How is bacteria linked to the development of rheumatoid arthritis?

Old hands with rheumatoid arthritis clasped together

The way the immune system interacts with oral and gut bacteria may lead to the development of rheumatoid arthritis, according to researchers from King’s College London.

These findings may one day help us predict who is likely to develop rheumatoid arthritis, and prevent and treat the condition in new ways.

Rheumatoid arthritis is an autoimmune condition in which the body’s immune system mistakenly attacks the lining of the joints. The condition affects 400,000 people in the UK, and leads to painful, swollen joints and reduced mobility.

This is the first time researchers have investigated how genes and bacteria may work together to lead to rheumatoid arthritis.

The review was published today in the Journal of Autoimmunity.

Why did they do this research?

We know that rheumatoid arthritis is largely inherited through certain genes, but only about a third of identical twins – who have identical genes – have matching cases of the condition. This suggests that in many cases, genes alone are not enough to lead to rheumatoid arthritis.

Researchers have also previously found differences in the oral, lung and gut bacteria of people diagnosed with rheumatoid arthritis and those without.

In this work, the team decided to review the available evidence to see how certain genetic factors and bacteria in the body – the microbiome – may lead to rheumatoid arthritis.

The work was led by Philippa Wells, a PhD student at the Department of Twin Research and Genetic Epidemiology at King’s College London.

What did they find?

The team analysed many previous studies that looked at how genes and the microbiome were linked with rheumatoid arthritis.

Based on their analysis, the researchers suggested that certain genes to do with the immune system are the key link between genes, the microbiome and rheumatoid arthritis.

Genes largely determine how the immune system behaves. The researchers proposed that the immune system then responds inappropriately to certain bacteria in the body, which ultimately leads to the immune system mistakenly attacking the joints.

What does this mean?

This is the first time researchers have investigated how interactions between genes and bacteria may lead to rheumatoid arthritis.

In the future, we may be able to use the microbiome to predict whether and when someone might develop rheumatoid arthritis. Researchers could also develop treatment strategies for the condition that work through targeting bacteria in the body.

Researcher Philippa Wells explained:

“These methods let us investigate what is happening with the microbiome before onset of rheumatoid arthritis, as well as unpicking what influences the microbiome differences we see in people with rheumatoid arthritis.

“From that, we can gain insight in to the direction of influence, i.e whether changes in the microbiome cause rheumatoid arthritis or vice versa, and get a clearer idea of the underlying biology.

“This will be important groundwork for future clinically focused studies.”

What’s the next step?

In their paper, the researchers stress that it will be important to understand the effect of current rheumatoid arthritis medication on the microbiome.

Life after death? Measuring metabolism beyond the grave

Back of a person wearing a high visibility yellow jacket with police written on it

Researchers have provided early evidence for a new method that could help forensic scientists determine time of death more accurately in criminal investigations.   

The team found that the levels of certain molecules in organs such as the heart, kidney and liver in mice change in particular patterns after death.  

These patterns could one day be used by forensic investigators to work out more accurately when someone died, according to the researchers. 

The studyled by Dr Marina Mora-Ortiz, Research Associate in the Department of Twin Research & Genetic Epidemiology of King’s College London, was published today in Metabolomics. 

Why did they do this research?

Although rare, it’s not always possible to work out when exactly someone has died.  

Forensic scientists for example working on criminal investigations have to rely on a number of different physical tests and checks to estimate time of death. 

In 2016, researchers were surprised to find that hundreds of genes actually increase their activity in the days after death.  

Dr Mora-Ortiz and her colleagues therefore decided to see whether there are also changes in the levels of certain molecules involved in metabolism – known as metabolites –  in the body after death.  

What did they do?

The team studied the heart, kidney, liver, spleen, skin and fat of 10 mice at three different time points after death, up to 24 hours. 

The researchers used a powerful technique known as NMR spectroscopy to determine the levels of certain metabolites in each of these body parts. 

What did they find?

The team identified 43 metabolites linked with post-mortem changes.  

The spleen, heart and kidneys had the most changes in metabolite levels over the 24-hour period.  

The liver and skin however were less affected, which suggests that these organs are more resistant to degradation after death. 

What does this mean?

These results are early evidence that the NMR spectroscopy technique could be used to help analyse changes in organs after death, and one day help forensics teams in their investigations.  

In the future, doctors could also use this method to check the quality of donated organs in more detail, and so improve outcomes for transplant recipients. 

