scholarly journals Oral iron exacerbates colitis and influences the intestinal microbiome

2018 ◽  
Author(s):  
Awad Mahalhal ◽  
Jonathan M. Williams ◽  
Sophie Johnson ◽  
Nicholas Ellaby ◽  
Carrie A. Duckworth ◽  
...  
Keyword(s):  
Iron Concentration ◽  
Intestinal Bacteria ◽  
Oral Iron ◽  
Intestinal Microbiome ◽  
Dietary Iron ◽  
Faecal Calprotectin ◽  
Inflammatory Bowel ◽  
Ad Libitum ◽  
The Impact ◽  
Iron Replacement

AbstractInflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS.

scholarly journals Disease monitoring of biologic treatment in IBD: early impact and future implications of COVID-19 pandemic

2020 ◽  
pp. flgastro-2020-101563
Author(s):  
Stephanie Shields ◽  
Allan Dunlop ◽  
John Paul Seenan ◽  
Jonathan Macdonald
Keyword(s):  
Clinical Care ◽  
Chronic Illnesses ◽  
Therapeutic Drug ◽  
Disease Monitoring ◽  
Biologic Treatment ◽  
Faecal Calprotectin ◽  
Routine Clinical Care ◽  
Risk Of Disease ◽  
Inflammatory Bowel ◽  
The Impact

COVID-19 has dominated life in 2020 with, at the time of writing, over 4.9M global cases and >320 000 deaths. The impact has been most intensely felt in acute and critical care environments. However, with most UK elective work postponed, laboratory testing of faecal calprotectin halted due to potential risk of viral transmission and non-emergency endoscopies and surgeries cancelled, the secondary impact on chronic illnesses such as inflammatory bowel disease (IBD) is becoming apparent. Data from the Scottish Biologic Therapeutic Drug Monitoring (TDM) service shows a dramatic drop in TDM testing since the pandemic onset. April 2020 saw a 75.6% reduction in adalimumab testing and a 36.2% reduction in infliximab testing when compared with February 2020 data, a reduction coinciding with the widespread cancellation of outpatient and elective activity. It is feared that disruption to normal patterns of care and disease monitoring of biologic patients could increase the risk of disease flare and adverse clinical outcomes. Urgent changes in clinical practice have been instigated to mitigate the effects of the pandemic on routine clinical care. Further transformations are needed to maintain safe, effective, patient-centred IBD care in the future.

scholarly journals Impact of COVID-19 on the diagnosis, assessment and management of children with inflammatory bowel disease in the UK: implications for practice

2020 ◽  
Vol 4 (1) ◽  
pp. e000786
Author(s):  
Abbie Maclean ◽  
James J Ashton ◽  
Vikki Garrick ◽  
R Mark Beattie ◽  
Richard Hansen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Delayed Diagnosis ◽  
High Standard ◽  
Current Evidence ◽  
Faecal Calprotectin ◽  
Paediatric Patients ◽  
Inflammatory Bowel ◽  
Working Practices ◽  
The Impact

The assessment and management of patients with known, or suspected, paediatric inflammatory bowel disease (PIBD) has been hugely impacted by the COVID-19 pandemic. Although current evidence of the impact of COVID-19 infection in children with PIBD has provided a degree of reassurance, there continues to be the potential for significant secondary harm caused by the changes to normal working practices and reorganisation of services.Disruption to the normal running of diagnostic and assessment procedures, such as endoscopy, has resulted in the potential for secondary harm to patients including delayed diagnosis and delay in treatment. Difficult management decisions have been made in order to minimise COVID-19 risk for this patient group while avoiding harm. Initiating and continuing immunosuppressive and biological therapies in the absence of normal surveillance and diagnostic procedures have posed many challenges.Despite this, changes to working practices, including virtual clinic appointments, home faecal calprotectin testing kits and continued intensive support from clinical nurse specialists and other members of the multidisciplinary team, have resulted in patients still receiving a high standard of care, with those who require face-to-face intervention being highlighted.These changes have the potential to revolutionise the way in which patients receive routine care in the future, with the inclusion of telemedicine increasingly attractive for stable patients. There is also the need to use lessons learnt from this pandemic to plan for a possible second wave, or future pandemics as well as implementing some permanent changes to normal working practices.In this review, we describe the diagnosis, management and direct impact of COVID-19 in paediatric patients with IBD. We summarise the guidance and describe the implemented changes, evolving evidence and the implications of this virus on paediatric patients with IBD and working practices.

