Bacteria keep us healthy – but could they keep us young?

This article is taken from European research magazine Horizon as part of our partnership to share natural environment science stories with readers of More than a Dodo. Our Bacterial World exhibition is open until 28 May.

A study in mice has indicated that the make-up of bacteria in the gut is linked with learning abilities and memory, providing a potential avenue of research into how to maintain cognitive functioning as we age.

It’s part of a field of research looking at the link between gut bacteria and ageing to help people live healthier lives in old age. The proportion of the EU population aged 80 or over is predicted to more than double between 2017 and 2080, with those aged 65-plus rising from 20 to almost 30%.

However, the connection between the make-up of microbiota in the gut, brain functions and ageing has been unclear – with cause and effect difficult to establish. Dr Damien Rei, a postdoctoral researcher into neurodegenerative and psychiatric diseases at the Pasteur Institute in France, decided to examine the different types of microbiome that appear in younger and older mice to understand better what might happen in people too.

Coloured scanning electron micrograph (SEM) of Escherichia coli bacteria (red) taken from the small intestine of a child. E. coli are part of the normal flora of the human gut, though some strains cause illness.

He found that when he transferred gut bacteria in older mice to young adult mice, there was a strong effect on reducing learning and memory. And when the opposite was done, with older mice receiving microbiota from younger mice, their cognitive abilities returned to normal. The older mice were aged about a year and a half – equivalent to about 60-plus human years.

‘Despite being aged animals, their learning abilities were almost indistinguishable from those of young adult mice after the microbiota transfer,’ said Dr Rei – adding that this indicated strong communication between the gut and brain. ‘When I saw the data, I couldn’t believe it. I had to redo the experiment at least a couple of times.’

Furthermore, by seeing what was happening to the neuronal pathways of communication between the gut and brain when the aged microbiota was transferred to the younger mice, they were then able to manipulate these pathways. By doing this, he says they could block or mimic the effects of the aged microbiota.

Dr Rei’s study, which was carried out as part of a project called Microbiota and Aging, has not yet been published, but he hopes this could happen by the end of the summer. He is also looking into human gut microbiota in older people and those with Alzheimer’s disease, but said it is too early to reveal further details about this research.

Translating

However, Dr Rei pointed out that there is a big challenge in translating results in mice to people, not only because of the significant ethical barriers, but also the differences in physiology. ‘The immune system of a mouse is very different to one of a human. The gut microbiota is also very different because mice eat very different things to what we do,’ he said.

Image credit - Horizon

Research is still a long way off from making real inroads into using this type of research to combat neurodegenerative diseases such as Alzheimer’s, says Dr Rei. Indeed, he says, there is no convincing evidence yet that looking at the gut microbiota is the way to go. But he believes the mouse study opens doors to further investigation into mechanisms behind age-related changes.

‘The data on the mice was really the first stepping stone, and it was a way for us to understand the potential of manipulating the gut microbiota,’ said Dr Rei.

Pinning down the link between gut bacteria and ageing is not straightforward, according to Dr Thorsten Brach, a postdoctoral researcher at the University of Copenhagen in Denmark. ‘It’s known that ageing is a multifactorial process and it’s hard, especially when it comes to the microbiome, to separate the effects of ageing specifically from all other aspects,’ he said.

He worked on a project called Gut-InflammAge, which looked at the link between gut microbes, inflammation and ageing, led by associate professor Manimozhiyan Arumugam.

As part of their work, the team investigated the effects of mild periodic calorie restriction in mice to explore the potential impact of healthy-ageing diets involving fasting. Unexpectedly, calorie-restricted mice accumulated more body fat – which the researchers speculate may have been down to overeating between these periods – but also saw a mild ‘rejuvenation’ of their blood profile so it more closely resembled that of younger mice.

Despite being aged animals, their learning abilities were almost indistinguishable from those of young adult mice after the microbiota transfer.
Damien Rei, Pasteur Institute, France

The researchers did observe a difference between the microbiota composition in the different groups, but overall in the study the differences found were not big enough to suggest more than healthy variability between individuals. The study therefore supported the view that diet and lifestyle are more critical than age and gender in shaping the microbiota, said the researchers – though Prof. Arumugam said it would be more revealing to follow changes in individual people’s microbiomes over time.

