to three disease states: control of intestinal microbiota, protection against infection, and allergy. In addition, we provide the evidence in which the quality as well as the quantity of IgA is critical for disease prevention. Therefore, we discuss about novel strategies to enhance mucosal barriers by induction of high-quality IgA.

The gut microbiome plays vital roles in human health, including mediating metabolism, immunity, and the gut-brain axis. Many ethnicities remain underrepresented in gut microbiome research, with significant variation between Indigenous and non-Indigenous peoples due to dietary, socioeconomic, health, and urbanization differences. Although research regarding the microbiomes of Indigenous peoples is increasing, Māori microbiome literature is lacking despite widespread inequities that Māori populations face. These inequities likely contribute to gut microbiome differences that exacerbate negative health outcomes. Characterizing the gut microbiomes of underrepresented populations is necessary to inform efforts to address health inequities. However, for microbiome research to be culturally responsible and meaningful, study design must improve to better protect the rights and interests of Indigenous peoples. Here, we discuss barriers to Indigenous participation in research and the role disparities may play in shaping the gut microbiomes of Indigenous peoples, with a particular focus on implications for Māori and areas for improvement.

Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.

Although dietary diversity (DD) has been confirmed to be associated with multiple health outcomes and longevity in older people, the related mechanisms have not been elucidated. In this study, we explored the mediating roles of physical activities and cognitive function in the relationship between DD and all-cause mortality.

We recruited 34 068 community-dwelling older adults aged ≥60 years from the Chinese Longitudinal Healthy Longevity Study and followed them up until 2018. Dietary diversity score (DDS) was assessed by the intake frequency of nine food sources. We evaluated physical activities and cognitive function using the Katz index and Mini-Mental State Examination. We explored the mediating roles of physical activities and cognitive function between DDS and all-cause mortality using mediated analyses in Cox proportional risk regression models.

A total of 25 362 deaths were recorded during 148 188.03 person-years of follow-up. Participants with physical disability and cognitive impairment had lower DDS than the normal group (P < 0.001). After controlling for all covariates, DDS, physical activities, and cognitive functioning were negatively associated with all-cause mortality. Physical activities and cognitive function mediated 18.29% (95% confidence interval (CI) = 12.90-23.10) and 27.84% (95% CI = 17.52-37.56) of the total effect of DDS on mortality, respectively.

Physical activities and cognitive function mediated the association between DDS and all-cause mortality. Maintaining DD may benefit early death prevention by reducing physical disability and cognitive impairment in community-dwelling older people.

Mulberry leaf polysaccharides (MLP) are integral components of Mulberry leaves that confer hypoglycemic and hypolipidemic properties. This study investigated the efficacy of MLP in treating Type 2 Diabetes Mellitus (T2DM) and the underlying mechanisms related to gut microbiota-bile acids metabolism in T2DM rats. The findings revealed that MLP apparently reduced fasting blood glucose and lipid levels, ameliorated disorders in glucose and lipid metabolism, and mitigated insulin resistance. MLP enhanced the abundance of Prevotella, Ruminococcus, and Lactobacillus, thereby rectifying the gut microbiota dysbiosis in rats, which effectively restored gut microbiota homeostasis and composition. Furthermore, the data demonstrated that MLP modulated bile acid metabolism, as evidenced by reduced serum cholesterol levels, enhanced mRNA expression of hepatic cholesterol 7α- hydroxylase (Cyp7a1) and cholesterol 12α- hydroxylase (Cyp8b1), and ileal G protein-coupled bile acid receptor (Tgr5), while suppressing hepatic and ileal farnesoid X receptor (Fxr) mRNA expression in T2DM rats. Additionally, MLP upregulated the protein expression of hepatic CYP7A1 and CYP8B1, and ileal TGR5, while inhibiting FXR protein levels in the liver and ileum of T2DM rats. These results suggest that MLP can rectify disorders in glucose and lipid metabolism via the gut microbiota-bile acids metabolic pathway.

Obesity has become a major public health concern worldwide, increasing the risk of T2DM. Growing evidence indicates gut microbiota dysbiosis is related to metabolic disorders. We aimed to firstly investigate the compositional and functional features of the gut microbiome between obesity with and without T2DM in the Chinese population.

A total of 32 obese individuals accompanied with T2DM and 18 age and gender-matched obesity with normal glucose tolerance (NGT) were enrolled. Fecal samples were collected, and the gut microbiota profile was determined using the Illumina MiSeq platform based on V3-V4 bacterial 16S rRNA gene.

