|
1
|
Pierce R, Jan NJ, Kumar P, Middleton J, Petri WA, Marie C. Persistent dysbiosis of duodenal microbiota in patients with controlled pediatric Crohn's disease after resolution of inflammation. Sci Rep 2024; 14:12668. [PMID: 38830904 PMCID: PMC11148174 DOI: 10.1038/s41598-024-63299-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 05/27/2024] [Indexed: 06/05/2024] Open
Abstract
Crohn's disease is an inflammatory condition of the intestine characterized by largely unknown etiology and a relapse remission cycle of disease control. While possible triggers have been identified, research is inconsistent on the precise cause of these relapses, especially in the under-researched pediatric population. We hypothesized that patients in remission would have persistent microbial and inflammatory changes in small intestinal tissue that might trigger relapse. To this end, we analyzed intestinal biopsy samples from six patients with pediatric Crohn's disease in remission and a control group of 16 pediatric patients with no evident pathogenic abnormality. We identified compositional microbiota differences, including decreases in the genera Streptococcus and Actinobacillus as well as increases in Oribacterium and Prevotella in patients with controlled Crohn's disease compared to controls. Further, a histologic analysis found that patients with controlled Crohn's disease had increased epithelial integrity, and decreased intraepithelial lymphocytes compared with controls. Additionally, we observed increased peripheral CD4+ T cells in patients with pediatric Crohn's disease. These results indicate that markers of intestinal inflammation are responsive to Crohn's disease treatment, however the interventions may not resolve the underlying dysbiosis. These findings suggest that persistent dysbiosis may increase vulnerability to relapse of pediatric Crohn's disease. This study used a nested cohort of patients from the Bangladesh Environmental Enteric Dysfunction (BEED) study (ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016).
Collapse
Affiliation(s)
- Rebecca Pierce
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Ning-Jiun Jan
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Pankaj Kumar
- Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Jeremy Middleton
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - William A Petri
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Chelsea Marie
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
| |
Collapse
|
|
2
|
Almhanna H, AL-Mahmodi AMM, Kadhim AB, Kumar AAHS. Network and structural analysis of quail mucins with expression pattern of mucin 1 and mucin 4 in the intestines of the Iraqi common quail ( Coturnix coturnix). Vet World 2024; 17:1227-1237. [PMID: 39077459 PMCID: PMC11283604 DOI: 10.14202/vetworld.2024.1227-1237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 05/14/2024] [Indexed: 07/31/2024] Open
Abstract
Background and Aim In avian and other species, mucins (MUCs) play a crucial role in the gastrointestinal tract (GIT), and constitute a large group of O-glycosylated glycoproteins, are glycoconjugate proteins. MUCs present in two forms: (1) membrane-attached on cell surfaces to repel external threats and (2) detachable, gel-forming proteins in the soluble form. In quail GIT, the specific types of MUCs that are expressed remain largely unknown. We investigated the expression of MUC1 and MUC4 MUCs in the GIT of Iraqi common quails and conducted network and structural analyses of all known MUC types across quail breeds. Materials and Methods Histological and gene expression analyses of MUC1 and MUC4 were conducted using fresh small intestine and large intestine samples from 10 quails. Using the STRING Database, Chimera software, and PrankWeb-ligand binding site prediction tool, network and structural analyses of all reported types of quail MUCs were conducted. Results Most intestinal MUCs in quails were acidic, with few neutral MUCs detectable through Alcian blue and periodic acid-schiff stains. Acidic MUCs were more expressed in the duodenum, ileum, cecum, and colon, whereas neutral MUCs were more expressed in the jejunum. MUC1 and MUC4 messenger RNA expression was significantly higher in the jejunum and colon than in the duodenum and ileum. The analysis of the network revealed that MUC 1, 15, 16, and 24 formed homologous networks, while MUC 2, 4, 5, and 6 formed heterologous networks. Specific MUC combinations, including MUC5A-MUC6, MUC5A-MUC5B, and MUC5B-MUC6, show higher intermolecular hydrogen bond formation affinity. MUC15, MUC16, and MUC24 showed minimal interaction with other MUC types. Among the analyzed MUCs, MUC5B, and MUC6 had the highest probability for binding, while MUC2, MUC4, and MUC5A showed lower probabilities despite greater numbers of binding sites. Conclusion This study's results offer significant insights into quails' MUCs' composition, expression, network interactions, and binding sites, advancing knowledge of MUC-related processes in gastrointestinal physiology and their potential connection to gastrointestinal diseases.
Collapse
Affiliation(s)
- Hazem Almhanna
- Department of Anatomy and Histology, College of Veterinary Medicine, University of Al-Qadisiyah, Al Diwaniyah, Iraq
| | | | - Abdulrazzaq B Kadhim
- Department of Anatomy and Histology, College of Veterinary Medicine, University of Al-Qadisiyah, Al Diwaniyah, Iraq
| | - aArun H. S. Kumar
- Department of Veterinary Biosciences, Stemcology, School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland
| |
Collapse
|
|
3
|
Spatz S, Afonso CL. Non-Targeted RNA Sequencing: Towards the Development of Universal Clinical Diagnosis Methods for Human and Veterinary Infectious Diseases. Vet Sci 2024; 11:239. [PMID: 38921986 PMCID: PMC11209166 DOI: 10.3390/vetsci11060239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 06/27/2024] Open
Abstract
Metagenomics offers the potential to replace and simplify classical methods used in the clinical diagnosis of human and veterinary infectious diseases. Metagenomics boasts a high pathogen discovery rate and high specificity, advantages absent in most classical approaches. However, its widespread adoption in clinical settings is still pending, with a slow transition from research to routine use. While longer turnaround times and higher costs were once concerns, these issues are currently being addressed by automation, better chemistries, improved sequencing platforms, better databases, and automated bioinformatics analysis. However, many technical options and steps, each producing highly variable outcomes, have reduced the technology's operational value, discouraging its implementation in diagnostic labs. We present a case for utilizing non-targeted RNA sequencing (NT-RNA-seq) as an ideal metagenomics method for the detection of infectious disease-causing agents in humans and animals. Additionally, to create operational value, we propose to identify best practices for the "core" of steps that are invariably shared among many human and veterinary protocols. Reference materials, sequencing procedures, and bioinformatics standards should accelerate the validation processes necessary for the widespread adoption of this technology. Best practices could be determined through "implementation research" by a consortium of interested institutions working on common samples.
