“Newly discovered vessels beneath skull could link brain and immune system,” The Guardian reports. It is has been suggested that the discovery, which has been described as textbook-changing, could lead to new treatments for a range of neurological conditions.

Until now, it was thought that the brain was not connected to the lymphatic system. This is an essential part of the immune system that helps fight infection, while draining excess fluid from tissue.

In this study, scientists discovered previously unknown lymphatic vessels in the outer layers of the brain. These vessels appeared to link the brain and spinal cord with the rest of the body’s immune system. This study used mice and human samples, vessel structure was investigated in the mice, and the observations followed up in the human samples.

Further study will be needed to confirm that the system works the same in humans, but the discovery may require a reassessment of our assumptions about lymph drainage in the brain and its role in diseases involving brain inflammation or degeneration, such as Alzheimer’s disease and multiple sclerosis.

It is too early to say whether the findings could one day have any implications for the treatment of these types of conditions.

Where did the story come from?

The study was carried out by researchers from The University of Virginia and was funded by Fondation pour la Recherche Médicale and by The National Institutes of Health. The study was published in the peer-reviewed scientific journal Nature.

The study has generated a great deal of media excitement, both in the UK and internationally.

This excitement seems largely driven by quotes released by the researchers themselves, such as Professor Kevin Lee, who was widely quoted as saying: “The first time these guys showed me the basic result, I just said one sentence: ‘They’ll have to change the textbooks’.”

However, media reports, such as the Mail Online stating that “[the discovery] could help treat conditions such as autism and Alzheimer’s” is premature, and cannot be concluded from this stage of the research.

What kind of research was this?

This was an animal study using mice to investigate the structure and function of lymphatic vessels in the brain.

It is said to have been previously understood that the central nervous system (brain and spinal cord) did not have a typical lymphatic drainage system. Lymph is the immune fluid that circulates round the body, containing white blood cells to fight infection and destroy abnormal cells.

This study aimed to look at the circulation of lymph in the mouse brain, potentially creating a greater understanding of the workings of the brain and disease processes. However, mice and humans do not have identical biology, so the findings may not be directly applicable. 

What did the research involve?

The scientists used adult mice to look at brain structure and the circulation of lymph.

The study involved complex laboratory techniques. This included the use of a fluorescent antibody to assess the alignment of cells within the brain, examination for markers associated with a lymphatic drainage system and looking at the functional capacity of identified vessels to carry lymphatic fluid to and from the brain. 

Human samples taken from the brain at autopsy were used to investigate any structures found in mice.

What were the basic results?

The scientists found that the outer protective layers of the mouse brain (the meninges) showed cells that were clearly lined up, which suggested that these were vessels with a unique function. These cells showed the characteristic features of functional lymphatic vessels. These vessels appeared able to carry both fluid and immune cells from the fluid surrounding the brain and spinal cord (the cerebrospinal fluid), and were connected to the lymph nodes in the neck.

The location of these vessels may have been the reason they have not been discovered to-date, thereby causing the belief that there is no lymphatic drainage system in the brain.

How did the researchers interpret the results?

The researchers state: “The presence of a functional and classical lymphatic system in the central nervous system [brain and spinal cord] suggests that current dogmas regarding brain tolerance and the immune privilege of the brain should be revisited”. This new understanding may mean current thinking about how the brain works needs to be reassessed. The researchers go on to say it could be the malfunction of these vessels that could be the cause of a variety of brain disorders, such as multiple sclerosis and Alzheimer’s disease.

Conclusion

This mouse study has examined the circulation of lymph in the brain. It discovered previously unknown lymphatic vessels in the outer layers of the mouse brain. If accurate, the findings may call for a review of how the immune system in the brain functions, and shed new light on its role in brain diseases involving brain inflammation or degeneration.

Though animal research can give a good insight into biological and disease processes, and how they may work in humans, the processes in humans and mice are not identical. Further studies are needed to confirm these findings and to assess whether this knowledge is transferable to humans.

As such, it is too early to say whether the findings could one day have any implications for the treatment of degenerative brain conditions such as multiple sclerosis or Alzheimer’s.  

Links To The Headlines

Newly discovered vessels beneath skull could link brain and immune system. The Guardian, June 5 2015

Landmark discovery about the brain 'will have scientists rewriting textbooks' - and could help treat conditions such as autism and Alzheimer's. Mail Online, June 5 2015

Links To Science

Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. Published online June 1 2015

"Sleepless nights… could raise your odds of developing Alzheimer's," is the claim in the Daily Mail. A new US study did find a link between poor sleep quality and higher levels of clumps of abnormal proteins in the brain (known as beta-amyloid plaques), but no cause and effect relationship between sleep quality and Alzheimer’s disease was proven.

