2024 |
Budden KF, Shukla SD, Bowerman KL, Vaughan A, Gellatly SL, Wood DLA, et al., 'Faecal microbial transfer and complex carbohydrates mediate protection against COPD.', Gut, (2024) [C1]
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2024 |
Mayall JR, Horvat JC, Mangan NE, Chevalier A, McCarthy H, Hampsey D, et al., 'Interferon-epsilon is a novel regulator of NK cell responses in the uterus', EMBO Molecular Medicine, 16 267-293 [C1]
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2023 |
Burns GL, Keely S, 'Understanding food allergy through neuroimmune interactions in the gastrointestinal tract.', Ann Allergy Asthma Immunol, 131 576-584 (2023) [C1]
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Nova |
2023 |
Mccarthy H, Keely S, 'Re-evaluating the Role of Deep Crypt Secretory Cells in Intestinal Homeostasis', CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 15 1020-1021 (2023)
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2023 |
Burns GL, Potter M, Mathe A, Bruce J, Minahan K, Barnes JL, et al., 'TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia.', Clin Transl Gastroenterol, 14 e00638 (2023) [C1]
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2023 |
Shanahan ER, Kang S, Staudacher H, Shah A, Do A, Burns G, et al., 'Alterations to the duodenal microbiota are linked to gastric emptying and symptoms in functional dyspepsia', GUT, 72 929-938 (2023) [C1]
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2023 |
Vishnoi V, Hoedt EC, Gould T, Carroll G, Carroll R, Lott N, et al., 'A pilot study: intraoperative 16S rRNA sequencing versus culture in predicting colorectal incisional surgical site infection', ANZ Journal of Surgery, 93 2464-2472 (2023) [C1]
Background: Surgical Site Infection (SSI) of the abdominal incision is a dreaded complication following colorectal surgery. Identifying the intraoperative surgical site microbes m... [more]
Background: Surgical Site Infection (SSI) of the abdominal incision is a dreaded complication following colorectal surgery. Identifying the intraoperative surgical site microbes may provide clarity in the pathogenesis of SSIs. Genomic sequencing has revolutionized the ability to identify microbes from clinical samples. Utilization of 16S rRNA amplicon sequencing to characterize the intraoperative surgical site may provide the critical information required to predict and prevent infection in colorectal surgery. Methods: This is a pilot, prospective observational study of 50 patients undergoing elective colorectal resection. At completion of surgery, prior to skin closure, swabs were taken from the subcutaneous tissue of the abdominal incision to investigate the microbial profile. Dual swabs were taken to compare standard culture technique and 16S rRNA sequencing to establish if a microbial profile was associated with postoperative SSI. Results: 8/50 patients developed an SSI, which was more likely in those undergoing open surgery (5/15 33.3% versus 3/35, 8.6%; P = 0.029). 16S rRNA amplicon sequencing was more sensitive in microbial detection compared to traditional culture. Both culture and 16S rRNA demonstrated contamination of the surgical site, predominantly with anaerobes. Culture was not statistically predictive of infection. 16S rRNA amplicon sequencing was not statistically predictive of infection, however, it demonstrated patients with an SSI had an increased biodiversity (not significant) and a greater relative abundance (not significant) of pathogens such as Bacteroidacaea and Enterobacteriaceae within the intraoperative site. Conclusions: 16S rRNA amplicon sequencing has demonstrated a potential difference in the intraoperative microbial profile of those that develop an infection. These findings require validation through powered experiments to determine the overall clinical significance.
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2023 |
Humphries S, Bond DR, Germon ZP, Keely S, Enjeti AK, Dun MD, Lee HJ, 'Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia', Clinical Epigenetics, 15 (2023) [C1]
Background: Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation ... [more]
Background: Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment. Main body: This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents. Conclusion: Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.
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2023 |
Cameron R, Walker MM, Jones M, Eslick GD, Keely S, Pockney P, et al., 'Increased mucosal eosinophils in colonic diverticulosis and diverticular disease.', J Gastroenterol Hepatol, 38 1355-1364 (2023) [C1]
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2023 |
Burns GL, Keely S, 'Targeting type 2 immune responses to treat eosinophilic gastritis', LANCET GASTROENTEROLOGY & HEPATOLOGY, 8 773-775 (2023)
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2022 |
Shah A, Fairlie T, Brown G, Jones MP, Eslick GD, Duncanson K, et al., 'DUODENAL EOSINOPHILS AND MAST CELLS IN FUNCTIONAL DYSPEPSIA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CASE-CONTROL STUDIES', GASTROENTEROLOGY, 162 S866-S866 (2022)
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2022 |
Prasad SS, Walker MM, Talley NJ, Keely S, Kairuz T, Jones MP, Duncanson K, 'Healthcare Needs and Perceptions of People Living with Inflammatory Bowel Disease in Australia: A Mixed-Methods Study', Crohn's and Colitis 360, 4 (2022) [C1]
Background: Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis are inflammatory bowel diseases (IBDs) that adversely affect the healthcare needs and qua... [more]
Background: Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis are inflammatory bowel diseases (IBDs) that adversely affect the healthcare needs and quality of life (QoL) of people with IBD. The aim of this study was to explore the needs and perceptions of people with IBD in a primary care setting. Methods: This sequential explanatory mixed-methods study consisted of a cross-sectional survey (included validated tools), followed by semistructured interviews on participants' perceptions: IBD management, healthcare professionals, IBD care, flare management, and pharmacist's IBD roles. Results: Sixty-seven participants completed the survey, and 8 completed interviews. Quantitative findings: Age at diagnosis had significant association with medication nonadherence (P =. 04), QoL (P =. 04), and disease control (P =. 01) among the respondents. The odds of medication nonadherence were 8 times (adjusted odds ratio [AOR] = 8.04, 95% confidence interval [CI] = 1.08, 60.10) higher among younger participants aged <30 years. Those diagnosed with CD (P =. 02) reported more likely to have unfavorable perceptions of pharmacists' role in managing their IBD (AOR = 9.45, 95% CI = 1.57, 56.62) than those with UC and indeterminate colitis. Qualitative findings: General practitioners were considered the most important care provider and the first point of contact for patients in managing all aspects of IBD. Participants identified their key need to be timely access to specialized IBD care and found that other primary healthcare professionals lacked disease-specific knowledge for managing IBD. Conclusions: Primary healthcare professionals are well positioned but need targeted training to influence the needs of IBD patients. The specialty role of an IBD educator could complement existing services to deliver and address patient-specific care.
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2022 |
Dowling LR, Strazzari MR, Keely S, Kaiko GE, 'Enteric nervous system and intestinal epithelial regulation of the gut-brain axis', Journal of Allergy and Clinical Immunology, 150 513-522 (2022) [C1]
The gut-brain axis describes a bidirectional interplay within the enteric environment between the intestinal epithelium, the mucosal immune system, and the microbiota with the ent... [more]
The gut-brain axis describes a bidirectional interplay within the enteric environment between the intestinal epithelium, the mucosal immune system, and the microbiota with the enteric nervous system. This interplay provides a link between exogenous environmental stimuli such as nutrient sensing, and nervous system function, as well as a mechanism of feedback from cortical and sensory centers of the brain to enteric activities. The intestinal epithelium is one of the human body's largest sources of hormones and neurotransmitters, which have critical effects on neuronal function. The influence of the gut microbiota on these processes appears to be profound; yet to date, it has been insufficiently explored. Disruption of the intestinal microbiota is linked not only to diseases in the gut but also to brain symptomatology, including neurodegenerative and behavioral disorders (Parkinson disease, Alzheimer disease, autism, and anxiety and/or depression). In this review we discuss the cellular wiring of the gut-brain axis, with a particular focus on the epithelial and neuronal interaction, the evidence that has led to our current understanding of the intestinal role in neurologic function, and future directions of research to unravel this important interaction in both health and allergic disease.
