ORCID Profile
0000-0003-2577-518X
Current Organisation
University of Aberdeen
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Publisher: SAGE Publications
Date: 2019
Abstract: The human gut virome includes a erse collection of viruses that infect our own cells as well as other commensal organisms, directly impacting on our well-being. Despite its predominance, the virome remains one of the least understood components of the gut microbiota, with appropriate analysis toolkits still in development. Based on its interconnectivity with all living cells, it is clear that the virome cannot be studied in isolation. Here we review the current understanding of the human gut virome, specifically in relation to other constituents of the microbiome, its evolution and life-long association with its host, and our current understanding in the context of inflammatory bowel disease and associated therapies. We propose that the gut virome and the gut bacterial microbiome share similar trajectories and interact in both health and disease and that future microbiota studies should in parallel characterize the gut virome to uncover its role in health and disease.
Publisher: Hindawi Limited
Date: 2011
DOI: 10.1155/2011/579650
Abstract: The gastrointestinal microbiota is a major source of immune stimulation. The interaction between host pattern-recognition receptors and conserved microbial ligands profoundly influences infection dynamics. Identifying and understanding the nature of these interactions is a key step towards obtaining a clearer picture of microbial pathogenesis. These interactions underpin a complex interplay between microbe and host that has far reaching consequences for both. Here, we review the role of pattern recognition receptors in three prototype diseases affecting the stomach, the small intestine, and large intestine, respectively ( Helicobacter pylori infection, Salmonella infection, and inflammatory bowel disease). Specifically, we review the nature and impact of pathogen:receptor interactions, their impact upon pathogenesis, and address the relevance of pattern recognition receptors in the development of therapies for gastrointestinal diseases.
Publisher: Public Library of Science (PLoS)
Date: 12-03-2013
Publisher: Informa UK Limited
Date: 26-06-2018
Publisher: Wiley
Date: 07-12-2017
Abstract: Ruminococcus bromii is a dominant member of the human colonic microbiota that plays a ‘keystone’ role in degrading dietary resistant starch. Recent evidence from one strain has uncovered a unique cell surface ‘amylosome’ complex that organizes starch‐degrading enzymes. New genome analysis presented here reveals further features of this complex and shows remarkable conservation of amylosome components between human colonic strains from three different continents and a R. bromii strain from the rumen of Australian cattle. These R. bromii strains encode a narrow spectrum of carbohydrate active enzymes (CAZymes) that reflect extreme specialization in starch utilization. Starch hydrolysis products are taken up mainly as oligosaccharides, with only one strain able to grow on glucose. The human strains, but not the rumen strain, also possess transporters that allow growth on galactose and fructose. R. bromii strains possess a full complement of sporulation and spore germination genes and we demonstrate the ability to form spores that survive exposure to air. Spore formation is likely to be a critical factor in the ecology of this nutritionally highly specialized bacterium, which was previously regarded as ‘non‐sporing’, helping to explain its widespread occurrence in the gut microbiota through the ability to transmit between hosts.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Wiley
Date: 16-10-2017
DOI: 10.1111/APT.14384
Abstract: The concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the "omics" era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics. To assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics. A Medline search including items 'intestinal microbiota/microbiome', 'inflammatory bowel disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial transplantation', 'dietary manipulation' was performed. Disease remission and relapse are associated with microbial changes in both mucosal and luminal s les. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice. Existing approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option.
Publisher: Oxford University Press (OUP)
Date: 29-10-2015
DOI: 10.1093/JAC/DKV335
Abstract: The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between in idual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy s les, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of in idual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection.
