Search Results (114)

Obesity is closely linked to dyslipidemia, hepatic injury, and chronic inflammation through disturbances in the gut–liver axis. Here, we evaluated the anti-obesity effects of L. rhamnosus (Lacticaseibacillus rhamnosus) CU262 in a high-fat diet (HFD) mouse model and elucidated mechanisms using an integrated multi-omics strategy. Male C57BL/6 mice received CU262 during 12 weeks of HFD feeding. Phenotypes, serum/liver biochemistry, gut microbiota (16S rRNA sequencing), fecal short-chain fatty acids (SCFAs), and hepatic transcriptomes (RNA-seq) were assessed. CU262 significantly attenuated weight gain and adiposity; improved serum TC, TG, LDL-C and HDL-C; lowered ALT/AST and FFA; and mitigated oxidative stress and inflammatory imbalance (↓ IL-6/TNF-α, ↑ IL-10). CU262 restored alpha diversity, reduced the Firmicutes/Bacteroidetes ratio, enriched beneficial taxa (e.g., Akkermansia), and increased acetate and butyrate. Liver transcriptomics showed CU262 reversed HFD-induced activation of cholesterol/steroid biosynthesis and endoplasmic reticulum stress, with downregulation of key genes (Mvk, Mvd, Fdps, Nsdhl, and Dhcr7) and Pcsk9, yielding negative enrichment of steroid and terpenoid backbone pathways and enhancement of oxidative phosphorylation and glutathione metabolism. Correlation analyses linked Akkermansia and SCFAs with improved lipid/inflammatory indices and repression of cholesterol-synthetic and stress-response genes. These findings demonstrate that CU262 alleviates HFD-induced metabolic derangements via microbiota-SCFA-hepatic gene network reprogramming along the gut–liver axis, supporting its potential as a functional probiotic for obesity management. Full article

The enteric nervous system (ENS) is a critical component of the gut–brain axis, playing a pivotal role in gastrointestinal homeostasis and systemic health. Emerging evidence suggests that ENS dysfunction precedes central neurodegenerative disorders. Progesterone, known for its neuroprotective and anti-inflammatory properties in the central nervous system (CNS), has received growing attention for its potential role in ENS physiology. This study aimed to map the expression of nuclear and membrane-bound progesterone receptors in the human ENS, considering regional intestinal, sex, and age variations. Immunofluorescence and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) were used to evaluate receptor distribution in anatomically distinct intestinal regions. Consistent expression of classical nuclear progesterone receptors (PR-A/B) and the non-classical Progesterone receptor membrane component 1 (PGRMC1) in myenteric ganglion cells across all intestinal segments was observed. RT-PCR confirmed the expression of PR-A/B, PGRMC1, mPRα, and mPRβ, with regional variations. Sex-specific patterns were evident along with age-related downregulation. Our findings provide a detailed characterization of progesterone receptor expression in human ENS, highlighting sex- and age-dependent regulation. The identification of progesterone signaling within the myenteric plexus suggests a hormonal influence in gut–brain communication. Targeting ENS progesterone receptors may open novel therapeutic avenues to modulate neurodegenerative CNS disorders via peripheral intervention along the gut–brain axis. Full article

The primary objective of this study was to investigate the mechanism through which small peptides regulate the productive performance and egg quality of laying hens during the late-laying period. A total of 200 Lohmann Pink laying hens, aged 400 days, were randomly assigned into a control treatment (CON) and a small peptide treatment (SP) for a 120-day treating period. Productive performance, egg quality, serum antioxidant capacity, intestinal morphology, microbial community, and hepatic gene expressions were measured. Results showed that SP supplementation significantly increased eggshell strength and albumen height, while reducing the rate of abnormal eggs (p < 0.05). SP notably enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and hepatic lipase (p < 0.05). Additionally, SP supplementation significantly increased microbial α-diversity (p < 0.05) and elevated the relative abundances of Ruminococcus, Lactobacillus, and Faecalibacterium (p < 0.05). Hepatic transcriptomic analysis revealed that up-regulated genes in the SP treatment were primarily enriched in steroid biosynthesis, while down-regulated genes were mainly associated with the Yersinia infection pathway. In conclusion, small peptide supplementation efficiently improved eggshell strength and albumen height while reducing the rate of abnormal eggs by modulating the interactions between gut microbiota and hepatic gene expressions. Our findings may provide an effective option for enhancing egg quality in the late-laying period. Full article

