• Adnab-9 antibody
• Crohn’s disease
• FERAD ratio
• Paneth cells
• immunohistochemistry (IHC)
• inflammatory bowel diseases
• innate immune system
• p87

• I01 BX004127 BLRD VA

• antigen-antibody complex
• arthritis
• complement
• inflammatory bowel diseases
• leaky gut
• mitochondrial dysfunction

• Animals
• Humans
• Antigen-Antibody Complex/therapeutic use
• Inflammatory Bowel Diseases
• Arthritis/etiology
• Inflammation
• Arthralgia/etiology

• Department of Finance of Jilin Province

• Microbiota
• Quantitative real-time PCR
• Ulcerative colitis

• Johne’s disease
• MAP
• experimental model
• immune function
• microbiome

• 15/S/651 (NexusMAP) and 11/S/141 (IconMAP). Department of Agriculture Food and the Marine

• Crohn’s disease
• IBD
• biomarkers
• immune cells
• inflammation
• neutrophil-to-lymphocyte
• platelet-to-lymphocytes
• ulcerative colitis

• Animals
• Bacteria
• Gastrointestinal Microbiome/physiology
• Humans
• Immunoglobulin G
• Inflammatory Bowel Diseases/microbiology
• Mice
• Microbiota

• P01 AI071713 NIAID NIH HHS
• R01 DK123446 NIDDK NIH HHS
• R01 AI095068 NIAID NIH HHS
• R24 AI067039 NIAID NIH HHS
• U01 AI043638 NIAID NIH HHS
• ZIA AI001115 Intramural NIH HHS
• P30 AI027763 NIAID NIH HHS
• UM1 AI068613 NIAID NIH HHS
• R01 HD074511 NICHD NIH HHS
• P01 AI074621 NIAID NIH HHS
• R24 AI106039 NIAID NIH HHS
• DP1 DK130687 NIDDK NIH HHS
• ZIA BC011153 Intramural NIH HHS

The healthcare burden of inflammatory bowel disease (IBD) is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis.

To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.

We performed serological profiling of 100 Crohn’s disease (CD) patients, 100 ulcerative colitis (UC) patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays. The study subjects were randomly divided into discovery (n = 150) and validation (n = 150) sets. Statistical analysis was performed using R packages.

Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses. We identified novel antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) showing higher prevalence in CD patients relative to healthy controls. We also identified antibodies against the antigen of Streptococcus pyogenes (SPy_2009) showing higher prevalence in healthy controls relative to UC patients. Using these novel antibodies, we built biomarker panels with area under the curve (AUC) of 0.81, 0.87, and 0.82 distinguishing CD vs control, UC vs control, and CD vs UC, respectively. Subgroup analysis revealed that penetrating CD behavior, colonic CD location, CD patients with a history of surgery, and extensive UC exhibited highest antibody prevalence among all patients. We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.

We have identified antibody signatures for CD and UC using a comprehensive analysis of anti-microbial antibody response in IBD. These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and, after future validation, should aid early and accurate diagnosis of IBD.

• Inflammatory bowel disease
• Anti-microbial antibody
• Protein microarray
• Crohn’s disease
• Ulcerative colitis
• Gut microbiome

• Autoantibodies
• Biomarkers
• Colitis, Ulcerative
• Crohn Disease
• Humans
• Inflammatory Bowel Diseases
• Viral Proteins

