Next-generation live biotherapeutics are promising to aid the treatment of obesity and metabolic diseases. Here, we reported a novel anti-obesity probiotic candidate, Roseburia hominis, that was depleted in stool samples of obese subjects compared with lean controls, and its abundance was negatively correlated with body mass index and serum triglycerides. Supplementation of R. hominis prevented body weight gain and disorders of glucose and lipid metabolism, prevented fatty liver, inhibited white adipose tissue expansion and brown adipose tissue whitening in mice fed with high-fat diet, and boosted the abundance of lean-related species. The effects of R. hominis could be partially attributed to the production of nicotinamide riboside and upregulation of the Sirtuin1/mTOR signaling pathway. These results indicated that R. hominis is a promising candidate for the development of next-generation live biotherapeutics for the prevention of obesity and metabolic diseases.

Arecoline, the main alkaloid in areca nut, has shown potential in modulating metabolism and gut microbiota. This study aimed to evaluate its therapeutic effects on glucose and lipid metabolism, inflammation, liver function, and potential mechanisms in a Type 2 diabetes mellitus (T2DM) mouse model.

T2DM was established in mice with a high-fat, high-sugar diet, and streptozotocin injections. Arecoline significantly reduced fasting blood glucose, enhanced glucose tolerance, and increased insulin sensitivity. Serum lipid profiles showed marked decreases in total cholesterol, triglycerides, and LDL-C levels. Systemic inflammation, as measured by serum levels of IL-1β, IL-6, and MCP-1, decreased significantly. Improvements in liver function were observed, as indicated by reductions in ALT and AST levels. Liver transcriptomic analysis revealed modulation of pathways related to glutathione metabolism, MAPK signaling, and cAMP signaling, which were involved in insulin signaling and oxidative stress response. Additionally, arecoline mitigated gut dysbiosis by restoring microbial diversity, altering gut microbiota composition, and regulating key pathways involved in NAD biosynthesis and fatty acid β-oxidation, which were critical for maintaining energy homeostasis.

Arecoline improves glucose metabolism, lipid profiles, and liver function, while modulating gut microbiota and liver metabolic pathways, showing potential as a therapeutic agent for T2DM.

Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.

This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.

The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.

RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.

This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.

Alpha-Momorcharin (α-MMC), as one of the most important type I RIPs, has been reported to exert inhibitory effects against various tumour cells through its N-glycosidase activity. The present study was designed to propose an efficient purification strategy and explored its mechanism of apoptosis signalling pathway against human liver cancer cells SK-Hep-1. α-MMC can be successfully obtained by our purification strategy combining ion-exchange and gel-filtration chromatography. The functional studies revealed that α-MMC obviously increased the level of ROS and apoptosis rate, induced cell cycle arrest in the G1 phase, and depolarised MMP of SK-Hep-1 cells. To further confirm whether α-MMC could induce mitochondria involved apoptosis, we found that PARP-1, Caspase-3, Caspase-9, and BCL-2 were downregulated upon α-MMC. Taken together, these results suggested that this natural purified α-MMC can induce apoptosis involved mitochondria and may serve as a potential novel therapeutic drug in the treatment of human liver cancer in the future.

Colorectal cancer (CRC) is one of the most prevalent forms of cancer globally. The human gut microbiome plays an important role in the development of CRC and serves as a biomarker for early detection and treatment. This research effort focuses on the identification of potential taxonomic biomarkers of CRC using a grouping-based feature selection method. Additionally, this study investigates the effect of incorporating biological domain knowledge into the feature selection process while identifying CRC-associated microorganisms. Conventional feature selection techniques often fail to leverage existing biological knowledge during metagenomic data analysis. To address this gap, we propose taxonomy-based Grouping Scoring Modeling (G-S-M) method that integrates biological domain knowledge into feature grouping and selection. In this study, using metagenomic data related to CRC, classification is performed at three taxonomic levels (genus, family and order). The MetaPhlAn tool is employed to determine the relative abundance values of species in each sample. Comparative performance analyses involve six feature selection methods and four classification algorithms. When experimented on two CRC associated metagenomics datasets, the highest performance metric, yielding an AUC of 0.90, is observed at the genus taxonomic level. At this level, 7 out of top 10 groups (Parvimonas, Peptostreptococcus, Fusobacterium, Gemella, Streptococcus, Porphyromonas and Solobacterium) were commonly identified for both datasets. Moreover, the identified microorganisms at genus, family, and order levels are thoroughly discussed via refering to CRC-related metagenomic literature. This study not only contributes to our understanding of CRC development, but also highlights the applicability of taxonomy-based G-S-M method in tackling various diseases.

Gestational Diabetes Mellitus (GDM) is among the most common complications during pregnancy, posing serious risks to both the patient's and offspring's health and well-being. Alterations in the maternal microbiome are closely associated with the pathogenesis of GDM, with Extracellular Vesicles (EVs) facilitating communication between microbiota and the host. However, little is known about the relationship between the microbial composition within EVs and the pathogenesis of GDM. Therefore, this study aims to characterize the microbiota within serum EVs of GDM Patients (GDM group) and to identify microbial communities that significantly differ from those in Women With Normal Pregnancies (NonGDM group).

Blood samples were collected from both groups of patients, and EVs derived from serum were isolated via centrifugation. Identification and characterization of EVs were performed using transmission electron microscopy and nanoparticle flow cytometry. Microbiome analysis of serum EVs from both groups was conducted using 16S rRNA sequencing.

Results indicated altered diversity in microbial communities within serum EVs of GDM patients. Further analysis at the phylum, family, genus, and species levels revealed that Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were the dominant taxa in the EVs of both the NonGDM and GDM groups. Specifically, Actinobacteria and Firmicutes showed increased relative abundance in GDM group EVs compared to NonGDM, leading to a higher Firmicutes/Bacteroidetes ratio, while Proteobacteria and Bacteroidetes exhibited decreased relative abundance. Tax4Fun analysis revealed enrichment of microbial functions related to amino acid metabolism, carbohydrate metabolism, energy metabolism, and metabolism of cofactors and vitamins in both patient groups.