scholarly journals High Dietary Iron Disrupts Iron Homeostasis and Induces Amyloid-β and Phospho-τ Expression in the Hippocampus of Adult Wild-Type and APP/PS1 Transgenic Mice

2019 ◽  
Vol 149 (12) ◽  
pp. 2247-2254 ◽  
Author(s):  
Min Chen ◽  
Jiashuo Zheng ◽  
Guohao Liu ◽  
Chong Zeng ◽  
En Xu ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Transgenic Mice ◽  
Iron Homeostasis ◽  
Iron Concentration ◽  
Amyloid Β ◽  
Dietary Iron ◽  
Wild Type ◽  
Brain Iron ◽  
Sod Activity ◽  
The Impact

ABSTRACT Background Brain iron deposition is a feature of Alzheimer disease and may contribute to its development. However, the relative contribution of dietary iron remains unclear. Objectives We investigated the impact of high dietary iron on brain pathological changes and cognitive function in adult wild-type (WT) mice and amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice. Methods Male WT mice and APP/PS1 mice aged 10 wk were fed either a control diet (66 mg Fe/kg) (WT-Ctrl and APP/PS1-Ctrl) or a high iron diet (14 g Fe/kg) (WT-High Fe and APP/PS1-High Fe) for 20 wk. Iron concentrations in brain regions were measured by atomic absorption spectrophotometry. Brain iron staining and amyloid-β (Aβ) immunostaining were performed. Protein expressions in the hippocampus were determined by immunoblotting. Superoxide dismutase (SOD) activity and malondialdehyde concentration were examined. Cognitive functions were tested with the Morris water maze system. Results In the hippocampus, APP/PS1-High Fe mice had significantly higher iron concentration (2.5-fold) and ferritin (2.0-fold) than APP/PS1-Ctrl mice (P < 0.001), and WT-High Fe mice had significantly higher ferritin (2.0-fold) than WT-Ctrl mice (P < 0.001). Interestingly, APP/PS1 mice had significantly higher iron concentration (2–3-fold) and ferritin (2–2.5-fold) than WT mice fed either diet (P < 0.001). Histological analysis indicated that iron accumulated in the hippocampal dentate gyrus region in APP/PS1 mice, consistent with the pattern of Aβ deposition. For both mouse strains, iron treatment induced Aβ and phospho-τ expression (1.5–3-fold) in the hippocampus, but had little impact on oxidative stress and cognitive function. Furthermore, APP/PS1 mice had significantly lower SOD activity and higher malondialdehyde concentration than WT mice in the hippocampus (P < 0.0001), paralleled by apparent cognitive dysfunction. Conclusions Dietary iron overload induces iron disorder and Aβ and phospho-τ expression in the hippocampus of adult WT and APP/PS1 transgenic mice.

scholarly journals Organisational changes and challenges for inflammatory bowel disease services in the UK during the COVID-19 pandemic

2020 ◽  
Vol 11 (5) ◽  
pp. 343-350 ◽  
Author(s):  
Nicholas A Kennedy ◽  
Richard Hansen ◽  
Lisa Younge ◽  
Joel Mawdsley ◽  
R Mark Beattie ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Elective Surgery ◽  
Quality Care ◽  
Faecal Calprotectin ◽  
Telephone Consultation ◽  
Ensure Patient Safety ◽  
Inflammatory Bowel ◽  
The Uk ◽  
The Impact

