This review and commentary outline the strong rationale for normalizing the abnormal microbiota of patients with ulcerative colitis, Crohn's disease, and pouchitis and focus on strategies to improve current variable outcomes of fecal microbial transplant (FMT) in ulcerative colitis. Applying lessons from successful FMT therapy of recurrent Clostridioides difficile and insights from basic scientific understanding of host/microbial interactions provide strategies to enhance clinical outcomes in IBD. We outline promising approaches to develop novel-defined consortia of live biotherapeutic products and combination treatments to improve current results and to optimize and personalize treatment approaches in individual patients and disease subsets.

Inflammatory bowel disease (IBD) is a chronic relapsing gastrointestinal disorder. Infliximab (INF) has shown good efficacy in IBD treatment, but its specific impact requires further exploration. This study aimed to assess the effects of intravenous INF on clinical symptom scores and serum cytokine levels in IBD patients.

A retrospective review of 126 IBD patients treated with INF was conducted. Baseline data, Mayo scores, Crohn's Disease Activity Index (CDAI) scores at 6 and 12 months, and serum levels of TNF-α, IL-6, IL-10, and CRP were recorded. Correlations between disease activity scores and inflammatory markers were analyzed, and the relationship between baseline indicators and treatment efficacy was examined.

At 12 months, Mayo and CDAI scores, TNF-α, IL-6, and CRP levels were significantly reduced, while IL-10 levels increased. Disease activity scores positively correlated with TNF-α, IL-6, and IL-1β, and negatively with IL-10. Factors such as Crohn's disease subtype, age, high baseline CDAI or Mayo scores, elevated TNF-α, IL-6, CRP, and longer disease duration were associated with poorer outcomes (p < 0.05). Multivariate analysis identified disease type, high baseline disease activity, long disease duration, and elevated inflammatory markers as independent risk factors. Adverse reactions were infrequent, with no serious adverse events reported.

Intravenous INF effectively improves clinical symptoms and modulates inflammatory cytokines in IBD patients, with favorable safety and increasing efficacy over time. However, the limited sample size and lack of long-term data warrant further validation in larger, prospective multicenter studies.

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.

Coccidiosis, caused by Eimeria parasites, is a major enteric disease in poultry, significantly impacting animal health, production performance, and welfare. This disease imposes a substantial economic burden, costing the global poultry industry up to $13 billion annually. However, effective mitigation strategies for coccidiosis remain elusive. While different chicken breeds exhibit varying resistance to coccidiosis, no commensal bacteria have been directly linked to this resistance.

To assess relative resistance of different breeds to coccidiosis, 10-day-old Fayoumi M5.1, Leghorn Ghs6, and Cobb chickens were challenged with 50,000 sporulated Eimeria maxima oocysts or mock-infected. Body weight changes, small intestinal lesions, and fecal oocyst shedding were evaluated on d 17. Ileal and cecal digesta were collected from individual animals on d 17 and subjected to microbiome analysis using 16S rRNA gene sequencing.  RESULTS: Fayoumi M5.1 chickens showed the lowest growth retardation, intestinal lesion score, fecal oocyst shedding, and pathobiont proliferation compared to Ghs6 and Cobb chickens. The intestinal microbiota of M5.1 chickens also differed markedly from the other two breeds under both healthy and coccidiosis conditions. Notably, group A Lactobacillus and Ligilactobacillus salivarius were the least prevalent in both the ileum and cecum of healthy M5.1 chickens, but became highly enriched and comparable to Ghs6 and Cobb chickens in response to coccidiosis. Conversely, Weissella, Staphylococcus gallinarum, and Enterococcus durans/hirae were more abundant in the ileum of healthy M5.1 chickens than in the other two breeds. Despite being reduced by Eimeria, these bacteria retained higher abundance in M5.1 chickens compared to the other breeds.

Fayoumi M5.1 chickens exhibit greater resistance to coccidiosis than Leghorn Ghs6 layers and Cobb broilers. Several commensal bacteria, including group A Lactobacillus, L. salivarius, Weissella, S. gallinarum, and E. durans/hirae, are differentially enriched in Fayoumi M5.1 chickens with strong correlation with coccidiosis resistance. These bacteria hold potential as probiotics for coccidiosis mitigation.

Inflammatory bowel disease (IBD) is a complex condition linked to the gut microbiota, host metabolism, and the immune system. Edible mushroom polysaccharides (EMPs) are gaining attention for their benefits, particularly as prebiotics that help balance gut microbial, a key factor in IBD. With their scalable production, diverse hydrophilic properties, and demonstrated anti-inflammatory effects in both laboratory and animal studies, EMPs show promise for easing IBD symptoms. By supporting a healthy gut microbiome through various mechanisms, EMPs can play an important role in preventing and managing IBD, ultimately benefiting overall health and opening new treatment avenues. This review examines how EMPs affect IBD, focusing on their role in shaping gut microbiota, restoring gut barriers, regulating immune function, and influencing pathways related to colitis. It also explores their impact on the microbiota-gut-multi organ axis and overall host health, as well as the relationship between EMPs preparation, structure, and bioactivity, along with their potential applications in food and medicine. This investigation provides valuable insights into the intricate connections between the gut, immune system, and systemic inflammation system, highlighting how EMPs are key players in this complex interaction.

Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome. Understanding these changes in the predisease phase provides a means of predicting IBD in high-risk populations and offers insights into possible mechanisms involved in disease pathogenesis. Finally, we discuss strategies to use this information to design interventions aimed at modulating the microbiome as a means of preventing or delaying the onset of IBD.

Microbial dysbiosis links to mucosal immune dysregulation, but the specific bacterial contributions to oral mucosal inflammation remain unclear. Escherichia coli (E. coli), a pathogen well-characterized in mucosal immunity and immune regulation studies, has been observed to be enriched in chronic oral inflammatory lesions and was reported to modulate T helper 17 cells (Th17)/T regulatory cells (Treg) homeostasis. Here, we developed an oral mucositis mouse model via tongue scratch and E. coli topical application to investigate its role in Th17/Treg imbalance.

The inflammatory infiltration was evaluated by macroscopic photography and HE staining. The expression of inflammatory factors in tongue tissue and peripheral blood of mice were detected by immunohistochemical staining and enzyme-linked immunosorbent assay. The number of Th17 and Treg in mice spleen lymphocytes were evaluated with flow cytometry. Differential gene expression analysis, functional enrichment analysis and immune infiltration analysis were performed using RNA-seq data from oral lichen planus (OLP).

E. coli stimulation aggravated inflammatory responses induced by scratching in lingual mucosa of mice, including increased local and systemic expression of interleukin 6 (IL6), interleukin 17 (IL17), chemokine receptor 6 (CCR6) and chemokine C-C motif ligand 20 (CCL20), increased proportions of Th17 cells and increased Th17/Treg ratio in spleen lymphocytes. Analysis of RNA-seq data from OLP revealed alterations in antimicrobial responses and inflammatory factors associated with upregulation of Th17/Treg balance.

This study supports the role of E. coli in promoting oral mucosal inflammation and provides an experimental basis for in vivo study of OLP from the perspective of microorganisms.

The gut microbiome contributes to chronic inflammatory responses in ulcerative colitis (UC), but molecular mechanisms and disease-relevant effectors remain unclear. Here we analyze the pro-inflammatory properties of colonic fluid obtained during colonoscopy from UC and control patients. In patients with UC, we find that the pelletable effector fraction is composed mostly of bacterial extracellular vesicles (BEVs) that exhibit high IgA-levels and incite strong pro-inflammatory responses in IgA receptor-positive (CD89+) immune cells. Biopsy analyses reveal higher infiltration of CD89+ immune cells in the colonic mucosa from patients with UC than control individuals. Further studies show that IgA-coated BEVs, but not host-derived vesicles nor soluble IgA, are potent activators of pro-inflammatory responses in CD89+ cells. IgA-coated BEVs also exacerbate intestinal inflammation in a dextran sodium sulfate colitis model using transgenic mice expressing human CD89. Our data thus implicate a link between IgA-coated BEVs and intestinal inflammation via CD89+ immune cells, and also hint a potential new therapeutic target for UC.

Inflammatory bowel disease (IBD) is a prevalent condition worldwide, characterized by complex etiologies, limited efficacy of clinical drug treatments, and potential adverse effects. In this study, we designed 269 nm selenium nanoparticles with double-cell targeting for ulcerative colitis treatment. Somatostatin (SST) and mannooligosaccharide (MOS) were employed to functionalize an Eucommia ulmoides polysaccharide selenium nanoparticle (EUP-SeNP), resulting in the formulation of SST/MOS@EUP-SeNP. Nanoparticles were engineered to target intestinal epithelial cells and macrophages through specific cell surface receptors, enabling dual-targeted treatment. In addition, sodium alginate (SA) microspheres incorporating SST/MOS@EUP-SeNP were prepared for oral administration, protecting the nanoparticles from gastric fluid. The results showed that SA/SST/MOS@EUP-SeNP could preferentially target the inflamed colon tissue and adhere to the colon, enhance the intestinal barrier function, regulate the level of colon inflammation, enhance antioxidant capacity, and regulate the composition of intestinal microbes to effectively relieve the colitis induced by sodium glucan sulfate (DSS). Meanwhile, SA/SST/MOS@EUP-SeNP had excellent biocompatibility both in vivo and in vitro. To some extent, this study can provide a reference for the treatment of IBD.

Thlaspi arvense (TA), commonly known as "Ximi" or "Subaijiang," is a traditional Chinese medicinal herb used to prevent and treat ulcerative colitis (UC). However, the precise mechanisms underlying its therapeutic effects remain unclear, necessitating further investigation to identify potential pharmaceutical applications for UC management. This study aims to elucidate the efficacy and mechanisms of TA and its active constituents in UC treatment.

This study first evaluated the effects of varying TA doses on 3% dextran sulfate sodium (DSS)-induced UC. Gut microbiota alterations in UC mice were analyzed via 16S rRNA sequencing, with correlation analyses to reveal the relationship between gut microbiota and cytokines. Then, network pharmacology was utilized to identified potential TA targets for UC treatment. Protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to explore TA's mechanisms. Molecular docking and dynamics simulations validated interactions between TA's active compounds and UC-related targets. Finally, TNF pathway modulation by TA and its active component, isovitexin, was verified in vitro and in vivo.

