In a study of 210 community-dwelling older adults who had surgery following hip fracture, participants who reported feeling high levels of psychological resilience were later able to walk faster and longer than those feeling less resilient. The results, published in the Journal of the American Geriatrics Society, will help the development of interventions such as targeted exercise programmes.
Walking capacity is a critically important outcome following hip fracture, in that it serves both as a surrogate measure of functional ability and physical health more globally, as well as a predictor of future survival, institutionalisation, social interaction and community engagement. Moreover, poor recovery after hip fracture causes considerable suffering for patients and imposes a financial burden on the social and health care sector. In 29%–50% of cases, older adults with hip fracture do not reach their pre-fracture levels of functioning a year after the fracture. Poorer pre-fracture function, greater cognitive impairment, greater co-morbidity burden, poorer social support, and poorer nutrition, have been identified as predictors for diminished post-fracture recovery.
Psychological resilience was measured through a questionnaire provided at the start of the study, and they assessed walking capacity at the start as well as 16 weeks later.
“We believe these results support opportunities to improve walking capacity following hip fracture in older adults by devising multicomponent interventions combining targeted exercise with psychological resilience-enhancing programmes,” said corresponding author Richard H. Fortinsky, PhD, of the University of Connecticut School of Medicine and the UConn Center of Aging.
Early exposure to antibiotics kills healthy bacteria in the digestive tract, possibly leading to asthma and allergies, according to a series of experiments in mouse models.
The experiments, reported in Mucosal Immunology, have provided the strongest evidence so far that the long-observed connection between antibiotic exposure in early childhood and later development of asthma and allergies is causal.
“The practical implication is simple: avoid antibiotic use in young children whenever you can because it may elevate the risk of significant, long-term problems with allergy and/or asthma,” said senior author Martin Blaser at Rutgers University.
In the study, the researchers noted that antibiotics, which are “among the most used medications in children, affect gut microbiome communities and metabolic functions. These changes in microbiota structure can impact host immunity.”
In the first part of the experiment, five-day-old mice received water, azithromycin or amoxicillin. After the mice matured, researchers exposed them to a common allergen derived from house dust mites. Mice that had received either of the antibiotics, especially azithromycin, exhibited elevated rates of immune responses – ie, allergies.
The second and third parts of the experiment tested whether early exposure to antibiotics (but not later exposure) causes allergies and asthma by killing some healthy gut bacteria that support proper immune system development.
Lead author Timothy Borbet first transferred bacteria-rich faecal samples from the first set of mice to a second set of adult mice with no previous exposure to any bacteria or germs. Some received samples from mice given azithromycin or amoxicillin in infancy. Others received normal samples from mice that had received water.
Mice that received antibiotic-altered samples were no more likely than other mice to develop immune responses to house dust mites, just as people who receive antibiotics in adulthood are no more likely to develop asthma or allergies than those who don’t.
Things were different, however, for the next generation. Offspring of mice that received antibiotic-altered samples reacted more to house dust mites than those whose parents received samples unaltered by antibiotics, just as mice that originally received antibiotics as babies reacted more to the allergen than those that received water.
“This was a carefully controlled experiment,” said Blaser. “The only variable in the first part was antibiotic exposure. The only variable in the second two parts was whether the mixture of gut bacteria had been affected by antibiotics. Everything else about the mice was identical.
Blaser added that “these experiments provide strong evidence that antibiotics cause unwanted immune responses to develop via their effect on gut bacteria, but only if gut bacteria are altered in early childhood.”
A pioneering new study from the University of Cincinnati shows promise that a new drug may help repair damage caused by strokes. The preclinical study appears in the journal Cell Reports.
Currently, there are no FDA approved drugs to repair the damage caused by a stroke. The study found that the new drug, NVG-291-R, enables nervous system repair and significant functional recovery in an animal model of severe ischaemic stroke. Deleting the gene for the drug’s molecular target also shows similar effect on neural stem cells. The drug has also proven to be safe and well-tolerated in volunteers with multiple sclerosis.