ObjectiveTo determine the challenges in diagnosis, monitoring, support provision in the management of inflammatory bowel disease (IBD) patients and explore the adaptations of IBD services.MethodsInternet-based survey by invitation of IBD services across the UK from 8 to 14 April 2020.ResultsRespondents from 125 IBD services completed the survey. The number of whole-time equivalent gastroenterologists and IBD nurses providing elective outpatient care decreased significantly between baseline (median 4, IQR 4–7.5 and median 3, IQR 2–4) to the point of survey (median 2, IQR 1–4.8 and median 2, IQR 1–3) in the 6-week period following the onset of the COVID-19 pandemic (p<0.001 for both comparisons). Almost all (94%; 112/119) services reported an increase in IBD helpline activity. Face-to-face clinics were substituted for telephone consultation by 86% and video consultation by 11% of services. A variation in the provision of laboratory faecal calprotectin testing was noted with 27% of services reporting no access to faecal calprotectin, and a further 32% reduced access. There was also significant curtailment of IBD-specific endoscopy and elective surgery.ConclusionsIBD services in the UK have implemented several adaptive strategies in order to continue to provide safe and high-quality care for patients. National Health Service organisations will need to consider the impact of these changes in current service delivery models and staffing levels when planning exit strategies for post-pandemic IBD care. Careful planning to manage the increased workload and to maintain IBD services is essential to ensure patient safety.

scholarly journals Mo1810 – Faecal Calprotectin Concentration in Inflammatory Bowel Disease and Controls: the Impact of Storage Time and Freeze-Thaw Cycles

2019 ◽  
Vol 156 (6) ◽  
pp. S-846
Author(s):  
Clara Caenepeel ◽  
Kathleen Machiels ◽  
Sara Vieira-Silva ◽  
Nooshin Ardeshir Davani ◽  
Marc Ferrante ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Storage Time ◽  
Faecal Calprotectin ◽  
Freeze Thaw ◽  
Inflammatory Bowel ◽  
The Impact

scholarly journals The Role of Gut Microbiota in an Ischemic Stroke

2021 ◽  
Vol 22 (2) ◽  
pp. 915
Author(s):  
Ryszard Pluta ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Ischemic Stroke ◽  
Intestinal Microflora ◽  
Intestinal Bacteria ◽  
Intestinal Microbiome ◽  
Gut Dysfunction ◽  
Development And Aging ◽  
Host Metabolism ◽  
The Impact ◽  
The Brain

The intestinal microbiome, the largest reservoir of microorganisms in the human body, plays an important role in neurological development and aging as well as in brain disorders such as an ischemic stroke. Increasing knowledge about mediators and triggered pathways has contributed to a better understanding of the interaction between the gut-brain axis and the brain-gut axis. Intestinal bacteria produce neuroactive compounds and can modulate neuronal function, which affects behavior after an ischemic stroke. In addition, intestinal microorganisms affect host metabolism and immune status, which in turn affects the neuronal network in the ischemic brain. Here we discuss the latest results of animal and human research on two-way communication along the gut-brain axis in an ischemic stroke. Moreover, several reports have revealed the impact of an ischemic stroke on gut dysfunction and intestinal dysbiosis, highlighting the delicate play between the brain, intestines and microbiome after this acute brain injury. Despite our growing knowledge of intestinal microflora in shaping brain health, host metabolism, the immune system and disease progression, its therapeutic options in an ischemic stroke have not yet been fully utilized. This review shows the role of the gut microflora-brain axis in an ischemic stroke and assesses the potential role of intestinal microflora in the onset, progression and recovery post-stroke.

scholarly journals Minor alterations in the intestinal microbiota composition upon Rotavirus infection do not affect susceptibility to DSS colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kedir Hussen Hamza ◽  
Emma Dunér ◽  
Isabel Ulmert ◽  
Armando Arias ◽  
Daniel Sorobetea ◽  
...  
Keyword(s):  
Dextran Sulfate ◽  
Intestinal Barrier ◽  
Intestinal Microbiome ◽  
Enteric Infection ◽  
Intestinal Integrity ◽  
Dss Colitis ◽  
Causative Factors ◽  
Intestinal Immune System ◽  
Inflammatory Bowel ◽  
The Impact

