Gut Microbiota In Inflammatory Bowel Disease Research Articles

Induction of Inflammatory Macrophages in the Gut and Extra-Gut Tissues by Colitis-Mediated Escherichia coli.

SummaryInflammatory macrophages play a critical role in gut and extra-gut inflammatory disorders, which may be promoted through the dysbiosis of gut microbiota. However, it is poorly understood how gut microbiota affect inflammatory macrophages. Here, we found that increased Escherichia coli (E. coli) in inflamed colon may induce inflammatory macrophages in gut and extra-gut tissues. These E. coli are different from other commensal and pathogenic E. coli in genomic components and also in ability to induce inflammatory responses. Dominant E. coli from colitic tissues induce gut inflammatory macrophages through a regulating network consisted of IL-18, IFN-γ, IL-12, and IL-22 in gut tissues. These E. coli also directly activate macrophages. Cytosolic inflammasome components PCKδ, NLRC4, caspase8, and caspase1/11 are involved in E. coli-mediated activation in both gut epithelial cells and macrophages. These disclose a novel mechanism for how dysbiosis of gut microbiota in colitis cause inflammatory macrophages related to multiple diseases.

Gut Microbiota-Mediated NLRP12 Expression Drives the Attenuation of Dextran Sulphate Sodium-Induced Ulcerative Colitis by Qingchang Wenzhong Decoction.

Qingchang Wenzhong Decoction (QCWZD) is a newly developed, effective traditional Chinese herbal formulation for ulcerative colitis (UC). In earlier studies, we found that QCWZD could relieve the clinical symptoms of UC patients, reduce inflammation, and improve the intestinal barrier function in dextran sulphate sodium (DSS)-induced UC rats. However, the relationship between QCWZD and the gut microbiota in colitis was not clarified. In this study, we established a rat model of DSS-induced UC and then investigated the regulatory effects of QCWZD on the gut microbiota using 16S rRNA analysis. We also determined the expression of NLRP12 after QCWZD administration. Our findings suggested that QCWZD administration could modulate gut microbiota composition and selectively promote the protective strains such as Butyricimonas, Blautia, and Odoribacter, whereas the enteric pathogens including Clostridium and Dorea were significantly reduced after QCWZD treatment. It is noteworthy that QCWZD administration was identified to promote gut microbiota-mediated NLRP12 expression by inhibiting the activity of the TLR4/Blimp-1 axis. In conclusion, our study supports the potential of QCWZD administration as a beneficial therapeutic strategy for UC.

Microbial Indole Metabolites Provide a Novel Pathway for Regulation of Intestinal Homeostasis

Inflammatory bowel disease (IBD) is a multifactorial chronic condition that result in numerous perturbations in the gastrointestinal mucosa. IBD is characterized by the continual breakdown of the intestinal epithelial barrier leading to an inappropriate immune response towards intestinal microbiota. This exposure promotes inflammation and continued mucosal injury, though the pathogenesis of the disease remains unknown. There is currently significant interest in understanding the role of gut microbiota in IBD. Loss of commensal bacteria and their metabolites may play a role in homeostasis of the intestinal epithelia. Microbes benefit the host through the local synthesis of numerous metabolites. One such metabolite is indole. Indoles are gut microbiota‐derived tryptophan metabolites that are abundant in the healthy mammalian gut and positively influence intestinal health. Using an unbiased metabolomics profiling approach, we identified a selective reduction in microbiota‐derived indole metabolites in active murine colitis. We have developed HPLC‐based technologies to validate these results and quantify indole and indole‐derived metabolites within murine and human colitis samples. We show that exposure of intestinal epithelial cells to indole metabolites induces genes important in formation and maintenance of intestinal barrier. For instance, the anti‐inflammatory cytokine IL‐10 functions through binding to the IL‐10 receptor alpha subunit (IL‐10R1), and colitis is strongly associated with the induction of the epithelial IL‐10R1. Our results have revealed a prominent induction of IL‐10R1 mRNA and protein expression following treatment of intestinal epithelial cells with indole metabolites. We also show a potential role for selective indole metabolites, particularly indole‐3‐propionic acid (IPA), to alleviate disease severity and decrease inflammatory mediators in models of murine colitis. Together, these data suggest that microbial‐derived indoles play a central role in mucosal homeostasis. Based on these findings and ongoing studies, we show that microbial‐derived indole metabolites inhibit inflammation‐induced damage and promote mucosal homeostasis. These studies elucidate a novel role for microbial metabolites in innate immune responses during intestinal inflammation using in vitro and in vivo models. This work will provide new insight and identify possible avenues to utilize indoles as therapeutic approaches for treating IBD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease.