Dr Mora-Ortiz explained:  

We think NMR metabolomics has a great potential to study post-mortem changes, but we need further studies to complete the whole picture and understand what is happening beyond the first 24 hours.  

This proof-of concept work opens the doors to a new field of research, Thanatometabolomics, that could be employed – paradoxically – to improve the lives of people.”  

What’s the next step?

As this work was carried out in mice, the next step will be to see if the same method can accurately capture changes in metabolites and time of death in humans. 

Body or brain behind back pain?

Wooden mannequin with arm on back

Back pain may be caused through the body or through the brain, according to the results of a new genetics study.

The international team, which included researchers from King’s College London, studied the genetic information of over 500,000 people.

They found genetic links between back pain and some of its known risk factors, such as depression, sleep disturbance, obesity and smoking.

Overall, the results highlight the complexity of the genetics behind back pain.

Why did they do this research?

Back pain is very common, and many adults will experience it during their lives. About one in ten people however go on to develop chronic back pain, which can be debilitating and affect people’s quality of life and ability to work.

Previously the team had identified genes linked to chronic back pain. The researchers therefore decided to carry out a much larger study, to get a better understanding of how genes are linked to back pain.

What did the team do?

The researchers used data from two existing research programmes.

The team analysed the genetic data of 509, 070 people who indicated they were experiencing back pain, and examined the links between back pain and known medical and social risk factors.

What did they find?

The team identified two further genes linked with back pain.

The researchers also found genetic links between back pain and depression, sleep disturbance, obesity and smoking, which are known risk factors for back pain.

Based on their findings and further analysis, the researchers proposed two key routes through which back pain may start.

One route was through the vertebrae – disks – that make up the backbone. The other route was through how people perceive and process pain.

What does this mean?

These results support what we currently understand about back pain. The findings will also help researchers and healthcare professionals develop strategies to treat and prevent back pain.

Dr Maxim Freidin, who led the study, explained:

“This study continues our ongoing efforts to identify genes underlying back pain.

“One of the most striking finding is shared genetic component of back pain with many other traits such as obesity, depression and anxiety, social and demographic factors. These traits co-occur with back pain and are considered as its risk factors.

“By identifying shared genetics for back pain and these traits, we provide evidence that this co-occurrence has strong biological ground. In turn, this finding may help identify causal links between back pain and its risk factors.”

Watch the short animation below to find out more about our back pain research.

Researchers identify key genes involved in chronic back pain

A team of researchers from around the world, led by TwinsUK’s Professor Frances Williams, has discovered three new genes linked to the development of chronic back pain. In a huge study of 440,000 people, ranging from 50 to 76 years old, the team studied the whole genome to look at genes that contribute to chronic back pain. They discovered that the genetics of back pain is very complex, with numerous different genes having an effect; however a group of three genes had a noticeably bigger effect.

The researchers had thought they would find that pain-related genes would be the main genes associated with chronic back pain. However, they instead found that the strongest link was with three genes involved in bone and intervertebral disc development. Crucially this suggests that degeneration of the spine influences chronic back pain, which is in line with previous TwinsUK research showing that spine degeneration predicts back pain episodes.

Spine degeneration is something that happens to us all as we age. The team hopes that further research into the three new genes will enable them to target new treatments to slow down the ageing process in the spine and therefore prevent long-term back pain.

Read more about this research on the King’s College London news pages, or read the open access paper, published in PLOS Genetics. This research has also been turned into an animation which you can view here.

 

Gut microbe diversity linked to lower arterial stiffness

New research from TwinsUK and the University of Nottingham has identified a link between gut microbe diversity and arterial stiffness.

Arterial stiffness, or hardening, happens naturally as we age and is a known risk factor for cardiovascular disease. The rate at which this hardening occurs varies from person to person.

The gut microbiome is implicated in various aspects of health, and has previously been linked to inflammation, which can increase the risk of developing heart disease.

Using data from 617 female twins, researchers found that gut microbiome diversity correlates with arterial stiffness; arterial stiffness is higher in women with lower diversity of healthy bacteria in the gut.

The researchers were also able to identify specific types of healthy bacteria that lowered the risk of arterial stiffening. These bacteria have previously been linked to a lower risk of obesity.

The results suggest that the gut microbiome could in future be used to identify those people at higher risk of a cardiovascular event in the absence of more traditional risk factors such as obesity or smoking.

This study was funded by the British Heart Foundation and MRC and was published by European Heart Journal.

