Search Results (3,508)

GLP-1 receptor agonists and dual GLP-1/GIP agonists have significantly transformed the treatment of obesity, enabling clinically meaningful weight reduction and improvements in cardiometabolic parameters. However, clinical trial data indicate that cessation of therapy is associated with biologically driven weight regain and a partial loss of metabolic benefits. This phenomenon underscores the chronic nature of obesity and the limited durability of effects achieved through pharmacotherapy alone. Nevertheless, structured clinical frameworks describing how to maintain satiety and metabolic stability after GLP-1/GIP dose reduction or discontinuation remain limited. The aim of this narrative review is to discuss the mechanisms underlying weight regain following dose reduction or discontinuation of GLP-1/GIP pharmacotherapy and to present strategies supporting long-term metabolic stabilisation. Weight regain is driven in part by persistent metabolic adaptations, including a reduction in resting energy expenditure (adaptive thermogenesis), alterations in the hunger–satiety axis (increased ghrelin, reduced leptin signalling), and potentially incomplete restoration of adipose tissue and liver-related metabolic function, although direct evidence in this specific setting remains limited. Weight loss is often accompanied by a reduction in fat-free mass, which further lowers energy expenditure and increases susceptibility to a positive energy balance after treatment cessation. It remains unclear whether pharmacological suppression of appetite results in sustained normalisation of endogenous satiety regulation after treatment cessation, and its effects on gut microbiota function remain uncertain. In clinical practice, key priorities include preserving muscle mass (adequate protein intake, resistance training), maintaining dietary nutrient density, stabilising postprandial glycaemia, and ensuring sufficient intake of fermentable fibre to support short-chain fatty acid production and gut–brain signalling. GLP-1/GIP pharmacotherapy should be viewed as a component of an integrated model of obesity treatment. We propose that long-term weight stabilisation may require a transition from pharmacologically induced satiety to satiety supported by diet quality, preserved fat-free mass, and metabolic stability. Further research is needed to define optimal post-treatment strategies and to identify patients in whom therapy can be safely reduced or discontinued. This transition should be regarded as a conceptual framework and forward-looking hypothesis requiring validation in prospective studies. Full article

Biological activity of diets consisting of dietary fibers, peptides and polyphenols is largely mediated by the gut microbiota, which converts these compounds into bioactive metabolites. This review examines the microbiota–epigenome axis, highlighting gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs), urolithins, and phenolic acids, that modulate host gene expression through DNA methylation, histone modifications, and non-coding RNA regulation. Current evidence from molecular and microbiome studies indicates that these metabolites influence key metabolic and inflammatory pathways, including lipid absorption via CD36, SIRT1 activation, and one-carbon metabolism involving folate and S-adenosylmethionine (SAM). Inter-individual variability in metabolic responses is associated with differences in microbial composition and metabotypes, which determine the magnitude of epigenetic regulation. Furthermore, dietary polyphenols derived from pomegranate, berries, tea, cocoa, and grapes are shown to modulate gut microbiota composition and enhance epigenetic effects. A “butyrate–polyphenol synergy” model is proposed, in which combined microbial metabolites optimize host epigenetic programming. Overall, agri-food by-products are suggested to function as modulators of the host epigenetic landscape, providing a framework for microbiome-targeted dietary strategies to improve metabolic and inflammatory health. Full article

