̽��ֱ�� of Cambridge - MRC Toxicology Unit

Students from across the country get a taste of studying at Cambridge at the Cambridge Festival

zs332 — Thu, 27 Mar 2025 10:17:46 +0000

We were delighted to welcome pupils from Warrington’s Lymm High School, Ipswich High School, ̽��ֱ��Charter School in North Dulwich, Rickmansworth School, Sutton Valance School in Maidstone as well as schools closer to home such as St Peter’s Huntingdon, Fenstanton Primary School, Barton Primary School, Impington Village College and St Andrews School in Soham.

Running over two days (25/26 March 2025) and held in the Cambridge Sports Centre, students went on a great alien hunt with Dr Matt Bothwell from the Institute of Astronomy, stepped back in time to explore Must Farm with Department of Archaeology and the Cambridge Archaeological Unit as well as learning to disagree well with Dr Elizabeth Phillips from ̽��ֱ��Woolf Institute.

Schools had a choice of workshops from a range of departments including, how to think like an engineer and making sustainable food with biotechnology with researchers from the Department of Chemical Engineering and Biotechnology, as well as the chance to get hands-on experience in the world of materials science and explore how properties of materials can be influenced by temperature at the Department of Materials Science and Metallurgy.

̽��ֱ��Department of Veterinary Medicine offered students the opportunity to find out what a career in veterinary medicine may look like with workshops on animal x-rays, how different professionals work together to treat animals in a veterinary hospital as well as meeting the departments horses and cows and learn how veterinarians diagnose and treat these large animals.

Students also had the opportunity to learn about antibodies and our immune system with the MRC Toxicology Unit. ̽��ֱ��students learnt about the incredible job antibodies do defending our bodies against harmful invaders like bacteria and viruses.

Alongside this, a maths trail, developed by Cambridgeshire County Council, guided students around the West Cambridge site whilst testing their maths skills with a number of problems to solve.

Now in their third year, the Cambridge Festival schools days are offering students the opportunity to experience studying at Cambridge with a series of curriculum linked talks and hands on workshops.

̽��ֱ��Cambridge Festival runs from 19 March – 4 April and is a mixture of online, on-demand and in-person events covering all aspects of the world-leading research happening at Cambridge. ̽��ֱ��public have the chance to meet some of the researchers and thought-leaders working in some of the pioneering fields that will impact us all.

Over 500 KS2 and KS3 students from as far away as Warrington got the chance to experience studying at the ̽��ֱ�� of Cambridge with a selection of lectures and workshops held as part of the Cambridge Festival.

Students make antibody keychains during a workshop with the MRC Toxicology Unit

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Supertroopers: CAR-T cell cancer therapy

lw355 — Wed, 16 Oct 2024 08:00:15 +0000

A life-saving cancer therapy is being scaled up in Cambridge to deliver more treatments to more patients for more cancers.

Researchers redesign future mRNA therapeutics to prevent potentially harmful immune responses

jg533 — Wed, 06 Dec 2023 16:02:31 +0000

mRNA - or ‘messenger ribonucleic acid’ - is the genetic material that tells cells in the body how to make a specific protein. Researchers from the Medical Research Council (MRC) Toxicology Unit have discovered that the cellular machinery that ‘reads’ mRNAs ‘slips’ when confronted with repeats of a chemical modification commonly found in mRNA therapeutics. In addition to the target protein, these slips lead to the production of ‘off-target’ proteins triggering an unintended immune response.

mRNA vaccines are considered game-changing. They have been used to control the COVID-19 pandemic and are already proposed to treat various cancers, cardiovascular, respiratory, and immunological diseases in the future.

This revolutionary class of therapeutics was made possible in part through the work of biochemist Katalin Karikó and immunologist Drew Weissman. They demonstrated that by adding chemical modifications to the bases – the building blocks of mRNA – the synthetic mRNAs could bypass some of our body’s immune defences allowing a therapeutic to enter the cell and exert its effects. This discovery led to their award of the Nobel Prize in Physiology and Medicine in 2023.

̽��ֱ��latest developments, led by biochemist Professor Anne Willis and immunologist Dr James Thaventhiran from the MRC Toxicology Unit at the ̽��ֱ�� of Cambridge, build upon previous advances to ensure the prevention of any safety issues linked with future mRNA-based therapeutics. Their report was published on 6 December in the journal Nature.

