Determinants of microbe-host responses in the gut across life

Lead Research Organisation: Institute of Food Research
Department Name: Contracts

Abstract

To probe specific mechanistic aspects of the gut microbiome's positive influence on health throughout life, we have developed a systems-level experimental approach. We will use innovative in vivo, in vitro, and in silico tools/models in tandem with a key longitudinal cohort (pregnancy and early life) to define and refine novel intervention strategies that will promote gut health. Our multi-disciplinary research theme managed by QIB and university research leaders, maps to three objectives. These objectives will determine how microbes (bacterial, viral, fungal) establish and maintain a balanced community that modulates host homeostatic cross-talk within the gut.
This theme involves a 250-particpant longitudinal population study of pregnancy mothers and their infants, up to 2 years of age.
Theme 1 focusses on the gut during the very first stages of life, and in the elderly, and will seek to unravel: (i) how pioneer/keystone microbial species facilitate healthy development (ii) which microbial mediators modulate microbe-microbe and microbe-host cross-talk and (iii) bi-directional immune system-microbiota interactions within the gut.
Theme 1 Outputs
• identification of critical pre- and post-natal periods for establishing a healthy intestinal microbiome and the contribution that host and environmental factors play
• define molecular mediators of microbe-microbe and microbe-host crosstalk important in microbial ecology and establishing tolerance
Our integrated plan of work will ultimately determine microbiome- and host-associated pathways that could represent key targets for lifestyle changes and therapies that reduce the incidence and burden of infectious, metabolic, and immune-mediated conditions.

Publications

10 25 50
 
Title Guardians of the Gut Exhibit 
Description "Guardians of the Gut": 6-meter-long, 2-meter-high gut, with internal game stations which allowed visitors to interact with their 'microbes 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2018 
Impact This exhbit has been shown at the Royal Society Summer Exhibition and Norwich Science Festivals 2018 
 
Description Membership of R&D Executive Committee influencing educational and research policy updated annually
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
 
Description UK Government PostNote
Geographic Reach National 
Policy Influence Type Citation in other policy documents
URL https://researchbriefings.parliament.uk/ResearchBriefing/Summary/POST-PN-0574
 
Description CLRN Flexibility & Sustainability Research Funding
Amount £55,975 (GBP)
Funding ID RDFSF025 
Organisation London North West Healthcare NHS Trust 
Sector Hospitals
Country United Kingdom
Start 08/2018 
End 07/2019
 
Description Immune cell circuits and tissue compartmentalisation in control of intestinal inflammation and tumerigenesis
Amount £10,000 (GBP)
Funding ID Haematology R&D a/c RD027/L 
Organisation London North West Healthcare NHS Trust 
Sector Hospitals
Country United Kingdom
Start 01/2019 
End 12/2019
 
Description New antimicrobials to target gut pathogens
Amount £20,000 (GBP)
Funding ID 42907000B 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2018 
End 09/2023
 
Description Norwich Research Park Bioscience Doctoral Training Partnership
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 10/2020
 
Description Norwich Research Park Bioscience Doctoral Training Partnership
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2018 
End 10/2022
 
Description Norwich Research Park Bioscience Doctoral Training Partnership
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description Training interdisciplinary glycoscientists to get a molecular- level grip on glycocodes at the human mucosa-microbiota
Amount £466,300 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2019 
End 12/2022
 
Description Identifying signalling pathways regulating antimicrobial peptide production in the gut using network biology and organoid transcriptomics Modularity of signaling proteins and networks 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Identifying signalling pathways regulating antimicrobial peptide production in the gut using network biology and organoid transcriptomics Modularity of signaling proteins and networks
Year(s) Of Engagement Activity 2018
 
Description Investigating regulation of intestinal function by Bifidobacteria using network biology and organoid approaches, Microbes in Norwich 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Investigating regulation of intestinal function by Bifidobacteria using network biology and organoid approaches, Microbes in Norwich
Year(s) Of Engagement Activity 2019
 
Description 17-21 July 2017_2nd Interdisciplinary Signaling Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact In this interdisciplinary workshop advanced science was combined with informal summer activities to solve multi-disciplinary scientific questions, by bringing early career scientists together with more established researchers in a relaxing and beautiful location.

Invited speakers presented talks on the topics of cell regulation, network modelling, genomics, systems biology, bioinformatics, structural biology, biochemistry, and cheminformatics. Then, selected talks from other participants will be followed by multi-disciplinary teamwork sessions in the afternoon, followed by cultural and social activities, such as medieval team building and handicraft activities in the Visegrad Castle. Poster sessions and plenty of informal opportunities allowed the participants to discuss complex and exciting questions as well as develop new collaborations. The renaissance surroundings of the venue nicely matched with the interdisciplinary nature of the workshop.
Year(s) Of Engagement Activity 2017
URL http://signalingworkshop.org/
 
Description 24-25 April 2017_Multiscale analysis of host-microbe interactions in plants, animals and humans 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact The aim of this workshop was to bring together key experts and early-stage scientists working on host-microbe interactions, including pathogen infections, commensals and microbiome level studies, to share novel scientific ideas on the multiscale investigation of host-microbe interactions and to provide an exciting opportunity to establish and improve cross-disciplinary and UK-wide collaborations.