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), which is marked by severe abdominal pain, weight loss, perianal bleeding, and diarrhea. This study successfully isolated and purified four low-molecular-weight fucoidan oligosaccharides through acid hydrolysis and Bio Gel P10 gel filtration. The molecular weights were 2.9 × 10⁴–1.36 × 10⁵ Da, 182–1012 Da, 161–939 Da and 161–939 Da, respectively. A mouse model of colitis was induced using Dextran Sulfate Sodium (DSS). The results indicated that fucoidan and fucoidan oligosaccharides could ameliorate murine ulcerative colitis, with the oligosaccharides (200 mg/kg/d) demonstrating superior therapeutic effects. This superiority was likely attributed to the lower molecular weight and higher content of total sugars and fucose. The primary mechanisms involved the modulation of gene and protein expression levels associated with the Toll-like receptor 4, Myeloid differentiation primary response 88, nuclear factor kappa-light-chain-enhancer of activated B cells, p65, and Inhibitor of kappa light polypeptide gene enhancer in B cells, alpha (TLR4, MYD88, NF-κB p65, and IκB-α) signaling pathways, which reduce the production of inflammatory cytokines such as tumor necrosis factor-alpha, Interleukin-1 beta and Interleukin-6 (TNF-α, IL-1β, and IL-6). Additionally, these oligosaccharides alleviated oxidative stress, enhanced the levels of intestinal barrier proteins (Claudin family member 4 and Zonula occludens protein 1), regulated the abundance and diversity of the gut microbiota, and increased the levels of short-chain fatty acids (SCFAs) in the intestine. It is worth emphasizing that this study can only demonstrate that fucoidan oligosaccharides have a mitigating effect on intestinal inflammation in mice. Further research is needed in the future to investigate the structure–activity relationship of fucoidan oligosaccharides and their impact on human intestinal microbiota, in order to further elucidate their anti-inflammatory mechanisms. Full article

Emerging evidence implicates the gut–brain axis in the pathophysiology of schizophrenia, yet literature regarding specific microbiome alterations remains inconsistent. This study aims to synthesize evidence on gut microbiota diversity and taxonomic composition in individuals with schizophrenia compared to healthy controls. Unlike prior meta-analyses, this study integrates quantitative alpha diversity synthesis with cross-taxonomic qualitative analysis and contextualizes findings within functional frameworks of the gut–brain axis, highlighting the methodological heterogeneity that limits biological interpretation. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. Electronic databases (Web of Science, PubMed, MDPI) were searched for observational studies published between 2017 and 2025. Forty-eight studies met inclusion criteria for qualitative synthesis, with 14 providing sufficient data for random-effects meta-analyses of alpha diversity. Meta-analyses revealed no statistically significant differences in alpha diversity indices (Shannon, Simpson, Chao1, ACE, Observed) between patients and controls, despite high heterogeneity. Conversely, beta diversity analyses generally demonstrated significant differences in microbial community composition. Taxonomic synthesis identified recurrent but heterogeneous dysbiotic patterns characterized by the depletion of short-chain fatty acid-producing taxa (e.g., Faecalibacterium, Roseburia, Lachnospiraceae) and enrichment of pro-inflammatory taxa (e.g., Proteobacteria, Fusobacterium). Schizophrenia is associated with evidence of compositional alterations and functional shifts rather than a global loss of microbial richness. These findings highlight candidate taxa that may warrant further investigation in biomarker-focused studies and microbiome-based therapeutics. However, these findings should be interpreted cautiously due to substantial heterogeneity and limited control for key confounders such as antipsychotic medication, diet, and life-style factors. Full article

The occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related to intestinal flora imbalance, intestinal barrier damage, and gut-liver axis dysfunction. Due to their multi-target regulatory effects and advantages in intestinal microecological intervention, Chinese herbal monomers have shown promising application prospects in the prevention and treatment of MASLD. However, basic research on their toxicity still lags behind, and issues related to safety and clinical translation urgently need attention. This article systematically reviews the research progress on how flavonoids, triterpenoids, alkaloids, and polysaccharides improve hepatic steatosis, inflammatory responses, and metabolic disorders from a toxicological perspective by reshaping the intestinal microbiota, repairing the intestinal mucosal barrier, regulating short-chain fatty acid and bile acid metabolism, and synergistically acting on signaling pathways such as TLR4/NF-kB, FXR, TGR5, SIRT1, and the NLRP3 inflammasome. Furthermore, by combining methods such as 16S rRNA sequencing, metagenomics, metabolomics, and multi-omics integration, the article analyzes their application value and limitations in toxicological mechanism research, and discusses the translational bottlenecks faced by Chinese herbal monomers in pharmacokinetics, bioavailability, quality standardization, targeted delivery, and toxicological safety. Existing evidence indicates that Chinese herbal monomers have a three-in-one intervention advantage of microecological remodeling-metabolic regulation-inflammation inhibition, but their long-term medication safety, toxic target organs, dose-effect/toxicity relationships, and potential drug interactions still need further clarification. This article aims to provide a systematic reference for the safety evaluation and clinical translational research of Chinese herbal monomers in the prevention and treatment of MASLD. Full article

