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In and on our bodies and those of animals, you can find many micro-organisms, including bacteria, viruses and yeasts. These are known as our microbiome. This helps process food that we would otherwise not be able to digest, provides important nutrients such as certain vitamins, and trains the immune system to act effectively against infections. This is how our microbiome helps us stay healthy.

In the future, we want to offer personalised medicine based on a specific microbiome

The microbiome is extremely flexible: through interactions with the host, the environment, food and other micro-organisms, it is constantly changing. This flexibility is often positive, but it can also be dangerous – for example, if bacteria become resistant to certain antibiotics. How exactly the microbiome works, and whether we can influence it through factors such as food, is still largely unknown. Researchers hope to learn more about this through various research projects involving both humans and animals.

'Environment has more influence than feed'

Chickens

A healthy gut microbiome protects chickens from pathogens. As a result, poultry farmers need to use fewer antibiotics. The chicken’s gut microbiome is influenced not only by its feed, but also by other factors, such as its environment. Annelies Kers, a postdoc at Wageningen ľ�ϸ���Ӱ�� & Research, and Francisca Velkers from the Faculty of Veterinary Medicine investigated the influence of the environment on the gut microbiome. They randomly assigned broilers to three research environments with different coops, but with similar management. They used a feed intervention to differentiate between the coops: in one environment, the hens in one half of the coops received one type of feed, and the other half received another type of feed. After 35 days, Kers examined the composition of the microbiome in the caecum, where fermentation takes place in chickens. In two of the three research environments, the diversity of bacteria in the gut microbiome was increased by the feed intervention. This explained 10% of the differences in the microbiome, while the environment explained as much as 28%.

Each coop is unique

‘I didn’t expect the impact of the environment to be so significant,’ says Kers. ‘This shows that food has an influence on the gut microbiome of a chicken, but that the influence of the environment can be even greater. We need to take this into account in future research and the feeding of chickens. It’s likely that every coop has its own specific and unique microbiome. In the future, we’d like to incorporate that into the treatment and try to offer more personalised medicine based on that specific microbiome. One type of coop will require a different treatment to another.’

'The dog and the fungus are competing for nutrients'

Dogs

In dogs (particularly labrador retrievers and golden retrievers), the fungus Aspergillus fumigatus causes inflammation of the nasal cavity, which can expand to the frontal sinus. Scientists from Utrecht ľ�ϸ���Ӱ��’s Faculty of Science conducted genetic research on dogs and the fungus and discovered that both the dog and the fungus are competing for nutrients. ‘The fungus suppresses the dog’s immune system,’ says researcher Hans de Cock from Utrecht ľ�ϸ���Ӱ��. ‘We also see that the fungus adapts genetically to its host during growth. This allows the fungus to survive better in the dog’s cavities.’ The new insights offer starting points for better treatment of the fungus in dogs.

Notorious fungi

But this fungus also causes problems for people. ‘This is one of the four notorious fungi that are collectively responsible for one and a half million human deaths worldwide each year. Obviously, we want to find out as much as we can about these pathogens, which cause all sorts of different infections.’

'Antibiotic resistance spreads through manure'

Horses

Mathijs Theelen is a specialist in Equine Internal Medicine at the Faculty of Veterinary Medicine. In his research, he maps the healthy gut microbiome of horses. Theelen: ‘This is a huge challenge, because there are so many factors that affect it. These include climate, stable environment, food and the other animals in the stable. When you’re investigating the microbiome, even the lab protocol you choose will affect the results – so it’s difficult to talk about a normal or standard gut microbiome. What we actually have to do is try and determine the “normal” microbiome for each situation.’

What can we do with this information?

‘Obesity is very common in horses and gut bacteria have an impact on this. A potential application for the future is therefore to target this problem through the microbiome,’ says Theelen. Another important goal is to study genes related to antibiotic resistance in the equine gut microbiome, and how bacteria share these genes. Resistant bacteria can spread between horses through manure in stables.

Raising awareness among veterinarians

Theelen: ‘We want to find out how antibiotics can be used more responsibly in horses. For example, we’ve already discovered that you can see the effect of a course of antibiotics in the gut microbiome as much as six months later. A course of this type gives a boost to all kinds of resistance genes in the microbiome, not just the genes for that particular antibiotic. Hopefully, our research will make vets even more aware of the problem of antibiotic resistance.’