TA alleviated DSS-induced weight loss in a dose-dependent manner, reduced disease activity indices, and preserved intestinal mucosal barrier integrity. Subsequently, fluorescence in situ hybridization (FISH) revealed TA suppressed microbial translocation in intestinal tissues. To further characterize inflammatory responses, ELISA demonstrated that TA modulated levels of key cytokines (TNF-α, IL-1β, IL-6, IL-10) and oxidative stress markers (SOD, MDA), indicating systemic anti-inflammatory effects. Building on these findings, 16S rRNA sequencing analyses showed that TA regulated gut microbiota alpha/beta diversity and inhibited infectious disease-related pathways. Notably, correlation heatmaps highlighted a strong association between TNF-α levels and Escherichia-Shigella abundance, with high-dose TA significantly reducing this pathogenic bacterial genus. To systematically explore molecular mechanisms, network pharmacology identified 220 potential TA targets for UC treatment. Consistent with experimental data, PPI and KEGG analyses implicated TNF-α, IL-6, and AKT as key targets, primarily through TNF signaling pathway modulation. To validate these predictions, molecular docking confirmed stable interactions between TA compounds and identified targets, while dynamics simulations specifically emphasized isovitexin's high affinity for TNF-α. Finally, experiments in vivo demonstrated TA's inhibition of TNF-α-mediated NF-κB pathway activation, and in vitro studies confirmed that isovitexin directly mitigated TNF-α-induced intestinal epithelial damage. Furthermore, TA demonstrated potent inhibition of TNF-α-mediated NF-κB inflammatory pathway activation in intestinal tissues, while its active constituent isovitexin effectively mitigated TNF-α-induced epithelial cell damage, collectively highlighting their complementary anti-inflammatory mechanisms.

Collectively, Thlaspi arvense (TA) ameliorates ulcerative colitis through synergistic mechanisms involving gut microbiota modulation, inflammatory pathway suppression, and intestinal barrier preservation. By remodeling microbial communities to reduce Escherichia-Shigella colonization and microbial translocation. TA concurrently inhibits TNF-α/NF-κB-driven inflammation, and oxidative stress regulation. Furthermore, its active constituent isovitexin directly attenuates TNF-α-induced epithelial damage, demonstrating multi-scale therapeutic efficacy. These findings establish TA's multi-target pharmacology spanning host-microbe interactions and intracellular signaling, while providing a rationale for standardizing TA-based formulations and advancing isovitexin as a precision therapeutic agent for inflammatory bowel diseases.

Mediterraneibacter gnavus, also known as Ruminococcus gnavus, is a Gram-positive anaerobic bacterium that resides in the human gut microbiota. Notably, this bacterium plays dual roles in health and disease. On one side it supports nutrient metabolism essential for bodily functions and on the other it contributes to the development of Inflammatory Bowel Disease (IBD) and other gastrointestinal disorders. R. gnavus strain RJX1120 is an encapsulated strain and has been linked to develop IBD. Despite the advances made on its role in gut homeostasis, limited information is available on strain-specific virulence factors, metabolic pathways, and regulatory mechanisms. The study of such aspects is crucial to make microbiota-targeted therapy and understand its implications in host health. A multi-epitope vaccine against R. gnavus strain RJX1120 was designed using reverse vaccinology-based subtractive proteomics approach. Among the 3,219 proteins identified in the R. gnavus strain RJX1120, two critical virulent and antigenic proteins, a Single-stranded DNA-binding protein SSB (A0A2N5PT08) and Cell division ATP-binding protein FtsE (A0A2N5NK05) were screened and identified as potential targets. The predicted B-cell and T-cell epitopes from these proteins were screened for essential immunological properties such as antigenicity, allergenicity, solubility, MHC binding affinity, and toxicity. Epitopes chosen were cross-linked using suitable spacers and an adjuvant to develop a multi-epitope vaccine. Structural refinement of the construct revealed that 95.7% of the amino acid residues were located in favored regions, indicating a high-quality structural model. Molecular docking analysis demonstrated a robust interaction between the vaccine construct and the human Toll-like receptor 4 (TLR4), with a binding energy of -1277.0 kcal/mol. The results of molecular dynamics simulations further confirmed the stability of the vaccine-receptor complex under physiological conditions. In silico cloning of the vaccine construct yielded a GC content of 48% and a Codon Adaptation Index (CAI) value of 1.0, indicating optimal expression in the host system. These results indicate the possibility of the designed vaccine construct as a candidate for the prevention of R. gnavus-associated diseases. However, experimental validation is required to confirm its immunogenicity and protective efficacy.

Inspired by the survival strategies of pyomelanin-producing microbes, we synthesize pyomelanin nanoparticles (PMNPs) from homogentisic acid- γ-lactone via auto-oxidation and investigate their biomedical potential. PMNPs possess distinct physicochemical properties, including reactive oxygen species scavenging and microenvironment-responsive self-disassembly. Under intestinal conditions, PMNPs self-disassemble and penetrate the nanoscale pores of the mucin layer. In an inflammatory bowel disease model, orally administered PMNPs withstand gastric acidity and, in their solubilized form, interact with macrophages and epithelial cells. They significantly reduce reactive oxygen species levels, exert anti-inflammatory effects, and restore gut microbiota composition. Compared to conventional nanoparticles and 5-aminosalicylic acid, PMNPs exhibit greater therapeutic efficacy. Clinical symptoms and intestinal inflammation are alleviated, and the gut microbiota is restored to near-normal levels. These findings underscore the therapeutic potential of PMNPs for inflammatory bowel disease treatment and suggest broader biomedical applications.

