scholarly journals Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling

2016 ◽  
Vol 10 (10) ◽  
pp. 2389-2404 ◽  
Author(s):  
Nicholas Edward Ilott ◽  
Julia Bollrath ◽  
Camille Danne ◽  
Chris Schiering ◽  
Matthew Shale ◽  
...  

Abstract The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess modifications to both bacterial community structure and transcriptional activity in a mouse model of colitis. By using transcriptomic analysis of colonic tissue and luminal RNA derived from the host, we have also characterised how host transcription relates to the microbial transcriptional response in inflammation. In colitis, increased abundance and transcription of diverse microbial gene families involved in responses to nutrient deprivation, antimicrobial peptide production and oxidative stress support an adaptation of multiple commensal genera to withstand a diverse set of environmental stressors in the inflammatory environment. These data are supported by a transcriptional signature of activated macrophages and granulocytes in the gut lumen during colitis, a signature that includes the transcription of the key antimicrobial genes S100a8 and S100a9 (calprotectin). Genes involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase were identified as changing to a greater extent at the level of transcription than would be predicted by DNA abundance changes, implicating a role for increased oxygen tension and/or host-derived reactive oxygen species in driving transcriptional changes in commensal microbes.

2019 ◽  
Vol 597 (9) ◽  
pp. 2361-2378 ◽  
Author(s):  
Vienna E. Brunt ◽  
Rachel A. Gioscia‐Ryan ◽  
James J. Richey ◽  
Melanie C. Zigler ◽  
Lauren M. Cuevas ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Rong Wang ◽  
Yongzheng Luo ◽  
Yadong Lu ◽  
Daojuan Wang ◽  
Tingyu Wang ◽  
...  

Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.


2019 ◽  
Vol 7 (8) ◽  
pp. 1008-1032 ◽  
Author(s):  
Fatouma Salem ◽  
Nadège Kindt ◽  
Julian R Marchesi ◽  
Patrick Netter ◽  
Anthony Lopez ◽  
...  

2016 ◽  
Vol 36 (4) ◽  
pp. 231-239 ◽  
Author(s):  
Francielli Licks ◽  
Renata Minuzzo Hartmann ◽  
Elizângela Schemitt ◽  
Josieli Raskopf Colares ◽  
Lúcio Sarubbi Fillmann ◽  
...  

2017 ◽  
Vol 21 (5) ◽  
pp. 603-610.e3 ◽  
Author(s):  
Ashwin N. Ananthakrishnan ◽  
Chengwei Luo ◽  
Vijay Yajnik ◽  
Hamed Khalili ◽  
John J. Garber ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Anna Socha-Banasiak ◽  
Patrycja Sputa-Grzegrzółka ◽  
Jędrzej Grzegrzółka ◽  
Krzysztof Pacześ ◽  
Piotr Dzięgiel ◽  
...  

Immunological disorders, increased oxidative stress, and damage to the epithelial barrier play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). In the treatment of patients with Crohn’s disease (CD) and ulcerative colitis (UC), it is increasingly common to use biological drugs that selectively affect individual components of the inflammatory cascade. However, administering the medicines currently available does not always result in obtaining and maintaining remission, and it may also lead to the development of resistance to a given agent over time. Metallothioneins (MTs) belong to the group of low molecular weight proteins, which, among others, regulate the inflammation and homeostasis of heavy metals as well as participating in the regulation of the intensity of oxidative stress. The results of the studies conducted so far do not clearly indicate the role of MTs in the process of inflammation in patients with IBD. However, there are reports that suggest the possibility of using MTs as a potential target in the treatment of this group of patients.


2020 ◽  
Author(s):  
Jun Miyoshi ◽  
Sonny T. M. Lee ◽  
Megan Kennedy ◽  
Mora Puertolas ◽  
Mary Frith ◽  
...  

AbstractBackground & AimsInflammatory bowel diseases (IBD) are chronic inflammatory disorders where predictive biomarkers for the disease development and clinical course are sorely needed for development of prevention and early intervention strategies that can be implemented to improve clinical outcomes. Since gut microbiome alterations can reflect and/or contribute to impending host health changes, we examined whether gut microbiota metagenomic profiles would provide more robust measures for predicting disease outcomes in colitis-prone hosts.MethodsUsing the IL-10 gene-deficient (IL-10 KO) murine model where early life dysbiosis from antibiotic (cefoperozone, CPZ) treated dams vertically-transferred to pups increases risk for colitis later in life, we investigated temporal metagenomic profiles in the gut microbiota of post-weaning offspring and determined their relationship to eventual clinical outcomes.ResultsCompared to controls, offspring acquiring maternal CPZ-induced dysbiosis exhibited a restructuring of intestinal microbial membership both in bacteriome and mycobiome that were associated with alterations in specific functional subsystems. Furthermore, among IL-10 KO offspring from CPZ-treated dams, several functional subsystems, particularly nitrogen metabolism, diverged between mice that developed spontaneous colitis (CPZ-colitis) versus those that did not (CPZ-no-colitis) at a time point prior to eventual clinical outcome.ConclusionsOur findings provide support that functional metagenomic profiling of gut microbes has potential and promise meriting further study for development of tools to assess risk and manage human IBD.SynopsisCurrently, predictive markers for the development and course of inflammatory bowel diseases (IBD) are not available. This study supports the notion that gut microbiome metagenomic profiles could be developed into a useful tool to assess risk and manage human IBD.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Sijing Cheng ◽  
Jun Hu ◽  
Xianrui Wu ◽  
Na Jiao ◽  
Yichen Li ◽  
...  

2016 ◽  
Vol 157 (45) ◽  
pp. 1781-1785 ◽  
Author(s):  
Iván Péter ◽  
Anna Jagicza ◽  
Zénó Ajtay ◽  
István Kiss ◽  
Balázs Németh

Psoriasis is among the most common dermatological diseases worldwide. Its significance is emphasized by adverse effects on quality of life, caused by chronic pain, physical and psychical disability due to psoriatic plaques. Besides the development of psoriatic arthritis, which often causes permanent joint damage, former studies revealed an increased risk of inflammatory bowel disease, cardiovascular disease and certain types of cancer. Genetic predisposition and oxidative stress caused by exogenous and endogenous factors can contribute to abnormal differentiation and hyperproliferation of keratinocytes, accordingly the development and maintenance of psoriasis. Moreover, excessive oxidative stress can be responsible for the onset of psoriasis complications. After a brief pathophysiological summary the authors discuss the role of oxidative stress in the development of psoriasis and its complications through several well studied biomarkers (asymmetric dimethylarginine, malondialdehyde, superoxide dismutase, catalase). Orv. Hetil., 2016, 157(45), 1781–1785.


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