Guidelines

This is also the aim of the Working Group on Veterinary Antibiotic Policy (WVAB). This group assesses guidelines for veterinary antibiotic use on the basis of the latest scientific insights, national and international laws and regulations and social interests, such as public health. The guidelines can be found at and are produced jointly by veterinary experts and practitioners.

'Stopping MRSA via the pig’s snout'

Pigs

The Methicillin-Resistant Staphylococcus Aureus (MRSA) bacterium is also popularly known as the ‘hospital bug’, because it mainly causes outbreaks in hospitals. The bacterium is resistant to treatment with the antibiotic methicillin and similar antibiotics and can therefore cause major problems. In the Netherlands, we are therefore working hard to prevent the spread of MRSA in the health care sector.

A specific type of MRSA occurs in various animal species, including pigs, and can be transmitted from animals to humans. The use of antibiotics in pig farming has decreased considerably in recent years, but MSRA is still widespread in pigs. What can we do to prevent this? Researchers Birgitta Duim, Abel Vlasblom and Aldert Zomer from the Faculty of Veterinary Medicine are trying to influence the microbiome in pigs to prevent infection with MRSA.

Bacteria that ‘drive MRSA away’

‘In young piglets, we see differences in the levels of MRSA,’ says Aldert Zomer. ‘We wonder if they carry bacteria that drive MRSA away, as it were? With that knowledge, we can try to reduce MRSA. By extracting good bacteria from these less susceptible piglets and planting them in the snouts of other piglets, we hope to make pigs resistant to MRSA.’ The project is ongoing and the researchers have presented the results of a first pilot study to a specialist journal.

'Microbiome of the ‘sentinels of the sea’

Seals

Does recovery at affect the gut microbiome of seals? To answer that question, researchers Ana Rubio-Garcia and Aldert Zomer from the Faculty of Veterinary Medicine are comparing the gut microbiome of 200 harbour seals and 50 grey seals at different times: on arrival in Pieterburen, on release, on day eight and day 15 of recovery and during any antibiotic treatments. Rubio-Garcia: ‘By analysing the microbiome at different points during the recovery, we hope to be able to see the effect of nutrition, contact with carers and any antibiotic treatment. If we know whether and, if so, how these factors affect the microbiome, positively or negatively, we can adjust factors such as diet or care to prevent or stimulate this.’

Sentinels of the sea

As things stand, almost nothing is known about the gut microbiome of seals. Zomer, Assistant Professor at the Faculty of Veterinary Medicine and the microbiome expert on several research projects, explains: ‘What we do know is that seals are the sentinels of the sea. They’re right at the top of the food chain. Everything they eat is therefore representative for all the animals below them in this chain. Because the DNA of these seals hasn’t been fully genetically researched yet, it’s often difficult to determine which DNA belongs to them. What DNA comes from their diet and what DNA comes from the microbiome? This makes it easy to draw the wrong conclusions. However, we now have over 900 samples, so we have enough data to draw clear conclusions.’

In another project, Zomer is looking at biting incidents in which grey seals attack porpoises, which can cause the porpoise to die from an infection of the wound. It's all part of microbiome research.

'Pneumonia more common around intensive livestock farms'

Humans

People who live near intensive livestock farms, especially within a two-kilometre radius of a poultry or goat farm, are at a greater risk of contracting pneumonia. ‘We’ve seen this in epidemiological research for years,’ says Lidwien Smit, an epidemiologist at the Faculty of Veterinary Medicine. ‘That’s why we investigated whether the microbiome in the airways of people living near livestock farms is different from that of people who don’t live near such farms.’ This research indicated that there is indeed a difference. The throat microbiome of local residents, for example, contains more pneumococci: bacteria that are common in humans, but can also cause pneumonia.

Putting the pieces of the puzzle together

Smit: ‘We think that this difference is caused by certain air pollutants from the livestock industry, such as particulates and ammonia. To check whether this is true, we’re now going to set up a large-scale study. This will include investigating the microbiome in the respiratory tracts of more than 100 goat farmers and some 1,500 people from the surrounding area. We’ll also look at the microbiome in the stable, in the manure, in the stable dust and in the outdoor air around the farm. We hope this information will enable us to put all the pieces of the puzzle together. It will be quite a challenge to find patterns and then to link them to the environment, though. We simply don’t know yet what environmental factors play a role in this microbiome.’

Dutch goat farmers can’t wait for the results. They hope that they will help in the design of preventive measures to prevent pneumonia in local residents.

This is an article from Vetscience issue 10 (in Dutch).