After kick off with three keynote speakers on current challenges, the program provides structured study groups to discuss 1) novel methodological approaches; 2) potential future projects requiring participants from different disciplines; 3) the best ways to get funding for such multi-disciplinary projects. We facilitated these goals with short presentations and brainstorming opportunities in coordinated team works, and with panel discussion with representatives of key relevant funding agencies and charities.
Year(s) Of Engagement Activity 2017
URL http://www.multiscalebiology.org.uk/events/event/multiscale-analysis-of-host-microbe-interactions/
 
Description 4th Annual European Microbiome Congress 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Attendance to 4th Annual European Microbiome Congress. This Conference has a high representation from the Industry: Pharmaceutical companies and Biotechnology companies and provided an excellent opportunity to make contact and discuss work relevant to the Institute Strategic Programmes. The PROMOTING WOMEN IN SCIENCE lunch session was inspiring.
Year(s) Of Engagement Activity 2018
 
Description Academia-Industry Networking CarboMet event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact I co-organised and chaired a two day workshop on 'The Role of Carbohydrates in the Gut Microbiome' June 2018 in Brussels attended by 40 delegates from academia and industry as apart of CarboMet. CarboMet (Metrology of Carbohydrates for European Bioindustries) is a four-year Coordination and Support Action (CSA) funded by Horizon 2020 FET-OPEN. It is an European Network that facilitates engagement between key players and stakeholders of the glycoscience community across Europe to identify the current state of the art and in particular future innovation and technological challenges in carbohydrate metrology. I co-wrote and edited the CarboMet positioning paper on 'The Essential Roles of Carbohydrates in Promoting Gut Microbiota Function Through All Stages of Life' which summarises discussions that took place during the workshop.
Year(s) Of Engagement Activity 2018
URL https://carbomet.eu/news/positioning-paper-on-role-of-carbohydrates-in-gut-microbiota-function/
 
Description Analysing intestinal organoids in a multi-omics, systems biology framework to investigate gut health and host-microbe interactions Scientific Advisory Board Meeting Earlham Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Analysing intestinal organoids in a multi-omics, systems biology framework to investigate gut health and host-microbe interactions Scientific Advisory Board Meeting Earlham Institute
Year(s) Of Engagement Activity 2019
 
Description Analyzing intestinal organoids in a multi-omics, systems biology framework to investigate gut health and host-microbe interactions SYSBIO 2018 - Advanced Lecture Course on Systems Biology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Analyzing intestinal organoids in a multi-omics, systems biology framework to investigate gut health and host-microbe interactions SYSBIO 2018 - Advanced Lecture Course on Systems Biology
Year(s) Of Engagement Activity 2019
 
Description Annual Aberdeen University Microbiology Schools Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talk to approx 150 17-18 year old school children about important of the gut microbiome and also gave a career talk. Feedback received was very positive with students thinking about microbiology as a degree.
Year(s) Of Engagement Activity 2018
 
Description Article for the 'Microbiologist' 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact Article written for SfAM magazine 'Microbiologist': First Contact: The importance of the early life microbiota
Year(s) Of Engagement Activity 2018
 
Description BIA Webinar 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Arjan Narbad, Lindsay Hall and Alan Walker gave a live BIA webinar to industry members. the webinar was then published on You tube that everyone can access. The title of the Webinar was Developing, feeding and restoring the human microbiome' where Dr Lindsay Hall explained 'Early Life Microbiota' , Dr Alana Walker presented 'Diet and the gut microbiota' and Professor Arjan Narbad gave a presentation on 'Restoring the gut microbiome
using FMT' more than 370 people have now seen the webinar.
Year(s) Of Engagement Activity 2018
URL https://www.youtube.com/watch?v=OtcoxvQvG34
 
Description BIA Webinar: Developing, feeding and restoring the human microbiome 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact BIA Webinar: Developing, feeding and restoring the human microbiome. In an interactive webinar with questions from industrial representatives.
Year(s) Of Engagement Activity 2018
 
Description Comparative analysis of Paneth cell and enteroendocrine cell transcriptomics: organoid and signalling network based approaches Research in progress talk at Quadram Institute. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Comparative analysis of Paneth cell and enteroendocrine cell transcriptomics: organoid and signalling network based approaches
Research in progress talk at Quadram Institute.
Year(s) Of Engagement Activity 2019
 
Description IBCarb 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Contributed to the final IBCarb workshop Glycobiotechnology 2018. IBCarb (Glycoscience Tools for Biotechnology and Bioenergy) is a growing network of glycoscientists from academia and industry. IBCarb was one of the Networks in Industrial Biotechnology and Bioenergy funded by the BBSRC. The workshop was very successful and attracted around 150 attendees (international audience from academia and industry) . This was an opportunity to showcase the Glycosciences carried out in the UK and in partnership with industrial/business partners.
Year(s) Of Engagement Activity 2018
URL https://ibcarb.com/events/
 
