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Gut pain may help to maintain a healthy microbiome in mice

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Neurons that transmit pain signals in the gut lining of mice are linked to the production of mucus that may maintain a healthy microbiome



Health



14 October 2022

Pain that affects the gut lining of mice may have some protective properties

Kevin Mackenzie/UNIVERSITY OF ABERDEEN/SCIENCE PHOTO LIBRARY

Neurons that transmit pain signals in the gastrointestinal lining of mice may help to maintain a healthy gut microbiome.

Isaac Chiu at Harvard University and his colleagues wanted to better understand the role that pain neurons play in the gut. “If you look for pain fibres in the gut, you usually see them close to epithelial cells [which cover the gut lining], which suggests that they can talk to each other,” says Chiu.

First, the team genetically modified mice to lack pain neurons in their gut lining.

Without these neurons, the mice had thinner layers of mucus lining their guts compared with rodents that hadn’t been genetically modified.

The modified mice also had a substantially different microbiome to their unmodified counterparts, indicating that a thicker mucus helps to maintain a healthy microbial community.

“These findings suggest that pain is quite important for keeping our mucus layer intact and also keeping our microbiome healthy,” says Chiu.

Pain that affects the gut lining may be linked to mucus production for several reasons. “Some harmful products in the GI [gastrointestinal] tract, such as salmonella or E. coli, may require immediate attention,” he says. “You may want to coat the gut with mucus to protect it or the mucus could even facilitate wound healing, though this is speculative.”

In a second part of the experiment, the researchers genetically sequenced several of the cells that were producing the mucus. They found that these goblet cells had receptors on their surface that bind to a chemical produced by neurons, specifically the neuropeptide CGRP.

“It suggests that pain fibres which make CGRP could be talking to goblet cells via this transmitter,” says Chiu.

Next, the team found that the activation of pain neurons in the mice’s gut lining led to mucus being produced by goblet cells within minutes.

In a laboratory experiment, the researchers looked at human goblet cells, finding that they also express high levels of the receptor for CGRP. “We think that human goblet cells could also respond to the same molecule from pain fibres,” says Chiu.

According to Chiu, many migraine medications block CGRP signalling. CGRP is expressed in both of the body’s nervous systems: the central nervous system, which comprises the brain and spinal cord, and the peripheral nervous system, made up of nerves that branch off from the spinal cord and extend to all other parts of the body.

“These drugs could be having a negative effect if they cause the mucus lining of the gut in people to be thinner and the microbiome in the gut to be dysregulated,” says Chiu.

The interaction between pain neurons and cells in the gut lining may be involved in the discomfort experienced by many people with ulcerative colitis, an inflammatory bowel disease, according to Chiu.

“This elegant study highlights another line of communication that has co-evolved between the intestinal microbiota and the mammalian host,” says Jon Swann at Imperial College London.

“This provides the host with a mechanism to maintain gut homeostasis and protection during intestinal inflammation and the microbes with influence over mucus secretion, a major factor in gut health.”

Journal reference: Cell, DOI: https://doi.org/10.1016/j.cell.2022.09.024

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WHO estimates 90% of world have some resistance to Covid | Coronavirus

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The World Health Organization estimates that 90% of the world population now has some resistance to Covid-19, but warned that a troubling new variant could still emerge.

Gaps in vigilance were leaving the door open for a new virus variant to appear and overtake the globally dominant Omicron, the WHO director general, Tedros Adhanom Ghebreyesus, said.

“WHO estimates that at least 90% of the world’s population now has some level of immunity to Sars-CoV-2, due to prior infection or vaccination,” said Tedros, referring to the virus that causes the Covid-19 disease.

“We are much closer to being able to say that the emergency phase of the pandemic is over – but we’re not there yet,” he told reporters.

“Gaps in surveillance, testing, sequencing and vaccination are continuing to create the perfect conditions for a new variant of concern to emerge that could cause significant mortality.”

Last weekend marked one year since the organisation announced Omicron as a new variant of concern in the Covid-19 pandemic, Tedros noted.

It has since swept round the world, proving significantly more transmissible than its predecessor, Delta.

Last week, the latest real-world study of updated Covid boosters showed that new vaccines by Pfizer/BioNTech and Moderna are likely to provide better protection compared with the original shots.

The study of more than 360,000 people indicated that the boosters offer increased protection against new variants in people who have previously received up to four doses of the older vaccine.

Since their introduction to the US in September, the vaccine boosters, which contain both original and Omicron BA.4/5 coronavirus strain, provided greater benefit to younger adults aged 18-49 years that those in the older age group.

Tedros said there were now more than 500 highly transmissible Omicron sub-lineages circulating – all able to get around built-up immunity more easily, even if they tended to be less severe than previous variants.

Around the world, 6.6 million Covid deaths have been reported to the WHO, from nearly 640 million registered cases. But the UN health agency says this will be a massive undercount and unreflective of the true toll.

Tedros said more than 8,500 people were recorded as having lost their lives to Covid last week, “which is not acceptable three years into the pandemic, when we have so many tools to prevent infections and save lives”.

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Kevin Durant, Nets beat Raptors to tally fourth win in a row

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Make it four in a row and seven of their last nine.