̽��ֱ��researchers identified that bases with a chemical modification called N1-methylpseudouridine – which are currently contained in mRNA therapies – are responsible for the ‘slips’ along the mRNA sequence.

In collaboration with researchers at the Universities of Kent, Oxford and Liverpool, the MRC Toxicology Unit team tested for evidence of the production of ‘off-target’ proteins in people who received the mRNA Pfizer vaccine against COVID-19. They found an unintended immune response occurred in one third of the 21 patients in the study who were vaccinated – but with no ill-effects, in keeping with the extensive safety data available on these COVID-19 vaccines.

̽��ֱ��team then redesigned mRNA sequences to avoid these ‘off-target’ effects, by correcting the error-prone genetic sequences in the synthetic mRNA. This produced the intended protein. Such design modifications can easily be applied to future mRNA vaccines to produce their desired effects while preventing hazardous and unintended immune responses.

“Research has shown beyond doubt that mRNA vaccination against COVID-19 is safe. Billions of doses of the Moderna and Pfizer mRNA vaccines have been safely delivered, saving lives worldwide,” said Dr James Thaventhiran from the MRC Toxicology Unit, joint senior author of the report.

He added: “We need to ensure that mRNA vaccines of the future are as reliable. Our demonstration of ‘slip-resistant’ mRNAs is a vital contribution to future safety of this medicine platform.”

“These new therapeutics hold much promise for the treatment of a wide range of diseases. As billions of pounds flow into the next set of mRNA treatments, it is essential that these therapeutics are designed to be free from unintended side-effects,” said Professor Anne Willis, Director of the MRC Toxicology Unit and joint senior author of the report.

Thaventhiran, who is also a practising clinician at Addenbrooke’s hospital, said: “We can remove the error-prone code from the mRNA in vaccines so the body will make the proteins we want for an immune response without inadvertently making other proteins as well. ̽��ֱ��safety concern for future mRNA medicines is that mis-directed immunity has huge potential to be harmful, so off-target immune responses should always be avoided.”

Willis added: “Our work presents both a concern and a solution for this new type of medicine, and result from crucial collaborations between researchers from different disciplines and backgrounds. These findings can be implemented rapidly to prevent any future safety problems arising and ensure that new mRNA therapies are as safe and effective as the COVID-19 vaccines.”

Using synthetic mRNA for therapeutic purposes is attractive because it is cheap to produce, so can address substantial health inequalities across the globe by making these medicines more accessible. Moreover, synthetic mRNAs can be changed rapidly – for example to create a new COVID-19 variant vaccine.

In the Moderna and Pfizer COVID-19 vaccines, synthetic mRNA is used to enable the body to make the spike protein from SARS-CoV-2. ̽��ֱ��body recognises the viral proteins generated by mRNA vaccines as foreign and generates protective immunity. This persists, and if the body is later exposed to the virus its immune cells can neutralise it before it can cause serious illness.

̽��ֱ��cell’s decoding machinery is called a ribosome. It ‘reads’ the genetic code of both natural and synthetic mRNAs to produce proteins. ̽��ֱ��precise positioning of the ribosome on the mRNA is essential to make the right proteins because the ribosome ‘reads’ the mRNA sequence three bases at a time. Those three bases determine what amino acid is added next into the protein chain. Therefore, even a tiny shift in the ribosome along the mRNA will massively distort the code and the resulting protein.

When the ribosome is confronted with a string of these modified bases called N1-methylpseudouridine in the mRNA, it slips around 10% of the time causing the mRNA to be misread and unintended proteins to be produced – enough to trigger an immune response. Removing these runs of N1-methylpseudouridine from the mRNAs prevents ‘off-target’ protein production.

This research was funded by the Medical Research Council and the Wellcome LEAP R3 programme, and supported by the NIHR Cambridge BRC.

Reference: Mulroney, T E et al: ‘(N)1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting.’ Nature, Dec 23. DOI: 10.1038/s41586-023-06800-3

Researchers have discovered that misreading of therapeutic mRNAs by the cell’s decoding machinery can cause an unintended immune response in the body. They have identified the sequence within the mRNA that causes this to occur and found a way to prevent ‘off-target’ immune responses to enable the safer design of future mRNA therapeutics.

As billions of pounds flow into the next set of mRNA treatments, it is essential that these therapeutics are designed to be free from unintended side-effects.

