Intestinal Inflammatory Disease Research Articles

5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.

Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient's life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis. To verify the anti-inflammatory effect of 5-MTP in vivo, we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin-eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level. This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis in vivo. Moreover, it inhibits inflammation and M1 polarization response in vitro. 5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.

Comparative analysis of pectin and prebiotics on human microbiota modulation in early life stages and adults.

The gut microbiota is essential in human health, influencing various physiological processes ranging from digestion and metabolism to immune function and mental health. Dietary fiber pectins and prebiotics have emerged as key modulators of gut microbiota composition and function, offering potential therapeutic implications for promoting gut health and preventing intestinal inflammatory diseases. In this review, we explore the modulation of gut microbiota by dietary fiber pectins and prebiotics in infants and adults. We begin with an overview of the gut microbiota composition and function in different age groups, highlighting the factors in shaping microbial communities in both age groups, especially the effect of diet. We then delve into the impact of dietary fiber pectins and prebiotics on gut microbiota composition and function, examining their effects on digestive health, intestinal barrier integrity, immune function, metabolic health, and mental health across different life stages. We further compare how aging affects the gut function and immune system, and we discuss the main health outcomes associated with dietary fiber intake and prebiotics, including the impact on digestive health, improvement in immune function, improvement in cholesterol and glucose metabolism, weight management, mental health, and prevention of diseases. Finally, we highlight the challenges and future directions for research. By advancing the understanding of gut microbiota dynamics and translating scientific insights into clinical practice, it could harness the full potential of dietary fiber pectins and prebiotics to optimize gut health, improve overall well-being across the lifespan, and increase longevity.

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.

Polystyrene nanobeads exacerbate chronic colitis in mice involving in oxidative stress and hepatic lipid metabolism

BackgroundNanoplastics (NPs) are omnipresent in our lives as a new type of pollution with a tiny size. It can enter organisms from the environment, accumulate in the body, and be passed down the food chain. Inflammatory bowel disease (IBD) is a nonspecific intestinal inflammatory disease that is recurrent and prevalent in the population. Given that the intestinal features of colitis may affect the behavior and toxicity of NPs, it is imperative to clarify the risk and toxicity mechanisms of NPs in colitis models.Methods and resultsIn this study, mice were subjected to three cycles of 5-day dextran sulfate sodium (DSS) exposures, with a break of 7 to 11 days between each cycle. After the first cycle of DSS exposure, the mice were fed gavagely with water containing 100 nm polystyrene nanobeads (PS-NPs, at concentrations of 1 mg/kg·BW, 5 mg/kg·BW and 25 mg/kg·BW, respectively) for 28 consecutive days. The results demonstrated that cyclic administration of DSS induced chronic inflammation in mice, while the standard drug “5-aminosalicylic acid (5-ASA)” treatment partially improved colitis manifestations. PS-NPs exacerbated intestinal inflammation in mice with chronic colitis by activating the MAPK signaling pathway. Furthermore, PS-NPs aggravated inflammation, oxidative stress, as well as hepatic lipid metabolism disturbance in the liver of mice with chronic colitis.ConclusionPS-NPs exacerbate intestinal inflammation and injury in mice with chronic colitis. This finding highlights chronically ill populations’ susceptibility to environmental hazards, which urgent more research and risk assessment studies.

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.

Multi-omics reveals the protective effects of curcumin against AFB1-induced oxidative stress and inflammatory damage in duckling intestines

Aflatoxin B1 (AFB1) is the most prevalent and toxic class of aflatoxins, which is considered a significant risk factor for food safety. Curcumin, a phytoconstituent with anti-inflammatory and antioxidant properties, has potential therapeutic value for intestinal inflammatory diseases. In this study, the duckling model susceptible to AFB1 was selected for toxicity testing, aiming to explore the effect of curcumin on AFB1 enterotoxicity and its possible mechanism of action. The results showed that curcumin promoted the growth and development of ducklings and mitigated the changes in morphology and permeability serological index (DAO and D-LA) after AFB1 exposure. Curcumin also mitigated AFB1-induced oxidative stress by activating the Nrf2 pathway, and ameliorated intestinal inflammation by inhibiting the NF-κB/IκB signaling pathway and boosting intestinal autophagy. In terms of gut flora and their metabolites, we found that curcumin supplementation significantly increased the intestinal flora's abundance index and diversity index compared to the AFB1 group, mitigating the decline in the abundance of Actinobacteria and the rise in that of harmful bacteria Clostridia. Furthermore, untargeted metabolomic analysis revealed that the protective effect of curcumin on the intestine was mainly through the regulation of AFB1-induced disorders of lipid metabolism, involving linoleic acid metabolism, α-linolenic acid metabolism, and glycerolipid metabolism. Overall, the enteroprotective effects of curcumin may be of significant value in the future for treating chronic AFB1 poisoning and also provide new therapeutic ideas for other mycotoxicosis.

