#	Pagina
attuale pagina	/open-h2020/projects/209021/results.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MIND THE GUT (Mind the Gut: Molecular Markers of Microbiome Evolution)

Teaser

Summary

Does microbiome evolution reflect major events of human history? The human gut microbiome consists of billions of beneficial bacteria, which profoundly affect health through their impact on metabolism, immunity and behavior. Despite its major role in human health, little is known about how the human microbiome evolved and its changing ecology. Further, the extent to which human evolution has impacted gut microbiomes through genetic mutations, population migrations and changes in lifestyle is poorly understood. These limitations prevent us from accurately defining a healthy human-microbes association, and from understanding how gut microbiomes have shaped our species. However, understanding the co-evolution of the man-gut community is more complex than a simple binary present-to-past comparison and requires a time-series approach associated with the determining moments in human evolution, e.g., migrations, admixture, domestication and industrialization. Current research on extant populations has potential to reveal the microbial impact of specific environmental and lifestyle changes that occurred throughout human history and prehistory. Recent studies show that the Western lifestyles and diets of industrialized populations threaten these bacterial communities, with a dramatic loss of biodiversity when compared to indigenous or rural populations. As globalization threatens non-industrialized lifestyles and diets, we risk losing this important human-associated biodiversity before it can be cataloged and studied. Such a sample set is critical to preserve the human microbiome heritage for future generations. Archaeology potentially offers remarkable insights into the role that these factors may have played in the evolution of the microbiome, but soft tissues rarely survive in the archaeological record. The only substrates that could allow us to approach the ancient microbiome are the dental calculus, coprolites and mummified guts.

The overall objectives of the project are to develop new markers of specific bacterial action applying lipidomic and proteomic tools to explore the diagenesis of microbiome substrates. MtG will analyze the mummified microbiomes of the aboriginal Canary islanders. The Canary mummies represent a unique model system to study the impact of diet and lifestyle in populations that evolved isolated but shared their microbiome during the peuplement of the islands. MtG will compare them with a group of naturally mummified bodies from Nubia that span a similar time period, and with modern microbiome samples from African populations with different lifestyles.

Work performed

Mind the Gut started on October 1st, 2017, establishing a collaboration between the laboratory of Roger Summons (MIT, USA) and the research team of Matthew Collins (UCPH, Denmark). During my stay at the Summons Lab at MIT, I have received training in mass spectrometric techniques such as GC-MS, Py-GCMS, HLPC-MS, microbiology culturing techniques, scientific writing, grant proposal writing, mentoring and public speaking. In order to develop a method using lipid and proteomic analysis to identify specific markers of bacterial action and therefore, be able to better understand the evolution of gut microbiome, I have used complementary approaches:
Lipid analysis of stool samples from extant populations with different lifestyles.
In collaboration with an ongoing project with the Alm Lab at MIT (Global Microbiome Conservancy) I have collected more than 2000 faecal samples from different populations with traditional lifestyles from more than 10 countries. Thus far we have analyzed the lipidome with GC-MS from more than 150 stool samples from different countries (Tanzania, Ghana, Cameroon, Rwanda, Nigeria, Malaysia, Finland and US).

The major finding of my work has been the stark differences in the capacity to biodegrade cholesterol between urban and non-urban populations. I was able to gain early access to the genomic analyses (Almâ€™s Lab) and could see that the levels of microbial diversity (from genomic data) were typically 30% higher in non-industrialized populations compared to westernized urban populations. A striking feature of this data was that a very significant fraction of Western populations lacked the ability to convert cholesterol to coprostanol.

Analysis of mummified gut contents

I have visited the team at the British Museum and Canary Islands and have been developing improved methods to microsample tissues from mummified remains. At present we have collected and analyzed more than 50 samples collected from the gastrointestinal tract of mummified tissues from Canary Islands and Sudan. Data processing from the lipid analysis is still ongoing, and proteomic analyses will be conducted during the return phase in KU. Preliminary results are very promising not only to inform us about ancient microbiomes but also about health and disease.

Assessment of the effect of diagenesis in fecal material.

The chronologies of the samples analyzed thus far ranges from 50000 years ago to the present, allowing us to better understand the process of diagenesis of lipids and the bacterial community succession over time. Preliminary results suggest that most lipids become stable around 2 months after deposition. Regarding the community succession, although lipids are quite stable, we are still processing the genomic and proteomic analysis, which will shed light onto the community structure of the samples.

Our research results are being disseminated through peer-reviewed open access scientific journals, in national and international conferences and seminars, and through public outreach.

Final results

For the first time, with Mind the Gut, we have approached the study of ancient microbiome, health and disease using a multiomic approach, combining lipid, proteomic and genomic analysis.
Our study on the mummies from Canary Islands, is providing insights on the lifestyle, health and disease of the aboriginals of these islands, bringing together a group of experts aiming at applying cutting edge technologies to Canary Islands Archaeology.
The development of methods of extraction and analysis of microsamples with Py-GCMS has allowed us to collect minimally invasive samples (less than 2mg) from these precious mummies. This will facilitate future sampling protocols and ease the concerns of museums about damage due to sample size requirements for molecular analysis.

During this first phase of the project, we have undertaken the largest analysis of lipids from modern stool samples from non-industrialized countries. These results, although still preliminary, have the potential to help these underrepresented communities to benefit from scientific advances currently tailored to well-studied populations.

Mind the Gut results will provide a framework for future studies on fossil material and contribute to illuminate the role of the microbiome in overcoming the challenges of diet, environment and lifestyle changes that took place during human history and prehistory. MtG represents a stepping stone to the integration of the ancient microbiomes in the study of human evolution.