Intestinal Inflammatory Disease Research Articles

Akkermansia muciniphila: A promising probiotic against inflammation and metabolic disorders.

Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, A. muciniphila regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of A. muciniphila are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live A. muciniphila, but also in pasteurized A. muciniphila, A. muciniphila-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and A. muciniphila, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of A. muciniphila on different diseases and summarize the potential mechanisms of action of A. muciniphila in the treatment of diseases. We provide a comprehensive understanding of A. muciniphila for improving host health and discuss the perspectives of A. muciniphila in the future studies.

Optimization and evaluation of gastroresistant microparticles designed for siRNA oral delivery

Oral administration of siRNA is a challenging strategy for the local treatment of intestinal diseases, including cancer and inflammatory bowel disease. Both nucleic acids and delivery systems, especially lipid nanoparticles (LNPs), are sensitive to the acidic pH of the stomach, bile salts and digestive enzymes. The present work focuses on the design and evaluation of gastroresistant alginate microparticles (MPs) prepared with an original process for oral delivery of siRNA. MPs with a mean diameter of less than 200 µm were obtained without extrusion and emulsification methods. Onpattro® marketed pharmaceutical product and TNF-α siRNA-loaded LNPs were successfully microencapsulated with an efficiency of at least 80 %. Gastroresistance properties and intestinal release were demonstrated in simulated gastric and intestinal fluids. After exposure to simulated gastric fluid, MPs in contact with hepatocyte and LPS-activated monocyte-derived macrophage cell lines reduced the expression of transthyretin and TNF-α, demonstrating the preservation of the siRNA activity.

Human milk extracellular vesicles modulate inflammation and cell survival in intestinal and immune cells.

Human milk contains extracellular vesicles (EVs) that carry bioactive molecules such as microRNA, to the newborn intestine. The downstream effects of EV cargo on signaling and immune modulation may shield neonates against inflammatory diseases, including necrotizing enterocolitis. Premature infants are especially at risk, while human milk-feeding may offer protection. The effect of gestational-age specific term and preterm EVs from transitional human milk was characterized on human intestinal epithelial cells (HIECs and Caco-2), primary macrophages, and THP-1 monocytes. We hypothesized that term and preterm EVs differentially influence immune-related cytokines and cell death. We found that preterm EVs were enriched in CD14 surface marker, while both term and preterm EVs increased epidermal growth factor secretion. Following inflammatory stimuli, only term EVs inhibited secretion of IL-6 in HIECs, and reduced expression of pro-inflammatory cytokine IL-1β in macrophages. Term and preterm EVs inhibited secretion of IL-1β and reduced inflammasome related cell death. We proposed that human milk EVs regulate immune-related signaling via their conserved microRNA cargo, which could promote tolerance and a homeostatic immune response. These findings provide basis for further studies into potential therapeutic supplementation with EVs in vulnerable newborn populations by considering functional, gestational age-specific effects. IMPACT: This study reveals distinct functional differences between term and preterm transitional human milk extracellular vesicles (EVs) highlighting the importance of gestational age in their bioactivity. Term EVs uniquely inhibited IL-6 secretion, IL-1β expression, and apoptosis following inflammatory stimuli. Both term and preterm human milk EVs reduced IL-1β secretion and inflammasome-induced cell death. Conserved human milk extracellular vesicle microRNA cargo could be a mediator of the anti-inflammatory effects, particularly targeting cytokine production, the inflammasome, and programmed cell death. These findings underscore the importance of considering gestational age in future research exploring the therapeutic potential of human milk extracellular vesicles to prevent or treat intestinal inflammatory diseases in neonates.

Heat-killed Lacticaseibacillus paracasei 6235 is more effective than live on DSS-induced colitis via modulation of intestinal microbiota and MAPK/NF-κB signaling pathways.