In conclusion, this study reveals a potential correlation between changes in the microbial composition and diversity of serum EVs and the onset and development of GDM. Furthermore, changes in the relative abundance of Actinobacteria, Proteobacteria, Bacteroidetes, and Firmicutes may play an important role in the pathogenesis of GDM.

Older individuals experience increased susceptibility and mortality to bacterial infections, but the underlying etiology remains unclear. Herein, it is shown that aging-associated reduction of commensal Parabacteroides goldsteinii (P. goldsteinii) in both aged mice and humans critically contributes to worse outcomes of bacterial infection. The colonization of live P. goldsteinii conferred protection against aging-associated bacterial infections. Metabolomic profiling reveals a protective compound, apigenin, generated by P. goldsteinii, antagonizes bacterial clearance defects in aged mice. AMP-binding protein (ampB) is identified as a key gene involved in apigenin synthesis in P. goldsteinii using homologous recombination in bacteria. Mechanistically, apigenin binds directly to the potential sites on Fgr (M341 and D404), preventing its inhibitory role on Vav1 phosphorylation, and therefore promoting the activation of Cdc42/Rac1, Arp2/3 expression and subsequent actin reorganization, which contributes to the enhanced phagocytosis of macrophages to bacteria. Collectively, the findings suggest that dysbiosis of the gut microbiota may impair host defense mechanisms and increase susceptibility to bacterial infections in older adults and highlight the microbiota-apigenin-Fgr axis as a possible route to ameliorate aging-associated antibacterial defects.

Ulva lactuca polysaccharide (ULP), a sulfated polysaccharide, has been widely used in Asia. However, its digestion process and utilization by gut microbiota remain poorly understood. In this study, the in vitro simulated digestion and fermentation were used to analyze the digestibility of ULP. The results showed that ULP was not degraded during simulated digestion, but was utilized by human fecal microbiota. 16S rRNA sequencing revealed that ULP significantly increased the abundance of Bacteroides. Further evaluation of seven Bacteroides species showed that only B. thetaiotaomicron and B. vulgatus could utilize ULP. Interestingly, these two species exhibited different utilization patterns. B. vulgatus preferentially utilized rhamnose of ULP over glucuronic acid to promote growth. Metabolite profiles of B. thetaiotaomicron and B. vulgatus during in vitro fermentation with ULP as the sole carbon source were different. Although both B. thetaiotaomicron and B. vulgatus utilized ULP to produce various metabolites such as acetic acid, propionic acid, cysteic acid and riboflavin, B. thetaiotaomicron accumulated metabolites, such as linoleic acid, that were not accumulated by B. vulgatus. The effects of ULP on the metabolic pathways of B. thetaiotaomicron and B. vulgatus differed. These findings provide a new perspective on the utilization of ULP by human gut microbiota.

Type 2 diabetes mellitus (T2DM), a widespread chronic metabolic disorder, presents a global challenge. Metformin hydrochloride, although widely prescribed, is associated with notable side effects. This study aims to explore safer, more effective alternatives by assessing the impact of Ruditapes philippinarum polysaccharides (RPPs) on glycemic control and modulation of microbiota in T2DM mice. A T2DM mouse model was established through a high-sucrose/high-fat diet and intraperitioneal streptozotocin injection. Glycometabolism indicators, histopathological features, and gut microbiota composition in caecum samples were assessed. Following 4 weeks of RPPs intervention, fasting blood glucose (FBG), glycated serum protein (GSP), area under the curve (AUC) of oral glucose tolerance test (OGTT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) levels were reduced in T2DM mice, while AKT-1 and GLUT-2 transcription levels were significant increased. Short-chain fatty acids (SCFAs) concentrations notably increased in the RPP-L group compared to the Model group, with improvements also observed in medium-chain fatty acids (MCFAs) and secondary bile acids (SBAs). Regarding gut microbiota, the Firmicutes-to-Bacteroidetes (F/B) ratio in RPP-L was substantially lower than in the Model group. At the genus level, beneficial bacteria, such as Akkermansia, Alloprevotella, Tidjanibacter, and Faecalibaculum demonstrated increased abundance. Correlation analysis identified Muribaculum, Paramuribaculum, Lacrimispora, and Turicibacter as microbial taxa associated with T2DM progression. RPPs significantly alleviated hyperglycemic symptoms in T2DM mice while enhancing the presence of beneficial gut bacteria, leading to a marked improvement in intestinal microbiota composition. This research offers foundational insights for the potential use of R. philippinarum in biomedical and nutraceutical applications.

Cholestatic liver injury is a hepatobiliary disorder primarily characterized by cholestasis, which significantly contributes to liver damage. The Yinzhihuang (YZH) oral preparation is an effective clinical treatment for cholestatic liver injury; however, the specific mechanism of action has not been clarified.

This study investigated YZH's pharmacological mechanisms associated with the microbe‒gut‒liver axis in cholestatic mice, offering new perspectives for the treatment of cholestasis.

YZH's protective effects were evaluated by evaluating serum liver injury indices and liver staining in an alpha-nephthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis mouse model. Colon hematoxylin‒eosin (H&E) and alcian blue staining and FITC‒dextran leakage assays were performed to assess intestinal barrier integrity. Fluorescence in situ hybridization was employed to analyze bacterial translocation. Additionally, 16S rRNA sequencing, fecal microbiota transplantation, and bile acid metabolomics analysis were conducted to examine the relationships among the microbiome, bile acid metabolism, and YZH formula.

We found that YZH administration alleviated symptoms of ANIT-induced hepatic pathological injury and fibrosis. In addition, YZH reduced the transfer of gut bacteria to liver tissue by maintaining an intact intestinal barrier. Notably, YZH influenced the intestinal microbiota composition, upregulated the abundance of bile acid metabolism-associated probiotic bacteria, including Clostridiales, Lachnospiraceae and Bifidobacterium pseudolongum; and downregulated the abundance of Escherichia-Shigella and Serratia, thereby promoting bile acid excretion.

YZH protects against cholestatic liver damage by promoting bile excretion and maintaining intestinal mucosal barrier integrity. Furthermore, YZH alleviates cholestasis in a gut microbiota-dependent manner, and upregulation of probiotics may be crucial for YZH's influence on bile acid metabolism.

