Malnutrition is prevalent in patients with inflammatory bowel disease (IBD); however, its ability to predict the disease activity in IBD remains unexplored. Therefore, this study aimed to explore the association between malnutrition and disease activity in IBD.

In this retrospective study, we enrolled 1006 patients diagnosed with IBD from the First Affiliated Hospital of Wenzhou Medical University from 2011 to 2022. Malnutrition was assessed based on the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) scores. Logistic regression analyses were performed to identify predictors for disease activity. Restricted cubic spline analysis was performed to evaluate the possible nonlinear relations, and subgroup analysis was performed to explore potential interactions. Additionally, prediction performances were compared through receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement.

The prevalence of malnutrition calculated by the PNI, GNRI, and CONUT scores in IBD was 16.9%, 72.1%, and 75.6%, respectively and significant correlations were observed among them. Multivariate logistic regression analysis showed that PNI, GNRI, and CONUT were independent risk factors for disease activity, and no significant nonlinear relationship was observed between disease activity and all three indexes. No statistically significant interactive effect was found in nearly all the subgroups. GNRI showed the highest predictive value compared with PNI and CONUT. Additionally, combining any of the three indexes improved the ability of C-reactive protein to predict IBD activity.

All three nutritional indexes evaluated malnutrition to be an independent risk factor for IBD activity.

Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.

Faecalibacterium prausnitzii is one of the most dominant commensal bacteria in the human gut, and certain anti-inflammatory functions have been attributed to a single microbial anti-inflammatory molecule (MAM). Simultaneously, substantial diversity among F. prausnitzii strains is acknowledged, emphasizing the need for strain-level functional studies aimed at developing innovative probiotics. Here, two distinct F. prausnitzii strains, KBL1026 and KBL1027, were isolated from Korean donors, exhibiting notable differences in the relative abundance of F. prausnitzii. Both strains were identified as the core Faecalibacterium amplicon sequence variant (ASV) within the healthy Korean cohort, and their MAM sequences showed a high similarity of 98.6%. However, when a single strain was introduced to mice with dextran sulfate sodium (DSS)-induced colitis, KBL1027 showed the most significant ameliorative effects, including alleviation of colonic inflammation and restoration of gut microbial dysbiosis. Moreover, the supernatant from KBL1027 elevated the secretion of IL-10 cytokine more than that of KBL1026 in mouse bone marrow-derived macrophage (BMDM) cells, suggesting that the strain-specific, anti-inflammatory efficacy of KBL1027 might involve effector compounds other than MAM. Through analysis of the Faecalibacterium pan-genome and comparative genomics, strain-specific functions related to extracellular polysaccharide biosynthesis were identified in KBL1027, which could contribute to the observed morphological disparities. Collectively, our findings highlight the strain-specific, anti-inflammatory functions of F. prausnitzii, even within the same core ASV, emphasizing the influence of their human origin.

The urobiome, or urinary tract microbiome, has emerged as a crucial component in maintaining urinary health and defending against infections. Recent advances in next-generation sequencing (NGS) have debunked the long-held belief that the urinary tract is sterile, revealing a unique ecosystem of microorganisms. The urobiome interacts with the urothelium and mucosa-associated lymphoid tissue (MALT) to support local immunity, playing an integral role in defending the urinary tract against pathogens. Through complex communication processes like quorum sensing, the urobiome regulates microbial behavior and controls interactions with host tissues, helping to prevent pathogen colonization and infection. However, dysbiosis in the urobiome can disrupt this balance, making the urinary tract more susceptible to infections, including urinary tract infections (UTIs). Studies have highlighted specific microbial compositions associated with both healthy and disease states, suggesting that shifts in the urobiome may correlate with various urological diseases. Furthermore, microbial diversity within the urinary tract differs by factors such as age and gender, reflecting the dynamic nature of the urobiome. Future research focusing on the interplay between the urobiome, host immune defenses, and pathogenic mechanisms may lead to innovative diagnostic and therapeutic approaches. Understanding how microbial composition changes during disease states could enable targeted treatments, potentially reducing reliance on antibiotics and minimizing resistance issues. The urobiome thus represents a promising frontier in urology, with implications for enhancing urinary health and treating infections more effectively.

The global incident shows that the number of inflammatory bowel disease (IBD) cases increased by 88.30% in 2021 and significantly influenced patients' quality of life. Synbiotics are recommended as an alternative or supplement for IBD. We formulated synbiotic mulberry (SM) by mixing mulberry powder, probiotic biomass, and inulin. However, the anti-inflammatory effect of SM and gut microbiota modulation in dextran-sodium-sulfate (DSS)-induced colitis rats has not been thoroughly investigated. Thus, the anti-inflammatory activity of SM and gut microbiota composition was explored using DSS-induced acute colitis rats. Rats were divided into seven groups: control, control+SM1000, DSS, DSS+SM250, DSS+SM500, DSS+SM1000, and DSS+Sulfazalazine (SUL). All DSS induction rats received dissolving 4% (w/v) DSS in drinking water for 7 days, and their respective treatment was once daily via oral gavage. In addition, DSS-aggravated colitis rats received 0.4% (w/v) DSS in drinking water and their respective treatments once daily for the next 7 days. SM improved the disease activity index (DAI), body weight (BW), hepatosplenomegaly, colon length, and colon histomorphology, with outcomes similar to the results of SUL administration. Furthermore, SM decreased the levels of IL-6 production and suppressed iNOS and IL-10 mRNA expression in the colon. SM induced significant modulation in gut microbiota by significantly increasing the abundance of Allobaculu. SM also affects the amount of metabolic enzyme classes. In conclusion, we propose that SM may hold promise as a functional food therapeutic approach for the treatment of colitis; however, additional clinical trials are considered necessary to confirm these effects.