This study compared the protective effects of both live Lacticaseibacillus paracasei 6235 (LLP 6235) and heat-killed Lacticaseibacillus paracasei 6235 (HK-LP 6235) on ulcerative colitis. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we evaluated physiological state, colon tissue integrity, inflammatory factors, tight junction (TJ) proteins, and intestinal microbiota variations. The findings demonstrated that both LLP 6235 and HK-LP 6235 have the capacity to mitigate colitis damage, enhance TJ protein levels, and restore colon morphology. In addition, these interventions modulated the intestinal inflammatory response by inhibiting pro-inflammatory factors and upregulating anti-inflammatory factors through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Moreover, treatment with LLP 6235 and HK-LP 6235 significantly altered intestinal microbiota diversity, increased the relative abundance of beneficial bacteria, and regulated the short-chain fatty acid (SCFA) levels. Spearman correlation analysis revealed a strong association between TJ proteins, SCFAs, intestinal microbiota, and inflammatory response, suggesting that LLP 6235 and HK-LP 6235 may provide an effective approach to colitis prevention. In conclusion, LLP 6235 and HK-LP 6235 have similar abilities; furthermore, HK-LP 6235 modulated the intestinal microbiota through lipid metabolic pathways, resulting in a greater improvement. Moreover, considering the high stability and safety of prebiotics and their wide applicability, HK-LP 6235 is recommended for use as a modulator of intestinal inflammatory diseases.

Single-cell integration reveals metaplasia in inflammatory gut diseases

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn’s disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner’s glands. Although previously linked to mucosal healing4, we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.

Faecal sample storage without ethanol for up to 24 h followed by freezing performs better than storage with ethanol for shotgun metagenomic microbiome analysis in patients with inflammatory and non-inflammatory intestinal diseases and healthy controls

ObjectiveThe influence of different faecal collection methods on metagenomic analyses remains under discussion, and there is no general agreement on which collection method is preferable for gut microbiome research. We compared faecal samples collected in tubes without preservatives with those containing 10 mL of 96% ethanol for gut microbiome research when the timeframe from defecation to freezing at – 80 °C was up to 24 h. We aimed to compare the collection methods on faeces from participants with inflammatory and non-inflammatory gastrointestinal disorders and healthy controls to investigate the most suitable method when considering data yield, human fraction of sequencing reads, and ease of use. We also examined the faecal sample homogeneity.ResultsFaeces collected in tubes without preservatives resulted in more sequencing reads compared to faeces collected in tubes with 96% ethanol and were also easier to handle. The human fraction of total reads in faeces collected in ethanol from participants with inflammatory bowel disease was higher than all other samples. DNA extraction and sequencing from two different locations in the same faecal sample gave similar results and showed sample homogeneity.

Postoperative continuation of antibiotic prophylaxis beyond 24 h is unnecessary for abdominal surgeries in children and neonates

PurposeDespite recent WHO recommendations, antibiotic prophylaxis is routinely continued for several days after surgery. We conducted a retrospective study to evaluate the safety and efficacy of antibiotic prophylaxis cessation within 24 h after abdominal surgeries MethodsWe retrospectively reviewed the charts of patients who underwent 3 representative gastrointestinal surgeries (1; transumbilical small bowel procedure for intestinal atresia or stenosis, 2; extrahepatic bile duct resection, and hepaticojejunostomy for congenital biliary dilatation, 3; stoma closure for intestinal perforation, anorectal malformation, or inflammatory bowel disease) at our institution between 2011 and 2023. The demographic data collected included age, preoperative hemoglobin level, albumin level, body mass index, and ASA class. Intraoperative and postoperative data were also collected. The patients were divided into 2 groups according to the duration of perioperative antibiotics (‘within 24 h’ and ‘beyond 24 h’), and the incidence of superficial incisional SSI (siSSI) was compared between the 2 groups in each procedure ResultsDuring the study period, 25 cases underwent transumbilical small bowel procedure, 23 cases underwent hepaticojejunostomy, and 45 cases underwent stoma closure. The preoperative care bundle including bowel preparation, cleansing, and operative procedures has not changed during the study period. First- and third-generation cephalosporins were administered to all the patients. All patients received their first single dose of antibiotics within 60 min before the skin incision. In particular, 14 patients who underwent small-bowel procedures received only a single dose. The SSI rates for small bowel procedures, hepaticojejunostomy, and stoma closure were 0%, 4.4%, and 4.4%, respectively. No SSIs were observed in any of the procedures in the 'within 24 h' group ConclusionBased on our study, we conclude that ≤24 h of postoperative continuation of antibiotic prophylaxis is sufficient for siSSI prevention in hepaticojejunostomy and stoma closure. Additionally, single-dose antibiotic prophylaxis is adequate for neonatal small bowel procedures.

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.