Collapse
Affiliation(s)
- Stephen Spatz
- Southeast Poultry Research Laboratory, Agricultural Research Service, United States Department of Agriculture, 934 College Station Road, Athens, GA 30605, USA;
| | | |
Collapse
|
|
4
|
Wang Z, Shen J. The role of goblet cells in Crohn' s disease. Cell Biosci 2024; 14:43. [PMID: 38561835 PMCID: PMC10985922 DOI: 10.1186/s13578-024-01220-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 03/14/2024] [Indexed: 04/04/2024] Open
Abstract
The prevalence of Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is increasing worldwide. The pathogenesis of CD is hypothesized to be related to environmental, genetic, immunological, and bacterial factors. Current studies have indicated that intestinal epithelial cells, including columnar, Paneth, M, tuft, and goblet cells dysfunctions, are strongly associated with these pathogenic factors. In particular, goblet cells dysfunctions have been shown to be related to CD pathogenesis by direct or indirect ways, according to the emerging studies. The mucus barrier was established with the help of mucins secreted by goblet cells. Not only do the mucins mediate the mucus barrier permeability and bacterium selection, but also, they are closely linked with the endothelial reticulum stress during the synthesis process. Goblet cells also play a vital role in immune response. It was indicated that goblet cells take part in the antigen presentation and cytokines secretion process. Disrupted goblet cells related immune process were widely discovered in CD patients. Meanwhile, dysbiosis of commensal and pathogenic microbiota can induce myriad immune responses through mucus and goblet cell-associated antigen passage. Microbiome dysbiosis lead to inflammatory reaction against pathogenic bacteria and abnormal tolerogenic response. All these three pathways, including the loss of mucus barrier function, abnormal immune reaction, and microbiome dysbiosis, may have independent or cooperative effect on the CD pathogenesis. However, many of the specific mechanisms underlying these pathways remain unclear. Based on the current understandings of goblet cell's role in CD pathogenesis, substances including butyrate, PPARγagonist, Farnesoid X receptor agonist, nuclear factor-Kappa B, nitrate, cytokines mediators, dietary and nutrient therapies were all found to have potential therapeutic effects on CD by regulating the goblet cells mediated pathways. Several monoclonal antibodies already in use for the treatment of CD in the clinical settings were also found to have some goblet cells related therapeutic targets. In this review, we introduce the disease-related functions of goblet cells, their relationship with CD, their possible mechanisms, and current CD treatments targeting goblet cells.
Collapse
Affiliation(s)
- Zichen Wang
- Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Ministry of Health, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, No.160 PuJian Road, Shanghai, 200127, China
| | - Jun Shen
- Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Ministry of Health, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, No.160 PuJian Road, Shanghai, 200127, China.
| |
Collapse
|
|
5
|
Pinto S, Benincà E, Galazzo G, Jonkers D, Penders J, Bogaards JA. Heterogeneous associations of gut microbiota with Crohn's disease activity. Gut Microbes 2024; 16:2292239. [PMID: 38105519 PMCID: PMC10730216 DOI: 10.1080/19490976.2023.2292239] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 12/04/2023] [Indexed: 12/19/2023] Open
Abstract
The multi-factorial involvement of gut microbiota with Crohn's disease (CD) necessitates robust analysis to uncover possible associations with particular microbes. CD has been linked to specific bacteria, but reported associations vary widely across studies. This inconsistency may result from heterogeneous associations across individual patients, resulting in no apparent or only weak relationships with the means of bacterial abundances. We investigated the relationship between bacterial relative abundances and disease activity in a longitudinal cohort of CD patients (n = 57) and healthy controls (n = 15). We applied quantile regression, a statistical technique that allows investigation of possible relationships outside the mean response. We found several significant and mostly negative associations with CD, especially in lower quantiles of relative abundance on family or genus level. Associations found by quantile regression deviated from the mean response in relative abundances of Coriobacteriaceae, Pasteurellaceae, Peptostreptococcaceae, Prevotellaceae, and Ruminococcaceae. For the family Streptococcaceae we found a significant elevation in relative abundance for patients experiencing an exacerbation relative to those who remained without self-reported symptoms or measurable inflammation. Our analysis suggests that specific bacterial families are related to CD and exacerbation, but associations vary between patients due to heterogeneity in disease course, medication history, therapy response, gut microbiota composition and historical contingency. Our study underscores that microbial diversity is reduced in the gut of CD patients, but suggests that the process of diversity loss is rather irregular with respect to specific taxonomic groups. This novel insight may advance our ecological understanding of this complex disease.
Collapse
Affiliation(s)
- Susanne Pinto
- Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
| | - Elisa Benincà
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
| | - Gianluca Galazzo
- School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht UMC, Maastricht, Netherlands
| | - Daisy Jonkers
- School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
- Department of Gastroenterology-Hepatology, Maastricht UMC, Maastricht, Netherlands
| | - John Penders
- School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht UMC, Maastricht, Netherlands
| | - Johannes A. Bogaards
- Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Institute for Infection and Immunity (AII), Amsterdam UMC, Amsterdam, Netherlands
| |
Collapse
|
|
6
|
Ramadan Q, Hazaymeh R, Zourob M. Immunity-on-a-Chip: Integration of Immune Components into the Scheme of Organ-on-a-Chip Systems. Adv Biol (Weinh) 2023; 7:e2200312. [PMID: 36866511 DOI: 10.1002/adbi.202200312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 01/16/2023] [Indexed: 03/04/2023]
Abstract
Studying the immune system in vitro aims to understand how, when, and where the immune cells migrate/differentiate and respond to the various triggering events and the decision points along the immune response journey. It becomes evident that organ-on-a-chip (OOC) technology has a superior capability to recapitulate the cell-cell and tissue-tissue interaction in the body, with a great potential to provide tools for tracking the paracrine signaling with high spatial-temporal precision and implementing in situ real-time, non-destructive detection assays, therefore, enabling extraction of mechanistic information rather than phenotypic information. However, despite the rapid development in this technology, integration of the immune system into OOC devices stays among the least navigated tasks, with immune cells still the major missing components in the developed models. This is mainly due to the complexity of the immune system and the reductionist methodology of the OOC modules. Dedicated research in this field is demanded to establish the understanding of mechanism-based disease endotypes rather than phenotypes. Herein, we systemically present a synthesis of the state-of-the-art of immune-cantered OOC technology. We comprehensively outlined what is achieved and identified the technology gaps emphasizing the missing components required to establish immune-competent OOCs and bridge these gaps.
Collapse
Affiliation(s)
- Qasem Ramadan
- Alfaisal University, Riyadh, 11533, Kingdom of Saudi Arabia
| | - Rana Hazaymeh
- Almaarefa University, Diriyah, 13713, Kingdom of Saudi Arabia
| | | |
Collapse
|
|
7
|
Hall CV, Radford-Smith G, Savage E, Robinson C, Cocchi L, Moran RJ. Brain signatures of chronic gut inflammation. Front Psychiatry 2023; 14:1250268. [PMID: 38025434 PMCID: PMC10661239 DOI: 10.3389/fpsyt.2023.1250268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 10/09/2023] [Indexed: 12/01/2023] Open
Abstract
Gut inflammation is thought to modify brain activity and behaviour via modulation of the gut-brain axis. However, how relapsing and remitting exposure to peripheral inflammation over the natural history of inflammatory bowel disease (IBD) contributes to altered brain dynamics is poorly understood. Here, we used electroencephalography (EEG) to characterise changes in spontaneous spatiotemporal brain states in Crohn's Disease (CD) (n = 40) and Ulcerative Colitis (UC) (n = 30), compared to healthy individuals (n = 28). We first provide evidence of a significantly perturbed and heterogeneous microbial profile in CD, consistent with previous work showing enduring and long-standing dysbiosis in clinical remission. Results from our brain state assessment show that CD and UC exhibit alterations in the temporal properties of states implicating default-mode network, parietal, and visual regions, reflecting a shift in the predominance from externally to internally-oriented attentional modes. We investigated these dynamics at a finer sub-network resolution, showing a CD-specific and highly selective enhancement of connectivity between the insula and medial prefrontal cortex (mPFC), regions implicated in cognitive-interoceptive appraisal mechanisms. Alongside overall higher anxiety scores in CD, we also provide preliminary support to suggest that the strength of chronic interoceptive hyper-signalling in the brain co-occurs with disease duration. Together, our results demonstrate that a long-standing diagnosis of CD is, in itself, a key factor in determining the risk of developing altered brain network signatures.