Extracellular vesicles (EVs), nanoparticles secreted by both gram-negative and gram-positive bacteria, carry various biomolecules and cross biological barriers. Gut microbiota-derived EVs are currently being investigated as a communication mechanism between the microbiota and the host. Few clinical studies, however, have investigated gut microbiota-derived EVs. Here, we show that machine learning models were able to accurately distinguish gut microbiota and respective microbiota-derived EV samples according to their taxonomic composition both within each data set (area under the curve [AUC] 0.764-1.00) and in a cross-study setting (AUC 0.701-0.997). These results show that gut microbiota-derived EVs form a distinct taxonomic entity from gut microbiota. Thus, conventional gut microbiota composition may not correctly reflect communication between the gut microbiota and the host unless microbiota-derived EVs are reported separately.IMPORTANCEGut microbiota-derived extracellular vesicles (EVs) have been suggested to be a communication mechanism between the gut microbiota and the human body. However, the data on EV secretion from the gut microbiota remain limited. To investigate and compare the composition of gut microbiota-derived EVs to gut microbiota composition, we used a machine learning approach to classify 16S rRNA gene sequencing data in seven clinical data sets incorporating both gut microbiota and gut microbiota-derived EV samples. The results of the study show that microbiota-derived EVs form a separate taxonomic entity from the gut microbiota. Gut microbiota-derived EVs should be included in clinical studies that investigate gut microbiota to gain more comprehensive insight into gut microbiota-host communication.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health vs IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

Background: Crohn's disease (CD) is a chronic inflammatory condition that can affect the gastrointestinal tract and cause significant extraintestinal manifestations. Diagnosing and monitoring disease activity, especially in pediatric patients, remains a challenge due to the variable clinical presentations and limitations of traditional imaging methods. Objective: This study aimed to evaluate and compare the diagnostic accuracy and clinical utility of small bowel capsule endoscopy (SBCE) versus magnetic resonance enterography (MRE) for assessing disease activity and extent in pediatric Crohn's disease using the Pediatric Crohn's Disease Activity Index (PCDAI) and Simple Endoscopic Score for Crohn's Disease (SES-CD) as reference standards. Methods: In this prospective study, 52 pediatric patients with newly diagnosed CD underwent upper and lower endoscopy, MRE, and SBCE. The SBCE images were analyzed using the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI), while the MRE images were scored using the Crohn's Disease MRI Index (CDMI). Correlations of these findings with PCDAI and SES-CD were statistically analyzed. Results: CECDAI and CDMI demonstrated strong correlations with PCDAI (r = 0.517 and r = 0.525, respectively; p < 0.001). The correlations between CECDAI and SES-CD were less pronounced but significant. SBCE and MRE showed comparable efficacy in detecting small bowel lesions, with both methods offering valuable insights into the disease status. Conclusions: SBCE is a reliable, non-invasive tool for diagnosing and monitoring pediatric CD, comparable to MRE. While SBCE offers higher resolution for mucosal evaluation, it requires additional expertise for optimal interpretation. The adoption of SBCE alongside MRE could enhance diagnostic accuracy and early therapeutic interventions for pediatric CD.

Inflammatory bowel disease (IBD) is a complex disorder influenced by genetic, environmental, and microbial factors, with emerging evidence highlighting the gut microbiome's role in disease pathogenesis. This study investigates the impact of microbiome-targeted interventions in pediatric IBD by integrating multi-omics analysis, including metagenomics, metabolomics, transcriptomics, and clinical biomarkers, to identify microbial dysbiosis patterns and potential therapeutic targets. A cohort of pediatric IBD patients underwent a personalized intervention involving dietary modifications, probiotic supplementation, and selective antibiotic therapy. Microbiome composition, inflammatory markers (fecal calprotectin, CRP), and disease activity scores (PCDAI/PUCAI) were assessed before and after treatment. At the 3-month follow-up, patients showed significant clinical improvement, with reduced stool frequency (p = 0.004) and improved stool consistency (p < 0.001). Symptoms such as bloating and abdominal pain decreased, while energy levels increased (p < 0.001). Dietary changes included higher fruit, meat, and dairy intake, and lower fast-food and sweets consumption (p < 0.001). Physician assessments classified 90% as "improved", reinforcing the effectiveness of personalized microbiome interventions. Microbiome-targeted interventions (diet, probiotics, and selective antibiotics) improved pediatric IBD outcomes by reducing pathogenic bacteria and increasing short-chain fatty acid (SCFA)-producing species, lowering inflammation and symptoms. Early-life factors (cesarean birth, and formula feeding) influence IBD risk. Personalized diets enhanced microbial balance. Integrating multi-omics supports precision medicine, offering microbiome-based biomarkers and reducing immunosuppressive reliance.