This small study involved 26 healthy older adults who were analysed with a brain scan to measure the amount of protein plaques in their brain. The researchers did find an association with increased amounts of plaques and reduced deep sleep during the night. This in turn was associated with reduced ability to remember word-pair associations from the night before.

It is important to note that these are just associations as this was a cross-sectional study. The study cannot prove that the plaques caused the poor sleep or poor performance on the memory test, or that poor sleep caused plaque development. Various unmeasured factors could account for the results, such as difficulty sleeping in a laboratory.

Additionally, despite the media headlines, this study cannot show whether improving the quality of sleep would reduce the risk of Alzheimer's disease or slow its progression. The participants did not have any symptoms of dementia and were only assessed at one time point.

Where did the story come from?

The study was carried out by researchers from the University of California, California Pacific Medical Center and the Lawrence Berkeley National Laboratory. It was funded by the US National Institutes of Health.

The study was published in the peer-reviewed medical journal Nature Neuroscience.

Some of the UK media’s reporting of the study was inaccurate. For example, the Daily Mirror reported that adults "deprived of regular sleep had the highest levels of beta-amyloid" when this was not assessed in the study. The participants’ sleep pattern was only monitored for one night; the researchers did not formally assess their usual sleep pattern or use this in their calculations. Their claim that the "the study also revealed a 'vicious cycle' in which the protein not only corrodes memory, but also disrupts sleep further" was not found in the study – it was a speculation by the authors.

The Daily Mail also overstated the findings of the study and neither reported on the limitations.

What kind of research was this?

This was a cross-sectional study looking for a link between beta-amyloid plaques, poor sleep and memory deficits. This type of study cannot prove cause and effect but can further our knowledge of associations between these factors.

Beta-amyloid precursor protein is a large protein that is found on the surface of cells and is essential for growth and repair of nerve cells. However, it can be broken up into fragments, one of them called beta-amyloid. These beta-amyloid proteins attach to each other, forming long fibrils that accumulate to form plaques. This occurs in normal ageing, but to a much greater extent in Alzheimer’s disease. The plaques usually start to appear in the grey matter, called the cerebral cortex. The plaques are associated with memory loss but the exact mechanisms for this are not known.

The researchers wanted to explore their theory that the plaques may be causing memory loss through interrupting non-rapid eye movement (NREM) sleep. This part of the sleep cycle occurs during:

• Stage one: when you start to go to sleep
• Stage two: light sleep
• Stage three: deep sleep, when the body repairs and regrows tissues and the immune system

During a night’s sleep, after around 90 minutes, NREM sleep changes into rapid eye movement (REM) sleep for about 10 minutes. REM sleep is when dreams occur. The cycle is then repeated, going back to NREM sleep, with progressively longer periods of REM sleep as the night progresses.

What did the research involve?

The researchers recruited 26 older adults with no cognitive impairment. The study involved participants having a brain scan to measure the amount of beta-amyloid plaques, and performing a word-pair task before and after a night of sleep in the laboratory to test their ability to lay down memory.

The study participants did not have any symptoms of dementia, mental health conditions or reported sleep problems. Each participant underwent a positron emission tomography (PET) brain scan to estimate the amount of beta-amyloid protein build-up in the grey matter of the brain.

The participants then performed a word-pair task before and after a night of sleep in the laboratory. The amount of REM and NREM sleep was measured using an electroencephalogram (EEG) – a test that measures the electrical activity of the brain. The word-pair task consisted of learning a series of word pairs. Short-delay memory was tested by asking the participants to remember some of the word pairs after 10 minutes. Long-delay memory was tested the following day when they were asked to remember the rest of the word pairs. This was performed at the same time as a behavioural and functional magnetic resonance imaging (fMRI) scan, so that the researchers could look at which areas of the brain were active, such as the hippocampus, which is involved in memory.

What were the basic results?

Increased beta-amyloid protein in the medial prefrontal cortex of the brain, was associated with reduced NREM sleep. In particular, it was associated with less slow wave activity of below one hertz (Hz) – a measurement of frequency, which is believed to be when memory is consolidated. These results remained significant after adjusting for age and volume of grey matter. Beta-amyloid protein in other areas of the brain was not associated with NREM sleep of slow wave activity below one Hz.