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2022 |
Burns GL, Talley NJ, Keely S, 'Immune responses in the irritable bowel syndromes: time to consider the small intestine', BMC MEDICINE, 20 (2022)
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2022 |
Burns GL, Bruce JK, Minahan K, Mathe A, Fairlie T, Cameron R, et al., 'Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia.', Front Immunol, 13 1051632 (2022) [C1]
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2022 |
Cuskelly A, Hoedt EC, Harms L, Talley NJ, Tadros MA, Keely S, Hodgson DM, 'Neonatal immune challenge influences the microbiota and behaviour in a sexually dimorphic manner', BRAIN BEHAVIOR AND IMMUNITY, 103 232-242 (2022) [C1]
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2022 |
Shah A, Kang S, Talley NJ, Anh D, Walker MM, Shanahan ER, et al., 'The duodenal mucosa associated microbiome, visceral sensory function, immune activation and psychological comorbidities in functional gastrointestinal disorders with and without self-reported non-celiac wheat sensitivity', GUT MICROBES, 14 (2022) [C1]
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2022 |
Bruce JK, Burns GL, Sinn Soh W, Nair PM, Sherwin S, Fan KN, et al., 'Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia', Brain, Behavior, and Immunity, 101 335-345 (2022) [C1]
Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identif... [more]
Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic¿pituitary¿adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients.
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2022 |
Shah A, Fairlie T, Brown G, Jones MP, Eslick GD, Duncanson K, et al., 'Duodenal Eosinophils and Mast Cells in Functional Dyspepsia: A Systematic Review and Meta-Analysis of Case-Control Studies', CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 20 2229-+ (2022) [C1]
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2022 |
Hu MD, Golovchenko NB, Burns GL, Nair PM, Kelly TJ, Agos J, et al., ' d Intraepithelial Lymphocytes Facilitate Pathological Epithelial Cell Shedding Via CD103-Mediated Granzyme Release.', Gastroenterology, 162 877-889.e7 (2022) [C1]
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2021 |
Turner A, Veysey M, Keely S, Scarlett CJ, Lucock M, Beckett EL, 'Genetic Variation in the Bitter Receptors Responsible for Epicatechin Detection Are Associated with BMI in an Elderly Cohort', NUTRIENTS, 13 (2021) [C1]
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2021 |
Pryor J, Eslick GD, Talley NJ, Duncanson K, Keely S, Hoedt EC, 'Clinical medicine journals lag behind science journals with regards to "microbiota sequence" data availability', CLINICAL AND TRANSLATIONAL MEDICINE, 11 (2021)
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2021 |
Bolan S, Seshadri B, Keely S, Kunhikrishnan A, Bruce J, Grainge I, et al., 'Bioavailability of arsenic, cadmium, lead and mercury as measured by intestinal permeability', Scientific Reports, 11 (2021) [C1]
In this study, the intestinal permeability of metal(loid)s (MLs) such as arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) was examined, as influenced by gut microbes and che... [more]
In this study, the intestinal permeability of metal(loid)s (MLs) such as arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) was examined, as influenced by gut microbes and chelating agents using an in vitro gastrointestinal/Caco-2 cell intestinal epithelium model. The results showed that in the presence of gut microbes or chelating agents, there was a significant decrease in the permeability of MLs (As-7.5%, Cd-6.3%, Pb-7.9% and Hg-8.2%) as measured by apparent permeability coefficient value (Papp), with differences in ML retention and complexation amongst the chelants and the gut microbes. The decrease in ML permeability varied amongst the MLs. Chelating agents reduce intestinal absorption of MLs by forming complexes thereby making them less permeable. In the case of gut bacteria, the decrease in the intestinal permeability of MLs may be associated to a direct protection of the intestinal barrier against the MLs or indirect intestinal ML sequestration by the gut bacteria through adsorption on bacterial surface. Thus, both gut microbes and chelating agents can be used to decrease the intestinal permeability of MLs, thereby mitigating their toxicity.
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2021 |
Alemao CA, Budden KF, Gomez HM, Rehman SF, Marshall JE, Shukla SD, et al., 'Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders', Allergy: European Journal of Allergy and Clinical Immunology, 76 714-734 (2021) [C1]
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmo... [more]
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a ¿poor¿ diet or protection against disease with a ¿healthy¿ diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.
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2021 |
Barnes JL, Plank MW, Asquith K, Maltby S, Sabino LR, Kaiko GE, et al., 'T-helper 22 cells develop as a distinct lineage from Th17 cells during bacterial infection and phenotypic stability is regulated by T-bet', MUCOSAL IMMUNOLOGY, 14 1077-1087 (2021) [C1]
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2021 |
Talley NJ, Walker MM, Jones M, Keely S, Koloski N, Cameron R, et al., 'Letter: budesonide for functional dyspepsia with duodenal eosinophilia-randomised, double-blind, placebo-controlled parallel-group trial', ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 53 1332-1333 (2021)
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2021 |
Hoedt EC, Shanahan ER, Keely S, Shah A, Burns GL, Holtmann GJ, et al., 'Draft Genome Sequence of Streptococcus salivarius AGIRA0003, Isolated from Functional Gastrointestinal Disorder Duodenal Tissue', MICROBIOLOGY RESOURCE ANNOUNCEMENTS, 10 (2021)
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2021 |
Goggins BJ, Minahan K, Sherwin S, Soh WS, Pryor J, Bruce J, et al., 'Pharmacological HIF-1 stabilization promotes intestinal epithelial healing through regulation of alpha-integrin expression and function', AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 320 G420-G438 (2021) [C1]
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2021 |
Koloski NA, Jones M, Walker MM, Keely S, Holtmann G, Talley NJ, 'Sleep disturbances in the irritable bowel syndrome and functional dyspepsia are independent of psychological distress: a population-based study of 1322 Australians', ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 54 627-636 (2021) [C1]
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Nova |
2021 |
Duncanson K, Burns G, Pryor J, Keely S, Talley NJ, 'Mechanisms of Food-Induced Symptom Induction and Dietary Management in Functional Dyspepsia', NUTRIENTS, 13 (2021) [C1]
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Nova |
2020 |
Liu G, Baird AW, Parsons MJ, Fan K, Skerrett-Byrne DA, Nair PM, et al., 'Platelet activating factor receptor acts to limit colitis-induced liver inflammation', FASEB JOURNAL, 34 7718-7732 (2020) [C1]
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2020 |
Shah A, Talley NJ, Koloski N, Macdonald GA, Kendall BJ, Shanahan ER, et al., 'Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease', Alimentary Pharmacology and Therapeutics, 52 155-167 (2020) [C1]
Background: Small intestinal bacterial overgrowth may play a role in gastrointestinal and non-gastrointestinal diseases. Aims: To use quantitative polymerase chain reaction (qPCR)... [more]
Background: Small intestinal bacterial overgrowth may play a role in gastrointestinal and non-gastrointestinal diseases. Aims: To use quantitative polymerase chain reaction (qPCR) to determine and compare bacterial loads of duodenal biopsies in asymptomatic controls, and patients with functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn¿s disease (CD). To define effects of gastric acid inhibition on bacterial load, explore links of bacterial load and gastrointestinal symptoms in response to a standardised nutrient challenge and compare bacterial load with glucose breath test results. Methods: In 237 patients (63 controls, 84 FGID and 90 IBD), we collected mucosal samples under aseptic conditions during endoscopy extracted and total DNA. Bacterial load metric was calculated utilising qPCR measurements of the bacterial 16S rRNA gene, normalised to human beta-actin expression. Standard glucose breath test and nutrient challenge test were performed. Results: The duodenal microbial load was higher in patients with FGID (0.22¿±¿0.03) than controls (0.07¿±¿0.05; P¿=¿0.007) and patients with UC (0.01¿±¿0.05) or CD (0.02¿±¿0.09), (P¿=¿0.0001). While patients treated with proton pump inhibitors (PPI) had significantly higher bacterial loads than non-users (P¿<¿0.05), this did not explain differences between patient groups and controls. Bacterial load was significantly (r¿=¿0.21, P¿<¿0.016) associated with the symptom response to standardised nutrient challenge test. Methane, but not hydrogen values on glucose breath test were associated with bacterial load measured utilising qPCR. Conclusions: Utilising qPCR, a diagnosis of FGID and treatment with PPI were independently associated with increased bacterial loads. Increased bacterial loads are associated with an augmented symptom response to a standardised nutrient challenge.