The Nets are one of the hottest teams in basketball and moved two games above .500 with a 114-105 victory over the Toronto Raptors in front of a sellout 17,732 fans at Barclays Center on Friday night.

They led by as many as 36 points before letting the Raptors creep back into the game late in the fourth quarter.

After digging a 2-6 hole to start the season, the Nets (13-11) have pulled a complete 180. They are inching closer toward contender status, though they still have tremendous ground to cover separating themselves from the cream of the NBA crop.

And it both looks and feels different when the Nets aren’t leaning too heavily on Kevin Durant — or Kyrie Irving, as they did for unending stretches last season.

Durant’s minutes have become a point of contention in Brooklyn, as they were last year. He entered Friday’s matchup as the league’s leader in minutes, points and field goals. At age 34 and in year 15, the Nets star is averaging 37 minutes per game for the second consecutive season.

“We’ve had to play Kevin more minutes than we’ve wanted to,” head coach Jacque Vaughn said ahead of tipoff. “That’s just kind of where we are. He understands that.”

It hits different, though, when Durant has help, and it reflects on the scoreboard.

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Sharpshooter Joe Harris got hot early, scoring 11 points in the first quarter alone. After breaking out of his shooting slump to hit four out of six threes in Wednesday’s win over the Washington Wizards, Harris, who is starting in place of the injured Ben Simmons (calf strain), hit another five threes for 17 points against the Raptors on Friday.

Royce O’Neale hit a trio of timely threes, and Kyrie Irving shouldered a large chunk of the scoring load, scoring 27 points on 17 shot attempts. Veteran forward TJ Warren, in his Nets debut after missing two-plus seasons with consecutive stress fractures in his left foot, scored 10 points on 5-of-11 shooting off the bench.

And Nic Claxton added 15 points and nine rebounds, sealing the game with a putback dunk, then offensive rebound and finish that extended the Nets’ lead back to 16.

He forced Raptors coach Nick Nurse to call his second to last timeout with four minutes left in the fourth.

It was Durant’s lightest workload of the season. He still played 38 minutes but they were low impact. He only took 10 shots and finished with 17 points, nine rebounds and seven assists.

The Nets built a lead as large as 36 and watched the Raptors whittle the deficit down to as little as seven in the final minute of the fourth quarter. It wasn’t a pretty finish but nothing has come easy for the Nets this season.

They have a chance to make it five in a row on Sunday, though they’ll have to go through last year’s Eastern Conference champion Boston Celtics to get there.

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Fourth child dies in UK after contracting Strep A infection | UK news

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A fourth child has died in the UK after contracting Strep A, as health officials issued warnings to parents and school staff about signs and symptoms of infection.

These include a sore throat, fever and minor skin infections. In rare incidences, it can become a severe illness, and anyone with high fever, severe muscle aches, pain in one area of the body and unexplained vomiting or diarrhoea should seek urgent medical help.

On Friday, the UK Health Security Agency (UKHSA) confirmed that a child who attended St John’s primary school in Ealing, west London, had died from the bacterial infection, while it also emerged that the parents of a four-year-old boy from Buckinghamshire have said he has died from Strep A.

Shabana Kousar, the mother of Muhammad Ibrahim Ali, who attended the Oakridge school and nursery in High Wycombe, told the Bucks Free Press: “The loss is great and nothing will replace that. He was very helpful around the house and quite adventurous, he loved exploring and enjoyed the forest school, his best day was a Monday and [he] said how Monday was the best day of the week.

“He also had a very close bond with his dad. He was his best friend and went everywhere with him. He just wanted to be with him.”

A pupil from Victoria primary school in Penarth, four miles south of Cardiff, has also died from the infection. A six-year-old died last week after an outbreak of the same infection at a school in Surrey.

Health officials are understood to have reported a slight rise recently in cases of Strep A, which can cause scarlet fever, although deaths and serious complications from the infection are rare.

Dr Yimmy Chow, a health protection consultant at UKHSA, said of the Ealing case: “We are extremely saddened to hear about the death of a child at St John’s primary school, and our thoughts are with their family, friends and the school community. Working with Ealing council public health team, we have provided precautionary advice to the school community to help prevent further cases and we continue to monitor the situation closely.

“Group A streptococcal infections usually result in mild illness, and information has been shared with parents and staff about the signs and symptoms. These include a sore throat, fever and minor skin infections and can be treated with a full course of antibiotics from the GP.

“In rare incidences, it can be a severe illness and anyone with high fever, severe muscle aches, pain in one area of the body and unexplained vomiting or diarrhoea should call NHS 111 and seek medical help immediately.”

Group A streptococcal bacteria can cause many different infections, ranging from minor illnesses to deadly diseases. Scarlet fever is caused by Strep A and mostly affects young children but is easily treated with antibiotics.

According to the NHS, the first signs of scarlet fever can be flu-like symptoms including a high temperature, sore throat and swollen neck glands. A rash appears 12 to 48 hours later that starts on the chest and stomach and then spreads. A white coating appears on the tongue, which peels, leaving the tongue red, swollen and covered in small bumps (often called “strawberry tongue”).

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