Enterobacter hormaechei is involved in multiple hospital-associated infections and is resistant to beta-lactam and tetracycline antibiotics. Due to emerging antibiotics resistance in E. hormaechei and lack of licensed vaccine availability, efforts are required to overcome the antibiotics crisis. In the current research study, a multi-epitope-based vaccine against E. hormaechei was designed using reverse vaccinology and immunoinformatic approaches. A total number of 50 strains were analyzed from which the core proteome was extracted. One extracellular (curlin minor subunit CsgB) and two periplasmic membrane proteins (flagellar basal-body rod protein (FlgF) and flagellar basal body P-ring protein (FlgI) were prioritized for B and T-cell epitope prediction. Only three filtered TPGKMDYTS, GADMTPGKM and RLSAESQAT epitopes were used when designing the vaccine construct. The epitopes were linked via GPGPG linkers and EAAAK linker-linked cholera toxin B-subunit adjuvant was used to enhance the immune stimulation efficacy of the vaccine. Docking studies of the vaccine construct with immune cell receptors revealed better interactions, vital for generating proper immune reactions. Docked complexes of vaccine with MHC-I, MHC-II and Tool-like receptor 4 (TLR-4) reported the lowest binding energy of −594.1 kcal/mol, −706.7 kcal/mol, −787.2 kcal/mol, respectively, and were further subjected to molecular dynamic simulations. Net binding free energy calculations also confirmed that the designed vaccine has a strong binding affinity for immune receptors and thus could be a good vaccine candidate for future experimental investigations.

• Helicobacter hepaticus
• CD103+ DCs
• CD40
• Colitis
• GroEL
• iTregs

• Animals
• Colitis, Ulcerative/chemically induced
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/microbiology
• Colitis, Ulcerative/prevention & control
• Colon/drug effects
• Colon/immunology
• Colon/microbiology
• Colon/pathology
• Cytokines/metabolism
• Dextran Sulfate/administration & dosage
• Dextran Sulfate/toxicity
• Disease Models, Animal
• Gastrointestinal Microbiome/drug effects
• Gastrointestinal Microbiome/immunology
• Humans
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/immunology
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/pathology
• Male
• Mice
• Signal Transduction/drug effects
• Signal Transduction/immunology
• Triterpenes/administration & dosage
• Ursolic Acid

• herb-partitioned moxibustion
• meta-analysis
• protocol
• systematic review
• ulcerative colitis

• Colitis, Ulcerative/therapy
• Drugs, Chinese Herbal/therapeutic use
• Humans
• Meta-Analysis as Topic
• Moxibustion/methods
• Systematic Reviews as Topic

• faecal microbiota transplantation
• immunology
• inflammatory bowel disease

• Antimicrobial peptides
• Crohn’s Disease
• IBD
• defensins
• gut microbiota
• mucosal barrier
• mucus
• probiotics
• ulcerative Colitis

• Animals
• Dog Diseases/immunology
• Dog Diseases/microbiology
• Dogs
• Escherichia coli/genetics
• Feces/microbiology
• Female
• Flow Cytometry/veterinary
• Gastrointestinal Microbiome/genetics
• Gastrointestinal Microbiome/immunology
• Immunity, Humoral
• Immunoglobulin A/immunology
• Immunoglobulin G/immunology
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/veterinary
• Macrophages/immunology
• Male
• Phagocytosis
• Prospective Studies
• RNA, Ribosomal, 16S/genetics

• Animals
• Enterococcus/genetics
• Enterococcus/pathogenicity
• Enterococcus/physiology
• Gram-Positive Bacterial Infections/microbiology
• Humans
• Interspersed Repetitive Sequences
• Virulence