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2020 |
Prasad SS, Keely S, Talley NJ, Kairuz T, Walker MM, 'Pharmacists' Confidence in Managing Patients with Inflammatory Bowel Disease.', Pharmacy, 8 (2020) [C1]
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Nova |
2020 |
Prasad SS, Potter M, Keely S, Talley NJ, Walker MM, Kairuz T, 'Roles of healthcare professionals in the management of chronic gastrointestinal diseases with a focus on primary care: A systematic review', JGH Open, 4 221-229 (2020) [C1]
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Nova |
2020 |
Sokulsky LA, Goggins B, Sherwin S, Eyers F, Kaiko GE, Board PG, et al., 'GSTO1-1 is an upstream suppressor of M2 macrophage skewing and HIF-1 alpha-induced eosinophilic airway inflammation', CLINICAL AND EXPERIMENTAL ALLERGY, 50 609-624 (2020) [C1]
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2020 |
Potter MDE, Jones MP, Walker MM, Koloski NA, Keely S, Holtmann G, Talley AC NJ, 'Incidence and prevalence of self-reported non-coeliac wheat sensitivity and gluten avoidance in Australia', Medical Journal of Australia, 212 126-131 (2020) [C1]
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Nova |
2020 |
Shukla SD, Walters EH, Simpson JL, Keely S, Wark PAB, O'Toole RF, Hansbro PM, 'Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease', RESPIROLOGY, 25 53-63 (2020) [C1]
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Nova |
2020 |
Makanyengo SO, Carroll GM, Goggins BJ, Smith SR, Pockney PG, Keely S, 'Systematic Review on the Influence of Tissue Oxygenation on Gut Microbiota and Anastomotic Healing', JOURNAL OF SURGICAL RESEARCH, 249 186-196 (2020) [C1]
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Nova |
2020 |
deZoeten EF, Battista KD, Colson SB, Lovell MA, Kessler BE, Isfort RW, et al., 'Markers of Hypoxia Correlate with Histologic and Endoscopic Severity of Colitis in Inflammatory Bowel Disease.', Hypoxia (Auckland, N.Z.), 8 1-12 (2020) [C1]
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Nova |
2020 |
Talley NJ, Irani M, Keely S, 'Bacterial therapy for irritable bowel syndrome', LANCET GASTROENTEROLOGY & HEPATOLOGY, 5 627-629 (2020)
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2020 |
Turner A, Veysey M, Keely S, Scarlett CJ, Lucock M, Beckett EL, 'Intense sweeteners, taste receptors and the gut microbiome: A metabolic health perspective', International Journal of Environmental Research and Public Health, 17 1-18 (2020) [C1]
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Nova |
2020 |
Carroll GM, Burns GL, Petit JA, Walker MM, Mathe A, Smith SR, et al., 'Does postoperative inflammation or sepsis generate neutrophil extracellular traps that influence colorectal cancer progression? A systematic review', Surgery Open Science, 2 57-69 (2020) [C1]
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Nova |
2020 |
Talley NJ, Holtmann GJ, Jones M, Koloski NA, Walker MM, Burns G, et al., 'Zonulin in serum as a biomarker fails to identify the IBS, functional dyspepsia and non-coeliac wheat sensitivity', GUT, 69 1719-1722 (2020)
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2020 |
Potter MDE, Duncanson K, Jones MP, Walker MM, Keely S, Talley NJ, 'Wheat sensitivity and functional dyspepsia: A pilot, double-blind, randomized, placebo-controlled dietary crossover trial with novel challenge protocol', Nutrients, 12 1-15 (2020) [C1]
Introduction: Functional dyspepsia (FD), characterised by symptoms of epigastric pain or early satiety and post prandial distress, has been associated with duodenal eosinophilia, ... [more]
Introduction: Functional dyspepsia (FD), characterised by symptoms of epigastric pain or early satiety and post prandial distress, has been associated with duodenal eosinophilia, raising the possibility that it is driven by an environmental allergen. Non-coeliac gluten or wheat sensitivity (NCG/WS) has also been associated with both dyspeptic symptoms and duodenal eosinophilia, suggesting an overlap between these two conditions. The aim of this study was to evaluate the role of wheat (specifically gluten and fructans) in symptom reduction in participants with FD in a pilot randomized double-blind, placebo controlled, dietary crossover trial. Methods: Patients with Rome III criteria FD were recruited from a single tertiary centre in Newcastle, Australia. All were individually counselled on a diet low in both gluten and fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) by a clinical dietitian, which was followed for four weeks (elimination diet phase). Those who had a >30% response to the run-in diet, as measured by the Nepean Dyspepsia Index, were then re-challenged with ¿muesli¿ bars containing either gluten, fructan, or placebo in randomised order. Those with symptoms which significantly reduced during the elimination diet, but reliably reappeared (a mean change in overall dyspeptic symptoms of >30%) with gluten or fructan re-challenge were deemed to have wheat induced FD. Results: Eleven participants were enrolled in the study (75% female, mean age 43 years). Of the initial cohort, nine participants completed the elimination diet phase of whom four qualified for the rechallenge phase. The gluten-free, low FODMAP diet led to an overall (albeit non-significant) improvement in symptoms of functional dyspepsia in the diet elimination phase (mean NDI symptom score 71.2 vs. 47.1, p = 0.087). A specific food trigger could not be reliably demonstrated. Conclusions: Although a gluten-free, low-FODMAP diet led to a modest overall reduction in symptoms in this cohort of FD patients, a specific trigger could not be identified. The modified Salerno criteria for NCG/WS identification trialled in this dietary rechallenge protocol was fit-for-purpose. However, larger trials are required to determine whether particular components of wheat induce symptoms in functional dyspepsia.
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2020 |
Prasad SS, Duncanson K, Keely S, Talley NJ, Kairuz T, Holtmann GJ, et al., 'A Role for Primary Care Pharmacists in the Management of Inflammatory Bowel Disease? Lessons from Chronic Disease: A Systematic Review.', Pharmacy (Basel), 8 1-13 (2020) [C1]
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2020 |
Wauters L, Burns G, Ceulemans M, Walker MM, Vanuytsel T, Keely S, Talley NJ, 'Duodenal inflammation: an emerging target for functional dyspepsia?', Expert Opinion on Therapeutic Targets, 24 511-523 (2020) [C1]
Introduction: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders and is classified into postprandial distress and epigastric pain syndrome. ... [more]
Introduction: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders and is classified into postprandial distress and epigastric pain syndrome. Despite the recognition of duodenal inflammation as a potential trigger of symptoms, only limited anti-inflammatory therapies exist. Areas covered: This narrative review summarizes the recent advances in the pathophysiology and treatment of FD; it identifies potential therapeutic targets and gaps in the field. An electronic literature search was conducted in Pubmed up to 31st of December 2019. Expert opinion: There is compelling evidence for the role of duodenal inflammation and the eosinophil-mast cell axis in the pathogenesis of dyspeptic symptoms. Traditional prokinetic drugs and neuromodulators target gastric dysmotility and visceral hypersensitivity but are hampered by limited efficacy and side effects. Independent of acid suppression, the anti-inflammatory action of proton pump inhibitors, which remain the first-line therapy in FD, may also explain their therapeutic effect. Other existing and newly established anti-inflammatory drugs should be investigated while trials including probiotics and selective antibiotics should examine the host microbiome and immune activation. Targeted treatments for potential causes of duodenal pathology, such as impaired permeability and dysbiosis, are likely to emerge in the future.