Ulcerative colitis (UC) is characterized clinically by intestinal inflammation and gut microbiota dysbiosis. The consumption of biologics, although effective in inflammation control, may lead to adverse effects and is inconvenient for at-home administration. Goat milk-derived extracellular vesicles (GMEVs) have been proposed as a supplement to prevent intestinal inflammation. However, their therapeutic potential for colitis remains elusive. This study aimed to explore the preventive effect of GMEVs on colitis and its underlying mechanisms through the microbiota-immune axis using a dextran sodium sulfate (DSS)-induced colitis mouse model. We found that a pre-treatment of 20 mg/kg/d GMEVs effectively prevented body weight loss, colon shortening, the depletion of colonic goblet cells, and the disappearance of crypts, while enhancing the intestinal mucosal barrier. Consistent with these phenotypes, GMEV pre-treatment increased levels of IL-22 and IL-10 and decreased levels of IL-1β, TNF-α, IL-6, and iNOS. However, GMEVs themselves had no effect on normal mice. Paralleling the alleviation of intestinal inflammation, GMEV pre-treatment also restored the reduction in unclassified Muribaculaceae, Dubosiella, and Lactobacillus and suppressed the expansion of Alistipes and Proteobacteria following DSS treatment. Additionally, GMEV intake significantly downregulated the expression of proteins in the NF-κB signaling pathway induced by DSS. In summary, GMEVs could prevent colitis by regulating intestinal inflammation, the intestinal mucosal barrier, gut microbiota, organ damage, and the immune microenvironment. This study demonstrated that GMEVs have potential application prospects for UC prevention.

Despite advances in metastatic colorectal cancer (mCRC) treatment, long-term survival remains poor, particularly in right-sided colorectal cancer (RCRC), which has a worse prognosis compared to left-sided CRC (LCRC). This disparity is driven by the complex biological diversity of these malignancies. RCRC and LCRC differ not only in clinical presentation and outcomes but also in their underlying molecular and genetic profiles. This article offers a detailed literature review focusing on the distinctions between RCRC and LCRC. We explore key differences across embryology, anatomy, pathology, omics, and the tumor microenvironment (TME), providing insights into how these factors contribute to prognosis and therapeutic responses. Furthermore, we examine the therapeutic implications of these differences, considering whether the conventional classification of CRC into right- and left-sided forms should be refined. Recent molecular findings suggest that this binary classification may overlook critical biological complexities. Therefore, we propose that future approaches should integrate molecular insights to better guide personalized treatments, especially anti-EGFR therapies, and improve patient outcomes.

Microcapsules composed of synthetic polymeric matrices have attracted considerable attention in delivering oral probiotics. However, existing polymeric microcapsules demonstrate inadequate acid resistance and adaptability, as well as deficiency in the inflamed colon-specificity and uncontrolled release of probiotics therein. Herein, a DNA microcapsule is prepared as a probiotic-transporting micromotor through photo-crosslinking of hyaluronic acid methacrylate and acrydite-modified A-/C-rich oligomers within the microfludically generated droplets in the presence of nitric oxide-cleavable crosslinker and gas donor manganese carbonyl (MnCO). As the microcapsules traverse stomach, duodenum, and ultimately colon, the formation and dissociation of A-motif and i-motif structures instigate a reversible shrinking-swelling transition of microcapsules to preserve probiotic viability. Subsequently, the microcapsules exhibit chemotaxis towards inflamed colon site, driven by a gas-generating reaction between MnCO and elevated reactive oxygen species. Following disintegration of the microcapsules, triggered by endogenous nitric oxide, probiotics are released to reshape the dysbiosis of intestinal microflora. This advanced delivery system offers significant promise for the effective clinical management of inflammatory bowel disease.

Fibroblasts that reside in the gut mucosa are among the key regulators of innate immune cells, but their role in the regulation of the defense functions of macrophages remains unknown. MyD88 is suggested to shape fibroblast responses in the intestinal microenvironment. We found that mice lacking MyD88 in fibroblasts showed a decrease in the colonic antimicrobial defense, developing dysbiosis and aggravated dextran sulfate sodium (DSS)-induced colitis. These pathological changes were associated with the accumulation of Arginase 1+ macrophages with low antimicrobial defense capability. Mechanistically, the production of interleukin (IL)-6 and CCL2 downstream of MyD88 was critically involved in fibroblast-mediated support of macrophage antimicrobial function, and IL-6/CCL2 neutralization resulted in the generation of macrophages with decreased production of the antimicrobial peptide cathelicidin and impaired bacterial clearance. Collectively, these findings revealed a critical role of fibroblast-intrinsic MyD88 signaling in regulating macrophage antimicrobial defense under colonic homeostasis, and its disruption results in dysbiosis, predisposing the host to the development of intestinal inflammation.

