The Role of the Gut Microbiome in Health and Disease

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: 20 May 2024 | Viewed by 22746

Special Issue Editors


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Guest Editor
Microbiome Research Centre, St George and Sutherland Clinical School, The University of New South Wales, Sydney 2052, Australia
Interests: gut microbiome; microbially driven GI cancer; gastric cancer; inflammatory bowel disease; helicobacter pylori infection

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Guest Editor
Microbiome Research Centre, St George and Sutherland Clinical School, UNSW Sydney, Kogarah, NSW, Australia
Interests: microbiome; inflammation; infectious diseases; healthy microbiome; mental health and neuroscience; women and children’s health; and natural therapies; sex-differences in immune responses

Special Issue Information

Dear Colleagues,

Our understanding of the impact of microbes on their human hosts is only just emerging. These microbial communities have coevolved with us, forming astonishing ‘symbiotic relationships’ with our bodies that are largely responsible for our overall health. Our intestinal lining usually forms tight junctions that control absorption into the bloodstream. However, when this barrier becomes leaky, microbes and their metabolites can enter the bloodstream and trigger widespread inflammation and changes in the gut microbiome, known as gut dysbiosis. Gut dysbiosis has been associated with diseases such as autism, obesity, diabetes, cancer, inflammatory bowel disease, and dementia. The associations between the gut microbiome and the pathogenesis of disease have positioned the gut microbiome as a potential novel target for therapeutics.

This Special Issue focuses on the complex interplay between the gut microbiome and the balance between health and disease. You are invited to submit state-of the art reviews as well as original research articles on the role of microbiota found in disease, across multiple systems including but not limited to hepatobiliary, cardiovascular and urogynecological. We welcome research on all aspects of the gut microbiome in health, particularly works that demonstrate a role of gut microbiota in the pathogenesis of disease, with a focus on host–microbiota interactions, or research on the microbiome regarding its potential to yield biomarkers or therapeutics in disease. 

Prof. Dr. Emad M. El-Omar
Dr. Fatima El-Assaad
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbiome
  • gut microbiome
  • intestinal permeability
  • bacteria
  • health
  • dysbiosis

Published Papers (10 papers)