Collapse
Affiliation(s)
- Caitlin V. Hall
- Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Graham Radford-Smith
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Gut Health Research Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
| | - Emma Savage
- Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Conor Robinson
- Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Luca Cocchi
- Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Rosalyn J. Moran
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom
| |
Collapse
|
|
8
|
Catalán-Serra I, Ricanek P, Grimstad T. "Out of the box" new therapeutic strategies for Crohn´s disease: moving beyond biologics. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:614-634. [PMID: 35748460 DOI: 10.17235/reed.2022.9010/2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
New treatment options beyond immunosuppression have emerged in recent years for patients with Crohn´s disease (CD), a chronic systemic condition affecting primarily the gut with great impact in the quality of life. The cause of CD is largely unknown, and a curative treatment is not yet available. In addition, despite the growing therapeutic armamentarium in recent years almost half of the patients don´t achieve a sustained response over time. Thus, new therapeutic strategies are urgently needed. In this review, we discuss the current state of promising new "out of the box" possibilities to control chronic inflammation beyond current pharmacological treatments, including: exclusive enteral nutrition, specific diets, cell therapies using T regs, hyperbaric oxygen, fecal microbiota transplantation, phage therapy, helminths, cannabis and vagal nerve stimulation. The exploration of original and novel therapeutic modalities is key to address their potential as main or complementary treatments in selected CD populations in order to increase efficacy, minimize side effects and improve quality of life of patients.
Collapse
|
|
9
|
Brasil VP, Siqueira RM, Campos FG, Yoshitani MM, Pereira GP, Mendonça RLDS, Kanno DT, Pereira JA, Martinez CAR. Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination. Acta Cir Bras 2023; 38:e384023. [PMID: 37851785 PMCID: PMC10578094 DOI: 10.1590/acb384023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 07/17/2023] [Indexed: 10/20/2023] Open
Abstract
PURPOSE To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. METHODS Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. RESULTS There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. CONCLUSIONS The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.
Collapse
Affiliation(s)
- Verena Palmeiras Brasil
- Universidade Estadual de Campinas – Postgraduate Program in Surgical Sciences – Campinas (São Paulo) – Brazil
| | - Rayama Moreira Siqueira
- Universidade Estadual de Campinas – Postgraduate Program in Surgical Sciences – Campinas (São Paulo) – Brazil
| | - Fabio Guilherme Campos
- Universidade de São Paulo – Department of Gastroenterology – Faculty of Medicine – São Paulo (São Paulo) – Brazil
| | - Mateus Magami Yoshitani
- Universidade São Francisco – Faculty of Medicine – Medical School – Bragança Paulista (São Paulo) – Brazil
| | - Geovanna Pacciulli Pereira
- Universidade São Francisco – Faculty of Medicine – Medical School – Bragança Paulista (São Paulo) – Brazil
| | | | - Danilo Toshio Kanno
- Universidade São Francisco – Faculty of Medicine – Medical School – Bragança Paulista (São Paulo) – Brazil
| | - José Aires Pereira
- Universidade São Francisco – Faculty of Medicine – Medical School – Bragança Paulista (São Paulo) – Brazil
| | - Carlos Augusto Real Martinez
- Universidade Estadual de Campinas – Postgraduate Program in Surgical Sciences – Campinas (São Paulo) – Brazil
- Universidade São Francisco – Faculty of Medicine – Medical School – Bragança Paulista (São Paulo) – Brazil
| |
Collapse
|
|
10
|
Di Martino L, Osme A, Ghannoum M, Cominelli F. A Novel Probiotic Combination Ameliorates Crohn's Disease-Like Ileitis by Increasing Short-Chain Fatty Acid Production and Modulating Essential Adaptive Immune Pathways. Inflamm Bowel Dis 2023; 29:1105-1117. [PMID: 36715169 PMCID: PMC10320237 DOI: 10.1093/ibd/izac284] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Crohn's disease (CD) represents a significant public health challenge. We identified a combination of beneficial probiotic strains (Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium breve) and amylase that may antagonize elevated bacterial pathogens in the inflamed gut. Our aim was to characterize the effect(s) of this novel probiotic supplement in SAMP1/YitFc (SAMP) mice with CD-like ileitis. METHODS Three groups of 7-week-old SAMP mice were used in this study. The first experimental group was administered 1 dose of the probiotic supplement (probiotic strains + amylase) diluted in sterile phosphate-buffered saline (PBS) (0.25 mg in 100 µL of PBS) every day for 56 days through the gavage technique, the second group had a probiotic supplement (probiotic strains without amylase), and the third group was a control group in which animals were administered sterile PBS. At the end of the treatment, mice were sacrificed and ilea were collected for histological scoring of ileitis and NanoString analysis. Stool samples were evaluated by 16S ribosomal RNA and gas chromatography-mass spectrometry analyses. RESULTS Histology scores showed that mice treated with probiotics + amylase had a significant decrease of ileitis severity compared with the other 2 groups. 16S ribosomal RNA and gas chromatography-mass spectrometry analysis showed that abundance of species belonging to genus Lachnoclostridium and Mucispirillum schaedleri were significantly increased compared with the other 2 groups, and this increase was associated with augmented production of short-chain fatty acids. NanoString data showed that 21 genes involved in B memory cell development and T cell infiltration were significantly upregulated in probiotic-treated mice and that 3 genes were significantly downregulated. CONCLUSIONS Our data provide experimental proof for a beneficial effect of the designed probiotic formulation on the severity of CD-like ileitis in the SAMP mouse model, involving both alteration of intestinal genetic pathways and microbial rearrangements. Thus, we propose that this novel probiotic mixture should be further tested as an adjuvant therapy in the treatment of biofilm-associated disorders such as CD, in which it has been proven that polymicrobial imbalance plays a critical role in dysbiosis and gut inflammation.
Collapse
Affiliation(s)
- Luca Di Martino
- Case Digestive Health Research Institute, Case Western University School of Medicine, Cleveland, OH, USA
- Department of Medicine, Case Western University School of Medicine, Cleveland, OH, USA
| | - Abdullah Osme
- Department of Pathology, Case Western University School of Medicine, Cleveland, OH, USA
| | - Mahmoud Ghannoum
- Center for Medical Mycology and Integrated Microbiome Core, Department of Dermatology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Fabio Cominelli
- Case Digestive Health Research Institute, Case Western University School of Medicine, Cleveland, OH, USA
- Department of Medicine, Case Western University School of Medicine, Cleveland, OH, USA
- Department of Pathology, Case Western University School of Medicine, Cleveland, OH, USA
| |
Collapse
|
|
11
|
Oliveira ECSD, Quaglio AEV, Magro DO, Di Stasi LC, Sassaki LY. Intestinal Microbiota and miRNA in IBD: A Narrative Review about Discoveries and Perspectives for the Future. Int J Mol Sci 2023; 24:ijms24087176. [PMID: 37108339 PMCID: PMC10138604 DOI: 10.3390/ijms24087176] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/04/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC) and comprises a chronic gastrointestinal tract disorder characterized by hyperactive and dysregulated immune responses to environmental factors, including gut microbiota and dietary components. An imbalance of the intestinal microbiota may contribute to the development and/or worsening of the inflammatory process. MicroRNAs (miRNAs) have been associated with various physiological processes, such as cell development and proliferation, apoptosis, and cancer. In addition, they play an important role in inflammatory processes, acting in the regulation of pro- and anti-inflammatory pathways. Differences in the profiles of miRNAs may represent a useful tool in the diagnosis of UC and CD and as a prognostic marker in both diseases. The relationship between miRNAs and the intestinal microbiota is not completely elucidated, but recently this topic has gained prominence and has become the target of several studies that demonstrate the role of miRNAs in the modulation of the intestinal microbiota and induction of dysbiosis; the microbiota, in turn, can regulate the expression of miRNAs and, consequently, alter the intestinal homeostasis. Therefore, this review aims to describe the interaction between the intestinal microbiota and miRNAs in IBD, recent discoveries, and perspectives for the future.