• K99 EY028222 NEI NIH HHS
• P01 AI083214 NIAID NIH HHS
• R00 EY028222 NEI NIH HHS

Inflammatory bowel diseases (IBD) are associated with compositional and functional changes of the intestinal microbiota, but specific contributions of individual bacteria to chronic intestinal inflammation remain unclear. Enterococcus faecalis is a resident member of the human intestinal core microbiota that has been linked to the pathogenesis of IBD and induces chronic colitis in susceptible monoassociated IL-10-deficient (IL-10^−/−) mice. In this study, we characterized the colitogenic activity of E. faecalis as part of a simplified human microbial consortium based on seven enteric bacterial strains (SIHUMI). RNA sequencing analysis of E. faecalis isolated from monoassociated wild type and IL-10^−/− mice identified 408 genes including 14 genes of the ethanolamine utilization (eut) locus that were significantly up-regulated in response to inflammation. Despite considerable up-regulation of eut genes, deletion of ethanolamine utilization (ΔeutVW) had no impact on E. faecalis colitogenic activity in monoassociated IL-10^−/− mice. However, replacement of the E. faecalis wild type bacteria by a ΔeutVW mutant in SIHUMI-colonized IL-10^−/− mice resulted in exacerbated colitis, suggesting protective functions of E. faecalis ethanolamine utilization in complex bacterial communities. To better understand E. faecalis gene response in the presence of other microbes, we purified wild type E. faecalis cells from the colon content of SIHUMI-colonized wild type and IL-10^−/− mice using immuno-magnetic separation and performed RNA sequencing. Transcriptional profiling revealed that the bacterial environment reprograms E. faecalis gene expression in response to inflammation, with the majority of differentially expressed genes not being shared between monocolonized and SIHUMI conditions. While in E. faecalis monoassociation a general bacterial stress response could be observed, expression of E. faecalis genes in SIHUMI-colonized mice was characterized by up-regulation of genes involved in growth and replication. Interestingly, in mice colonized with SIHUMI lacking E. faecalis enhanced inflammation was observed in comparison to SIHUMI-colonized mice, supporting the hypothesis that E. faecalis ethanolamine metabolism protects against colitis in complex consortia. In conclusion, this study demonstrates that complex bacterial consortia interactions reprogram the gene expression profile and colitogenic activity of the opportunistic pathogen E. faecalis toward a protective function.

• Enterococcus faecalis
• IBD
• IL-10 deficient mouse
• RNA sequencing
• SIHUMI
• ethanolamine utilization
• gnotobiotic mouse models
• microbial consortium

The gastrointestinal (GI) tract provides a compartmentalized interface with an enormous repertoire of immune and metabolic activities, where the multicellular structure of the mucosa has acquired mechanisms to sense luminal factors, such as nutrients, microbes, and a variety of host-derived and microbial metabolites. The GI tract is colonized by a complex ecosystem of microorganisms, which have developed a highly coevolved relationship with the host’s cellular and immune system. Intestinal epithelial pattern recognition receptors (PRRs) substantially contribute to tissue homeostasis and immune surveillance. The role of bacteria-derived signals in intestinal epithelial homeostasis and repair has been addressed in mouse models deficient in PRRs and signaling adaptors. While critical for host physiology and the fortification of barrier function, the intestinal microbiota poses a considerable health challenge. Accumulating evidence indicates that dysbiosis is associated with the pathogenesis of numerous GI tract diseases, including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Aberrant signal integration at the epithelial cell level contributes to such diseases. An increased understanding of bacterial-specific structure recognition and signaling mechanisms at the intestinal epithelial interface is of great importance in the translation to future treatment strategies. In this review, we summarize the growing understanding of the regulation and function of the intestinal epithelial barrier, and discuss microbial signaling in the dynamic host–microbe mutualism in both health and disease.

• bacterial signaling
• colorectal cancer
• inflammation
• intestinal epithelium
• intestinal microbiota

Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon. Current medical treatment of UC relies predominantly on the use of traditional drugs, including aminosalicylates, corticosteroids, and immunosuppressants, which failed to effectively control this disease's progression and produced various side effects. Here, we report a new Chinese medicine intestine formula (CIF) which greatly improved the effect of mesalazine, an aminosalicylate, on UC. In the present study, 60 patients with chronic UC were treated with oral mesalazine alone or in combination with CIF enema. The combination of mesalazine and CIF greatly and significantly improved the clinical symptoms and colon mucosal condition and improved the Mayo Clinic Disease Activity Index and health-related quality of life, when compared to mesalazine alone. In particular, the addition of CIF further decreased serum levels of tumor necrosis factor-alpha and hypersensitivity C-reactive protein but in contrast increased interleukin-4. Thus, the results demonstrate the beneficial role of CIF in UC treatment, which may be mediated by the regulation of inflammation.