AbstractViral triggers at the intestinal mucosa can have multiple global effects on intestinal integrity, causing elevated intestinal barrier strength and relative protection from subsequent inflammatory bowel disease (IBD) induction in various models. As viruses can interfere with the intestinal immune system both directly and indirectly through commensal bacteria, cause-effect relationships are difficult to define. Due to the complexity of putatively causative factors, our understanding of such virus-mediated protection is currently very limited. We here set out to better understand the impact that adult enteric infection with rotavirus (RV) might have on the composition of the intestinal microbiome and on the severity of IBD. We found that RV infection neither induced significant long-lasting microbiota community changes in the small or large intestine nor affected the severity of subsequent dextran sulfate sodium-induced colitis. Hence, adult murine RV infection does not exert lasting effects on intestinal homeostasis.

scholarly journals Oral Ferric Maltol Does Not Adversely Affect the Intestinal Microbiome of Patients or Mice, But Ferrous Sulphate Does

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2269
Author(s):  
Awad Mahalhal ◽  
Alessandra Frau ◽  
Michael D. Burkitt ◽  
Umer Z. Ijaz ◽  
Christopher A. Lamb ◽  
...  
Keyword(s):  
Ferrous Sulphate ◽  
Sodium Sulphate ◽  
Intestinal Microbiome ◽  
Dextran Sodium Sulphate ◽  
Principal Coordinates Analysis ◽  
Statistical Inferences ◽  
Principal Coordinates ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Measurable Change

Background and Aims: Altering dietary ferrous sulphate (FS) consumption exacerbates a murine model of colitis and alters the intestinal microbiome. We investigated the impact of oral ferric maltol (FM) and FS on mice with dextran sodium sulphate (DSS) induced colitis, and the microbiome of patients with iron deficiency. Methods: Mice had acute colitis induced, with 2% DSS for 5 days, followed by water. During this period, groups of mice were fed standard chow (200 ppm iron, SC, n = 8), or SC with 200ppm FS supplementation (n = 16, FSS), or SC with 200 ppm FM supplementation (n = 16, FMS). Clinical, pathological and microbiome assessments were compared at days 1 and 10. Fecal bacterial gDNA was extracted and the microbiome assessed by sequencing. Statistical inferences were made using MacQIIME. Principal Coordinates Analysis were used to visualize beta-diversity cluster analysis. Ten patients with IDA were treated with FS, and six with inactive inflammatory bowel disease received FM, supplements for four weeks: pre- and mid-treatment fecal samples were collected: the microbiome was assessed (see above). Results: In mice, after DSS treatment, there was a decrease in many genera in the SC and FSS groups: Lactobacillales increased in mice that received FMS. In humans, FS treatment led to an increase in five genera, but FM was not associated with any measurable change. The severity of DSS-induced colitis was greater with FSS than FMS. Conclusions: This study demonstrates differential and unique influences of ferric maltol and ferrous sulphate supplements on intestinal microbiota. These differences might contribute to the different side effects associated with these preparations.

scholarly journals Deleterious Genetic Variation Across the NOD Signaling Pathway Is Associated With Reduced NFKB Signaling Transcription and Upregulation of Alternative Inflammatory Transcripts in Pediatric Inflammatory Bowel Disease