Reduced NREM slow wave sleep and increased beta-amyloid protein in the medial prefrontal cortex of the brain was associated with poorer overnight memory. It was also associated with an increase in the activity of the hippocampus area of the brain.

The amount of beta-amyloid protein was not directly associated with poorer ability to form new memories. The link was only formed when reduced NREM sleep was included in the statistical analyses.

How did the researchers interpret the results?

The researchers concluded that their data "implicate sleep disruption as a mechanistic pathway through which β-amyloid [beta-amyloid] pathology may contribute to hippocampus-dependent cognitive decline in the elderly". They say that "cortical Aβ [beta-amyloid] pathology is associated with impaired generation of NREM slow wave oscillations that, in turn, predict the failure in long-term hippocampus-dependent memory consolidation".

The researchers go on to speculate from previous animal studies that NREM sleep disruption increases the build-up of beta-amyloid plaques and that this then reduces the amount of NREM sleep, creating a vicious cycle. However, they are clear that this is a hypothesis and has not been proven by this study.

Conclusion

This small study of 26 healthy older adults has found a link between the build-up of protein plaques in the brain, poor quality sleep and difficulty in laying down memory overnight.

The main limitations of this study are the cross-sectional study design. This means that the study cannot prove that the increased beta-amyloid plaques caused the poor NREM sleep or that either caused the memory difficulties. Similarly it does not show that poor sleep quality increases plaque build-up and so could be associated with Alzheimer’s development. Other factors could have accounted for the results seen, such as poor sleep from trying to sleep in a laboratory setting.

Additionally, despite the media claims, the study was taken at one point in time and so cannot show that increased NREM sleep would reduce the risk of dementia such as Alzheimer’s disease or slow its progression.

Overall this is an interesting piece of research, but further studies over a long period of time are needed to better understand the associations seen. That said, improving the quality of your sleep may have numerous health benefits, and tips can be found on our Better sleep hub

Links To The Headlines

Are sleepness nights to blame for Alzheimer's disease? Lack of shut-eye may cause long-term memory loss. Daily Mail, June 1 2015

How to fight Alzheimer's: New study says improving sleep could slash rise of cruel disease. Daily Express, June 2 2015

Sleep Could Help Stave Off Alzheimer's And Memory Loss, According To New Study. Huffington Post, June 2 2015

Links To Science

Mander BA, Marks SM, Vogel JW, et al. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nature. Published online June 1 2015

"Smartphone behaviour 'could diagnose depression' says new scientific study," the Daily Mirror reports. But based on the data presented in the study the paper is reporting on, we would disagree.

The story was prompted by a small US study of adults who agreed to have a freeware app – Purple Robot – installed on their phone. The app tracks phone usage and physical movement via GPS.

Researchers found people who reported depressive symptoms used their phone more often, visited fewer locations, and spent more time at home than the group of people who did not have symptoms of depression.

The results should not be taken too seriously as these two groups of people were not matched, so other factors could have influenced the results (confounders).

A major factor that was not accounted for was whether any of the people involved in the study were employed, the nature of the employment, or whether they were looking after children or caring for someone. This would have had a major impact on their phone use and the amount of time they spent going out to different places.

Other factors commonly taken into account but not included in this study are a history of mental health problems, age, sex and any medical or psychiatric conditions.

In short, this study does not show smartphone use can diagnose depression.  

Where did the story come from?

The study was carried out by researchers from Northwestern University and Michigan State University, and was funded by the US National Institute of Mental Health.

It was published in the peer-reviewed Journal of Medical Internet Research.

The authors do not declare any conflict of interest. They developed an open-source app called Purple Robot, which is designed to collect mobile phone sensor data.

Purple Robot has also been used in studies designed to optimise adherence to treatment regimes for people with HIV, ulcerative colitis and Crohn's disease.

The Mail Online coverage of the story included some inaccuracies, such as saying, "The phone data turned out to be a more reliable way of detecting depression than asking participants questions about how sad they were feeling on a scale of one to 10".

But the scales used were from one to three, and it is not clear how the phone data could be "more reliable" when none of the participants were assessed for symptoms of depression other than their answers to this symptom-scale questionnaire.

The Mail also says that, "Using a phone stops people dealing with difficult feelings" without pointing out this was just the authors' hypothesis and not actually assessed in the study.