Cognitive impairment induced by a high-fat high-fructose diet (HFFD) is associated with gut–liver–brain axis dysfunction, yet whether polysaccharide intervention can modulate this axis to achieve cognitive rescue remains unexplored. This study investigated whether Elaeagnus angustifolia polysaccharide (EAP) is associated with protection against HFFD-induced cognitive decline by modulating this axis. Male C57BL/6J mice (n = 15/group) received Control, HFFD, HFFD + LEAP (300 mg/kg/day EAP), or HFFD + HEAP (800 mg/kg/day EAP) for 14 weeks. HEAP improved spatial memory, reducing escape latency by 31.2% on day 5 (p < 0.01). Multi-omics and histopathological analyses revealed that EAP was dose-dependently associated with restructuring of the gut microbiota, expanding Muribaculaceae and other SCFA-producers while suppressing pathobionts, thereby reversing the Firmicutes/Bacteroidota ratio from 1.71 to 0.94 (p < 0.01). Elevated cecal, hepatic, and cerebral acetate, propionate, and butyrate (p < 0.01) were associated with improved intestinal barrier integrity, attenuated systemic LPS translocation, and reduced hepatic inflammation and changes consistent with normalization toward control levels of PPARα/γ signaling. These peripheral improvements were accompanied by changes in the hippocampus, where EAP suppressed IBA-1 microglial activation (from 4.5-fold to 2.1-fold of control, p < 0.01) and IL-6/TNF-α signaling, changes in neurotransmitter balance (Glu, 5-HT, DA), and preserved postsynaptic density ultrastructure and PSD-95 expression (p < 0.01). These findings support a role for EAP in modulating the gut–liver–brain axis and may help prevent diet-related cognitive impairment, supporting its development as a microbiome-targeted functional food ingredient. Full article

Tributyrin, a short-chain fatty acid derivative, has been shown to hold potential in improving intestinal health in livestock and poultry. However, its multidimensional effects on the health of meat pigeons, particularly during the young pigeon stage, remain unclear. This study aimed to investigate the comprehensive effects of dietary tributyrin supplementation on the growth, health status, intestinal function, and metabolic profile of young pigeons. A total of 100 healthy 29-day-old White King pigeons, with half male and half female, were randomly divided into a control group (fed a basal diet) and a treatment group (fed a basal diet supplemented with 1500 mg/kg tributyrin) for a 35-day trial. The results showed that compared with the control group, young pigeons in the treatment group had significantly reduced serum triglyceride levels, alanine aminotransferase activity, and concentrations of pro-inflammatory cytokines (TNF-α, IL-6), along with significantly increased levels of high-density lipoprotein, immunoglobulin G, total antioxidant capacity, and glutathione peroxidase activity. Concurrently, the villus height-to-crypt depth ratio in the jejunum and ileum was significantly elevated, indicating improved intestinal morphological structure. Untargeted metabolomics analysis further revealed significant changes in the relative abundances of 13 key differential metabolites (e.g., L-carnitine, pyridoxamine, indoleacetic acid) in the small intestinal contents of the treatment group. These metabolites were mainly enriched in metabolic pathways such as 2-oxoCarboxylic acid metabolism, tryptophan metabolism, and vitamin B6 metabolism. In conclusion, dietary supplementation with 1500 mg/kg tributyrin can exert multifaceted beneficial effects on young pigeon health by improving lipid metabolism, enhancing immune and antioxidant functions, optimizing intestinal structure, and regulating the local metabolic network. This study provides a theoretical basis for the application of tributyrin as a functional additive in the green and healthy production of meat pigeons. Full article