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2020 |
Keely S, Talley NJ, 'Duodenal bile acids as determinants of intestinal mucosal homeostasis and disease', NEUROGASTROENTEROLOGY AND MOTILITY, 32 (2020) [C1]
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Nova |
2020 |
Pryor J, Burns GL, Duncanson K, Horvat JC, Walker MM, Talley NJ, Keely S, 'Functional Dyspepsia and Food: Immune Overlap with Food Sensitivity Disorders.', Current gastroenterology reports, 22 (2020) [C1]
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Nova |
2019 |
B Biomed GB, Carroll G, Mathe A, Horvat J, Foster P, Walker MM, et al., 'Evidence for Local and Systemic Immune Activation in Functional Dyspepsia and the Irritable Bowel Syndrome: A Systematic Review', American Journal of Gastroenterology, 114 429-436 (2019) [C1]
BACKGROUND:Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional ... [more]
BACKGROUND:Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and the irritable bowel syndrome (IBS). The mechanisms that drive recruitment of these cells to the gastrointestinal tract remain unexplained, largely due to the heterogeneity in phenotypes among patients diagnosed with such conditions. We aimed to systematically review the literature and collate the evidence for immune activation in FD and IBS, and where possible, detail the nature of activation.METHODS:Seven literature databases were searched using the keywords: 'functional gastrointestinal disorder', FGID, 'functional dyspepsia', 'non-ulcer dyspepsia', 'idiopathic dyspepsia', 'irritable bowel syndrome', IBS and 'immun*'.RESULTS:Fifty-one papers reporting discordant immune features met the selection criteria for this review. Changes in lymphocyte populations, including B and T lymphocyte numbers and activation status were reported in IBS and FD, in conjunction with duodenal eosinophilia in FD and increased colonic mast cells in IBS. Increases in circulating a4+ß7+ gut-homing T cells appear to be linked to the pathophysiology of both FD and IBS. Studies in the area are complicated by poor phenotyping of patients into subgroups and the subtle nature of the immune activity involved in FD and IBS.CONCLUSIONS:Alterations in proportions of gut-homing T lymphocytes in both FD and IBS indicate that a loss of mucosal homeostasis may drive the symptoms of FD and IBS. There is indirect evidence that Th17 responses may play a role in FGIDs, however the evidence for a Th2 immune phenotype in FD and IBS is limited. Although immune involvement is evident, large, well-characterised patient cohorts are required to elucidate the immune mechanisms driving the development of FGIDs.
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2019 |
Carroll GM, Burns GL, Petit JA, Walker MM, Mathe A, Smith SR, et al., 'Does Surgery Generate Neutrophil Extracellular Traps that Influence Colorectal Cancer Progression? A Systematic Review', SSRN Electronic Journal,
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2019 |
Shah A, Crawford D, Burger D, Martin N, Walker M, Talley NJ, et al., 'Effects of Antibiotic Therapy in Primary Sclerosing Cholangitis with and without Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis', Seminars in Liver Disease, 39 432-441 (2019) [C1]
The authors conducted a systematic review and meta-analysis to assess the effect of antibiotic therapy in primary sclerosing cholangitis (PSC). Effect of antibiotic therapy on May... [more]
The authors conducted a systematic review and meta-analysis to assess the effect of antibiotic therapy in primary sclerosing cholangitis (PSC). Effect of antibiotic therapy on Mayo PSC Risk Score (MRS), serum alkaline phosphatase (ALP), total serum bilirubin (TSB), and adverse events (AEs) rates were calculated and expressed as standardized difference of means or proportions. Five studies including 124 PSC patients who received antibiotics were included. Overall, antibiotic treatment was associated with a statistically significant reduction in ALP, MRS, and TSB by 33.2, 36.1, and 28.8%, respectively. ALP reduction was greatest for vancomycin (65.6%, p < 0.002) and smallest with metronidazole (22.7%, p = 0.18). Overall, 8.9% (95% confidence interval: 3.9-13.9) of patients had AEs severe enough to discontinue antibiotic therapy. In PSC patients, antibiotic treatment results in a significant improvement in markers of cholestasis and MRS. Antibiotics, particularly vancomycin, may have a positive effect on PSC either via direct effects on the microbiome or via host-mediated mechanisms.
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2019 |
Burns G, Pryor J, Holtmann G, Walker MM, Talley NJ, Keely S, 'Immune Activation in Functional Gastrointestinal Disorders.', Gastroenterology & hepatology, 15 539-548 (2019) [C1]
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Nova |
2019 |
Turner A, Chijoff E, Veysey M, Keely S, Scarlett CJ, Lucock M, Beckett EL, 'Interactions between taste receptors and the gastrointestinal microbiome in inflammatory bowel disease', Journal of Nutrition and Intermediary Metabolism, 18 (2019) [C1]
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2019 |
Walker MM, Talley NJ, Keely S, 'Follow up on atopy and the gastrointestinal tract - a review of a common association 2018.', Expert review of gastroenterology & hepatology, 13 437-445 (2019) [C1]
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Nova |
2019 |
Parsons MJ, Keely S, 'FOXO3 Loss Drives Inflammation-Associated CRC: The Consequences of Being (Knock)Out-FOX'd', CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 7 295-296 (2019)
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2019 |
Koloski N, Jones M, Walker MM, Veysey M, Zala A, Keely S, et al., 'Population based study: atopy and autoimmune diseases are associated with functional dyspepsia and irritable bowel syndrome, independent of psychological distress', Alimentary Pharmacology and Therapeutics, 49 546-555 (2019) [C1]
Background: The pathogenesis of functional GI disorders (FGIDs) is uncertain. However, underlying immune activation and psychological distress has been documented in irritable bow... [more]
Background: The pathogenesis of functional GI disorders (FGIDs) is uncertain. However, underlying immune activation and psychological distress has been documented in irritable bowel syndrome (IBS) and functional dyspepsia (FD). Epidemiological data from the UK suggest that FGIDs are linked to atopy and certain autoimmune diseases but this has not been confirmed. Aim: To test if allergic or autoimmune diseases are independently associated with FGIDs, irrespective of psychological distress in a large population based study. Methods: A total of 3542 people (mean age 57.9¿years and 52.7% females) randomly selected from the Australian population, returned a mail survey (response rate¿=¿43%). The survey asked about a physician diagnosis of autoimmune disease (scleroderma, psoriasis, rheumatoid arthritis and diabetes mellitus) or allergic conditions (asthma, food, pollen and/or animal allergy). The questionnaire assessed psychological distress and Rome III criteria for FD and IBS. Results: Asthma, food, pollen and animal allergies, psoriasis and rheumatoid arthritis were univariately significantly associated with IBS and FD. Food allergy (OR¿=¿1.66; 95% CI¿=¿1.15-2.40, P¿=¿0.007), psoriasis (OR¿=¿1.81; 95% CI¿=¿1.19-2.74, P¿=¿0.006) and rheumatoid arthritis (OR¿=¿1.68; 95% CI¿=¿1.15-2.4, P¿=¿0.007) were independent risk factors for IBS, controlling for age, gender and psychological distress. In FD, asthma (OR¿=¿1.32; 95% CI¿=¿1.04-1.68, P¿=¿0.025) and food allergy (OR¿=¿1.78; 95% CI¿=¿1.28-2.49, P¿=¿0.001) were independent predictors, controlling for age, sex and psychological distress. Conclusions: There is evidence that both atopic and autoimmune diseases are risk factors for FGIDs, independent of psychological distress, differing in IBS and FD. This provides evidence that different peripheral pathways may be involved in the pathogenesis of certain FGIDs.