Similarly, the Daily Mirror carried a number of quotes from the lead author, such as, "We now have an objective measure of behaviour related to depression", without subjecting these comments to any scrutiny.  

What kind of research was this?

This observational study aimed to see if people who self-reported symptoms of depression were likely to use their mobile phones more than people who did not have symptoms of depression.

It also aimed to see if they were less likely to go out to different places.

This type of study can only show an association and cannot prove cause and effect.

What did the research involve?

Forty adults aged between 19 and 58 were recruited to take part in the study. They were asked to download an app called Purple Robot on to their phone.

This app measured their phone usage and mapped their location using GPS. The participants were asked to keep the phone with them at all times for two weeks.

At the beginning of the study they completed the Patient Health Questionnaire-9 (PHQ-9) to record any self-reported symptoms of depression. This questionnaire asks people to rate nine different symptoms of depression from 0 (not at all) to three (nearly every day). Scores can range from 0 to 27.

This screening questionnaire gives an indication of whether a person is likely to be depressed, but a diagnosis would require further clinical assessment. The scores suggest the following:

• 5 to 9 – mild depression
• 10 to 14 – moderate depression
• 15 to 19 – moderately severe depression
• 20 or more – severe depression

The researchers split the people into two groups – one group scored less than five on the PHQ-9 and the other group scored five or more. The researchers then analysed the results looking for any associations between depressive symptoms, phone usage and how much a person was out and about.  

What were the basic results?

Data was available for only 28 of the participants, with 14 in each group. The average PHQ-9 score for the depressive group was 9.6, which would be rated as mild.

People with depressive symptoms went out less often and spent more time at home. They also used their phone more often, but the study doesn't report if these participants used their phone for texting, surfing the internet or talking to someone.  

How did the researchers interpret the results?

The researchers concluded mobile phone use could be used to help identify people with depressive symptoms.

They say that, "While these findings must be replicated in a larger study among participants with confirmed clinical symptoms, they suggest that phone sensors offer numerous clinical opportunities, including continuous monitoring of at-risk populations with little patient burden and interventions that can provide just-in-time outreach." 

Conclusion

This small study suggests people who report higher levels of depressive symptoms may use their phone more and go out less.

However, these findings should not be taken too seriously as this study has many limitations, including:

• a small sample size – data from only nine people in each group was used for the location data
• there was no attempt to ensure the two groups were matched in terms of any medical illness, age, sex, whether they were employed, or any other potential confounding factors
• it's not known whether any of the participants in either group had a diagnosis of depression or any other mental illness
• the analysis relied on the participants keeping their mobile phone with them continuously, which may or may not have actually happened

In short, this study does not show that mobile phone use can diagnose depression. As the researchers point out, a much larger – and, in our opinion, better designed – study would be required to see if a depression app or similar would be a viable idea.

If you are feeling low, it is a good idea to talk to someone or seek professional help. The Samaritans are available 24 hours a day, 365 days a year if you are in distress and can be reached on 08457 90 90 90.

Links To The Headlines

Smartphone behaviour 'could diagnose depression' says new scientific study. Daily Mirror, July 15 2015

How your SMARTPHONE could diagnose you with depression: Using it for 68 minutes a day 'may be a sign of mental illness’. Daily Mail, July 15 2015

Links To Science

Saeb S, Zhang MI, Karr CJ, et al. Mobile Phone Sensor Correlates of Depressive Symptom Severity in Daily-Life Behavior: An Exploratory Study. Journal of Medical Internet Research.

"A household mouthwash may be creating superbugs," the Daily Mail reports.

A laboratory study found the ingredient chlorhexidine, used in a wide range of antiseptic products, increased bacterial resistance to the antibiotic colistin.

Despite the headline to the contrary, researchers did not specifically test mouthwash or any other household products.

Colistin is what is known as an "antibiotic of last resort" and is used to treat Klebsiella pneumoniae bacterium that has evolved resistance to other more widely used antibiotics.

Klebsiella pneumoniae can cause pneumonia, meningitis and other infections.

Researchers found these bacteria became resistant to increasing concentrations of the antiseptic chlorhexidine, which is found in products such as mouthwash and wound dressings.

The results are of potential concern as the rate of Klebsiella pneumoniae is increasing in UK hospitals.

But in a related press release, the study's lead author, Dr Mark Sutton, stressed that disinfectants containing chlorhexidine and similar antibacterial products currently play a vital role in infection control in both the home and in hospitals.