• Antigens/immunology
• B-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/immunology
• Chronic Disease
• Food
• Gene Expression Regulation
• HIV Infections/immunology
• HIV Infections/virology
• HIV-1/immunology
• Humans
• Immunity, Humoral
• Immunoglobulin A/immunology
• Immunoglobulin Class Switching
• Immunoglobulin G/immunology
• Inflammation
• Intestinal Mucosa/immunology
• Intestinal Mucosa/virology
• Microbiota/immunology

• P30 AI027767 NIAID NIH HHS
• T32 AI007051 NIAID NIH HHS
• P30 CA013148 NCI NIH HHS
• R01 AI074438 NIAID NIH HHS
• C06 RR020136 NCRR NIH HHS
• R21 AI104458 NIAID NIH HHS
• R01 DK108353 NIDDK NIH HHS
• R01 HL129878 NHLBI NIH HHS
• National Institute of Allergy and Infectious Diseases
• National Institute of Diabetes and Digestive and Kidney Diseases

• Animals
• Anti-Inflammatory Agents/therapeutic use
• Antioxidants/therapeutic use
• Colitis, Ulcerative/blood
• Colitis, Ulcerative/chemically induced
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/pathology
• Colon/drug effects
• Colon/pathology
• Dextran Sulfate
• Interleukin-1beta/blood
• Male
• Malondialdehyde/analysis
• Mice
• Mice, Inbred BALB C
• NF-kappa B/analysis
• Triterpenes/therapeutic use
• Tumor Necrosis Factor-alpha/blood
• Ursolic Acid

The commensal Enterococcus faecalis is among the most common causes of nosocomial infections. Recent findings regarding increased abundance of enterococci in the intestinal microbiota of patients with inflammatory bowel diseases and induction of colitis in IL-10-deficient (IL-10-/-) mice put a new perspective on the contribution of E. faecalis to chronic intestinal inflammation. Based on the expression of virulence-related genes in the inflammatory milieu of IL-10-/- mice using RNA-sequencing analysis, we characterized the colitogenic role of two bacterial structures that substantially impact on E. faecalis virulence by different mechanisms: the enterococcal polysaccharide antigen and cell surface-associated lipoproteins. Germ-free wild type and IL-10-/- mice were monoassociated with E. faecalis wild type OG1RF or the respective isogenic mutants for 16 weeks. Intestinal tissue and mesenteric lymph nodes (MLN) were collected to characterize tissue pathology, loss of intestinal barrier function, bacterial adhesion to intestinal epithelium and immune cell activation. Bone marrow-derived dendritic cells (BMDC) were stimulated with bacterial lysates and E. faecalis virulence was additionally investigated in three invertebrate models. Colitogenic activity of wild type E. faecalis (OG1RF score: 7.2±1.2) in monoassociated IL-10-/- mice was partially impaired in E. faecalis lacking enterococcal polysaccharide antigen (ΔepaB score: 4.7±2.3; p<0.05) and was almost completely abrogated in E. faecalis deficient for lipoproteins (Δlgt score: 2.3±2.3; p<0.0001). Consistently both E. faecalis mutants showed significantly impaired virulence in Galleria mellonella and Caenorhabditis elegans. Loss of E-cadherin in the epithelium was shown for all bacterial strains in inflamed IL-10-/- but not wild type mice. Inactivation of epaB in E. faecalis reduced microcolony and biofilm formation in vitro, altered bacterial adhesion to intestinal epithelium of germ-free Manduca sexta larvae and impaired penetration into the colonic mucus layer of IL-10-/- mice. Lipoprotein-deficient E. faecalis exhibited an impaired TLR2-mediated activation of BMDCs in vitro despite their ability to fully reactivate MLN cells as well as MLN-derived colitogenic T cells ex vivo. E. faecalis virulence factors accounting for bacterial adhesion to mucosal surfaces as well as intestinal barrier disruption partially contribute to colitogenic activity of E. faecalis. Beyond their well-known role in infections, cell surface-associated lipoproteins are essential structures for colitogenic activity of E. faecalis by mediating innate immune cell activation.