Background/Objectives: Lactobacillus strains are widely used as probiotics in the functional food industry and show potential for treating inflammatory bowel disease (IBD). However, the strain specificity and limited stress resistance of Lactobacillus restricts its therapeutic effectiveness. The aim of this study was to investigate the effects of dietary supplementation with microencapsulated Lactobacillus plantarum 17-1 on the intestinal immune responses, gut microbiota composition, and metabolic characteristics in colitis mice. Methods: Mice were pre-fed a diet containing microencapsulated Lactobacillus plantarum 17-1 for 3 weeks and then treated with 2.5% dextran sulfate sodium (DSS) in drinking water for 8 days to induce colitis. Results: The results showed that microencapsulated Lactobacillus plantarum 17-1 effectively alleviated clinical symptoms and histopathological features of colitis mice and suppressed the up-regulation of pro-inflammatory cytokines IL-6 and IL-17 in the colon of colitis mice. Additionally, Lactobacillus plantarum 17-1 significantly increased the relative abundance of several beneficial bacterial taxa, including Ruminococcaceae_UCG_014, Bacteroides, Prevotellaceae_UCG_001, Lactococcus, Weissella, Pediococcus, and so on. Moreover, it regulated the levels of multiple inflammation-related metabolites involved in linolenic acid metabolism, arachidonic acid metabolism, primary bile acid biosynthesis, and tyrosine metabolism. Conclusions: These results suggest that dietary supplementation with microencapsulated Lactobacillus plantarum 17-1 reduced colitis inflammation in mice by modulating the intestinal microbiota composition and metabolic characteristics, which may serve as a potential therapeutic strategy for IBD.

Clinical applications of fecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonization of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of the administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching.

Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 fecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one-patient-to-one-donor strategy.

Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (P = .027), immunosuppressants (P = .049), and biologics (P = .029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; P = .03, LTR; P = .05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (P < .05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric-acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (P < .05).

This study provides important insights for developing patient-tailored FMT-based therapies for UC.

Ulcerative colitis (UC) is a complex, chronic inflammatory disease that primarily impacts the colon mucosa. One of the key pathological contributors to the development and progression of inflammatory bowel disease (IBD) is oxidative stress, which results in reactive oxygen species (ROS)-induced mucosal damage. This stress leads to dysfunction of the intestinal barrier.

The purpose of this study is to examine the expression levels of genes involved in various inflammatory pathways, including autophagy, unfolded protein response (UPR), ubiquitination, metabolic pathways, and immune responses in the colon mucosa of patients with UC.

Patients diagnosed with UC at Çukurova University, Balcalı Hospital, Gastroenterology Department between December 2023 and January 2024 were included in this prospective study. A total of 40 participants were included in the study: 27 ulcerative colitis patients and 13 controls. To isolate high-quality RNA, colon biopsy material obtained during colonoscopy was immediately placed in stabilization solution and stored at - 80 degrees Celsius. The relative quantification of target gene mRNA was determined using a Light Cycler. Subsequently, differences in gene expression between patients and the control group were evaluated using the Mann-Whitney U and Kruskal-Wallis tests.

In our study, FOXO4 gene expression increased in UC patients during both active and remission phases compared to the control group. The high expression of this gene is associated with its role in inflammation and cell death processes. Additionally, the high expression of ALDOB and SLC26A genes is linked to increased inflammation and energy demand. Lastly, the elevated expression of the SOD2 gene can be considered a response to oxidative stress-related inflammatory processes in the disease.

These findings propose that these genes could serve as potential biomarkers for genomic identification and understanding the pathogenesis of UC.

Inflammatory bowel disease (IBD) is a relapsing disorder characterized by uncontrolled chronic inflammation of the gastrointestinal tract, posing a significant therapeutic challenge owing to the limited efficacy and undesirable side effects of current therapeutic options. A key pathological hallmark of IBD is the excessive production of reactive oxygen species (ROS). Hence, therapeutic strategies aimed at reducing ROS levels are promising for relieving these inflammatory conditions. Vitamin C-a natural nutrient for the human body-is well known for its potent antioxidant effects. However, the clinical development of vitamin C as a therapeutic drug has been hindered by its poor stability, rapid metabolism, and inadequate tissue accumulation. Herein, we report that the bioavailability of vitamin C can be enhanced by chemically reprogramming it with a small panel of long-chain fatty acids that aid in the aqueous self-assembly of the resulting drug conjugates to create self-deliverable nanoassemblies, enhancing their inflammation disease-oriented delivery and cellular uptake. In mice with dextran sulfate sodium-induced colitis, the optimal vitamin C-lipid nanoassemblies preferentially accumulated in inflamed colonic tissues following systemic administration and substantially ameliorated disease severity. We extended this strategy to incorporate the clinically approved glucocorticoid budesonide into the vitamin C nanosystem, facilitating a synergistic combination. In the chronic colitis model, the combination treatment reduced inflammation without compromising global immunity. Mechanistically, the treatment modulated the intestinal inflammatory microenvironment and altered the immune cell landscape, partly through regulation of the gut microbiome. Given its anticipated negligible side effects, this novel nanoassembly platform leveraging small-molecule lipidation may become a promising therapeutic for treating various inflammatory diseases.