2022 ◽  
Author(s):  
James J Ashton ◽  
Konstantinos Boukas ◽  
Imogen S Stafford ◽  
Guo Cheng ◽  
Rachel Haggarty ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Intestinal Bacteria ◽  
Genomic Variation ◽  
Gene Score ◽  
Diagnostic Endoscopy ◽  
Pediatric Inflammatory Bowel Disease ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Background Inflammatory bowel disease may arise with inadequate immune response to intestinal bacteria. NOD2 is an established gene in Crohn’s disease pathogenesis, with deleterious variation associated with reduced NFKB signaling. We hypothesized that deleterious variation across the NOD2 signaling pathway impacts on transcription. Methods Treatment-naïve pediatric inflammatory bowel disease patients had ileal biopsies for targeted autoimmune RNA-sequencing and blood for whole exome sequencing collected at diagnostic endoscopy. Utilizing GenePy, a per-individual, per-gene score, genes within the NOD signaling pathway were assigned a quantitative score representing total variant burden. Where multiple genes formed complexes, GenePy scores were summed to create a “complex” score. Normalized transcript expression of 95 genes within this pathway was retrieved. Regression analysis was performed to determine the impact of genomic variation on gene transcription. Results Thirty-nine patients were included. Limited clustering of patients based on NOD signaling transcripts was related to underlying genomic variation. Patients harboring deleterious variation in NOD2 had reduced NOD2 (β = -0.702, P = 4.3 × 10-5) and increased NFKBIA (β = 0.486, P = .001), reflecting reduced NFKB signal activation. Deleterious variation in the NOD2-RIPK2 complex was associated with increased NLRP3 (β = 0.8, P = 3.1475 × 10-8) and TXN (β = -0.417, P = 8.4 × 10-5) transcription, components of the NLRP3 inflammasome. Deleterious variation in the TAK1-TAB complex resulted in reduced MAPK14 transcription (β = -0.677, P = 1.7 × 10-5), a key signal transduction protein in the NOD2 signaling cascade and increased IFNA1 (β = 0.479, P = .001), indicating reduced transcription of NFKB activators and alternative interferon transcription in these patients. Conclusions Data integration identified perturbation of NOD2 signaling transcription correlated with genomic variation. A hypoimmune NFKB signaling transcription response was observed. Alternative inflammatory pathways were activated and may represent therapeutic targets in specific patients.

scholarly journals N12 An evaluation of the impact of IBDoc in clinical practice 5 years after introduction

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S662-S663
Author(s):  
K Sugrue ◽  
S Gleeson ◽  
J McCarthy ◽  
M Buckley
Keyword(s):  
Clinical Practice ◽  
Medical Therapy ◽  
Fast Track ◽  
Medication Compliance ◽  
Cost Savings ◽  
University Hospital ◽  
Faecal Calprotectin ◽  
Track System ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Background Faecal Calprotectin is a well-established biomarker to measure the level of inflammation in the gut. Assessment of calprotectin is important to measure disease activity, effectiveness of treatments as well as predicting relapses in inflammatory bowel disease (IBD). IBDoc® allows reliable testing of faecal calprotectin using a smartphone at home. IBDoc® was introduced at Mercy University Hospital in 2014 and now has 733 users. It has proved hugely popular with patients, has increased medication compliance and promoted self management. The objective of this study was to evaluate the impact of IBDoc® in clinical practice. Methods IBDoc® results were monitored over a 6 month period. A total of 240 tests were performed by patients with IBD (age 18–52 years). The results were evaluated to determine suitable clinical interventions, fast track clinic appointments, urgent colonoscopies, change of medical therapy and suitability for Virtual Clinics (VC’s). Results Of the 240 tests performed 40% had a normal result, 40% were moderate and 20% were high. All of the normal results avoided clinic appointments which freed up clinic time for patients with active disease and resulted in cost savings for the hospital. 70% of these patients were deemed suitable for future Virtual Clinics which resulted in further cost savings and freed up Consultant time. The majority of patients 60% had moderate or high results. The 20% of results that were high were all booked for urgent colonoscopy. All of the moderate results were fast tracked to clinic and 20% of these had a change of medical therapy. Conclusion This study shows the benefits of using IBDoc® in clinical practice. It is central to facilitating a fast track system for patients which results in better outcomes for patients.

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