Collapse
Affiliation(s)
- Ellen Cristina Souza de Oliveira
- Department of Internal Medicine, Medical School, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-970, Brazil
| | - Ana Elisa Valencise Quaglio
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-689, Brazil
| | - Daniéla Oliveira Magro
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Sao Paulo CEP 13083-970, Brazil
| | - Luiz Claudio Di Stasi
- Laboratory of Phytomedicines, Pharmacology and Biotechnology (PhytoPharmaTec), Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-689, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, Sao Paulo State University (UNESP), Campus Botucatu, Sao Paulo CEP 18618-970, Brazil
| |
Collapse
|
|
12
|
El-Sayed A, Aleya L, Kamel M. Epigenetics and the role of nutraceuticals in health and disease. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:28480-28505. [PMID: 36694069 DOI: 10.1007/s11356-023-25236-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 01/05/2023] [Indexed: 06/17/2023]
Abstract
In the post-genomic era, the data provided by complete genome sequencing could not answer several fundamental questions about the causes of many noninfectious diseases, diagnostic biomarkers, and novel therapeutic approaches. The rapidly expanding understanding of epigenetic mechanisms, as well as widespread acceptance of their hypothesized role in disease induction, facilitated the development of a number of novel diagnostic markers and therapeutic concepts. Epigenetic aberrations are reversible in nature, which enables the treatment of serious incurable diseases. Therefore, the interest in epigenetic modulatory effects has increased over the last decade, so about 60,000 publications discussing the expression of epigenetics could be detected in the PubMed database. Out of these, 58,442 were published alone in the last 10 years, including 17,672 reviews (69 historical articles), 314 clinical trials, 202 case reports, 197 meta-analyses, 156 letters to the editor, 108 randomized controlled trials, 87 observation studies, 40 book chapters, 22 published lectures, and 2 clinical trial protocols. The remaining publications are either miscellaneous or a mixture of the previously mentioned items. According to the species and gender, the publications included 44,589 human studies (17,106 females, 14,509 males, and the gender is not mentioned in the remaining papers) and 30,253 animal studies. In the present work, the role of epigenetic modulations in health and disease and the influencing factors in epigenetics are discussed.
Collapse
Affiliation(s)
- Amr El-Sayed
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Lotfi Aleya
- Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, 25030, Besançon Cedex, France
| | - Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
| |
Collapse
|
|
13
|
Qu D, Yu L, Tian F, Zhang H, Chen W, Gu Z, Zhai Q. Bifidobacterium bifidum FJSWX19M5 alleviated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis by mitigating gut barrier injury and increasing regulatory T cells. Food Funct 2023; 14:181-194. [PMID: 36477762 DOI: 10.1039/d2fo02659g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Probiotics have been evaluated as alternative approaches for preventing the relapse of Crohn's disease (CD). Previously, we observed strain-specific anti-inflammatory properties of Bifidobacterium bifidum in 2,4,6-trinitrobenzene sulfonic acid (TNBS) acute colitis models. In this study, we further assessed the effects of several B. bifidum strains on colonic damage, fibrosis, inflammatory factors, intestinal microbial and metabolic profiles, and peripheral regulatory T cells (Tregs) in the context of TNBS chronic colitis in mice. These results indicated that B. bifidum FJSWX19M5, but not FXJWS17M4, ameliorated body weight loss, reduced colonic shortening and injury, decreased markers of gut inflammation, and rebalanced colonic metabolism in TNBS-treated mice. FJSWX19M5 supplementation also promoted Treg cell differentiation and intestinal barrier restoration compared to other strains. All living B. bifidum strains (FJSWX19M5, FXJWS17M4 and FHENJZ3M6) seemed to restore the disruption of the gut microbiota caused by TNBS. The co-culture of B. bifidum strains and mesenteric lymph node cells from TNBS-treated mice showed that those strains with anti-colitis could induce higher IL-10 levels and a lower ratio of IL-22/IL-10 and IL-17/IL-10 when compared to those strains that were not protective. Furthermore, heat-killed FJSWX19M5 exhibited a relief effect on colitis-related symptoms (including body weight loss, colonic shortening and injury). These data imply that specific B. bifidum strains or their lysates may be the current therapeutic alternatives for CD.
Collapse
Affiliation(s)
- Dingwu Qu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. .,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. .,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. .,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. .,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China.,Wuxi Translational Medicine Research Center and Jiangsu Translational, Medicine Research Institute, Wuxi Branch, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. .,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Zhennan Gu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. .,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R. China. .,School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| |
Collapse
|
|
14
|
Wu P, Wu B, Zhuang Z, Liu J, Hong L, Ma B, Lin B, Wang J, Lin C, Chen J, Chen S. Intestinal mucosal and fecal microbiota profiles in Crohn's disease in Chinese children. MEDICINE IN MICROECOLOGY 2022. [DOI: 10.1016/j.medmic.2022.100071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
|
|
15
|
Crohn’s Disease, Host–Microbiota Interactions, and Immunonutrition: Dietary Strategies Targeting Gut Microbiome as Novel Therapeutic Approaches. Int J Mol Sci 2022; 23:ijms23158361. [PMID: 35955491 PMCID: PMC9369148 DOI: 10.3390/ijms23158361] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/22/2022] [Accepted: 07/26/2022] [Indexed: 11/16/2022] Open
Abstract
Crohn’s disease (CD) is a complex, disabling, idiopathic, progressive, and destructive disorder with an unknown etiology. The pathogenesis of CD is multifactorial and involves the interplay between host genetics, and environmental factors, resulting in an aberrant immune response leading to intestinal inflammation. Due to the high morbidity and long-term management of CD, the development of non-pharmacological approaches to mitigate the severity of CD has recently attracted great attention. The gut microbiota has been recognized as an important player in the development of CD, and general alterations in the gut microbiome have been established in these patients. Thus, the gut microbiome has emerged as a pre-eminent target for potential new treatments in CD. Epidemiological and interventional studies have demonstrated that diet could impact the gut microbiome in terms of composition and functionality. However, how specific dietary strategies could modulate the gut microbiota composition and how this would impact host–microbe interactions in CD are still unclear. In this review, we discuss the most recent knowledge on host–microbe interactions and their involvement in CD pathogenesis and severity, and we highlight the most up-to-date information on gut microbiota modulation through nutritional strategies, focusing on the role of the microbiota in gut inflammation and immunity.