Ulcerative colitis (UC) is effectively alleviated by Saccharomyces boulardii (S. boulardii), an important probiotic. Postbiotics, defined as beneficial non-viable microorganisms and/or their components, can potentially improve gut health. In this study, we utilized S. boulardii to prepare postbiotics via freeze-drying and spray-drying methods, characterized the resulting postbiotics, and investigated their efficacy and underlying mechanisms in preventing UC. In a mouse model of UC induced by dextran sulfate sodium (DSS), we found that prevention with two forms of S. boulardii postbiotics alleviated colitis symptoms triggered by DSS, mitigated colon tissue damage, maintained the distribution of intestinal occludin and ZO-1 proteins, and suppressed the secretion and expression of TNF-α, IL-1β, and IL-6 in serum and colon tissues. Additionally, S. boulardii postbiotics mitigated dysbiosis by modulating gut microbiota composition, including the balance between Bacteroidota and Firmicutes (F/B), as well as the levels of Akkermansia, Muribaculaceae, Dubosiella, and Turicibacter. In conclusion, as a novel biotherapeutic agent, S. boulardii postbiotics effectively prevent DSS-induced UC in mice. Compared to live S. boulardii, postbiotics may hold greater potential for UC prevention.

The gut plays a crucial role in digestion and immunity, so its balance is essential to overall health. This balance relies on dynamic interactions between intestinal epithelial cells, immune cells, and crypt stem cells. Inflammatory bowel disease (IBD), which consists of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory disease of the gastrointestinal tract closely related to immune dysfunction. Stem cells, known for their ability to self-renew and differentiate, play an important role in repairing damaged intestinal epithelium and maintaining homeostasis in vivo. Macrophages are key gatekeepers of intestinal immune homeostasis and have a significant impact on IBD. Current research has focused on the link between epithelial cells and stem cells, but interactions with macrophages, which have been recognized as attractive targets for the development of new therapeutic approaches to disease, have been less explored. Recently, the developing field of immunometabolism has reinforced that metabolic reprogramming is a key determinant of macrophage function and subsequent disease progression. The aim of this review is to explore the role of the macrophage-stem cell axis in the maintenance of intestinal homeostasis and to summarize potential approaches to treating IBD by manipulating the cellular metabolism of macrophages, as well as the main opportunities and challenges faced. In summary, our overview provides a framework for understanding the critical role of macrophage immunometabolism in maintaining gut health and potential therapeutic targets.

Gut microbiota plays an important role in gut health, and its dysbiosis is closely related to the pathogenesis of various intestinal diseases. The field of gut microbiota and intestinal diseases has not yet been systematically quantified through bibliometric methods. This study conducted bibliometric analysis to delineate the evolution of research on gut microbiota and intestinal diseases. Data were sourced from the Web of Science Core Collection database from 2009 to 2023 and were scientometrically analyzed using CiteSpace. We have found that the number of annual publications has been steadily increasing and showing an upward trend. China and the Chinese Academy of Sciences are the country and institution with the most contributions, respectively. Frontiers in Microbiology and Nutrients are the journals with the most publications, while Plos One and Nature are the journals with the most citations. The field has shifted from focusing on traditional descriptive analysis of gut microbiota composition to exploring the causal relationship between gut microbiota and intestinal diseases. The research hotspots and trends mainly include the correlation between specific intestinal diseases and gut microbiota diversity, the mechanism of gut microbiota involvement in intestinal diseases, the exploration of important gut microbiota related to intestinal diseases, and the relationship between gut microbiota and human gut health. This study provides a comprehensive knowledge map of gut microbiota and intestinal diseases, highlights key research areas, and outlines potential future directions.

As one of the most common inflammatory bowel diseases (IBDs), ulcerative colitis (UC) has become a rising global health issue that affects people's quality of life. Conventional therapeutic drugs have low bioavailability and may cause serious side effects due to their lack of acidic resistance and lesion-targeting capabilities. The development of novel nanomedicines to overcome these problems is urgently needed. Nanozymes have attracted attention because of their excellent catalytic efficiency in various harsh environments. In this study, tannic acid-vanadium (TA-V) nanozymes with multienzymatic and excellent antioxidant abilities, which exhibit acidic resistance and a negative surface charge, were successfully developed. All these characteristics make it possible that these nanozymes are not easily decomposed by gastric acid and can effectively accumulate in colitis lesions with a positive charge through oral delivery. In vitro and in vivo experiments further demonstrated the excellent prophylactic and therapeutic value of these compounds in the treatment of UC by scavenging reactive oxygen/nitrogen species (ROS/RNS) and mitigating the oxidative stress environment, thus downregulating the levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α. Furthermore, TA-V also showed excellent biosafety and biocompatibility without causing obvious damage to the main organs. This work provides novel preventative and therapeutic TA-V nanozymes that might have potential clinical applications in UC treatment.