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Research

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12 pages, 346 KiB  
Article
Next-Generation Sequencing-Based Monitoring of Intestinal Bacteria and Bacteriophages Following Fecal Microbiota Transplantation in Inflammatory Bowel Diseases
by Oleg V. Goloshchapov, Oksana B. Shchukina, Aleksey V. Kusakin, Viktoria V. Tsai, Roman S. Kalinin, Yury A. Eismont, Oleg S. Glotov and Alexei B. Chukhlovin
Pathogens 2023, 12(12), 1438; https://doi.org/10.3390/pathogens12121438 - 11 Dec 2023
Viewed by 1042
Abstract
Inflammatory bowel diseases (IBD) and acute graft-versus-host disease (GVHD) are associated with persistent intestinal dysfunction preceded by gut bacterial dysbiosis. There are limited data on intestinal bacteriophages in these conditions. The aim of the present work was to detect associations between dominant intestinal [...] Read more.
Inflammatory bowel diseases (IBD) and acute graft-versus-host disease (GVHD) are associated with persistent intestinal dysfunction preceded by gut bacterial dysbiosis. There are limited data on intestinal bacteriophages in these conditions. The aim of the present work was to detect associations between dominant intestinal bacteria by means of 16S rRNA gene sequencing, and some clinically significant viruses detected with a customized primer panel for NGS-based study. The clinical group included patients with Crohn’s disease (IBD, n = 9), or GVHD (n = 6) subjected to fecal microbiota transplantation (FMT) from healthy donors. The stool specimens were taken initially, and 5 times post-FMT until day 120. Using NGS approach, we have found a higher abundance of Proteobacterota phylum in GVHD, especially, at later terms post-FMT. Moreover, we found an early increase of Klebsiella and E. coli/Shigella abundance in GVHD, along with decreased relative content of Faecalibacterium. Upon evaluation of intestinal phageome, the relative amount of Caudoviricetes class was higher in GVHD. A significant correlation was found between Proteobacteria and Caudoviricetes, thus suggesting their association during the post-FMT period. Moreover, the relative amounts of five Caudoviricetes phage species showed distinct correlations with Klebsiella and Enterococcus ratios at different terms of FMT. In conclusion, parallel use of 16S rRNA gene sequencing and targeted NGS viral panel is a feasible and useful option for tracing specific viral strains in fecal microbiota. The developed array of viral primers may be extended to detect other phages infecting the clinically relevant bacteria. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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23 pages, 45074 KiB  
Article
Lactobacillus rhamnosus Attenuates Cisplatin-Induced Intestinal Mucositis in Mice via Modulating the Gut Microbiota and Improving Intestinal Inflammation
by Duaa M. Alsholi, Ghazi Suleiman Yacoub, Ata Ur Rehman, Hidayat Ullah, Asif Iqbal Khan, Ting Deng, Nimra Zafar Siddiqui, Yamina Alioui, Nabeel Ahmed Farooqui, Maroua Elkharti, Yanxia Li, Liang Wang and Yi Xin
Pathogens 2023, 12(11), 1340; https://doi.org/10.3390/pathogens12111340 - 11 Nov 2023
Viewed by 2041
Abstract
Lactobacillus rhamnosus (LBS) is a well-documented probiotic strain in oncology and has a pivotal role in clinical applications. Here, we have investigated the protective effect of Lactobacillus rhamnosus on intestinal mucositis induced by cisplatin (CP) and explored the underlying mechanisms targeting inflammatory proteins, [...] Read more.
Lactobacillus rhamnosus (LBS) is a well-documented probiotic strain in oncology and has a pivotal role in clinical applications. Here, we have investigated the protective effect of Lactobacillus rhamnosus on intestinal mucositis induced by cisplatin (CP) and explored the underlying mechanisms targeting inflammatory proteins, as well as the histological changes in the intestinal tissue of mice, in addition, the bacterial strains that may be related to the health-enhancing properties. BALB/c mice were pre-treated with or without LBS via oral gavage, followed by mucositis induction with cisplatin. Our results revealed that the LBS-treated groups significantly attenuated proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α) compared to the CP group. Furthermore, LBS mitigated the damaged tight junction integrity caused by CP via up-regulating the levels of claudin, occludin, ZO-1, and mucin-2 protein (MUC-2). Finally, the 16S rRNA fecal microbiome genomic analysis showed that LBS administration enhanced the growth of beneficial bacteria, i.e., Firmicutes and Lachnospiraceae, while the relative abundance of the opportunistic bacteria Bacteroides and Proteobacteria decreased. Collectively, LBS was found to beneficially modulate microbial composition structure and functions and enrich the ecological diversity in the gut. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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13 pages, 2570 KiB  
Article
Compositional Differences of Meconium Microbiomes of Preterm and Term Infants, and Infants That Developed Necrotizing Enterocolitis or Feeding Intolerance
by Hyun Mi Kang, Sol Kim, Seok Hwang-Bo, In Hyuk Yoo, Yu-Mi Seo, Moon Yeon Oh, Soo-Ah Im and Young-Ah Youn
Pathogens 2023, 12(1), 55; https://doi.org/10.3390/pathogens12010055 - 29 Dec 2022
Cited by 1 | Viewed by 1619
Abstract
The primary aim of this study was to investigate the compositional differences of the first passed meconium microbiome in preterm and term infants, and the secondary aim was to compare the meconium microbiomes of preterm and term infants that later developed necrotizing enterocolitis [...] Read more.
The primary aim of this study was to investigate the compositional differences of the first passed meconium microbiome in preterm and term infants, and the secondary aim was to compare the meconium microbiomes of preterm and term infants that later developed necrotizing enterocolitis (NEC)/Feeding intolerance (FI) compared to those that did not develop NEC/FI. During the study period, a total of 108 preterm and term newborns' first passed meconium occurring within 72 hours of birth were collected and microbiome analyzed. Meconium microbiomes showed a disruption in the percentages of the core microbiome constituents in both the phylum and genus levels in infants born < 30 weeks of gestational age (GA) compared to those born ≥ 30 weeks of GA. In the phylum level, Bacteroidetes and Firmicutes, and in the genus level, Prevotella and Bacteroides, were predominant, with Prevotella accounting for 20–30% of the relative abundance. As GA increased, a significant increase in the relative abundance of Bacteroidetes (P for trend < 0.001) and decrease in Proteobacteria (P for trend = 0.049) was observed in the phylum level. In the genus level, as GA increased, Prevotella (P for trend < 0.001) and Bacteroides (P for trend = 0.002) increased significantly, whereas Enterococcus (P for trend = 0.020) decreased. Compared to the control group, the meconium of infants that later developed NEC/FI had significantly lower alpha diversities but similar beta-diversities. Furthermore, the NEC/FI group showed a significantly lower abundance of Bacteroidetes (P < 0.001), and higher abundance of Firmicutes (P = 0.034). To conclude, differences were observed in the composition of the first passed meconium in preterm and term infants that later develop NEC/FI compared to those that did not. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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16 pages, 5939 KiB  
Article
Dysbiosis in Head and Neck Cancer: Determining Optimal Sampling Site for Oral Microbiome Collection
by Dheeraj Pandey, Michal Szczesniak, Julia Maclean, Howard Chi Ho Yim, Fan Zhang, Peter Graham, Emad M. El-Omar and Peter Wu
Pathogens 2022, 11(12), 1550; https://doi.org/10.3390/pathogens11121550 - 16 Dec 2022
Cited by 3 | Viewed by 1735
Abstract
Recent research suggests that dysbiosis of the oral microbial community is associated with head and neck cancer (HNC). It remains unclear whether this dysbiosis causes chemo-radiotherapy (CRT)-related complications. However, to address this question, it is essential to determine the most representative oral site [...] Read more.