Collapse
|
|
16
|
Liñares-Blanco J, Fernandez-Lozano C, Seoane JA, López-Campos G. Machine Learning Based Microbiome Signature to Predict Inflammatory Bowel Disease Subtypes. Front Microbiol 2022; 13:872671. [PMID: 35663898 PMCID: PMC9157387 DOI: 10.3389/fmicb.2022.872671] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/26/2022] [Indexed: 11/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic disease with unknown pathophysiological mechanisms. There is evidence of the role of microorganims in this disease development. Thanks to the open access to multiple omics data, it is possible to develop predictive models that are able to prognosticate the course and development of the disease. The interpretability of these models, and the study of the variables used, allows the identification of biological aspects of great importance in the development of the disease. In this work we generated a metagenomic signature with predictive capacity to identify IBD from fecal samples. Different Machine Learning models were trained, obtaining high performance measures. The predictive capacity of the identified signature was validated in two external cohorts. More precisely a cohort containing samples from patients suffering Ulcerative Colitis and another from patients suffering Crohn's Disease, the two major subtypes of IBD. The results obtained in this validation (AUC 0.74 and AUC = 0.76, respectively) show that our signature presents a generalization capacity in both subtypes. The study of the variables within the model, and a correlation study based on text mining, identified different genera that play an important and common role in the development of these two subtypes.
Collapse
Affiliation(s)
- Jose Liñares-Blanco
- Department of Computer Science and Information Technologies, Faculty of Computer Science, CITIC, University of A Coruña, A Coruña, Spain.,GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government PTS Granada, Granada, Spain.,Department of Statistics and Operational Research, University of Granada, Granada, Spain
| | - Carlos Fernandez-Lozano
- Department of Computer Science and Information Technologies, Faculty of Computer Science, CITIC, University of A Coruña, A Coruña, Spain
| | - Jose A Seoane
- Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - Guillermo López-Campos
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom
| |
Collapse
|
|
17
|
Hu S, Mok J, Gowans M, Ong DEH, Hartono JL, Lee JWJ. Oral Microbiome of Crohn's Disease Patients With and Without Oral Manifestations. J Crohns Colitis 2022; 16:1628-1636. [PMID: 35511486 PMCID: PMC9624293 DOI: 10.1093/ecco-jcc/jjac063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 04/03/2022] [Accepted: 04/27/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Microbiome dysbiosis is associated with inflammatory destruction in Crohn's disease [CD]. Although gut microbiome dysbiosis is well established in CD, the oral microbiome is comparatively under-studied. This study aims to characterize the oral microbiome of CD patients with/without oral manifestations. METHODS Patients with CD were recruited with age-, gender- and race-matched controls. Potential confounders such as dental caries and periodontal condition were recorded. The oral microbiome was collected using saliva samples. Microbial DNA was extracted and sequenced using shotgun sequencing. Metagenomic taxonomic and functional profiles were generated and analysed. RESULTS The study recruited 41 patients with CD and 24 healthy controls. Within the CD subjects, 39.0% had oral manifestations with the majority presenting with cobblestoning and/or oral ulcers. Principal coordinate analysis demonstrated distinct oral microbiome profiles between subjects with and without CD, with four key variables responsible for overall oral microbiome variance: [1] diagnosis of CD, [2] concomitant use of steroids, [3] concomitant use of azathioprine and 4] presence of oral ulcers. Thirty-two significant differentially abundant microbial species were identified, with the majority associated with the diagnosis of CD. A predictive model based on differences in the oral microbiome found that the oral microbiome has strong discriminatory function to distinguish subjects with and without CD [AUROC 0.84]. Functional analysis found that an increased representation of microbial enzymes [n = 5] in the butyrate pathway was positively associated with the presence of oral ulcers. CONCLUSIONS The oral microbiome can aid in the diagnosis of CD and its composition was associated with oral manifestations.
Collapse
Affiliation(s)
- Shijia Hu
- Faculty of Dentistry, National University of Singapore, Singapore
| | - John Mok
- Division of Gastroenterology & Hepatology, National University Hospital, Singapore
| | - Michelle Gowans
- Division of Gastroenterology & Hepatology, National University Hospital, Singapore
| | - David E H Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Juanda Leo Hartono
- Division of Gastroenterology & Hepatology, National University Hospital, Singapore,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jonathan Wei Jie Lee
- Corresponding author: Jonathan Wei Jie Lee, Division of Gastroenterology & Hepatology, National University Hospital, Singapore, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore.
| |
Collapse
|
|
18
|
Abbas-Egbariya H, Haberman Y, Braun T, Hadar R, Denson L, Gal-Mor O, Amir A. Meta-analysis defines predominant shared microbial responses in various diseases and a specific inflammatory bowel disease signal. Genome Biol 2022; 23:61. [PMID: 35197084 PMCID: PMC8867743 DOI: 10.1186/s13059-022-02637-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/15/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gut microbial alteration is implicated in inflammatory bowel disease but is noted in other diseases. Systematic comparison to define similarities and specificities is hampered since most studies focus on a single disease. RESULTS We develop a pipeline to compare between disease cohorts starting from the raw V4 16S amplicon sequence variants. Including 12,838 subjects, from 59 disease cohorts, we demonstrate a predominant shared signature across diseases, indicating a common bacterial response to different diseases. We show that classifiers trained on one disease cohort predict relatively well other diseases due to this shared signal, and hence, caution should be taken when using such classifiers in real-world scenarios, where diseases are intermixed. Based on this common signature across a large array of diseases, we develop a universal dysbiosis index that successfully differentiates between cases and controls across various diseases and can be used for prioritizing fecal donors and samples with lower disease probability. Finally, we identify a set of IBD-specific bacteria, which can direct mechanistic studies and design of IBD-specific microbial interventions. CONCLUSIONS A robust non-specific general response of the gut microbiome is detected in a large array of diseases. Disease classifiers may confuse between different diseases due to this shared microbial response. Our universal dysbiosis index can be used as a tool to prioritize fecal samples and donors. Finally, the IBD-specific taxa may indicate a more direct association to gut inflammation and disease pathogenesis, and those can be further used as biomarkers and as future targets for interventions.
Collapse
Affiliation(s)
- Haya Abbas-Egbariya
- Sheba Medical Center, Tel-HaShomer, affiliated with the Tel-Aviv University, Tel Aviv, Israel
| | - Yael Haberman
- Sheba Medical Center, Tel-HaShomer, affiliated with the Tel-Aviv University, Tel Aviv, Israel
- Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH USA
| | - Tzipi Braun
- Sheba Medical Center, Tel-HaShomer, affiliated with the Tel-Aviv University, Tel Aviv, Israel
| | - Rotem Hadar
- Sheba Medical Center, Tel-HaShomer, affiliated with the Tel-Aviv University, Tel Aviv, Israel
| | - Lee Denson
- Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH USA
| | - Ohad Gal-Mor
- The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer, and the Department of Clinical Microbiology and Immunology, Tel Aviv University, Tel Aviv, Israel
| | - Amnon Amir
- Sheba Medical Center, Tel-HaShomer, affiliated with the Tel-Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
19
|
Jang S, Kim Y, Lee C, Kwon B, Noh J, Jee JJ, Yoon SS, Koh H, Park S. The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model. J Korean Med Sci 2021; 36:e342. [PMID: 34962114 PMCID: PMC8728592 DOI: 10.3346/jkms.2021.36.e342] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 10/29/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy. METHODS Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology. RESULTS Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. Verrucomicrobia and Proteobacteria abundances tended to increase and Bacteroidetes abundance decreased in the EEN group. In the EEN group, significant changes in the β-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of Akkermansia muciniphila, Clostridium cocleatum, mucin-degrading bacteria, Flintibacter butyricus, and Parabacteroides goldsteinii, which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier. CONCLUSION EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.
