A New Frontier in Diagnosing Gut Health

A New Frontier in Diagnosing Gut Health

Every year, more than 200 million children worldwide do not reach their developmental potential. This is primarily due to infectious diseases as well as malnutrition and related disorders. Normal gut development and function are critical for determining a child’s development and health throughout life. Despite this, diagnostics that can measure the health status of the gut are severely lacking.  As part of the BRCCH’s Multi-Investigator funding programme, Prof Randall Platt (ETH Zürich), Prof Andrew Macpherson (University Hospital Bern) and fellow consortium members seek to develop a non-invasive, microbe-based diagnostic that is capable of sensing and recording the status of the gut.

In a new groundbreaking study published in Science*, Prof Platt, Prof Macpherson and co-authors have achieved the first critical steps towards making this ambitious idea a reality.

Behind this work is the innovative Record-seq technology pioneered by Prof Platt in 20181. The technology is based on CRISPR-engineered bacteria that can sense and create a molecular record of changes in their surrounding environment over time. These bacteria, or ''transcriptional recorders'' can then be analysed via sequencing approaches to reveal the history of events that they encountered. This technology holds enormous potential to provide real-time information on the status of the gut environment, which could then be harnessed to guide personalised therapeutic interventions.

In this new study, the researchers first set out to understand how the transcriptional recorders behave in a real-life gut environment and what they are able to report on whilst travelling through the intestine. The team demonstrated that these bacteria survive and traverse through the gut of mice, and that they can be successfully collected from faecal samples for further analysis. Importantly, the study revealed that the transcriptional recorders are able to capture important biological information throughout all regions of the gut. This represents a major advance over current omics-based technologies that are used to study the gut, as they are unable to provide insights into intestinal regions that are more difficult to access, such as the proximal colon.

The CRISPR-engineered bacteria (or transcriptional recorders) create molecular records of information about their surrounding environment as they transit through the gut. These bacteria can then be retrieved via faecal samples and their molecular records analysed through sequencing and computational methods. Image courtesy of Prof Randall Platt

 

Following these exciting results, the team then embarked on testing if the transcriptional recorders can reliably report on two elements which are critical for determining gut health: nutrition and inflammation.

To do this, mice were fed with different diets and the transcriptional recorders were collected from faecal samples over time. A Record-seq analysis revealed that these bacteria record unique molecular signatures that are diet-specific and are retained by the bacteria, even following a dietary switch. Therefore, not only are these transcriptional recorders capable of reporting on the real-time dietary status in vivo, these findings also suggest that they can provide a window into the nutritional history of the gut.

The researchers then took one step further by studying the transcriptional recorders in a mouse model of gut inflammation, to mimic the local environment in the presence of gastrointestinal disease.  Remarkably, the team discovered that the molecular signatures recorded by the bacteria could be used to distinguish healthy mice from those with gastrointestinal inflammation. Moreover, they could also provide a read-out for measuring the severity and biological indicators of inflammation within the gut.

Following this landmark work, we asked Prof Randall Platt about where the consortium plans to take Record-Seq from here:

''This highly collaborative and interdisciplinary project lays the groundwork towards realising the technology’s true potential for improving human health. The consortium is now focusing on translation, which primarily includes further rigorous testing in animal models of human conditions as well as ensuring robust safety and environmental containment of the genetically engineered bacteria''.

 

*Read the paper: https://www.science.org/doi/10.1126/science.abm6038

Schmidt F, Zimmermann J, Tanna T, Farouni R, Conway T, Macpherson AJ, Platt RJ: Noninvasive assessment of gut function using transcriptional recording sentinel cells. Science, 12 May 2022, doi: 10.1126/science.abm6038

About the researchers 

Professor Randall Platt is an Associate Professor at the Department of Biosystems Science and Engineering (D-BSSE) at ETH Zürich and the Department of Chemistry at the University of Basel.

Professor Andrew Macpherson is Professor and Director of Gastroenterology at University Hospital Bern.

Professors Platt and Macpherson, together with fellow consortium members, lead the BRCCH Multi-Investigator Project: Living Microbial Diagnostics to Enable Individualised Child Health Interventions.