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.

Dietary therapy is a common adjunctive treatment for Crohn's disease (CD). However, previous studies have presented conflicting views on whether dairy products should be included in dietary therapy. This controversy may be due to confounding factors. Thus, this study employed Mendelian randomization to investigate the effects of consumption of 6 different dairy products on CD. In addition, the mediating effects of 8 amino acids were explored. Three sensitivity analysis methods were employed to exclude horizontal pleiotropy and heterogeneity, ensuring the robustness of the conclusions. Ultimately, the study found that whole milk consumption can reduce the risk of CD (odds ratio = 0.504, 95% CI: 0.324-0.784). Mediation analysis demonstrated that serum isoleucine (mediation effect: -0.265, 95%CI: -0.533 to -0.068) and valine (mediation effect: -0.083, 95%CI: -0.198 to -0.002) are influenced by full-cream milk and modulate the onset of CD, with mediation effects accounting for 38.685% and 12.083%, respectively.

The unfolded protein response (UPR) is a complex intracellular signal transduction system that orchestrates the cellular response during Endoplasmic Reticulum (ER) stress conditions to reestablish cellular proteostasis. If, on one side, prolonged ER stress conditions can lead to programmed cell death and autophagy as a cytoprotective mechanism, on the other, unresolved ER stress and improper UPR activation represent a perilous condition able to trigger or exacerbate inflammatory responses. Notably, intestinal and immune cells experience ER stress physiologically due to their high protein secretory rate. Indeed, there is evidence of UPR's involvement in both physiological and pathological intestinal conditions, while less is known about its bidirectional interaction with gut microbiota. However, gut microbes and their metabolites can influence ER stress and UPR pathways, and, in turn, ER stress conditions can shape gut microbiota composition, with important implications for overall intestinal health. Thus, targeting UPR components is an intriguing strategy for treating ER stress-linked dysbiosis and diseases, particularly intestinal inflammation.

The current study aims to investigate the potential interaction between glycosylation profiles of the Ningxiang breed (NX) and Western Duroc × Landrace × Yorkshire breed (DLY) weaned piglets, and their characteristic microbes, employing integrated analyses of transcriptomics and metagenomics. Twenty-four (12 NX and 12 DLY) at 28 days of age were transported into an experimental house and fed the same weaned piglet diet. The trail period was 7 days. Results revealed that the NX piglets had a higher growth-to-feed ratio, body weight gain scale, and lower pathological score of intestinal injury compared with the DLY piglets (P < 0.01). DLY piglets displayed elevated mRNA expression levels of MUC2 and MUC5AC in colonic mucosal tissue than NX piglets (P < 0.05). Within the O-linked glycosylated differentially expressed genes (DEGs), FNTA, GALNT18, POMGNT1, POMGNT2, and POMT1 were significantly upregulated in DLY piglets relative to NX piglets (P < 0.05). Conversely, C1GALT2, GALNT1, KMT2C, and OGT were significantly downregulated in DLY piglets compared to NX piglets (P < 0.05). The KMT2C gene was hardly expressed in the transcriptome of DLY piglets. At the phylum taxonomic level, NX piglets had a higher abundance of Firmicutes, while DLY piglets had a higher abundance of Proteobacteria. At the genus taxonomic level, NX piglets had a higher abundance of Lactobacillus, whereas DLY piglets had a higher abundance of Collinsella, Enterococcus and Escherichia. The results of the correlation between intestinal differential bacteria and O-chain glycosylated DEG showed that C1GALT2, GALNT1 and KMT2 were associated with Lactobacillus_pontis showed a positive correlation (R = 0.67). Through comparative analysis of differentially glycosylated genes and their associated functions, this study highlights the potential role of reduced expression of GALNT1 and KMT2C genes, involved in O-linked protein and glycan reactions, in impairing the intestinal barrier function of DLY piglets. Furthermore, members of the Lactobacillus and Prevotella genera may actively contribute to the regulation of piglet colon glycosylation profiles.

A 75-year-old male, hospitalized with back pain, remained hospitalized for tests for unexplained colitis, which was diagnosed as inflammatory bowel disease unclassified and treated with antibiotics and prednisolone, resulting in Clostridioides difficile colitis. Therefore, antibiotics were discontinued, and oral metronidazole treatment was initiated; however, as the patient's fever persisted, blood cultures were performed. An anaerobic bottle of blood culture turned positive the following day. Initial Gram staining of the positive blood culture fluid showed negative rods, and restaining detected small numbers of Gram-positive rods among the Gram-negative rods. The gray colonies on the subculture medium contained only Gram-negative rods. The bacterium was identified as Flavonifractor plautii using mass spectrometry. We ordered the ATCC 29863 F. plautii strain and compared with the strain of this case. The biochemical test result and the change in colony fluorescence under ultraviolet light of the strain isolated from the patient were identical to those of the ATCC strain, supporting the mass spectrometry results. Bacterial translocation from colonic mucosa was suspected, which improved following levofloxacin and metronidazole therapy. Only eight cases of human F. plautii infection have been reported, and we summarized them as a review. Careful and thorough isolation and identification of bacteria that are rarely isolated clinically, such as F. plautii, is crucial in accumulating evidence on rare infectious diseases.

