Publications
444 results found
Mullish BH, Pechlivanis A, Barker GF, et al., 2018, Functional microbiomics: evaluation of gut microbiota-bile acid metabolism interactions in health and disease, Methods, Vol: 149, Pages: 49-58, ISSN: 1046-2023
There is an ever-increasing recognition that bile acids are not purely simple surfactant molecules that aid in lipid digestion, but are a family of molecules contributing to a diverse range of key systemic functions in the host. It is now also understood that the specific composition of the bile acid milieu within the host is related to the expression and activity of bacterially-derived enzymes within the gastrointestinal tract, as such creating a direct link between the physiology of the host and the gut microbiota. Coupled to the knowledge that perturbation of the structure and/or function of the gut microbiota may contribute to the pathogenesis of a range of diseases, there is a high level of interest in the potential for manipulation of the gut microbiota-host bile acid axis as a novel approach to therapeutics. Much of the growing understanding of the biology of this area reflects the recent development and refinement of a range of novel techniques; this study applies a number of those techniques to the analysis of human samples, aiming to illustrate their strengths, drawbacks and biological significance at all stages. Specifically, we used microbial profiling (using 16S rRNA gene sequencing), bile acid profiling (using liquid chromatography–mass spectrometry), bsh and baiCD qPCR, and a BSH enzyme activity assay to demonstrate differences in the gut microbiota and bile metabolism in stool samples from healthy and antibiotic-exposed individuals.
Ghani R, Mookerjee S, Mullish BH, et al., 2018, Impact on Length of Stay and Antibiotic Use in Allogenic and Autologous Stem Cell Transplant Patients Colonized with Carbapenemase-producing Enterobacteriaceae, IDWeek, Publisher: Oxford University Press, ISSN: 2328-8957
Gallacher D, Alber D, Logan G, et al., 2018, Early life lung microbiome in preterm infants, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Gallacher D, Triantafilou M, Marchesi J, et al., 2018, The role of ASC signalling in preterm infants at risk of chronic lung disease of prematurity, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Gallacher D, Alber D, Logan G, et al., 2018, Pulmonary microbes identified by 16S sequencing of tracheal aspirate samples in two neonatal units in the UK, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Mullish BH, Osborne LS, Marchesi JR, et al., 2018, The implementation of omics technologies in cancer microbiome research, Ecancermedicalscience, Vol: 12, Pages: 1-11, ISSN: 1754-6605
Whilst the interplay between host genetics and the environment plays a pivotal role in the aetiopathogenesis of cancer, there are other key contributors of importance as well. One such factor of central and growing interest is the contribution of the microbiota to cancer. Even though the field is only a few years old, investigation of the ’cancer microbiome’ has already lead to major advances in knowledge of the basic biology of cancer risk and progression, opened novel avenues for biomarkers and diagnostics, and given better understanding of mechanisms underlying response to therapy. Recent developments in microbial DNA sequencing techniques (and the bioinformatics required for analysis of these datasets) has allowed much more in-depth profiling of the structure of microbial communities than was previously possible. However, for more complete assessment of the functional implications of microbial changes, there is a growing recognition of the importance of the integration of microbial profiling with other ‘omics modalities, with metabonomics (metabolite profiling) and proteomics (protein profiling) both gaining particular recent attention. In this review, we give an overview of some of the key scientific techniques being used to unravel the role of the cancer microbiome. We have aimed to highlight practical aspects related to sample collection and preparation, choice of modality of analysis, and examples of where different ‘omics technologies have been complementary to each other to highlighting the significance of the cancer microbiome.
Pouncey AL, Scott AJ, Alexander JL, et al., 2018, Gut microbiota, chemotherapy and the host: the influence of the gut microbiota on cancer treatment, Ecancermedicalscience, Vol: 12, ISSN: 1754-6605
The gut microbiota exists in a dynamic balance between symbiosis and pathogenesis and can influence almost any aspect of host physiology. Growing evidence suggests that the gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of anticancer therapy. The microbiota modulates the host response to chemotherapy via numerous mechanisms, including immunomodulation, xenometabolism and alteration of community structure. Furthermore, exploitation of the microbiota offers opportunities for the personalisation of chemotherapeutic regimens and the development of novel therapies. In this article, we explore the host-chemotherapeutic microbiota axis, from basic science to clinical research, and describe how it may change the face of cancer treatment.