Recent research suggests that dysbiosis of the oral microbial community is associated with head and neck cancer (HNC). It remains unclear whether this dysbiosis causes chemo-radiotherapy (CRT)-related complications. However, to address this question, it is essential to determine the most representative oral site for microbiome sampling. In this study, our purpose was to determine the optimal site for oral sample collection and whether the presence of HNC is associated with altered oral microbiome from this site. In 21 newly diagnosed HNC patients and 27 healthy controls, microbiome samples were collected from saliva, swabs from buccal mucosa, tongue, hard palate, faucial pillars and all mucosal sites combined. Microbial DNA was extracted and underwent 16S rRNA amplicon gene sequencing. In healthy controls, analysis of observed taxonomic units detected differences in alpha- and beta-diversity between sampling sites. Saliva was found to have the highest intra-community microbial diversity and lowest within-subject (temporal) and between-subject variance. Feature intersection showed that most species were shared between all sites, with saliva demonstrating the most unique species as well as highest overlap with other sites. In HNC patients, saliva was found to have the highest diversity but differences between sites were not statistically significant. Across all sites, HNC patients had lower alpha diversity than healthy controls. Beta-diversity analysis showed HNC patients’ microbiome to be compositionally distinct from healthy controls. This pattern was confirmed when the salivary microbiome was considered alone. HNC patients exhibited reduced diversity of the oral microbiome. Salivary samples demonstrate temporal stability, have the richest diversity and are sufficient to detect perturbation due to presence of HNC. Hence, they can be used as representative oral samples for microbiome studies in HNC patients. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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14 pages, 1073 KiB  
Article
The Role of the Microbiome in the Metabolic Health of People with Schizophrenia and Related Psychoses: Cross-Sectional and Pre-Post Lifestyle Intervention Analyses
by Maryanne O’Donnell, Scott B. Teasdale, Xin-Yi Chua, Jamie Hardman, Nan Wu, Jackie Curtis, Katherine Samaras, Patrick Bolton, Margaret J. Morris, Cyndi Shannon Weickert, Tertia Purves-Tyson, Fatima El-Assaad, Xiao-Tao Jiang, Georgina L. Hold and Emad El-Omar
Pathogens 2022, 11(11), 1279; https://doi.org/10.3390/pathogens11111279 - 01 Nov 2022
Cited by 1 | Viewed by 1896
Abstract
The microbiome has been implicated in the development of metabolic conditions which occur at high rates in people with schizophrenia and related psychoses. This exploratory proof-of-concept study aimed to: (i) characterize the gut microbiota in antipsychotic naïve or quasi-naïve people with first-episode psychosis, [...] Read more.
The microbiome has been implicated in the development of metabolic conditions which occur at high rates in people with schizophrenia and related psychoses. This exploratory proof-of-concept study aimed to: (i) characterize the gut microbiota in antipsychotic naïve or quasi-naïve people with first-episode psychosis, and people with established schizophrenia receiving clozapine therapy; (ii) test for microbiome changes following a lifestyle intervention which included diet and exercise education and physical activity. Participants were recruited from the Eastern Suburbs Mental Health Service, Sydney, Australia. Anthropometric, lifestyle and gut microbiota data were collected at baseline and following a 12-week lifestyle intervention. Stool samples underwent 16S rRNA sequencing to analyse microbiota diversity and composition. Seventeen people with established schizophrenia and five people with first-episode psychosis were recruited and matched with 22 age-sex, BMI and ethnicity matched controls from a concurrent study for baseline comparisons. There was no difference in α-diversity between groups at baseline, but microbial composition differed by 21 taxa between the established schizophrenia group and controls. In people with established illness pre-post comparison of α-diversity showed significant increases after the 12-week lifestyle intervention. This pilot study adds to the current literature that detail compositional differences in the gut microbiota of people with schizophrenia compared to those without mental illness and suggests that lifestyle interventions may increase gut microbial diversity in patients with established illness. These results show that microbiome studies are feasible in patients with established schizophrenia and larger studies are warranted to validate microbial signatures and understand the relevance of lifestyle change in the development of metabolic conditions in this population. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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10 pages, 738 KiB  
Article
Integrating the Gut Microbiome and Stress-Diathesis to Explore Post-Trauma Recovery: An Updated Model
by Manasi Murthy Mittinty, Joshua Y. Lee, David M. Walton, Emad M. El-Omar and James M. Elliott
Pathogens 2022, 11(7), 716; https://doi.org/10.3390/pathogens11070716 - 23 Jun 2022
Cited by 3 | Viewed by 2137
Abstract
Musculoskeletal conditions of traumatic and non-traumatic origin represent an ongoing health challenge. While the last three decades have seen significant advancement in our understanding of musculoskeletal conditions, the mechanisms of a delayed or lack of recovery are still a mystery. Here, we present [...] Read more.
Musculoskeletal conditions of traumatic and non-traumatic origin represent an ongoing health challenge. While the last three decades have seen significant advancement in our understanding of musculoskeletal conditions, the mechanisms of a delayed or lack of recovery are still a mystery. Here, we present an expansion of the integrated stress-diathesis model through the inclusion of the gut microbiome. Connecting the microbiome with known adverse neurobiologic, microbiologic and pathophysiologic sequelae following an injury, trauma or stressful event may help improve our knowledge of the pathogenesis of poor recovery. Such knowledge could provide a foundation for the exploration and development of more effective interventions to prevent the transition from acute to chronic pain. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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14 pages, 1888 KiB  
Article
Fecal DNA Virome Is Associated with the Development of Colorectal Neoplasia in a Murine Model of Colorectal Cancer
by Yingshi Li, Fan Zhang, Huimin Zheng, Sanjna Kalasabail, Chloe Hicks, Ka Yee Fung, Adele Preaudet, Tracy Putoczki, Julia Beretov, Ewan K. A. Millar, Emad El-Omar, Xiao-Tao Jiang and Howard Chi Ho Yim
Pathogens 2022, 11(4), 457; https://doi.org/10.3390/pathogens11040457 - 11 Apr 2022
Cited by 6 | Viewed by 3374
Abstract
Alteration of the gut virome has been associated with colorectal cancer (CRC); however, when and how the alteration takes place has not been studied. Here, we employ a longitudinal study in mice to characterize the gut virome alteration in azoxymethane (AOM)-induced colorectal neoplasia [...] Read more.
Alteration of the gut virome has been associated with colorectal cancer (CRC); however, when and how the alteration takes place has not been studied. Here, we employ a longitudinal study in mice to characterize the gut virome alteration in azoxymethane (AOM)-induced colorectal neoplasia and identify important viruses associated with tumor growth. The number and size of the tumors increased as the mice aged in the AOM treated group, as compared to the control group. Tumors were first observed in the AOM group at week 12. We observed a significantly lower alpha diversity and shift in viral profile when tumors first appeared. In addition, we identified novel viruses from the genera Brunovirus, Hpunavirus that are positively associated with tumor growth and enriched at a late time point in AOM group, whereas members from Lubbockvirus show a negative correlation with tumor growth. Moreover, network analysis revealed two clusters of viruses in the AOM virome, a group that is positively correlated with tumor growth and another that is negatively correlated with tumor growth, all of which are bacteriophages. Our findings suggest that the gut virome changes along with tumor formation and provides strong evidence of a potential role for bacteriophage in the development of colorectal neoplasia. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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Review