A mitochondria-targeted nitric oxide probe with large Stokes shift for real-time imaging and evaluation of inflammatory bowel disease in situ

BackgroundInflammatory bowel disease (IBD) is a prevalent inflammatory disorder, and the abnormal expression of nitric oxide (NO) produced by biocatalysis of iNOS enzyme in mitochondria is directly associated with the occurrence and progression of IBD. Activatable fluorescent probes offer promising tools for early diagnosis of IBD, however, inadequate biodistribution and limited targeting properties of these probes in vivo severely impede accurate diagnosis of IBD and real-time evaluation of inflammatory levels in situ. Therefore, it is necessary to design a highly efficient fluorescent probe towards NO to overcome inadequate biodistribution and achieve accurate diagnosis and evaluation of IBD in situ. ResultsWe designed a highly efficient mitochondria-targeted “turn-on” NIR fluorescent probe Cy-OMe which has excellent targeting properties and imaging ability. The response mechanism is probe Cy-OMe rapidly undergoes N-nitrosation reaction resulting in “turn-on” NIR fluorescence signal when exposed to NO. Cy-OMe exhibits high sensitivity and specificity in detecting NO content in vitro, owing to its large Stokes shift. Furthermore, the probe Cy-OMe not only efficiently targets mitochondria but also enables precise assessment of fluctuations in endogenous NO concertation across various cell types. Importantly, by virtue of large Stokes shift and excellent mitochondrial targeting ability, Cy-OMe has the capability to specifically evaluate dynamic fluctuations of NO in lipopolysaccharide (LPS)‐stimulated IBD mouse models in situ and Cy-OMe was achieved high-contrast imaging and precision diagnosis of intestinal inflammation diseases. SignificanceCy-OMe can accurately assess fluctuations in NO levels and show high signal fidelity in the diseased intestine region, which has prospects in the non-invasive diagnosis of intestinal inflammation in vivo. At the same time, it is expected to serve as a potential diagnose platform for investigating the physiological processes underlying NO-related inflammatory diseases and promoting understanding of the pathological functions of NO across diverse inflammatory diseases.

Evaluation of the Protective Effect of Hydroalcoholic and Aqueous Extracts of Ulmus minor Leaves on Ulcerative Colitis Induced by Acetic Acid in Rats

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the large intestine that cannot be cured, but its symptoms can be managed. Objectives: This study aimed to evaluate the protective effects of hydroalcoholic and aqueous extracts of Ulmus minor leaves on UC induced by acetic acid in rats. Methods: Rats were randomly divided into seven groups of five, and 3% acetic acid was used to induce colitis. To assess the protective effect of Ulmus minor leaves, macroscopic, microscopic, and histological evaluations were performed on the different study groups. Results: Macroscopic examinations of both the hydroalcoholic and aqueous extract groups showed that the aqueous extract at a dose of 200 mg/kg provided the best protective effect on colon tissue. Rats treated with hydroalcoholic extracts at doses of 100 mg/kg and 200 mg/kg, as well as those treated with aqueous extract at 100 mg/kg, also showed favorable outcomes compared to the control group, with a significant difference (P < 0.05). Furthermore, among the groups treated with hydroalcoholic and aqueous extracts, the aqueous extract at 200 mg/kg demonstrated the most protective effects based on microscopic and histological evaluations of the colon. Conclusions: The extracts of Ulmus minor leaves demonstrated anti-inflammatory properties in an animal model of colitis. Further studies are required to evaluate their potential therapeutic benefits in patients with UC.

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.

Synergistic effect and mechanism of monoacylglycerol lipase inhibitor and Icaritin in the treatment of ulcerative colitis

Ulcerative colitis (UC) is a chronic, relapsing nonspecific intestinal inflammatory disease. It is difficult for a single drug to treat UC effectively and maintain long-term efficacy. There is an urgent need to find new drugs and treatment strategies. MAGL11 is a new kind of single acylglycerol lipase (MAGL) inhibitor. Icaritin (Y003) is the major metabolite of icariin in vivo. Several studies have confirmed the role of MAGL inhibitors and icariin in anti-inflammatory and regulation of intestinal stability. Therefore, this study adopted a new strategy of combining MAGL inhibitor with Icaritin to further explore the role and mechanism of drugs in the treatment of UC. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining (HE), immunohistochemical (IHC) and Western blot were used to detect the synergistic protective effects of MAGL11 and Y003 on intestinal pathological injury, intestinal mucosal permeability and inflammation in UC mice. 16S rDNA sequencing was used to detect the synergistic effect of MAGL11 and Y003 on gut microbiota. The effects of MAGL11 and Y003 combined therapy on serum and fecal metabolism of UC mice were analyzed by untargeted metabolomics. Proteomics method was applied to investigate the molecular mechanisms underlying MAGL11 and Y003 synergy in the treatment of UC. The results showed that MAGL11 and Y003 could synergistically improve the clinical symptoms, reduce intestinal inflammation and pathological damage, and improve intestinal mucosal permeability in UC mice. The mechanism study found that MAGL11 and Y003 could synergistically inhibit Toll-like receptors 4 (TLR4) / Myeloid differentiation primary response gene (Myd88)/Nuclear factor kappa-B (NF-κB) pathway and further regulate gut microbiota imbalance and metabolic disorders to treat UC.