Dr Sutton also added: "This is early research in a laboratory setting and more work needs to be done to understand the potential implications." 

Where did the story come from?

The study was carried out by researchers from the Technology Development Group, Public Health England, Microbiology Services Division in the UK.

It was funded by Public Health England, and the authors declared no conflicts of interest.

The study was published in the peer-reviewed journal, Antimicrobial Agents and Chemotherapy. It is an open access study, so you can read it free online.

While the Mail's overall reporting was accurate, it does seem somewhat odd that they focused on mouthwash in general, and specifically on the Corsodyl brand. Many other commercial products contain chlorhexidine.

As the manufacturers of Corsodyl, GlaxoSmithKline, point out in the Mail article: "Corsodyl mouth rinse contains a very low concentration of chlorhexidine (0.2%) and is intended for short-term use only."

The results of the article would seem to be more of a potential concern for health professionals responsible for infection control in hospitals than members of the public trying to keep their teeth clean and gums healthy.

What kind of research was this?

This laboratory study investigated the adaptation of the pathogen Klebsiella pneumoniae to the antiseptic chlorhexidine, and whether this caused cross-resistance to other antibiotics.

While laboratory studies are useful ways of seeing the biological mechanisms and how things may work in humans, their findings cannot necessarily be extrapolated to beyond the lab.

It may be that the conditions in the laboratory do not reflect real life.

What did the research involve?

Researchers took clinical strains of Klebsiella pneumoniae that were placed in a concentration of the antiseptic chlorhexidine to find out if it builds up immunity.

Adapted strains of Klebsiella pneumoniae were also added to colistin, a last-resort antibiotic, to investigate if there was cross-resistance of Klebsiella pneumoniae to this antibiotic.

Strains were cultured in a concentration of chlorhexidine or colistin and put in a new concentration – double that of the previous – every two days. This continued six times.

The researchers then measured the resistance of these strains of Klebsiella pneumoniae to different concentrations of chlorhexidine and colistin.

What were the basic results?

Klebsiella pneumoniae strains are able to adapt to increasing concentrations of chlorhexidine. This leads to increased minimum inhibitory concentrations.

These are the lowest concentration of an antibiotic (chlorhexidine) that will inhibit the visible growth of a micro-organism (Klebsiella pneumoniae).

This means that lower concentrations of chlorhexidine became less effective at inhibiting Klebsiella pneumoniae growth.

These adapted strains of Klebsiella pneumoniae were also more resistant to the antibiotic colistin. This means the chlorhexidine exposure had led to what is termed antibiotic cross-resistance.

In five out of six strains, the minimum inhibitory concentration values for colistin increased from 2-4mg/L to more than 64mg/L, meaning lower concentrations of colistin became less effective at inhibiting Klebsiella pneumoniae.

How did the researchers interpret the results?

The authors concluded that, "increased colistin and chlorhexidine resistance may occur in clinical isolates without significant loss of fitness/virulence".

They added that this "highlights the potential challenges associated with critical infection control procedures and the use of chlorhexidine as an antiseptic to control healthcare-associated infections".

Conclusion

The authors show that Klebsiella pneumoniae strains are able to become more resistant to the widely used antiseptic chlorhexidine.

They also show that in five of six strains, adaptation to chlorhexidine also led to resistance to colistin, a last-resort antibiotic.

There is a potential risk that colistin resistance will emerge in Klebsiella pneumoniae as a result of exposure to chlorhexidine, given the wide range of products sold to the NHS that contain active concentrations of chlorhexidine.

Klebsiella pneumoniae infections and outbreaks are becoming increasingly common in hospitals and can cause a range of diseases, including pneumonia, bloodstream infections, wound infections, surgical site infections, meningitis and urinary tract infections.

While it is true that chlorhexidine is in a range of products, including mouthwash and wound dressings, the study did not specifically look at mouthwash or any other household products. There is no evidence that using these products is unsafe or has caused an increase in infections.

As lead author, Dr Mark Sutton, concluded in a press release: "Chlorhexidine is a common ingredient in a number of disinfectants used widely in the home and in healthcare settings, where it is an important part of many infection control practices.

"People should continue to practice good infection control, including the use of disinfectants, in order to prevent infections in the first place.

"This is early research in a laboratory setting and more work needs to be done to understand the potential implications."