Anne Willis

Libre de droit/ Getty Images

Strand of mRNA

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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MICROBIOME: the kingdom of the gut

jg533 — Thu, 24 Aug 2023 08:50:40 +0000

What's so special about the bacteria in our bowels?

‘Ageing’ immune cell levels could predict how well we respond to vaccines

cjb250 — Tue, 27 Jun 2023 09:00:30 +0000

During the COVID-19 pandemic, it has become clear that some patients are better protected by vaccination than others. Many studies have shown that SARS-CoV-2 vaccines are less effective in people with weakened immune systems, but also that this effect is not uniform.

Vaccination involves priming the immune system to look for – and get rid of – invading pathogens, such as viruses and bacteria. In part, this involves stimulating the production of antibodies uniquely programmed to identify a particular invader. These antibodies are themselves produced by a type of immune cell known as a B cell.

One specific subset of B cells is known as age-associated B cells (ABCs). While, on average, less than one in 20 of a healthy individual’s B cells is an ABC, the proportion gradually increases as we get older. ̽��ֱ��reasons for this increase are not yet fully understood, but may include previous infections. Certain people with weakened immune systems accumulate ABCs still faster.

A team from the Medical Research Council (MRC) Toxicology Unit at the ̽��ֱ�� of Cambridge, led by Dr James Thaventhiran, examined ABCs from two very different patient groups – one comprised of people with an inherited condition that impairs the activity of their immune systems and a second group comprised of cancer patients taking immunotherapy drugs – as well as from healthy individuals.

Emily Horner, from Thaventhiran’s lab, explained the aim of this research: “By looking at patients’ B cells, we hoped to learn how we could stratify vulnerable patients – in other words, work out whether some patients were at greater risk from infection, even after vaccination, than others.”

̽��ֱ��researchers measured the relative proportion of ABCs compared to healthy B cells, and used a technique known as single cell RNA sequencing to look in detail at the activity of cells. They also teamed up with Dr Nicholas Matheson, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease, to test how these factors influenced the ability of a vaccinated individual’s immune system to neutralise live SARS-CoV-2 virus.

Dr Juan Carlos Yam-Puc, also from the MRC Toxicology Unit, said: “What we found, much to our surprise, was that the age-associated B cells in these very different groups looked the same. ̽��ֱ��key difference was in the amount of these cells – the greater the proportion of ABCs in an individual’s blood, the less effective that individual was post-vaccination at neutralising the virus.”

This could help explain the variability seen within particular patient groups in responses to the vaccine: people with fewer ABCs are likely to respond better to vaccines.

Although the researchers examined ABCs in the context of responses to the SARS-CoV-2 vaccine, they believe that this phenomenon will almost certainly apply more widely, for example to the annual influenza vaccine.

Dr Pehuén Pereyra Gerber, who performed the experiments with live SARS-CoV-2 virus in Matheson’s lab, added: “Looking at blood levels of ABCs could tell us that person A should respond well to a vaccine, while person B might need a stronger vaccine or to be prioritised to receive a booster.”

Thaventhiran added: “Ultimately, this research could lead to the development of a clinical test to predict vaccine efficacy for immunodeficient patients, and for the population more generally.”

̽��ֱ��research was funded by the Medical Research Council, the Medical Research Foundation, and ̽��ֱ��Evelyn Trust.

Reference
Yam-Puc, JC et al. Age-Associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade. Nat Comms; 27 June 2023; DOI: 10.1038/s41467-023-38810-0

Cambridge scientists have identified a signature in the blood that could help predict how well an individual will respond to vaccines. ̽��ֱ��discovery, published today in Nature Communications, may explain why, even among vulnerable patient groups, some individuals have better responses to vaccines than others.

By looking at patients’ B cells, we hoped to learn how we could stratify vulnerable patients – in other words, work out whether some patients were at greater risk from infection, even after vaccination, than others

Emily Horner

Ed Us

Vaccination

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Obesity accelerates loss of COVID-19 vaccination immunity, study finds

ta385 — Thu, 11 May 2023 14:59:00 +0000

Clinical trials have shown that COVID-19 vaccines are highly effective at reducing symptoms, hospitalisation and deaths caused by the virus, including for people with obesity. Previous studies have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. ̽��ֱ��reasons for this have, however, remained unclear.

This study, published in the journal Nature Medicine, shows that the ability of antibodies to neutralise the virus declines faster in vaccinated people who have obesity. ̽��ֱ��findings have important implications for vaccine prioritisation policies around the world.