Collapse
Affiliation(s)
- Sooyoung Jang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Fecal Microbiota Transplantation Center, Severance Hospital, Seoul, Korea
| | - Younjuong Kim
- Department of Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Changjun Lee
- Department of Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Bomi Kwon
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Fecal Microbiota Transplantation Center, Severance Hospital, Seoul, Korea
| | - Jihye Noh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Fecal Microbiota Transplantation Center, Severance Hospital, Seoul, Korea
| | - Jai J Jee
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Fecal Microbiota Transplantation Center, Severance Hospital, Seoul, Korea
| | - Sang Sun Yoon
- Department of Microbiology and Immunology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea
- Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Fecal Microbiota Transplantation Center, Severance Hospital, Seoul, Korea
| | - Sowon Park
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Yonsei University College of Medicine, Severance Fecal Microbiota Transplantation Center, Severance Hospital, Seoul, Korea.
| |
Collapse
|
|
20
|
Altered fecal microbiota composition in individuals who abuse methamphetamine. Sci Rep 2021; 11:18178. [PMID: 34518605 PMCID: PMC8437956 DOI: 10.1038/s41598-021-97548-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 08/25/2021] [Indexed: 02/07/2023] Open
Abstract
As a severe public health problem, methamphetamine (METH) abuse places a heavy burden on families and society. A growing amount of evidence has indicated communication between gut microbiota and the CNS in drug addiction, with associations to neural, endocrine and immune pathways. Thus, we searched for alterations in the gut microbiota and their potential effects in METH users through 16S rRNA gene sequencing. A decreased Shannon index indicated lower bacterial diversity in the METH users than in the age-matched control group. The gut microbial community composition in the METH users was also altered, including reductions in Deltaproteobacteria and Bacteroidaceae abundances and increases in Sphingomonadales, Xanthomonadales, Romboutsia and Lachnospiraceae abundances. Moreover, the Fusobacteria abundance was correlated with the duration of METH use. Enterobacteriaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium had statistically significant correlations with items related to the positive and negative symptoms of schizophrenia and to general psychopathology in the METH users, and all have previously been reported to be altered in individuals with psychotic syndromes, especially depression. Abstraction, one of the items of the cognitive assessment, was positively related to Blautia. These findings revealed alterations in the gut microbiota of METH users, and these alterations may play a role in psychotic syndrome and cognitive impairment. Although the mechanisms behind the links between these disorders and METH abuse are unknown, the relationships may indicate similarities in the pathogenesis of psychosis induced by METH abuse and other causes, providing a new paradigm for addiction and METH use disorder treatment.
Collapse
|
|
21
|
El-Sayed A, Aleya L, Kamel M. Microbiota and epigenetics: promising therapeutic approaches? ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:49343-49361. [PMID: 34319520 PMCID: PMC8316543 DOI: 10.1007/s11356-021-15623-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 07/20/2021] [Indexed: 04/15/2023]
Abstract
The direct/indirect responsibility of the gut microbiome in disease induction in and outside the digestive tract is well studied. These results are usually from the overpopulation of certain species on the cost of others, interaction with beneficial microflora, interference with normal epigenetic control mechanisms, or suppression of the immune system. Consequently, it is theoretically possible to cure such disorders by rebalancing the microbiome inside our bodies. This can be achieved by changing the lifestyle pattern and diet or by supplementation with beneficial bacteria or their metabolites. Various approaches have been explored to manipulate the normal microbial inhabitants, including nutraceutical, supplementations with prebiotics, probiotics, postbiotics, synbiotics, and antibiotics, or through microbiome transplantation (fecal, skin, or vaginal microbiome transplantation). In the present review, the interaction between the microbiome and epigenetics and their role in disease induction is discussed. Possible future therapeutic approaches via the reestablishment of equilibrium in our internal micro-ecosystem are also highlighted.
Collapse
Affiliation(s)
- Amr El-Sayed
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Lotfi Aleya
- Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, F-25030, Besançon Cedex, France
| | - Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
| |
Collapse
|
|
22
|
Scannapieco FA, Dongari-Bagtzoglou A. Dysbiosis revisited: Understanding the role of the oral microbiome in the pathogenesis of gingivitis and periodontitis: A critical assessment. J Periodontol 2021; 92:1071-1078. [PMID: 33902163 DOI: 10.1002/jper.21-0120] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/02/2021] [Accepted: 04/18/2021] [Indexed: 12/22/2022]
Abstract
This commentary provides background, historical context, and a critical assessment of the concept that microbial dysbiosis drives the pathogenesis of periodontal diseases. It is long known that periodontal pathogenesis is dependent on tooth-borne microbial biofilms (dental plaque) that trigger host inflammation resulting in periodontal destruction and tooth loss in some patients. Ecological principles governing plaque biofilm development, along with localized host responses, are both rooted in evolution. Interpretation of available evidence suggests that, in most patients, alveolar bone loss results from interactions of a highly diverse commensal microbiota with the host, and not from "overgrowth" of a few "pathobionts" that results in a "dysbiosis." Most previously described dysbiotic chronic diseases, for example, inflammatory bowel diseases and dermatitis, are characterized by decreased microbial diversity (likely due to frank overgrowth of one or a few microbial taxa). Most common forms of periodontitis do not appear to conform to this general principle, and the associated microbiome in fact almost always shows increased bacterial diversity compared with periodontal health. This diversity is driven by interactions of genetic and environmental factors working in concert within specific windows of time. Periodontal pathogenesis is likely the result of "personalized pathology," insofar as each patient likely has a variable constellation of microbes and host risk factors influencing specific tissue sites where disease activity occurs, and during a limited window of time (a tissue-destructive "burst"). The concept of cooperative virulence of higher abundance commensals in periodontal pathogenesis, which does not conform to the model of dysbiosis observed for other diseases, is discussed.
Collapse
Affiliation(s)
- Frank A Scannapieco
- Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY
| | - Anna Dongari-Bagtzoglou
- Department of Oral Health and Diagnostic Sciences, Division of Periodontology, UConn Health, Farmington, CT
| |
Collapse
|
|
23
|
Aldars-García L, Chaparro M, Gisbert JP. Systematic Review: The Gut Microbiome and Its Potential Clinical Application in Inflammatory Bowel Disease. Microorganisms 2021; 9:microorganisms9050977. [PMID: 33946482 PMCID: PMC8147118 DOI: 10.3390/microorganisms9050977] [Citation(s) in RCA: 108] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing-remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.