Enterococcus faecalis is a commensal of the human intestinal core microbiota harboring several putative virulence factors, which highlight its role as opportunistic pathogen. This dualistic character is supported by recent evidence linking Enterococcus spp. to the pathogenesis of inflammatory bowel diseases (IBD). Although several studies suggest a crucial role for opportunistic pathogens in IBD pathogenesis targeting genetically susceptible individuals, the dynamic relationship between disease-relevant host compartments and specific bacterial structures able to trigger intestinal inflammation remain unclear. Here, we report that cell surface-associated lipoproteins and the enterococcal polysaccharide antigen, which are relevant for E. faecalis virulence in invertebrate infection models, but whose expression is minimally affected by the intestinal inflammatory milieu, exhibit colitogenic activity in a mouse model susceptible for chronic colitis. Bacterial lipoproteins trigger innate immune cell activation and are a critical prerequisite for E. faecalis-induced colitis. The enterococcal polysaccharide antigen mediates bacterial mucus penetration and adhesion to mucosal surfaces, promotes the formation of biofilm and contributes to E. faecalis colitogenic activity. Using E. faecalis as a model organism, we demonstrate that colitogenic activity of opportunistic pathogens can be assigned to specific bacterial structures, a finding that may help to identify the most essential steps in IBD-related microbe-host interactions.

• Animals
• Blotting, Western
• Colitis/microbiology
• Enterococcus faecalis/immunology
• Enterococcus faecalis/metabolism
• Enterococcus faecalis/pathogenicity
• Fluorescent Antibody Technique
• Gram-Positive Bacterial Infections/immunology
• Gram-Positive Bacterial Infections/metabolism
• In Situ Hybridization, Fluorescence
• Interleukin-10/deficiency
• Interleukin-10/metabolism
• Lipoproteins/metabolism
• Mice
• Mice, Knockout
• Virulence

• P40 OD010995 NIH HHS
• P30 DK034987 NIDDK NIH HHS
• R01 AI047923 NIAID NIH HHS
• 5-P39-DK034987 NIDDK NIH HHS
• P30 CA091842 NCI NIH HHS
• UL1 TR000448 NCATS NIH HHS
• R01 AI 47923 NIAID NIH HHS
• 5-P40-OD010995 NIH HHS
• UL1RR024992 NCRR NIH HHS
• UL1 RR024992 NCRR NIH HHS
• P30 CA91842 NCI NIH HHS

• Adult
• Antibodies/blood
• Antibodies/immunology
• Bacterial Proteins/immunology
• Bacterial Proteins/isolation & purification
• Bifidobacterium/immunology
• Bifidobacterium/pathogenicity
• Colitis, Ulcerative/blood
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/microbiology
• Crohn Disease/blood
• Crohn Disease/immunology
• Crohn Disease/microbiology
• Female
• Food Microbiology
• Humans
• Immunity, Cellular
• Immunoglobulin A/blood
• Immunoglobulin G/blood
• Inflammatory Bowel Diseases/blood
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/pathology
• Lactobacillus/immunology
• Lactobacillus/pathogenicity
• Lacticaseibacillus casei/immunology
• Lacticaseibacillus casei/pathogenicity
• Male
• Middle Aged
• Probiotics

Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy.

• Actins/metabolism
• Adolescent
• Adult
• Aged
• Amoxicillin/therapeutic use
• Anti-Bacterial Agents/therapeutic use
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/microbiology
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Fusobacterium/genetics
• Fusobacterium/isolation & purification
• Fusobacterium Infections/drug therapy
• Fusobacterium Infections/microbiology
• Humans
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/microbiology
• Male
• Metronidazole/therapeutic use
• Microbiota/genetics
• Middle Aged
• Tetracycline/therapeutic use

In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity.