New genes implicated in whether skin will burn in the sun

Researchers at TwinsUK have identified ten new genetic regions involved in whether a person is likely to tan or burn. These new regions also suggest who may be more likely to develop skin cancer.

Sunburn is already a known risk factor for skin cancer, the most common type of cancer in Europe, but whether a person’s skin will burn or tan varies widely from person to person.

In the largest study to date of skin’s tendency to tan or burn, TwinsUK researchers Mario Falchi and Alessia Visconti of King’s Department of Twin Research, in a collaborative effort with colleagues from across the world, analysed genetic data from 176,678 individuals of European ancestry. As well as identifying new genetic regions that indicate whether or not a person will tan or burn, one of these regions, which has previously been associated with melanoma, may directly increase the risk of cancer by reducing the ability of the skin to tan.

The study’s results have doubled the number of genetic regions known to be involved in tanning versus burning. Their discovery paves the way for further research to explore how the genetic regions contribute to the risk of skin cancer.

This research is published in Nature Communications. Find out more and read the paper here.

More than 100 genes determine hair colour

Dr Pirro Hysi and a group of researchers from Kings’s College London and Erasmus MC University Medical Center Rotterdam have discovered 124 genes that play a major role in human hair colour. The study is the largest of its kind, using DNA data and self-reported hair colour information from nearly 300,000 people.

Previous studies have found that much of the variation in human hair colour is down to genetics, with around a dozen known genes, but this study largely completes the knowledge gap of which genes control hair colour. Around 100 of the genes the team discovered were not previously known to contribute to pigmentation. These new genes have also allowed the team to predict hair colour much more accurately than before.

The study is the largest genetic study on pigmentation ever undertaken and could advance our knowledge of diseases that are linked to pigmentation, such as skin cancer. The results could also be applied to forensic science.

Read the paper, published in Nature Genetics.

Genes affect fat deposition and Type 2 diabetes risk

A new paper from Dr Kerrin Small and her team has found that a variant of the KLF14 gene, previously identified in earlier research by the same group, not only changes where fat is deposited (on the hips versus on the waist), but that it also affects the generation of new fat cells.

Using biopsy and blood samples from 856 female twins, fat biopsies from the Oxford BioBank and genetic data from the UK Biobank, their latest study found that variations of the KLF14 gene also makes it harder to generate new fat cells, leaving carriers of the gene with fewer, larger fat cells that are less efficient. These less efficient fat cells reduce the body’s sensitivity to insulin and suggests that there is an increased chance of developing Type 2 diabetes.

Even more strikingly, these effects are specific to females; the researchers found that the gene only acts in women who inherit the diabetes-associated version from their mother. These women had around a 30% higher chance of developing diabetes than those without the diabetes-associated version.

These exciting results mean that we now have such a detailed level of understanding of this variant of the KLF14 gene that we know where and how it acts in the body as well as who it acts in. The team hope that these results will allow them to understand why the gene variant only affects women’s chance of developing diabetes so that they can help develop better prevention and treatment options.

Read the paper, published in Nature Genetics.

Dietary omega-3 improves the diversity of gut bacteria

New research from TwinsUK, published in the Nature journal Scientific Reports last week suggests that including more dietary omega-3 fatty acids improves the diversity of bacteria found in our gut.

The study, carried out in 876 women from the TwinsUK cohort, looked at whether dietary intake of fatty acids affects the diversity of the gut microbiome. The authors found that the amount of omega-3 fatty acids correlates with improved bacterial diversity in the gut, and is specifically associated with “good” bacterial species. The effects of dietary omega-3 were also seen in metabolites produced by gut bacteria. Higher levels of beneficial compounds, including omega-3 itself as well as n-carbamyl glutamate (NCG) which has been linked to reduced gut inflammation in rats, were found in people with more omega-3 in their diets.

The findings suggest that we could improve our gut health through our diets and the team is now planning a new study to test whether giving omega-3 supplements might improve the diversity of gut bacteria in healthy volunteers.

The open access paper is available to read here.

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Old hands with rheumatoid arthritis clasped together

How is bacteria linked to the development of rheumatoid arthritis?

New research from TwinsUK, published in the Nature journal Scientific Reports last week suggests that including more dietary omega-3 fatty...

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Life after death? Measuring metabolism beyond the grave

New research from TwinsUK, published in the Nature journal Scientific Reports last week suggests that including more dietary omega-3 fatty...

Wooden mannequin with arm on back

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