Background/Objectives: Obesity represents a significant global health challenge. Although alternate-day fasting (ADF) has been shown to effectively improve metabolic parameters, long-term adherence to this regimen remains limited. This study aimed to investigate whether highly polymerized persimmon tannin (DP31) could serve as a practical alternative to ADF for the prevention of high-fat diet (HFD)-induced obesity in mice. Methods: Male C57BL/6J mice (n = 10 per group) were subjected to an HFD for 11 weeks, during which they concurrently received either DP31 or ADF. Body weight, fat mass, serum lipid levels, glucose tolerance, fasting glucose, and insulin levels were assessed. Additionally, hepatic transcriptomics, Western blotting, 16S rRNA sequencing, and short-chain fatty acids (SCFAs) analysis were conducted. Results: DP31 demonstrated comparable efficacy to ADF in reducing body weight gain and improving lipid profiles, while exhibiting superior effects on glucose tolerance and fasting glucose levels (p < 0.05). Both interventions effectively reversed HFD-induced hepatic gene dysregulation, leading to the upregulation of genes involved in processes related to steroid metabolism. In addition, both treatments activated the hepatic AMPK-mTORC1-Lpin1 axis, suppressed lipogenesis, upregulated PGC1α, and increased β-hydroxybutyrate levels, indicating enhanced fatty acid oxidation (p < 0.05). Notably, DP31 outperformed ADF in enriching beneficial gut genera, such as Akkermansia, and boosting SCFAs production, which may elucidate its superior glycemic control. Overall, DP31 exhibits comparable effects to ADF in preventing obesity-related metabolic disorders, while demonstrating superior effects on glucose homeostasis. Full article

Background: Type 2 diabetes mellitus (T2DM) represents a pressing global health challenge, underscoring the urgency of developing effective dietary interventions derived from natural resources. Zaojiaomi polysaccharide (ZJMP) from the endosperm of Gleditsia sinensis seeds (zaojiaomi), a traditional edible product, exhibits largely underexplored potential in T2DM management. Methods: In the present study, the antidiabetic effects and underlying mechanisms of ZJMP were investigated using a rat model of T2DM induced by a high-fat diet (HFD) combined with streptozotocin (STZ). Relevant biochemical indicators were detected, and histopathological examination was performed. The expression levels of key components of the TLR4/MyD88/NF-κB signaling pathway, as well as the inflammatory cytokines IL-6 and IL-1β in renal tissues, were further analyzed. Additionally, gut microbiota composition and the levels of short-chain fatty acids were determined. Results: ZJMP treatment significantly ameliorated hyperglycemia and dyslipidemia, elevated serum insulin levels, reduced intestinal mucosal permeability, and attenuated histopathological lesions in the heart, kidney, and pancreas of T2DM rats. Meanwhile, ZJMP notably alleviated renal inflammation by suppressing the production of IL-1β and IL-6, as well as inhibiting the TLR4/MyD88/NF-κB pathway. Furthermore, ZJMP administration effectively modulated gut microbiota composition and increased fecal concentrations of acetic acid and propionic acid. Conclusions: Collectively, these findings elucidate the novel bioactivity of ZJMP and highlight its potential as a promising functional food ingredient or dietary supplement for T2DM management. Full article

Growing evidence indicates that the gut microbiota is a central regulator of systemic immunity, acting through epithelial barrier integrity, microbial metabolites, and bidirectional signaling with innate and adaptive immune cells. Within this framework, probiotics have attracted substantial interest as tools for immune modulation; however, their effects are not uniform and should not be generalized across species or formulations. This review synthesizes current evidence on the gut microbiota–immune axis and examines how defined probiotic strains influence immune homeostasis, inflammation, and clinical outcomes. Particular emphasis is placed on strain-specific effects among lactic acid bacteria, bifidobacteria, yeast probiotics, and emerging nontraditional candidates, with attention to mechanisms involving cytokine signaling, regulatory T-cell induction, nuclear factor kappa B (NF-κB) modulation, toll-like receptor (TLR) pathways, short-chain fatty acids (SCFAs), tryptophan metabolites, and bile-acid-dependent signaling. The available literature indicates that the most meaningful immunological effects arise from precisely characterized strains acting in specific host contexts, whereas inconsistent trial design, small sample sizes, variable dosing, and poor strain resolution continue to limit translation. Overall, current data support a shift from generic probiotic use toward mechanism-based, strain-specific, and increasingly personalized strategies for immune modulation. Full article