Links To The Headlines

Why using popular mouthwash to cure gum disease could be fueling deadly antibiotic resistance. Daily Mail, October 31 2016

Links To Science

Wand ME, Bock LJ, Bonney LC, Sutton JM. Mechanisms of increased resistance to chlorhexidine and cross-resistance to colistin following exposure of Klebsiella pneumoniae clinical isolates to chlorhexidine. Antimicrobial Agents and Chemotherapy. Published online October 31 2016

“Breakthrough pill can cure diabetes,” is the completely misleading report in the Daily Express. While researchers have achieved some level of success in using bacteria to improve diabetes control in rats, this in no way amounts to a cure for humans.

The rats had an equivalent of type 1 diabetes, where the pancreas fails to produce the insulin needed by the body to regulate glucose.

The rats were given a daily pill of a genetically modified bacterium. This engineered bacterium secreted a compound that converted cells in the lining of the gut to produce insulin. 

After 90 days, these diabetic rats were able to reduce blood glucose levels in a similar way to healthy rats. While diabetic rats fed a normal type of this bacterium had 60% lower levels of insulin and were not able to reduce their blood glucose levels adequately.

Though the treated diabetic rats were able to produce more insulin, the overall level of insulin was still half that of normal rats.

This is preliminary research and there are many questions unanswered, such as how many cells might be converted over time. In addition, it should be made clear that this was not a probiotic pill. This was a genetically modified bacterium.

And, even assuming the engineered bacterium was safe to use in humans, an increase in insulin levels, while welcome, does not amount to a cure for diabetes.

Where did the story come from?

The study was carried out by researchers from Cornell University, New York and was funded by the US National Institutes of Health and the Hartwell Foundation. A conflict of interest has been declared by one of the authors as he is involved with a company that has licensed this technology.

The study was published in the peer-reviewed medical journal Diabetes.

The pill is not strictly a “probiotic” as reported by the media. Probiotics are live bacteria and yeasts that are usually present in the human body. The bacteria in the pill in this study has been genetically engineered to secrete a compound called GLP-1, and it is not known what effects this might have if ingested by humans.

Any talk of a cure for diabetes is highly misleading, and arguably irresponsible, as it may offer false hope to people living with diabetes.

What kind of research was this?

This was an animal study in which diabetic rats were given a daily pill of a modified bacterium to see what effect it had on their glucose and insulin levels.

Insulin regulates the level of glucose in the blood and is produced by beta cells in the pancreas. In type 1 diabetes, the pancreas no longer produces insulin as the beta cells have been destroyed by the body’s immune system, and so insulin injections are required. While people with type 2 diabetes have a reduced response to insulin, so higher levels are needed to maintain healthy blood glucose levels.

Initially the pancreas responds by making extra insulin, but over time this fails. Type 2 diabetes is managed through diet, medication and in some cases, insulin.

Previous research found that a compound called GLP-1 can convert intestinal cells into cells that produce insulin. The problem is that GLP-1 in humans breaks down quickly in the blood (it has a very short half-life) so the challenge is to find a way to move the compound into the intestine.

These experiments were conducted on cells in the laboratory setting. The researchers wanted to see if they could find a way to get GLP-1 to intestinal cells in rats and whether these cells could be reprogrammed as they were in the laboratory.

What did the research involve?

The researchers engineered Lactobacillus, a bacterium that is usually present in the human gut, to secrete a compound called GLP-1. They created a pill of these bacteria and gave it to rats with type 1 diabetes to see if it could deliver GLP-1 to the gut wall. They then investigated whether it changed the type of cells lining the intestine so that they could produce insulin.

Rats with type 1 diabetes were given two pills daily for 90 days of either:

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• engineered Lactobacillus that secrete GLP-1
• normal Lactobacillus

Healthy rats were kept in the same conditions and given a placebo to act as a control.

To test whether the GLP-1 had converted any cells to produce insulin, after 51 days the rats were fasted for 10 hours and then given an injection of glucose. Blood glucose and insulin levels were measured after 30 minutes, one hour, one and a half hours and two hours.

At the end of the 90 days, the cells lining the intestine and the pancreas were examined and the level of gut bacteria was measured.

What were the basic results?

There was no significant difference in the blood glucose or insulin levels in diabetic rats fed engineered Lactobacillus compared with healthy control rats. Whereas diabetic rats fed normal Lactobacillus had higher blood glucose and lower blood insulin levels, as would be expected.

The level of insulin in the intestines of rats fed engineered Lactobacillus was more than five times higher than either of the other groups of rats. These rats had insulin-secreting cells in their intestines that had features of beta cells (the cells that produce insulin in the pancreas). These cells appeared to produce insulin in response to glucose. On average, 0.06% of the intestinal cells had been converted to secrete insulin.

