Chronic Intestinal Inflammatory Disease Research Articles

P1335 Dietary Carnosic Acid Eases Colitis by Activating NRF2 Signal via Regulating Gut Microbiota and Metabolites

Abstract Background Ulcerative colitis (UC) is a chronic intestinal inflammatory disease, which is closely related to the imbalance of intestinal microbiota and metabolic alterations. We have studied the role of dietary carnosic acid (CA) in alleviating intestinal inflammation through regulating the intestinal microbiota and its metabolites. Methods Mice were fed with a diet supplemented with CA or a normal diet, and the enteritis model was established using dextran sulfate sodium (DSS). The feces of mice fed with different diets were transplanted into germ-free mice to determine the direct role of the CA-regulated microbiota in alleviating colitis. The intestinal microbiota was analyzed by 16S rRNA sequencing, serum metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) metabolomics, and downstream targets were analyzed by RNA sequencing. Results Through the analysis of the microbiota based on the 16S rRNA gene, we found for the first time that the addition of CA to the diet improved the imbalance of the intestinal microbiota induced by DSS. The protective mechanism of CA against DSS-induced colitis is to improve the function of the intestinal mucosal barrier by activating the Nrf2 signaling pathway. It is worth noting that the addition of CA to the diet can enrich the microbe-derived 3-indolepropionic acid, thereby activating the Nrf2 signaling in human colonic epithelial cells. In addition, exogenous 3-indolepropionic acid treatment has a similar protective effect on DSS-induced colitis by improving the Nrf2 signaling-dependent mucosal barrier function. Conclusion In conclusion, our research results indicate that the intestinal microbiota - 3-indolepropionic acid - Nrf2 axis plays an important role in maintaining intestinal homeostasis, which may represent a new method for preventing colitis by manipulating the metabolites of the intestinal microbiota.

Metagenomic analysis of goat feces from Ogliastra (Sardinia, Italy)

With its constitutive and functional characteristics, the intestinal microbiota plays a crucial role in the health condition of the animals. Variations in the composition and gene expression of the intestinal microbiota are associated with the risk of the onset of various pathologies of the gastrointestinal tract and chronic inflammatory intestinal diseases. The objectives of this study were to evaluate the variability in the composition of the intestinal microbiota of goats of different breeds (Sarda, Maltese, and Alpine) farmed in different flocks of the region of Ogliastra (Sardegna, Italy) and to assess whether the type of feeding (natural pasture grazing-based versus intensive) could affect the intestinal bacterial composition. We also evaluated possible differences in the composition of the intestinal microbiota between healthy and Caprine arthritis encephalitis (CAE)-affected goats. The economic damage caused by this pathology is due to the reduction in milk production, with infected animals having greater susceptibility to contract diseases. The results of our study highlighted a statistically significant difference (P = 0.001–0.005) in the intestinal bacterial composition between the intensively managed flock and the other natural pasture-based flock.g In particular, a significantly greater abundance of Acidoaminococcaceae in the intensive flock was obgserved. Furthermore, a significantly greater abundance of Prevotellaceae was found in two localities in which, out of a total of 29 animals, only four tested negative for CAE. From these data, we deduced that the presence of Prevotellaceae can be an indication of the disease. This difference could be attributed to the farming system, the Cardedu farm being the only intensive one, and to the geographical distance of this location from the other sampling sites. Therefore, the results of the present study suggest that extensive or intensive farm management may affect the intestinal microbiota of goats.

Clinical study of Jianpi Qingchang decoction in the treatment of ulcerative colitis patients with spleen deficiency and dampness-heat syndrome accompanied by fatigue: Study protocol for a randomized controlled trial.

Ulcerative colitis (UC) is a chronic non-specific inflammatory intestinal disease, categoried under "dysentery" and "intestinal bleeding" in Traditional Chinese Medicine (TCM). Jianpi Qingchang decoction (JPQC) is a combination formula specifically designed for the treatment of UC. The primary objective of this study is to examine the clinical efficacy of JPQC in individuals diagnosed with UC who exhibit both spleen deficiency and dampness-heat syndrome, along with the presence of fatigue. The investigation will focus on assessing the impact of JPQC on the gut microbiota and metabolites in these patients, aiming to elucidate the regulatory mechanism that JPQC exerts on the gut microbiota and metabolites in the context of UC-related fatigue. In this randomized clinical trial, 140 subjects diagnosed with UC will be recruited and randomized into two groups. They will receive either JPQC combined with mesalazine or mesalazine alone for 12 weeks. Follow-up visits will be conducted every four weeks, with a post-treatment visit scheduled at 6 months. The primary outcome measures include the Inflammatory bowel disease fatigue scale(IBD-F). Secondary efficacy indicators comprise the assessment of TCM syndrome and individual syndrome efficacy before and after treatment, Modified Mayo score, Simple clinical colitis activity index (SCCAI), as well as the Inflammatory Bowel Disease Questionnaire (IBDQ) for each group. The other outcomes are the Intestinal microbial diversity and non-targeted metabonomics, which will be measured at baseline and 12 weeks after randomization. If effective, JPQC will provide substantial clinical evidence concerning the effectiveness and safety in the treatment of patients with UC experiencing spleen deficiency and dampness-heat syndrome accompanied by fatigue. ChiCTR2300068348.