“We are very excited about the data showing significant improvement in motor function, sensory function, spatial learning and memory,” said Agnes (Yu) Luo, PhD, associate professor UC and the study’s senior author.
Prof Luo said the drug would be a “substantial breakthrough” if the early results translate into clinical settings. Further study and validation of results from independent groups will be needed to determine if the drug is similarly effective to repair the damage of ischaemic strokes in human patients. Additional studies will be needed to research if NVG-291-R effectively repairs damage caused by haemorrhagic strokes in both animal models and human patients.
“Most therapies being researched today primarily focus on reducing the early damage from stroke,” Assoc Prof Luo said. “However, our group has focused on neurorepair as an alternative and now has shown that treatment with NVG-291-R not only results in neuroprotection to reduce neuronal death but also robust neuroreparative effects.”
The drug proved to be effective even when treatment began as late as seven days after the stroke’s onset.
“The only current FDA-approved drug for treatment of stroke does not repair damage and must be administered within 4.5 hours of stroke onset.” Luo said. “Most therapies being researched need to be applied within 24–48 hours of a stroke’s onset. A product that works to repair damage from stroke even a week after symptom onset would change the paradigm for stroke treatment.”
Jerry Silver, PhD, co-author of the study and professor of neurosciences at CWRU’s School of Medicine, said the study showed the drug repaired damage in at least two ways: creating new neuronal connections and enhancing migration of new neurons derived from neuronal stem cells to the damage site.
“NVG-291-R’s ability to enhance plasticity was demonstrated by using staining techniques that clearly showed an increase in axonal sprouting to the damaged part of the brain,” Prof Silver said. “This enhanced plasticity is an excellent validation of the same powerful mechanisms that we and other researchers were able to demonstrate using NVG-291-R in spinal cord injury.”
The gut microbiome has been linked to aspects ranging from the immune system to mental health. However, pinpointing how and which bacteria specifically affect which biological process has eluded researchers, until now – a new study figured it out the link between immunity and a major gut bacterium.
Such knowledge is essential for learning how to manipulate gut bacteria to treat or prevent illness.
“Microbiome studies need to move from making associations to determining function and causation,” said Professor Ramnik Xavier, co-author of the study which appears in Nature.
“The real significance of this work was connecting a bacterium, the molecule it makes, the pathway it operates through, and the biological outcome,” said Professor at HMS and co-senior author of the study with Prof Xavier. “That’s very rare.”
Profs Clardy and Xavier and colleagues focused on Akkermansia muciniphila, a species that makes up 3% of the gut microbiome. It gets its name from the intestinal mucus it breaks down.
Studies had suggested that A. muciniphila has a key role in maintaining healthy immune processes, seeming to protect against diseases such as type 2 diabetes and inflammatory bowel disease and make cancer cells more responsive to immune checkpoint therapies. Until now, no research could confirm how that connection worked.
Start to finish
The researchers show that the links begin with a lipid in A. muciniphila‘s cell membrane.
“That discovery was quite surprising. The usual suspects for triggering an immune response would be a protein or a sugar,” said Prof Clardy.
After discovering the molecular structure of the lipid, the team found that it communicates toll-like receptors (TLR) 2 and TLR 1. Found on many immune cells, they detect bacteria and identify hostile ones for the immune system. In this case, versions of TLR2 and TLR1 bound together in a way scientists hadn’t seen before.
The researchers showed in cell cultures that the fat’s activation of TLR2-TLR1 can trigger the release of certain cytokines — immune proteins involved in inflammation — while leaving other cytokines alone.
They also confirmed that the lipid helps maintain immune homeostasis. They found that low doses of the lipid act like a leash, preventing the immune system from reacting to a potentially harmful molecule until that molecule reaches significant levels. On the other end, they saw that high doses of the lipid don’t stimulate an immune response much more than low or medium doses, keeping a healthy ceiling on inflammation.