The prevalence of noncommunicable inflammatory disease is increasing in modern urban societies, posing significant challenges to public health. Novel prevention and therapeutic strategies are needed to effectively deal with this issue. One promising approach is leveraging microorganisms such as Mycobacterium vaccae ATCC 15483, known for its anti-inflammatory, immunoregulatory, and stress-resilience properties. This study aimed to assess whether weekly subcutaneous administrations of a whole-cell, heat-killed preparation of M. vaccae ATCC 15483 (eleven injections initiated one week before the onset of the diet intervention), relative to vehicle injections, in adolescent male C57BL/6N mice can mitigate inflammation associated with Western-style diet-induced obesity, which is considered a risk factor for a number of metabolic and inflammatory diseases. Our results show that treatment with M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations. The Western-style diet, relative to a control diet condition, decreased alpha diversity and altered the community composition of the gut microbiome, increasing the Bacillota to Bacteroidota ratio (formerly referred to as the Firmicutes to Bacteroidetes ratio). Despite the finding that M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations, it had no effect on the diversity or community composition of the gut microbiome, suggesting that it acts downstream of the gut microbiome to alter immunometabolic signaling. M. vaccae ATCC 15483 reduced baseline levels of biomarkers of hippocampal neuroinflammation and microglial priming, such as Nfkbia and Nlrp3, and notably decreased anxiety-like defensive behavioral responses. The current findings provide compelling evidence supporting the potential for M. vaccae ATCC 15483 as a promising intervention for prevention or treatment of adverse immunometabolic outcomes linked to the consumption of a Western-style diet and the associated dysbiosis of the gut microbiome.

The role of dietary and nutritional factors in inflammatory bowel disease (IBD) remains poorly understood, necessitating further investigation. This study aims to explore the association between nutrient intake and the risk of IBD.

This cross-sectional study utilized data from the 2009-2010 NHANES cycle, focusing on individuals with complete 24-hour dietary intake records and clinically assessed IBD information. Nutrient intake was assessed through dietary recalls and supplement data. Associations between nutrient intake and IBD risk were analyzed by propensity score matching (PSM) with balanced baseline characteristics and logistic regression. Dose-response relationships were examined by restricted cubic splines (RCS). Statistical significance was set at P < 0.05, and analyses were conducted using R software.

The study included 4,072 participants with clinically assessed IBD and complete nutrient intake data. In adjusted analyses, lower intake of vitamin B3, copper, phosphorus, selenium, sodium, and protein below the recommended dietary allowance may increase the risk of developing IBD. Similarly, reduced intake of vitamin B6, vitamin E, and total PUFA is associated with elevated susceptibility to IBD.

This study elucidates the intricate relationship between nutrient intake and the onset of IBD, underscoring the importance of maintaining a balanced diet for gastrointestinal health. These findings emphasize the significance of informed dietary choices in promoting intestinal wellness and potentially reducing the risk of IBD development.

Radiotherapy is a method of treating cancer through radiation aimed at killing cancer cells or inhibiting their growth. However, radiotherapy has numerous side effects because it kills tumors while causing damage to normal cells or tissues. The literature shows that radiation can cause damage to heart tissue. This study found that engineered yeast that produced butyrate can maintain small intestinal barrier function by recovering GPR109A to reduce intestinal damage caused by abdominal irradiation in mice. We unexpectedly found that engineered yeast could mitigate irradiation-induced heart damage via the gut-heart axis. Mechanistically, engineered yeast enhanced taurine and nicotinamide metabolism by increasing the relative abundance of Akkermansia and Lachnospiraceae_NK4A136; then, yeast modulated cardiac function by activating the Sgcg and Nppa genes to attenuate cardiac damage induced by abdominal irradiation. Finally, we confirmed that engineered yeast mitigated cardiac damage caused by total body irradiation, which protected other vital organs through the intestinal tract. This study has a profound impact on cancer treatment, the emergence of engineered yeast will alleviate radiotherapy side effects and benefit patients.

Inflammatory bowel disease (IBD), a chronic and relapsing-remitting condition, is inadequately managed by conventional therapies that often lack targeting specificity and carry significant side effects, particularly failing to address intestinal barrier repair and microbial balance. Probiotics, with their strong colonization capabilities, present a novel approach to drug delivery. Various engineering strategies have been developed to enhance the targeting ability of probiotics to inflammation sites, enabling precise delivery or in situ synthesis of therapeutic molecules to expand their multifunctional potential. This review discusses the recent advancements in bacterial modifications, including surface physico-chemical and biological coating, genetic engineering, outer membrane vesicles, minicells, and bacterial ghosts, all of which can enhance therapeutic localization. We also outline critical preclinical considerations, such as delivery frequency, systemic distribution, immune evasion, and gene contamination risks, for clinical translation. These engineered bacteria and bacterial derivatives hold great promise for personalized and sustained IBD treatments, providing a new frontier for therapy tailored to the complex inflammatory environment of IBD.