Obesity is a global pandemic threatening public health, excess fat accumulation and overweight are its characteristics. In this study, the interplay between gut microbiota and retinol metabolism in modulating fat accumulation was verified. We observed gut microbiota depletion reduced the body weight and the ratios of white adipose tissues (WATs) to body weight in high-fat diet (HFD) fed-mice. The kyoto encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network of RNA-seq results indicated that retinol metabolism signaling may be involved in the microbiota-regulated fat deposition. Furthermore, activated retinol metabolism signaling by all-trans retinoic acid (atRA) supplementation reduced body weight and WAT accumulation in obese mice. 16S rRNA gene sequencing of the ileal microbiota suggested that atRA supplementation increased the microbial diversity and induced the growth of beneficial bacteria including Parabacteroides, Bacteroides, Clostridium_XVIII, Bifidobacterium, Enterococcus, Bacillus, Leuconostoc, and Lactobacillus in obese mice. Spearman correlation showed that the microbiota altered by atRA were associated with body and WAT weights. Together, this study reveals the interaction between the gut microbiota and retinol metabolism signaling in regulating adipose accumulation and obesity. It is expected of this finding to provide new insights to prevent and develop therapeutic measures of obesity-related metabolic syndrome.

p-hydroxycinnamic acids (p-HCAs), a class of natural phenolic acid compounds extracted from plant resources and widely distributed, feature a C6-C3 phenylpropanoid structure. Their antioxidant, anti-inflammatory, and antibacterial activities have shown great potential for applications in food and animal feed. The interactions between p-HCAs and the gut microbiota, as well as their subsequent effects on animal health, have increasingly attracted the attention of researchers. In the context of a greener and safer future, the progress and innovation in biosynthetic technology have occupied a central position in ensuring the safety of food and feed. This review emphasizes the complex mechanisms underlying the interactions between p-HCAs and the gut microbiota, providing a solid explanation for the remarkable bioactivities of p-HCAs and their subsequent impact on animal health. Furthermore, it explores the advancements in the synthetic biology of p-HCAs. This review could aid in a basis for better understanding the underlying interactions between p-HCAs and gut microbiota and animal health.

Resveratrol (RSV) is a naturally occurring astragalus-like polyphenolic compound with remarkable weight loss properties. However, the mechanism of RSV in treating obesity is unclear. In this narrative review, we explored electronic databases (PubMed) for research articles from 2021 to the present using the keywords "resveratrol" and "obesity". This article explores the mechanisms involved in the alleviation of obesity-related metabolic disorders by RSV. RSV affects obesity by modulating mitochondrial function, insulin signaling, and gut microbiota, regulating lipid metabolism, inhibiting oxidative stress, and regulating epigenetic regulation. Administering RSV to pregnant animals exhibits maternal and first-generation offspring benefits, and RSV administration to lactating animals has long-term benefits, which involve the epigenetic modulations by RSV. A comprehensive understanding of the epigenetic mechanisms of RSV regulation could help in developing drugs suitable for pregnancy preparation groups, pregnant women, and nursing infants.

Fecal microbiota transplantation (FMT) could significantly alter the recipient's gut bacteria composition and attenuate obesity and obesity-related metabolic syndromes. DL-norvaline is a nonproteinogenic amino acid and possesses anti-obesity potential. However, the specific mechanisms by which gut microbiota might mediate beneficial effects of DL-norvaline have not been completely elucidated. In this study, DL-norvaline-mediated FMT upregulated the beneficial bacteria (Clostridia_UCG_014, Christensenellales, Bacilli, Ileibacterium, Dubosiella, Lactobacillus, Muribaculaceae, and Bacteroidaceae) and downregulated the harmful bacteria (Tuzzerella and Marinifilaceae), further intestinal inflammation, oxidative stress, and intestinal barrier were alleviated as well as short chain fatty acids levels were increased, thus alleviating glucose and insulin metabolism, improving biochemical indexes and energy metabolism and decreasing body weight gain and tissue weight. However, heat-inactivated FMT did not demonstrate any of those improvements in obese mice. Notably, both DL-norvaline-mediated FMT and heat-inactivated FMT increased Bacteroidaceae and Muribaculaceae, this being a signature of alterations to the gut microbiota marker caused by DL-norvaline. Therefore, the beneficial effects of DL-norvaline were transmissible via FMT. This study highlighted the pivotal involvement of the gut microbiota in the development of obesity and provided a novel insight into the underlying mechanisms of FMT, thereby potentially enhancing the efficacy and refinement of FMT utilization.

Current treatment options for cholestatic liver diseases are limited, and addressing impaired intestinal barrier has emerged as a promising therapeutic approach. Si-Ni-San (SNS) is a Traditional Chinese Medicine (TCM) formula commonly utilized in the management of chronic liver diseases. Our previous studies have indicated that SNS effectively enhanced intestinal barrier function through the modulation of gut microbiota.

This study aims to verify the therapeutic effects of SNS on cholestatic liver injury, focusing on elucidating the underlying mechanism involving the gut-liver axis.

The 16s RNA gene sequencing, non-targeted metabolomics were used to investigate the effects of SNS on the gut microbiota dysbiosis. Fecal microbiota transplantation (FMT) was conducted to identify potential beneficial probiotics underlying the therapeutic effects of SNS.

Our results demonstrated that SNS significantly ameliorated cholestatic liver injury induced by partial bile duct ligation (pBDL). Additionally, SNS effectively suppressed cholestasis-induced inflammation and barrier dysfunction in both the small intestine and colon. While SNS did not impact the intestinal FXR-FGF15-hepatic CYP7A1 axis, it notably improved gut microbiota dysbiosis and modulated the profile of microbial metabolites, including beneficial secondary bile acids and tryptophan derivatives. Furthermore, gut microbiota depletion experiments and FMT confirmed that the therapeutic benefits of SNS in cholestatic liver disease are dependent on gut microbiota modulation, particularly through the promotion of the growth of potential probiotic P. goldsteinii. Moreover, a synergistic improvement in cholestatic liver injury was observed with the co-administration of P. goldsteinii and SNS.