Alexander JL, Scott AJ, Pouncey AL, et al., 2018, Colorectal carcinogenesis: an archetype of gut microbiota-host interaction, Ecancermedicalscience, Vol: 12, ISSN: 1754-6605
Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as Fusobacterium nucleatum and Escherichia coli (E. Coli) are found in abundance in patients with CRC and have been shown in experimental studies to promote neoplasia. A whole armamentarium of bacteria-derived oncogenic mechanisms has been defined, including the subversion of apoptosis and the production of genotoxins and pro-inflammatory factors. But the microbiota may also be protective: for example, they are implicated in the metabolism of dietary fibre to produce butyrate, a short chain fatty acid, which is anti-inflammatory and anti-carcinogenic. Indeed, although our understanding of this immensely complex, highly individualised and multi-faceted relationship is expanding rapidly, many questions remain: Can we define friends and foes, and drivers and passengers? What are the critical functions of the microbiota in the context of colorectal neoplasia?
Monaghan T, Mullish BH, Patterson J, et al., 2018, Effective fecal microbiota transplantation for recurrent Clostridioides difficile in humans is associated with increased signalling in bile acid-farnesoid X receptor-fibroblast growth factor pathway, Gut Microbes, Vol: 10, Pages: 142-148, ISSN: 1949-0984
The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.
Mullish BH, McDonald JAK, Thursz MR, et al., 2018, Antibiotic‐associated disruption of microbiota composition and function in cirrhosis is restored by fecal transplant, Hepatology, Vol: 68, Pages: 1205-1205, ISSN: 0270-9139
Walsh K, Calder N, Olupot-Olupot P, et al., 2018, Modifying Intestinal Integrity and MicroBiome in Severe Malnutrition with Legume-Based Feeds (MIMBLE 2.0): protocol for a phase II refined feed and intervention trial, Wellcome Open Research, Vol: 3, ISSN: 2398-502X
Background: Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome. Methods: We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal/ml) and F100 (1 kcal/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g/kg/day), ii) de novo development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin). Discussion: We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outco
Walsh K, Calder N, Olupot-Olupot P, et al., 2018, Modifying Intestinal Integrity and Micro Biome in Severe Malnutrition with Legume-Based Feeds (MIMBLE 2.0): protocol for a phase II refined feed and intervention trial [version 1; referees: 2 approved], Wellcome Open Research, Vol: 3, Pages: 95-95, ISSN: 2398-502X
Background: Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome. Methods: We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal/ml) and F100 (1 kcal/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g/kg/day), ii) de novo development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin). Discussion: We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outco
Marchesi JR, 2018, Advancing microbiome research, MICROBIOLOGY-SGM, Vol: 164, Pages: 1005-1006, ISSN: 1350-0872
Marchesi JR, 2018, Advancing microbiome research, IMMUNOLOGY, Vol: 154, Pages: 535-536, ISSN: 0019-2805
Martin G, Kolida S, Marchesi J, et al., 2018, In vitro modeling of bile acid processing by the human fecal microbiota, Frontiers in Microbiology, Vol: 9, ISSN: 1664-302X
Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel in vitro approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing. Anaerobic, pH-controlled batch cultures were inoculated with human fecal microbiota and treated with individual conjugated primary bile acids (500 μg/ml) to serve as the sole substrate for 24 h. Samples were collected throughout the experiment (0, 5, 10, and 24 h) and the bacterial composition was determined by 16S rRNA gene sequencing and the bile acid signatures were characterized using a targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) approach. Data fusion techniques were used to identify statistical bacterial-metabolic linkages. An increase in gut bacteria associated bile acids was observed over 24 h with variation in the rate of bile acid metabolism across the volunteers (n = 7). Correlation analysis identified a significant association between the Gemmiger genus and the deconjugation of glycine conjugated bile acids while the deconjugation of taurocholic acid was associated with bacteria from the Eubacterium and Ruminococcus genera. A positive correlation between Dorea and deoxycholic acid production suggest a potential role for this genus in cholic acid dehydroxylation. A slower deconjugation of taurocholic acid was observed in individuals with a greater abundance of Parasutterella and Akkermansia. This work demonstrates the utility of integrating compositional (metataxonomics) and functional (metabonomics) systems biology approaches
