What can we learn about microbiomes by studying wild mice?

TALK LIKE A MICROBIOME SCIENTIST

MICROBIOME — the microscopic life that lives in or on another organism, including bacteria, archaea and protists

ARCHAEA — single-celled organisms that do not have a nucleus, but are distinct from bacteria

DNA SEQUENCING — the process of determining the order of nucleotides in a strand of DNA. This method can be used to identify which microbes are present in a sample

FAECAL MICROBIOME TRANSPLANT — an experimental technique that allows a microbiome to be transferred from one individual to another

LIVE TRAPPING — a technique used to temporarily capture wild animals designed not to harm them, that allows scientists to sample and measure them

PROTISTS — single-celled organisms that have a nucleus, such as algae

We humans often pride ourselves on our independence and self-reliance. We strive to navigate the trials and tribulations of life as resilient individuals – if we are lucky, receiving help and support from family and friends in times of need. But there is, in fact, something that is always with us, that helps to keep us functioning as we should, even though we rarely think of it – our microbiome! At this very moment, your body is home to roughly 38 trillion cells that do not belong to you, and only 30 trillion cells that do. These 38 trillion ‘foreign’ cells make up your microbiome – a collection of microscopic organisms that play an important role in keeping you alive and healthy.

Much of our microbiome is found within our guts. Hundreds of species of bacteria live in our intestines, alongside a menagerie of viruses, fungi, protists and archaea. The microorganisms that make their homes in our intestines perform a range of different roles that help keep us healthy. They help us digest food, some play a role in regulating our immune system, and may even influence our moods by producing serotonin, which has antidepressant properties.

Research into microbiomes has exploded over the last couple of decades. However, most microbiome studies so far have focused on humans or animals in labs. Dr Sarah Knowles, of the Department of Biology at the University of Oxford, believes that more research should be conducted on wild animals. She says, “My view is that if we want to gain a deep understanding of how microbes affect animals, we need to study microbiomes across as broad a range of animals as possible, and in wild settings, not just in the lab.”

WHY IS IT IMPORTANT TO STUDY MICROBIOMES IN WILD ANIMALS?

The ways in which an animal behaves and interacts with its environment can have an impact on its microbiome and how this influences its health. Laboratory settings are, by definition, controlled and artificial. Therefore, any studies conducted under these conditions may have limited relevance to animals in the real world. Lab animals are not exposed to the same microbes that wild animals are, and the ways in which this exposure happens can be very different. In lab studies, animals are also not free to behave as they normally would and are kept secure and well-fed by humans. On the other hand, wild animals are subject to the forces of natural selection and must fend for themselves.

Mice, for example, behave very differently in the wild than they do when confined to laboratories. In the wild, they spend much of their time foraging for food, are constantly on the look-out for danger, and need to find a mate to reproduce. In labs, all their food is provided, they are safe from natural predators, and can only reproduce when humans allow.

WHAT MAKES MICE SUCH IDEAL SUBJECTS FOR SARAH’S WORK?

Mice make great test subjects because they are common, easy to find in large numbers and relatively comfortable being handled by humans. A lot of Sarah’s work involves marking individual wild mice so that they can be monitored in their natural habitat throughout their lives. Mice rarely travel very far, and they will often return to live traps, which means that Sarah’s team can study the same individuals and their microbiomes repeatedly over time. “This is important as their microbiomes are not static but constantly changing, in ways that could alter their effects,” she explains.

Another advantage of studying wild mice is that mice have been studied extensively in lab settings. This means that there is already a wealth of literature and research techniques for mice and their microbiomes that Sarah can use to inform her own studies. “This makes the research I do more insightful and powerful than it might be if I focused on a more obscure species,” explains Sarah.

WHAT RESEARCH TECHNIQUES DOES SARAH USE?

Sarah’s research involves a lot of fieldwork, with teams of two to six researchers setting out into the wild to sample mice. Some fieldwork is conducted locally in Oxford University’s research woodland, Wytham Woods, although sometimes the team also travels further afield. One current study is being conducted on the remote island of Skokholm, off the coast of Wales in the UK, where small teams of researchers stay for several weeks at a time. “It involves a lot of early mornings and hard work, but it is also great fun and wonderful to be in the great outdoors; there’s great team spirit and camaraderie on fieldwork,” Sarah explains.

Sarah often uses a technique known as ‘capture-mark-recapture’ when conducting fieldwork. This involves catching mice in live traps, marking them and then releasing them back into the wild so that they can be caught again at a later date. Sarah’s team sprays a little sesame oil outside the trap door to attract the mice and, when the mice are captured, the team takes measurements and collects data on characteristics such as their weight, sex and age. The team also collects a faecal sample.

Back in the lab, Sarah’s team makes use of molecular biology to analyse the samples. The researchers extract DNA from each faecal sample and sequence it to get a profile of the mouse’s entire community of microbes. “That gives us a window into which microbes are present within the gut, and in what numbers,” says Sarah. The team then uses statistical tests to analyse this microbiome data alongside information about the mice themselves, to answer questions about what affects the microbiome and how.

WHAT FACTORS CAN AFFECT A MOUSE’S GUT MICROBIOME?

When mice come into contact with each other, they often exchange microbes. Therefore, the social networks they form have a big impact on the composition of their gut microbiome. Sarah and her team study the influence of social contact by tracking mice with passive integrated transponder (PIT) tags. Sarah explains, “These are the same sort of tag some people use to identify their pet cats and dogs, only much smaller.” Comparing the patterns of social contact among mice with their microbiome profiles has taught Sarah a lot about how microbes are exchanged in wild settings.

Diet can also influence a mouse’s microbiome. Although it is hard to observe what mice eat, as they are nocturnal and like to stay hidden, Sarah’s team can analyse the faecal samples to get an idea of what each mouse has been eating. The researchers can then compare each mouse’s diet to their microbiome profile to understand how diet shapes this important microbial community.

WHAT FINDINGS HAS SARAH MADE?

“One key thing we’ve learnt, so far,” says Sarah, “is that each wild mouse’s microbiome is rather unique – a bit like a fingerprint. The microbiomes are highly responsive to each mouse’s external environment. A mouse’s microbiome is influenced by the other mice they encounter, including their mother in early life and social contacts, and by what they eat. For example, the microbiome of wild mice changes with the seasons as different food sources become available.”