Project description:The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases.
Project description:BackgroundIncreasing evidence suggests a close association between the intestinal microbiome and the respiratory system, drawing attention to studying the gut-lung axis. This research employs bibliometric methods to conduct a visual analysis of literature in the field of intestinal microbiota and lung diseases over the past two decades. It offers scientific foundations for research directions and critical issues in this field.MethodsWe retrieved all articles on intestinal microbiota and lung diseases from the SCI-Expanded of WoSCC on October 25, 2023. The analysis included original articles and reviews published in English from 2011 to 2023. We utilized Python, VOSviewer, and CiteSpace to analyze the retrieved data visually.ResultsA total of 794 publications were analyzed. China ranked first in the number of publications, while the United States had the highest citations and H-index. Jian Wang was the most prolific author. Zhejiang University was the institution with the highest number of publications. Frontiers in Microbiology was the journal with the most publications. Author keywords appearing more than 100 times included "intestinal microbiota/microbiome", "microbiota/microbiome", and "gut-lung axis".ConclusionThe correlation and underlying mechanisms between intestinal microbiota and lung diseases, including asthma, COPD, lung cancer, and respiratory infections, remain hot topics in research. However, understanding the mechanisms involving the gut-lung axis is still in its infancy and requires further elucidation.
Project description:Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract (GIT), including Crohn's disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α,25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g., butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD/VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.
Project description:BackgroundCardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and women afflicted with CHD and delineate these against a non-CVD control group for each sex.MethodsOur research was conducted in the framework of the CORDIOPREV study, a clinical trial which involved 837 men and 165 women with CHD. We contrasted our findings with a reference group of 375 individuals (270 men, 105 women) without CVD. The intestinal microbiota was examined through 16S metagenomics on the Illumina MiSeq platform and the data processed with Quiime2 software.ResultsOur results showed a sex-specific variation (beta diversity) in the intestinal microbiota, while alpha-biodiversity remained consistent across both sexes. Linear discriminant analysis effect size (LEfSe) analysis revealed sex-centric alterations in the intestinal microbiota linked to CVD. Moreover, using random forest (RF) methodology, we identified seven bacterial taxa-g_UBA1819 (Ruminococcaceae), g_Bilophila, g_Subdoligranulum, g_Phascolarctobacterium, f_Barnesiellaceae, g_Ruminococcus, and an unknown genus from the Ruminococcaceae family (Ruminococcaceae incertae sedis)-as key discriminators between men and women diagnosed with CHD. The same taxa also emerged as critical discriminators between CHD-afflicted and non-CVD individuals, when analyzed separately by sex.ConclusionOur findings suggest a sex-specific dysbiosis in the intestinal microbiota linked to CHD, potentially contributing to the sex disparity observed in CVD incidence. Trial registration Clinical Trials.gov.Identifier NCT00924937.
Project description:BackgroundThe performance of the microbiota is observed in several digestive tract diseases. Therefore, reaching the biliary microbiota may suggest ways for studies of biomarkers, diagnoses, tests and therapies in hepatobiliopancreatic diseases.MethodsBile samples will be collected in endoscopic retrograde cholangiopancreatography patients (case group) and living liver transplantation donors (control group). We will characterize the microbiome based on two types of sequence data: the V3/V4 regions of the 16S ribosomal RNA (rRNA) gene and total shotgun DNA. For 16S sequencing data a standard 16S processing pipeline based on the Amplicon Sequence Variant concept and the qiime2 software package will be employed; for shotgun data, for each sample we will assemble the reads and obtain and analyze metagenome-assembled genomes.ResultsThe primary expected results of the study is to characterize the specific composition of the biliary microbiota in situations of disease and health. In addition, it seeks to demonstrate the existence of changes in the case of illness and also possible disease biomarkers, diagnosis, interventions and therapies in hepatobiliopancreatic diseases.Trial registrationNCT04391426. Registered 18 May 2020, https://clinicaltrials.gov/ct2/show/NCT04391426.
Project description:Phage therapy has been overshadowed by antibiotics for decades. However, it is being revisited as a powerful approach against antimicrobial-resistant bacteria. As bacterial microbiota have been mechanistically linked to gastrointestinal and liver diseases, precise editing of the gut microbiota via the selective bactericidal action of phages has prompted renewed interest in phage therapy. In this review, we summarise the basic virological properties of phages and the latest findings on the composition of the intestinal phageome and the changes associated with liver diseases. We also review preclinical and clinical studies assessing phage therapy for the treatment of gastrointestinal and liver diseases, as well as future prospects and challenges.
Project description:Biliary obstruction diseases are often complicated by an impaired intestinal barrier, which aggravates liver injury. Treatment of the intestinal barrier is often neglected. To investigate the mechanism by which intestinal bile acid deficiency mediates intestinal barrier dysfunction after biliary obstruction and identify a potential therapeutic modality, we mainly used a bile duct ligation (BDL) mouse model to simulate biliary obstruction and determine the important role of the bile acid receptor FXR in maintaining intestinal barrier function and stemness. Through RNA-seq analysis of BDL and sham mouse crypts and qRT-PCR performed on intestinal epithelial-specific Fxr knockout (FxrΔIEC) and wild-type mouse crypts, we found that FXR might maintain intestinal stemness by regulating CYP11A1 expression. Given the key role of CYP11A1 during glucocorticoid production, we also found that FXR activation could promote intestinal corticosterone (CORT) synthesis by ELISA. Intestinal organoid culture showed that an FXR agonist or corticosterone increased crypt formation and organoid growth. Further animal experiments showed that corticosterone gavage treatment could maintain intestinal barrier function and stemness, decrease LPS translocation, and attenuate liver injury in BDL mice. Our study hopefully provides a new theoretical basis for the prevention of intestinal complications and alleviation of liver injury after biliary obstruction.
Project description:The concept of designer microbiota in chicken is focused on early exposure of the hatchlings to pathogen-free microbiota inoculum, limiting the early access to harmful and pathogenic microorganisms, thus promoting colonisation of the gut with beneficial and natural poultry microbiota. In this study, we controlled colonisation of the intestine in broiler chickens in a large-scale industrial setting via at-hatch administration of a commercial product containing a highly diverse microbiota originating from the chicken caecum. The treatment significantly transformed the microbiota membership in the crop, proventriculus, jejunum and caecum and significantly altered the taxa abundance in the jejunum, jejunum mucosa, and caecum estimated using PERMANOVA and unweighted and weighted UniFrac distances, respectively. The treatment also improved the growth rate in chickens with no significant alteration in feed conversion ratio. A comparison of inoculum product microbiota structure revealed that the inoculum had the highest Shannon diversity index compared to all investigated gut sections, and the number of Observed Species second only to the caecal community. PCoA plots using weighted or unweighted UniFrac placed the inoculum samples together with the samples from the caecal origin.
Project description:Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health.
Project description:γδT cells are unconventional T lymphocytes that bridge innate and adaptive immunity. Based on the composition of T cell receptor and the cytokines produced, γδT cells can be divided into diverse subsets that may be present at different locations, including the liver, epithelial layer of the gut, the dermis and so on. Many of these cells perform specific functions in liver diseases, such as viral hepatitis, autoimmune liver diseases, non-alcoholic fatty liver disease, liver cirrhosis and liver cancers. In this review, we discuss the distribution, subsets, functions of γδT cells and the relationship between the microbiota and γδT cells in common hepatic diseases. As γδT cells have been used to cure hematological and solid tumors, we are interested in γδT cell-based immunotherapies to treat liver diseases.