Our study underscores that SNS effectively alleviates cholestatic liver injury by addressing gut microbiota dysbiosis and enhancing intestinal barrier function, supporting its rational clinical utilization. Furthermore, we highlight P. goldsteinii as a promising probiotic candidate for the management of cholestatic liver diseases.

Norvaline is a nonproteinogenic amino acid and an important food ingredient supplement for healthy food. In this study, dl-norvaline administration reduced body weight by more than 40% and improved glucose metabolism and energy metabolism in obese mice induced by a high-fat diet (HFD). Combination analysis of microbiome and metabolomics showed that dl-norvaline supplementation regulated gut bacteria structure, such as increasing beneficial bacteria (Mollicutes_RF39, Ruminococcaceae, Bacteroidaceae, Rikenellaceae, Lactobacillaceae, Clostridiaceae_1, uncultured_bacterium_f_Muribaculaceae, and Rikenellaceae_RC9_gut_group) and decreasing harmful bacteria (Fusobacteriia, Desulfovibrionales, Enterobacteriaceae, Burkholderiaceae, Helicobacteraceae, and Veillonellaceae) and modulated the metabolites involved in arachidonic acid metabolism, thus further promoting short-chain fatty acid production and improving gut barrier, thereby inflammatory responses and oxidative stress were ameliorated. In addition, the pseudogerm-free mouse model verified that dl-norvaline ameliorated obesity-associated disorders in HFD-fed obese mice by targeting gut microbiota. These results clarified that dl-norvaline may be promising for developing and innovating potential functional food products.

Metabolic syndrome (MetS) is a difficult-to-manage disease that poses a significant risk to human health. Here, we show that the supplementation of Lactobacillus reuteri ZJ617 ameliorates symptoms of MetS in mice induced by the high-fat diet. L. reuteri ZJ617 modulates host metabolism by interacting with the microbiome, resulting in the production of spermidine synthesized by the microbiota. L. reuteri ZJ617 serves as a source of substrates for the microbiota to synthesize spermidine, hence preventing the decline of bacteria responsible for spermidine production. Spermidine treatment mimics the metabolic effects of L. reuteri ZJ617, whereas pharmacological inhibition of spermidine biosynthesis in mice abolishes these benefits. Our findings reveal the mechanism by which L. reuteri ZJ617 alleviates MetS symptoms and provide support for its potential use as a probiotic for promoting metabolic health.

Obesity is a serious public health challenge worldwide, the present study is aimed to investigate the structural characteristic and anti-obesity effect of a water-soluble galactomannan (PEC) extracted from Eurotium cristatum (E. cristatum). Detailed analysis of the PEC structure showed a weight-average molecular weight of 32,305 Da and a composition of mainly mannose, galactose and small amounts of glucose. Nuclear magnetic resonance spectroscopy combined with methylation analysis indicated that the main chain of PEC is →5)-β-D-Galf-(1 → 6)-α-D-Manp-(1 → glycosidic bond, and the branched chain →2)-α-D-Manp-(1 → through →2,6)-α-D-Manp-(1 → is connected to the main chain by an O-2 bond. Furthermore, PEC was found to ameliorate body weight gain, metabolic disorders, and to modulate the gut microbiota in HFD-fed mice. Fecal microbiota transplantation trial confirmed that PEC prevented obesity development and metabolic disorders by reversing gut dysbiosis in HFD-fed mice. This is the first report of the isolation of PEC from E. cristatum, and the findings suggested that PEC exerted its antiobesity and related beneficial effects by regulating the gut microbiota. In conclusion, as a polysaccharide, PEC could reduce obesity by modulating the gut microbiota and has potential been a prophylactic agent for obesity and related metabolic diseases.

Human gut Bacteroides and Parabacteroides species play crucial roles in human health and are known for their capacity to utilize diverse polysaccharides. Understanding how these bacteria utilize medicinal polysaccharides is foundational for developing polysaccharides-based prebiotics and drugs. Here, we systematically mapped the utilization profiles of 20 different medicinal polysaccharides by 28 human gut Bacteroides and Parabacteroides species. The growth profiles exhibited substantial variation across different bacterial species and medicinal polysaccharides. Ginseng polysaccharides promoted the growth of multiple Bacteroides and Parabacteroides species; in contrast, Dendrobium polysaccharides selectively promoted the growth of Bacteroides uniformis. This distinct utilization profile was associated with genomic variation in carbohydrate-active enzymes, rather than monosaccharides composition variation among medicinal polysaccharides. Through comparative transcriptomics and genetical manipulation, we validated that the polysaccharide utilization locus PUL34_Bu enabled Bacteroides uniformis to utilize Dendrobium polysaccharides (i.e. glucomannan). In addition, we found that the GH26 enzyme in PUL34_Bu allowed Bacteroides uniformis to utilize multiple plant-derived mannan. Overall, our results revealed the selective utilization of medicinal polysaccharide by Bacteroides and Parabacteroides species and provided insights into the use of polysaccharides in engineering the human gut microbiome.

Adlay seed bran, typically discarded or used as animal feed, represents a significant resource waste. This study investigates the structural and physicochemical properties, in vitro digestive behavior, and fecal fermentation profiles of adlay seed bran polysaccharides (ASBPs) prepared using different methods. These methods include hot water extraction, Aspergillus niger solid-state fermentation (SSF), and enzyme-assisted SSF with β-glucosidase, cellulase, and xylanase, referred to as ASBP, ASBP-F, ASBP-GF, ASBP-CF, and ASBP-XF, respectively. Results showed that enzyme-assisted SSF with A. niger improved extraction efficiency and uniformity of ASBPs, increasing total neutral sugars, uronic acids, mannose, and galactose while reducing glucose content, molecular weight, and particle size. ASBP-CF had the best extraction rate, sugar content, lowest molecular weight, finest uniformity, and smallest particle size. In simulated digestion tests, all ASBP variants were stable in stomach and small intestine conditions but degradable by human fecal microbiota, showing varying fermentability levels. ASBPs increased Bacteroidetes populations, inhibited Proteobacteria growth, and enhanced short-chain fatty acid (SCFAs) production, with ASBP-CF showing the highest fermentability and prebiotic efficacy. ASBP-CF was particularly effective in promoting beneficial bacteria like Bacteroides and restraining harmful bacteria such as Escherichia_Shigella, producing more SCFAs during fermentation. These findings suggest that ASBP-CF has potential as a dietary supplement to improve gut health, presenting a high-value utilization strategy for adlay seed bran.