• Staphylococcus aureus
• T cells
• colonization
• host response
• immunomodulation
• microbiota
• vaccine

• Animals
• Bacteria/classification
• Bacteria/genetics
• Bacteria/immunology
• Bacterial Translocation/immunology
• Colitis/chemically induced
• Colitis/genetics
• Colitis/microbiology
• Colon/immunology
• Colon/metabolism
• Colon/microbiology
• Cytokines/immunology
• Cytokines/metabolism
• Dextran Sulfate
• Ecosystem
• Epithelium/immunology
• Epithelium/metabolism
• Epithelium/microbiology
• Genetic Variation
• Genotype
• Host-Pathogen Interactions/immunology
• Inflammatory Bowel Diseases/chemically induced
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/microbiology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/microbiology
• Metagenome/genetics
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Molecular Sequence Data
• Nod2 Signaling Adaptor Protein/deficiency
• Nod2 Signaling Adaptor Protein/genetics
• Phylogeny
• RNA, Ribosomal, 16S/genetics

• copd
• ibd
• crohn’s disease
• ulcerative colitis
• inflammation
• cross-talk
• smoking
• microbiome
• lymphocyte
• autoimmunity

• Animals
• Antibodies/blood
• Antibody Formation
• Bacteria/immunology
• Bacterial Translocation/immunology
• Gastrointestinal Tract/immunology
• HIV Infections/complications
• HIV Infections/immunology
• Humans
• Immunity, Mucosal
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/immunology
• Mice

• Bacteria
• Biofilms
• Gastrointestinal Tract/microbiology
• Humans
• Intestines
• Mucous Membrane
• Probiotics

• neonatal fc receptor
• immunoglobulin g
• albumin
• immune complexes
• gastrointestinal tract

• Animals
• Antigen-Antibody Complex/immunology
• Female
• Histocompatibility Antigens Class I/immunology
• Humans
• Immunoglobulin G/immunology
• Intestines/immunology
• Maternal-Fetal Exchange/immunology
• Pregnancy
• Protein Transport/immunology
• Receptors, Fc/immunology
• Serum Albumin/immunology

• R01 DK053056 NIDDK NIH HHS
• P30 DK034854 NIDDK NIH HHS
• DK34854 NIDDK NIH HHS
• DK53056 NIDDK NIH HHS
• R56 DK053056 NIDDK NIH HHS

• Bifidobacterium
• Colitis
• Fermented milk
• Intestinal microbiota
• Probiotics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Esophageal Diseases/classification
• Esophageal Diseases/physiopathology
• Esophagus/physiopathology
• Female
• Gastrointestinal Motility/physiology
• Humans
• Image Processing, Computer-Assisted/methods
• Male
• Manometry/methods
• Middle Aged
• Pressure
• Reproducibility of Results
• Severity of Illness Index

• K23 DK062170-01 NIDDK NIH HHS
• R01 DC00646 NIDCD NIH HHS

• Adult
• Aged
• Biopsy
• Colitis, Ulcerative/immunology
• Crohn Disease/immunology
• Female
• Flow Cytometry
• Humans
• Immunohistochemistry
• Intestinal Mucosa/immunology
• Intestinal Mucosa/pathology
• Male
• Mast Cells/immunology
• Mast Cells/pathology
• Middle Aged
• Monocytes/immunology
• Monocytes/pathology
• Receptors, IgG/biosynthesis
• Receptors, IgG/immunology
• Toll-Like Receptor 4/biosynthesis
• Toll-Like Receptor 4/immunology
• Tryptases/immunology
• Tumor Necrosis Factor-alpha/biosynthesis
• Tumor Necrosis Factor-alpha/immunology

• Animals
• Anti-Inflammatory Agents/pharmacology
• Endoplasmic Reticulum/metabolism
• Endoplasmic Reticulum Chaperone BiP
• Epithelial Cells/immunology
• Epithelial Cells/metabolism
• Feedback, Physiological
• Genetic Predisposition to Disease
• Heat-Shock Proteins/metabolism
• Humans
• Inflammation/genetics
• Inflammatory Bowel Diseases/metabolism
• Interleukin-10/metabolism
• Molecular Chaperones/metabolism
• NF-kappa B/metabolism
• Protein Structure, Tertiary
• Toll-Like Receptors/metabolism
• Transforming Growth Factor beta/metabolism

AIM: To evaluate the efficacy and mechanism of action of NCB-02, a standardized Curcumin preparation, against 2, 4-dinitrochlorobenzene (DNCB)-induced ulcerative colitis in rats.