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2019 |
Keely S, Talley NJ, 'In the ZOne: How Impedance Facilitates Progress in Functional Dyspepsia Research', DIGESTIVE DISEASES AND SCIENCES, 64 3027-3029 (2019)
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2019 |
Duncanson K, Burrows T, Keely S, Potter M, Das G, Walker M, Talley NJ, 'The alignment of dietary intake and symptom-reporting capture periods in studies assessing associations between food and functional gastrointestinal disorder symptoms: A systematic review', Nutrients, 11 (2019) [C1]
Food ingestion is heavily implicated in inducing symptoms of irritable bowel syndrome (IBS) and functional dyspepsia (FD), which affect over one-third of adults in developed count... [more]
Food ingestion is heavily implicated in inducing symptoms of irritable bowel syndrome (IBS) and functional dyspepsia (FD), which affect over one-third of adults in developed countries. The primary aim of this paper was to assess the alignment of dietary assessment and symptom-reporting capture periods in diet-related studies on IBS or FD in adults. Secondary aims were to compare the degree of alignment, validity of symptom-reporting tools and reported significant associations between food ingestion and symptoms. A five-database systematic literature search resulted in 40 included studies, from which data were extracted and collated. The food/diet and symptom capture periods matched exactly in 60% (n = 24/40) of studies, overlapped in 30% (n = 12/40) of studies and were not aligned in 10% (n = 4/40) of studies. Only 30% (n = 12/40) of studies that reported a significant association between food and global gastrointestinal symptoms used a validated symptom-reporting tool. Of the thirty (75%) studies that reported at least one significant association between individual gastrointestinal symptoms and dietary intake, only four (13%) used a validated symptom tool. Guidelines to ensure that validated symptom-reporting tools are matched with fit-for-purpose dietary assessment methods are needed to minimise discrepancies in the alignment of food and symptom tools, in order to progress functional gastrointestinal disorder research.
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Nova |
2019 |
Shukla SD, Shastri MD, Chong WC, Dua K, Budden KF, Mahmood MQ, et al., 'Microbiome-focused asthma management strategies', Current Opinion in Pharmacology, 46 143-149 (2019) [C1]
Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effectiv... [more]
Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effective therapies and it exerts substantial healthcare and societal burden. The role of microbiomes, particularly in chronic diseases has generated considerable interest in recent times. Existing evidence clearly demonstrates an association between asthma initiation and the microbiome, both respiratory and gastro-intestinal, although its¿ roles are poorly understood when assessing the asthma progression or heterogeneity (i.e. phenotypes/endotypes) across different geographical locations. Moreover, modulating microbiomes could be preventive and/or therapeutic in patients with asthma warrants urgent attention. Here, we review recent advances in assessing the role of microbiomes in asthma and present the challenges associated with the potential therapeutic utility of modifying microbiomes in management.
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Nova |
2019 |
Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P, et al., 'Functional effects of the microbiota in chronic respiratory disease', The Lancet Respiratory Medicine, 7 907-920 (2019) [C1]
The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respirator... [more]
The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respiratory diseases such as asthma, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. However, the precise effects of the microbiome on pulmonary health and the functional mechanisms by which it regulates host immunity are only now beginning to be elucidated. Bacteria, viruses, and fungi from both the upper and lower respiratory tract produce structural ligands and metabolites that interact with the host and alter the development and progression of chronic respiratory diseases. Here, we review recent advances in our understanding of the composition of the lung microbiome, including the virome and mycobiome, the mechanisms by which these microbes interact with host immunity, and their functional effects on the pathogenesis, exacerbations, and comorbidities of chronic respiratory diseases. We also describe the present understanding of how respiratory microbiota can influence the efficacy of common therapies for chronic respiratory disease, and the potential of manipulation of the microbiome as a therapeutic strategy. Finally, we highlight some of the limitations in the field and propose how these could be addressed in future research.
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Nova |
2019 |
Talley NJ, Holtmann G, Walker MM, Burns G, Potter M, Shah A, et al., 'Circulating Anti-cytolethal Distending Toxin B and Anti-vinculin Antibodies as Biomarkers in Community and Healthcare Populations With Functional Dyspepsia and Irritable Bowel Syndrome.', Clin Transl Gastroenterol, 10 e00064 (2019) [C1]
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Nova |
2019 |
Liu G, Mateer SW, Hsu A, Goggins BJ, Tay H, Mathe A, et al., 'Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome', Mucosal Immunology, 12 862-873 (2019) [C1]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patient... [more]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1ß levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1ß in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.
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Nova |
2019 |
Kaiko GE, Chen F, Lai C-W, Chiang I-L, Perrigoue J, Stojmirovic A, et al., 'PAI-1 augments mucosal damage in colitis', SCIENCE TRANSLATIONAL MEDICINE, 11 (2019) [C1]
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Nova |
2018 |
McIlroy DJ, Minahan K, Keely S, Lott N, Hansbro P, Smith DW, Balogh ZJ, 'Reduced deoxyribonuclease enzyme activity in response to high postinjury mitochondrial DNA concentration provides a therapeutic target for Systemic Inflammatory Response Syndrome', JOURNAL OF TRAUMA AND ACUTE CARE SURGERY, 85 354-358 (2018) [C1]
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Nova |
2018 |
Turner A, Veysey M, Keely S, Scarlett C, Lucock M, Beckett EL, 'Interactions between Bitter Taste, Diet and Dysbiosis: Consequences for Appetite and Obesity.', Nutrients, 10 (2018) [C1]
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Nova |
2018 |
Potter MDE, Walker MM, Jones MP, Koloski NA, Keely S, Talley NJ, 'Wheat Intolerance and Chronic Gastrointestinal Symptoms in an Australian Population-based Study: Association Between Wheat Sensitivity, Celiac Disease and Functional Gastrointestinal Disorders', American Journal of Gastroenterology, 113 1036-1044 (2018) [C1]
OBJECTIVES: Wheat avoidance in the absence of celiac disease (CD) is common but occurrence of concurrent functional gastrointestinal disorders (FGIDs) in this group is uncertain. ... [more]
OBJECTIVES: Wheat avoidance in the absence of celiac disease (CD) is common but occurrence of concurrent functional gastrointestinal disorders (FGIDs) in this group is uncertain. The aims of this study were to determine the prevalence of self-reported wheat or gluten sensitivity and doctor diagnosed CD in an Australian population, define the associated gastrointestinal (GI) symptoms and FGIDs, and determine the relationship between self-reported wheat sensitivity, demographic and medical factors. Methods: A total of 3542 people randomly selected from the Australian population returned a mail survey which contained questions on wheat avoidance, GI symptoms, demographic, medical, and lifestyle factors. We defined self-reported wheat sensitivity as people who reported gastrointestinal symptoms on ingestion of wheat based foods, but did not suffer from celiac disease, inflammatory bowel disease or colorectal cancer. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed by Rome III criteria. CD status was self-reported. Results: The prevalence of self-reported wheat sensitivity in this cohort was 14.9% (95% CI 13.7¿16.2). The prevalence of CD was 1.2% (95%CI 0.8¿1.6). Doctor diagnosed CD was significantly associated with a diagnosis of FD (OR 3.35, 95%CI 1.72¿6.52) and IBS (OR 2.28, 95%CI 1.08¿4.81). Those with self-reported wheat sensitivity were more likely to report multiple abdominal symptoms (of the 18 assessed) than those without (3.9 symptoms with self-reported wheat sensitivity vs. 1.6 without, p = 0.0001). In a multivariate analysis, self-reported wheat sensitivity was independently associated with IBS (OR 3.55, 95%CI 2.71¿4.65) and FD (1.48, 95%CI 1.13¿1.94). Conclusions: Self-reported wheat sensitivity is common, with a prevalence of 14.9% in this cohort. There is a strong association between both celiac disease and self-reported wheat sensitivity, and chronic gastrointestinal symptoms, as well as a diagnosis of FD and IBS.
