Persistence pays off in the human gut microbiome

14 June 2021

Persistence pays off in the human gut microbiome

The human gut microbiome is a complex community of trillions of microbes that are constantly interacting with each other and our bodies. It supports our wellbeing, immune system and mental health - but how is it sustained?

Researchers in the UK and Germany, alongside other international collaborators, have investigated the evolution of bacteria in the human gut microbiome - asking how these microbes persist throughout their lifetimes - taking into account internal and external influencing factors. 

The results of the study will help inform tailored probiotics, live bacteria found in particular foods or supplements, as well as dietary or medical interventions to treat gut disease and maintain a healthy gut microbiome. 

Keeping a stable, healthy gut microbial population is mutually beneficial to us and the bacteria. In exchange for nutrition and a comfortable habitat, the microbe community returns the favour by providing us with health benefits, which we are now starting to understand. 

Lead author and Group Leader Dr Falk Hildebrand from the Quadram Institute and Earlham Institute, explains: “We know that certain microbes colonise us at birth and some can live with us for decades. Yet, although studies have looked at individual microbe species, the mechanisms and scale of persistence in the microbiome as a whole haven’t been explored.”

To examine this, a team of scientists at the Earlham Institute and Quadram Institute on the Norwich Research Park, along with the European Molecular Biology Laboratory (EMBL) in Germany, used metagenomics to analyse the evolutionary strategies and persistence of different bacteria in the human gut microbiome. 

Metagenomics is the study of all of the genes from many different organisms in a population. In terms of the human gut microbiome, this process not only provides detailed information about the bacteria strains present but also indicates the enhancing capabilities of those different strains, based on their genetics, to keep the gut in good working order.

From analysing stool samples, the team re-examined metagenomes from over 2,000 adult and infant samples, including several from the same families and found three major dispersal strategies underlying human gut bacterial persistence. The data came from previously published studies looking at microbiome changes over time, with each individual providing on average 2-3 samples several months apart.

Last author and Director EMBL Heidelberg (Scientific Activities) Prof Peer Bork, said: "By looking into time series from individuals and family members and overlaying this with geographic information, ranging from household via city to country, we identified groups of bacterial strains that show different dispersal strategies. This presented very different persistence patterns in the host, regional spreading and the geographical distributions of hundreds of bacterial species."

The data was built into a diverse dataset of 5,278 metagenomes, which were probed to analyse patterns of persistence in the different types of bacteria and how these were influenced by the common factors: age, family members, geographic region, and antibiotic usage.

“Our analysis shows that most strains of bacteria present in the microbiome are very persistent - with the chances of a strain persisting for at least a year being over 90%,” said Dr Hildebrand

“Some microbe species did show consistent differences being either highly persistent taxonomic groups, or being low-persistent, relying more on exchanges between family members. In babies, however, the average persistence of bacterial strains dropped to 80%. This isn’t unexpected; we know that especially in newborn babies there is an ongoing exchange of gut microbes.”

Prof Bork, added: “What the study shows is that the intrinsic persistence levels of bacteria seen in adults are also reflected in children, and gradually we start to acquire those persistent bacteria up to about ten-years-old at which point the microbiome reaches a steady state. “

“Antibiotics had different effects of different types of bacteria, with the overall effect depending on how resilient different bacteria are, their intrinsic persistence, and to what extent they were replaceable within the microbiome.”

To delve deeper into what drives persistence, the researchers compared microbiome communities beyond an individual level, but also across families, countries and regions. This allowed them to group bacteria based on their persistence characteristics and, through genomic analysis, look for clues to the evolution of these groups’ strategies in dispersing among new human hosts.

The human gut microbiome is an integral and lifelong part of us. However, not every microbial species is equally persistent through its lifetime, some bacteria preferring a 'travelling' lifestyle of often switching between hosts (heredipersistent), while others can stay not only with us for a long time, but have also a higher chance to be inherited in our children (tenacious).

Tenacious persistence

The first group, termed ‘tenacious’ bacteria, were the most persistent and well adapted for survival in the human gut. For example, these bacteria were able to survive by switching to different nutrition sources as the host moved through infancy and into adulthood. 

Tenacious bacteria, however, are the ones most likely to be lost from the microbiome following antibiotic use. If we have been carrying these bacteria in us since childhood, their loss may be permanent. This is a particular concern in relation to over- and misuse of antibiotics. 