METHODS: Ulcerative colitis was induced in male rats by sensitizing with topical application of DNCB in acetone for 14 d and intra-colonol challenge with DNCB on day 15. A separate group of animals with vehicle treatment in similar fashion served as control group. Colitis rats were divided into different groups and treated with NCB-02 at doses of 25, 50 and 100 mg/kg b.wt p.o. for 10 d. Sulfasalazine at a dose of 100 mg/kg b.wt for 10 d served as a reference group. On day 10 after respective assigned treatment, all the animals were euthanized and the length of the colon, weight of entire colon and distal 8 cm of the colon were recorded. The distal part of the colon was immediately observed under a stereomicroscope and the degree of damage was scored. Further distal 8 cm of the colon was subject to the determination of colonic myeloperoxidase (MPO), lipid peroxidation (LPO) and alkaline phosphatase (ALP) activities. A small piece of the sample from distal colon of each animal was fixed in 10% neutral buffered formalin and embedded in paraffin wax and sectioned for immunohistochemical examination of NFκ-B and iNOS expression.

RESULTS: NCB-02 showed a dose dependent protection against DNCB-induced alteration in colon length and weight. NCB-02 treatment also showed a dose dependent protection against the elevated levels of MPO, LPO and ALP, induced by DNCB. NCB-02 demonstrated a significant effect at a dose of 100 mg/kg b.wt., which was almost equipotent to 100 mg/kg b.wt. of sulfasalazine. Treatment with sulfasalazine and curcumin at a dose of 100 mg/kg b.wt. inhibited the DNCB-induced overexpression of NFκ-B and iNOS in the colon.

CONCLUSION: Curcumin treatment ameliorates colonic damage in DNCB-induced colitic rats, an effect associated with an improvement in intestinal oxidative stress and downregulation of colonic NFκ-B and iNOS expression.

• Curcumin
• Colitis
• Dinitrochlorobenzene
• NFκ-B
• iNOS

• Alkaline Phosphatase/metabolism
• Animals
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Colitis, Ulcerative/chemically induced
• Colitis, Ulcerative/metabolism
• Colitis, Ulcerative/prevention & control
• Colon/metabolism
• Colon/pathology
• Curcumin/pharmacology
• Curcumin/therapeutic use
• Dinitrochlorobenzene
• Dose-Response Relationship, Drug
• Down-Regulation/drug effects
• Gene Expression Regulation
• Irritants
• Lipid Peroxidation/drug effects
• Lipid Peroxidation/physiology
• Male
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Nitric Oxide Synthase Type II/genetics
• Nitric Oxide Synthase Type II/metabolism
• Oxidative Stress/drug effects
• Oxidative Stress/physiology
• Peroxidase/metabolism
• Rats
• Rats, Wistar

• Adolescent
• Bacteria, Aerobic/isolation & purification
• Bacteria, Anaerobic/isolation & purification
• Bacteroides/chemistry
• Bacteroides/isolation & purification
• Cecum/microbiology
• Child
• Child, Preschool
• Colitis/microbiology
• Colitis, Ulcerative/microbiology
• Crohn Disease/microbiology
• DNA, Bacterial/analysis
• Humans
• Hyperplasia/microbiology
• Ileum/microbiology
• Ileum/pathology
• Inflammatory Bowel Diseases/microbiology
• Intestinal Mucosa/microbiology
• Polymerase Chain Reaction/methods
• Rectum/microbiology

• ulcerative colitis
• inflammatory bowel disease
• aetiology
• pathogenesis

• Appendicitis/etiology
• Bacterial Infections/microbiology
• Colitis, Ulcerative/etiology
• Colitis, Ulcerative/microbiology
• Colitis, Ulcerative/pathology
• Contraceptives, Oral/adverse effects
• Diet/adverse effects
• Epithelial Cells/physiology
• Genetic Predisposition to Disease
• Humans
• Smoking/adverse effects
• Stress, Psychological/complications