Inflammatory bowel disease (IBD) is a chronic autoimmune condition whose pathogenesis has not been fully elucidated, and current treatments are not definitive and often carry several side effects. The Complementary and Alternative Medicine (CAM) offers a new approach to conventional medicine. However, their clinical application and mechanisms remain limited.Objective: The aim of this review is to evaluate the anti-inflammatory, impact on microbiota and antioxidant efficacy of currently available CAM for IBD.Methods: The literature collection was obtained from Google Scholar, MEDLINE, PubMed and Web of Science (WOS). Studies in both human and animal models, published in English language between 2018 and 2024, were selected. Sixty-seven studies were included in the current review after inclusion and exclusion screening processes.Results: Mostly, studies showed significant anti-inflammatory, gut microbiota restoring, antioxidant effects of polyphenols, polysaccharides, emodin, short-chain fatty acids (SCFA; including butyrate, propionate and acetate), and probiotics although some contrasting results were noted. Current evidence shows that polyphenols exhibit the most consistent result in alleviating IBD pathophysiology, primarily due to their significant SCFA-elevating effect.Discussion: Future studies may focus on human studies, narrowing down on individual factors which may change natural product's metabolism. Further research studies are also essential to obtain therapeutic recommendations.

Inflammatory Bowel Disease (IBD) is a chronic autoimmune disorder that severely affects the gastrointestinal tract and is difficult to cure. This study explored the mechanism by which human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Ex) alleviate IBD through O-GlcNAc glycosylation modification and the expression of related proteins. The study analyzed the effects of HucMSC-Ex on the inhibition of pro-inflammatory factors and promotion of intestinal epithelial cells regeneration in vitro and in vivo, with a focus on the role of the O-GlcNAc glycosylation of the RACK1 protein. The findings indicated that HucMSC-Ex reverses epithelial-mesenchymal transition (EMT) by upregulating O-GlcNAc glycosylation levels and effectively alleviates IBD symptoms and inflammatory responses in mouse intestinal epithelial cells. By modulating O-GlcNAc glycosylation, HucMSC-Ex exhibits significant therapeutic potential in immune regulation and gut microbiota remodeling, offering new perspectives for IBD treatment.

Angoroside C (AgrC) is a compound with many pharmacological properties. However, its antitumour potential has not been well studied. The low bioavailability of AgrC suggests a strong link to gut bacteria. Therefore, we identified and quantified four AgrC metabolites in gut microbiota. Molecular docking and inhibitor-based experiments demonstrated that carboxylesterase played a key role in AgrC metabolism. Both AgrC and its metabolites inhibited the viability of CT-26 cells, and potential antitumour targets were further explored. Additionally, AgrC significantly increased the levels of propionic, butyric, valeric and isovaleric acids. This provides a new insight for the antitumour effects of AgrC.

Inflammation-associated diseases have become widespread and pose a significant threat to human health, and the therapeutic methods for diverse diseases are inadequate due to the undesirable effects of synthetic ingredients. Recently, more and more evidence indicated that phytochemicals, plant secondary metabolites, have numerous therapeutic functions against human diseases via affecting a variety of mechanisms with their distinct advantages of high efficiency and low toxicity. Here, we highlight the mechanisms of phytochemicals to hinder inflammation-associated diseases (including Inflammatory diseases, cardiovascular diseases, metabolic syndrome, neurological disorders, skin diseases, respiratory diseases, kidney diseases, gastrointestinal diseases, retinal diseases, viral infections) by regulating the crosstalk among various signal cascades (including MicroRNAs, SIRT1, DNMTs, NF-κB, NLRP3, TGF-β, the Gasdermin-mediated pyroptosis pathway), which can be considered as a novel and potential therapeutic strategy. Furthermore, phytochemicals could prevent virus infection by disturbing different targets in the virus replication cycle. However, natural plants have shown limited bioavailability due to their low water solubility, the use of adjuvants such as liposomal phytochemicals, phytochemical nanoparticles and phytochemicals-phospholipid complex promote their bioavailability to exhibit beneficial effects against various diseases. The purpose of this review is to explore the molecular mechanisms and promising applications of phytochemicals in the fields of inflammation-associated diseases and virus infection to provide some direction.

Environmental factors, including poor dietary habits and unhealthy drinking patterns, contribute to ulcerative colitis (UC). While the relationship between diet-related malnutrition and UC has been extensively explored, the impact of drinking water temperature remains largely overlooked, prompting us to investigate its influence on UC pathogenesis and explore the underlying mechanisms. In the present study, we observed that, unlike external thermal and cold therapy, varying drinking water temperatures transiently altered the internal body temperature of the digestive tract. Specifically, chronic drinking of 0°C water had significant anti-inflammatory effects and preserved the integrity of the mucosal barrier in a colitis mouse model. Mechanistically, this temperature spectrum changed the composition of the gut microbiota from inflammation-prone (25°C drinking water) to a resting pattern similar to that of the negative control. Specifically, the abundances of Blautia and Parasutterella, two beneficial genera, were strongly increased in response to 0°C water, accompanied by elevated levels of short-chain fatty acids. In contrast, drinking 40°C water had opposite effects on all the examined parameters and generally aggravated the development of colitis. This study is the first to demonstrate how modifying the temperature of habitual drinking water can modulate colitis progression, providing a novel and noninvasive approach to UC management. Specifically, chronic consumption of 0°C water alleviated the severity of colitis, whereas 40°C water aggravated the disease. Therefore, by focusing on commonly consumed drinking water temperatures, our findings suggest that this simple intervention could be a safe, convenient, and effective therapeutic strategy.

