Dataset Information

Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis.

ABSTRACT: Ulcerative colitis (UC), a nonspecific inflammatory disease, is characterized by inflammation and mucosal damage in the colon, and its prevalence in the world is increasing. Nevertheless, the exact pathogenesis of UC is still unclear. Accumulating data have suggested that its pathogenesis is multifactorial, involving genetic predisposition, environmental factors, microbial dysbiosis, and dysregulated immune responses. Generally, UC is aroused by inappropriate immune activation based on the interaction of host and intestinal microbiota. The relationship between microbiota and host immune system in the pathogenesis of UC is complicated. However, increasing evidence indicates that the shift of microbiota composition can substantially influence intestinal immunity. In this review, we primarily focus on the delicate balance between microbiota and gut mucosal immunity during UC progression.

SUBMITTER: Zou J

PROVIDER: S-EPMC8370674 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis.

Zou Junfeng J Liu Chen C Jiang Shu S Qian Dawei D Duan Jinao J

Infection and immunity 20210816 9

Ulcerative colitis (UC), a nonspecific inflammatory disease, is characterized by inflammation and mucosal damage in the colon, and its prevalence in the world is increasing. Nevertheless, the exact pathogenesis of UC is still unclear. Accumulating data have suggested that its pathogenesis is multifactorial, involving genetic predisposition, environmental factors, microbial dysbiosis, and dysregulated immune responses. Generally, UC is aroused by inappropriate immune activation based on the inter ...[more]

PMID: 33526559

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Project description:Intestinal chronic inflammation is associated with microbial dysbiosis and accumulation of various immune cells including myeloid-derived suppressor cells (MDSC), which profoundly impact the immune microenvironment, perturb homeostasis and increase the risk to develop colitis-associated colorectal cancer (CAC). However, the specific MDSCs-dysbiotic microbiota interactions and their collective impact on CAC development remain poorly understood. In this study, using a murine model of CAC, we demonstrate that CAC-bearing mice exhibit significantly elevated levels of highly immunosuppressive MDSCs, accompanied by microbiota alterations. Both MDSCs and bacteria that infiltrate the colon tissue and developing tumors can be found in close proximity, suggesting intricate MDSC-microbiota cross-talk within the tumor microenvironment. To investigate this phenomenon, we employed antibiotic treatment to disrupt MDSC-microbiota interactions. This intervention yielded a remarkable reduction in intestinal inflammation, decreased MDSC levels, and alleviated immunosuppression, all of which were associated with a significant reduction in tumor burden. Furthermore, we underscore the causative role of dysbiotic microbiota in the predisposition toward tumor development, highlighting their potential as biomarkers for predicting tumor load. We shed light on the intimate MDSCs-microbiota cross-talk, revealing how bacteria enhance MDSC suppressive features and activities, inhibit their differentiation into mature beneficial myeloid cells, and redirect some toward M2 macrophage phenotype. Collectively, this study uncovers the role of MDSC-bacteria cross-talk in impairing immune responses and promoting tumor growth, providing new insights into potential therapeutic strategies for CAC.SignificanceMDSCs-dysbiotic bacteria interactions in the intestine play a crucial role in intensifying immunosuppression within the CAC microenvironment, ultimately facilitating tumor growth, highlighting potential therapeutic targets for improving the treatment outcomes of CAC.

Project description:ObjectiveThe pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study aims to characterise the mucosal virome and their functions in health and UC.DesignDeep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2.ResultsIn UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls. Escherichia phage and Enterobacteria phage were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC.ConclusionWe demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.

Project description:Probiotics can effectively improve ulcerative colitis (UC), but the mechanism is still unclear. Here, shotgun metagenome and transcriptome analyses were performed to explore the therapeutic effect and the mechanism of the probiotic Lactobacillus plantarum HNU082 (Lp082) on UC. The results showed that Lp082 treatment significantly ameliorated dextran sulfate sodium (DSS)-induced UC in mice, which was manifested as increases in body weight, water intake, food intake, and colon length and decreases in disease activity index (DAI), immune organ index, inflammatory factors, and histopathological scores after Lp082 intake. An in-depth study discovered that Lp082 could improve the intestinal mucosal barrier and relieve inflammation by cooptimizing the biological barrier, chemical barrier, mechanical barrier, and immune barrier. Specifically, Lp082 rebuilt the biological barrier by regulating the intestinal microbiome and increasing the production of short-chain fatty acids (SCFAs). Lp082 improved the chemical barrier by reducing intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) and increasing goblet cells and mucin2. Lp082 ameliorated the mechanical barrier by increasing zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), and occludin while decreasing claudin-1 and claudin-2. Lp082 optimized the immune barrier by reducing the content of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO), and interferon-γ (IFN-γ) and increasing IL-10, transforming growth factor-β1 (TGF-β1), and TGF-β2, inhibiting the NF-κB signaling pathway. Taken together, probiotic Lp082 can play a protective role in a DSS-induced colitis mouse model by protecting the intestinal mucosal barrier, attenuating the inflammatory response, and regulating microbial imbalance. This study provides support for the development of probiotic-based microbial products as an alternative treatment strategy for UC. IMPORTANCE Many studies have focused on the therapeutic effect of probiotics on ulcerative colitis (UC), but few studies have paid attention to the mechanism of probiotics, especially the therapeutic effect. This study suggests that Lp082 has a therapeutic effect on colitis in mice. Its mechanisms of action include protecting the mucosal barrier and actively modulating the gut microbiome, modulating inflammatory pathways, and reducing neutrophil infiltration. Our study enriches the mechanism and provides a new prospect for probiotics in the treatment of colitis, helps to deepen the understanding of the intestinal mucosal barrier, and provides guidance for the future probiotic treatment of human colitis.

Dataset Information

Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis.

Publications

Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis.

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