Intestinal flora and inflammatory bowel disease: Causal relationships and predictive models

BackgroundInflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is significantly influenced by intestinal flora. Understanding the genetic and microbiotic interplay is crucial for IBD prediction and treatment. MethodsWe used Mendelian randomization (MR), transcriptomic analysis, and machine learning techniques, integrating data from the MiBioGen Consortium and various GWAS datasets. SNPs associated with intestinal flora were mapped to genes, with LASSO regression refining gene selection. Differentially expressed genes (DEGs) and immune infiltration patterns were identified through transcriptomic analysis. Six machine learning models were used for predictive modeling. FindingsMR analysis identified 25 gut microbiota classifications causally related to IBD. SNP mapping and gene expression analysis highlighted 24 significant genes. Drug target MR and colocalization validated these genes' causal relationships with IBD. Key pathways identified included the PI3K-Akt signaling pathway and epithelial-mesenchymal transition. Immune infiltration analysis revealed distinct patterns between high and low LASSO score groups. Machine learning models demonstrated high predictive value, with soft voting enhancing reliability. InterpretationBy integrating MR, transcriptomic analysis, and sophisticated machine learning approaches, this study elucidates the causal relationships between intestinal flora and IBD. The application of machine learning not only enhanced predictive modeling but also offered new insights into IBD pathogenesis, highlighted potential therapeutic targets, and established a robust framework for predicting IBD onset.

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.

Indole-3-aldehyde Alleviates High-Fat Diet-Induced Gut Barrier Disruption by Increasing Intestinal Stem Cell Expansion.

High-fat diet (HFD) feeding is known to cause intestinal barrier disruption, thereby triggering severe intestinal inflammatory disease. Indole-3-aldehyde (IAld) has emerged as a potential candidate for mitigating inflammatory responses and maintaining intestinal homeostasis. However, the role of IAld in the HFD-related intestinal disruption remains unclear. In this study, 48 7 week-old male C57BL/6J mice were assigned to four groups: the normal chow diet (NCD) group received a NCD; the HFD group was fed an HFD; the HFD + IAld200 group was supplemented with 200 mg/kg IAld in the HFD; and the HFD + IAld600 group was supplemented with 600 mg/kg IAld in the HFD. The results showed that dietary IAld supplementation ameliorated fat accumulation and metabolic disorders, which are associated with reduced intestinal permeability. This reduction potentially led to decreased systemic inflammation and enhanced intestinal barrier function in HFD-fed mice. Furthermore, we found that IAld promoted intestinal stem cell (ISC) proliferation by activating aryl hydrocarbon receptors (AHRs) in vivo and ex vivo. These findings suggest that IAld restores the HFD-induced intestinal barrier disruption by promoting AHR-mediated ISC proliferation.

Evaluation of the Antifibrotic Effects of Drugs Commonly Used in Inflammatory Intestinal Diseases on In Vitro Intestinal Cellular Models.

The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-β1 (TGF-β1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-β1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-β1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.

Microbiota-Derived Extracellular Vesicle as Emerging Actors in Host Interactions.

The human microbiota is an intricate micro-ecosystem comprising a diverse range of dynamic microbial populations mainly consisting of bacteria, whose interactions with hosts strongly affect several physiological and pathological processes. The gut microbiota is being increasingly recognized as a critical player in maintaining homeostasis, contributing to the main functions of the intestine and distal organs such as the brain. However, gut dysbiosis, characterized by composition and function alterations of microbiota with intestinal barrier dysfunction has been linked to the development and progression of several pathologies, including intestinal inflammatory diseases, systemic autoimmune diseases, such as rheumatic arthritis, and neurodegenerative diseases, such as Alzheimer's disease. Moreover, oral microbiota research has gained significant interest in recent years due to its potential impact on overall health. Emerging evidence on the role of microbiota-host interactions in health and disease has triggered a marked interest on the functional role of bacterial extracellular vesicles (BEVs) as mediators of inter-kingdom communication. Accumulating evidence reveals that BEVs mediate host interactions by transporting and delivering into host cells effector molecules that modulate host signaling pathways and cell processes, influencing health and disease. This review discusses the critical role of BEVs from the gut, lung, skin and oral cavity in the epithelium, immune system, and CNS interactions.

