Transmission of the human microbiome and its impact on health

Project Information

microTOUCH

Grant agreement ID: 101045015

DOI

10.3030/101045015

EC signature date 9 August 2022

Start date 1 October 2022

End date 30 September 2027

Funded under

• European Research Council (ERC)

Total cost

€ 2 394 779,00

EU contribution

€ 2 394 779,00

Coordinated by

UNIVERSITA DEGLI STUDI DI TRENTO
Italy

Periodic Reporting for period 1 - microTOUCH (Transmission of the human microbiome and its impact on health)

Reporting period: 2022-10-01 to 2025-03-31

Summary of the context and overall objectives of the project

The human microbiome is a key component of our own biology and has important biomedical applications, but while its composition has been studied in depth and linked with several lifestyle and disease factors, it is still highly unknown how its members are acquired, spread, and transmitted across hosts. Our preliminary results suggest that person-to-person microbiome transmission (MT) is extensive and shapes the microbiome according to host interaction networks, leading to the hypothesis that microbiome-linked diseases that are considered non-communicable are instead partially communicable. microTOUCH will (i) develop the methods needed to model MT in human populations from metagenomic sequencing, (ii) unravel the features of microbial transmissibility, and (iii) detail the contribution of MT to host conditions that are currently considered non-communicable. We will first empower metagenomics with the ability to track and model the transmission of known and unknown members of the microbiome, and will then apply these methods to specific case studies of MT in humans (children and adults) and non-human primates across diverse family, social, and interaction networks. Meta-analysis of MT integrating publicly available datasets will unravel the factors impacting MT the most and the degree of transmissibility of each microbiome member. Exploiting the large and deeply phenotyped metagenomic datasets available to the PI, microTOUCH will characterize the role of MT in shaping the connections between the gut/oral microbiome and (i) nutrition and cardiometabolic health, (ii) oral diseases, (iii) cancer and cancer immunotherapy, (iv) autism, and (v) the Westernization process. microTOUCH will advance our understanding of the epidemiological forces shaping the human microbiome and will link MT with host conditions and risk factors, thus enabling the development of biomedical strategies promoting or limiting the transmission of specific disease-associated microbiome components.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project progressed for all 4 Aims.
Aim 1: Developing Better Tools to Study Microbiome Transmission
We’ve made exciting progress in improving the methodologies enabling the study of microbiome transmission between people, animals, and environments:
- We expanded our dataset to include over 1 million metagenome-assembled genomes and cataloged over 20,000 human metagenomes. This database, called MetaRef-SGB, supports cutting-edge tools like MetaPhlAn and StrainPhlAn, now in their most advanced version (4.0).
- Using these tools, we created models to track how microbial strains (specific genetic variants within a microbial species) are shared. This tracking is effective also for the so-called "dark matter" of the microbiome—microbes that have no isolated representative but are key microbiome members.
- We have developed new computational metagenomic methods to study and model transmission for microbiome members we know less about, such as viruses, micro-eukaryotes (tiny organisms like fungi).

Aim 2: Exploring Microbiome Transmission in Real-Life Settings
We’re investigating how microbes spread between individuals and communities in in different settings:
- In a landmark study we already published we investigated nearly 10,000 samples from around the world revealing the basic patterns of microbiome sharing across ages, regions, and social connections.
- In daycare centers, we tracked hundreds of infants, their families, and educators over six months. Our preliminary and unpublished results show how social interactions at daycare shape the developing microbiome of infants.
- In a unique study on captive primates, we are exploring how social behavior and group changes influence microbiome sharing between chimpanzees and their human caretakers.
- In a school-based study we are following children for two years to learn how sharing a classroom environment affects their microbiomes.

Aim 3: Understanding How and Why Microbes Spread
We are uncovering how microbes are transmitted in different ways—between family members, across households, through shared environments, or even via food. We published rankings of the most transmissible microbes and started studying uncultured, harder-to-detect species. We also created a microbial biobank to preserve and study these microbes further. We are now focusing on understanding which microbes preferentially use which transmission modes.

Aim 4: Linking Microbiome Transmission to Health
We have started exploring how the movement of microbes between individuals is linked to diseases. Early findings suggest weak but likely meaningful links between microbiome transmission and conditions like autism and obesity. Ongoing studies are focusing on colorectal cancer and cardiometabolic diseases.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our laboratory has achieved significant breakthroughs, establishing itself as a referent in the field of microbiome research and computational metagenomics.
Key advances include:
- Microbiome Transmission Research driving progress in understanding how microbes spread between individuals, environments, and even across species.
- State-of-the-Art Computational Metagenomics Tools creating and improving software tools, which are open-access resources enabling researchers to profile microbial communities and strains with high accuracy.
- Cross-Disciplinary Impact by using our tools and methods in various fields as in oncology by studying role of the microbiome in responses; in nutrition by understanding the microbiome influences nutrition and health, as demonstrated in studies on dietary impacts on microbial ecosystems; in food Microbiomes by investigations revealing how microbes in food impact human health.