Rats fed engineered Lactobacillus had 60% more total insulin than those fed normal Lactobacillus.

The overall level was half that of the control rats.

How did the researchers interpret the results?

The authors concluded that feeding diabetic rats the genetically engineered bacteria can cause them to produce insulin in response to eating, which significantly reduced their blood glucose levels. They say this appeared to have been produced from cells in the intestine that had been transformed from normal gut cells to insulin secreting cells. The researchers call for further work to be done to fully understand the mechanism involved.

Conclusion

This animal research has shown that a pill of genetically engineered Lactobacillus can convert cells lining the gut into cells that produce insulin in rats. This conversion was made by stimulating the cells with a compound called GLP-1 that was secreted by these modified bacteria that are usually present in the human gut.

The researchers were able to demonstrate that the cells had changed function to become more like the beta cells that usually produce insulin in the pancreas. They also showed that the insulin reduced the rats’ blood glucose levels to that of control rats.

There are a number of questions that need to be addressed before this new technique progresses to primate studies on the long road to becoming a treatment for either form of diabetes. Over the 90 days 0.06% of the intestinal cells were converted but it is unclear whether this proportion would increase over time and whether this depends on the dose of bacteria given. It is also not known whether these cells need daily bacteria to continue to behave like cells from the pancreas or whether the change is permanent and the cells can renew.

There are also unanswered questions about what effect having a reduced number of normal intestinal cells could have on the function of the gut. Finally, it will need to be determined how any such cell renewal is controlled so that it does not go into overdrive and produce too many insulin producing cells.

Overall, the results of this preliminary piece of research are encouraging in the search for a possible cure for diabetes, though this is still a long way off.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Breakthrough pill can CURE diabetes: New drug fights both types of killer disease. Daily Express, February 3 2015

Both types of diabetes could be CURED by a daily probiotic pill that 'rewires' the body, scientists claim. Mail Online, February 3 2015

Links To Science

Duan FF, Liu JH, March JC. Engineered Commensal Bacteria Reprogram Intestinal Cells Into Glucose-Responsive Insulin-Secreting Cells for the Treatment of Diabetes. Diabetes. Published online January 27 2015

“Antibiotic-resistant typhoid is spreading across Africa and Asia and poses a major global health threat,” BBC News reports.

Typhoid fever is a bacterial infection. If left untreated, it can lead to potentially fatal complications, such as internal bleeding.

Uncommon in the UK (there were 33 confirmed UK cases in the first quarter of 2015 and it is thought most of these were contracted abroad), it is more widespread in countries where there is poor sanitation and hygiene.

The headline is based on a study that looked at the genetics of the bacteria that causes typhoid fever, Salmonella typhi, to trace their origins.

The study analysed genetic data from almost 2,000 samples of Salmonella typhi collected between 1903 and 2013. It was looking for a strain called H58 that is often antibiotic-resistant. It found that this strain was likely to have originated in South Asia around the early 1990s, and has spread to other countries in Africa and Southeast Asia. It accounted for about 40% of samples collected each year. Over two-thirds of the H58 samples had genes that would allow them to be resistant to antibiotics.

It would be complacent to assume that this is just a problem for people in the developing world, as antibiotic resistance is a major threat facing human health worldwide. Studies such as this help researchers to identify and track how such bacteria spread. This may help them to use existing antibiotics more effectively, by identifying where specific types of resistance are common.

Where did the story come from?

The study was carried out by a large number of researchers from international institutions, including the Wellcome Trust Sanger Institute, in the UK. The researchers were also funded by a wide range of international organisations, including the Wellcome Trust and Novartis Vaccines Institute for Global Health.

The study was published in the peer-reviewed journal Nature Genetics.

The news sources cover this story reasonably. Some reporting implies that it is the H58 strain that is killing 200,000 people a year, but this study has not assessed this.

The 200,000 figure seems to be taken from information provided by the US’s Centers for Disease Control and Prevention (CDC), and is an estimate of all types of typhoid fever, not just the H58 strain.

What kind of research was this?

This was a genetic study looking at the origins and spread of the H58 strain of Salmonella typhi – the bacteria that causes typhoid fever. This strain is often found to be antibiotic-resistant.

