Newly discovered species of bacteria in the microbiome may be a culprit behind rheumatoid arthritis
By Meagan Chriswell, University of Colorado Anschutz Medical Campus
Aurora (The Conversation)(PTI): Rheumatoid arthritis affects 1 in 100 people worldwide. It causes inflamed, painful and swollen joints, often in the hands and wrists, and can lead to loss of joint function as well as chronic pain and joint deformities and damage.
What causes this condition has been unknown.
In our recently published study, my colleagues and I found an important clue to a potential culprit behind this disease: the bacteria in your gut.
What causes rheumatoid arthritis?
Rheumatoid arthritis is an autoimmune condition, meaning it develops when the body's immune system starts to attack itself. Proteins called antibodies, which usually help fight off viruses and bacteria, begin to attack the joints instead.
The origins of the antibodies that cause rheumatoid arthritis have been an area of study for many years.
Some research has shown that these antibodies can start forming at sites like the mouth, lung and intestines over 10 years before symptoms arise.
But until now, it was unclear why researchers were finding these antibodies in these particular areas.
We wanted to investigate what could trigger the formation of these antibodies. Specifically, we wondered if bacteria in the microbiome, a community of microorganisms that live in the intestines, might be the ones activating the immune response that leads to rheumatoid arthritis.
Since microbes commonly live at the same sites as the antibodies driving rheumatoid arthritis, we hypothesised that these bacteria could be triggering the production of these antibodies.
We reasoned that though these antibodies were meant to attack the bacteria, rheumatoid arthritis develops when they spread beyond the intestines to attack the joints.
First, we sought to identify the intestinal bacteria targeted by these antibodies. To do this, we exposed the bacteria in the feces of a subset of people at risk for developing rheumatoid arthritis to these antibodies, allowing us to isolate just the bacterial species that reacted and bound to the antibodies.
We found that one previously unknown species of bacteria was present in the intestines of around 20 per cent of people who were either diagnosed with rheumatoid arthritis or produce the antibodies that cause the disease.
As a member of the Cherokee Nation of Oklahoma, I suggested we name this species Subdoligranulum didolesgii ( didolesgii means arthritis or rheumatism in Cherokee) as a nod to the contributions that other Indigenous scholars have made to science as well as the fact that rheumatoid arthritis affects Indigenous people at a higher rate than other populations.
Subdoligranulum didolesgii has not been detected in the feces of healthy people before, and it is currently unknown how prevalent this bacteria is in the general population.
We also found that these bacteria can activate specialised immune cells called T cells in people with rheumatoid arthritis.
T cells drive inflammatory responses in the body, and have been linked to the development of different autoimmune diseases.
These findings suggest that these gut bacteria may be activating the immune systems of people with rheumatoid arthritis. But instead of attacking the bacteria, their immune system attacks the joints.
Why this bacteria?
It is still unknown why people with rheumatoid arthritis develop an immune response to Subdoligranulum didolesgii.
But we think it may be the culprit when it comes to rheumatoid arthritis because this bacteria is found only in the intestines of people with rheumatoid arthritis, and not in the intestines of healthy people.
While many immune responses happen in the intestines, they are usually self-contained and do not spread to other areas of the body.
However, we believe that a particularly strong intestinal immune response against Subdoligranulum didolesgii could allow antibodies to bypass the intestinal firewall and spread to the joints.
To confirm our hypothesis, we gave mice an oral dose of Subdoligranulum didolesgii and monitored their reaction.
Within 14 days, the mice began to develop joint swelling and antibodies that attacked their joints.
The future of rheumatoid arthritis treatment
My colleagues and I hope this research can shed light on the origins of rheumatoid arthritis.
Our next goal is to discover how common these bacteria are in the general population and test whether the presence of these bacteria in the gut may lead to the development of rheumatoid arthritis in people.
It's important to note that antibiotics are unlikely to be helpful treatment for the microbiomes of patients with rheumatoid arthritis.
Although Subdoligranulum didolesgii may be triggering an autoimmune response for some people with rheumatoid arthritis, antibiotics eliminate both helpful and harmful bacteria in the gut.
Additionally, removing the bacteria won't necessarily stop the immune system from attacking the joints once it has started.