Inflammation and oxidative stress are important features of traumatic ulcerative colitis (UC). Turmeric has been used as a dietary and functional ingredient for its potent anti-inflammatory effects in UC therapy. However, its practical effectiveness is hindered by limited reactive oxygen species (ROS) elimination properties. To address this, we constructed a unique treatment agent by growing cerium oxide (CeO2) nanocrystals on the membranes of turmeric-derived nanovesicles (TNVs), named as TNV-Ce. The resulted TNV-Ce could suppress inflammation and exhibit exceptional ROS-scavenging activity, which was validated both in lipopolysaccharide-induced macrophages and dextran sulfate sodium salt-induced chronic colitis mouse model. Following oral administration, TNV-Ce significantly accumulated at inflamed sites, effectively eliminating ROS and inhibiting pro-inflammatory cytokines for synergistic action against UC.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), accompanied by intense inflammation, oxidative stress, and intestinal microbiota dysbiosis. Current treatments using chemotherapeutic drugs or immunosuppressants have limited effectiveness and side effects. Therefore, the development of safe, effective, and multi-targeting therapies for IBD is of great importance. Momordica charantia exhibits antioxidant, anti-inflammatory, and intestinal microbiota-regulating properties, suggesting that Momordica charantia-derived extracellular vesicles (MCEVs) have the potential for UC management.

We extracted MCEVs using differential centrifugation and density gradient centrifugation. The results showed that MCEVs possessed high purity, even particle size, and excellent stability. In vitro, MCEVs were shown to inhibit macrophage inflammatory responses, scavenge reactive oxygen species (ROS), and protect cells from oxidative damage. Transcriptomics analysis revealed that MCEVs may alleviate mitochondria-dependent apoptosis by safeguarding the integrity of the mitochondrial structure and regulating the expression of apoptosis-related proteins. Furthermore, all components of MCEVs contributed to their pharmacological activity. In vivo, MCEVs had better retention in the inflamed colon and significantly alleviated UC through a comprehensive renovation of the intestinal microenvironment.

These findings suggested that MCEVs own considerable potential as natural nanotherapeutics for UC treatment.

N6-methyladenosine (m6A), a prevalent and essential RNA modification, serves a key function in driving autoimmune disease pathogenesis. By modulating immune cell development, activation, migration, and polarization, as well as inflammatory pathways, m6A is crucial in forming innate defenses and adaptive immunity. This article provides a comprehensive overview of m6A modification features and reveals how its dysregulation affects the intensity and persistence of immune responses, disrupts immune tolerance, exacerbates tissue damage, and promotes the development of autoimmunity. Specific examples include its contributions to systemic autoimmune disorders like lupus and rheumatoid arthritis, as well as conditions that targeting specific organs like multiple sclerosis and type 1 diabetes. Furthermore, this review explores the therapeutic promise of target m6A-related enzymes ("writers," "erasers," and "readers") and summarizes recent advances in intervention strategies. By focusing on the mechanistic and therapeutic implications of m6A modification, this review sheds light on its role as a promising tool for both diagnosis and treatment in autoimmune disorders, laying the foundation for advancements in customized medicine.

Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.

TNFα has long stood as a hallmark feature of both inflammatory bowel disease and arthritis with its therapeutic potential demonstrated in neutralizing monoclonal antibody treatments such as Infliximab. Due to the high global burden of latent Mycobacterium tuberculosis (TB) infections, prior to receiving anti-TNF therapy, patients testing positive for latent TB are given prophylactic treatment with anti-tuberculoid medications including the first described TB-selective antibiotic, Isoniazid. While this is common clinical practice to prevent the emergence of TB, little is known about whether Isoniazid modifies intestinal inflammation alone. The aim of this study, therefore, was to determine whether Isoniazid presents a novel TB-independent therapeutic option for the treatment of Crohn's disease (CD)-like ileitis and uncover new mechanisms predisposing the host to intestinal inflammation.

The transgenic TNFΔARE mouse model of Crohn's-like terminal ileitis was used. The impact of Isoniazid administration (10 mg/kg/day dose in drinking water) on disease development was monitored between 8 and 12 weeks of age using a variety of behavioral and serological assays. Behavioral and motor functions were assessed using the LABORAS automated monitoring system while systemic and local tissue inflammation were determined at experimental termination using multiplex cytokine analysis. Whole-mount tissue immunofluorescence and fluorescent in situ hybridization were used to qualify changes within the host as well as the microbial compartment of the ileum and associated mesentery. Proposed cellular mechanisms of altered cytokine decay were performed on isolated primary splenocytes in vitro using selective pharmacological agents.

Compared to age-matched wild-type littermates, TNFΔARE mice display prominent progressive sickness behaviors from 8 through 12 weeks of age indicated by reduced movement, climbing, and rearing. Prophylactic administration of Isoniazid (10 mg/kg/day) is effectively able to protect TNFΔARE mice from this loss of function during the same period. Analysis revealed that Isoniazid was able to significantly reduce both systemic and intestinal inflammation compared to untreated vehicle controls impacting the epithelial colonization of known pathobiont segmented filamentous bacteria (SFB). Reduction in terminal ileal inflammation was also associated to the diminished formation of precursor-tertiary lymphoid organs within the associated ileal mesentery which were found to be associated with endospores derived SFB itself. Finally, we reveal that due to their genetic manipulation, TNFΔARE mice display accelerated posttranscriptional decay of IL-22 mRNA resulting in diminished IL-22 protein production and associated downstream antimicrobial peptide production.