The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD.With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD.This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.

The Gut Microbiota in the Pathogenesis and Therapeutics of Inflammatory Bowel Disease.

In the twenty first century, the changing epidemiology of inflammatory bowel disease (IBD) globally with increasing disease incidence across many countries relates to the altered gut microbiota, due to a combinatorial effect of environmental factors, human immune responses and genetics. IBD is a gastrointestinal disease associated with a gut microbial dysbiosis, including an expansion of facultative anaerobic bacteria of the family Enterobacteriaceae. Advances in high-throughput sequencing enable us to entangle the gut microbiota in human health and IBD beyond the gut bacterial microbiota, expanding insights into the mycobiota, virobiota and helminthes. Caudovirales (viruses) and Basidiomycota, Ascomycota, and Candida albicans (fungi) are revealed to be increased in IBD. The deconvolution of the gut microbiota in IBD lays the basis for unveiling the roles of these various gut microbiota components in IBD pathogenesis and being conductive to instructing on future IBD diagnosis and therapeutics. Here we comprehensively elucidate the alterations in the gut microbiota in IBD, discuss the effect of diets in the gut microbiota in relation to IBD, and illustrate the potential of manipulation of gut microbiota for IBD therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in IBD.

Dysbiosis and Ecotypes of the Salivary Microbiome Associated With Inflammatory Bowel Diseases and the Assistance in Diagnosis of Diseases Using Oral Bacterial Profiles.

Inflammatory bowel diseases (IBDs) are chronic, idiopathic, relapsing disorders of unclear etiology affecting millions of people worldwide. Aberrant interactions between the human microbiota and immune system in genetically susceptible populations underlie IBD pathogenesis. Despite extensive studies examining the involvement of the gut microbiota in IBD using culture-independent techniques, information is lacking regarding other human microbiome components relevant to IBD. Since accumulated knowledge has underscored the role of the oral microbiota in various systemic diseases, we hypothesized that dissonant oral microbial structure, composition, and function, and different community ecotypes are associated with IBD; and we explored potentially available oral indicators for predicting diseases. We examined the 16S rRNA V3–V4 region of salivary bacterial DNA from 54 ulcerative colitis (UC), 13 Crohn’s disease (CD), and 25 healthy individuals using Illumina sequencing. Distinctive sample clusters were driven by disease or health based on principal coordinate analysis (PCoA) of both the Operational Taxonomic Unit profile and Kyoto Encyclopedia of Genes and Genomes pathways. Comparisons of taxa abundances revealed enrichment of Streptococcaceae (Streptococcus) and Enterobacteriaceae in UC and Veillonellaceae (Veillonella) in CD, accompanied by depletion of Lachnospiraceae and [Prevotella] in UC and Neisseriaceae (Neisseria) and Haemophilus in CD, most of which have been demonstrated to exhibit the same variation tendencies in the gut of IBD patients. IBD-related oral microorganisms were associated with white blood cells, reduced basic metabolic processes, and increased biosynthesis and transport of substances facilitating oxidative stress and virulence. Furthermore, UC and CD communities showed robust sub-ecotypes that were not demographic or severity-specific, suggesting their value for future applications in precision medicine. Additionally, indicator species analysis revealed several genera indicative of UC and CD, which were confirmed in a longitudinal cohort. Collectively, this study demonstrates evident salivary dysbiosis and different ecotypes in IBD communities and provides an option for identifying at-risk populations, not only enhancing our understanding of the IBD microbiome apart from the gut but also offering a clinically useful strategy to track IBD as saliva can be sampled conveniently and non-invasively.