The typhoid bacteria are spread by ingestion of infected faecal matter from a person with the disease. This means that it is a problem in countries where there is poor sanitation and hygiene. Typhoid fever is uncommon in the UK, and most cases in this country are people who have travelled to high-risk areas where the infection still occurs, including the Indian subcontinent, South and Southeast Asia, and Africa. The researchers say that 20-30 million cases of typhoid are estimated to occur each year worldwide.

Typhoid fever has been traditionally treated with the antibiotics chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole. Since the 1970s, strains of typhoid have started to emerge that are resistant to these antibiotics (called multidrug-resistant strains). Different antibiotics, such as fluoroquinolones, have been used since the 1990s, but strains resistant to these antibiotics have been identified recently in Asia and Africa. One such strain, H58, is becoming more common, and was the focus of this study.

What did the research involve?

The researchers used genetic sequence data from 1,832 samples of Salmonella typhi bacteria collected across the world. They used this data to assess when the H58 strain (which has identifiable genetic characteristics) had arisen and how it had spread.

They first identified which of the samples belonged to the H58 strain, and in what year it was first identified. They also looked at what the proportion of samples collected in each year were of this strain, to see if it was becoming more common.

Over time, DNA accumulates changes, and the researchers used computer programmes to analyse the genetic changes present in each sample to identify how each strain is likely to be related to the others. By combining this information with the origin and year of each sample, the researchers developed an idea of how the strain had spread.

What were the basic results?

The researchers found that nearly half of their samples (47%) belonged to the H58 strain. The first sample identified as part of this strain was from Fiji in 1992, and continued to be identified up to the latest samples, from 2013. H58 strain samples were identified from 21 countries in Asia, Africa and Oceania, showing that it is now widespread. Overall, 68% of these H58 samples had genes that would allow them to be antibiotic-resistant.

There were some very genetically closely related samples found in different countries, suggesting that there was human transfer of the bacteria between these countries. Their genetic analyses suggested that the strain was initially located in South Asia, and then spread to Southeast Asia, western Asia and East Africa, as well as Fiji.

There was evidence of multiple transfers of the strain from Asia to Africa. The H58 strain accounted for 63% of samples from eastern and southern Africa. The analysis suggested that there had been a recent wave of transmission of the H58 strain from Kenya to Tanzania, and on to Malawi and South Africa. This had not previously been reported, and the researchers described it as an “ongoing epidemic of H58 typhoid across countries in eastern and southern Africa”.

Multidrug resistance was reported to be common among H58 samples from Southeast Asia in the 1990s and, more recently, samples from this region have acquired mutations which have made them less susceptible to fluoroquinolones. These have become more common in the area, and researchers suggested that this is due to the use of fluoroquinolones to treat typhoid fever over this period, leading to these resistant strains having a survival advantage.

In South Asia, there are lower rates of multidrug resistance in recent samples than in Southeast Asia. In Africa, most samples showed multidrug resistance to the older antibiotics, but not fluoroquinolones, as these are not frequently used there.

How did the researchers interpret the results?

The researchers say that their analysis is the first of its kind for the H58 typhoid strain, and that the spread of this strain “requires urgent international attention”. They say that their study “highlights the need for longstanding routine surveillance to capture epidemics and monitor changes in bacterial populations as a means to facilitate public health measures, such as the use of effective antimicrobials and the introduction of vaccine programs, to reduce the vast and neglected morbidity and mortality caused by typhoid”.

Conclusion

This study has provided information about the spread of a strain of typhoid called H58, which is commonly antibiotic-resistant, by looking at the genetics of samples collected between 1903 and 2013. It has shown that the strain was likely to have arisen in South Asia and then spread to Southeast Asia and Africa. The strain showed different patterns of antibiotic resistance in different regions – likely driven by different patterns in the use of antibiotics.

While this study has not estimated the number of cases or deaths worldwide attributable to this strain specifically, there are reported to be 20-30 million cases of typhoid fever globally each year.

The spread of antibiotic resistance is a major threat to human health, and studies like this can help us to monitor them and target treatment more effectively.

Read more about the battle against antibacterial resistance and how we can all help do our bit.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Drug-resistant typhoid 'concerning'. BBC News, May 11 2015

Antibiotic-resistant typhoid spreading in silent epidemic, says study. The Guardian, May 11 2015

Deadly typhoid superbug poses global threat after 'rapidly spreading' through Asia and Africa, experts warn. Mail Online, May 11 2015

Links To Science

Wong VK, Baker S, Pickard DJ, et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nature Genetics. Published online May 11 2015