Background: Polysaccharides produced by the edible fungus Cordyceps cicadae can regulate blood sugar levels and may represent a suitable candidate for the treatment of diabetes and its complications. However, there is limited information available about the mechanism of how C. cicadae polysaccharide (CCP) might improve diabetic conditions. Methods: This study investigated its effects on the intestinal microbiota, intestinal mucosal barrier, and inflammation in mice with type 2 diabetes mellitus (T2DM) induced by streptozotocin, and its potential mechanisms. Results: Compared with the DC (diabetes model control group), CCPH oral treatment significantly increased the number of beneficial bifidobacteria, bifidobacteria, and lactobacilli (p < 0.01), restored the diversity of intestinal microorganisms in diabetic mice, and the proportions of Firmicutes and Bacteroidetes (34.36%/54.65%) were significantly lower than those of the DC (52.15%/32.09%). Moreover, CCPH significantly reduced the content of endotoxin (lipopolysaccharide, LPS) and D-lactic acid(D-LA) (p < 0.05), the activities of antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.01), and the content of proinflammatory cytokines TNF-α, IL-6, and IL-1β were reduced by 42.05%, 51.28%, and 52.79%, respectively, compared with the DC. The TLR4/NF-κB signaling pathway, as a therapeutic target for diabetic intestinal diseases, plays a role in regulating the inflammatory response and protecting the intestinal barrier function. Molecular mechanism studies showed that oral treatment with CCPH down-regulated the expression of NF-κB, TLR-4, and TNF-α genes by 18.66%, 21.58%, and 34.87%, respectively, while up-regulating the expression of ZO-1 and occludin genes by 32.70% and 25.11%, respectively. CCPH regulates the expression of short-chain fatty acid levels, increases microbial diversity, and ameliorates mouse colon lesions by inhibiting the TLR4/NF-κB signaling pathway. Conclusions: In conclusion, it is demonstrated that in this murine model, the treatment of diabetes with C. cicadae polysaccharide can effectively regulate intestinal microbiota imbalance, protect intestinal mucosal barrier function, and reduce inflammation in vivo, suggesting this natural product can provide a suitable strategy for the treatment of T2D-induced gut dysbiosis and intestinal health.

Presently, the mitigation and governance of obesity have surfaced as significant public health dilemmas on a global scale. A wealth of studies indicated that the host gut microbiota is instrumental in regulating the interplay between high-fat diet (HFD) intake and the pathogenesis of obesity. Physiological premature fruit drop, a major byproduct of citrus, is rich in a variety of bioactive constituents, yet its potential has remained underutilized for an extended period.

The objective of this investigation is to examine the chemical constituents of Citrus aurantium'Changshan-huyou' premature fruit drop (HYFD) and investigate its anti-obesity effects, elucidating its potential pathways.

Volatile compounds and flavonoids in HYFD were analyzed using chromatographic and mass spectrometric techniques. Furthermore, this study utilized biochemical assays and histopathological examinations to evaluate the effects of HYFD on HFD-fed mice. The impact of HYFD on the gut microbiota of the mice was examined through 16S rRNA gene sequencing, and fecal microbiota transplantation was employed to validate the role of the gut microbial community in host obesity prevention. Concurrently, transcriptome was employed to identify differentially expressed genes, providing further insights into the molecular mechanisms through which HYFD manifests its anti-obesity effects.

Our findings demonstrated that HYFD supplementation significantly alleviated adiposity and ameliorated the dysbiosis of gut microbiota in HFD-induced mice. HYFD rectified the HFD-induced gut microbiota dysregulation, enhanced the presence of beneficial microbial taxa linked to lipid metabolism, including Parabacteroides and Alistipes, and elevated concentrations of the anti-obesity short-chain fatty acids, comprising caproic acid and isocaproic acid. Additionally, transcriptomic analyses confirmed that HYFD prevented obesity in mice by enhancing fatty acid catabolism via the activation of the AMPK/PPARα/CPT1a signaling pathway.

Our results provided novel insights into the mechanism of citrus physiological premature fruit drop and its potential role in preventing obesity, while sparking greater interest in leveraging more biomass waste.

Colorectal cancer (CRC) is among the top three causes of global cancer mortality. In Vietnam, CRC is the third leading cause of death in women and the fourth cause of cancer mortality in men. A large number of metagenomic studies have reported the relationship between altered composition and function of the gut microbiota with CRC, but this relationship in low- and middle-income countries including Vietnam (with an estimated population of 100.3 million people in 2023, ranking 16th largest country by population in the world) is not well-explored.

We collected clinical data and fecal samples from 43 CRC patients and 44 healthy control subjects. The total community DNA of microorganisms was extracted from the fecal samples and analyzed for microbiota composition using Illumina MiSeq amplicon sequencing targeting the V3-V4 region of the 16S rRNA gene.

We identified a significant difference in the overall fecal microbiota composition between CRC patients and healthy controls, and we detected several CRC-associated microbial signatures in fecal samples of Vietnamese patients with CRC, which overlapped with signatures from other countries and meta-analyses. Although patients with (n = 8) and without (n = 35) type 2 diabetes (T2D) exhibited distinct gut microbiota composition compared to healthy controls, increased relative abundances of putatively pathogenic species including Parvimonas micra, Peptostreptococcus stomatis, and Prevotella intermedia were consistent biomarkers for CRC. In contrast, several health-associated species were significantly depleted in CRC patients such as Lactobacillus johnsonii and Bifidobacterium longum in CRC/non-T2D patients, Ruminococcus species, Bacteroides uniformis, and Phascolarctobacterium faecium in CRC/T2D patients, and Butyricicoccus pullicaecorum in both CRC groups combined.