Liupao tea is known for its anti-inflammatory antioxidant and regulation of gut microecological balance properties. This study aims to investigate the therapeutic effects of Liupao tea aqueous extract (LPTAE) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The rats were randomly divided into five groups: the Normal group, the DSS group, the LPTL group, the LPTM group, and the LPTH group. Throughout the experiment, the rats' activity levels, stool consistency, and body weights were observed and recorded daily. After the experiment, colon length was measured, and colon tissues were collected for pathological analysis. Additionally, the colon contents were analyzed for gut microbiota composition and short-chain fatty acid (SCFA) level, while serum samples were collected to determine inflammatory and oxidative factors. The results indicated that treatment with low, medium, and high doses of LPTAE significantly inhibited weight loss, alleviated rectal bleeding, and reduced colon shortening compared to the DSS group. It also decreased the disease activity index and histopathological activity index scores in the rats. Furthermore, LPTAE reduced the levels of inflammatory cytokines such as IL-1β, IL-6, TNF-α, and malondialdehyde, while simultaneously increasing the levels of superoxide dismutase and SCFAs, including acetic acid, propionic acid, and butyric acid. 16S rDNA gene sequencing of the gut microbiota revealed that all doses of LPTAE reversed the decrease in both α and β diversities caused by UC, increased the relative abundance of beneficial bacteria such as Lactobacillus, Muribaculaceae, Alloprevotella, and Blautia, and decreased the levels of harmful bacteria such as Prevotella, Romboutsia, and Bacteroides. In summary, within the tested doses (100, 150, 250 mg/kg), LPTAE alleviated DSS-induced colitis by modulating the gut microbiota and correcting the metabolic imbalance of SCFAs.

Inflammatory bowel disease (IBD) involves the complex interplay among the mucosal barrier, microbiota, immunity and genetic factors. There are currently no satisfactory treatments for IBD. Administration of the probiotic Bacillus licheniformis (Bl) can improves colitis by regulating the gut microbiota. The phytohormone abscisic acid (ABA) treatment has favorable effects on immunity, as well as on inflammatory diseases like colitis. We hypothesized that the expression of an additional cyp gene by the Bl to increase its ABA production would enhance its effects.

In this study, we found that a Bl-cyp strain overexpressing the cyp gene secreted more ABA into its supernatant than either the parental Bl stain or a Bl-pET82a strain expressing only a vector pET82a when these bacteria were grown in Nfb medium for 48 h. The prophylactic administration of the Bl-cyp strain culture more effectively attenuated dextran sodium sulfate (DSS)-induced colitis in mice compared to the Bl and Bl-pET28a strains. These findings were associated with significantly reduced epithelial barrier damage, as well as increased number of goblet cells and expression levels of occludin gene in the colonic epithelial layer, and decreased serum LPS levels in the Bl-cyp group. In addition, the administration of Bl-cyp strain effectively regulated the disordered gut microbiota by improving their diversity, richness and compositions more than the Bl or Bl-pET82a strain, including the ratio of Bacteroidota: Bacillota. It also inhibited the excessive growth of opportunistic pathogen Escherichia just like the Bl or Bl-pET82a strain. Moreover, the preventive administration of the Bl-cyp strain to mice following DSS-induced colitis enhanced the proportion of Treg cells and suppressed the proportion of Th17 cells in mesenteric lymph nodes (MLNs), decreased the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-22, and increased the level of anti-inflammatory IL-10 in colon tissues, similar to treatment with a high concentration of the ABA standard (ABA-H). Notably, the treatment with the Bl-cyp strain more effectively regulated the disordered microbiota than the ABA-H.

The administration of the Bl-cyp strain may provide a novel preventive approach for IBD, and may exert its effects by modulating the gut microbiota and host's immune status.

Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.

Ulcerative colitis (UC) is a chronic inflammatory disease primarily affecting the colon, characterized by mucosal inflammation and ulceration. Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide derived from Entamoeba histolytica, has demonstrated the anti-inflammatory capacity. The aim of the current work was to test the protective effects of MLIF in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings indicated that MLIF significantly inhibition of colitis development, including body weight, DAI score, colon length, and spleen index. MLIF slowing the progression of inflammation in the colon of mice exposed to DSS, evidenced by HE staining and mRNA expression levels of Il1b, Il6, Il18 and Il10. MLIF significantly alleviated intestinal barrier dysfunction in mice exposed to DSS, evidenced by AB-PAS staining and mRNA expression levels of Tjp1, Ocln and Muc2. Importantly, the administration of MLIF in colitis mice exerted beneficial effects on the gut microbiota, enhancing microbial diversity and abundance, and promoting the restoration of gut microbiota homeostasis. Non-targeted metabolomics results suggest that the benefits of MLIF may arise from its modulation of tryptophan metabolism pathways. In conclusion, MLIF prevention inflammation induction and preserves intestinal homeostasis against colitis induced by DSS.

Camellia oleifera shells (COS) are a by-product of camellia oil processing and are rich in polyphenols. To date, the polyphenols extracted from COS have not been fully developed. In this study, two polyphenol fractions, referred to as 20P and 40P, were obtained by sequentially eluting the COS crude extract from an AB-8 macroporous resin column using ethanol at concentrations of 20% and 40% with different polarities. In addition, the biotransformation processes of these two polyphenols and their effects on the gut microbiota were studied.

The results of in vitro digestion showed that at the end of the intestinal digestion stage the total phenolic content (TPC) content (0.34 ± 0.050 mg gallic acid equivalent (GAE) mg-1 dry weight (DW)) and antioxidant activity (0.53 ± 0.0076 mg vitamin C (Vc) mg-1 DW) of the 20P component were significantly higher than those of the 40P component (0.19 ± 0.020 mg GAE mg-1 DW; 0.39 ± 0.016 mg Vc mg-1 DW). In addition, the experiment also found that the phenolic composition and transformation process of 20P and 40P components were significantly different, and the TPC content (0.30 ± 0.058 mg GAE mg-1 DW) and antioxidant capacity (0.73 ± 0.034 mg Vc mg-1 DW) of the 40P component were significantly higher than that of the 20P (0.13 ± 0.035 mg GAE mg-1 DW); (0.19 ± 0.013 mg Vc mg-1 DW) component during in vitro fermentation. This may be related to the types of compounds extracted by solvents with different polarities. In addition, both 20P and 40P components significantly regulated the gut microbiota and promoted the production of short-chain fatty acids.