The studies carried out so far indicate there is still a long way to go in painting an accurate picture of the link between microbiota and the ageing process. Prof. Arumugam also pointed out that microbiome analysis is lagging behind technologically compared with genetics research, with disease cause and effect harder to establish than with genes.

But research is gradually improving our understanding. Prof. Arumugam said that though his team’s study did not achieve a ‘breakthrough’, it helped give more insight into this area and raised questions over previous assumptions.

And research in this area could ultimately change how we view ageing, says Dr Rei, seeing it as more fluid than just ‘a totally one-way road with no turning back, except in the movies like Benjamin Button.’

The research in this article was funded by the EU.

Top image: Flickr/Pedro Simoes CC BY 2.0

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This post Bacteria keep us healthy – but could they keep us young? was originally published on Horizon: the EU Research & Innovation magazine | European Commission.

Bacteria that changed the world: Alcanivorax

In our Bacterial World exhibition we offer a selection of ten bacteria that have changed the world, some in profound ways. In this series of short fact-file posts we present one of the ten each week. This week’s bacteria are…

Alcanivorax borkumensis
– the oil-eaters

Where they live
Seas around the world are host to small numbers of Alcanivorax borkumensis. But if there is an oil spill, its numbers skyrocket, as the species feeds on crude oil.

Why they are important
After the Deepwater Horizon oil spill, when the equivalent of 4.2 million barrels of oil gushed into the sea off Houston, Texas, Alcanivorax borkumensis unexpectedly helped reduce the environmental impact of the disaster.

How they are named
Alcanivorax borkumensis voraciously eats oil molecules called alkanes, giving the first part of the name. The second part recalls where scientists first spotted the species, around Borkum Island in the North Sea.

How they work
The species breaks down crude oil using a range of enzymes it produces naturally. It can consume a wider range of alkane molecules than other bacterial species, and so it becomes the dominant species in a contaminated area.

Top image: : Dr. Joanna Lecka, Tayssir Kadri, Prof. Satinder Kaur Brar (INRS)

Lynn Margulis and the origins of multicellular life

To mark International Women’s Day Professor Judith Armitage, lead scientist on the Bacterial World exhibition, reflects on the ground-breaking – and controversial – work of evolutionary biologist Lynn Margulis

Iconoclastic, vivacious, intuitive, gregarious, insatiably and omnivorously curious, partisan, bighearted, fiercely protective of friends and family, mischievous, and a passionate advocate of the small and overlooked.

Lynn Margulis at the III Congress about Scientific Vulgarization in La Coruña, Spain, on November 9, 2005. Image: Jpedreira, CC BY-SA 2.5

These are all words used to describe evolutionary biologist and public intellectual Lynn Margulis. Intellectually precocious, Margulis got her first degree from the University of Chicago aged 19, but it was her exposure to an idea about the evolution of a certain type of cell that ignited a lifelong focus of her work.

This idea claimed that eukaryotic cells – cells with a nucleus, found in all plants and animals, but not bacteria – were first formed billions of years ago when one single-celled organism – a prokaryote – engulfed another to create a new type of cell. This theory, known as endosymbiosis, was laid down in a paper by Margulis in 1967. It brought her into conflict with others, including the so-called neo-Darwinists who believed in slow step-wise evolution driven by competition between organisms, not cooperation.

So what happened in the earliest evolution of these crucial cells? Initially, one bacterium ate a different, oxygen-using bacterium but didn’t digest it. Over time the two became interdependent and the bacterium took over almost all of the energy-generating processes of the host cell, becoming what we now call a mitochondrion. This allowed the cell to evolve into bigger cells and eventually form communities and develop into multicellular organisms.

Animal cells evolved when one single cell, possibly an archaeon, engulfed an aerobic bacterium – one that used oxygen to release energy. The bacterium evolved into the mitochondrion, the powerhouse of the cells of humans and other animals. A similar process created the chloroplasts found in plant cells.

These early mitochondria-containing organisms continued to eat other bacteria, and on more than one occasion they ate a photosynthesising cyanobacterium which evolved into a chloroplast, a structure now found inside plant cells.

The revolution in DNA sequencing that started in the 1970s, and continues today, eventually vindicated Margulis’ position on this ancient sequence of events. It revealed that chloroplasts and mitochondria both contain DNA with the same ancestry as cyanobacteria and proteobacteria respectively. In other words, both chloroplasts and mitochondria have evolved from ancient bacteria.