Analysis of the Preventive Effect of Lonicera caerulea Pomace and Its Isolated Components on Colitis in Mice Based on Gut Microbiota and Serum Metabolomics.

Inflammatory bowel disease (IBD), including relapsing-remitting ulcerative colitis and Crohn's disease, is a non-specific chronic intestinal inflammatory disease. Lonicera caerulea, which is rich in polyphenolic compounds, has been shown to exert antioxidative and anti-inflammatory effects. The research evaluates the dietary impacts of Lonicera caerulea pomace, its polyphenol-rich extract, and fiber-rich residue on colitis symptoms. Colitis was induced with 2.5% DSS (dextran sulfate sodium) aqueous solution after continuous feeding of customized Lonicera caerulea feed for 2.5 weeks. The results indicate that the intake of the polyphenol-rich extract has an effect in preventing colitis in mice, but the effect is less than that by the pomace itself, and the fiber residue alone does not prevent the condition when ingested. The pomace and polyphenol-rich extract have a positive regulatory effect on the gut microbiota of mice with colitis, and the intake of Lonicera caerulea pomace significantly restores 15 metabolites in mice with colitis, significantly improving five metabolic pathways, including steroid biosynthesis, with the regulation of metabolites and metabolic pathways being significantly correlated with the gut microbiota.

Research progress of probiotics and their protective strategy in the field of inflammatory bowel disease treatment: A review.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disease characterized by recurrent episodes and difficult-to-cure symptoms. Although the pathogenesis of IBD is closely related to host genetic susceptibility, intestinal microbiota, environmental factors, and immune responses, leading to mucosal damage and increased intestinal permeability. Intestinal mucosal injury in IBD patients causes pathogenic bacteria and pathogenic factors to invade the intestine, leading to disturb the structure and metabolic products of intestinal flora. Researchers have found that probiotics, as live microbial agents, can effectively inhibit the growth of pathogenic bacteria, regulate intestinal flora, optimize intestinal microecology, restore intestinal homeostasis, and promote intestinal mucosal repairing. During the oral delivery process, probiotics are susceptible to adverse physiological factors, leading to reduced bioavailability. Additionally, the oxidative stress microenvironment induced by intestinal mucosal damage makes it difficult for probiotics to colonize the intestinal tract of IBD patients, thereby affecting their probiotic effect. This research mainly introduces and reviews the advantages and disadvantages of probiotics and their protective strategies in the treatment of IBD, and prospects the future development trends of probiotics and their protective strategies. Probiotics can effectively inhibit the growth of harmful microorganisms, regulate the structure of the intestinal microbiota, and promote mucosal repairing, thereby reducing immune stress and alleviating intestinal inflammation, providing a new perspective for the treatment of IBD. The development of single-cell encapsulation technology not only effectively maintaining the biological activity of probiotics during oral delivery, but also endowing probiotics with additional biological functions naturally achieved through surface programming, which has multiple benefits for intestinal health.

ONIS-STOMA: An observational multicentre prospective protocol study of stoma patients

Approximately 70,000 Italians live with urinary or intestinal stomas, primarily due to cancer, chronic inflammatory intestinal diseases, and trauma. These individuals face physical, psychological, and social challenges, reducing their quality of life. No study has yet mapped this situation in Italy. The ONIS-STOMA study aims to collect sociodemographic, clinical, health status, and quality of life data from patients with stomas to identify pathways and interventions for improving clinical outcomes and overall quality of life. This multicenter observational prospective study will involve at least four centers and adhere to the Strengthening the Reporting of Observational Studies in Epidemiology Checklist. Eligible participants are adults with temporary or permanent intestinal or urinary stomas attending specialized outpatient clinics. Data will be collected via ONIS, a dedicated online platform. Descriptive and correlation analyses will be conducted, targeting a sample size of 3,000–6,000 patients.•The study will provide valuable insights into the lives of patients with stomas in Italy, guiding personalized interventions.•The number of patients with stomas is expected to increase due to the aging population and rising prevalence of chronic conditions.•The registry could enroll patients to monitor their progress and provide decision-makers with information on the overall health status of this population.