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13 pages, 3277 KiB  
Review
The History of the Intestinal Microbiota and the Gut-Brain Axis
by Zuzanna Lewandowska-Pietruszka, Magdalena Figlerowicz and Katarzyna Mazur-Melewska
Pathogens 2022, 11(12), 1540; https://doi.org/10.3390/pathogens11121540 - 15 Dec 2022
Cited by 5 | Viewed by 4052
Abstract
The gut-brain axis and the intestinal microbiota have been an area of an intensive research in the last few years. However, it is not a completely novel area of interest for physicians and scientists. From the earliest centuries, both professionals and patients turned [...] Read more.
The gut-brain axis and the intestinal microbiota have been an area of an intensive research in the last few years. However, it is not a completely novel area of interest for physicians and scientists. From the earliest centuries, both professionals and patients turned their attention to the gastrointestinal system in order to find the root of physical and mental disturbances. The approach to the gut-brain axis and the therapeutic methods have changed alongside the development of different medical approaches to health and illness. They often reflected the social changes. The authors of this article aim to provide a brief history of the gut-brain axis and the intestinal microbiota in order to demonstrate how important the study of these systems is for both scientists and medical professionals, as well as for the general public. We analysed the publications accessible through PubMed regarding the microbiota and gut-brain axis history. If available, we accessed the original historical sources. We conclude that although the history of this science might be long, there are still many areas that need to be researched, analysed, and understood in future projects. The interest in the subject is not diminishing, but rather it has increased throughout the years. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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Other

