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Lactobacillus rhamnosus GG supplementation modulates the gut microbiota to promote butyrate production, protecting against deoxynivalenol exposure in nude mice.

鼠李糖乳杆菌 GG 补充剂调节肠道菌群促进丁酸生成,保护裸鼠免受脱氧雪腐镰刀菌烯醇暴露。

  • 影响因子:4.42
  • DOI:10.1016/j.bcp.2020.113868
  • 作者列表:"Lin R","Sun Y","Mu P","Zheng T","Mu H","Deng F","Deng Y","Wen J
  • 发表时间:2020-02-20

:Deoxynivalenol (DON) is the most common mycotoxin in grains, and DON exposure causes gastrointestinal inflammation and systemic immunosuppression. The immunosuppression caused by DON has raised serious concerns about whether it is safe to use probiotics in immunocompromised hosts. Gut microbiota remodeling by Lactobacillus is a potential effective strategy to prevent DON exposure. The athymic nude mice were chose as the model of immunocompromised animals. We tested the effect of the probiotic Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus (LA) supplementation on host protection against DON exposure and the underlying mechanisms in nude mice. DON exposure induced endoplasmic reticulum (ER) stress and impaired intestinal barrier function and microbiota, which were relieved by LGG supplementation but not LA supplementation. LGG supplementation significantly enhanced the intestinal barrier function, increased the body weight and the survival rate in nude mice that exposed to DON for two weeks. Furthermore, LGG supplementation modulated the gut microbiota by increasing the abundance of Bacteroidetes and the levels of the butyrate-producing genes But and Buk to promote butyrate production. Butyrate inhibited the IRE1α/XBP1 signaling pathway to reduce DON-induced intestine injury. In conclusion, LGG supplementation modulated the gut microbiota to promote butyrate production, protecting against DON exposure in nude mice. Both LGG and butyrate show promise for use in protecting against DON exposure.


: 脱氧雪腐镰刀菌烯醇 (DON) 是谷物中最常见的霉菌毒素,DON 暴露引起胃肠道炎症和全身免疫抑制。DON 引起的免疫抑制引起了人们对在免疫功能低下的宿主中使用益生菌是否安全的严重担忧。乳酸杆菌的肠道菌群重塑是防止 DON 暴露的潜在有效策略。选择无胸腺裸鼠作为免疫低下动物模型。我们在裸鼠中测试了益生菌鼠李糖乳杆菌 GG (LGG) 或嗜酸乳杆菌 (LA) 补充对宿主保护免受 DON 暴露的影响以及潜在机制。DON 暴露诱导内质网 (ER) 应激和肠屏障功能和微生物群受损,通过补充 LGG 而不是补充 LA 缓解。在暴露于 DON 两周的裸鼠中,补充 LGG 可显著增强肠屏障功能,增加体重和存活率。此外,LGG 补充通过增加拟杆菌的丰度和产生丁酸的基因 But 和 Buk 的水平来调节肠道菌群,以促进丁酸的产生。丁酸盐抑制 ire1 α/XBP1 信号通路减轻 DON 诱导的肠损伤。总之,补充 LGG 调节肠道菌群促进丁酸生成,保护裸鼠免受 DON 暴露。LGG 和丁酸盐都显示出用于防止 DON 暴露的前景。



来源期刊:The FEBS journal
作者列表:["Sayed IM","Suarez K","Lim E","Singh S","Pereira M","Ibeawuchi SR","Katkar G","Dunkel Y","Mittal Y","Chattopadhyay R","Guma M","Boland BS","Dulai PS","Sandborn WJ","Ghosh P","Das S"]

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.

作者列表:["Prathapan KM","Ramos Rivers C","Anderson A","Koutroumpakis F","Koutroubakis IE","Babichenko D","Tan X","Tang G","Schwartz M","Proksell S","Johnston E","Hashash JG","Dunn M","Wilson A","Barrie A","Harrison J","Hartman D","Kim SC","Binion DG"]

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.

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作者列表:["Ronchetti S","Gentili M","Ricci E","Migliorati G","Riccardi C"]

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.

关键词: GILZ IBD 自身免疫 炎症
翻译标题与摘要 下载文献