These results indicate that polyphenols from different polar sources of COS can serve as valuable bioactive compounds with potential health-regulating properties. © 2025 Society of Chemical Industry.

Plantamajoside (PMS) is a natural bioactive compound derived from medicinal, food homologous plants of the genus Plantago.

This study aimed to investigate the protective effects of PMS on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and explore the associated mechanisms.

We found that PMS treatment significantly alleviated UC symptoms in mice by preventing body weight loss, increasing colon length, and reducing disease activity index scores. Moreover, PMS alleviated colonic lesions, increased the number of goblet cells, upregulated the expression of intestinal barrier proteins (ZO-1, occludin, and claudin-3), and decreased the levels of pro-inflammatory factors. PMS treatment modulated the gut microbiota by increasing the relative abundance of Bacteroidota and Verrucomicrobiota and decreasing that of Firmicutes and Proteobacteria at the phylum level. At the genus level, PMS suppressed the abundance of pathogenic bacteria, such as Turicibacter and upregulated the abundance of [Eubacterium]_xylanophilum_group. Fecal microbiota transplantation experiments further confirmed that PMS treatment alleviated UC by modulating the gut microbiota. Transcriptomic analysis of colon tissues, coupled with reverse transcription-quantitative polymerase chain reaction and western blotting, showed that PMS treatment upregulated cystathionine beta-synthase (CBS) expression and inhibited NF-κB pathway activation. In a lipopolysaccharide-induced inflammation model in RAW264.7 cells, PMS treatment inhibited the secretion of pro-inflammatory cytokines, upregulated CBS expression, and prevented NF-κB pathway activation.

PMS protects against UC in mice via multiple mechanisms, including modulating the gut microbiota, increasing the expression levels of CBS, and inhibiting the NF-κB pathway.

Clostridium difficile infection (CDI) is a significant infectious disease with limited treatment options. Pterostilbene, an active compound found in blueberries, is known for its antioxidant and anti-inflammatory properties. This study investigated the effects of pterostilbene on intestinal barrier damage and secondary liver oxidative stress induced by CDI in mice. Pathological changes in the colon and liver, the levels of anti-inflammatory cytokines and antioxidants, and the expression of related genes were evaluated. Additionally, 16S rRNA sequencing and targeted metabolomics analyses of the gut microbiota and bile acids were conducted. Pterostilbene reduced the abundance of harmful bacteria such as Enterococcus, while increasing beneficial bacteria like Lactobacillus, thereby reshaping the gut microbiota and bile acid profile and reducing the accumulation of T-βMCA. This process activated intestinal FXR signaling, which alleviated colonic inflammation and reduced intestinal permeability. The reduction in intestinal permeability prevented the translocation of bacteria and bacterial toxins into the liver via the portal vein, thereby reducing liver inflammation and oxidative stress. Pterostilbene presented a promising strategy for maintaining intestinal health through the regulation of dysbiosis and bile acid disturbances caused by CDI. When integrated into the food system, pterostilbene has the potential to improve intestinal health, mitigate the risk of CDI associated with contaminated agricultural products, and enhance public health and food safety. Additionally, we identified that regulating the intestinal bile acid profile and the FXR receptor could serve as potential therapeutic targets for CDI, thereby facilitating the development of novel treatment options and dietary strategies.

Gut microbiota has a crucial role in the pathophysiology of metabolic-associated steatotic liver disease (MASLD), influencing various metabolic mechanisms and contributing to the development of the disease. Dietary interventions targeting gut microbiota have shown potential in modulating microbial composition and mitigating MASLD progression. In this context, the integration of multi-omics analysis and artificial intelligence (AI) in personalized nutrition offers new opportunities for tailoring dietary strategies based on individual microbiome profiles and metabolic responses. The use of chatbots and other AI-based health solutions offers a unique opportunity to democratize access to health interventions due to their low cost, accessibility, and scalability. Future research should focus on the clinical validation of AI-powered dietary strategies, integrating microbiome-based therapies and precision nutrition approaches. Establishing standardized protocols and ethical guidelines will be crucial for implementing AI in MASLD management, paving the way for a more personalized, data-driven approach to disease prevention and treatment.

The probiotic Lactiplantibacillus plantarum (L. plantarum) could ameliorate colitis. Alterations in the composition of gut microbiota (GM) have been proved in cases of colitis. The exopolysaccharides from L. plantarum HMPM2111 (LPE) could be effective in colitis through altering the composition of the GM. These effects were linked to inhibiting intestinal inflammation, regulating the TXNIP/NLRP3 inflammasome axis, and attenuating colonic barrier dysfunction. The combination of fecal microbiota transplantation (FMT) and antibiotic inducement showed that gut bacteria susceptible to vancomycin were inversely associated with colitis features and were necessary for the anti-inflammatory effects of LPE. The elevated abundances of gut commensal Lachnospiraceae bacteria were associated with the restoration of colitis treated by LPE. Metabolomics analysis showed that colitis mice treated with LPE had higher levels of propionate and tryptophan metabolites generated from gut bacteria. The administration of these metabolites protected colitis and resulted in a reduction in inflammatory responses. The outcomes of our investigation emerge the significance of the GM in controlling the protective implications of LPE against colitis. Lachnospiraceae bacteria, together with downstream metabolites, contribute substantially to protection. This work elucidates the essential function of the GM-metabolite axis in producing comprehensive protection versus colitis and identifies prospective treatment targets.