This study investigated the molecular and microbial factors behind the higher disease resistance of hybrid taimen by combining gut microbiome profiling with host transcriptomic analysis of intestinal and liver tissues. Both hybrid taimen and H. taimen were raised under the same recirculating aquaculture system (RAS) conditions. After recording survival rates following three enteritis outbreaks, samples of intestinal contents and tissues were collected from both groups. The gut microbiota was analyzed using full-length 16S rRNA sequencing in PacBio, and host gene expression was assessed with Illumina RNA-seq. Functional predictions were made using PICRUSt2 and Gene Set Enrichment Analysis (GSEA). Results showed that hybrids had significantly higher survival rates after enteritis (p < 0.05). Although microbial alpha diversity was similar, beta diversity revealed slight compositional differences. Hybrids showed higher levels of Hapalosiphon and Tepidimicrobium, microbes associated with antimicrobial compounds and the metabolism of short-chain fatty acids (SCFAs). Functional predictions indicated enrichment in selenocompound metabolism and ansamycin biosynthesis in hybrids. Transcriptomic analysis identified 4233 differentially expressed genes (DEGs) in the intestine and 3980 in the liver. In hybrids, intestinal tissues exhibited increased expression of immune pathways, including complement activation, lysosomal activity, and the transforming growth factor-beta (TGF-β) signaling pathway. Liver tissues demonstrated higher expression of genes related to cholesterol synthesis, fatty acid degradation, and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. qRT-PCR validated the expression patterns of 20 selected DEGs. These findings tentatively suggest that the elevated disease resistance of hybrid taimen may be linked, at least in part, to a combination of microbial taxa inferred to produce antimicrobial metabolites and short-chain fatty acids, as well as an apparent intensification of intestinal immune and barrier-related gene expression, and hepatic pathways that possibly support energy supply and steroid-based immunity. However, this multi-omics data set is only correlational. We still do not know whether a single strain or a few host genes are enough to produce the resistant phenotype. Gnotobiotic trials, microbiota transplants, and targeted metabolomics will be necessary to turn these interesting associations into solid evidence. Full article

Most probiotics require separate administration from antibiotics due to sensitivity issues. Clostridium butyricum, however, exhibits intrinsic resistance, making it a promising candidate for combined therapy against diarrhea. In this study, a diarrhea model was established in mice induced by Escherichia coli, followed by treatment with azithromycin (AZM), C. butyricum (RH₂), or their combination (COM) to assess therapeutic efficacy. The results demonstrated that mice in RH₂ and COM groups achieved full body weight recovery and significant alleviation of diarrhea, accompanied by normalized fecal E. coli loads, preserved tissue integrity, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and elevated anti-inflammatory IL-10. In contrast, AZM treatment led to sex-specific disparities in weight recovery and E. coli loads, and both sexes experienced relapse-prone diarrhea. Furthermore, the AZM group displayed shortened colons, sustained inflammatory infiltration, epithelial damage, and elevated IL-1β and male-specific IL-6. Gut microbiota analysis revealed that the COM group retained beneficial genera (e.g., Parabacteroides, Blautia) from the AZM group while uniquely enriching Lachnospiraceae taxa (e.g., NK4A136_group, FCS020_group). Untargeted metabolomics demonstrated the COM group activated GABA/arginine pathways, enhancing anti-inflammatory and barrier functions, whereas azithromycin disrupted butyrate synthesis and steroid metabolism. These findings highlight the advantage of combining C. butyricum with azithromycin for intestinal protection. Full article

The gut microbiome plays a vital role in metabolism and can be significantly influenced by body mass index (BMI). This study investigated the variations in gut microbial composition and function across different BMI categories by analyzing 16S rRNA sequencing data of 126 stool samples. While our analysis of microbial diversity did not reveal significant differences among BMI groups, a differential abundance analysis identified specific bacterial genera associated with BMI status. Notably, Lachnospira, Lactobacillus, and Roseburia were enriched in non-obese individuals, while Phascolarctobacterium showed greater abundance in obese subjects. Functional profiling utilizing PICRUSt2 and DESeq2 revealed fifteen KEGG pathways that exhibited significant alterations across varying BMI groups. Notably, several of these pathways were associated with short-chain fatty acid (SCFA)-producing taxa, including Lactobacillales and Tannerellaceae. Additionally, covariance network analysis identified the microbial genera Alistipes and Bilophila as central participants in multiple metabolic pathways, particularly those associated with steroid biosynthesis and pathogenic Escherichia coli, which showed a notable enrichment in individuals with obesity. These findings suggest that BMI influences the composition and metabolic potential of the gut microbiome, highlighting the importance of functional profiling to better understand the mechanisms underlying obesity. Full article

