Brazil Partnering Award: Influence of gut microbiota derived short chain fatty acids on intestinal immunity

Lead Research Organisation: Babraham Institute
Department Name: Nuclear Dynamics

Abstract

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Publications

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Description The primary purpose of this award to stimulate and foster collaborations between various groups in Sao paulo State, Brazil, and groups at the Babraham Institute. The award facilited collaborations bteween the group of Marc Veldhoen and Niels Olsen Saraiva Camara, Brazil. This award was instrumental to forge a successful collaboration between the group of Marco Vinolo (University of Campinas, Brazil) and Patrick Varga-Weisz. Therefore, the primary purpose of this award was fullfilled very well so far. Furthermore, the award facilitated obtaining a BBSRC-FAPESP Pump Priming Award between Marco Vinolo and Varga-Weisz, which was important for us to obtain the data described below. The award faciliatetd a change of research direction in both my and Marco Vinolo's group that has now been well published (Fellows et al. Nat Comms, 2018). The gut is home to innumerable bacteria that are 'good bacteria' in that they help in digesting food, especially plant fibres. They also generate vitamines, help to fend off pathogenic bacteria and train and instruct the immune system. How these 'good bacteria' interact with the host is an important question for our understanding of health and disease. We provided new insights into this field through the discovery of a new mechanism by which the bacteria affect gene expression in the gut. The gut bacteria generate metabolites through their digestion of plant fibres. These metabolites are taking up by the gut cells. We showed new ways by which metabolites affect the packing of the host cells' genome which, in turn, affects gene regulation. I will provide a more detailed description of the outcomes in my return to the BBSRC-FAPESP Pump priming award, which resulted from the Brazil Partnering award. Award began November 2014. A workshop partially financed by the award took place in Sao Paulo, Brazil end of November 2014. The title of this workshop was:
"Nature versus Nurture: the Influence of Genes, Nutrition and the Microbiome on Immunity and Metabolism". We are currently organising a follow up workshop to be held in Brazil in the Summer 2018. I will also host another Brazilian researcher from the University of Campinas, Prof. Hosana Rodrigues, for seveal months starting in April 2018.
Exploitation Route I will provide a more detailed description of next steps in my return to the BBSRC-FAPESP Pump priming award, which resulted from the Brazil Partnering award.
Sectors Agriculture, Food and Drink,Education,Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://www.nature.com/articles/s41467-017-02651-5
 
Description FAPESP Pump-Priming Awards
Amount £13,500 (GBP)
Funding ID BB/N013565/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2015 
End 05/2017
 
Title Analysis of histone decrotonylation 
Description We describe a method to measure histone decrotonylation in vitro. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact We discovered that histone deacetylases (HDACs, more specifically class I HDACs) are also histone decrotonylases. This is important, as HDACs are important new drug targets in the fight against cancer. Our discovery may lead to more refined drug development. 
URL https://www.nature.com/articles/s41467-017-02651-5
 
Description Collaboration with Marc Veldhoen 
Organisation Babraham Institute
Department Lymphocyte Signalling
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution My team provided expertise in chromatin analysis, including genome-wide profiling of histone modifications. We also contributed expertise in transcriptome analysis.
Collaborator Contribution Marc Veldhoen established gut organoid culture for our lab and provided reagents for this.
Impact Our collaboration resulted in a joint authorship: Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Fellows R, et al., Nat Commun. 2018 Jan 9;9(1):105. doi: 10.1038/s41467-017-02651-5.
Start Year 2013
 
Description Collaboration with Niels Camara Olson (São Paulo University) 
Organisation University of Sao Paulo
Country Brazil 
Sector Academic/University 
PI Contribution Hosting a PhD student, visit to Mucosal Immunonlogy/Brazilian Society for Immunology meeting. Ongoing discussions for shared grant application. Mouse line was transferred to Brazil.
Collaborator Contribution .
Impact .
Start Year 2015
 
Description Collaboration with Professor Marco Aurelia Ramirez Vinolo and his lab, University of Campinas, Brazil 
Organisation State University of Campinas
Department Institute of Biology
Country Brazil 
Sector Academic/University 
PI Contribution As a result of meeting through the BBSRC-Brazil Partnering Award, my lab and the lab of Marco Vinolo set up a collaboration, in part funded through a BBSRC-FAPESP Pump priming Award. In this collaboration, my lab defined the overall research agenda, which was the elucidation of the link between the microbiota in the gut and gene regulation through histone modifications. My team and I provided the expertise in chromatin biology, histone modifications and the initial observation that have been generated, in aprt, in collaboration with Dr Tiziana Bonald, Italy. We also provided expertise in genome-wide chromatin and gene expression analysis. I also largely wrote the manuscript that was generated through this collaboration:Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases R Fellows etal., Nature communications 9 (1), 105; 10.1038/s41467-017-02651-5.
Collaborator Contribution The lab of Prof. Marco Vinolo provided expertise regarding then role and analysis of short chain fatty acids and manipulation of microbiota in mice. This expertise was pivotal for our work examining the role of microbiota in shaping chromatin and gene expression in the colon epithelium. Therefore, the BBSRC-Brazil partnering award was instrumental and succeeded in its aim to foster a productive collaboration between UK and Brazilian scientists.
Impact This collaboration resulted in a publication in Nature Communications that elicited much attention, as indicated by its current Altmetric score of 273: Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nat Commun. 2018 Jan 9;9(1):105. doi: 10.1038/s41467-017-02651-5.
Start Year 2015
 
Description Radio Interview at BBC 3 Cambridgeshire 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Radio Interviews of PhD student Rachel Fellows from the Varga-Weisz lab concerning her research on gut microbiota and gene regulation, in the wake of the publication of her paper.
Year(s) Of Engagement Activity 2018