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Nova |
2018 |
Mateer SW, Mathe A, Bruce J, Liu G, Maltby S, Fricker M, et al., 'IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis', American Journal of Pathology, 188 1625-1639 (2018) [C1]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathol... [more]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases, such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid¿ and dextran sulfate sodium¿induced models of colitis. Analysis of systemic inflammation identified that neutrophilia was associated with bacteremia and pyrexia in animal models of colitis. We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD. Targeting IL-6 may reduce neutrophil-associated extraintestinal manifestations in IBD patients.
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Nova |
2018 |
Keely S, Talley NJ, 'Endophenotyping eosinophilic oesophagitis: a new era for management?', LANCET GASTROENTEROLOGY & HEPATOLOGY, 3 449-450 (2018)
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2018 |
Fricker M, Goggins BJ, Mateer S, Jones B, Kim RY, Gellatly SL, et al., 'Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction.', JCI insight, 3 1-19 (2018) [C1]
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Nova |
2018 |
Potter MD, Walker MM, Jones MP, Koloski NA, Keely S, Talley NJ, 'Letter: gluten sensitivity in patients with inflammatory bowel disease', ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 48 1167-1168 (2018)
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2018 |
Hollins SL, Brock L, Barreto R, Harms L, Dunn A, Garcia-Sobrinho P, et al., 'A rodent model of anxiety: The effect of perinatal immune challenges on gastrointestinal inflammation and integrity', NeuroImmunoModulation, 25 163-175 (2018) [C1]
Objectives: Gastrointestinal (GI) inflammation and GI integrity deficits are common comorbidities of neuropsychiatric disorders. Ongoing research suggests that these aberrations m... [more]
Objectives: Gastrointestinal (GI) inflammation and GI integrity deficits are common comorbidities of neuropsychiatric disorders. Ongoing research suggests that these aberrations may be contributing to heightened immune signals that have the potential to disrupt neuronal homeostasis and exacerbate behavioural deficits. The current study aimed to determine whether the well-characterized animal model of neuropsychopathology, the maternal immune activation (MIA) model, produced GI inflammation and integrity disruptions in association with anxiety-like behaviour. Methods: Pregnant Wistar rats were exposed to the viral mimetic polyriboinosinic:polyribocytidilic acid (polyI:C) on gestational days (GD) 10 and 19. Evidence of ANS activation, GI inflammation, and GI barrier integrity was assessed in both neonatal (postnatal day, P7) and adult (P84) offspring. Anxiety-like behaviour was assessed at P100. Results: Neonatal MIA offspring exhibited an altered intestinal inflammatory profile and evidence of an increase in lymphoid aggregates. MIA neonates also displayed disruptions to GI barrier tight junction protein mRNA. In addition, adult MIA offspring exhibited an increase in anxiety-like behaviours. Conclusion: These results indicate that the MIA rat model, which is well documented to produce behavioural, neurochemical, and neuroanatomical abnormalities, also produces GI inflammation and integrity disruptions. We suggest that this model may be a useful tool to elucidate biological pathways associated with neuropsychiatric disorders.
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Nova |
2018 |
Mroz MS, Lajczak NK, Goggins BJ, Keely S, Keely SJ, 'The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing', American Journal of Physiology - Gastrointestinal and Liver Physiology, 314 G378-G387 (2018) [C1]
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regula... [more]
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50¿150 µM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl- channels, whereas inhibition of CFTR activity with either CFTR-inh -172 (10 µM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50¿150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes wound healing, suggesting it may provide an alternative approach to prevent the losses of barrier function that are associated with mucosal inflammation in IBD patients.
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Nova |
2018 |
Potter MDE, Walker MM, Keely S, Talley NJ, 'What's in a name? 'Non-coeliac gluten or wheat sensitivity': controversies and mechanisms related to wheat and gluten causing gastrointestinal symptoms or disease.', Gut, 67 2073-2077 (2018) [C1]
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Nova |
2017 |
Farrell KE, Keely S, Walker MM, Brichta AM, Graham BA, Callister RJ, 'Altered intrinsic and synaptic properties of lumbosacral dorsal horn neurons in a mouse model of colitis', Neuroscience, 362 152-167 (2017) [C1]
Visceral pain in inflammatory and functional gastrointestinal conditions is a major clinical problem. The exact mechanisms underlying the development of pain, during and after vis... [more]
Visceral pain in inflammatory and functional gastrointestinal conditions is a major clinical problem. The exact mechanisms underlying the development of pain, during and after visceral inflammation are unknown. However, clinical and pre-clinical evidence suggests plasticity within the spinal cord dorsal horn is a contributing factor. Here we use an in vivo preparation and patch-clamp electrophysiology to test whether the synaptic and intrinsic properties of superficial dorsal horn (SDH) neurons are altered 5 days after the induction of mild colitis in adult male mice (i.e. during acute inflammation of the colon). Whole-cell recordings were made from lumbosacral (L6-S1) superficial dorsal horn neurons (SDH), in animals under isoflurane anesthesia. Noxious colorectal distension (CRD) was used to identify SDH neurons with colonic inputs, while stimulation of the hind paw and tail was employed to assess convergent cutaneous input. Following inflammation, a significantly increased proportion of SDH neurons received both colonic and cutaneous inputs, compared to neurons in naïve animals. In addition, the nature and magnitude of responses to CRD and cutaneous stimulation differed in inflamed animals, as was spontaneous excitatory synaptic drive. Conversely, several measures of intrinsic excitability were altered in a manner that would decrease SDH network excitability following colitis. We propose that during inflammation, sensitization of colonic afferents results in increased signaling to the SDH. This is accompanied by plasticity in SDH neurons whereby their intrinsic properties are changed to compensate for altered afferent activity.
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Nova |
2017 |
Ward JBJ, Lajczak NK, Kelly OB, O Dwyer AM, Giddam AK, Ní Gabhann J, et al., 'Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon', American Journal of Physiology - Gastrointestinal and Liver Physiology, 312 G550-G558 (2017) [C1]
Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The na... [more]
Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6a-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-a, IL-6, Il-1ß, and IFN-¿) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic inflammation and suggest that microbial metabolism of UDCA is necessary for the full expression of its protective actions. NEW & NOTEWORTHY On the basis of its cytoprotective and anti-inflammatory actions, the secondary bile acid ursodeoxycholic acid (UDCA) has well-established uses in both traditional and Western medicine. We identify a new role for the primary metabolite of UDCA, lithocholic acid, as a potent inhibitor of intestinal inflammatory responses, and we present data to suggest that microbial metabolism of UDCA is necessary for the full expression of its protective effects against colonic inflammation.
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Nova |
2017 |
Kim RY, Horvat JC, Pinkerton JW, Starkey MR, Essilfie AT, Mayall JR, et al., 'MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase mediated suppression of histone deacetylase 2', Journal of Allergy and Clinical Immunology, 139 519-532 (2017) [C1]
Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of und... [more]
Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The¿mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. Objective We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Methods Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory¿tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Results Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21¿specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. Conclusion We identify a previously unrecognized role for an¿miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.