Our findings confirm alterations in gut microbiota composition in CRC in a pilot Vietnamese cohort and highlight several gut microbial taxa that may have inhibitory or driver roles in CRC. This and future studies will enable the development of cancer diagnostics and treatment strategies for CRC in Vietnam, with a focus on targeting the microbiota.

Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.

Intestinal tract is the largest immune system of human body. Gut microbiota (GM) can produce a large number of metabolites, such as short-chain fatty acids and bile acids, which regulate the physiological health of the host and affect the development of disease. In recent years, traditional Chinese medicine (TCM) polysaccharides have attracted extensive attention with multiple biological activities and low toxicity. TCM polysaccharides can promote the growth of intestinal beneficial bacteria and inhibit the growth of harmful bacteria by regulating the structure and function of GM, thus playing a crucial role in preventing or treating chronic diseases such as inflammatory bowel disease (IBD), obesity, type 2 diabetes mellitus (T2DM), liver diseases, cancer, etc. In this paper, the research progress of TCM polysaccharides in the treatment of chronic diseases such as inflammatory bowel disease, obesity, T2DM, liver diseases, cancer, etc. by modulating GM was reviewed. Meanwhile, this review makes an in-depth discussion on the shortcomings of the research of TCM polysaccharides on chronic diseases by modulating GM, and new valuable prospection for the future researches of TCM polysaccharides are proposed, which will provide new ideas for the further study of TCM polysaccharides.

Elevated circulating branched-chain amino acids (BCAAs) have been associated with obesity, insulin resistance, and MASLD. Nonetheless, BCAA supplementation has been shown to provide protective outcomes towards the intervention of MASLD. Currently, there is a lack of study towards the contribution of the BCAA: valine on MASLD. Herein, the effect of low-dose valine supplementation was investigated for its role in the progression of MASLD.

C57BL/6J mice were fed a high-fat/high-cholesterol diet (HFD) to induce MASLD. Upon the establishment of MASLD, valine was supplemented via voluntary oral administration. Clinical and biochemical parameters associated with MASLD were measured, and molecular mechanism and gut microbiota modulation from the effect of valine were investigated.

Low-dose valine was found to attenuate the progression of MASLD, significantly reducing the gain in body weight, liver weight, and epididymal white adipose tissue (eWAT) weight, while also attenuating hyperglycemia and hyperleptinemia, and improving serum lipid profiles. Mechanistically, in the liver, genes related to hepatic lipogenesis and cholesterol biosynthesis were downregulated, while those associated with fatty acid oxidation, autophagy, and antioxidant capacity were upregulated, and AMPK pathway activity was enhanced. Liver and hypothalamic leptin resistance and inflammation were also attenuated, allowing better appetite control in mice fed a HFD and leading to reduced food intake. Additionally, metabolic flexibility in the eWAT was improved, and the gut microbiome was modulated by low-dose valine supplementation.

Low-dose valine supplementation attenuates MASLD by enhancing systemic leptin sensitivity and modulating the gut microbiome.

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.

Adhere to the concept of low-carbon environmental protection and turning waste into treasure, polysaccharides from Flammulina velutipes residue polysaccharide (FVRP) has been developed and possesses diverse bioactivities, comprising antioxidant, hypoglycemic, and relieving heavy metal damage, which still has the disadvantages of high molecular weight and low bioavailability. The current work is the first to prepare a degraded polysaccharide (FVRPV) from FVRP by ultrasonic assisted H2O2-Vc technique in order to reduce its molecular weight, thereby improving its activity and bioavailability. Our results found that the molecular weight and average particle size were declined, but the monosaccharide composition and characteristic functional group types of FVRPV had no impact. The structural changes of polysaccharides analyzed by XRD, Congo Red test, I2-KI, SEM, and methylation analysis indicated that the surface morphology and glycosidic bond composition of FVRPV possessed longer side chains and a greater number of branches with an amorphous crystal structure devoid of a triple helix configuration, and had experienced notable alterations after ultrasonic assisted H2O2-Vc treatment. Meanwhile, the in vitro antioxidant capacity of FVRPV had significantly increased compared to FVRP, implying ultrasonic assisted H2O2-Vc technique maybe a effective method to enhance the bioactivity of polysaccharides. In addition, the content of polysaccharide, reducing sugar, and uronic acid in FVRPV was significantly decreased, but antioxidant capacity of fermentation broth was stronger by in vitro human fecal fermentation. The 16S rDNA sequencing data displayed that FVRPV can enrich probiotics and reduce the abundance of pathogenic bacteria through different metabolic pathways mediated by gut microbiota, thereby exerting its potential probiotic effects. The interesting work provides a novel degraded polysaccharide by ultrasonic assisted H2O2-Vc technique, laying a foundation for developing FVRPV as a new antioxidant and prebiotic.

Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and impaired insulin secretion, with growing evidence highlighting the critical role of the gut-microbiota-brain axis in modulating glucose and lipid metabolism.

To evaluate the effects of Jiang Tang San Hao Formula (JTSHF) on blood glucose control in type 2 diabetic mouse model and to explore its mechanism through the gut- microbiota-brain axis.

A type 2 diabetes model was established using six-week-old male C57BL6/J mice, induced by a high-fat diet combined with streptozotocin injection. The diabetic mice then randomly assigned to the model group, metformin (Glucophage) group and JTSHF group, receiving 11 weeks of treatment by gavage. Body weight and fasting blood glucose were monitored biweekly. The oral glucose tolerance test was performed during the fifth and 10th weeks of the intervention. The measurements of body composition were conducted pre- and post-treatment. After the intervention, serum insulin, lipid levels, glucagon like peptide-1 (GLP-1), peptide YY, ghrelin, and leptin were detected. The fresh feces of mice were collected before sacrifice for gut microbiota analysis and short chain fatty acids quantification. The colon tissues of mice in each group were collected to observe the morphological structure and to measure the expression levels of GPR41 and GPR43. The hypothalamus was collected to assess the expression of POMC, AgRP and NPY.