Isoniazid protects against the development of intestinal and systemic inflammation in the TNFΔARE model of terminal ileitis by limiting the expansion of mucosal SFB and progression of the associated microbial-driven inflammation. This work highlights a possible mycobacterial-independent function of Isoniazid in limiting CD pathophysiology through limiting the mucosal establishment of pathobionts such as SFB and the association of such microbe-derived endospores linked to the formation of ectopic tertiary lymphoid organs seen commonly in patients.

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic.

The human gut microbiome plays a crucial role in regulating intestinal and systemic health, impacting host immune response and metabolic function. Dysbiosis of the gut microbiome is linked to various diseases, including steatotic liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), a chronic liver disease characterized by excess hepatic lipid content and impaired metabolism, is the leading cause of liver disease worldwide. Among the gut microbes, Ruminococcus gnavus (R. gnavus) has garnered attention for its association with inflammatory and metabolic diseases. While R. gnavus abundance correlates to liver fat accumulation, further research is needed to identify a causal role or therapeutic intervention in steatotic liver disease. This review surveys our current understanding of R. gnavus in the development and progression of steatotic liver diseases, highlighting its potential mechanisms through metabolite secretion, and emphasizes the need for comprehensive microbiome analyses and longitudinal studies to better understand R. gnavus' impact on liver health. This knowledge could pave the way for targeted interventions aimed at modulating gut microbiota to treat and prevent MASLD and its comorbidities.

Inflammatory bowel diseases (IBDs) are classified into two distinct types based on the area and severity of inflammation: Crohn's disease (CD) and ulcerative colitis. In CD, gut bacteria can infiltrate mesenteric fat, causing expansion known as creeping fat, which may limit bacterial spread and inflammation but can promote fibrosis. The gut bacteria composition varies depending on whether the colon or ileum is affected. Fecal microbiota transplantation (FMT) transfers feces from a healthy donor to restore gut microbiota balance, often used in IBD patients to reduce inflammation and promote mucosal repair. The use of FMT for CD remains uncertain, with insufficient evidence to fully endorse it as a definitive treatment. While some studies suggest it may improve symptoms, questions about the duration of these improvements and the need for repeated treatments persist. There is a pressing need for methods that provide long-term benefits, as highlighted by Wu et al's research.

Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.

Ulcerative colitis (UC) is a type of inflammatory bowel disease, and current treatments often fall short, necessitating new therapeutic options. Baicalin shows therapeutic promise in UC animal models, but a systematic review is needed.

A systematic search was conducted across databases including PubMed, EBSCO, Web of Science, and Science Direct, up to March 2024, identifying randomized controlled trials (RCTs) examining baicalin's impact on UC in animal models. Seventeen studies were selected through manual screening. Meta-analyses and subgroup analyses utilized Rev Man 5.3 and Stata 15.0 software to assess symptom improvement.

From 1304 citations, 17 were analyzed. Baicalin significantly modulated various biomarkers: HCS (SMD = -3.91), DAI (MD = -2.75), spleen index (MD = -12.76), MDA (SMD = -3.88), IL-6 (SMD = -10.59), IL-1β (SMD = -3.98), TNF-α (SMD = -8.05), NF-κB (SMD = -5.46), TLR4 (MD = -0.38), RORγ (MD = -0.89), MCP-1 (MD = -153.25), MPO (SMD = -7.34), Caspase-9 (MD = -0.93), Caspase-3 (MD = -0.45), FasL (MD = -1.20)) and enhanced BWC (MD = 0.06), CL (MD = 1.39), ZO-1 (MD = 0.44), SOD (SMD = 3.04), IL-10 mRNA (MD = 3.14), and FOXP3 (MD = 0.45) levels. Baicalin's actions may involve the PI3K/AKT, TLR4/NF-κB, IKK/IKB, Bcl-2/Bax, Th17/Treg, and TLRs/MyD88 pathways. Optimal therapeutic outcomes were predicted at dosages of 60-150 mg/kg over 10-14 weeks.

Baicalin demonstrates a multifaceted therapeutic potential in UC, attributed to its anti-inflammatory, antioxidant, anti-apoptotic, and intestinal barrier repair properties. While higher doses and longer treatments appear beneficial, further research, particularly human clinical trials, is necessary to verify its effectiveness and safety in people.

Maintaining gut health is a persistent and unresolved challenge in the poultry industry. Given the critical role of gut health in chicken performance and welfare, there is a pressing need to identify effective gut health intervention (GHI) strategies to ensure optimal outcomes in poultry farming. In this study, across three broiler production cycles, we compared the metagenomes and performance of broilers provided with ionophores (as the control group) against birds subjected to five different GHI combinations involving vaccination, probiotics, prebiotics, essential oils, and reduction of ionophore use.