In this study, epicatechin gallate (ECG), a natural anti-inflammatory agent, was conjugated onto dialdehyde starch (DAS) to achieve high physiological stability. The anti-inflammatory effect of DAS-ECG conjugate was evaluated by lipopolysaccharide (LPS)-stimulated RAW264.7 cells and dextran sulfate sodium (DSS)-induced colitis mice models. Results showed that 25-800 μg/mL of DAS-ECG conjugate was non-cytotoxic to RAW264.7 cells. DAS-ECG conjugate effectively inhibited the abnormal morphology, the production of nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and reactive oxygen species, and the apoptosis of LPS-stimulated RAW264.7 cells in a dose-dependent manner. DAS-ECG conjugate significantly reduced the disease activity index, thymus atrophy, spleen enlargement, colon shortening and colon damage of DSS-induced colitis mice. Meanwhile, DAS-ECG conjugate remarkably reduced the levels of TNF-α, IL-6, IL-1β and malondialdehyde but increased the levels of superoxide dismutase and glutathione in the colon tissue of DSS-induced colitis mice. Moreover, DAS-ECG conjugate increased the relative abundance of beneficial bacteria (Akkermansia, Candidatus_Saccharimonas, unclassified_f_Muribaculaceae, Alistipes and Parabacteroides), promoted the production of short-chain fatty acids, and decreased the relative abundance of harmful bacterium (norank_f_Ruminococcaceae) in DSS-induced colitis mice. Therefore, DAS-ECG conjugate could be considered as a promising anti-inflammatory agent.

Nanoplastics pollution is a global issue, with the digestive tract being one of the first affected organs, requiring further research on its impact on intestinal health. This study involved orally exposing mice to polystyrene nanoplastics (PS-NPs) at doses of 0.1, 0.5, or 2.5 mg/d for 42 days. The effects on intestinal health were thoroughly assessed via microbiomics, metabolomics, transcriptomics, and molecular biology. Our study demonstrated that the administration of all three doses of PS-NPs resulted in increased colonic permeability, heightened colonic and peripheral inflammation, reduced levels of antimicrobial peptides, and shortened colonic length. These effects may be attributed to a reduction in the abundance of probiotic bacteria, such as Clostridia_UCG-014, Roseburia, and Akkermansia, alongside an increase in the abundance of the pathogenic bacterium Desulfovibrionaceae induced by PS-NPs. Furthermore, we underscored the crucial role of histidine metabolism in PS-NPs-induced colonic injury, characterized by a significant reduction of L-histidine, which is closely related to microbial ecological dysregulation. Corresponding to microbiota deterioration and metabolic dysregulation, transcriptome analysis revealed that PS-NPs may disrupt colonic immune homeostasis by activating the TLR4/MyD88/NF-κB/NLRP3 signaling pathway. In conclusion, this study provided novel insights into the mechanisms by which PS-NPs disrupt intestinal homeostasis through integrated multiomics analysis, revealing critical molecular pathway and providing a scientific basis for future risk assessment of nanoplastics exposure.

Skin aging is a multifaceted process. Glycation significantly contributes to skin aging and the development of complications. Researchers are currently investigating various substances, particularly those from natural sources, to combat skin glycation.

This study aimed to comprehensively evaluate the anti-glycation effect of a new natural combination, EBB, which includes (-)-epigallocatechin-3 gallate (EGCG), bamboo leaf flavonoids, and broccoli seed water extracts, using cell and animal models and to explore its potential anti-glycation mechanism.

The components of EBB were identified using HPLC and UHPLC-MS/MS. Additionally, a glycation cell model induced by glyceraldehyde, advanced glycation end products (AGEs), and methylglyoxal was established in HaCaT cells to evaluate the efficacy of EBB in alleviating glycation. Differential genes, signalling pathways, and biological processes were analysed through RNA sequencing to explore the mechanisms of the anti-glycation effects of EBB, which were further validated using qRT-PCR and Western blotting. Finally, the protective effects of EBB against glycation and skin damage were assessed in zebrafish and mouse in vivo models through histological studies and the measurement of various skin physiological parameters.

Glucoraphanin, Sinapine and orientin were identified in EBB, which effectively reduced the formation of AGEs and decreased the expression level of the RAGE protein in HaCaT cells. Transcriptomic analyses revealed that EBB regulated the expression of 576 differentially expressed genes. These genes were enriched in various biological processes, such as chronic inflammation and immune responses, and participated in the regulation of multiple signalling pathways, including TNF. Glycation upregulated the expression of the ROS1 gene and protein, while EBB reversed this effect. Furthermore, EBB attenuated the glycation response by downregulating the expression levels of proteins such as p-p38, p-ERK1/2, p-p65, and TNF-α. Additionally, the reduction of AGE accumulation by EBB was confirmed in a zebrafish model. Similarly, histological analyses of mouse skin tissue and various physiological parameters demonstrated that EBB significantly mitigated damage induced by glycation.

Our results show that EBB effectively inhibited glycation reactions. The mechanism of action may involve the reduction of inflammation by downregulating the expression levels of RAGE and ROS1, thereby decreasing the accumulation of AGEs in keratinocytes and alleviating skin damage. This paves the way for the potential application of EBB as a valuable anti-glycation functional ingredient in the food and cosmetic industries.