During the pandemic, people with obesity were more likely to be hospitalised, require ventilators and to die from COVID-19. In this study, supported by the NIHR Bioresource and funded by UKRI, the researchers set out to investigate how far two of the most extensively used vaccines protect people with obesity compared to those with a normal weight, over time.

A team from the ̽��ֱ�� of Edinburgh, led by Prof Sir Aziz Sheikh, looked at real-time data tracking the health of 3.5 million people in the Scottish population as part of the EAVE II study. They looked at hospitalisation and mortality from COVID-19 in adults who received two doses of COVID-19 vaccine (either Pfizer-BioNTech BNT162b2 mRNA or AstraZeneca ChAdOx1).

They found that people with severe obesity (a BMI greater than 40 kg/m2) had a 76% higher risk of severe COVID-19 outcomes, compared to those with a normal BMI. A modest increase in risk was also seen in people with obesity (30-39.9kg/m2), which affects a quarter of the UK population, and those who were underweight. ‘Break-through infections’ after the second vaccine dose also led to hospitalisation and death sooner (from 10 weeks) among people with severe obesity, and among people with obesity (after 15 weeks), than among individuals with normal weight (after 20 weeks).

Prof Sir Aziz Sheikh said: “Our findings demonstrate that protection gained through COVID-19 vaccination drops off faster for people with severe obesity than those with a normal body mass index. Using large-scale data assets such as the EAVE II Platform in Scotland have enabled us to generate important and timely insights that enable improvements to the delivery of COVID-19 vaccine schedules in a post-pandemic UK.”

̽��ֱ�� ̽��ֱ�� of Cambridge team – jointly led by Dr James Thaventhiran, from the MRC Toxicology Unit and Prof Sadaf Farooqi from the Wellcome-MRC Institute of Metabolic Science – studied people with severe obesity attending the Obesity clinic at Addenbrooke’s Hospital in Cambridge, and compared the number and function of immune cells in their blood to those of people of normal weight.

They studied people six months after their second vaccine dose and then looked at the response to a third 'booster' vaccine dose over time. ̽��ֱ��Cambridge researchers found that six months after a second vaccine dose, people with severe obesity had similar levels of antibodies to the COVID-19 virus as those with a normal weight.

But the ability of those antibodies to work efficiently to fight against the virus (known as ‘neutralisation capacity’) was reduced in people with obesity. 55% of individuals with severe obesity were found to have unquantifiable or undetectable ‘neutralising capacity’ compared to 12% of people with normal BMI.

“This study further emphasises that obesity alters the vaccine response and also impacts on the risk of infection,” said Dr Agatha van der Klaauw from the Wellcome-MRC Institute of Metabolic Science and first author of the paper. “We urgently need to understand how to restore immune function and minimise these health risks.”

̽��ֱ��researchers found that antibodies produced by people with severe obesity were less effective at neutralising the SARS-CoV-2 virus, potentially because the antibodies were not able to bind to the virus with the same strength.

When given a third (booster) dose of a COVID-19 vaccine, the ability of the antibodies to neutralise the virus was restored in both the normal weight and severely obese groups. But the researchers found that immunity again declined more rapidly in people with severe obesity, putting them at greater risk of infection with time.

Dr James Thaventhiran, a Group Leader from the MRC Toxicology Unit in Cambridge and co-lead author of the SCORPIO study said: “It is promising to see that booster vaccines restore the effectiveness of antibodies for people with severe obesity, but it is concerning that their levels decrease more quickly, after just 15 weeks. This shows that the vaccines work as well in people with obesity, but the protection doesn’t last as long.”

Prof Sadaf Farooqi from the Wellcome-MRC Institute of Metabolic Science and co-lead author of the SCORPIO study said: “More frequent booster doses are likely to be needed to maintain protection against COVID-19 in people with obesity. Because of the high prevalence of obesity across the globe, this poses a major challenge for health services”.

Reference

A A van der Klaauw et al., ‘Accelerated waning of the humoral response to COVID-19 vaccines in obesity’, Nature Medicine (2023). DOI: 10.1038/s41591-023-02343-2

̽��ֱ��protection offered by COVID-19 vaccination declines more rapidly in people with severe obesity than in those with normal weight, scientists at the Universities of Cambridge and Edinburgh have found. ̽��ֱ��study suggests that people with obesity are likely to need more frequent booster doses to maintain their immunity.