JTSHF significantly boosted sugar and lipid metabolism and contributed to weight reduction in diabetic mice (p < 0.05). At the genus level, JTSHF increased the relative abundance of Bacteroides, Prevotella, and Parabacteroides, and decreased Clostridium, Lactobacillus, and Oscillibacter in the gut microbiota. JTSHF enhanced the content of short chain fatty acids, improved the expression level of GPR43/41 in colonic tissue (p < 0.05), and increased POMC expression while decreasing AgRP and NPY expression in the hypothalamus (p < 0.05). Serum GLP-1 was increased, and ghrelin was decreased significantly after JTSHF intervention (p < 0.05).

By affecting the composition, relative abundance, and metabolites of gut microbiota, JTSHF regulates various gut brain peptides, affects the hypothalamic feeding center, improves glucose and lipid metabolism, and thus plays the anti-diabetic role. The study provides novel insights into how traditional Chinese medicine modulates the gut-brain connection to exert anti-diabetic effects, highlighting the innovative potential of JTSHF in metabolic disease management.

Natural plant polysaccharides are renowned for their broad spectrum of biological activities, making them invaluable in both the pharmaceutical and food industries. Their safety, characterized by low toxicity and minimal side effects, coupled with their potential therapeutic properties, positions them as crucial elements in health-related applications. The functional effectiveness of these polysaccharides is deeply connected to their structural attributes, including molecular weight, monosaccharide components, and types of glycosidic bonds. These structural elements influence how polysaccharides interact with the gut microbiota, potentially alleviating various metabolic and inflammatory disorders such as inflammatory bowel disease, diabetes, liver-associated pathologies, obesity, and kidney diseases. The polysaccharides operate through a range of biological mechanisms. They enhance the formation of short-chain fatty acids, which are pivotal in keeping intestinal health and metabolic balance. Additionally, they strengthen the intestinal mucosal barrier, crucial for deterring the ingress of pathogens and toxins into the host system. By modulating the immune responses within the gut, they help in managing immune-mediated disorders, and their role in activating specific cellular signaling pathways further underscores their therapeutic potential. The review delves into the intricate structure-activity relationships of various natural polysaccharides and their interactions with the intestinal flora. By understanding these relationships, the scientific community can develop targeted strategies for the use of polysaccharides in therapeutics, potentially leading to innovative treatments for a range of diseases. Furthermore, the insights gained can drive the advancement of research in natural polysaccharide applications, providing direction for novel dietary supplements and functional foods designed to support gut health and overall well-being.

Gut commensals play important roles in maintaining the homeostasis of human health. Previous studies indicated that the abundance of P. goldsteinii in animal hosts was increased by the administration of prebiotics such as polysaccharides purified from iconic oriental medicinal fungi. Subsequently, P. goldsteinii was found to exert beneficial effects on the amelioration of multiple chronic inflammation-associated diseases. Even so, during the process of the development of P. goldsteinii as a next-generation probiotic (NGP), care has to be taken when it is used as a functional food ingredient. In this study, we isolated a novel P. goldsteinii strain, RV-01, from the feces of a healthy adult and carried out comprehensive analyses of its genomic and phenotypic characteristics. Bioinformatic analysis of P. goldsteinii RV-01 revealed the absence of potential virulence genes, as well as the presence of genes and traits potentially beneficial to human health, such as the production of short-chain fatty acids, anti-inflammatory lipopolysaccharides, and zwitterionic capsular polysaccharides, as well as immune regulatory proteins. To circumvent any potential side effects, the P. goldsteinii RV-01 was autoclaved before proceeding to the nonclinical safety assessment. The autoclaved P. goldsteinii RV-01 retained its anti-inflammatory effect in human colon epithelial cells. In addition to the three genotoxicity assays, 28-day subacute and 90-day subchronic animal toxicity studies (the highest dose tested was equivalent to 8.109 × 1010P. goldsteinii RV-01 cells/kg body weight/day) were also implemented. The results of all studies were negative for toxicity. These results support the conclusion that autoclaved P. goldsteinii RV-01 is safe for use as a food ingredient.

Recently, with changes in dietary patterns, there has been increased interest in the concept of food and medicine homology, which can help prevent disease development. This has led to a growing focus on the development of functional health foods derived from edible herbal sources. Polysaccharides, found in many edible herbal sources, are gaining popularity as natural ingredients in the production of functional food products. The gut microbiota can effectively utilize most edible herbal polysaccharides (EHPs) and produce beneficial metabolites; therefore, the prebiotic potential of EHPs is gradually being recognized. In this review, we comprehensively discuss the structural features and characterization of EHPs to promote gut microbiota regulation as well as the structure-activity relationship between EHPs and gut microbiota. As prebiotics, intestinal microbiota can use EHPs to indirectly produce metabolites such as short-chain fatty acids to promote overall health; on the other hand, different EHP structures possess some degree of selectivity on gut microbiota regulation. Moreover, we evaluate the functionality and mechanism underlying EHPs in terms of anticancer activity, antimetabolic diseases, anti-inflammatory activity, and anti-neuropsychiatric diseases.

Restriction of lipid uptake and absorption from the diet is regarded as an efficient strategy for the management of obesity, while lipase inhibition could successfully block the digestion of dietary lipids. Mume Fructus (MF) and Schisandrae Chinensis Fructus (SCF) were used as fruits, the biological effect of which on obesity desired more attention. Herein, the extracts of MF and SCF displayed significant efficacy in managing obesity in mice fed with a high-fat diet, via the inhibition of hydrolase activity of lipase in the digestive tract. Using the bioactivity guidance strategy, citric acid and malic acid were identified as the major lipase inhibitors from MF and SCF, respectively, which could prevent body weight gain, along with adipose tissue formation, and alleviate hyperlipidemia and hepatic steatosis in obese mice. Above all, MF and SCF could be used for the management of obesity via the lipase inhibition by citric acid and malic acid, displaying potential applications in healthy foods, nutritional supplements, and pharmaceutical materials.