Using a binning strategy, 84 (≥ 75% completeness, ≤ 5% contamination) metagenome-assembled genomes (MAGs) from 118 caecal samples were recovered and annotated for their metabolic potential. The majority of these (n = 52, 61%) had a differential response across all cohorts and are associated with the performance parameter - European poultry efficiency factor (EPEF). The control group exhibited the highest EPEF, followed closely by the cohort where probiotics are used in conjunction with vaccination. The use of probiotics B, a commercial Bacillus strain-based formulation, was determined to contribute to the superior performance of birds. GHI supplementation generally affected the abundance of microbial enzymes relating to carbohydrate and protein digestion and metabolic pathways relating to energy, nucleotide synthesis, short-chain fatty acid synthesis, and drug-transport systems. These shifts are hypothesised to differentiate performance among groups and cycles, highlighting the beneficial role of several bacteria, including Rikenella microfusus and UBA7160 species.

All GHIs are shown to be effective methods for gut microbial modulation, with varying influences on MAG diversity, composition, and microbial functions. These metagenomic insights greatly enhance our understanding of microbiota-related metabolic pathways, enabling us to devise strategies against enteric pathogens related to poultry products and presenting new opportunities to improve overall poultry performance and health. Video Abstract.

Putranjiva roxburghii is an important medicinal plant utilized for remedy of female reproductive ailments. Its seed extract is being used as a uterine health booster due to the presence of several pharmaceutically important phytochemicals. However, the presence of phytochemicals in its leaf is still unexplored. The present study was designed to explore phytochemical finger printing and assessment of anti-oxidant and anti-inflammatory activities of hydroalcoholic leaf extract of P. roxburghii (HALEPR). The qualitative, quantitative phytochemical of flavonoid, phenol and HRA-MS analysis of HALEPR carried out along with antioxidant and in vitro membrane stabilization and protein denaturation assay of anti-inflammatory activity were have been analyzed. Results of qualitative phytochemical screening of HALEPR denotes the existence of phenol, flavonoids, alkaloids, coumarins, steroids, saponins, tannins, anthroquinone and carbohydrates. The quantitative phytochemical of flavonoid and phenol was done which revealed the presents of total phenol and flavonoid. High resolution accurate-mass spectrometry (HRA-MS) study was also done for the identification of bioactive compounds from the HALEPR, which showed the presence of various phytochemicals such as luteolin 3'- (3″-acetylglucuronide), luteolin 4'-methyl ether 7-glucoside, quercetin-3β-D-glucoside, 8-hydroxyluteolin 4'-methyl ether 8-glucuronide, quercetin 3-xylosyl- (1- > 2) -rha mnosyl- (1- > 6) -glucoside, quercetin-3β-D-glucoside, myricetin 3- (3-6-diacetylglucosyl) - (1- > 4) - (2″,3″-diacetylrhamnoside), apigetrin, isorhamnetin, catechin 7,3'-Di-O-β-D glucopyranoside, luteolin 7-methylglucuronide, apigenin-8-C-α -l-arabinopyranoside, naringenin 7- O-β-D-glucoside 6″-acetate,ohobanin, shogaol, ginkgetin and amoritin. The HELPER is shown to have the presence of anti-oxidant and anti-inflammatory activities as demonstrated by DPPH (1, 1-diphenyl,2-picrylhydrazyl) and membrane lysis assays. Our findings reveal the presence of phytochemicals in HALEPR that have significant antioxidant and anti-inflammatory activity. The bioactivities were identified using chemical characterization like HRA/MS and biological assessments like anti-inflammatory and antioxidant assays. Future research may focus on isolating specific molecules, conducting in vivo tests, and creating HALEPR-based formulations for clinical application as anti-inflammatory drugs.

Administering medication precisely to the inflamed intestinal sites to treat ulcerative colitis (UC), with minimized side effects, is of urgent need. In UC, the inflammation damaged mucosa contains a large number of amino groups which are positively charged, providing new opportunities for drug delivery system design. Here, we report an oral drug delivery system utilizing the tacrolimus-loaded poly (lactic-co-glycolic acid) (TAC/PLGA) particles with an adhesion coating by in situ UV-triggered polymerization of polyacrylic acid and N-hydroxysuccinimide (PAA-NHS). The negatively charged carboxyl groups effectively interact with the positively charged focal mucosa, and the NHS ester groups form the covalent bonds with the amino groups, thereby synergically enhancing the adhesion of the PLGA particles to the focal mucosa. Our findings reveal that, compared to the naked particles, the PAA-NHS coating increases the adhesion of particles to the inflammatory intestine. In a dextran sulfate sodium-induced acute colitis mouse model, the TAC/PLGA particles with PAA-NHS coating exhibits substantial retention of TAC within the inflammatory intestine, enhancing drug delivery efficiency and therapeutic effects. This approach holds promise for UC management, minimizing systemic side effects and optimizing therapeutic outcomes.

The global rise in Crohn's Disease (CD) incidence has intensified diagnostic challenges. This study identified circadian rhythm-related biomarkers for CD using datasets from the GEO database. Differentially expressed genes underwent Weighted Gene Co-Expression Network Analysis, with 49 hub genes intersected from GeneCards data. Diagnostic models were constructed using machine learning algorithms, and biologic therapy efficacy was predicted with advanced regression techniques. Single-cell sequencing showed high gene expression in stem cells, immune, and endothelial cells, with validation confirming significant differences between CD patients and controls. These findings suggest circadian rhythm-related genes as promising diagnostic biomarkers for CD.