Dysbiosis of gut microbiome is one of the most important factors leading to inflammatory bowel disease (IBD). Intake of phytochemicals from fruits and vegetables is an effective way to improve IBD, but how these bioactivators regulate gut microbiota to exert healthy effects remains unclear. Here, we found that pretreatment with CiLi juice, particularly its polyphenol component, alleviated dextran sulfate sodium (DSS)-induced colitis while preserving intestinal barrier integrity. CiLi polyphenols (CL_PP) reduced inflammation and oxidative stress in colon tissue and enriched fecal short-chain fatty acids. Importantly, CL_PP significantly regulated the gut microbiome diversity, increasing beneficial bacteria (e.g., Clostridia_UCG-014, f_Muribaculaceae and Ileibacterium_valens) while decreasing harmful bacteria (Escherichia-Shigella and Romboutsia). Multiomics analysis revealed that CL_PP upregulated bioactive lipid metabolites, particularly those derived from polyunsaturated fatty acids (e.g., resolvin D2, prostaglandin A1, and glycerophosphocholine) related gene expressions (Pltp, Alox15 and Pld4). Additionally, CL-PP downregulated the oxidative stress markers (oxidized glutathione and glutathione peroxidase 3), and immune cell markers (CD8 and CD68). Fecal microbiota transplantation confirmed that the fecal microbiota from CL_PP-treated mice exhibited anti-colitis effects. These effects were diminished in antibiotic-treated mice, underscoring the importance of the gut microbiota in mediating the CL_PP's anti-inflammatory benefits. This study suggests that CL_PP is a potential modulator of gut microbiome dysbiosis for the prevention and treatment of colitis.

Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica, species Angelica dahurica (Hoffm.)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.

Fluxapyroxad is the most commonly used succinate dehydrogenase inhibitor fungicide. This work investigated its adverse effects on colitis susceptibility and explored the underlying mechanisms based on a mouse model. After 13 weeks of exposure at the acceptable daily intake (ADI) level, fluxapyroxad exacerbated the susceptibility to colitis, impaired the intestinal barrier, and elevated proinflammatory cytokines and chemokines of the colon in mice. It was found that this toxic effect was caused by the disruption of the gut microbiome. Specifically, the abundance of Lachnospiraceae and Muribaculaceae decreased, while Desulfovibrionaceae and Eggerthellaceae increased. Altered microbiota reduced fecal indole derivatives, including indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), and indole-3-acrylic acid (IArA), inhibiting aryl hydrocarbon receptor (AHR) activation, disrupting immune homeostasis by overactivating Th17 cells and insufficient Treg cell differentiation, and causing mild colonic inflammation. Oral antibiotic-treated mice and fecal transfer experiments validated the pathway. Susceptibility to colitis induced by fluxapyroxad was not detected in the oral antibiotic-treated mice. Fecal transfer of the disordered gut microbiota caused by fluxapyroxad could aggravate the severity of colitis in recipient oral antibiotic-treated mice that did not receive fluxapyroxad exposure. In conclusion, chronic fluxapyroxad exposure at the ADI level exacerbated colitis via a gut microbiota-indole derivatives-Treg/Th17 cell balance axis, offering a new risk assessment perspective of fluxapyroxad.

The effects of dietary supplementation with epigallocatechin-3-gallate (EGCG) on growth performance, antioxidant capacity, immune function, and gut microbiota in geese were investigated. Seventy-two healthy 35-day-old male geese were randomly divided into a control group (basal diet) or an EGCG group (basal diet + 200 mg/kg EGCG), with 36 geese per group, which was further subdivided into 6 replicates (6 geese per replicate). The experiment lasted 21 days. Geese in the EGCG group exhibited significantly higher final body weight (2.93 kg vs. 2.28 kg, P < 0.01) and average daily gain (72.38 g/d vs. 41.4 g/d, P < 0.01) along with a 42.8 % reduction in the feed conversion ratio (3.95 vs. 6.91, P < 0.01) versus the control. Liver weights in the EGCG group were significantly elevated compared to the CON group on days 14 and 21 (P < 0.05) and a strong correlation between liver weight and body weight. EGCG significantly increased catalase, glutathione peroxidase, and superoxide dismutase activities, and the total antioxidant capacity in serum and jejunum while decreasing malondialdehyde (MDA) levels (P < 0.05). Immunological analyses revealed elevated serum immunoglobulin (Ig)A, IgG, and IgM and lysozyme in the EGCG group (P < 0.05), accompanied by a decrease in the pro-inflammatory cytokines interleukin-6 and interferon-γ. Intestinal morphology demonstrated increased villus height-to-crypt depth ratios in the duodenum and ileum (P < 0.05). 16S rRNA sequencing indicated that EGCG increased the relative abundance of Akkermansia and Verrucomicrobiota (P < 0.05) in the cecal content and enriched microbial functions related to inorganic ion transport and metabolism. Correlation analysis revealed positive associations between Akkermansia and IgA, and between Firmicutes and oxidative damage markers (MDA). Overall, dietary supplementation with 200 mg/kg EGCG could improve growth performance, antioxidant capacity, immune response, and gut microbiota structure in geese, supporting its potential as a plant-based feed additive.

The gut microbiota plays a role in triggering innate immunity and regulating the immune microenvironment (IME) of hepatocellular carcinoma (HCC) by acting on various signaling receptors and transcription factors through its metabolites and related molecules. Furthermore, there is an increasing recognition of the gut microbiota as a potential therapeutic target for HCC, given its ability to modulate the efficacy of immune checkpoint inhibitors (ICIs).

This review will discuss the mechanisms of gut microbiota in modulating immunotherapy of HCC, the predictive value of efficacy, and the therapeutic strategies for modulating the gut microbiota in detail.

We conducted a systematic literature search in PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Chinese databases for articles involving the influence of gut microbiota on HCC immunotherapy.

The mechanisms underlying the effect of gut microbiota on HCC immunotherapy include gut-liver axis, tumor immune microenvironment (TIME), and antibodies. Patients who benefit from ICIs exhibit a higher abundance of gut microbiota. Antibiotics, fecal microbiota transplantation (FMT), probiotics, and prebiotics are effective methods to regulate gut microbiota.

The strong connection between the liver and gut will provide numerous opportunities for the development of microbiome-based diagnostics, treatments, or prevention strategies for HCC patients.