Parkinson’s disease (PD) and type 2 diabetes mellitus (T2DM) exhibit increasing comorbidity, yet the shared contribution of gut microbiota remains unclear. To investigate parallel microbial and functional alterations underlying PD, T2DM, and PD with diabetes (PDDM), we performed fecal metagenomic sequencing in 156 PD, 41 T2DM, and 44 PD with diabetes (PDDM) patients and 83 healthy controls (HC). PD and T2DM showed highly concordant microbial shifts, with 22 genera and 91 species consistently altered across disease groups compared with HC. Functional enrichment highlighted common perturbations in taurine and hypotaurine metabolism, retinol metabolism, the hypoxia-inducible factor-1 (HIF-1) pathway, and xenobiotic degradation, implicating disrupted oxidative stress responses, neuro-metabolic regulation, and detoxification. Key taxa, including Limosilactobacillus fermentum, Lactobacillus porci, and Lactobacillus delbrueckii, were increased and showed moderate positive correlations (|ρ| ≥ 0.3) with antioxidant/retinol–HIF-1, taurine–hypotaurine, and xenobiotic degradation pathways. Bifidobacterium breve (unadjusted analysis) was increased in PD and further enriched in PDDM, correlating with multiple beneficial pathways. Bifidobacterium simiarum (covariate-adjusted analyses) showed the broadest positive pathway associations, while selected Bacteroides species (e.g., B. acidifaciens) exhibited negative correlations with insulin-resistance pathways and positive correlations with steroid hormone biosynthesis. By contrast, Butyricimonas vaginalis showed negative correlations with HIF-1 and insulin signaling and with cytochrome P450-related drug metabolism. These findings provide the first systematic evidence of parallel taxonomic and functional dysbiosis in PD and T2DM, supporting gut microbiota as a shared mediator and potential therapeutic target in comorbidity. Full article

Peimine (PM), a steroidal alkaloid derived from aged garlic (Allium sativum L.), demonstrates potent therapeutic efficacy against ulcerative colitis (UC) through multi-target mechanisms. Integrating network pharmacology and in vivo validation, we reveal that PM suppresses colitis by concurrently inhibiting PI3K-AKT, JAK-STAT, and HIF-1 signaling pathways—key drivers of inflammation and oxidative stress. In a murine model of dextran sulfate sodium (DSS)-induced UC, oral PM administration (4 mg/kg) significantly attenuated disease severity, evidenced by reduced disease activity index, restored colon length, and improved epithelial barrier integrity. PM treatment diminished pro-inflammatory cytokines TNF-α (4.2-fold) and IL-6 (3.1-fold) and oxidative damage while reshaping gut microbiota composition to enrich beneficial taxa (Akkermansia muciniphila, Lactobacillus spp.). Critically, PM rescued fecal short-chain fatty acid (SCFA) production (acetate, propionate, butyrate), directly linking microbial remodeling to mucosal healing. These findings establish PM as a novel natural compound targeting inflammation-redox-microbiota crosstalk, offering a promising pharmacological strategy for UC management. Full article

Non-alcoholic fatty liver disease (NAFLD) represents a prevalent chronic hepatic disorder worldwide, with its incidence continuing to rise in recent years. At the core of its pathological progression lie multiple interconnected mechanisms, including dysregulated lipid metabolism (e.g., abnormal accumulation of triglycerides in hepatocytes), impaired insulin sensitivity (which exacerbates hepatic lipid deposition), excessive production of reactive oxygen species (ROS) leading to oxidative stress, and sustained low-grade chronic inflammation that further amplifies liver tissue damage. Saponins have emerged as a crucial research direction for NAFLD intervention due to their advantage of multi-target regulation. This review synthesizes the mode of action of commonly studied saponins, including triterpenoid saponins and steroidal saponins: they regulate lipid metabolism by inhibiting fatty acid synthesis; modulate the gut microbiota; scavenge reactive oxygen species (ROS); alleviate endoplasmic reticulum stress; exert anti-inflammatory effects by inhibiting inflammasomes; and simultaneously regulate autophagy, restrain the activation of hepatic stellate cells, and modulate the gut microbiota, thereby achieving anti-apoptotic and anti-hepatic fibrosis effects. In conclusion, saponins can synergistically intervene in NAFLD through multiple mechanisms with good safety, while low bioavailability constitutes the main bottleneck for their clinical translation. In the future, it is necessary to further optimize formulation processes to improve absorption efficiency and conduct high-quality clinical studies to verify their long-term efficacy and drug–drug interactions, thus providing a new possible direction for NAFLD treatment. Full article