Nevertheless, we believe that these bacteria can be used as tools to develop treatments for rheumatoid arthritis and hopefully ways to prevent disease from happening in the first place.
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Actress sexual assault: Court says Prosecution 'miserably' failed to prove conspiracy against Dileep
Kochi (PTI): The prosecution had "miserably" failed to prove the conspiracy charge against Dileep in the sensational 2017 actress sexual assault case, a local court has observed while citing inconsistencies and lack of sufficient evidence against the Malayalam star.
The full judgement of Ernakulam District and Principal Sessions Court Judge Honey M Varghese was released late on Friday, and has revealed the judge also pointing out at unsustainable arguments put forth by the prosecution.
"The prosecution miserably failed to prove the conspiracy between accused No.1 (Pulsar Suni) and accused No.8 (Dileep) in executing the offence against the victim," the court held.
It examined in detail, the prosecution's allegation that Dileep had hired the prime accused to sexually assault the survivor and record visuals, including close-up footage of a gold ring she was wearing, to establish her identity.
On page 1130 of the judgment, under paragraph 703, the court framed the issue as whether the prosecution's contention that NS Sunil (Pulsar Suni) recorded visuals of the gold ring worn by the victim at the time of the occurrence, so as to clearly disclose her identity, was sustainable.
The prosecution contended Dileep and Suni had planned the recording so that the actress' identity would be unmistakable, with the video of the gold ring intended to convince Dileep that the visuals were genuine.
However, the court noted that this contention was not stated in the first charge sheet and was introduced only in the second one.
As part of this claim, a gold ring was seized after the victim produced it before the police.
The court observed that multiple statements of the victim were recorded from February 18, 2017, following the incident, and that she first raised allegations against Dileep only on June 3, 2017.
Even on that day, nothing was mentioned about filming of the ring as claimed by the prosecution, the court said.
The prosecution failed to explain why the victim did not disclose this fact at the earliest available opportunities.
It further noted that although the victim had viewed the sexual assault visuals twice, she did not mention any specific recording of the gold ring on those occasions, which remained unexplained.
The court also examined the approvers' statements.
One approver told the magistrate that Dileep had instructed Pulsar Suni to record the victim's wedding ring.
The court observed that no such wedding ring was available with her at that time.
During the trial, the approver changed his version, the court said.
The Special Public Prosecutor put a leading question to the approver on whether Dileep had instructed the recording of the ring, after which he deposed that the instruction was to record it to prove the victim's identity.
The court observed that the approver changed his account to corroborate the victim's evidence.
When the same question was put to another approver, he repeated the claim during the trial but admitted he had never stated this fact before the investigating officer.
The court noted that the second approver even went to the extent of claiming Dileep had instructed the execution of the crime as the victim's engagement was over.
This showed that the evidence of the second approver regarding the shooting of the ring was untrue, as her engagement had taken place after the crime.
The court further observed that the visuals themselves clearly revealed the victim's identity and that there was no need to capture images of the ring to establish identity.
In paragraph 887, the court examined the alleged motive behind the crime and noted that in the first charge sheet, the prosecution had claimed that accused persons 1 to 6 had kidnapped the victim with the common intention of capturing nude visuals to extort money by threatening to circulate them and there was no mention about Dileep's role in it.
The court also rejected the prosecution's claim that the accused had been planning the assault on Dileep's instructions since 2013, noting that the allegation was not supported by reliable evidence.
It similarly ruled out the claim that Suni attempted to sexually assault the victim in Goa in January 2017, stating that witness statements showed no such misconduct when he served as the driver of the vehicle used by the actress there.
The court also discussed various controversies that followed Dileep's arrest and the evidence relied upon by the prosecution, ultimately finding that the case had not been proved.
Pronouning its verdict on the sensational case on December 8, the court acquitted Dileep and three others.
Later, the court sentenced six accused, including the prime accused Suni, to 20 years' rigorous imprisonment.
The assault on the multilingual actress, after the accused allegedly forced their way into her car and held it under their control for two hours on February 17, 2017, had shocked Kerala.
Pulsar Suni sexually assaulted the actress and video recorded the act with the help of the other convicted persons in the moving car.