Description Identification of master regulators in goblet cells and Paneth cells using transcriptomics profiling of gut organoids and multi-layered networks. QIB Research in Progress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Identification of master regulators in goblet cells and Paneth cells using transcriptomics profiling of gut organoids and multi-layered networks. QIB Research in Progress
Year(s) Of Engagement Activity 2019
 
Description Interviewed and quoted in BBC Future article 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Was interviewed and quoted in BBC Future article: What we and don't know about gut health
Year(s) Of Engagement Activity 2019
URL http://www.bbc.com/future/story/20190121-what-we-do-and-dont-know-about-gut-health
 
Description Introduction to Multiomics Data Integration 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Tamas Korcsmaros delivered a talk on the nature of different data types, and provided a training on Cytoscape
Year(s) Of Engagement Activity 2009,2018
URL https://www.ebi.ac.uk/training/events/2018/introduction-multiomics-data-integration-0
 
Description Microbiology Society 2018 selected talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact Dr Zoe Schofield was selected to give an oral short talk talk at the annual Microbiology Society Meeting (Birmingham 2018): Bifidobacterium breve stimulates immune development in germ-free mice
Year(s) Of Engagement Activity 2018
 
Description Norwich Science Festival 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Took our Guardians of the Gut exhibit to Norwich Science festival for 2-day event (26th-27th October).
Year(s) Of Engagement Activity 2018
URL https://norwichsciencefestival.co.uk/events/science-without-borders-day/
 
Description Organoid transcriptomics to study cell regulation Internal research presentation at the Earlham Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Organoid transcriptomics to study cell regulation Internal research presentation at the Earlham Institute
Year(s) Of Engagement Activity 2019
 
Description Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine Stem Cells @ Lunch, a fortnightly lunchtime seminar series, hosted by Dr. Davide Danovi at the Centre for Stem Cells & Regenerative Medicine at Guy's Hospital, King's College London, UK. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine Stem Cells @ Lunch, a fortnightly lunchtime seminar series, hosted by Dr. Davide Danovi at the Centre for Stem Cells & Regenerative Medicine at Guy's Hospital, King's College London, UK.
Year(s) Of Engagement Activity 2019
 
Description Pathway Analysis to Study the Effect of Bifidobacteria on Autophagy in the Intestine 2nd Interdisciplinary Signaling Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Pathway Analysis to Study the Effect of Bifidobacteria on Autophagy in the Intestine 2nd Interdisciplinary Signaling Workshop
Year(s) Of Engagement Activity 2017
 
Description Podcast for Economist 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Podcast with the 'Economist' about the gut microbiome and celiac disease
Year(s) Of Engagement Activity 2018
 
Description Policy publication by Microbiology Society 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Contributed to the publication of the Policy document by The Microbiology society. The aim was to To help the microbiology community to consider how it might best take advantage of the opportunities stemming from microbiome research. but at the same time the document woul dbe useful to the wider audience.
Year(s) Of Engagement Activity 2018
URL https://microbiologysociety.org/policy/microbiome-policy-project/unlocking-the-microbiome-report.htm...
 
Description Poster presentation: SignaLink 3, a tissue specific and extended multi-layered signaling network resource 2nd Interdisciplinary Signalling Workshop 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Fazekas D., Kadlecsik T., Sudhakar P., Modos D., Turei D., Csabai L., Gul L., Korcsmaros T. (2017) SignaLink 3, a tissue specific and extended multi-layered signaling network resource 2nd Interdisciplinary Signalling Workshop 2017
Year(s) Of Engagement Activity 2017
URL http://signalingworkshop.org/
 
Description Radio Interview for BBC Radio Norfolk 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Radio interview about our Guardians of the Gut exhibit and the microbiome - in response to the interview we had additional people visit the exhibit during the science festival
Year(s) Of Engagement Activity 2018
 
Description Royal Society Summer Exhibition 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Royal Society Summer Science Exhibition 2018 - Guardians of the Gut. Week long engagement with ~10,000 visitors.
We are fascinated about understanding how our resident gut microbes (i.e. the microbiota) impact our health, and we are particularly interested in what happens during early life. In our Guardians of the Gut exhibit we explore the amazing variety of microbes that colonise the gut right from the start, from their initial 'seeding', and where we get them from (exploring natural vs. C-section birth), and how specific types, e.g. Bifidobacterium, our favourite bacteria(!), act as Guardians of the Gut. We discuss how microbes play a key role in healthy development; helping to digest components of our food (breast or formula milk), and also how these microbes 'talk' to our immune cells. As these bacteria are so important for our wellbeing, we also explore how disturbing these early life microbial communities through e.g. antibiotics, can have short- and long-term consequences, and may predispose us to chronic diseases such as Ulcerative Colitis. Finally, we showcase some of the approaches and therapies, we and others, are developing to promote healthy early life microbial ecosystems with the aim of maintaining health and treating disease.
Year(s) Of Engagement Activity 2018
URL https://royalsociety.org/science-events-and-lectures/2018/summer-science-exhibition/exhibits/guardia...
 
Description TV interview - BBC Look East 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact TV interview on BBC Look East about our Guardians of the Gut exhibition - people specifically attended the exhibit after they had watch the interview.
Year(s) Of Engagement Activity 2018