In this article, we explored the role of adipose tissue, especially mesenteric adipose tissue and creeping fat, and its association with the gut microbiota in the pathophysiology and progression of Crohn's disease (CD). CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, influenced by genetic predisposition, gut microbiota dysbiosis, and environmental factors. Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD. Further, visceral adipose tissue, particularly creeping fat, a mesenteric adipose tissue characterized by hypertrophy and fibrosis, has been implicated in CD pathogenesis, inflammation, and fibrosis. The bacteria from the gut microbiota may translocate into mesenteric adipose tissue, contributing to the formation of creeping fat and influencing CD progression. Although creeping fat may be a protective barrier against bacterial invasion, its expansion can damage adjacent tissues, leading to complications. Modulating gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and prebiotics has shown potential in managing CD. However, more research is needed to clarify the mechanisms linking gut dysbiosis, creeping fat, and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.

Inflammatory bowel disease (IBD) is a chronic condition characterized by inflammation in the gastrointestinal tract. Previous studies have suggested a potential association between mental disorders, such as depression and anxiety, and the risk and flare of IBD. However, the findings have been inconsistent. This study aimed to conduct a systematic review and meta-analysis to assess the relationship between mental disorders and IBD. A comprehensive literature search was performed to identify relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the association between mental disorders and the risk and flare of IBD. Heterogeneity between studies was assessed using the I2 statistic. Sensitivity analysis was conducted to evaluate the stability of the results. A total of seven studies met the inclusion criteria and were included in the meta-analysis. The pooled results demonstrated a significant association between symptoms of depression at baseline and an increased risk of disease activity flare during longitudinal follow-up, with an OR of 1.69 (95% CI 1.34, 2.13). However, there was high heterogeneity between studies (I2 = 82%). Furthermore, patients who underwent surgery had a higher risk of disease activity flare (OR: 1.49, 95% CI 1.13, 1.95), and hospitalization was also identified as a contributing factor (OR: 1.22, 95% CI 1.10, 1.36). This meta-analysis provides evidence for a significant association between symptoms of depression and the risk of disease activity flare in IBD. However, the high heterogeneity observed between studies suggests the need for further research to explore potential moderators and underlying mechanisms. These findings highlight the importance of addressing mental health in the management and treatment of patients with IBD.

Inflammatory bowel disease (IBD), a chronic inflammatory condition of the human intestine, comprises Crohn's disease (CD) and ulcerative colitis (UC). IBD causes severe gastrointestinal symptoms and increases the risk of developing colorectal carcinoma. Although the etiology of IBD remains ambiguous, complex interactions between genetic predisposition, microbiota, epithelial barrier, and immune factors have been implicated. The disruption of intestinal homeostasis is a cardinal characteristic of IBD. Patients with IBD exhibit intestinal microbiota dysbiosis, impaired epithelial tight junctions, and immune dysregulation; however, the relationship between them is not completely understood. As the largest body surface is exposed to the external environment, the gastrointestinal tract epithelium is continuously subjected to environmental and endogenous stressors that can disrupt cellular homeostasis and survival. Heat shock proteins (HSPs) are endogenous factors that play crucial roles in various physiological processes, such as maintaining intestinal homeostasis and influencing IBD progression. Specifically, HSPs share an intricate association with microbes, intestinal epithelium, and the immune system. In this review, we aim to elucidate the impact of HSPs on IBD development by examining their involvement in the interactions between the intestinal microbiota, epithelial barrier, and immune system. The recent clinical and animal models and cellular research delineating the relationship between HSPs and IBD are summarized. Additionally, new perspectives on IBD treatment approaches have been proposed.

The interplay between gut microbiota and immune responses is crucial in ulcerative colitis (UC). Though Akkermansia muciniphila (Akk) shows therapeutic potential, the mechanisms remain unclear. This study sought to investigate differences in therapeutic efficacy among different forms or strains of Akk and elucidate the underlying mechanisms.

Employing a dextran sulfate sodium (DSS)-induced colitis mouse model, we assessed Akk's impact on colitis using cellular cytokine analysis, immune phenotyping, proteomics, and biochemical methods. Our results suggest that treatment with live Akk effectively reduced colitis in the DSS-induced model, whereas heat-inactivated Akk did not yield the same results. Notably, Akk exhibited protective properties by promoting the secretion of IL-22 by Group 3 innate lymphoid cells (ILC3s), as evidenced by the absence of protection in IL-22 knockout mice. Additionally, Akk augmented the population of CD103+CD11b- dendritic cells (DCs) and enhanced their retinoic acid (RA) synthesis through the modulation of RALDH2, a crucial enzyme in RA metabolism. The depletion of RALDH2 in DCs diminished Akk's protective properties and impaired IL-22-mediated mucosal healing. Mechanistically, Akk activated RA production in DCs by enhancing the JAK2-STAT3 signaling pathway. Additionally, various strains of Akk may exhibit differing abilities to alleviate colitis, with the novel strain Am06 derived from breast milk showing consistent efficacy similar to the reference strain.

In summary, our findings indicate that certain strains of Akk may mitigate colitis through the promotion of RA synthesis and IL-22 secretion, underscoring the potential efficacy of Akk as a therapeutic intervention for the management of UC. Video Abstract.