Orally Administrated Inflamed Colon-Targeted Nanotherapeutics for Inflammatory Bowel Disease Treatment by Oxidative Stress Level Modulation in Colitis.

Inflammatory bowel disease (IBD) is characterized by an inappropriate and persistent inflammatory immune response and is often accompanied by excessive reactive oxygen species (ROS) production. For effective IBD treatment, there is a high demand for safe and targeted therapy that can be orally administered. In this study, we aimed to propose the use of inflamed colon-targeted antioxidant nanotherapeutics (ICANs) for in situ oxidative stress level modulation in colitis. ICANs consist of mesoporous silica nanoparticles (MSNs) with surface-attached ROS-scavenging ceria nanoparticles (CeNPs), which are further coated with poly(acrylic acid) (PAA) to facilitate preferential adherence to inflamed colon tissues through electrostatic interaction. We achieved a high ROS-scavenging property that remained effective even after artificial gastrointestinal fluid incubation by optimization of the molecular weight and PAA-coating pH. The orally administered ICANs demonstrated enhanced adherence to inflamed colon tissues in an acute inflammation mouse model of IBD induced by dextran sulfate sodium. This targeted delivery resulted in gut microenvironment modulation by regulating redox balance and reducing inflammatory cell infiltration, thereby suppressing the colitis-associated immune response. These findings highlight the potential of noninvasive ICANs as a promising candidate for treating inflammatory intestinal diseases by oxidative stress level modulation in colitis.

When hemorrhagic enterititis can cause anemia and thrombocytopenia without significant kidney damage.

A healthy 9-years-old boy was brought to the Emergency Department for widespread abdominal pain associated with bloody diarrhoea and significant tenesmus, in the absence of fever. Blood tests were compatible with an acute gastroenteritis, even though microbiological tests on stools resulted negative. Given the haemorrhagic dysentery, the boy was hospitalized to start empiric antibiotic therapy and intravenous rehydration. Abdominal ultrasound showed a thickening of colonic walls, mimicking an inflammatory intestinal disease at the onset (subsequently denied by gastro-colonoscopy). Seven days after the onset of symptoms, blood tests revealed microangiopathic anaemia with negative Coombs test, associated with thrombocytopenia. Urine dipstick revealed haematuria and proteinuria in nephritic range. No contraction of diuresis or alteration of renal function were observed (being creatinine values always within the normal range). Laboratory tests were consistent with the diagnosis of Haemolytic Uremic Syndrome (Hus) at the onset. Approximately 1% of paediatric patients with bloody diarrhoea can develop Hus. Positivity for Escherichia coli is not always evident in the stools. Thus, the triad of haemolytic anaemia, thrombocytopenia and renal failure could be present in only 60% of Hus at the onset. The finding of haematuria and/or proteinuria on the urine dipstick may be indicative of early kidney damage, allowing for careful monitoring and a rehydration program that can prevent progression of kidney damage and extrarenal complications.

Human intestinal organoids: Modeling gastrointestinal physiology and immunopathology - current applications and limitations.

Human intestinal organoids are an ideal model system for studying gastrointestinal physiology and immunopathology. Altered physiology and mucosal immune response are hallmarks of numerous intestinal functional and inflammatory diseases, including inflammatory bowel disease (IBD), coeliac disease, irritable bowel syndrome (IBS), and obesity. These conditions impact the normal epithelial functions of the intestine, such as absorption, barrier function, secretion, and host-microbiome communication. They are accompanied by characteristic intestinal symptoms and have significant societal, economic, and healthcare burdens. To develop new treatment options, cutting-edge research is required to investigate their etiology and pathology. Human intestinal organoids derived from patient tissue recapitulate the key physiological and immunopathological aspects of these conditions, providing a promising platform for elucidating disease mechanisms. This review will summarize recent reports on patient-derived human small intestinal and colonic organoids and highlight how these models have been used to study intestinal epithelial functions in the context of inflammation, altered physiology, and immune response. Furthermore, it will elaborate on the various organoid systems in use and the techniques/assays currently available to study epithelial functions. Finally, it will conclude by discussing the limitations and future perspectives of organoid technology.