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Nova |
2017 |
Marks E, Naudin C, Nolan G, Goggins BJ, Burns G, Mateer SW, et al., 'Regulation of IL-12p40 by HIF controls Th1/Th17 responses to prevent mucosal inflammation', MUCOSAL IMMUNOLOGY, 10 1224-1236 (2017) [C1]
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Nova |
2016 |
Walker MM, Keely SJ, Scott RJ, Talley NJ, 'Genetics, Mucosal Inflammation and the Environment in Post-Infectious Chronic Gut Syndromes', The American Journal of Gastroenterology Supplements, 3 46-51 (2016) [C1]
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Nova |
2016 |
Farrell KE, Rank MM, Keely S, Brichta AM, Graham BA, Callister RJ, 'In vivo characterization of colorectal and cutaneous inputs to lumbosacral dorsal horn neurons in the mouse spinal cord', Neuroscience, 316 13-25 (2016) [C1]
Chronic abdominal pain is a common symptom of inflammatory bowel disease and often persists in the absence of gut inflammation. Although the mechanisms responsible for ongoing pai... [more]
Chronic abdominal pain is a common symptom of inflammatory bowel disease and often persists in the absence of gut inflammation. Although the mechanisms responsible for ongoing pain are unknown, clinical and preclinical evidence suggests lumbosacral spinal cord dorsal horn neurons contribute to these symptoms. At present, we know little about the intrinsic and synaptic properties of this population of neurons in either normal or inflammed conditions. Therefore, we developed an in vivo preparation to make patch-clamp recordings from superficial dorsal horn (SDH) neurons receiving colonic inputs in naïve male mice. Recordings were made in the lumbosacral spinal cord (L6-S1) under isoflurane anesthesia. Noxious colorectal distension (CRD) was used to determine whether SDH neurons received inputs from mechanical stimulation/distension of the colon. Responses to hind paw/tail cutaneous stimulation and intrinsic and synaptic properties were also assessed, as well as action potential discharge properties. Approximately 11% of lumbosacral SDH neurons in the cohort of neurons sampled responded to CRD and a majority of these responses were subthreshold. Most CRD-responsive neurons (80%) also responded to cutaneous stimuli, compared with <50% of CRD-non-responsive neurons. Furthermore, CRD-responsive neurons had more hyperpolarized resting membrane potentials, larger rheobase currents, and reduced levels of excitatory drive, compared to CRD-non-responsive neurons. Our results demonstrate that CRD-responsive neurons can be distinguished from CRD-non-responsive neurons by several differences in their membrane properties and excitatory synaptic inputs. We also demonstrate that SDH neurons with colonic inputs show predominately subthreshold responses to CRD and exhibit a high degree of viscerosomatic convergence.
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Nova |
2016 |
Cuív P, Begun J, Keely S, Lewindon PJ, Morrison M, 'Towards an integrated understanding of the therapeutic utility of exclusive enteral nutrition in the treatment of Crohn's disease', Food and Function, 7 1741-1751 (2016) [C1]
Crohn's disease (CD) is a chronic disease characterized by episodic and disabling inflammation of the gastrointestinal tract in genetically susceptible individuals. The incid... [more]
Crohn's disease (CD) is a chronic disease characterized by episodic and disabling inflammation of the gastrointestinal tract in genetically susceptible individuals. The incidence and prevalence of CD is rising rapidly across the world emphasising that disease risk is also influenced by environmental and lifestyle factors, as well as the microbial community resident in the gut. Childhood-onset CD is associated with an aggressive disease course that can adversely impact patient growth and development. There is no cure for CD however new onset and recurrent cases of paediatric CD are often responsive to exclusive enteral nutrition (EEN) treatment. EEN treatment involves the exclusive consumption of an elemental or polymeric formula for several weeks and it is well established as a primary intervention strategy. EEN treatments typically achieve remission rates of over 80% and importantly they are associated with a high rate of mucosal healing, far superior to steroids, which is prognostic of improved long-term health outcomes. Furthermore, they are safe, have few side effects, and improve nutritional status and linear growth. Surprisingly, despite the utility of EEN our understanding of the host-microbe-diet interactions that underpin clinical remission and mucosal healing are limited. Here, we review the current state of knowledge and propose that the induction of autophagy, in addition to modulation of the microbiota and coordinated effects on inflammation and epithelial cell biology, may be critical for the therapeutic effects associated with EEN. A better understanding of EEN treatment will provide new opportunities to restore gut homeostasis and prolong periods of remission, as well as provide new insights into the factors that trigger and perhaps prevent CD.
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Nova |
2016 |
Mateer SW, Cardona J, Marks E, Goggin BJ, Hua S, Keely S, 'Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease.', J Vis Exp, e53250 (2016) [C1]
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Nova |
2015 |
Hua S, Marks E, Schneider JJ, Keely S, 'Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.', Nanomedicine, 11 1117-1132 (2015) [C1]
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Nova |
2015 |
Keely S, Walker MM, Marks E, Talley NJ, 'Immune dysregulation in the functional gastrointestinal disorders', European Journal of Clinical Investigation, 45 1350-1359 (2015) [C1]
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Nova |
2015 |
Keely S, Veysey M, Walker MM, Talley NJ, 'Letter: oxidative stress, cause or consequence of constipation-associated colorectal cancer?', Aliment Pharmacol Ther, 42 941-942 (2015) [C3]
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2015 |
Marks E, Goggins BJ, Cardona J, Cole S, Minahan K, Mateer S, et al., 'Oral Delivery of Prolyl Hydroxylase Inhibitor: AKB-4924 Promotes Localized Mucosal Healing in a Mouse Model of Colitis.', Inflammatory bowel diseases, 21 267-275 (2015) [C1]
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Nova |
2015 |
Keely S, Foster PS, 'Stop Press: Eosinophils Drafted to Join the Th17 Team', IMMUNITY, 43 7-9 (2015) [C3]
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Nova |
2014 |
Keely S, Hansbro PM, 'Lung-Gut Cross Talk A Potential Mechanism for Intestinal Dysfunction in Patients With COPD', CHEST, 145 199-200 (2014) [C3]
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2014 |
Ward JBJ, Keely SJ, Keely SJ, 'Oxygen in the regulation of intestinal epithelial transport', Journal of Physiology, 592 2473-2489 (2014) [C1]
The transport of fluid, nutrients and electrolytes to and from the intestinal lumen is a primary function of epithelial cells. Normally, the intestine absorbs approximately 9 l of... [more]
The transport of fluid, nutrients and electrolytes to and from the intestinal lumen is a primary function of epithelial cells. Normally, the intestine absorbs approximately 9 l of fluid and 1 kg of nutrients daily, driven by epithelial transport processes that consume large amounts of cellular energy and O2. The epithelium exists at the interface of the richly vascularised mucosa, and the anoxic luminal environment and this steep O2 gradient play a key role in determining the expression pattern of proteins involved in fluid, nutrient and electrolyte transport. However, the dynamic nature of the splanchnic circulation necessitates that the epithelium can evoke co-ordinated responses to fluctuations in O2 availability, which occur either as a part of the normal digestive process or as a consequence of several pathophysiological conditions. While it is known that hypoxia-responsive signals, such as reactive oxygen species, AMP-activated kinase, hypoxia-inducible factors, and prolyl hydroxylases are all important in regulating epithelial responses to altered O2 supply, our understanding of the molecular mechanisms involved is still limited. Here, we aim to review the current literature regarding the role that O2 plays in regulating intestinal transport processes and to highlight areas of research that still need to be addressed. © 2014 The Physiological Society.