Dietary sodium excess is a primary driver of hypertension, yet individuals differ markedly in their blood pressure response to salt. This variation, termed salt sensitivity, cannot currently be predicted from clinical variables alone. This review examines three aspects of salt-gut physiology: intestinal sodium handling, salt-induced changes in gut microbiome composition, and microbiota-mediated effects on immune function, metabolite production, and gut barrier integrity. The intestine absorbs dietary sodium through regulated transporters whose activity adapts to luminal and hormonal conditions, making the gut a key regulator of sodium balance. High salt intake consistently alters gut microbiota composition in animal models, most reproducibly depleting Lactobacillus species, with variable effects on overall diversity. These compositional shifts, supported by human data, activate intestinal Th17 cells and deplete short-chain fatty acid producers, contributing to systemic inflammation and elevated blood pressure. The presence of inducible osmoadaptation responses varies substantially across microbes, though activation under dietary sodium conditions has not been demonstrated in vivo. If salt-driven microbial changes contribute causally to hypertension, microbiota-targeted interventions could complement sodium restriction in patients for whom long-term dietary adherence is poor. Controlled sodium intervention studies in animals and humans are needed to establish whether such a causal contribution exists. Full article

Crohn’s disease (CD) is a chronic immune-mediated inflammatory disorder characterized by transmural inflammation and a progressive course that frequently leads to structural complications such as intestinal fibrosis. Fibrostenosing disease represents a major clinical challenge, affecting up to 50% of patients over time and often requiring surgical intervention. Despite advances in anti-inflammatory therapies, no effective treatments currently exist to prevent or reverse established fibrosis. Intestinal fibrosis arises from a dysregulated tissue remodeling process driven by excessive extracellular matrix deposition and persistent activation of mesenchymal cells, particularly fibroblasts and myofibroblasts. This process is orchestrated through complex interactions between immune and non-immune cells and mediated by key signaling pathways, including transforming growth factor beta (TGF-β1) and the TL1A/DR3 axis. Genetic susceptibility, notably variants in NOD2 and other fibrosis-related genes, contributes not only to disease risk but also to phenotype progression. Epigenetic mechanisms, particularly microRNAs such as the miR-29 and miR-200 families, further modulate fibrogenesis and represent promising non-invasive biomarkers. Additionally, intestinal dysbiosis and specific microbial signatures, including reduced short-chain fatty acid-producing bacteria and the presence of adherent-invasive Escherichia coli, play a critical role in promoting fibrotic pathways. Mesenteric adipose tissue, especially creeping fat, also contributes to fibrosis through immune and metabolic signaling. Emerging biomarkers related to collagen metabolism and advances in molecular profiling are improving early detection strategies. Novel therapeutic approaches targeting fibrogenic pathways, including anti-TL1A agents, show promising preliminary results. A deeper understanding of these mechanisms is essential to develop effective antifibrotic therapies and improve long-term outcomes in CD. Full article

To investigate the effects of Wuwei Jianpi San (WJPS), a Chinese herbal compound feed additive, on rumen microecology, host metabolism, and immune function in healthy yaks (Bos grunniens), and to determine the optimal supplementation level, 32 yaks with similar initial body weight were randomly assigned to four groups: a control group and three groups receiving 0.5%, 1.0%, or 2.0% WJPS for 90 days. Growth performance, hematological indices, serum antioxidant and immune parameters, tryptophan metabolites, ruminal short-chain fatty acids (SCFAs), and rumen microbiota were analyzed. WJPS supplementation improved growth performance, as shown by a reduced feed-to-gain ratio in all treated groups and tended to increase average daily gain in the 2.0% group. It also enhanced hematological, antioxidant, and immune status, evidenced by increased white blood cell (WBC) and lymphocyte (Lym) counts and elevated interleukin-2 (IL-2), immunoglobulin G (IgG), and superoxide dismutase (SOD) levels. Moreover, 2.0% WJPS increased total SCFAs, acetate, and n-butyrate, while WJPS reduced kynurenine pathway metabolites, including kynurenine, 3-hydroxykynurenine, and quinolinic acid. Metagenomic analysis showed that WJPS tended to shape rumen microbial composition by increasing Bacillota and decreasing Bacteroidota, and these microbial changes were associated with host immune indices and tryptophan metabolism. Overall, 2.0% WJPS showed the best comprehensive effect. Full article