Margulis’ enthusiastic support for these ideas led her to think about the role of biology in the geology of Earth and some of its major changes, in particular the oxygenation of the atmosphere by cyanobacteria around 2.5 billion years ago. Mitochondria use oxygen, and so must have evolved from bacterial ancestors that arose after the cyanobacteria started to produce oxygen through photosynthesis.

Margulis met Gaia theorist James Lovelock soon after her seminal publication on endosymbiosis. At the time, Lovelock was looking at the composition of the atmosphere and factors causing change, including oxygen levels. He was starting to think of the Earth as a system – Gaia as it became known – where the planetary environment is regulated and kept stable by biological activity.

This meeting brought together two scientific outliers. Together they produced highly controversial articles on the “atmosphere as a biological contrivance”. Lovelock believed in concentrating on examining the systems as they are now, while Margulis brought deep time and evolutionary depth into the picture.

Margulis’ ideas were not always right, and she was enormously controversial in her time, but she made people think again. And in doing so she moved our understanding of things as apparently academically distant as the evolution of tiny cells billions of years ago to the stability of Earth’s environment today.

Top image: Euglena, a single cell eukaryotic. By Deuterostome [CC BY-SA 3.0]

Bacteria that changed the world: Prochlorococcus

In our Bacterial World exhibition we offer a selection of ten bacteria that have changed the world, some in profound ways. In this series of short fact-file posts we present one of the ten each week. This week’s bacteria are…

Prochlorococcus
– the Oxygen-Makers

Where they live
Prochlorococcus bacteria grow anywhere damp, in salt water or fresh. They are similar to the blue cyanobacteria which thrived in the far-distant past on Earth.

Why they are important
2.3-2.4 billion years ago, cyanobacteria in the oceans began producing oxygen for the first time, changing the Earth’s environment completely.

How they are named
The Greek word for blue is cyan, giving the blue cyanobacteria their name. Until recently, they were known as blue-green algae, but cyanobacteria are actually an earlier and simpler form of life than algae.

How they work
Like all cyanobacteria, Prochlorococcus bacteria harvest energy from the Sun, absorb carbon dioxide and give out oxygen – the process called photosynthesis.

Top image: Transmission Electron Micrograph (TEM) image of Prochlorococcus coloured green
Copyright: Luke Thompson, Chisholm Lab; Nikki Watson, Whitehead (MIT), 2007

Bacterial Girl


We couldn’t resist. The moment we came up with the title of our special exhibition, Bacterial World, we were all humming Madonna’s 1985 hit. So here it is – a bacteria-themed version of Material Girl – written, performed and illustrated by the talented Museum team.

In place of “cold hard cash”, you’ll learn that bacteria were involved in the creation of life on Earth, and you’ll find DNA exchange and photosynthesis in place of kisses and hugs. Have a listen… and try to stop yourself dancing.

Of course, you’ll need the full lyrics to sing it in your bedroom with a hairbrush:

BACTERIAL GIRL

Some bugs make you feel unwell
And we’ve all heard of them
But look inside and you will find
That bacteria are your friend

They’ve been around since way back when
In the ocean life began
But nowadays they’re everywhere
So I think you’ll understand, that we are…

Living in a bacterial world
And I am a bacterial girl
You know that we are
Living in a bacterial world
And I am a bacterial girl

They spent some time in the sun
Began to photosynthesise
Put oxygen in the air we breathe
I’m telling you no lies

Now E. coli’s got a real bad rep
For causing people pain
But what you got to realise
Is it’s only one bad strain

’cause we are
Living in a bacterial world
And I am a bacterial girl
You know that we are
Living in a bacterial world
And I am a bacterial girl

Now some bugs love to snuggle up to
Exchange their DNA
Other cells are armed with spears
That wipe enemies away

Resistance to our medicines
You could call it evolution
But microbes might just hold the key
To a medical solution, ’cause we are

Living in a bacterial world
And I am a bacterial girl
You know that we are
Living in a bacterial world
And I am a bacterial girl

You know that we are

Living in a bacterial world
And I am a bacterial girl!

Bacterial World is open until 28 May 2019.