McDonald JAK, Kimhofer T, West K, et al., 2018, Role of the gut microbiota in autism spectrum disorder, ISME17, Publisher: Nature Publishing Group
Masetti G, Moshkelgosha S, Kohling H-L, et al., 2018, Gut microbiota in experimental murine model of Graves' orbitopathy established in different environments may modulate clinical presentation of disease, MICROBIOME, Vol: 6, ISSN: 2049-2618
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- Citations: 45
Mansukhani S, Davidson M, Gillbanks A, et al., 2018, Iconic: Peri-operative immuno-chemotherapy in operable oesophageal and gastric cancer., Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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- Citations: 5
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, A novel route for controlling Clostridioides difficile growth via bile acid and short chain fatty acid modulation, ISME17
Alexander JL, Scott A, Poynter LR, et al., 2018, Sa1840 - The colorectal cancer mucosal microbiome is defined by disease stage and the tumour metabonome, Digestive Disease Week 2018, Publisher: Elsevier, Pages: S415-S415, ISSN: 0016-5085
Allegretti JR, Mullish BH, Bogart E, et al., 2018, 25 - Microbiome and metabolic markers of Clostridium Difficile recurrance, Digestive Diseases Week, Publisher: Elsevier, Pages: S8-S9, ISSN: 0016-5085
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, 24 - A novel route to controlling Clostridioides Difficile growth via short chain fatty acid and bile acid modulation, Digestive Diseases Week, Publisher: Elsevier, Pages: S8-S8, ISSN: 0016-5085
Misra R, Sarafian M, Pechlivanis A, et al., 2018, SOUTH ASIAN ETHNICITY DRIVES DIFFERENCES IN MICROBIAL AND METABOLIC PROFILING IN A NEWLY DIAGNOSED ULCERATIVE COLITIS COHORT, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S33-S34, ISSN: 0016-5085
Alexander JL, Scott A, Poynter LR, et al., 2018, THE COLORECTAL CANCER MUCOSAL MICROBIOME IS DEFINED BY DISEASE STAGE AND THE TUMOUR METABONOME, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S415-S415, ISSN: 0016-5085
Alexander JL, Scott A, Poynter LR, et al., 2018, THE EFFECT OF BOWEL PURGATIVE MEDICATION ON THE MUCOSA-ASSOCIATED MICROBIOTA MAY BE LESS SIGNIFICANT THAN WE THOUGHT, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1044-S1045, ISSN: 0016-5085
Powles ST, Hicks LC, Chong LW, et al., 2018, EFFECT OF BOWEL PURGATIVES ON URINARY METABOLIC PROFILING ASSOCIATED WITH THE FAECAL MICROBIOME, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week (DDW) / 59th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S860-S860, ISSN: 0016-5085
Ferreira MR, Andreyev HJN, Gulliford S, et al., 2018, Longitudinal analysis of the microbiota by GI toxicity during IMRT for high-risk prostate cancer., 37th Meeting of the European-Society-for-Radiotherapy-and-Oncology (ESTRO), Publisher: ELSEVIER IRELAND LTD, Pages: S330-S331, ISSN: 0167-8140
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Misra R, Sarafian M, Pechilvanis A, et al., 2018, South Asian ethnicity drives differences in microbial and metabolic profiling in a newly diagnosed ulcerative colitis cohort, Publisher: OXFORD UNIV PRESS, Pages: S120-S121, ISSN: 1873-9946
Osborne LS, Marchesi J, 2018, The functional exoproteome as a driver and predictor of IBD status: Proteases from bacteria influence host health, Publisher: OXFORD UNIV PRESS, Pages: S551-S551, ISSN: 1873-9946
MacIntyre DA, Brown R, Marchesi J, et al., 2018, Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin, BMC Medicine, Vol: 16, ISSN: 1741-7015
Background: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection prophylactic antibiotics are widely used. The evolution of vaginal microbiota composition associated with PPROM and the impact of antibiotics on bacterial composition is unknown. Methods: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.Results: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion, was present prior to the rupture of fetal membranes in approximately a third of cases (0% versus 27%, P= 0.026) and persisted following membrane rupture (31%, P= 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P= 0.00009) particularly in women initially colonised by Lactobacillus species. Lactobacillus depletion and increased relative abundance of Sneathia spp. was associated with subsequent funisitis and early onset neonatal sepsis. Conclusions:Our data show that vaginal microbiota composition is a risk-factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
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