ABSTRACT
Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain-gut interactions, but their role in microbiota-neuro-immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut-neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.
Subject(s)
Caspase 1/physiology , Gastrointestinal Microbiome , Inflammasomes/immunology , Inflammation/complications , Neuroimmunomodulation , Visceral Pain/pathology , Animals , Anti-Bacterial Agents/pharmacology , Brain/drug effects , Brain/immunology , Brain/microbiology , Brain/pathology , Capsaicin/toxicity , Colon/drug effects , Colon/immunology , Colon/microbiology , Colon/pathology , Female , Inflammasomes/drug effects , Inflammation/immunology , Inflammation/microbiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Signal Transduction , Visceral Pain/etiology , Visceral Pain/metabolismABSTRACT
INTRODUCTION: Cadaveric studies provide a means of safely assessing new technologies and optimizing scanning prior to clinical validation. Reducing radiation exposure in a clinical setting can entail incremental dose reductions to avoid missing important clinical findings. The use of cadavers allows assessment of the impact of more substantial dose reductions on image quality. Our aim was to identify a suitable low-dose abdominopelvic CT protocol for subsequent clinical validation. METHODS: Five human cadavers were scanned at one conventional dose and three low-dose settings. All scans were reconstructed using three different reconstruction algorithms: filtered back projection (FBP), hybrid iterative reconstruction (60% FBP and 40% adaptive statistical iterative reconstruction (ASIR40)), and model-based iterative reconstruction (MBIR). Two readers rated the image quality both quantitatively and qualitatively. RESULTS: Model-based iterative reconstruction images had significantly better objective image noise and higher qualitative scores compared with both FBP and ASIR40 images at all dose levels. The greatest absolute noise reduction, between MBIR and FBP, of 34.3 HU (equating to a 68% reduction) was at the lowest dose level. MBIR reduced image noise and improved image quality even in CT images acquired with a mean radiation dose reduction of 62% compared with conventional dose studies reconstructed with ASIR40, with lower levels of objective image noise, superior diagnostic acceptability and contrast resolution, and comparable subjective image noise and streak artefact scores. CONCLUSION: This cadaveric study demonstrates that MBIR reduces image noise and improves image quality in abdominopelvic CT images acquired with dose reductions of up to 62%.