Collapse
Affiliation(s)
- Laila Aldars-García
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - María Chaparro
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - Javier P. Gisbert
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
- Correspondence: ; Tel.: +34-913-093-911; Fax: +34-915-204-013
| |
Collapse
|
|
24
|
Thaler DS. Is Global Microbial Biodiversity Increasing, Decreasing, or Staying the Same? Front Ecol Evol 2021. [DOI: 10.3389/fevo.2021.565649] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Animal and plant biodiversity is decreasing. In contrast, the global direction and the pace of change in microbial, including viral, biodiversity is unknown. Important niches for microbial diversity occur in highly specific associations with plants and animals, and these niches are lost as hosts become extinct. The taxonomic diversity of human gut bacteria is reported to be decreasing. On the other hand, SARS-CoV-2 variation is increasing. Where microbes are concerned, Darwin’s “tangled bank” of interdependent organisms may be composed mostly of other microbes. There is the likelihood that as some classes of microbes become extinct, others evolve and diversify. A better handle on all processes that affect microbial biodiversity and their net balance is needed. Lack of insight into the dynamics of evolution of microbial biodiversity is arguably the single most profound and consequential unknown with regard to human knowledge of the biosphere. If some or all parts of microbial diversity are relentlessly increasing, then survey approaches may be too slow to ever catch up. New approaches, including single-molecule or single-cell sequencing in populations, as well as focused attention on modulators and vectors of vertical and horizontal evolution may offer more direct insights into some aspects of the pace of microbial evolution.
Collapse
|
|
25
|
Fernández-Ponce C, Navarro Quiroz R, Díaz Perez A, Aroca Martinez G, Cadena Bonfanti A, Acosta Hoyos A, Gómez Escorcia L, Hernández Agudelo S, Orozco Sánchez C, Villarreal Camacho J, Atencio Ibarra L, Consuegra Machado J, Espinoza Garavito A, García-Cózar F, Navarro Quiroz E. MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis. Clin Epigenetics 2021; 13:39. [PMID: 33602320 PMCID: PMC7890887 DOI: 10.1186/s13148-021-01022-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 02/02/2021] [Indexed: 12/14/2022] Open
Abstract
Background In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. Methods We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. Results We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. Conclusion The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-021-01022-8.
Collapse
Affiliation(s)
- Cecilia Fernández-Ponce
- Department of Biomedicine, Biotechnology and Public Health, University of Cadiz, Cadiz, Spain
| | - Roberto Navarro Quiroz
- CMCC-Centro de Matemática, Computação E Cognição, Laboratório do Biología Computacional e Bioinformática-LBCB, Universidade Federal Do ABC, Sao Paulo, 01023, Brazil
| | - Anderson Díaz Perez
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia.,Universidad Rafael Nuñez, 130001, Cartagena, Colombia
| | - Gustavo Aroca Martinez
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia.,Department of Nephrology, Clinica de La Costa, 080001, Barranquilla, Colombia
| | - Andrés Cadena Bonfanti
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia.,Department of Nephrology, Clinica de La Costa, 080001, Barranquilla, Colombia
| | - Antonio Acosta Hoyos
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia
| | - Lorena Gómez Escorcia
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia.,Universidad Rafael Nuñez, 130001, Cartagena, Colombia
| | - Sandra Hernández Agudelo
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia.,Department of Nephrology, Clinica de La Costa, 080001, Barranquilla, Colombia
| | - Christian Orozco Sánchez
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia
| | | | | | | | - Alberto Espinoza Garavito
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia
| | - Francisco García-Cózar
- Department of Biomedicine, Biotechnology and Public Health, University of Cadiz, Cadiz, Spain
| | - Elkin Navarro Quiroz
- Facultad de Ciencias Básicas y Biomédicas, Universidad Simon Bolivar, 080001, Barranquilla, Colombia. .,Centro de Investigación E Innovación en Biomoléculas, C4U S.A.S, 080001, Barranquilla, Colombia.
| |
Collapse
|
|
26
|
Beheshti-Maal A, Shahrokh S, Ansari S, Mirsamadi ES, Yadegar A, Mirjalali H, Zali MR. Gut mycobiome: The probable determinative role of fungi in IBD patients. Mycoses 2021; 64:468-476. [PMID: 33421192 DOI: 10.1111/myc.13238] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 12/15/2020] [Accepted: 01/04/2021] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel disease (IBD) is a multi-factorial autoimmune disorder that its causative agents are unknown. The gut microbiota comprises of bacteria, viruses, fungi and protozoa that its role in IBD has remained controversially. Bacteria constitute more than 99% of the gut microbiota composition, and the main core of the gut microbiota is composed from Bacteroidetes and Firmicutes. The gut microbiota plays an important role in training, development and haemostasis of the immune responses during the life. Fungi compose a very small portion of gut microbiota, but play determinative roles in homeostasis of the gut bacterial composition and the mucosal immune responses. An interkingdom correlation between bacteria and fungi has been suggested. For example, the presence of Salmonella enterica serovar Typhimurium reduces the viability and colonisation of C albicans. Alterations in the composition and function of the gut microbiota, which is known as dysbiosis, are a usual event in patients who suffer from IBD. Although the main reason for this alteration is not clear, the interaction between gut bacteria and gut fungi seems to be an important subject in IBD patients. This review covers new findings on the interaction between fungi and bacteria and the role of fungi in the pathophysiology of IBD.
Collapse
Affiliation(s)
- Alireza Beheshti-Maal
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saham Ansari
- Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elnaz Sadat Mirsamadi
- Department of Microbiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
27
|
Li GH, Huang SJ, Li X, Liu XS, Du QL. Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients. World J Gastroenterol 2020; 26:7338-7351. [PMID: 33362388 PMCID: PMC7739160 DOI: 10.3748/wjg.v26.i46.7338] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/09/2020] [Accepted: 11/04/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood.
AIM To investigate the link between the gut microbiota and serum metabolome in ICP patients.
METHODS In this study, a total of 30 patients were recruited, including 15 patients with ICP (disease group) and 15 healthy pregnant patients (healthy group). The serum nontarget metabolomes from both groups were determined. Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups. By comparing the differences in the microbiota and metabolite compositions between the two groups, the relationship between the gut microbiota and serum metabolites was also investigated.
RESULTS The Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis, bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls. In addition, some pathways related to protein metabolism were also enriched in the ICP patients. The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition (beta diversity) between the ICP patients and healthy controls. At the phylum level, we observed that the relative abundance of Firmicutes was higher in the healthy group, while Bacteroidetes were enriched in the disease group. At the genus level, most of the bacteria depleted in ICP are able to produce short-chain fatty acids (e.g., Faecalibacterium, Blautia and Eubacterium hallii), while the bacteria enriched in ICP are associated with bile acid metabolism (e.g., Parabacteroides and Bilophila). Our results also showed that specific genera were associated with the serum metabolome.
CONCLUSION Our study showed that the serum metabolome was altered in ICP patients compared to healthy controls, with significant differences in the bile, taurine and hypotaurine metabolite pathways. Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota, which may further affect the course of progression of ICP.