Another group was termed the ‘heredipersistent’ bacteria, which are strains that are ‘inherited’ and cluster within families. These have a lower persistence in childhood and a higher turnover rate, suggesting cycles of reinfection is key to their persistence in an individual. 

Genomic analysis showed that these bacteria tend to have genes allowing them to spread by spores, which would help transmission from, say, a parent to child, but also across a family unit. 

A third group, named ‘spatiopersistent’, appear to cluster to their own geographic areas, but not associate to families.

With much current interest in maintaining or manipulating the microbiome for health, the research team hopes their holistic exploration of the evolution of different persistence in gut microbes will lead to better, more well-informed clinical strategies. 

For example, one-off interventions like Faecal Microbiota Transplantation (FMT) may be suitable to introduce or even replace tenacious bacteria but not bacteria that rely on reinfection. These might benefit more from probiotic-based therapies or dietary changes that, over time, alter the gut environment to favour their colonisation and persistence. 

The new insights into the wide-ranging and potentially permanent damage antibiotics can do to the microbiome could also point to new strategies to mitigate these differing effects. 

“Our study gave us a much better idea of which gut bacteria are closely associated with their host, and which are more prone to switch between hosts. This is important information to inform pro-prebiotics and most medical applications targeting the human gut microbiome,” added Dr Hildebrand.

The paper ‘Dispersal strategies shape persistence and evolution of human gut bacteria’ is published in Cell Host and Microbiome. 

The study was funded by the Biotechnology and Biological Sciences Research Council and the European Research Council.

Notes to editors

For more information, please contact:

Hayley London

Marketing & Communications Officer, Earlham Institute (EI)

+44 (0)1603 450 107

hayley.london@earlham.ac.uk

The Earlham Institute (EI) is a world-leading research Institute focusing on the development of genomics and computational biology. EI is based within the Norwich Research Park and is one of eight institutes that receive strategic funding from Biotechnology and Biological Science Research Council (BBSRC) - £5.43m in 2017/18 - as well as support from other research funders. EI operates a National Capability to promote the application of genomics and bioinformatics to advance bioscience research and innovation.

EI offers a state of the art DNA sequencing facility, unique by its operation of multiple complementary technologies for data generation. The Institute is a UK hub for innovative bioinformatics through research, analysis and interpretation of multiple, complex data sets. It hosts one of the largest computing hardware facilities dedicated to life science research in Europe. It is also actively involved in developing novel platforms to provide access to computational tools and processing capacity for multiple academic and industrial users and promoting applications of computational Bioscience. Additionally, the Institute offers a training programme through courses and workshops, and an outreach programme targeting key stakeholders, and wider public audiences through dialogue and science communication activities.

www.earlham.ac.uk

@EarlhamInst

The Quadram Institute (quadram.ac.uk) is an interdisciplinary research centre at the forefront of a new era of food and health research. It brings together researchers and clinicians under one roof and houses one of Europe’s largest endoscopy units and a clinical trial facility. It focuses on lifelong health – from birth and throughout the lifecourse, increasing healthspan as well as lifespan. It undertakes both fundamental and translational research working with industry to accelerate innovation and bring novel therapeutics and new food products to patients and consumers.

Based on the Norwich Research Park, The Quadram Institute is a partnership between Quadram Institute Bioscience, the Norfolk and Norwich University Hospitals NHS Foundation Trust, the University of East Anglia and the Biotechnology and Biological Sciences Research Council (BBSRC).

Four interconnected interdisciplinary research themes in Quadram Institute Bioscience deliver a pipeline of research in plants, microbes, food and health: microbes in the food chain; the gut and the microbiome; food innovation and population health.

EMBL is Europe’s flagship laboratory for the life sciences. Established in 1974 as an intergovernmental organisation, EMBL is supported by 27 member states, 2 prospective member states and 1 associate member state.

EMBL performs fundamental research in molecular biology, studying the story of life. The institute offers services to the scientific community; trains the next generation of scientists and strives to integrate the life sciences across Europe.

EMBL is international, innovative and interdisciplinary. Its more than 1800 staff, from over 80 countries, operate across six sites in Barcelona (Spain), Grenoble (France), Hamburg (Germany), Heidelberg (Germany), Hinxton (UK) and Rome (Italy). EMBL scientists work in independent groups and conduct research and offer services in all areas of molecular biology.

EMBL research drives the development of new technology and methods in the life sciences. The institute works to transfer this knowledge for the benefit of society.

www.embl.org