Acute severe ulcerative colitis (ASUC) often requires surgical intervention, such as proctocolectomy with ileal pouch-anal anastomosis (IPAA). While IPAA improves patient outcomes, it can be associated with pouchitis, a common and debilitating complication characterized by inflammation of the pouch. The development of pouchitis is closely linked to dysbiosis-an imbalance in the gut microbiota. Understanding the role of the microbiota in pouch health has spurred interest in probiotics as a therapeutic strategy. Probiotics represent a promising avenue in the management of pouchitis, offering a natural and targeted approach to improving outcomes for UC patients. This review explores the role of probiotics in the management of UC patients, with a specific focus on preventing and treating pouchitis. We compare the microbiota of healthy pouches to those with pouchitis, highlighting key microbial shifts linked to disease onset and discussing the growing evidence for probiotics as a prevention and therapeutic approach. Future directions should prioritize advancing research to optimize probiotic therapies and establish personalized approaches based on individual microbiome profiles, highlighting their significant potential as a promising treatment strategy for pouchitis.

The gut microbiota (GM) may be associated with uveitis. However, the causal relationship between the GM and uveitis and whether blood metabolites act as mediators of the GM remain unclear. We extracted the GM, blood metabolites, and uveitis data from genome-wide association study (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships among GM, blood metabolites, and uveitis. The primary statistical method used was the inverse variance weighted (IVW) method. In addition, we used 2-sample MR, bidirectional MR, 2-step method and multiple MR to explore whether blood metabolites were mediators of the association between the GM and uveitis. After removing confounding factors, the abundances of the order Bacillales and the genus Holdemanella are risk factors for uveitis, and the abundances of Peptococcus and Ruminococcaceae UCG010 are protective factors. The inverse analysis revealed that uveitis affected 6 GM taxa - 4 positively and 2 negatively. In addition, N-methyl proline and 2-hydroxy sebacate were identified as risk factors for uveitis, and N-formy1 phenylalanine, 1-ribosyl-imidazole acetate, 1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) and alpha-ketoglutarate/pyruvate were identified as protective factors for uveitis. Finally, there was a causal association between 3 GM taxa and 6 blood metabolites, with 6 positive and 2 negative effects. N-methylproline possessed the greatest mediated effect (9.41%) between Ruminococcaceae UCG010 and uveitis. These results provide new insights into the pathogenesis of uveitis and offer a new approach to uveitis prevention and treatment from GM and blood metabolites perspective.

Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.

A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.

The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.

LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway.

To investigate the prevalence and risk factors of psychological symptoms and quality of life (QoL) in early patients with inflammatory bowel disease (IBD).

From September 2021 to May 2022, a unified questionnaire was developed to collect clinical data from early patients with IBD from 42 tertiary care hospitals. The influencing factors of psychological symptoms and poor QoL are screened by logistic regression analysis for constructing model in predicting poor QoL. The consistency index, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the model.

A total of 939 early patients with IBD were surveyed, Among them, 20.3% exhibited anxiety, 21.7% had depression, 57.3% experienced sleep disturbance, and 41.9% reported poor QoL. The factors influencing psychological symptoms varied between ulcerative colitis (UC) and Crohn's disease (CD) patients. The QoL was primarily affected by disease activity, income level and depression. The AUC value of the model in the training group was 0.781 (95% CI: 0.748-0.814). The calibration diagram of the model closely matched the ideal curve. Compared to other prediction models, our model showed superior predictive capability, with NRI and IDI values of 0.324 (95%CI:0.196-0.4513) and 0.026 (95%CI:0.014-0.038), respectively. DCA indicated that the nomogram model could provide clinical benefits.

Early patients with IBD exhibit a high prevalence of psychological symptoms and poor QoL. The nomogram prediction model we constructed demonstrates high accuracy and performance in predicting QoL in early patients with IBD.

The human Inhibitor of Differentiation-2 (hID2) protein is a promising candidate for the treatment of colitis. However, its relatively low molecular weight limits its clinical application. To extend the therapeutic half-life, an albumin-binding domain (ABD), known for its high affinity for human serum albumin (HSA), was fused to hID2, resulting in a recombinant ABD-hID2. The anti-colitis bioactivity of ABD-hID2 than that of hID2 was evaluated in this study.

Western blotting, size-exclusion high-performance chromatography, HSA binding assay, and pharmacokinetic studies were used to characterise ABD-hID2, which was induced by dextran sulfate sodium salt (DSS), Citrobacter rodentium (CR), and ABD-hID2 and hID2. The Disease Activity Index, histological pathologies, inflammatory response, Alcian blue or tuft cell staining, and tight junction proteins were determined. Alterations in the intestinal microbiota after ABD-hID2 treatment were analysed via 16S rRNA gene sequencing.

Compared with hID2, ABD-hID2 exhibited a decreased dimer complex, bound to HSA with high affinity, and demonstrated an extended blood retention time in vivo. Consequently, ABD-hID2 exhibited increased therapeutic efficacy in both DSS- and CR-induced colitis mouse models, as evidenced by the alleviation of colitis symptoms, preservation of goblet and tuft cell functions, restoration of the intestinal mucus barrier, and suppression of abnormal immune-inflammatory responses. Additionally, the modulation of the gut microbiota may play a role in the protective effects of ABD-hID2 in mice with CR-induced ulcerative colitis.

ABD-hID2 enhances the bioactivity of hID2 and has the potential for further development as a treatment for colitis.

Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD.

Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs).

Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner.

These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.