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Nova |
2014 |
Farrell KE, Keely S, Graham BA, Callister R, Callister RJ, 'A Systematic Review of the Evidence for Central Nervous System Plasticity in Animal Models of Inflammatory-mediated Gastrointestinal Pain', INFLAMMATORY BOWEL DISEASES, 20 176-195 (2014) [C1]
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Nova |
2014 |
Farrell KE, Callister RJ, Keely S, 'Understanding and targeting centrally mediated visceral pain in inflammatory bowel disease', Frontiers in Pharmacology, 5 1-4 (2014) [C3]
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Nova |
2014 |
Keely S, Campbell EL, Baird AW, Hansbro PM, Shalwitz RA, Kotsakis A, et al., 'Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis', Mucosal Immunology, 7 114-123 (2014) [C1]
Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However... [more]
Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However, little is known about how PHD inhibitors (PHDi) influence systemic immune function during mucosal inflammation or the relative importance of immunological changes to mucosal protection. We hypothesized that PHDi enhances systemic innate immune responses to colitis-associated bacteremia. Mice with colitis induced by trinitrobenzene sulfonic acid were treated with AKB-4924, a new HIF-1 isoform-predominant PHDi, and clinical, immunological, and biochemical endpoints were assessed. Administration of AKB-4924 led to significantly reduced weight loss and disease activity compared with vehicle controls. Treated groups were pyrexic but did not become subsequently hypothermic. PHDi treatment augmented epithelial barrier function and led to an approximately 50-fold reduction in serum endotoxin during colitis. AKB-4924 also decreased cytokines involved in pyrogenesis and hypothermia, significantly reducing serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-a while increasing IL-10. Treatment offered no protection against colitis in epithelial-specific HIF-1a-deficient mice, strongly implicating epithelial HIF-1a as the tissue target for AKB-4924-mediated protection. Taken together, these results indicate that inhibition of prolyl hydroxylase with AKB-4924 enhances innate immunity and identifies that the epithelium is a central site of inflammatory protection afforded by PHDi in murine colitis. © 2014 Society for Mucosal Immunology.
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2014 |
Goggins B, Minahan K, Kostakis A, Shalwitz R, Horvat J, Keely S, 'Stabilisation of epithelial hypoxia-inducible factor reverses colitis through accelerated restitution', FASEB JOURNAL, 28 (2014)
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2013 |
Goggins BJ, Chaney C, Radford-Smith GL, Horvat JC, Keely S, 'Hypoxia and Integrin-Mediated Epithelial Restitution during Mucosal Inflammation.', Front Immunol, 4 272 (2013) [C1]
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Nova |
2013 |
Hansbro P, Beckett E, Stevens R, Jarnicki A, Wark P, Foster P, 'A short-term model of COPD identifies a role for mast cell tryptase', EUROPEAN RESPIRATORY JOURNAL, 42 (2013) [C3]
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2013 |
Beckett EL, Stevens RL, Jarnicki AG, Kim RY, Hanish I, Hansbro NG, et al., 'A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis', The Journal of Allergy and Clinical Immunology, 131 752-762 (2013) [C1]
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Nova |
2012 |
Keely S, Kelly C, Weissmueller T, Burgess A, Wagner B, Robertson CE, et al., 'Activated fluid transport regulates bacterial-epithelial interactions and significantly shifts the murine colonic microbiome', Gut Microbes, 3 250-260 (2012) [C1]
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2012 |
Keely S, Talley NJ, Hansbro PM, 'Pulmonary-intestinal cross-talk in mucosal inflammatory disease', Mucosal Immunology, 5 7-18 (2012) [C1]
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Nova |
2011 |
Macmanus C, Campbell E, Keely S, Adrienne B, Kominsky D, Colgan S, 'Anti-inflammatory actions of adrenomedullin through fine tuning of HIF stabilization', The FASEB Journal, 25 1856-1864 (2011) [C1]
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2011 |
Keely S, Feighery L, Campion DP, O'Brien L, Brayden DJ, Baird AW, 'Chloride-led disruption of the intestinal mucous layer impedes salmonella invasion: Evidence for an 'enteric tear' mechanism', Cellular Physiology and Biochemistry, 28 743-752 (2011) [C1]
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Nova |
2011 |
Kominsky D, Keely S, Macmanus C, Glover L, Scully M, Collins C, et al., 'An Endogenously Anti-Inflammatory Role for Methylation in Mucosal Inflammation Identified through Metabolite Profiling.', Journal of Immunology, 186 6505-6514 (2011) [C1]
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2010 |
Campbell E, Macmanus C, Kominsky D, Keely S, Glover L, Scully M, et al., 'Resolvin E1-induced Intestinal Alkaline Phosphatase Promotes Resolution of Inflammation through LPS detoxification.', Proceedings of the National Academy of Sciences of USA, 107 4298-4303 (2010) [C1]
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2010 |
Keely S, Glover L, Weissmueller T, Macmanus C, Fillon S, Fennimore B, Colgan S, 'Hypoxia-inducible factor-dependent regulation of platelet-activating factor receptor as a route for gram-positive bacterial translocation across epithelia', Molecular Biology of the Cell, 21 538-546 (2010) [C1]
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2009 |
Keely S, Ryan S, Haddleton D, Limer A, Mantovani G, Murphy E, Brayden D, 'Dexamethasone-pDMAEMA polymeric conjugates reduce inflammatory biomarkers in human intestinal epithelial monolayers.', Journal of Controlled Release, 135 35-43 (2009) [C1]
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2009 |
Keely S, Glover L, Macmanus C, Campbell E, Scully M, Furuta G, Colgan S, 'Selective induction of integrin beta1 by hypoxia-inducible factor: implications for wound healing.', The FASEB Journal, 23 1338-1346 (2009) [C1]
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2008 |
Robinson A, Keely S, Karhausen J, Gerich M, Furuta G, Colgan S, 'Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition.', Gastroenterology, 134 346-348 (2008) [C1]
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2008 |
Feighery L, Smyth A, Keely S, Baird A, O'Connor W, Callanan J, Brayden D, 'Increased intestinal permeability in rats subjected to traumatic frontal lobe percussion brain injury.', Journal of Trauma: Injury Infection and Critical Care, 64 131-137 (2008) [C1]
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2008 |
Boland T, Hayes L, Sweeney T, Callanan J, Baird A, Keely S, Crosby T, 'The effects of cobalt and iodine supplementation of the pregnant ewe diet on immunoglobulin G, vitamin E, T-3 and T-4 levels in the progeny.', Animal: the international journal of animal biosciences, 2 197-206 (2008) [C1]
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2008 |
Fanning R, Campion D, Collins C, Keely S, Briggs L, O'Connor J, Carey M, 'A comparison of the inhibitory effects of bupivacaine and levobupivacaine on isolated human pregnant myometrium contractility.', Anesthesia and Analgesia, 107 1303-1307 (2008) [C1]
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2008 |
Keely S, Rawlinson L-AB, Haddleton DM, Brayden DJ, 'A tertiary amino-containing polymethacrylate polymer protects mucus-covered intestinal epithelial monolayers against pathogenic challenge', Pharmaceutical Research, 25 1193-1201 (2008) [C1]
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2006 |
Limer A, Attvinder R, San Miguel V, Peinado C, Keely S, Fitzpatrick E, et al., 'Fluorescently tagged star polymers by living radical polymerisation for mucoadhesion and bioadhesion.', Reactive and Functional Polymers, 66 51-64 (2006) [C1]
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2005 |
Keely S, Atvinder R, Wilson C, Carmichael A, Carrington S, Corfield A, et al., 'In vitro and ex vivo intestinal tissue models to measure mucoadhesion of poly (methacrylate) and N-trimethylated chitosan polymers.', Pharmaceutical Research, 22 38-49 (2005) [C1]
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