Credits for this little bit of brilliance go to:
Vocals, violin: Laura Ashby
Words, banjo, guitar, recording: Scott Billings
Illustrations: Chris Jarvis

Precision antibiotics – the future treatment of infections?

by Hannah Behrens

In our Bacterial World Science Short event series, researchers present their latest findings related to themes in the exhibition. At a recent Science Short, Hannah Behrens, a University of Oxford PhD student, explained how bacteria become resistant to antibiotics and how the species-specific antibiotics she studies might reduce the worrying rise in antimicrobial resistance.

Bacteria that are resistant to antibiotics present a huge problem. I work on developing new antibiotics that will slow the development of bacterial resistance.

But let’s not get ahead of ourselves. Your body is full of bacteria. In fact, there are more bacteria than human cells in your body. Most of these bacteria are good for you; they help you digest food and protect you from diseases.

But once in a while a harmful bacterium causes an infection. This could be a lung, wound, or bladder infection, or something with a fancy name like, Black Death, tuberculosis, leprosy, syphilis or chlamydia. The doctor will then prescribe you antibiotics to kill the offending bacteria.

Hannah Behrens delivers her Science Short talk at the Museum

The development of antibiotics in the 20th century was a major breakthrough. For the first time bacterial infections could be effectively and rapidly treated. Since 1942, when antibiotics first became available, we have discovered many new antibiotics which have saved millions of lives.

However, in the last 30 years we have not managed to develop any new antibiotics. During the same time, many bacteria have adapted to become resistant to the antibiotics we do have. In 2017, a woman in the US died because she had an infection with bacteria that were resistant to all available antibiotics. It is estimated that already 700,000 people in Europe alone die because of resistant bacteria per year. What is happening?

Bacteria are forming a lawn on this plate (light areas); where an antibiotic has been spotted on the bacteria they die and leave the surface blank (dark areas).

Every time we treat bacteria with antibiotics, most die, yet a few resistant bacterial cells survive. Like Rudolph the red nosed reindeer, the resistant bacteria are usually at a disadvantage until a special situation arises (a foggy night for Rudolph; treatment with antibiotics for resistant bacteria).

Under usual circumstances, producing a resistance mechanism is a disadvantage: it wastes energy and slows down growth, so very few bacteria are resistant. Only when all the non-resistant bacteria are killed by antibiotics do the resistant ones thrive. They have no more competition, and have all the resources, such as food and space, to themselves.

The more we use antibiotics, the more resistant bacteria we get. It is essential not to use antibiotics carelessly.

More antibiotics are used in animal farming than on humans. If we eat less meat, and so reduce the farming of livestock for food, we may reduce the growth of resistance bacteria. Another approach is to only take antibiotics when the doctor prescribes them. Antibiotics do not help against viral infections like colds. In many low and middle income countries, antibiotics are available in supermarkets and it is no coincidence that these countries have higher levels of resistant bacteria.

The precision antibiotics research group in the Department of Biochemistry at the University of Oxford

Apart from avoiding the unnecessary use of antibiotics, scientists – including me – are trying to develop better therapies against bacteria. I study precision antibiotics: drugs that specifically kill one species of bacteria. The advantage of this is that all good bacteria remain unharmed and only the disease-causing species is targeted. This also means that only resistant bacteria from this one species get an advantage to thrive.

I am interested in species-specific antibiotics against Pseudomonas aeruginosa. This bacterial species causes lung and wound infections and, according to the World Health Organization, is one of the three bacteria for which we most urgently need new antibiotics. Colleagues of mine tested different precision antibiotics against Pseudomonas and found one that is better than the others, called Pyocin S5.

Hannah’s painting of how researchers think pyocin antibiotics kill bacteria. The pink bacterium produces pyocins (pink balls), which enter the susceptible blue bacteria through pores (blue). The blue bacteria mistake the antibiotic for a nutrient and open the pore to let it in. Once inside the bacterium it forms a pore in the inner membrane which causes leakage of the cell contents and kills the cell.

I am now investigating how stable this antibiotic is, how it recognises this specific species of bacteria and how it enters the bacterial cells. This knowledge is important to decide on how to store, transport and administer the drug. I also hope that understanding why Pyocin S5 is more effective than the other antibiotics will allow us to design more effective, targeted antibiotics in the future.

My hope is that one day we will treat all bacterial infections with precision antibiotics and that antibiotic resistance will become a problem of the past.