1 Related articles

Recording device for cell history (ETH News 03.10.2018)

Bacteria with recording function capture gut health status (ETH News 12.05.2022)

 

 

BRCCH Early-Career Programme

BRCCH's Early-Career Events 2021-2022

The BRCCH endeavours to foster the development of aspiring young researchers who will pioneer the next frontiers in global paediatric medicine and health. The BRCCH’s Early Career Programme aims to provide unique opportunities for its community members to gain know-how in research areas at the heart of the Centre’s mission and to grow their global network.

This upcoming year (late 2021-mid 2022), the BRCCH invites its early-career community members to join local and international speakers in a series of interactive workshops on topics across the Centre’s mandate.

For more information and registration, contact Dr. Amandine Bovay, BRCCH Scientific Officer and Development Manager (amandine.bovay@brc.ch)

Webinar: Community-based COVID-19 Testing in Lesotho and Zambia

Webinar: Community-based COVID-19 Testing in Lesotho and Zambia

Visual: SolidarMed & Swiss TPH

 

Description:  The BRCCH cordially invites you to join us online for a webinar looking at Community-based COVID-19 testing in Lesotho and Zambia. This event will highlight research progress of the collaborative project between Dr Kwame Shanaube (Zambart) and Dr Klaus Reither (Swiss TPH) on the effects of community-led interventions in mitigating the COVID-19 epidemics in Lesotho and Zambia. The BRCCH and the European & Developing Countries Clinical Trials Partnership (EDCTP) partnered on a joint initiative to support multi-national collaborations for research to mitigate COVID-19, particularly in low- and middle-income countries.

When: Wednesday, April 27th, 2022 from 15:30-17:00 CET

Where: Online, Zoom seminar

Registration: HERE

Schedule:

      • Welcome by BRCCH Director Prof Georg Holländer
      • Keynote lecture by Dr Kwame Shanaube (Zambart), Dr Klaus Reither (Swiss TPH) & their research teams:
              1. Overview of the joint BRCCH-EDCTP project: Improving Access to SARS-CoV-2 Screening and Testing through Community-based COVID-19 Case-Finding and the Use of Digital Solutions in Lesotho and Zambia
              2. Comparing different approaches of community-based SARS-CoV-2 testing in Lesotho and Zambia
              3. Barriers and facilitators to SARS-CoV-2 testing at community-based testing sites
              4. Evaluation of SARS-CoV-2 tests and testing approaches
      • Plenary discussion
      • Closing

Keynote Speakers:

 

 

Dr Kwame Shanaube

Zambart & School of Public Health, University of Zambia

Dr Kwame Shanaube is Deputy Director of Research (Quantitative) at Zambart, a multidisciplinary research organisation that conducts a range of studies including clinical trials, epidemiological studies and laboratory-based diagnostic studies. She is a clinician with a Master’s degree in public health and a PhD in TB clinical epidemiology. She is also an honorary lecturer at the University of Zambia School of Public Health. Her research interests cover a wide range of disciplines, including TB/HIV epidemiology, community-based cluster randomised trials, operational research through evaluation of field diagnostics and adolescent health. She is also the country’s Principal Investigator for a large international TB consortium (the TREATS Project) and the overall Principal Investigator for the TREATS-COVID study, both funded by the EDCTP.

 

Dr Klaus Reither

Clinical Research Unit, Swiss Tropical and Public Health Institute

Dr Klaus Reither is Head of the Clinical Research Unit and the leader of the Clinical TB Research Group at the Swiss Tropical and Public Health Institute (Swiss TPH). He oversees and coordinates clinical research projects conducted by Swiss TPH and his research responsibilities comprise the set-up, implementation, coordination and supervision of clinical research projects, with an emphasis on TB clinical trials at Swiss TPH’s international partner organisations such as the Ifakara Health Institute in Tanzania, the National Centre of Tuberculosis and Lung Diseases in Georgia and SolidarMed in Lesotho.

Dr Reither is Lead Investigator of the BRCCH COVID-19 project: MistraL - Mitigation Strategies for Communities with COVID-19 Transmission in Lesotho Using Artificial Intelligence on Chest X-rays and Novel Rapid Diagnostic Tests. Together with Dr Kwame Shanaube, he also co-leads a BRCCH-EDCTP collaborative project on Improving Access to SARS-CoV-2 Screening and Testing through Community-based COVID-19 Case-Finding and the Use of Digital Solutions in Lesotho and Zambia.