Lemairamin (Wgx-50) Attenuates DSS-Induced Intestinal Inflammation in Zebrafish.

Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.

Probiotic bacteria can modulate immune responses to paratuberculosis vaccination.

Mycobacterium avium subsp. paratuberculosis (Map) is the etiological agent of paratuberculosis (PTB), a chronic intestinal inflammatory disease that causes high economical losses in dairy livestock worldwide. Due to the absence of widely available preventive or therapeutical treatments, new alternative therapies are needed. In this study, the effect of a probiotic alone or in combination with a commercial vaccine has been evaluated in a rabbit model. Vaccination enhanced the humoral response, exerted a training effect of peripheral polymorphonuclear neutrophils (PMNs) against homologous and heterologous stimuli, stimulated the release of pro-inflammatory cytokines by gut-associated lymphoid tissue (GALT) macrophages, and reduced the bacterial burden in GALT as well. However, the administration of the probiotic after vaccination did not affect the PMN activity, increased metabolic demand, and supressed pro-inflammatory cytokines, although humoral response and bacterial burden decrease in GALT was maintained similar to vaccination alone. The administration of the probiotic alone did not enhance the humoral response or PMN activity, and the bacterial burden in GALT was further increased compared to the only challenged group. In conclusion, the probiotic was able to modulate the immune response hampering the clearance of the infection and was also able to affect the response of innate immune cells after vaccination. This study shows that the administration of a probiotic can modulate the immune response pathways triggered by vaccination and/or infection and even exacerbate the outcome of the disease, bringing forward the importance of verifying treatment combinations in the context of each particular infectious agent.

N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.

Effect of screening colonoscopy frequency on colorectal cancer mortality in patients with a family history of colorectal cancer.

Colorectal cancer is a common malignant tumor in China, and its incidence in the elderly is increasing annually. Inflammatory bowel disease is a group of chronic non-specific intestinal inflammatory diseases, including ulcerative colitis and Crohn's disease. To assess the effect of screening colonoscopy frequency on colorectal cancer mortality. We included the clinicopathological and follow-up data of patients with colorectal cancer who underwent laparoscopic colectomy or open colectomy at our Gastrointestinal Department between January 2019 and December 2022. Surgical indicators, oncological indicators, and survival rates were compared between the groups. The results of 104 patients who met the above criteria were extracted from the database (laparoscopic colectomy group = 63, open colectomy group = 41), and there were no statistically significant differences in the baseline data or follow-up time between the two groups. Intraoperative blood loss, time to first ambulation, and time to first fluid intake were significantly lower in the laparoscopic colectomy group than in the open colectomy group. The differences in overall mortality, tumor-related mortality, and recurrence rates between the two groups were not statistically significant, and survival analysis showed that the differences in the cumulative overall survival, tumor-related survival, and cumulative recurrence-free rates between the two groups were not statistically significant. In elderly patients with colorectal cancer, laparoscopic colectomy has better short-term outcomes than open colectomy, and laparoscopic colectomy has superior long-term survival outcomes compared with open colectomy.

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL-35 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T-cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL-35-mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL-35, a colitis model was successfully induced by giving BALB/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia/IL-35, empty plasmid-transformed Pichia (Pichia/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL-35 treatment was detected. After administration of Pichia/IL-35, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia/IL-35 treatment group was alleviated. Notably, Pichia/IL-35 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL-6 in the colon. With Pichia/IL-35 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. In vitro experiments, IL-35 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia/IL-35 group also expressed more TCPTP than that of the untreated group and the Pichia/0 group.

The association between circulating leukocytes and inflammatory bowel disease: a two-sample Mendelian randomization study.

Inflammatory bowel disease (IBD) is a highly prevalent, recurrent, chronic intestinal inflammatory disease. Several observational studies have shown that circulating leukocytes are strongly associated with IBD. However, whether alterations in leukocytes are causally related to IBD remains uncertain. The present study explores this issue with the Mendelian randomization (MR) analysis method. The Genome wide association study (GWAS) statistical data related to circulating leukocytes and IBD were obtained from the Blood Cell Consortium and the IEU Qpen GWAS project, respectively. Inverse variance weighting (IVW) was used as the main MR analytical method, coupled with a series of sensitivity analyses to ensure the reliability of the results. The results of IVW showed that increased monocyte count (especially CD14- CD16+ monocyte absolute counts) was negatively correlated with the risk of IBD and its main subtypes. Increased neutrophil count was positively associated with the risk of IBD and ulcerative colitis. Meanwhile, there was no causal relationship between basophil, eosinophil, lymphocyte counts and IBD risk. These results indicate that a causal relationship exists between circulating leukocytes and the risk of IBD and its subtypes, which confirms the important role that the leukocyte immune system plays in IBD. Our findings provide additional research directions for the clinical prevention and treatment of IBD.