In recent years, an increasing number of studies have revealed a close relationship between the gut microbiota and a variety of human diseases. At the same time, it has also been shown that dysregulation of the oral microbiota may lead to changes in the gut microbiota. However, it remains unclear whether the gut microbiota affects the occurrence and development of oral diseases. Therefore, the aim of this study was to explore the potential effects of gut microbiota on dental caries and to reveal possible mechanisms of the gut-oral microbiota axis.

First, gut microbiota and dental caries data from genome-wide association studies (GWAS) were analyzed using Mendelian randomization analysis. Inverse variance weighted (IVW) was used as the main criterion (P value < 0.05). Then, MR-Egger regression, IVW regression and leave-one-out tests were used to test the reliability and stability of the mendelian randomization results. Finally, the potential mechanisms and significance of the relationship between gut microbiota and dental caries were explored.

The analysis showed that Eubacteriumbrachygroup [odds ratio (OR) = 1.001, 95% confidence interval (CI): 1.000-1.002, P = 0.046] and Terrisporobacter (OR = 1.002, 95% CI: 1.0001-1.0041, P = 0.035) were positively correlated with dental caries. Escherichia.Shigella (OR = 0.997, 95% CI: 0.995-0.999, P = 0.047), Oscillibacter (OR = 0.998, 95% CI: 0.997-0.999, P = 0.038), RuminococcaceaeUCG014 (OR = 0.998, 95% CI: 0.996-0.999, P = 0.044) and Oscillospira (OR = 0.997, 95% CI: 0.995-0.999, P = 0.038) were negatively correlated with dental caries.

The present study demonstrated a significant causal relationship between the gut microbiota and the development of dental caries, providing new insights into influencing the development of dental caries by affecting the composition of the gut microbiota.

The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.

Diabetes is one common clinical symptoms of metabolic disorders. The peel of Zea mays L. is a folk remedy for diabetes that has not been thoroughly studied. The effects and mechanisms on diabetes complicated glucose and lipid metabolism disorders are still unknown now.

The research is intended to elucidate the constituent of phenylpropanoid enriched of Zea mays L. (YMP), and investigate the treatment and mechanism on amending glucose and lipid metabolism disorders.

The constituents of YMP were systematacially identified by HPLC-Q-TOF-MS/MS and NMR. To assess the effects of varying YMP doses, diabetic mice induced by streptozotocin and a high-fat diet were divided into groups. Targeted serum metabolomics investigations were conducted using UHPLC-LTQ-Orbitrap MS. Moreover, 16S rRNA analysis was employed to elucidate the intricate mechanisms through the gut microbiota modulates lipid and glucose metabolism.

It demonstrated that the primary component of YMP was luteolin. At a high dosage of 160 mg/kg/day, YMP considerably reduced the values of the oral glucose tolerance test, insulin, and blood glucose (p < 0.001). After administration, insulin resistance indexes decreased. YMP reversed the accumulation of glycogen in the liver and reduced hepatic lipid deposition. Compared to MOD group, the concentration of luteolin is higher and its metabolite, indicating that luteolin may be adequately absorbed and have an influence on the circulatory system. The results of 16S rRNA sequencing demonstrated that YMP and gut microbiota interacted to positively regulate beneficial bacteria such as Bifidobacterium, Ligilactobacillus, and Lactobacillus.

This work investigated the regulating effect of YMP on the liver glycolipid metabolism for the first time, and it also showed the underlying mechanism through gut microbiota. According to these studies, YMP has a lot of potential to be used as a supplemental treatment for complex metabolic illnesses like diabetes. It offered empirical support for the use of alternative medicine in the area to treat complex problems of glucose and lipid metabolism in diabetes.

Gut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.

Firstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-κB signaling pathway.

PDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses. Video Abstract.

Inflammatory bowel disease (IBD) represents a significant challenge to global health, characterized by intestinal inflammation, impaired barrier function, and dysbiosis, with limited therapeutic options. In this study, we isolated a novel strain of Bacillus subtilis (B. subtilis) and observed promising effects in protecting against disruption of the gut barrier. Our findings indicate that the enhancement of intestinal barrier function is primarily attributed to its metabolites. We identified a novel metabolite, 2-hydroxy-4-methylpentanoic acid (HMP), derived from B. subtilis, that significantly improved intestinal barrier function. We also show that growth arrest and DNA damage 45A (GADD45A) is a key regulator of mucosal barrier integrity, which is activated by HMP and subsequently activates the downstream Wnt/β-catenin pathway. Our findings potentially contribute to the development of probiotics-derived metabolites or targeted "postbiotics" as novel therapeutics for the treatment or prevention of IBD and other diseases associated with intestinal barrier dysfunction.

The currently available polyphenols delivery systems require the complicated preparation process and participation of multiple food-graded materials. Yeast membranes (YMS), as unitary encapsulation material, not only can load natural products by their porous structure but also can be specifically degraded by β-glucanase in intestine. Therefore, this study fabricated Malus baccata (Linn.) polyphenols loaded nanoparticles based on yeast membranes (YMS@MBP) by hydrogen bonding and hydrophobic interaction. YMS@MBP with the lamellar aggregated morphology possessed the non-crystalline feature and excellent thermal stability, and their average particle size was 997.2 ± 22.1 nm. Through establishing the model of gastrointestinal digestion in vitro, YMS@MBP presented the sustained release and intestinal targeting release characteristics, and the maximum release rates in gastric and small intestine were 16.04 % and 79.39 %, respectively. HPLC-MS/MS analysis showed that MBP were mainly composed by quercetin and its derivatives, phloretin, catechins, anthocyanins and phenolic acids. After digestion, the phenolic composition of MBP was perfectly protected by encapsulation of YMS, which was much closer to that of undigested MBP. This study provides a new strategy for construction of polyphenols delivery system applied in functional food field.