Immunomodulatory Effects of a Probiotic Mixture: Alleviating Colitis in a Mouse Model through Modulation of Cell Activation Markers and the Gut Microbiota.

Ulcerative colitis (UC) is a persistent inflammatory intestinal disease that consistently affects the colon and rectum. Its exact cause remains unknown. UC causes a considerable challenge in healthcare, prompting research for novel therapeutic strategies. Although probiotics have gained popularity as possible candidates for managing UC, studies are still ongoing to identify the best probiotics or probiotic mixtures for clinical applications. This study aimed to determine the efficacy of a multi-strain probiotic mixture in mitigating intestinal inflammation in a colitis mouse model induced by dextran sulfate sodium. Specifically, a multi-strain probiotic mixture consisting of Tetragenococcus halophilus and Eubacterium rectale was used to study its impact on colitis symptoms. Anti-inflammatory effects were evaluated using ELISA and flow cytometry. The configuration of gut microbial communities was determined using 16S rRNA metagenomic analysis. According to this study, colitis mice treated with the probiotic mixture experienced reduced weight loss and significantly less colonic shortening compared to untreated mice. Additionally, the treated mice exhibited increased levels of forkhead box P3 (Foxp3) and interleukin 10, along with decreased expression of dendritic cell activation markers, such as CD40+, CD80+, and CD83+, in peripheral blood leukocytes and intraepithelial lymphocytes. Furthermore, there was a significant decrease in the frequencies of CD8+N.K1.1+ cells and CD11b+Ly6G+ cells. In terms of the gut microbiota, probiotic-mixture treatment of colitis mice significantly increased the abundance of the phyla Actinobacteria and Verrucomicrobia (p < 0.05). These results provide valuable insights into the therapeutic promise of multi-strain probiotics, shedding light on their potential to alleviate colitis symptoms. This research contributes to the ongoing exploration of effective probiotic interventions for managing inflammatory bowel disease.

Gastrointestinal and Hepatobiliary Manifestations Associated with Untreated Celiac Disease in Adults and Children: A Narrative Overview.

Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a major risk factor for various CeD-associated morbidities, genetic, immunological, and environmental factors also play an important role. The clinical presentation of CeD widely varies and can range from asymptomatic to full-blown symptoms due to the multi-system nature of CeD. The typical gastrointestinal (GI) manifestations of CeD include abdominal pain, diarrhea, bloating, and weight loss, but several hepatobiliary manifestations and a poor nutritional status have also been described. Currently, a gluten-free diet (GFD) is the only current evidence-based treatment that leads to the complete recovery of mucosal damage and the reversibility of its progression. Conversely, undiagnosed CeD might have severe consequences in children as well as in adult patients. This narrative overview aims to characterize the GI and hepatobiliary manifestations, nutritional deficiencies, and delayed pediatric development associated with unrecognized CeD in order to identify it promptly. Moreover, the role of GFD and how it could prevent long-term complications of CeD are described.

Gut Microbiota Defines Functional Direction of Colonic Regulatory T Cells with Unique TCR Repertoires.

Intestinal microbiota and selected strains of commensal bacteria influence regulatory T (Treg) cell functionality in the colon. Nevertheless, whether and how microbiota changes the transcriptome profile and TCR specificities of colonic Tregs remain to be precisely defined. In this study, we have employed single-cell RNA sequencing and comparatively analyzed colonic Tregs from specific pathogen-free and germ-free (GF) mice. We found that microbiota shifts the activation trajectory of colonic Tregs toward a distinct phenotypic subset enriched in specific pathogen-free but not in GF mice. Moreover, microbiota induced the expansion of specific Treg clonotypes with shared transcriptional specificities. The microbiota-induced subset of colonic Tregs, identified as PD-1- CXCR3+ Tregs, displayed enhanced suppressive capabilities compared with colonic Tregs derived from GF mice, enhanced production of IL-10, and were the primary regulators of enteric inflammation in dextran sodium sulfate-induced colitis. These findings identify a hitherto unknown gut microbiota and immune cell interaction module that could contribute to the development of a therapeutic modality for intestinal inflammatory diseases.