This poses a major challenge for health services

Sadaf Farooqi

Steven Cornfield

Patient receiving a COVID-19 vaccination in their arm

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Gut bacteria accumulate many common medications and may reduce their effectiveness

jg533 — Wed, 08 Sep 2021 15:00:00 +0000

These interactions - seen for many drugs including those used to treat depression, diabetes, and asthma - could help researchers to better understand how drug effectiveness and side-effects differ between individuals. ̽��ֱ��study is published today in the journal Nature.

It is known that bacteria can chemically modify some drugs, a process known as biotransformation. This study, led by researchers from the Medical Research Council (MRC) Toxicology Unit at the ̽��ֱ�� of Cambridge and the European Molecular Biology Laboratory (EMBL) in Germany, is the first to show that certain species of gut bacteria accumulate human drugs, altering the types of bacteria in the gut and their activity.

This could change the effectiveness of the drug both directly, as the accumulation could reduce the availability of the drug to the body, and indirectly, as altered bacterial function and composition could be linked to side-effects.

̽��ֱ��human gut naturally contains communities of hundreds of different species of bacteria, which are important in health and disease, called the gut microbiome. ̽��ֱ��composition of bacterial species varies significantly between people and has previously been shown to be associated with a wide range of conditions including obesity, immune response, and mental health.

In this study, the researchers grew 25 common gut bacteria and studied how they interacted with 15 drugs that are taken orally. ̽��ֱ��drugs were chosen to represent a range of different types of common drugs, including antidepressant medications, which are known to affect individuals dissimilarly and cause side effects such as gut problems and weight gain.

̽��ֱ��researchers tested how each of the 15 drugs interacted with the selected bacterial strains – a total of 375 bacteria-drug tests. They found 70 interactions between the bacteria and the drugs studied, of which 29 had not been previously reported.

While earlier research has shown bacteria can chemically modify drugs, when the scientists studied these interactions further they found that for 17 of the 29 new interactions the drug accumulated within the bacteria without being modified.

Dr Kiran Patil at the ̽��ֱ�� of Cambridge’s MRC Toxicology Unit, who co-led the study, said: “It was surprising that the majority of the new interactions we saw between bacteria and drugs were the drugs accumulating in the bacteria. Until now, biotransformation was thought to be the main way that bacteria affect the availability of drugs to the body.”

“These will likely be very personal differences between individuals, depending on the composition of their gut microbiota. We saw differences even between different strains of the same species of bacteria.”

Examples of drugs that accumulated in bacteria include antidepressant duloxetine and anti-diabetic rosiglitazone. For some drugs, such as montelukast (an asthma drug) and roflumilast (for chronic obstructive pulmonary disease), both changes happened in different bacteria - they were accumulated by some species of bacteria and modified by others.

̽��ֱ��researchers also found the bioaccumulation of drugs alters the metabolism of the accumulating bacteria. For example, the antidepressant drug duloxetine bound to several metabolic enzymes within the bacteria and altered their secreted metabolites.

̽��ֱ��researchers grew a small community of several bacterial species together and found the antidepressant duloxetine dramatically altered the balance of bacterial species. ̽��ֱ��drug altered the molecules produced by the drug-accumulating bacteria, which other bacteria feed on, so the consuming bacteria grew much more and unbalanced the community composition.

̽��ֱ��researchers tested the effects further using C. elegans, a nematode worm commonly used to study gut bacteria. They studied duloxetine, which had been shown to accumulate in certain bacteria but not others. In worms grown with the species of bacteria that had been shown to accumulate the drug, the behavior of the worms was altered after being exposed to duloxetine, compared with worms that were grown with bacteria that did not accumulate duloxetine.

Dr Athanasios Typas at EMBL, who co-led the study, said: “Only now are people recognising that drugs and our microbiome impact each other with a critical consequence to our health.”

Dr Peer Bork at EMBL, and a co-lead of the study, said: “This calls for us to start treating the microbiome as one of our organs.”

Dr Patil said: “ ̽��ֱ��next steps for us will be to take forward this basic molecular research and investigate how an individual’s gut bacteria tie with the differing individual responses to drugs such as antidepressants – differences in whether you respond, the drug dose needed, and side effects like weight gain. If we can characterise how people respond depending on the composition of their microbiome, then drug treatments could be individualised.”

