The Natural History of IBD: Lessons Learned

Weimers, Petra; Munkholm, Pia

doi:10.1007/s11938-018-0173-3

Cited by 38 publications

(34 citation statements)

References 108 publications

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“…A common misconception is that NEC is quite simply Crohn's disease as seen in the premature infant. Although NEC does share some pathogenetic similarities with inflammatory bowel disease—including an associative role for a dysbiotic microbiome, an imbalance between proinflammatory and anti-inflammatory cells in the intestinal mucosa, a genetic predisposition, and a predilection for the terminal ileum and cecum 45 , 46 , 47 —the 2 diseases are very different. Specifically, Crohn's disease is characterized by the full-thickness involvement of parts of the small and large intestine, is a relapsing condition that may be associated with fistularization, is not associated with intestinal necrosis, and rarely is associated with sepsis or death.…”

Section: Why Nec Is Not Just Inflammatory Bowel Disease In Premature mentioning

confidence: 99%

Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis

Hackam

Sodhi

2018

Cellular and Molecular Gastroenterology and Hepatology

129

134

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Necrotizing enterocolitis (NEC) remains the leading cause of death from gastrointestinal disease in premature infants and attacks the most fragile patients at a time when they appear to be the most stable. Despite significant advances in our overall care of the premature infant, NEC mortality remains stubbornly high. There is no specific treatment for NEC beyond broad-spectrum antibiotics and intestinal resection, and current efforts have focused on preventive strategies. Over the past decade, we have proposed a unifying hypothesis to explain the pathogenesis of NEC in premature infants that suggests that NEC develops in response to an imbalance between exaggerated proinflammatory signaling in the mucosa of the premature gut leading to mucosal injury, which is not countered effectively by endogenous repair processes, and in the setting of impaired mesenteric perfusion leads to intestinal ischemia and disease development. One of the most important pathways that mediates the balance between injury and repair in the premature intestine, and that plays a key role in NEC pathogenesis, is Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide on gram-negative bacteria. This review focuses on the role that the TLR4-mediated imbalance between proinflammatory and anti-inflammatory signaling in the premature intestinal epithelium leads to the development of NEC, and will explore how an understanding of the role of TLR4 in NEC pathogenesis has led to the identification of novel preventive or treatment approaches for this devastating disease.

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Section: Why Nec Is Not Just Inflammatory Bowel Disease In Premature mentioning

confidence: 99%

Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis

Hackam

Sodhi

2018

Cellular and Molecular Gastroenterology and Hepatology

129

134

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“…1 IBD cause a significant impairment of the patient's healthrelated quality of life, leading to persistent diarrhea, abdominal pain, fatigue, and even colorectal cancer. 2 The exact etiology of IBD is still unclear, but dysfunctional immune responses of the gut, in connection with an individual's genetic predisposition and many environmental triggers, is thought as the main culprit. 3 Oxidative stress contributes a great part to immune activation and mucosal injury in the pathogenesis of IBD, and therefore antioxidants are being taken into account when designing novel anti-IBD therapies.…”

Section: Introductionmentioning

confidence: 99%

<p>Platinum Nanoparticles As A Therapeutic Agent Against Dextran Sodium Sulfate-Induced Colitis In Mice</p>

Zhu

Zeng²,

Feng³

et al. 2019

IJN

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Purpose: This study aimed to evaluate the anti-colitis potential of platinum nanoparticles (PtNPs). Materials and methods: 5-, 30-and 70-nm PtNPs were administered to C57BL/6 mice once daily by intragastric gavage for 8 d during and after 5-d dextran sodium sulfate treatment. Results: According to body weight change, stool blood and consistency, and colon length and histopathology, PtNPs size-dependently alleviated DSS-induced murine colitis. PtNPs enhanced gut-barrier function by upregulating the colonic expressions of heat-shock protein 25 and tight junction proteins. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of white blood cells, PtNPs attenuated colonic and systemic inflammation. By suppressing lipopolysaccharide-triggered production of proinflammatory mediators, including nitric oxide, tumor necrosis factor-α and interleukin-6, PtNPs exerted direct anti-inflammatory activities in RAW264.7 macrophages through a mechanism involving intracellular reactive oxygen species scavenging and Toll-like receptor 4/NF-κB signaling suppression. High-throughput 16S rRNA sequencing of fecal samples unveiled that PtNPs induced gut dysbiosis by unfavorably altering α-diversity, Firmicutes/Bacteroidetes ratio, and richness of certain specific bacteria. Conclusion: PtNPs are a promising anti-colitis agent, but may negatively impact gut-microbiota.

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“…This is so far unsettled due to the lack of long-term studies. [22][23][24] There is increasing knowledge of the pathophysiological events mediating the mucosal inflammation in IBD including cytokine and chemokine responses. 25, 26 So far there are few reports on how these crucial mediators can be used as biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis

Florholmen

Johnsen

Renate

et al. 2020

Preprint

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Background There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. Methods Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004–2014, followed by a validation study from 2014–2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts. Results We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54. Conclusions The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.

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The Natural History of IBD: Lessons Learned

Cited by 38 publications

References 108 publications

Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis

Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis

<p>Platinum Nanoparticles As A Therapeutic Agent Against Dextran Sodium Sulfate-Induced Colitis In Mice</p>

Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis

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