Defining foetus-microbiota interactions
Lead Research Organisation:
QUADRAM INSTITUTE BIOSCIENCE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
During pregnancy, the maternal environment including the maternal microbiota may have a significant impact on foetal development as well as early and later life health outcomes. However it is currently unclear how microbiota members and/or their products are transmitted to the foetus from the gut to facilitate this very early life development. This project tackles this issue by identifying the microbial and host factors required for this process.
We will test the hypothesis that specific microbiota members (including Bifidobacterium) can translocate to the developing foetus via specific microbial factors and interact with specific immune cells to facilitate this gut-in utero transfer. Real time, longitudinal imaging in vivo and microscopy will be used to track bacteria and determine what bacterial molecules are critical for the process. We will focus on Bifidobacterium (using bioluminescence or fluorescence labelled bacteria), and using a similar labelling approach we will tract host cells (e.g. Natural Killer cells) to explore this process, confirming importance of these cells with transgenic models. Host and immune profiling will be via flow cytometry and RNASeq as described below. For comprehensive characterisation and profiling of the microbiota we will employ a variety of Next Generation Sequencing methods (DNA and RNA, including 16s, shotgun sequencing and RNASeq for microbiome profiles at different stages of pregnancy [mother and foetus] and also transcriptional responses [bacterium and host responses].
We will test the hypothesis that specific microbiota members (including Bifidobacterium) can translocate to the developing foetus via specific microbial factors and interact with specific immune cells to facilitate this gut-in utero transfer. Real time, longitudinal imaging in vivo and microscopy will be used to track bacteria and determine what bacterial molecules are critical for the process. We will focus on Bifidobacterium (using bioluminescence or fluorescence labelled bacteria), and using a similar labelling approach we will tract host cells (e.g. Natural Killer cells) to explore this process, confirming importance of these cells with transgenic models. Host and immune profiling will be via flow cytometry and RNASeq as described below. For comprehensive characterisation and profiling of the microbiota we will employ a variety of Next Generation Sequencing methods (DNA and RNA, including 16s, shotgun sequencing and RNASeq for microbiome profiles at different stages of pregnancy [mother and foetus] and also transcriptional responses [bacterium and host responses].
Planned Impact
unavailable
Publications
A James S
(2020)
Preterm Infants Harbour a Rapidly Changing Mycobiota That Includes Candida Pathobionts.
in Journal of fungi (Basel, Switzerland)
Acuna-Gonzalez A
(2023)
Bifidobacterium bacteraemia is rare with routine probiotics use in preterm infants: A further case report with literature review.
in Anaerobe
Alcon-Giner C
(2017)
Optimisation of 16S rRNA gut microbiota profiling of extremely low birth weight infants.
in BMC genomics
Alcon-Giner C
(2020)
Microbiota Supplementation with Bifidobacterium and Lactobacillus Modifies the Preterm Infant Gut Microbiota and Metabolome: An Observational Study.
in Cell reports. Medicine
Carruthers LV
(2019)
The impact of storage conditions on human stool 16S rRNA microbiome composition and diversity.
in PeerJ
Chen Y
(2019)
Draft Genome Sequences of Citrobacter freundii and Citrobacter murliniae Strains Isolated from the Feces of Preterm Infants.
in Microbiology resource announcements
Chen Y
(2019)
Draft Genome Sequence of Raoultella ornithinolytica P079F W, Isolated from the Feces of a Preterm Infant.
in Microbiology resource announcements
Chung The H
(2021)
Exploring the Genomic Diversity and Antimicrobial Susceptibility of Bifidobacterium pseudocatenulatum in a Vietnamese Population.
in Microbiology spectrum
| Title | Bifidobacterium bronze and perfume sculpture - Wellcome Collection (Being Human) |
| Description | Food historian and artist Tasha Marks of AVM Curiosities has developed a playful bronze and perfume sculpture which suggests the smell of breast milk and celebrates the microbiome and our symbiotic relationship with bacteria. This was in collaboration with Dr Lindsay J Hall |
| Type Of Art | Artwork |
| Year Produced | 2019 |
| Impact | This has enhanced the public's knowledge on the links between certain microbiota members i.e. Bifidobacterium and early life diet - breast milk. |
| URL | https://wellcomecollection.org/pages/XW5QMBEAACUAELBV |
| 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 | This was a short project towards the end of the 2013-2018 ISP as the PDRA started mid-2016. Due to staff leaving and other studies that have been impacted by covid, we are still writing up the main study. Key findings have revealed that Bifidobacterium significantly modulates mucosal and systemic immune responses in germ free mice. Studies towards the end of this grant (delayed due to issues as below) have indicated pregnant mice have changes in the placenta and fetal development after Bifidobacterium supplementation - this work has now been carried over to the current ISP. Update 2020: We have one manuscript preprinted and under review - and another is in the final stages for drafting. Update 2021: We now have a manuscript published, with another in draft form (that will be pre-printed). |
| Exploitation Route | The findings of these studies may be used to develop live bio-therapeutics for immune regulation both during pregnancy and infancy. |
| Sectors | Agriculture Food and Drink Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | A number of studies and collaborations have allowed us to show that specific strains of probiotic Bifidobacterium and Lactobacillus bacteria given to preterm babies with breast milk, beneficially shapes their microbial populations and gut health to levels that match those of babies born at full-term (Cell Reports Medicine, Nature Microbiology, amongst others). This helps vulnerable babies survive, fight infections, derive the full benefits from breast milk, and get the healthiest start in life. We showed a 50% reduction in the devastating disease necrotising enterocolitis and late onset sepsis due to routine administration of probiotic in at-risk preterm infants (BMJ Arc Dis Neonatology). Less than 20% of neonatal wards were using routine probiotics on premature babies, but as a result of our work, other Neonatal Intensive Care Units have already changed their policies to use probiotic supplementation in at-risk infants as standard. This work has also recently been cited in WHO preterm infant care guidelines. |
| First Year Of Impact | 2020 |
| Sector | Healthcare |
| Impact Types | Societal Policy & public services |
| 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 | Reservoirs of mobile antibiotic resistance genes in the gut microbiome of preterm infants |
| Amount | £588,844 (GBP) |
| Funding ID | BB/S017941/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2019 |
| End | 08/2023 |
