- 作者列表："Ducray HAG","Globa L","Pustovyy O","Roberts MD","Rudisill M","Vodyanoy V","Sorokulova I
AIMS:To characterize efficacy of the Bacillus subtilis BSB3 (BSB3) strain in the prevention of excessive exercise-induced side effects and in maintaining stability of the gut microbiota. METHODS AND RESULTS:Rats were pretreated by oral gavage with B. subtilis BSB3 (BSB3) or with phosphate-buffered saline (PBS) twice a day for 2 days, and were either exposed forced treadmill running or remained sedentary. Histological analysis of intestine, immunofluorescence staining of tight junction (TJ) proteins, serum lipopolysaccharide and intestinal fatty acid-binding protein assay, culture-based analysis and pyrosequencing for the gut microbiota were performed for each rat. Forced running resulted in a substantial decrease in intestinal villi height and total mucosa thickness, the depletion of Paneth cells, an inhibition of TJ proteins expression. Short-term treatment of rats with BSB3 before running prevented these adverse effects. Culture-based analysis of the gut microbiota revealed significant elevation of pathogenic microorganisms only in treadmill-exercised rats pretreated with PBS. High-throughput 16S rRNA gene sequencing also revealed an increase in pathobionts in this group. Preventive treatment of animals with BSB3 resulted in predominance of beneficial bacteria. CONCLUSIONS:BSB3 prevents excessive exercise-associated complications by beneficial modulation of the gut microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY:Our study shows a new application of beneficial bacteria for prevention the adverse effects of excessive exercise.
目的: 表征枯草芽孢杆菌 BSB3 (BSB3) 菌株在预防过度运动引起的副作用和维持肠道菌群稳定方面的功效。 方法和结果: 大鼠经口灌胃 B.枯草杆菌 BSB3 (BSB3) 或用磷酸盐缓冲盐水 (PBS)，每天两次，持续 2 天，要么暴露于强制跑台，要么保持久坐不动。肠组织学分析，紧密连接 (TJ) 蛋白免疫荧光染色，血清脂多糖和肠脂肪酸结合蛋白测定,对每只大鼠进行基于培养的分析和肠道菌群的焦磷酸测序。强迫跑步导致肠绒毛高度和总粘膜厚度大幅下降，潘氏细胞耗竭，抑制 TJ 蛋白表达。跑步前用 BSB3 短期治疗大鼠可预防这些不良反应。基于培养的肠道菌群分析显示，仅在用 PBS 预处理的跑台运动大鼠中，病原微生物显著升高。高通量 16S rRNA 基因测序也揭示了该组中致病基因的增加。用 BSB3 对动物进行预防性治疗，导致有益菌占优势。 结论: BSB3 通过有益的肠道菌群调节防止过度运动相关的并发症。 研究的意义和影响: 我们的研究显示了有益细菌的新应用，用于预防过度运动的不良影响。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.