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders of the gastrointestinal tract. Despite substantial advances in our understanding of IBD pathogenesis, the currently available therapeutic options remain limited in their efficacy and often come with significant side effects. Therefore, there is an urgent need to explore novel approaches for the management of IBD. One promising avenue of investigation revolves around the use of histone deacetylase (HDAC) inhibitors, which have garnered considerable attention for their potential in modulating gene expression and curbing inflammatory responses. This review emphasizes the pressing need for innovative drugs in the treatment of IBD, and drawing from a wealth of preclinical studies and clinical trials, we underscore the multifaceted roles and the therapeutic effects of HDAC inhibitors in IBD models and patients. This review aims to contribute significantly to the understanding of HDAC inhibitors' importance and prospects in the management of IBD, ultimately paving the way for improved therapeutic strategies in this challenging clinical landscape.

The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.

While surgery plays a pivotal role in the management of ileal Crohn's disease, the risk of endoscopic recurrence following an ileocaecal resection can be greater than 65% within 12 months of surgery. More than 90% of patients with Crohn's disease have a concomitant diagnosis of bile acid diarrhea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in patients with Crohn's disease who have undergone a primary terminal ileal resection with concomitant bile acid diarrhea can alter the microbiome and prevent disease recurrence.

Patients with Crohn's disease who underwent a primary terminal ileal resection and had symptoms of diarrhea within 1-3 months of surgery underwent 75SeHCAT testing for bile acid diarrhea. If positive (75SeHCAT ≤ 15%), patients were treated with colesevelam and stool samples were collected at 4 weeks, 8 weeks, and 6-12 months posttreatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in the clinic as per local guidelines. All patients underwent a 6-12 month postoperative colonoscopy where further stool samples and mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeert's score

RESULTS

A total of 14 patients who completed the study, 10 of whom had a 75SeHCAT positive diagnosis of bile acid diarrhea and were started on treatment with colesevelam. Four patients did not require treatment as 3 were asymptomatic and 1 had a negative 75SeHCAT scan. Three of the fourteen patients had disease recurrence at their 6-12 month postoperative colonoscopy assessment, of which 1 patient was taking colesevelam and 2 patients were not taking colesevelam. A total of 44 fecal samples and 44 mucosal biopsies underwent 16S ribosomal RNA gene analysis to assess α/β-diversity and microbial composition. In the colesevelam treated patients there was no significant difference in α/β-diversity pre- and posttreatment. Pretreatment, the 3 most abundant bacterial classes in all patients were Bacteroidia, Clostridia, and Gammaproteobacteria. Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the 2 patients not given colesevelam, one showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria.

CONCLUSIONS

This small pilot study demonstrated that patients who were given colesevelam, were more likely to be in disease remission at their 6-12 months colonoscopy review compared with those not treated. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in postoperative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance as well as investigate whether this benefit may be present even in those patients with 75SeHCAT negative disease.

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Intestinal fibrous stenosis due to Crohn's disease (CD) is highly prevalent. Although several clinical risk factors for fibrous stenosis have been identified, such as perianal fistulizing disease, small bowel disease location, and deep mucosal ulceration, predicting fibrous stenosis remains challenging. The intestinal microbiota plays a crucial role in the development and progression of CD. However, its role in intestinal fibrous stenosis is poorly understood. Leveraging a single-center cross-sectional study, we aimed to investigate the role of fecal microbiota in CD-associated fibrous stenosis.

Using metagenomic analysis, we examined the differences in fecal microbiota between CD patients with intestinal fibrous stenosis and those without stenosis. We identified specific microbiota and assessed their predictive accuracy for intestinal fibrous stenosis. Additionally, we explored functional differences in intestinal microbiota between the two groups.

: Our investigation of fecal samples revealed no significant differences in the gut microbiota structure between patients with fibrous stenosis and those without stenosis in CD. However, taxonomically, we found 70 taxa with significantly different abundance (p < 0.05) between the two groups. Furthermore, LEfSe analysis indicated that g_Bacteroides and g_Enterocloster could predict intestinal fibrous stenosis while p_Actinobacteria, c_Actinomycetia, c_Bacilli, o_Lactobacillales, f_Streptococcaceae and g_Streptococcus could predict CD without stenosis. Functional analysis revealed differential enrichment in five metabolic pathways at the KEGG pathway level in CD patients with fibrous stenosis, including sphingolipid metabolism, lipoic acid metabolism, and biosynthesis of neomycin, kanamycin and gentamicin. In the eggNOG database, we observed differences in four functional categories between the two groups, encompassing cellular process, signaling, and metabolism.

Fecal microbiota significantly impacted intestinal fibrous stenosis in CD. Although there were no significant differences in alpha and beta diversities, fibrous stenosis was associated with changes in microbiota composition and function, suggesting the potential of fecal microbiota in predicting CD-associated fibrous stenosis.