Research progress in the treatment of inflammatory bowel disease with natural polysaccharides and related structure-activity relationships.

Inflammatory bowel disease (IBD) comprises a group of highly prevalent and chronic inflammatory intestinal tract diseases caused by multiple factors. Despite extensive research into the causes of the disease, IBD's pathogenic mechanisms remain unclear. Moreover, side effects of current IBD therapies restrict their long-term clinical use. In contrast, natural polysaccharides exert beneficial anti-IBD effects and offer advantages over current anti-IBD drugs, including enhanced safety and straightforward isolation from abundant and reliable sources, and thus may serve as components of functional foods and health products for use in IBD prevention and treatment. However, few reviews have explored natural polysaccharides with anti-IBD activities or the relationship between polysaccharide conformation and anti-IBD biological activity. Therefore, this review aims to summarize anti-IBD activities and potential clinical applications of polysaccharides isolated from plant, animal, microorganismal, and algal sources, while also exploring the relationship between polysaccharide conformation and anti-IBD bioactivity for the first time. Furthermore, potential mechanisms underlying polysaccharide anti-IBD effects are summarized, including intestinal microbiota modulation, intestinal inflammation alleviation, and intestinal barrier protection from IBD-induced damage. Ultimately, this review provides a theoretical foundation and valuable insights to guide the development of natural polysaccharide-containing functional foods and nutraceuticals for use as dietary IBD therapies.

Monocyte CD36 Expression Predicts Disease Activity in Patients With Crohn's Disease.

Background: Crohn's disease (CD) is a chronic intestinal inflammatory disease associated with genetic, environmental, and other unknown factors. Cluster of differentiation 36 (CD36) plays an important role in cancer, inflammation, and metabolic diseases. Although CD36 has recently been implicated in various diseases, its role in CD is still unclear. Methods: Blood samples were collected from patients with CD and healthy volunteers. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation over Ficoll-Paque and labeled with monoclonal antibodies (CD14-APC and CD36-PE). Flow cytometer CytoFlex is used for analysis. Results: Twenty-nine patients with CD in remission, 42 patients with active CD, and 23 healthy volunteers were included in the study. Our results showed that the frequency of the CD14+CD36+ monocyte subset was increased in PBMCs from patients with active CD compared with patients in remission and healthy controls. However, CD36 on monocytes was lower in CD compared with the healthy controls. CD36 expression was decreased in patients with active CD compared with that of patients with CD in remission and healthy control subjects, but no difference was found between patients with CD in remission and healthy controls. Interestingly, we found negative correlations of CD36 with HBI, SES-CD, C-reactive protein, and neutrophil-to-lymphocyte ratio. Conclusions: These data indicate that monocyte CD36 associates with disease activity in CD and might be a potential biomarker for assessing the activity of CD.

The impact of gut microbiome enterotypes on ulcerative colitis: identifying key bacterial species and revealing species co-occurrence networks using machine learning

ABSTRACT Ulcerative colitis (UC) is a chronic inflammatory intestinal disease affecting the colon and rectum, with its pathogenesis attributed to genetic background, environmental factors, and gut microbes. This study aimed to investigate the role of enterotypes in UC by conducting a hierarchical analysis, determining differential bacteria using machine learning, and performing Species Co-occurrence Network (SCN) analysis. Fecal bacterial data were collected from UC patients, and a 16S rRNA metagenomic analysis was performed using the QIIME2 bioinformatics pipeline. Enterotype clustering was conducted at the family level, and deep neural network (DNN) classification models were trained for UC and healthy controls (HC) in each enterotype. Results from eleven 16S rRNA gut microbiome datasets revealed three enterotypes: Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Clostridiaceae (ET-C). Ruminococcus (R. gnavus) abundance was significantly higher in UC subjects with ET-B and ET-C than in those with ET-L. R. gnavus also showed a positive correlation with Clostridia in UC SCN for ET-B and ET-C subjects, with a higher correlation in ET-C subjects. Conversely, Odoribacter (O.) splanchnicus and Bacteroides (B.) uniformis exhibited a positive correlation with tryptophan metabolism and AMP-activated protein kinase (AMPK) signaling pathways, while R. gnavus showed a negative correlation. In vitro co-culture experiments with Clostridium (C.) difficile demonstrated that fecal microbiota from ET-B subjects had a higher abundance of C. difficile than ET-L subjects. In conclusion, the ET-B enterotype predisposes individuals to UC, with R. gnavus as a potential risk factor and O. splanchnicus and B. uniformis as protective bacteria, and those with UC may have ultimately become ET-C.