Background/Objectives: Polygonati rhizoma (PR) is a common traditional Chinese medicine that has been used for 2000 years in China, serving as both food and medicine. It is known for various health benefits, including antidiabetic effects, regulation of gut microbiota, and enhancement of immunity. The most popular PR varieties are Polygonatum kingianum Coll. et Hemsl. (PK), Polygonatum sibiricum Red. (PS), Polygonatum cyrtonema Hua (PC), and Polygonatum odoratum (Mill.) Druce (PO). We aimed to determine the differences among these four PR species. Methods: Using an untargeted mass spectrometer we conducted a metabolomic analysis. Results: We detected 2360, 2336, 2381, and 2355 unique polysaccharide, steroid, alkaloid, nucleoside, and peptide metabolites, among which 10, 36, 5, and 26 were specific to PK, PS, PC, and PO, respectively. Differentially expressed polysaccharide, steroid, and alkaloid metabolites were identified in the four species. A total of 61, 56, 61, and 57 carbohydrates were identified in the PK, PS, PC, and PO, respectively; 33, 32, 29, and 30 steroids were identified in the PK, PS, PC, and PO, respectively; and 10, 12, 12, and 11 alkaloids were identified in PK, PS, PC, and PO, respectively. Conclusions: Our findings provide novel insights into the overall metabolome of the four PR species, improve understanding of their functions and effectiveness, and provide a theoretical basis for qualitative evaluation and comprehensive PR applications. Full article

Improving feed efficiency (FE) is essential for enhancing productivity, reducing production costs, and minimizing environmental impacts in the swine industry. Fecal microbiota and their metabolites play important roles in nutrient metabolism and energy utilization. This study aimed to investigate the fecal microbiota and associated metabolites in pigs with divergent feed conversion ratios (FCR). Fecal samples were collected from 20 Duroc × (Landrace × Yorkshire) (DLY) commercial pigs exhibiting extremely high (HFCR, n = 10) and low (LFCR, n = 10) FCR for analysis using 16S rRNA gene sequencing and liquid chromatography–mass spectrometry (LC-MS). The microbiota analysis revealed significantly higher abundances of Ruminococcus, Prevotella, Akkermansia, and Eubacterium in LFCR pigs (p < 0.05), while pathogenic bacteria predominated in HFCR pigs (p < 0.05). LC-MS metabolomics identified significant variations in metabolites involved in steroid hormone biosynthesis and primary bile acid metabolism between the two groups (p < 0.05). Spearman correlation analysis further demonstrated significant positive correlations between Ruminococcaceae_NK4A214_group and [Eubacterium]_coprostanogenes_group with bile acid metabolites, as well as between Akkermansia and steroid hormone synthesis (p < 0.05). These findings suggest a potential role for specific microbes and metabolites that are associated with feed efficiency, and warrant validation in pig feeding trials and fecal microbiota transplantation (FMT). Full article

The escalating global threat of antimicrobial resistance (AMR) necessitates innovative therapeutic strategies beyond traditional antibiotic development. Drug repurposing offers a rapid, cost-effective approach by identifying new antibacterial applications for existing non-antibiotic drugs with established safety profiles. Emerging evidence indicates that diverse classes of non-antibiotic drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), statins, antipsychotics, calcium channel blockers and antidepressants, exhibit intrinsic antibacterial activity, or potentiate antibiotic efficacy. This review critically explores the mechanisms by which drugs that are not recognised as antibiotics exert antibacterial effects, including efflux pump inhibition, membrane disruption, biofilm inhibition, and quorum sensing interference. We discuss specific examples that demonstrate reductions in minimum inhibitory concentrations (MICs) of antibiotics when combined with these drugs, underscoring their potential as antibiotic adjuvants. Furthermore, we examine pharmacokinetic considerations, toxicity challenges, and clinical feasibility for repurposing these agents as standalone antibacterials or in combination therapies. Finally, we highlight future directions, including the integration of artificial intelligence and machine learning to prioritise drug candidates for repurposing, and the development of targeted delivery systems to enhance bacterial selectivity while minimising host toxicity. By exploring the overlooked potential of non-antibiotic drugs, this review seeks to stimulate translational research aimed at leveraging these agents in combating resistant bacterial infections. Nonetheless, it is crucial to acknowledge that such drugs may also pose unintended risks, including gut microbiota disruption and facilitation of resistance development. Hence, future research should pursue these opportunities with equal emphasis on efficacy, safety, and resistance mitigation. Full article