| Title | Bifidobacterium and compositions thereof for breast cancer treatment |
| Description | Bifidobacterium and compositions thereof for breast cancer treatment |
| IP Reference | GB2118611.9 |
| Protection | Patent application published |
| Year Protection Granted | 2021 |
| Licensed | No |
| Impact | Patent only filed in Dec 2021 so still in early stages |
| 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 | BBC Radio Leeds (Gayle Lofthouse show). |
| 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 | BBC Radio Leeds (Gayle Lofthouse show). Interview about You Are What You Eat TV show and also wider questions about diet and the gut microbiota. |
| Year(s) Of Engagement Activity | 2022 |
| 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 | British Science Week activity - Guardians of the Gut |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | We contributed an activity to British Science Week 2021 based on our own Guardians of the Gut. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.britishscienceweek.org/plan-your-activities/activity-packs/ |
| Description | Expert reaction via Science Media Centre |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Expert reaction to study looking at neonatal antibiotics and growth and BMI in children, as published in Nature Communications* via Science Media Centre. Quotes taken up by press associtaion and used in multiple online newspaper articles and print (Mail, Times and Telegraph) |
| Year(s) Of Engagement Activity | 2021 |
| Description | Guardians of the Gut Classroom Pack |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Guardians of the Gut is an exciting new resource for children to learn about the importance of their gut microbes. It is a teacher-led online resource that is freely available. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://guardiansofthegut.org/ |
| Description | Interview for Radio 4 |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Invited interviewee for Radio 4 programme: Inside Health. Numerous followups for further information and also engagement from Industry for new collaborations has resulted from broadcast. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.bbc.co.uk/programmes/m000dpky |
| 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 | Invited speaker at the University of the third age (U3A). |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Other audiences |
| Results and Impact | 40 people attended for a visit arranged by the U3A to the IFR. This sparked questions and discussion afterwards and increased the interest in science related areas for the U3A. They showed much interest in the work and had many questions regarding the project. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Latitude Music Festival: Exhibited Guardians of the Gut |
| 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 | We exhibited our Guardians of the Gut Exhibit at Latitude Festival in July 2019 over 3 days to members of the public (over 5000), We also had several specific school visits (~60 children in total). We received excellent feedback and strong engagement and questions. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Member of expert working group for design of new permanent exhibit 'Being Human' at the Wellcome collection. |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | This a large permanent exhibit housed in the Wellcome Collection (London) that was opened in September 2019. Wellcome are collecting feedback on exhibit. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://wellcomecollection.org/pages/XW5QMBEAACUAELBV |
| 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 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Norwich Science Festival Stand; Tummy Time. The Hall lab team, including PDRA funded on this grant, presented a 2-D model gut system explaining the role of beneficial bacteria, including their impact on chronic disease outcomes. Feedback received was very positive and has been used to design a bigger exhibition to be shown at the Royal Society Summer Exhibition July 2018. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://norwichsciencefestival.co.uk/events/tummy-time-meet-microbes/ |
| 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 | 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 | Populating preterms with probiotics - Clasado online seminar day (QIB hosted event - virtual) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Online workshop and talks about the gut microbiome and diet - for healthcare professionals |
| Year(s) Of Engagement Activity | 2022 |
| Description | Public Debate |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | I was involved in a public debate at Dragons Hall in Norwich (October 2019) as part of the Norwich Science Festival. There was very strong engagement form the audience with lots of follow up questions and results for further information. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://norwichsciencefestival.co.uk/events/dragon-hall-debates-guts/ |
| Description | Public Talk (Richmond Scientific Society) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | 'Gut bacteria': how microbes influence our health - talk to Richmond Scientific Society, London. There was very strong engagement form the audience with lots of follow up questions and results for further information. |
| Year(s) Of Engagement Activity | 2021 |
| 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 | Save Money: Good Health ITV 1 |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Discussed the role of the gut microbiota on health and associated 'products' on the market including self-testing kits with Sian Williams (August 2019). |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.itv.com/presscentre/ep4week35/save-money-good-health |
| 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 |
| Description | The Human Microbiome MOOC |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Learn how a healthy microbiome can combat disease Contributed to new MOOK: The Human Microbiome. The microbiome - the microbes that live within the human body - can have a huge impact on human health. As such, it's vital to understand the complexity of the microbiome, and how it can impact on disease and wellbeing. On this course, you'll go on a fascinating journey into the human body - down to the gut - where the ecology and roles of the human microbiome will be narrated. You'll explore how your microbiome changes throughout your life, reflect on the role of food in its modulation, and explain the functions the microbiome has in the gastrointestinal tract in daily life. Over 4000 people registered and completed 3 week course. There was lots of engagement via the FutureLearn MOOK platform. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.futurelearn.com/courses/the-human-microbiome/1 |
| Description | You Are What You Eat (Channel 5 - 6 episodes across series running Jan-Feb 2022) |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | You Are What You Eat (Channel 5 - 6 episodes across series running Jan-Feb 2022). I was an the microbiome expert for the TV series. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.channel5.com/show/you-are-what-you-eat |