Gut microbiota plays a crucial role in the development and progression of atherosclerosis. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and the Edgeworthia genus, has been previously shown in our studies to attenuate atherogenesis when administered orally as an ethanolic extract (EEEG). However, the interaction between EEEG and gut microbiota, and the mechanism by which gut microbiota exerts anti-atherosclerotic effects, remains unclear.

This study aims to determine whether the anti-atherosclerotic properties of EEEG are associated with gut microbiota remodeling.

Atherosclerosis was induced in ApoE-/- mice using a high-fat diet (HFD). The mice were treated with EEEG or Lactobacillus plantarum for 16 weeks. The composition of gut microbiota was analyzed through 16S rDNA sequencing. To assess whether the anti-atherosclerotic effects of EEEG depend on the gut microbiota, HFD-fed mice were treated with a cocktail of antibiotics or underwent fecal microbiota transplantation (FMT). Simultaneously, plaque areas in the aortic roots and whole aortas of apolipoprotein E deficient (ApoE-/-) mice were evaluated using oil red O staining and hematoxylin-eosin staining. Serum levels of LPS, fluorescein isothiocyanate-dextran, and expression levels of tight junction proteins were measured to identify the effects of EEEG on gut barrier dysfunction in HFD-fed ApoE-/- mice.

The results revealed that EEEG treatment significantly reduced atherosclerotic lesions by ameliorating lipid accumulation and preserving gut barrier integrity. The protective effects were abrogated by antibiotics administration, concomitant with an increase in gut barrier permeability by decreasing expression of tight junction proteins. The microbial analysis indicated an augmented abundance of Lactobacillus, Turicibacter, Faecalibacterium, Akkermansia, and Desulfovibrio following EEEG treatment. Meanwhile, transplantation of fecal microbiota from EEEG-treated mice exerted the anti-atherosclerotic effect in the high-fat diet (HFD)-fed ApoE-/- recipient mice, accompanied by improvement of gut barrier integrity through upregulation of tight junction protein expression. Furthermore, exogenous supplementation of Lactobacillus plantarum mitigated AS in ApoE-/- mice and improved the gut epithelial barrier function by increasing the expression level of Zo-1.

These results suggest that the anti-atherosclerotic efficacy of EEEG is attributed to the preservation of gut barrier integrity mediated by gut microbiota. EEEG and its enriched Lactobacillus plantarum may be promising adjuncts for AS management.

Atherosclerosis (AS) is the primary pathological basis of cardiovascular disease (CVD). The gut microbiota is known to play an important role in the development and progression of atherosclerosis. In the clinical management of AS, pharmacological classes such as antioxidants, lipid-lowering drugs, and antiplatelet agents are commonly utilized. Despite their ability to decelerate the progression of AS, complications and adverse reactions still limit their application. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and Edgeworthia Meisn genus, has been shown in previous studies to attenuate atherogenesis when orally administered as an ethanolic extract (EEEG). However, the interaction between EEEG and the gut microbiota, as well as the mechanism by which the gut microbiota exerts its anti-atherosclerotic effects, remain unclear. The significance of our research lies in identifying the mechanism behind the anti-atherosclerotic effect of Edgeworthia gardneri. The expected results will provide an important scientific basis for the clinical development and application of Edgeworthia gardneri in the prevention and treatment of AS.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Oxidative stress, dysbiosis, and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease (IBD). Herein, we design copper ion-luteolin nanocomplexes (CuL NCs) through a metal-polyphenol coordination strategy, which plays a multifaceted role in the amelioration of IBD. The fabricated CuL NCs function as therapeutic agents with exceptional antioxidant and anti-inflammatory capabilities because of their great stability and capacity to scavenge reactive oxygen species (ROS). It can effectively modulate the inflammatory microenvironment including facilitating the efficient reduction of pro-inflammatory cytokine levels, protecting intestinal epithelial cells, promoting mucosal barrier repair and regulating intestinal microbiota. In addition, CuL NCs have been found to enhance cellular antioxidant and anti-inflammatory capacities by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) oxidative stress pathway and nuclear factor kappa B (NF-κB) signaling pathway, respectively. Notably, CuL NCs demonstrate significant prophylactic and therapeutic efficacy in mouse models with typical IBD, including ulcerative colitis (UC) and Crohn's disease (CD). This study provides a new approach for building multifaceted therapeutic platforms for natural products to treat IBD.

Thymol (THY) is a phenolic monoterpene compound that has garnered attention due to its various biological properties, including antioxidant, anti-inflammatory, and immune-regulatory effects. The purpose of this study was to determine the therapeutic and protective effects of THY in colitic mice, with a particular focus on the mechanisms involving gut microbiota. The results showed that early intervention with THY (40 and 80 mg/kg) not only alleviated the clinical symptoms and colonic damage in mice with dextran sodium sulfate (DSS)-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, and IL-18) and enhanced the expression of mucins (MUC1 and MUC2) and trefoil factor family 3 (TFF3), thereby improving the integrity of the intestinal epithelial barrier. In addition, THY altered the composition of the gut microbiota in colitis mice by increasing the abundance of Bacteroides and reducing the abundance of Proteobacteria. Fecal microbial transplantation (FMT) results demonstrated that FM from THY donor mice significantly improved symptoms of inflammatory bowel disease (IBD), confirming the crucial role of the gut microbiota. Metagenomic and untargeted metabolomic studies found that the characteristic microbiota of THY is Prevotellaceae, and THY significantly upregulated the amino acid metabolic pathways related to arginine and proline metabolism, arginine biosynthesis, and glycerophospholipid metabolism. In summary, THY holds significant potential as a functional additive to enhance host intestinal activity.