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42 pages, 1054 KiB  
Systematic Review
Assessing the Relationship between the Gut Microbiota and Inflammatory Bowel Disease Therapeutics: A Systematic Review
by Cassandra Mah, Thisun Jayawardana, Gary Leong, Sabrina Koentgen, Daniel Lemberg, Susan J. Connor, Theodore Rokkas, Michael C. Grimm, Steven T. Leach and Georgina L. Hold
Pathogens 2023, 12(2), 262; https://doi.org/10.3390/pathogens12020262 - 06 Feb 2023
Cited by 8 | Viewed by 2265
Abstract
Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was [...] Read more.
Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was to conduct a systematic review and meta-analysis to define changes in the gut microbiota following IBD treatment and to identify microbial predictors of treatment response. A systematic search using MEDLINE/Embase and PubMed was performed in July 2022. The review was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies were included if they reported longitudinal microbiota analysis (>2 weeks) using next-generation sequencing or high-throughput sequencing of faecal/mucosal samples from IBD patients commencing treatment. Meta-analysis on alpha-diversity changes following infliximab treatment was conducted. Thirty-nine studies met the inclusion criteria, and four studies were included in the meta-analysis. An increase in alpha diversity was observed following treatment with 5-aminosalicylates, corticosteroids, and biological therapies in most studies. Characteristic signatures involving the enrichment of short-chain-fatty-acid-producing bacteria including Faecalibacterium prausnitzii and a reduction of pathogenic bacteria including various Proteobacteria were demonstrated following treatment with specific signatures identified based on treatment outcome. The meta-analysis demonstrated a statistically significant increase in bacterial richness following infliximab treatment (standardised mean difference −1.16 (−1.50, −0.83), p < 0.00001). Conclusion: Distinct microbial signatures are seen following treatment and are associated with treatment response. The interrogation of large longitudinal studies is needed to establish the link between the gut microbiota and IBD therapeutic outcomes. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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4 pages, 4330 KiB  
Case Report
Rectal Cancer Presenting with Absceding Infection Due to Fusobacterium nucleatum
by Sebastian Zundler, Christian Mardin, Simone Bertz, Francesco Vitali, Richard Strauß, Julia Fürst, Markus F. Neurath and Deike Strobel
Pathogens 2022, 11(10), 1113; https://doi.org/10.3390/pathogens11101113 - 28 Sep 2022
Cited by 2 | Viewed by 1100
Abstract
Intestinal microbiota such as Fusobacterium nucleatum play an important role in the pathogenesis of colorectal cancer. Here, we describe the case of a 47-year-old patient presenting with endophthalmitis and a liver abscess due to Fusobacterium nucleatum that prompted the diagnosis of colorectal cancer [...] Read more.
Intestinal microbiota such as Fusobacterium nucleatum play an important role in the pathogenesis of colorectal cancer. Here, we describe the case of a 47-year-old patient presenting with endophthalmitis and a liver abscess due to Fusobacterium nucleatum that prompted the diagnosis of colorectal cancer as the most likely source of infection. This case highlights that colorectal cancer needs to be considered in patients with systemic infection with Fusobacterium nucleatum and colonoscopy should be performed. Full article
(This article belongs to the Special Issue The Role of the Gut Microbiome in Health and Disease)
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