Cordyceps sinensis (Berk.) Sacc. (Ophiocordyceps sinensis) is an edible and medicinal fungus used as a natural superior tonic. It is considered as scarce fungus with a high market demand. Therefore, as an alternative, fermentation technology has been proposed to produce artificial cordyceps (fermented C. sinensis) to address the shortage of cordyceps resources for industrialization and commercial utilization. Numerous studies have proved that polysaccharides are the important bioactive substances in the fermented C. sinensis, but the research data lack systematic review. In this review, current relevant research data regarding the preparation (including extraction, fractionation, and purification), structural characterization (including molecular weight, monosaccharide composition, glycosidic bond type, structural and conformational features), bioactivities, structure-activity relationships (SAR) and applications of polysaccharides from different sources of fermented C. sinensis last decade were analyzed and discussed. The findings highlight that the most commonly employed methods for preparing fermented Cordyceps sinensis polysaccharides (FCSPs) involve water extraction and alcohol precipitation, combing with sophisticated chromatographic techniques such as ion exchange and gel permeation chromatography. From these processes, 34 different polysaccharides were identified including 5 glucans and 7 heteropolysaccharides that were thoroughly characterized. FCSPs exhibited a broad spectrum of biological activities, ranging from antioxidant and renal protective effects to immunomodulatory, antitumor, and hypolipidemic properties. The structure-activity relationships (SAR) demonstrated that key factors, such as molecular weight, monosaccharide composition and glucosidic bond types, play critical roles in determining the bioactivity of FCSPs. Nevertheless, there remain unknown elements that continue to influence SAR, leaving room for further exploration. Furthermore, the limitation of existing studies and some new perspectives for future investigations on FCSPs were proposed.

Glioma poses a serious threat to human health and has a high mortality rate. Therefore, developing natural anti-tumour drugs for cancer treatment is an urgent priority. Schizophyllum commune is an edible and medicinal fungus, with polysaccharides as its main active components, which may have anti-tumour properties. Herein, we characterised S. commune fruiting body polysaccharides (SCFP) structure and evaluated its anti-glioma activity in vitro and in vivo. UV and FTIR spectra, high-performance gel chromatography, and monosaccharide composition analyses demonstrated that SCFP was a heteropolysaccharide with a molecular weight of 290.92 kDa. Among the monosaccharide compositions, mannose, galactose, and glucose were the most abundant. SCFP significantly inhibited the survival of the glioma cell lines U251 and U-87MG. U251 xenograft tumours treated with SCFP via gavage showed a 47.39 % inhibition, with no significant toxic side effects observed. SCFP upregulated aplasia Ras homologue member I (ARHI) expression, thereby regulating PI3K/AKT signalling, inhibiting tumour migration, and inducing apoptosis, to inhibit tumour growth. Furthermore, SCFP treatment increased the relative abundance of beneficial bacteria, including Akkermansia muciniphila, Ligilactobacillus murinus, and Parabacteroides goldsteinii, in tumour-bearing mice and restored the gut microbiota structure to that of the normal group (NG group) mice without tumours. Thus, SCFP has the potential for application as a natural anticancer drug.

Gut microbiota dysbiosis and gut barrier disruption are key events associated with high-fat diet (HFD)-induced systemic metabolic disorders. Gymnemic acid (GA) has been reported to have an important role in alleviating HFD-induced disorders of glycolipid metabolism, but its regulatory role in HFD-induced disorders of the gut microbiota and gut barrier function has not been elucidated. Here we showed that GA intervention in HFD-induced hamsters increased the relative abundance of short-chain fatty acid (SCFA)-producing microbes including Lactobacillus (P<.05) and Lachnoclostridium (P<.01) in the gut, and reduced the relative abundance of lipopolysaccharide (LPS)-producing microbes including Enterococcus (P<.05) and Bacteroides (P<.05), subsequently improving HFD-induced intestinal barrier dysfunction and systemic inflammation. Specifically, GA intervention reduced mRNA expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α (P<.01), increased mRNA expression of antioxidant-related genes, including Nfe2l2, Ho-1, and Nqo1 (P<.01), and increased mRNA expression of intestinal tight junction proteins, including Occludin and Claudin-1 (P<.01), thereby improving gut barrier function of HFD hamsters. This ameliorative effect of GA on the gut of HFD hamsters may further promote lipid metabolic balance in liver and adipose tissue by regulating the Toll-like receptor 4 (TLR4)-nuclear factor-κB (NF-κB) signaling pathway. Taken together, these results systematically revealed the important role of GA in regulating HFD-induced gut microbiota disturbance and gut barrier function impairment, providing a potential clinical theoretical basis for targeted treatment of HFD-induced microbiota dysbiosis.

Akkermansia muciniphila (Akk), a second-generation probiotic known for its ability to regulate intestinal function in mammals, is not yet fully understood in the context of aquaculture. This study aims to investigate the effects of different forms of Akk on intestinal barrier function and immune response in zebrafish (Danio rerio) under high-fat diet conditions. The experimental groups included a control group, a high-fat diet group, an Akk group, and a group receiving various concentrations of pasteurized Akkermansia muciniphila (P-Akk) along with a high-fat diet. Evaluation methods included histological examination with hematoxylin and eosin staining, ultrastructural analysis using transmission electron microscopy, real-time fluorescence quantitative analysis, and transcriptome sequencing technology. The results showed that both the Akk and P-Akk groups exhibited a significant increase in villi number and length compared to the high-fat group. Furthermore the expression levels of claudin, claudin-2, occludin A, occludin B, and other genes were significantly upregulated, while the expression levels of intestinal proinflammatory factors genes and proteins were significantly downregulated. Compared to the high-fat group, the Akk group showed a more complete and well-preserved nucleus, mitochondria, and tight junction structures. Additionally, the morphology of intestinal epithelial microvilli in the medium and high concentration Akk group was complete and dense. The expressions of tlr2 and nf-κb were upregulated, while the expressions of myd88 and nod2 were downregulated in the medium- and high-concentration Akk groups. Akk may improve immune dysfunction in high-fat fed zebrafish through the TLR2/NF-κB signaling pathway, which requires further study. Transcriptome analysis revealed significant upregulation of the immune-related gene pigr, significant downregulation of stat3, and significant upregulation of the intercellular adhesion molecule f11r. In conclusion, dietary Akk supplementation alleviated intestinal barrier damage and immune dysfunction in high-fat zebrafish. This study provides important insights into the potential use of Akk in fish and lays the foundation for further studies on its role in fish immunity.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.