̽��ֱ��researchers caution that the study findings are only on bacteria grown in the lab, and more research is needed to understand how bioaccumulation of medications by gut bacteria manifests inside the human body.

̽��ֱ��study started as a collaborative project at EMBL Heidelberg and was concluded in the group of Kiran Patil after his move to Cambridge.

This study was funded by the European Commission Horizon 2020, MRC and EMBL.

Reference

Klunemann, M. et al: 'Bioaccumulation of therapeutic drugs by human gut bacteria’, Nature, Sept 2021.

Adapted from a press release by EMBL.

Common medications can accumulate in gut bacteria, a new study has found, altering bacterial function and potentially reducing the medications’ effectiveness.

If we can characterise how people respond depending on the composition of their microbiome, then drug treatments could be individualised

Kiran Patil

Paul Appleton, ̽��ֱ�� of Dundee. Attribution 4.0

Villi in the colon

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cooperation is key to success in microbial communities

jg533 — Mon, 04 Jan 2021 16:15:20 +0000

̽��ֱ��results are published today in the journal Nature Microbiology.

̽��ֱ��study used kefir as a model to study metabolic interactions within microbial communities. It is easy to grow, and consists of around 40 different species - providing a ‘Goldilocks zone’ of complexity that is not too small yet not too unwieldy to study in detail. Kefir is composed of ‘grains’ - resembling small pieces of cauliflower - that have fermented in milk to produce a probiotic drink composed of bacteria and yeasts.

̽��ֱ��researchers were surprised to discover that the dominant species of Lactobacillus bacteria found in kefir grains cannot survive on their own in milk. However, the different species work together, feeding on each other’s metabolites in the kefir culture to support each other.

“ ̽��ֱ��kefir grain acts as a ‘base camp’ for the kefir community, from which microbes colonise the milk in a complex, yet organised and cooperative manner,” said Dr Kiran Patil, Director of Research at the ̽��ֱ�� of Cambridge’s MRC Toxicology Unit, group leader at EMBL, and senior author of the study.

̽��ֱ��researchers combined a variety of state-of-the-art methods including metabolomics (studying metabolites’ chemical processes), transcriptomics (studying the genome-produced RNA transcripts), and mathematical modelling. This revealed not only key molecular interaction agents like amino acids, but also the contrasting species dynamics between the grains and the milk.

While scientists know that microorganisms often live in communities and depend on their fellow community members for survival, there was previously very little understanding of how this works. Lab models have historically been limited to two or three different microbial species.

“Kefir microbial communities have many member species, with individual growth patterns that adapt to their current environment. This means fast- and slow-growing species and some that alter their speed according to nutrient availability,” said Sonja Blasche, a postdoc in the Patil group at EMBL and joint first author of the paper.

Kefir is one of the world’s oldest fermented foods and has many purported health benefits, including improving digestion and lowering blood pressure and blood glucose levels.

This phenomenon of microbial cooperation is not limited to kefir. In another paper from Patil’s group, published today in the journal Nature Ecology and Evolution, scientists combined data from thousands of microbial communities across the globe - from soil to the human gut - to understand similar cooperative relationships.

Advanced metabolic modelling showed that the co-occurring groups of bacteria are either highly competitive or highly cooperative. This stark polarisation has not been observed before and sheds light on evolutionary processes that shape microbial ecosystems. While both competitive and cooperative communities are prevalent, the cooperators seem to be more successful: they are more abundant and occupy a more diverse range of habitats.

“We see this phenomenon in kefir, and then we see it’s not limited to kefir,” said Patil. “If you look at the whole world of microbiomes, cooperation is also key to their structure and function.”

References
Patil, K.R. ‘Metabolic cooperation and spatiotemporal niche partitioning in a kefir microbial community.’ Nature Microbiology, Jan 2021. DOI: 10.1038/s41564-020-00816-5.

Patil, K.R. ‘Polarisation of microbial communities between competitive and cooperative metabolism.’ Nature Ecology & Evolution, Jan 2021. DOI: 10.1038/s41559-020-01353-4.

Adapted from a press release by EMBL.

New research from the ̽��ֱ�� of Cambridge and European Molecular Biology Laboratory (EMBL) shows how cooperation among bacterial species allows them to thrive as a community.

If you look at the whole world of microbiomes, cooperation is key to their structure and function.

Kiran Patil

Svorad on Wikimedia Commons

Milk kefir grains with jar of kefir in background

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