Compared with obesity- NGT, obesity-T2DM showed a significantly higher alpha diversity. Principal coordinates analysis based on both Bray-Curtis distance and weighted Unifrac revealed that the global microbial composition was significantly different between the two groups (P = 0.007 and P = 0.005, respectively). At the phylum level, Obesity-T2DM patients exhibited a significant decrease in Bacteroidetes, and a pronounced increase in Firmicutes. Regarding the genus level, Bacteroides and Escherichia-Shigella were found to increase considerably, while Prevotella_9 and Sutterella had an evident decrease in Obesity-T2DM. Furthermore, Spearman correlation analysis revealed that Prevotella_9 and Sutterella were negatively associated with HbA1c and fasting blood glucose.

We found clear differences in the gut microbiota composition in obesity-T2DM compared with obesity-NGT. Obesity accompanied with T2DM may aggravate the obesity-associated gut microbiota, and gut microbiota is expected to be a promising novel intervention target for obese management. However, larger sample size and more in-depth taxonomic identification studies are warranted.

The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.

Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI.

This study aims to elucidate the connections between miR-30a-5p, MI, gut microbiota, and gut microbial metabolite-related pathways, to explore potential strategy for preventing and treating MI.

We evaluated the effects of knocking out (KO) or overexpressing (OE) miR-30a-5p on MI by assessing cardiac structure and function, myocardial enzyme levels, and apoptosis. Then, we applied 16S rDNA sequencing and metabolomics to explore how intestinal microecology and its microorganisms affect miR-30a-5p-regulated MI.

The results showed that KO exacerbated MI, whereas OE improved MI damage, compared to the wild-type (WT) mice. KO exacerbated intestinal barrier structure deterioration and further downregulated the expression of Cloudin-1, Occludin, and ZO-1 in MI mice. 16S rDNA sequencing-analyzed gut microbiome of KO and WT mice found that KO mainly reduced g_Lactobacillus. Transplanting fecal microorganisms from KO mice aggravated MI damage in WT mice. However, administering probiotics (mainly containing Lactobacillus) helped neutralize these damages. Intriguingly, fecal microbiota transplantation from OE mice reduced MI damage. Analysis of intestinal microbial metabolites in KO and WT mice found that KO may mainly affect ABC transporters. ABCC1 was identified as the target of KO-aggravated MI. Furthermore, fecal transplantation microorganisms of MI patients aggravated MI injury in mice and miR-30a-5p and ABCC1 were involved in the process.

Our findings demonstrate that miR-30a-5p regulates MI by affecting intestinal microbiota homeostasis and targeting ABCC1. This highlights the critical importance of maintaining a healthy gut microbiota homeostasis in MI management.

The gut microbiota (GM), comprising trillions of microorganisms in the gastrointestinal tract, is a key player in the development of obesity and related metabolic disorders, such as type 2 diabetes (T2D), metabolic syndrome (MS), and cardiovascular diseases. This mini-review delves into the intricate roles and mechanisms of the GM in these conditions, offering insights into potential therapeutic strategies targeting the microbiota. The review elucidates the diversity and development of the human GM, highlighting its pivotal functions in host physiology, including nutrient absorption, immune regulation, and energy metabolism. Studies show that GM dysbiosis is linked to increased energy extraction, altered metabolic pathways, and inflammation, contributing to obesity, MS, and T2D. The interplay between dietary habits and GM composition is explored, underscoring the influence of diet on microbial diversity and metabolic functions. Additionally, the review addresses the impact of common medications and therapeutic interventions like fecal microbiota transplantation on GM composition. The evidence so far advocates for further research to delineate the therapeutic potential of GM modulation in mitigating obesity and metabolic diseases, emphasizing the necessity of clinical trials to establish effective and sustainable treatment protocols.

Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, which is associated with diverse metabolic abnormalities. We hypothesized that elevated cortisol levels in dogs with HAC disrupt the gut microbiome (GM), and this disruption persists even after trilostane treatment. This study explored GM composition in dogs with HAC. We included 24 dogs, 15 with HAC and 9 healthy controls, and followed up with 5 dogs with HAC who received trilostane treatment. The GM analysis revealed significant compositional changes in dogs with HAC, including reduced microbiome diversity compared to healthy controls, particularly in rare taxa, as indicated by the Shannon index (p = 0.0148). Beta diversity analysis further showed a distinct clustering of microbiomes in dogs with HAC, separating them from healthy dogs (p < 0.003). Specifically, an overrepresentation of Proteobacteria (Pseudomonadota), Actinobacteria, Bacteroides, Enterococcus, Corynebacterium, Escherichia, and Proteus populations occurred alongside a decreased Firmicutes (Bacillota) population. Despite trilostane treatment, gut dysbiosis persisted in dogs with HAC at a median of 41 d post treatment, suggesting its potential role in ongoing metabolic issues. We identified GM dysbiosis in dogs with HAC by examining key bacterial genera, offering insights into potential interventions like probiotics or fecal microbiota transplants for better HAC management.