New doors open
The work introduces new possibilities for developing drugs that piggyback on A. muciniphila‘s ability to manipulate the immune system and fight disease. Members of Prof Clardy’s lab have made that job easier by revealing the molecular structure of the lipid and figuring out how scientists can make it and similar ones easily in the lab.
The study also serves as a model for pinpointing how other members of the gut microbiome act on the body.
“You can change the bacterium and apply the same set of tests,” said Prof Clardy.
Also, contrary to the expectations of many people in the field, such work doesn’t require fancy techniques. The researchers used traditional methods, spectroscopic analysis and chemical synthesis, to find and understand the lipid molecule.
In fact, despite its “remarkable activity,” the lipid has a “generic structure” that would have flown under the radar of more advanced genomic or metabolomic analyses, Prof Clardy said.
“The gut microbiome and the immune system are very complicated, which makes you expect that answers will be complicated too,” he said. “But sometimes complicated things are just lots of simple things.”
A trial in people with hereditary colon cancer has shown that daily supplements of resistant starch, equivalent to a slightly green banana per day, had a major preventative effect against many cancers. Published in Cancer Prevention Research, the findings showed that, while bowel cancers were unaffected, the supplement reduced cancers in other parts of the body by more than half.
This effect was particularly pronounced for upper gastrointestinal cancers including oesophageal, gastric, biliary tract, pancreatic and duodenum cancers. What is even more remarkable is that the effects lasted for 10 years after the participants stopped taking the supplements.
The CAPP2 trial involved almost 1000 patients with Lynch syndrome from around the world and revealed that a regular dose of resistant starch, also known as fermentable fibre, taken for an average of two years, cut their risk for many cancers.
The present study is a planned double blind 10 year follow-up, supplemented with comprehensive national cancer registry data for up to 20 years in 369 of the participants.
A previous study as part of the same trial and published in The Lancet revealed that aspirin reduced cancer of the large bowel by 50%.
“We found that resistant starch reduces a range of cancers by over 60%. The effect was most obvious in the upper part of the gut,” explained Professor John Mathers at Newcastle University. “This is important as cancers of the upper GI tract are difficult to diagnose and often are not caught early on.
“Resistant starch can be taken as a powder supplement and is found naturally in peas, beans, oats and other starchy foods. The dose used in the trial is equivalent to eating a daily banana; before they become too ripe and soft, the starch in bananas resists breakdown and reaches the bowel where it can change the type of bacteria that live there.
“Resistant starch is a type of carbohydrate that isn’t digested in your small intestine, instead it ferments in your large intestine, feeding beneficial gut bacteria – it acts in effect, like dietary fibre in your digestive system. This type of starch has several health benefits and fewer calories than regular starch. We think that resistant starch may reduce cancer development by changing the bacterial metabolism of bile acids and to reduce those types of bile acids that can damage our DNA and eventually cause cancer. However, this needs further research.”
Professor Sir John Burn, from Newcastle University and Newcastle Hospitals NHS Foundation Trust who ran the trial with Prof Mathers, said: “When we started the studies over 20 years ago, we thought that people with a genetic predisposition to colon cancer could help us to test whether we could reduce the risk of cancer with either aspirin or resistant starch.
“Patients with Lynch syndrome are high risk as they are more likely to develop cancers so finding that aspirin can reduce the risk of large bowel cancers and resistant starch other cancers by half is vitally important.
“Based on our trial, NICE now recommend Aspirin for people at high genetic risk of cancer, the benefits are clear – aspirin and resistant starch work.”
Between 1999 and 2005, nearly 1000 participants began either taking resistant starch in a powder form every day for two years or aspirin or a placebo.
At the end of the treatment stage, there was no overall difference between those who had taken resistant starch or aspirin and those who had not. However, the research team anticipated a longer-term effect and designed the study for further follow-up.
During follow-up, only five new cases of upper GI cancers were diagnosed among the 463 participants who had taken the resistant starch compared with 21 among the 455 who were on the placebo.
The team are now leading the international trial, CaPP3, involving more than 1800 participants with Lynch syndrome to look at whether smaller, safer doses of aspirin can be used to help reduce the cancer risk.