Ulcerative colitis (UC) pathogenesis is strongly linked to gut microbiota dysbiosis and compromised intestinal barrier integrity. Emerging evidence suggests that targeted dietary interventions may restore microbial homeostasis and ameliorate colitis progression. In this study, we evaluated the therapeutic potential of Fu Brick tea (FBT) using a dextran sulfate sodium (DSS)-induced murine colitis model. The results indicated that oral administration of FBT extract significantly improved the disease index, reduced inflammatory response, protected intestinal barrier protein (e.g., ZO-1), and maintained intestinal structure integrity. Furthermore, FBT intake increased the diversity of gut microbiota, promoted the growth of beneficial bacteria (e.g., Akkermansia), inhibited the proliferation of harmful bacteria (e.g., Desulfovibrioceae, Escherichia, and Helicobacter), restored intestinal homeostasis, and alleviated colitis symptoms including diarrhea. These findings position FBT as a promising nutraceutical candidate for UC management via multi-target modulation of mucosal immunity and microbial ecology.

Qiwenghuangbo powder (QP), composed of Astragalus, Phellodendron chinensis, and Radix pulsatilla, is a traditional Chinese herbal formula, but its effects on weaned piglets remained unclear.

Weaned piglets fed with 0.5 kg/t QP (QP1), 1 kg/t QP (QP2), low-zinc oxide (ZnO; negative control), and high-ZnO (positive control) diets in two phases, respectively, and the growth performance, intestinal morphology, cytokines, and microbial communities were profiled. The mouse models of colitis induced by Citrobacter rodentium and dextran sulfate sodium (DSS) were employed to elucidate the potential role of QP-fed enriched key species.

Dietary 1.0 kg/t QP alleviated diarrhea and inflammation and improved intestinal development and growth performance of weaned piglets. Moreover, this dietary intervention notably altered microbiota composition, characterized by the enrichment of Limosilactobacillus reuteri. Furthermore, out of three isolated L. reuteri, two strains could alleviate pathogen infection and intestinal inflammation, respectively. Specifically, the anti-inflammatory effect of one strain was achieved by promoting the colonization resistance of C. rodentium as significantly reduced pathogen loads. The other strain mitigated DSS-induced colitis by enhancing the goblet cell function and inhibiting the secretion of pro-inflammatory cytokines, particularly interleukin-1β (IL-1ß) and tumor necrosis factor-α (TNF-α).

Dietary QP improved the growth performance and intestinal health of weaned piglets by promoting the colonization of L. reuteri. The isolated commensal L. reuteri control colitis in a strain-specific mechanism, highlighting the potential of QP and L. reuteri in providing evidence for gut health promotion.

The clinical use of conventional medications for inflammatory bowel disease (IBD) is often limited by significant side effects. The extracellular vesicles derived from plant-based diets have shown promise in mitigating disease. Here, we discovered that natural extracellular vesicles from tea (TEVs) can achieve an appropriate transition from proinflammatory (M1) to anti-inflammatory (M2) macrophages and inhibit inflammation response both in vitro and in vivo. More importantly, the therapeutic effects of TEVs were at least partially attributed to RNA in a DSS-induced colitis model. Small RNA sequencing revealed a distinct enrichment of miRNAs in TEVs, with target genes primarily linked to IBD. TEVs were absorbed by macrophages in a time-dependent manner, carrying miRNAs that modulate gene expression within host cells. Notably, TEV-derived osa-miR166d-5p and gma-miR396a-3p were shown to enhance M2 macrophage polarization and reduce inflammation in vitro. Mechanistically, the osa-miR166d-5p- and gma-miR396a-3p-mediated targeting of the 3'-UTRs of AKT1 and IKBKB decreased NF-κB levels. Overall, we demonstrated that TEVs can ameliorate mouse colitis by reprogramming macrophage polarization and contain a unique miRNA repertoire, including osa-miR166d-5p and gma-miR396a-3p, with a novel function of alleviating intestinal inflammation.

Elevated oxidative stress and inflammation, bacterial infections, and vascular impairment undoubtedly impede the normal diabetic wound healing process, which has encouraged the development of high-performance dressings for wound management. Herein, a new type of multiple-crosslinked injectable hydrogel, GCP, was developed via the radical polymerization of propenyl groups and the formation of copper‒polyphenol coordination bonds and Schiff base bonds. The copper‒polyphenol coordination and Schiff base bonds in the GCP hydrogel were disrupted in the acidic microenvironment of diabetic wound, resulting in the release of copper ions and protocatechualdehyde (PA) to scavenge reactive oxygen species (ROS), promote angiogenesis and cell migration, and exert antibacterial and anti-inflammatory activities via the CuPA complexes. Consequently, markedly accelerated infected diabetic wounds healing was achieved through this tissue microenvironment remodeling strategy. Moreover, the underlying mechanism of the antibacterial properties was investigated by 16S rRNA sequencing. The results indicated that the CuPA complexes can clearly inhibit the growth and reproduction of S. aureus by downregulating specific genes associated with ABC transporters, hindering bacterial protein synthesis, and enhancing oxidoreductase activity. This innovative hydrogel platform for wound management may inspire new methods for the preparation of high-performance biomedical materials and the treatment of other clinical diseases.

The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.

This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.

Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.

GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).

L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.

The prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing annually, which is a global public health issue. Although clinical trials are lacking, observational studies indicate that bariatric surgery can alleviate the progression of MASH. Here, we performed sleeve gastrectomy (SG) and Sham surgery on 8-week-old mice, and then fed a AMLN diet for 24 weeks to construct a diet-inducted MASH mice model after 4-week post-surgery recovery. Applying a multi-omics approach combining metagenomics, metabolomics, and transcriptomics, we found that SG prevents the development of hepatic steatosis, inflammation, and fibrosis in MASH mice not only by significantly altering the structure of gut microbiota including s_Akkermansia muciniphila, s_Alistiples dispar, g_Helicobacter and s_uc_Oscillospiraceae, but also by modulating the levels of serum metabolites including l-arginine and taurocholic acid (TCA). These results suggest that SG and the alteration of gut microbiota and its related serum metabolites can be served as the effective therapeutic strategies for MASH.