Gut microbiota and Crohn’s disease

INTRODUCTION: Crohn’s disease (CD) is characterized by a chronic inflammation of the gastrointestinal tract causing abdominal pain, diarrhea, weight loss and systemic symptoms. Although the etiology of this disease is unknown, current knowledge suggests a multifactorial genesis involving genetic, environmental and immunological factors. EVIDENCE ACQUISITION: We focused our attention on critical analysis of the recent literature on the role of gut microbiota in inflammatory bowel disease (IBD), by evaluating the differences of composition, functions and role of intestinal flora. In particular, we focused on evidences about the interaction between gut microbiota and pathogenesis of IBD. In this setting, we conducted a PUBMED search for guidelines, systematic reviews (SR) and primary studies. EVIDENCE SYNTHESIS: Some data suggest that, in a significant percentage of patients, the microbiota plays an important role in the genesis and maintenance of CD. Probiotic supplementation and antibiotic treatment appear to be a valid therapeutic approach, although the clinical data remain controversial. CONCLUSIONS: Despite the exciting and growing research on the role of gut microbiota in IBD, our knowledge remains fairly limited. Further studies are needed to measure the diversity, function and resistance to antibiotics of the intestinal microbiota in CD.

Abstract B40: Effect of Sasa quelpaertensis leaf extracts on the gut microbiota in dextran sodium sulfate-induced colitis in mice

Abstract Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of gastrointestinal tract. Although the etiology of IBD is not clear, it may be associated with genetics and lifestyle factors, diet and gut microbiome. In particular, the imbalance among the immune system and gut microbiota and diet may play a key role in developing IBD. Sasa quelpaertensis leaves have shown anti-inflammatory and anticarcinogenic effects, although the effect of these leaves on gut microbiota in colitis remains unclear. The present study hypothesized that Sasa quelpaertensis leaves extract (SQE) exerts a protective effect against a dextran sulfate sodium (DSS)-induced colitis in mice through modulating gut microbiota. SQE (100 mg/kg or 300 mg/kg b.w.) were pre-treated to mice by gavage two weeks before inflammation which was induced by 2.5% DSS in drinking water for two cycles of each 7 days and tap water for 7 days was provided between DSS treatment. Disease activity index (DAI), colon length were measured and microbiota were analyzed using pyrosequencing in fecal samples. SQE attenuated the severity of DSS-induced colitis. In addition, SQE group had more Firmicutes in phylum level compared to DSS group, Bacteroidetes/Firmicutes ratio of DSS group was significantly higher than control and SQE groups. Furthermore, major microbiota compositions were different in class, family, genus, and species level among control, DSS control, and SQE group. Estimator of community richness, the OTUs, in DSS group tended to lower compared with SQE groups and estimator of evenness and diversity, Chao-1, ACE, Shannon, NP Simpson, were significantly lower in DSS group compared with SQE groups (p<0.05). Our results suggest that SQE affects microbiome composition and number change on DSS-induced colitis mouse model, these change in the microbiome may be beneficial and can be an effective strategy for prevention of IBD (This work was conducted with the support of the Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ009777) Rural Development Administration, Republic of Korea, and the Brain Korea 21 Plus (Project No. 22A20130012143). Citation Format: Yiseul Yeom, Yuri Kim. Effect of Sasa quelpaertensis leaf extracts on the gut microbiota in dextran sodium sulfate-induced colitis in mice. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr B40.

Serological studies in inflammatory bowel disease: how important are they?

Serum antibodies have the potential role to assist in the diagnosis, disease stratification and prognostication of inflammatory bowel disease (IBD). Understanding antibody formation might provide insight into the dysregulated immunological response to the gut microbiota in IBD. This review summarizes recent evidence regarding the role of serology in IBD. There is accumulating evidence from cross-sectional and longitudinal studies and from recent meta-analyses that supports the value of serological markers in identifying patients with complicated disease phenotype and increased risk of surgery in patients with Crohn's disease. Anti-Saccharomyces cerevisiae antibody remains the most accurate single marker, and recently identified exocrine pancreas antibodies (GP2 and CUZD1) have been suggested as evidence for a role of antibodies in the pathogenesis of Crohn's disease. Despite these various developments, the use of the serum antibodies remains complementary in clinical practice. New markers are being currently evaluated that may reflect events relevant to the pathogenesis of IBD.

Gut Microbiota in Inflammatory Bowel Disease

The gut mucosal barrier plays an important role in maintaining a delicate immune homeostasis. The pathogenesis of inflammatory bowel disease (IBD) is considered to involve a defective mucosal immunity along with a genetic predisposition. Recent views have suggested an excessive response to components of the gut microbiota in IBD. A condition of "dysbiosis", with alterations of the gut microbial composition, has been observed in patients with IBD. In this article, the author review recent studies of gut microbiota in IBD, particularly the importance of the gut microbiota in the pathogenesis of pediatric IBD.