The intricate ecosystem of microorganisms residing within and on the human body, collectively known as the microbiome, significantly influences human health. Imbalances in this microbiome, referred to as dysbiosis, have been associated with various diseases, prompting the exploration of novel therapeutic approaches. Personalized medicine, Tailors treatments to individual patient characteristics, offers a promising avenue for addressing microbiome-related health issues. This review highlights recent developments in utilizing personalized medicine to target the microbiome, aiming to enhance health outcomes. Noteworthy strategies include fecal microbiota transplantation (FMT), where healthy donor microbes are transferred to patients, showing promise in treating conditions such as recurrent Clostridium difficile infection. Additionally, probiotics, which are live microorganisms similar to beneficial gut inhabitants, and prebiotics, non-digestible compounds promoting microbial growth, are emerging as tools to restore microbiome balance. The integration of these approaches, known as synbiotics, enhances microbial colonization and therapeutic effects. Advances in metagenomics and sequencing technologies provide the means to understand individual microbiome profiles, enabling tailored interventions. This paper aims to present the latest insights in leveraging personalized medicine to address microbiome-related health concerns, envisioning a future where microbiome-based therapies reshape disease management and promote human health.

Metabolic syndrome (MetS) is recognized as a group of metabolic abnormalities, characterized by clustered interconnected traits that elevate the risks of obesity, cardiovascular and atherosclerotic diseases, hyperlipidemia, and type 2 diabetes mellitus. Non-nutritive sweeteners (NNS) are commonly consumed by those with imbalanced calorie intake, especially in the perinatal period. In the past, accumulating evidence showed the transgenerational and mediated roles of human microbiota in the development of early-life MetS. Maternal exposure to NNS has been recognized as a risk factor for filial metabolic disturbance through various mechanisms, among which gut microbiota and derived metabolites function as nodes linking NNS and MetS in early life. Despite the widespread consumption of NNS, there remain growing concerns about their transgenerational impact on metabolic health. There is growing evidence of NNS being implicated in the development of metabolic abnormalities. Intricate complexities exist and a comprehensive understanding of how the gut microbiota interacts with mechanisms related to maternal NNS intake and disrupts metabolic homeostasis of offspring is critical to realize its full potential in preventing early-life MetS. This review aims to elucidate the effects of early-life gut microbiota and links to maternal NNS exposure and imbalanced offspring metabolic homeostasis and discusses potential perspectives and challenges, which may provide enlightenment and understanding into optimal perinatal nutritional management.

Metabolic syndrome (MetS) is a disease condition incorporating the abnormal accumulation of various metabolic components, including overweight or abdominal obesity, insulin resistance and abnormal glucose tolerance, hypertension, atherosclerosis, or dyslipidemia. It has been proved that the gut microbiota and microbial-derived products play an important role in regulating lipid metabolism and thus the onset and development of MetS. Previous studies have demonstrated that oligosaccharides with prebiotic effects, such as chitosan oligosaccharides, can regulate the structure of the microbial community and its derived products to control weight and reduce MetS associated with obesity. Alginate oligosaccharides (AOS), natural products extracted from degraded alginate salts with high solubility and extensive biological activity, have also been found to modulate gut microbiota. This review aims to summarize experimental evidence on the positive effects of AOS on different types of MetS while providing insights into mechanisms through which AOS regulates gut microbiota for preventing and treating MetS.

The gut microbiota and the host maintain a conjoint relationship and together achieve optimal physiology via a multitude of interactive signalling cues. Dietary-derived L-tryptophan (L-trp) is enzymatically metabolized by the resident symbiotic gut microbiota to indole and various indole derivatives. Indole and indole metabolites secreted by the gut bacteria act locally in the intestinal cells as well as distally and modulate tissue-specific functions which are beneficial to the host. Functions attributed to these microbial indole metabolites in the host include regulation of intestinal permeability, immunity and mucosal roles, inflammation, and insulin sensitivity. On the other hand, dysregulation of gut microbiota L-trp metabolism compromises the optimal availability of indole and indole metabolites and can induce the onset of metabolic disorders, inflammation, liver steatosis, and decrease gut barrier integrity. Gut dysbiosis is regarded as one of the prime reasons for this deregulated microbial-derived indole metabolites. A number of indole metabolites from the gut bacteria have been identified recently displaying variable affinity towards xenobiotic nuclear receptors. Microbial metabolite mimicry concept can be used to design and develop novel indole-moiety-containing compounds with higher affinity towards the receptors and efficacy in preclinical studies. Such compounds may serve as therapeutic drugs in clinical trials in the future. In this article, I review L-trp metabolism in the host and gut microbiota and the various physiological functions, patho-physiologies associated with the microbial-released indole metabolites in the host, including the metabolite mimicry-based concept to develop tailored indole-containing novel experimental drugs.

Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases. Gualou-Xiebai-Banxia-Tang decoction (GT) was first described in the Synopsis of the Golden Chamber, the earliest traditional Chinese medicine (TCM) monograph on diagnosis and treatment of miscellaneous diseases in China. According to TCM precepts, based on its ability to activate yang to release stagnation, activate qi to reduce depression, remove phlegm, and broaden the chest, GT has been used for more than 2,000 years to treat cardiovascular ailments. However, the molecular bases of its therapeutic mechanisms remain unclear.

The aim of this study was to identify lipid- and glucose-related hepatic genes differentially regulated by GT, and to assess GT impact on gut microbiota composition, in mice with high-fat diet (HFD)-induced MetS.

ApoE-/- mice were fed with an HFD for 24 weeks, with or without concurrent GT supplementation, to induce MetS. At the study's end, body weight, visceral fat weight, blood lipid levels, and insulin sensitivity were measured, and histopathological staining was used to evaluate hepatosteatosis and intestinal barrier integrity. Liver transcriptomics was used for analysis of differentially expressed genes in liver and prediction of relevant regulatory pathways. Hepatic lipid/glucose metabolism-related genes and proteins were detected by RT-qPCR and western blotting. Gut microbial composition was determined by 16S rRNA gene sequencing.

GT administration reduced MetS-related liver steatosis and weight gain, promoted insulin sensitivity and lipid metabolism, and beneficially modulated gut microbiota composition by decreasing the relative abundance of g_Lachnospiraceae_NK4A136_group and increasing the relative abundance of g_Alistipes. Liver transcriptomics revealed that GT regulated the expression of genes related to lipid and glucose metabolism (Pparγ, Igf1, Gpnmb, and Trem2) and of genes encoding chemokines/chemokine receptors (e.g. Cxcl9 and Cx3cr1). Significant, positive correlations were found for Ccr2, Ccl4, Ccr1, and Cx3cr1 and the g_Lachnospiraceae_NK4A136_group, and between Cxcl9, Ccr2, Ccl4, and Cx3cr1 and g_Desulfovibrio. GT treatment downregulated the protein expressions of SCD1 and CX3CR1 and upregulated the expression of PCK1 protein.

GT supplementation alleviates HFD-induced MetS in mice by improving hepatic lipid and glucose metabolism. The anti-metabolic syndrome effects of GT may be related to the regulation of the gut-liver axis.

Pituitary adenomas are benign tumors located in the anterior hypophysis. Its appearance is associated with the development of parameters related to metabolic syndrome; therefore, surgical treatment could reduce associated morbimortality.

Pre- and post-surgical MRI, using the Hardy-Wilson and Knosp classification, and clinical data according to the American Association of Clinical Endocrinology (AACE) criteria for metabolic syndrome: all the patients were followed-up until 208.57 days were reviewed on 217 consecutive patients with pituitary surgery.

Seventy-four patients were included in this study. There was a significant reduction in tumor size in mm3 [average pre- and post-surgery respectively: 12,362 mm3 (±12,397); 3,910 mm3 (±7,160)], (p < 0.0001). This was confirmed by the Hardy-Wilson and Knosp classification, where most patients went from grade IV C (33.7%) to grade 0 (12.1%), IA (20.2%), IIB (21.36%), and IIC (16.2%); as well as from grade 4 (24.3%) to grade 0 (45.9%), respectively. After surgery, there were statistically significant reductions in total serum levels of glucose [average pre- and post-surgery, respectively: 116 mg/dL (±26.9); 90 mg/dL (±10.2)], (p < 0.001), triglycerides [average pre- and post-surgery, 240 mg/dL (±102); 171 mg/dL (±60.5)], (p = 0.001); and HDL-c [average pre- and post-surgery, respectively: 39 mg/dL (±11.8); 44.6 mg/dL (±8.4)], (p = 0.029). The other parameters remained unchanged.