Protective effects of metformin in the pro-inflammatory cytokine induced intestinal organoids injury model

Pathogenesis of inflammatory bowel disease (IBD) accompanies disrupted intestinal tight junctions. However, many approaches of therapeutics for IBD are focused only on anti-inflammatory effects and most cellular experiments are based on two-dimensional cell lines which have insufficient circumstances of intestine. Thus, here, we used three-dimensional structure intestinal organoids to investigate effects of metformin in the in vitro IBD condition. In this study, we focused on both tight junctions and the levels of inflammatory cytokines. Metformin enhances the intestinal barrier in injured intestine via upregulation of AMP-activated protein kinase, dysfunction of which contributes to the pathogenesis of intestinal diseases. We aim to investigate the effects of metformin on cytokine-induced injured intestinal organoids. Tumor necrosis factor-alpha (TNF-α) was used to induce intestinal injury in an organoid model, and the effects of metformin were assessed. Cell viability and levels of inflammatory cytokines were quantified in addition to tight junction markers. Furthermore, 4 kDa FITC-dextran was used to assess intestinal permeability. The upregulation of inflammatory cytokine levels was alleviated by metformin, which also restored the intestinal epithelium permeability in TNF-α-treated injury organoids. We confirmed that claudin-2 and claudin-7, representative tight junction markers, were also protected by metformin treatment. This study confirms the protective effects of metformin, which could be used as a therapeutic strategy for inflammatory intestinal diseases.

Distribution of P2Y and P2X purinergic receptor expression within the intestine.

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond to extracellular nucleotide signals. Using the Human Protein Atlas and Gut Cell Survey, we queried single-cell RNA sequencing (RNAseq) data for the P2 purinergic receptors in the small and large intestines. In silico analysis reveals robust mRNA expression of P2RY1, P2RY2, P2RY11, and P2RX4 throughout the gastrointestinal tract. Human intestinal organoids exhibited a similar expression pattern with a prominent expression of P2RY1, P2RY2, and P2RX4, but this purinergic receptor repertoire was not conserved in T84, Caco2, and HT29 intestinal epithelial cell lines. Finally, P2YR1 and P2YR2 agonists elicited robust calcium responses in human intestinal organoids, but calcium responses were weaker or absent in the cell lines. These findings suggest that the gastrointestinal epithelia respond to extracellular purinergic signaling via P2RY1, P2RY2, P2RY11, and P2RX4 receptors and highlight the benefit of using intestinal organoids as a model of intestinal purinergic signaling.NEW & NOTEWORTHY Several studies have revealed crucial roles for P2 receptors during inflammatory and infectious diseases, however, these have largely been demonstrated in immune cells and the enteric nervous system. Although epithelial cells serve as the first barrier against infection and inflammation, the role of purinergic signaling within the gastrointestinal tract remains largely unknown. This work expands our knowledge of purinergic receptor distribution and relative expression along the intestine.

Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice

Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer’s patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.

Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function

ABSTRACT Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4+, CD8+ T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.

Establishment and characterization of an intestinal epithelial cell line from Japanese flounder (Paralichthys olivaceus)

The Japanese flounder Paralichthys olivaceus is a high-value mariculture species. However, the aquaculture industry worldwide faces significant challenges due to flounder ascites, a serious disease caused by gram-negative bacterium Edwardsiella infection of fish cultures. Studies have confirmed that Edwardsiella tarda infection of flounder causes intestinal inflammatory disease. The recognition of pathogenic microorganisms by intestinal epithelial cells is the primary cause of inflammatory responses. In this study, a new cell line derived from the distal intestine (mainly the mid and posterior intestine) of Japanese flounder was established and characterized. This cell line, designated as the PoIEC line, was maintained in DMEM with 15% fetal bovine serum at 24 °C for >1 year, and subcultured >55 times. The PoIECs were epithelial-like cells with cobblestone-like shapes. Microvilli were observed on the surface of the PoIECs through transmission electron microscopy and the existence of epithelial markers was confirmed. PoIECs transfected with a pEGFP-N3 plasmid emitted an intense green fluorescence signal. Transfection efficiency of these cells was calculated to be approximately 37%, making this cell line a potential tool for future exogenous gene function research. Furthermore, PoIECs were stimulated by LPS and live E. tarda, and the expression profiles of immune-related genes (MHC Iα, MHC IIα, TNFα, IL-8, and IL-1β) confirmed that these cells recognized antigens and activated immune responses. In conclusion, a new cell line derived from the intestine of Japanese flounder was established, and this cell line was an ideal cellular platform for the study of mucosal immunity, probiotic flora and nutrient metabolism in the fish gut.