Collapse
Affiliation(s)
- Guo-Hua Li
- Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Shi-Jia Huang
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Xiang Li
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Xiao-Song Liu
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| | - Qiao-Ling Du
- Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, China
| |
Collapse
|
|
28
|
Cornelian Cherry Iridoid-Polyphenolic Extract Improves Mucosal Epithelial Barrier Integrity in Rat Experimental Colitis and Exerts Antimicrobial and Antiadhesive Activities In Vitro. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:7697851. [PMID: 33299531 PMCID: PMC7707999 DOI: 10.1155/2020/7697851] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 10/18/2020] [Accepted: 11/01/2020] [Indexed: 12/15/2022]
Abstract
Background and Aims Inflammatory bowel disease pharmacotherapy, despite substantial progress, is still not satisfactory for both patients and clinicians. In view of the chronic and relapsing disease course and not always effective treatment with adverse effects, attempts to search for new, more efficient, and safer substances are essential and reasonable. This study was designed to elucidate the impact of cornelian cherry iridoid-polyphenolic extract (CE) and loganic acid (LA) on adherent-invasive E. coli growth and adhesion in vitro and to assess the effect of pretreatment with CE or LA on the course of intestinal inflammation in rat experimental colitis compared with sulfasalazine. Methods Antibacterial and antiadhesive activities of CE and LA were assessed using microdilution, Int407 cell adherence, and yeast agglutination assays. The colitis model was induced by 2,4,6-trinitrobenzenesulfonic acid. Studied substances were administered intragastrically for 16 days prior to colitis induction. Body weight loss; colon index; histological injuries; IL-23, IL-17, TNF-α, and chemerin levels; and STAT3, Muc2, and TFF3 mRNA expression were evaluated. Results Only CE exerted antimicrobial and antiadhesive activities in vitro and alleviated colonic symptoms. CE coadministrated with sulfasalazine was more effective than single compounds in reversing increased concentrations of TNF-α, IL-17, and chemerin and decreased Muc2 mRNA expression. Conclusions CE exerted a protective effect against experimental colitis via impaired mucosal epithelial barrier restoration and intestinal inflammatory response attenuation and given concomitantly with sulfasalazine counteracted colitis in a more effective way than sulfasalazine alone, which indicates their synergistic interaction. The beneficial effect of CE may also be due to its bacteriostatic and antiadhesive activities.
Collapse
|
|
29
|
Ng CH, Chin YH, Lin SY, Koh JWH, Lieske B, Koh FHX, Chong CS, Foo FJ. Kono-S anastomosis for Crohn's disease: a systemic review, meta-analysis, and meta-regression. Surg Today 2020; 51:493-501. [PMID: 32894346 DOI: 10.1007/s00595-020-02130-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 07/25/2020] [Indexed: 12/13/2022]
Abstract
The Kono-S anastomosis was introduced in 2011 as an alternative anastomosis in Crohn's disease (CD) surgery. Since then, prevailing evidence of the favorable results of the Kono-S anastomosis has been published from around the world. We conducted this study to analyze the effectiveness of the Kono-S anastomosis, by searching Medline, Embase, CNKI, and google scholar. Binominal data were analyzed after Freeman-Tukey double-arcsine transformation. Comparative data were analyzed using the Mantel-Haenszel model for dichotomous outcomes and the mean difference for continuous outcomes. We identified 676 patients who underwent surgery with a Kono-S anastomosis. Surgical recurrence was pooled at an average of 0% (CI: 0.00-0.01) and a reduced mean Rutgeerts score of 1.375 (CI: 0.727-2.023) after Kono-S anastomosis. Endoscopic recurrence after sensitivity analysis was 5% (CI: 0.00-0.15). Complications were rare, with a 3% incidence of ileus (CI: 0.01-0.05), a 4% incidence of small bowel obstruction (CI: 0.01-0.10), a 1% incidence of an anastomotic leak incidence (CI: 0.00-0.03), and a 10% incidence of postoperative infection (CI: 0.03-0.20). Evidence from this meta-analysis favors the Kono-S anastomosis for CD patients, especially for ileocolic anastomosis. Thus, clinicians should consider the applicability of Kono-S anastomosis in respective institutions.
Collapse
Affiliation(s)
- Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Yip Han Chin
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | | | - Bettina Lieske
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore
| | | | - Choon Seng Chong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore. .,Division of Colorectal Surgery, Department of Surgery, National University Hospital, Singapore, Singapore.
| | - Fung Joon Foo
- Department of General Surgery, Sengkang General Hospital, Singapore, Singapore
| |
Collapse
|
|
30
|
Li R, Huang X, Liang X, Su M, Lai KP, Chen J. Integrated omics analysis reveals the alteration of gut microbe-metabolites in obese adults. Brief Bioinform 2020; 22:5882185. [PMID: 32770198 DOI: 10.1093/bib/bbaa165] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/01/2020] [Accepted: 07/02/2020] [Indexed: 12/13/2022] Open
Abstract
Obesity, a risk to health, is a global problem in modern society. The prevalence of obesity was approximately 13% among world's adult population. Recently, several reports suggested that the interference of gut microbiota composition and function is associated with metabolic disorders, including obesity. Gut microbiota produce a board range of metabolites involved in energy and glucose homeostasis, leading to the alteration in host metabolism. However, systematic evaluation of the relationship between gut microbiota, gut metabolite and host metabolite profiles in obese adults is still lacking. In this study, we used comparative metagenomics and metabolomics analysis to determine the gut microbiota and gut-host metabolite profiles in six normal and obese adults of Chinese origin, respectively. Following the functional and pathway analysis, we aimed to understand the possible impact of gut microbiota on the host metabolites via the change in gut metabolites. The result showed that the change in gut microbiota may result in the modulation of gut metabolites contributing to glycolysis, tricarboxylic acid cycle and homolactic fermentation. Furthermore, integrated metabolomic analysis demonstrated a possible positive correlation of dysregulated metabolites in the gut and host, including l-phenylalanine, l-tyrosine, uric acid, kynurenic acid, cholesterol sulfate and glucosamine, which were reported to contribute to metabolic disorders such as obesity and diabetes. The findings of this study provide the possible association between gut microbiota-metabolites and host metabolism in obese adults. The identified metabolite changes could serve as biomarkers for the evaluation of obesity and metabolic disorders.
Collapse
Affiliation(s)
| | | | | | - Min Su
- Guilin Medical University
| | | | | |
Collapse
|
|
31
|
Ambrosini YM, Shin W, Min S, Kim HJ. Microphysiological Engineering of Immune Responses in Intestinal Inflammation. Immune Netw 2020; 20:e13. [PMID: 32395365 PMCID: PMC7192834 DOI: 10.4110/in.2020.20.e13] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/18/2020] [Accepted: 03/10/2020] [Indexed: 02/07/2023] Open
Abstract
The epithelial barrier in the gastrointestinal (GI) tract is a protective interface that endures constant exposure to the external environment while maintaining its close contact with the local immune system. Growing evidence has suggested that the intercellular crosstalk in the GI tract contributes to maintaining the homeostasis in coordination with the intestinal microbiome as well as the tissue-specific local immune elements. Thus, it is critical to map the complex crosstalks in the intestinal epithelial-microbiome-immune (EMI) axis to identify a pathological trigger in the development of intestinal inflammation, including inflammatory bowel disease. However, deciphering a specific contributor to the onset of pathophysiological cascades has been considerably hindered by the challenges in current in vivo and in vitro models. Here, we introduce various microphysiological engineering models of human immune responses in the EMI axis under the healthy conditions and gut inflammation. As a prospective model, we highlight how the human “gut inflammation-on-a-chip” can reconstitute the pathophysiological immune responses and contribute to understanding the independent role of inflammatory factors in the EMI axis on the initiation of immune responses under barrier dysfunction. We envision that the microengineered immune models can be useful to build a customizable patient's chip for the advance in precision medicine.
Collapse
Affiliation(s)
- Yoko M Ambrosini
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.,Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011 USA
| | - Woojung Shin
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
| | - Soyoun Min
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
| | - Hyun Jung Kim
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.,Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
| |
Collapse
|