Publisher: Public Library of Science (PLoS)
Date: 23-02-2011
Publisher: Springer Science and Business Media LLC
Date: 21-02-2012
Abstract: The gastrointestinal microbiota has come to the fore in the search for the causes of IBD. This shift has largely been driven by the finding of genetic polymorphisms involved in gastrointestinal innate immunity (particularly polymorphisms in NOD2 and genes involved in autophagy) and alterations in the composition of the microbiota that might result in inflammation (so-called dysbiosis). Microbial ersity studies have continually demonstrated an expansion of the Proteobacteria phylum in patients with IBD. In idual Proteobacteria, in particular (adherent-invasive) Escherichia coli, C ylobacter concisus and enterohepatic Helicobacter, have all been associated with the pathogenesis of IBD. In this Review, we comprehensively describe the various associations of Proteobacteria and IBD. We also examine the importance of pattern recognition in the extracellular innate immune response of the host with particular reference to Proteobacteria, and postulate that Proteobacteria with adherent and invasive properties might exploit host defenses, drive proinflammatory change, alter the intestinal microbiota in favor of dysbiosis and ultimately lead to the development of IBD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2012
DOI: 10.1038/AJG.2012.335
Abstract: The gastrointestinal microbiota is considered important in inflammatory bowel disease (IBD) pathogenesis. Discoveries from established disease cohorts report reduced bacterial ersity, changes in bacterial composition, and a protective role for Faecalibacterium prausnitzii in Crohn's disease (CD). The majority of studies to date are however potentially confounded by the effect of treatment and a reliance on established rather than de-novo disease. Microbial changes at diagnosis were examined by biopsying the colonic mucosa of 37 children: 25 with newly presenting, untreated IBD with active colitis (13 CD and 12 ulcerative colitis (UC)), and 12 pediatric controls with a macroscopically and microscopically normal colon. We utilized a dual-methodology approach with pyrosequencing (threshold >10,000 reads) and confirmatory real-time PCR (RT-PCR). Threshold pyrosequencing output was obtained on 34 subjects (11 CD, 11 UC, 12 controls). No significant changes were noted at phylum level among the Bacteroidetes, Firmicutes, or Proteobacteria. A significant reduction in bacterial α- ersity was noted in CD vs. controls by three methods (Shannon, Simpson, and phylogenetic ersity) but not in UC vs. controls. An increase in Faecalibacterium was observed in CD compared with controls by pyrosequencing (mean 16.7% vs. 9.1% of reads, P=0.02) and replicated by specific F. prausnitzii RT-PCR (36.0% vs. 19.0% of total bacteria, P=0.02). No disease-specific clustering was evident on principal components analysis. Our results offer a comprehensive examination of the IBD mucosal microbiota at diagnosis, unaffected by therapeutic confounders or changes over time. Our results challenge the current model of a protective role for F. prausnitzii in CD, suggesting a more dynamic role for this organism than previously described.
Publisher: Baishideng Publishing Group Inc.
Date: 2014
Publisher: American Chemical Society (ACS)
Date: 11-08-2016
DOI: 10.1021/ACS.MOLPHARMACEUT.6B00351
Abstract: CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood s les by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.
Publisher: Informa UK Limited
Date: 2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2011
Publisher: Wiley
Date: 09-2011
DOI: 10.1111/J.1523-5378.2011.00884.X
Abstract: The last year has seen an interesting and important collection of evidence presented in the field of the "other" than Helicobacter pylori Helicobacters. Associations with adult ulcerative colitis and biliary/hepatic disease have been described. New insights into the immune response and subsequent pathogenesis associated with infection have also been published. Genomic advances include description of new and unique species and the complete genome description for both Helicobacter felis and Helicobacter suis. Molecular studies have also elucidated the mechanism of action of some functional components of these organisms.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.VACCINE.2016.11.028
Abstract: Rotaviruses (RV) are the leading cause of gastroenteritis in children less than five years of age worldwide. Rotarix®, a live attenuated monovalent vaccine containing a RV strain of G1P[8] specificity has been included in the childhood immunisation schedule from June 2013 in Scotland. This study aimed to characterise the prevalent RV strains in Scotland before and after the introduction of the RV vaccine. RV positive faecal s les from Scottish virology laboratories covering the years 2012-2015 were genotyped. Viral RNA was extracted from faecal suspensions. VP7 and VP4 gene specific primers were used for multiplex hemi-nested PCRs and sequencing. Mann-Whitney U test and Chi-square test were used for statistical comparison. There was a decrease in RV positive s les from the Scottish virology laboratories from 7409 s les in the pre-vaccination years (2009-2013) to 760 in 2014-2015, with an annual reduction of RV infections by 74.4% (RR-3.95 95%-CI, 3.53-4.42, p<0.001). 362 s les from the pre-vaccination period and 278 s les from the post-vaccination were genotyped. There was a drop in prevalence of G1P[8] strains (72.1%, 95%-CI, 67.42-76.33 to 15%, 95%-CI, 11.38-19.79) after introduction of the vaccine. In the post-vaccination period G2P[4] was the dominant strain in Scotland (21.9%, 95%-CI, 17.48-27.17) with increase in G9P[8] (12.9%, 95%-CI, 9.50-7.41), G12P[8] (12.2%, 95%-CI, 8.89-16.60) and G3P[8] (11.9%, 95%-CI, 8.58-16.20) infections. Phylogenetic analysis of the VP7 and VP4 genes showed no major differences between the pre and post-vaccination G1P[8] strains. This laboratory based surveillance study shows significant reduction in reported RV cases and a shift in proportion from G1P[8] to G2P[4] strains after introduction of RV vaccination in Scotland. The genotyping data from a subset of the total reported RV cases will be used to ascertain cross protection against strains and identify vaccine induced RV strain shifts in the years to come.
Publisher: Public Library of Science (PLoS)
Date: 31-10-2011
Publisher: Public Library of Science (PLoS)
Date: 27-06-2011
Publisher: American Association for the Advancement of Science (AAAS)
Date: 18-11-2022
Abstract: The Hayabusa2 spacecraft returned to Earth from the asteroid 162173 Ryugu on 6 December 2020. One day after the recovery, the gas species retained in the s le container were extracted and measured on-site and stored in gas collection bottles. The container gas consists of helium and neon with an extraterrestrial
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Indrani Mukhopadhya.