Ophiopogon japonicus (O. japonicus) by-products contain abundant nutrients and bioactive substances. In this study, we evaluated their effects on production performance and intestinal health in meat rabbits. Firstly, we measured the nutrient levels of O. japonicus by-products along with its digestibility in meat rabbits. Then, we replaced dietary alfalfa meal with O. japonicus by-products to evaluate its effects on growth performance, carcass traits, apparent digestibility, and intestinal immunity in meat rabbits. The results showed that the effects of O. japonicus by-products on growing meat rabbits varied over time. In the early phase (days 1–21), it significantly depressed average daily gain (ADG, p < 0.001) and average daily feed intake (ADFI, p < 0.001), and increased feed to gain ratio (F:G) (p < 0.001). However, in the later phase (days 22–35), a compensatory response emerged, with significantly increased ADG (p < 0.001) and reduced ADFI (p < 0.01) and F:G (p < 0.001). Despite this compensatory growth, the growth performance and feed efficiency for the entire experimental period were not improved. O. japonicus by-products decreased carcass weight significantly (p < 0.001), but did not significantly affect dressing percentage and meat traits (p > 0.05), while it significantly reduced the digestibility of crude protein (CP, p < 0.05), increased that of crude fiber (CF, p < 0.001), and reduced the activities of amylase (p < 0.01) and increased trypsin in cecal contents (p < 0.05). Additionally, O. japonicus by-products elevated the levels of secretory immunoglobulin A (sIgA) and interleukin-10 (IL-10) in ileal mucosa (p < 0.05). They did not significantly affect the cecal microbial community or short chain fatty acid (SCFA) levels (p > 0.05). Our research indicated that O. japonicus by-products possess a balanced nutritional composition and improve intestinal immunity in rabbit production, making them a viable feed ingredient to partially replace alfalfa meal. Full article

The gut microbiota produces molecules that trigger responses at the local and distant levels. It affects the brain through several metabolic products, including serotonin (5-HT). Tryptophan hydroxylase type 1 (Tph1) is the rate-limiting enzyme during 5-HT biosynthesis in the gut. Efavirenz (EFV), an antiretroviral agent against HIV, is associated with depression disorders and Tryptophan hydroxylase type 2 (Tph2) deregulation in mice. The possible association between the depressive effects of EFV secondary to dysbiosis and the expression of Tph1 in the intestine is yet to be studied. Therefore, we aimed to elucidate the role of the gut microbiota in depression mechanisms. We reviewed the gut microbiota, their metabolites (short-chain fatty acids [SCFA]), Tph1 expression in the gut, and systemic 5-HT and tryptophan levels in CD1 mice after 36 days of oral EFV (10 mg/kg) treatment. The proportions of Bacteroidota and Bacillota_A_368345 decreased and increased, respectively, following EFV treatment. Additionally, the abundance of Lactobacillus spp. and Faecalbaculum decreased, whereas that of Dubosiella spp., Blautia_A_141780, and Anaerostipes increased. These bacteria contribute to SCFA production and may have counteracted the lack of protective effects provided by Lactobacillus. Tph1 expression was dysregulated in the gut, whereas serum 5-HT levels decreased following EFV treatment. Lactobacillus species promote 5-HT production in the gut, and the deregulation of Tph1 affects 5-HT synthesis. This disruption in the gut–brain axis decreased peripheral 5-HT levels. This affects the serotonergic system in the brain, which could contribute to depression. Full article