Recent studies suggest a role for the gut microbiota in the onset, progression, and prognosis of prostate cancer (PCa), one of the most common neoplasms in males. PCa screening relies on PSA testing, whose usefulness remains controversial due to its low specificity. This study was aimed at investigating the differences in the gut microbiota of PCa patients and healthy controls (HCs) and finding correlations between gut microbes and the clinical laboratory parameter assessed in the evaluation of PCa, to identify bacteria which could be used as diagnostic and prognostic biomarkers. Fecal samples collected from 18 PCa patients and 18 HCs were used to isolate bacterial DNA. 16S rRNA gene sequencing provided the gut microbial profiles of the enrolled subjects, whose functional impact was also predicted. A recursive partitioning tree method allowed us to identify a bacterial signature discriminating PCa from HC. A correlation analysis was performed between gut bacteria and the clinical laboratory parameters assessed in the evaluation of PCa. Differential bacterial patterns emerged between PCa patients and HCs, together with significant differences in beta-diversity, alpha-diversity, and richness. The functional prediction of the microbial profiles revealed several metabolic processes differentially regulated, including an enrichment in the Krebs cycle and in steroid hormone synthesis in PCa patients. A bacterial signature based on the abundance of Lactobacillus and Collinsella was found to discriminate between the two groups. Significant correlations were found between gut bacteria and the clinical laboratory parameters generally assessed in the evaluation of PCa. These results indicate that gut microbiota profiles may, in the future, represent potential biomarkers associated with prostate cancer risk or progression; however, further prospective studies and clinical validation are needed before considering their use as diagnostic or prognostic tools. Full article

Background/Objectives: Recent evidence suggests that gut microbiota plays an important role in anxiety and stress-related disorders through interactions along the gut–brain axis. Our aim was to determine the microbiological diversity of intestinal microorganisms in individuals with acute and remission phases of PD when compared to healthy individuals. Another aim was also to analyze the differences in the metabolic pathways occurring in the intestinal microbiota of individuals from the three analyzed groups. Methods: A diagnosis was established using the Mini-International Neuropsychiatric Interview (M.I.N.I). The gut’s microbiota composition was analyzed through bacterial 16S rRNA gene sequencing (V1–V2 regions). The clinical evaluations included a BMI measurement, Short Form-36 Health Survey (SF-36), Hamilton Anxiety Scale (HAM-A), Montgomery–Åsberg Depression Rating Scale (MADRS), Columbia-Suicide Severity Rating Scale (C-SSRS), and State-Trait Anxiety Inventory (STAI). Results: We recruited 62 participants (31 PD and 31 controls). After conducting quality control filtering, data from 54 participants were analyzed (25 PD, 11 acute, 14 remission, and 29 controls). Observed richness was lower in the acute PD (63) group than in the control (74) and remission (66) (p = 0.038) groups, whereas the Shannon and Simpson indices and beta diversity (PERMANOVA) were not significantly different. The Ruminococcus gnavus group was enriched in acute PD; no other deconfounded differences in microbial composition were detected. Predicted functional differences were detected by edgeR only and included the pathways that are related to steroid biosynthesis and innate immune signaling. Conclusions: Distinct gut microbial signatures were associated with PD, implicating both the metabolic and inflammatory pathways in disease pathophysiology. Full article

This study investigated the beneficial effect of sea cucumber polysaccharides (SCP) on gut microbiota composition, metabolic profiles, and liver gene expression in mice. Using an integrative approach combining microbiome, metabolome, and transcriptome analyses, we demonstrated that SCP supplementation led to a marked rise in norank_f_Muribaculaceae levels and reduced the Firmicutes-to-Bacteroidota ratio. Metabolomic analysis revealed key alterations in amino acid and lipid metabolism, with L-arginine and 7-dehydrocholesterol identified as potential mediators of SCP’s beneficial effects. Transcriptomics revealed genes expression across nine metabolic pathways, with genes involved in steroid biosynthesis being upregulated, while those related to protein digestion and absorption were downregulated. Spearman’s correlation analysis highlighted strong associations between gut microbiota, lipid metabolism-related genes, and corresponding metabolites. Integration omics data further suggested that SCP primarily supports arginine biosynthesis through gut–liver axis crosstalk. These results provide an important basis for developing SCP-based functional food with prebiotic properties to support metabolic and liver health. Full article