This is the first study to demonstrate the relationship between the presence of pituitary adenoma and significative changes in serum glucose, triglycerides and c-HDL related to metabolic syndrome.

Noncommunicable chronic disorders (NCDs) are multifactorial disorders that share a state of chronic, low-grade inflammation together with an imbalance of gut microbiota. NCDs are becoming increasingly prevalent worldwide, and mainly in Western countries, with a significant impact on global health. Societal changes, together with the widespread diffusion of modern agricultural methods and food processing, have led to a significant shift in dietary habits over the past century, with an increased diffusion of the Western diet (WD). WD includes foods high in saturated fat, refined sugars, salt, sweeteners, and low in fiber, and is characterized by overeating, frequent snacking, and a prolonged postprandial state. An increasing body of evidence supports the association between the diffusion of WD and the rising prevalence of NCDs. WD also negatively affects both gut microbiota and the immune system by driving to microbial alterations, gut barrier dysfunction, increased intestinal permeability, and leakage of harmful bacterial metabolites into the bloodstream, with consequent contribution to the development of systemic low-grade inflammation. In this review article we aim to dissect the role of gut microbiota imbalance and gut barrier impairment in mediating the detrimental effects of WD on the development of NCDs, and to identify potential therapeutic strategies.

Obesity has a pivotal and multifaceted role in pain associated with osteoarthritis (OA), extending beyond the mechanistic influence of BMI. It exerts its effects both directly and indirectly through various modifiable risk factors associated with OA-related pain. Adipose tissue dysfunction is highly involved in OA-related pain through local and systemic inflammation, immune dysfunction, and the production of pro-inflammatory cytokines and adipokines. Adipose tissue dysfunction is intricately connected with metabolic syndrome, which independently exerts specific effects on OA-related pain, distinct from its association with BMI. The interplay among obesity, adipose tissue dysfunction and metabolic syndrome influences OA-related pain through diverse pain mechanisms, including nociceptive pain, peripheral sensitization and central sensitization. These complex interactions contribute to the heightened pain experience observed in individuals with OA and obesity. In addition, pain management strategies are less efficient in individuals with obesity. Importantly, therapeutic interventions targeting obesity and metabolic syndrome hold promise in managing OA-related pain. A deeper understanding of the intricate relationship between obesity, metabolic syndrome and OA-related pain is crucial and could have important implications for improving pain management and developing innovative therapeutic options in OA.

Bacteriocins are potent antimicrobial peptides that are produced by bacteria. Since their discovery almost a century ago, diverse peptides have been discovered and described, and some are currently used as commercial food preservatives. Many bacteriocins exhibit extensively post-translationally modified structures encoded on complex gene clusters, whereas others have simple linear structures. The molecular structures, mechanisms of action and resistance have been determined for a number of bacteriocins, but most remain incompletely characterized. These gene-encoded peptides are amenable to bioengineering strategies and heterologous expression, enabling metagenomic mining and modification of novel antimicrobials. The ongoing global antimicrobial resistance crisis demands that novel therapeutics be developed to combat infectious pathogens. New compounds that are target-specific and compatible with the resident microbiota would be valuable alternatives to current antimicrobials. As bacteriocins can be broad or narrow spectrum in nature, they are promising tools for this purpose. However, few bacteriocins have gone beyond preclinical trials and none is currently used therapeutically in humans. In this Review, we explore the broad diversity in bacteriocin structure and function, describe identification and optimization methods and discuss the reasons behind the lack of translation beyond the laboratory of these potentially valuable antimicrobials.

Metabolic syndrome (MetS) is a complex condition characterized by abdominal obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of cardiovascular disease and type 2 diabetes. The gut microbiome plays a significant role in metabolic health, influencing digestion, immune function, and energy metabolism. When the gut microbiota becomes imbalanced due to poor diet and antibiotic use, it can lead to systemic inflammation, insulin resistance, and abnormal lipid metabolism, which are central features of MetS. This review explores the connection between gut microbial imbalances and MetS, focusing on the impact of the gut microbiome on metabolic health. Supplementation therapies targeting the gut microbiome, such as probiotics, prebiotics, synbiotics, and postbiotics, are evaluated for their potential to improve metabolic parameters in MetS patients. These interventions hold promise for enhancing insulin sensitivity, reducing inflammation, and improving lipid profiles. However, further research is needed to optimize these approaches for managing MetS. Understanding how to leverage the gut microbiome could lead to innovative, non-invasive treatments for this growing global health concern.