Composition of gut microbiota and its correlations with neurological, intestinal, cardiovascular and metabolic diseases.

The intestinal microbiota is a microenvironment that has been the subject of studies for several decades.Over time, it has been reconsidered as a possible cofactor of multiple acute and chronic humandiseases. In fact, alterations of the intestinal bacterial flora have been found in various neurological diseases. There are three modes of interaction between the intestinal microbiota and the gut-brain-axis: chemical signals, neural pathways and immune system. Even at the gastrointestinal level, the gut microbiota plays certainly an important role in the etiopathogenesis of chronic intestinal inflammatory diseases but also in irritable bowel syndrome. An important correlation has also been demonstrated with non-alcoholic fatty liver disease, as well as in other metabolic, cardiovascular and oncological diseases. Bacteria, viruses, fungi and various microorganisms that normally reside in our intestines can also be called into question as protective factors against these diseases. All this evidence leads researchers to consider the gut microbiota as a key element in the determination of aforementioned diseases. Therefore, it would be foreseeable in the future to associate the use of probiotics with the therapies used in the treatment of all these diseases. In this review we have condensed the main current knowledge regarding the link between the most frequent diseases and the gut microbiota.

Macrophage-biomimetic liposomes delivery of carbon dots nanozymes ameliorate ulcerative colitis by modulating inflammation pathways and remodeling the redox microenvironment

As a recurrent chronic inflammatory intestinal disease, ulcerative colitis (UC) has seriously affected the life quality of patients. Numerous studies have demonstrated excessive reactive oxygen species (ROS) are involved in the occurrence and development of UC, and manipulating ROS expression in the intestinal microenvironment to lower the redox signaling and oxidative stress is a promising strategy in UC therapeutics. We previously demonstrated that carbon-dots (C-dots) nanozymes with superoxide dismutase-like activity could effectively clear ROS and alleviate inflammation, while the accurate lesion location targeting is still a crucial factor in impacting their therapeutic efficiency. In this study, inspired by naturally occurring intercellular interactions, macrophage cell membrane-coated liposomes were constructed to deliver C-dots to amplify their efficiency. The obtained C-dots@Lipo-M endowed C-dots with prolonged circulation time and inflammation targeting capability. In addition, this delivery platform could be co-localized with mitochondria where ROS generated. In dextran sulfate sodium (DSS)-induced UC models, C-dots@Lipo-M exerted satisfactory preventive and therapeutic effects on colitis by reversing the shortened colon length, scavenging ROS, decreasing the expression of pro-inflammatory cytokines, and reducing barrier protein expression at colon sites. Further transcriptome sequencing revealed that C-dots@Lipo-M might alleviate intestinal inflammation by modulating inflammation pathways and remodeling the redox microenvironment. Collectively, this study provides a new targeted strategy to improve nanozymes therapeutic efficiency and extends their biomedical applications on inflammation-related diseases.

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects more than 3.5 million people, with rising prevalence. It deeply affects patients' daily life, increasing the burden on patients, families, and society. Presently, the etiology of IBD remains incompletely clarified, while emerging evidence has demonstrated that altered gut microbiota and decreased aryl hydrocarbon receptor (AHR) activity are closely associated with IBD. Furthermore, microbial metabolites are capable of AHR activation as AHR ligands, while the AHR, in turn, affects the microbiota through various pathways. In light of the complex connection among gut microbiota, the AHR, and IBD, it is urgent to review the latest research progress in this field. In this review, we describe the role of gut microbiota and AHR activation in IBD and discussed the crosstalk between gut microbiota and the AHR in the context of IBD. Taken as a whole, we propose new therapeutic strategies targeting the AHR-microbiota axis for IBD, even for other related diseases caused by AHR-microbiota dysbiosis.

Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease

Ulcerative colitis and Crohn’s disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils. Using spatial transcriptomics in human tissue at single-cell resolution (CosMx Spatial Molecular Imaging) we spatially localize each of the macrophage and neutrophil subsets identified by single-cell RNA-sequencing and unravel further macrophage diversity based on their tissue localization. Finally, single-cell RNA-sequencing combined with single-cell spatial analysis reveals a strong communication network involving macrophages and inflammatory fibroblasts. Our data sheds light on the cellular complexity of these diseases and points towards the myeloid and stromal compartments as important cellular subsets for understanding patient-to-patient heterogeneity.