Ameliorating effects of Acacia arabica and Ocimum basilicum on acetic acid-induced ulcerative colitis model through mitigation of inflammation and oxidative stress

IntroductionUlcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum. The disease is characterized by oxidative stress and severe inflammation. Research has shown the anti-oxidative and anti-inflammatory effects induced by consuming the Acacia arabia and Ocimum basilicum. The present study aimed to evaluate the effect of treatment with O. basilicum together with A. arabica on healing, inflammation, and oxidative stress in the course of experimental colitis in rats. MethodsA total number of 50 male rats were selected and randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with a 4 % acetic acid solution. Four days after the colitis induction, the rats were orally treated for the next 4 days with saline or a combination of A. arabica and O. basilicum (1000 mg/kg) or sulfasalazine (100 mg/kg). ResultsAcetic acid-induced colitis increased the colon's macroscopic and histopathological damage scores; increased colon levels of MDA (Malondialdehyde), MPO (Myeloperoxidase), TNF-α (Tissue necrosis factor α), IL6 (Interleukin 6), and IL17 (Interleukin 17); and decreased SOD (Superoxide Dismutase), GPx (Glutathione Peroxidase), and IL10 (Interleukin 10) levels in the treated rats compared with the control group (P < 0.001). Overall, a combination of A. arabica and O. basilicum reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, and MDA, MPO, TNF-α, IL6 (P < 0.001), and IL17 (P < 0.01) levels of the colon. Furthermore, it increased SOD, GPx, and IL10 levels compared to the colitis group (P < 0.01). ConclusionA. arabica and O. basilicum have improving effects on UC by reducing inflammation and oxidative stress.

The Role of Mitochondrial in Intestinal Epithelial Barrier Dysfunction during Inflammatory Bowel Disease

Inflammatory bowel diseases are widely spread in industrial countries with every 20th citizen being affected. Dysregulation of epithelial barrier function is considered to play a key role in the development of inflammatory bowel diseases. Intestinal epithelium permeability depends mostly on the condition of intercellular contacts and epithelial cells' renewal ability. Mitochondria participate in the regulation of various intracellular processes besides performing the energetic function. Recent data indicate the potential role of mitochondria in intestinal epithelial barrier regulation and inflammatory bowel diseases onset. Mitochondrial dysfunction may be one of the reasons for disruption of the structure of tight junctions and the cytoskeleton of intestinal epithelial cells, as well as a decrease in the ability of the epithelial lining to self-renewal. All this leads to a decrease in the barrier function of the intestinal epithelium and the development of inflammatory bowel diseases. Nevertheless, the mechanisms of these processes are still unclear and further research is required.

L. plantarum and L. lactis as a promising agent in treatment of inflammatory bowel disease and colorectal cancer.

It has been understood for nearly a century that patients with intestinal inflammatory disease (IBD) have a higher risk of developing colorectal cancer (CRC). Recently, two species of lactic acid bacteria, Lactobacillus plantarum and Lactococcus lactis, have been investigated as therapeutic agents for IBD. These bacteria havebeen shown to survive gastric transit, to adhere and colonize in the intestinal tract of humans and modulate the intestinal microbiota and immune response. L. plantarum and L. lactis might be used as multifunctionaldrugs for the treatment of IBD and the prevention or treatment of CRC. This article summarizes current knowledge of L. plantarum and L. lactis as therapeutic and preventative agents for IBD and CRC, respectively.

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.

Host fecal DNA specific methylation signatures mark gut dysbiosis and inflammation in children affected by autism spectrum disorder

The gut-brain axis involves several bidirectional pathway communications including microbiome, bacterial metabolites, neurotransmitters as well as immune system and is perturbed both in brain and in gastrointestinal disorders. Consistently, microbiota-gut-brain axis has been found altered in autism spectrum disorder (ASD). We reasoned that such alterations occurring in ASD may impact both on methylation signatures of human host fecal DNA (HFD) and possibly on the types of human cells shed in the stools from intestinal tract giving origin to HFD. To test this hypothesis, we have performed whole genome methylation analysis of HFD from an age-restricted cohort of young children with ASD (N = 8) and healthy controls (N = 7). In the same cohort we have previously investigated the fecal microbiota composition and here we refined such analysis and searched for eventual associations with data derived from HFD methylome analysis. Our results showed that specific epigenetic signatures in human fecal DNA, especially at genes related to inflammation, associated with the disease. By applying methylation-based deconvolution algorithm, we found that the HFD derived mainly from immune cells and the relative abundance of those differed between patients and controls. Consistently, most of differentially methylated regions fitted with genes involved in inflammatory response. Interestingly, using Horvath epigenetic clock, we found that ASD affected children showed both epigenetic and microbiota age accelerated. We believe that the present unprecedented approach may be useful for the identification of the ASD associated HFD epigenetic signatures and may be potentially extended to other brain disorders and intestinal inflammatory 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.