Posted on Cardiovascular disease, Mental health

Deep meditation may alter gut microbes for better health


Regular deep meditation, practised for several years, may help to regulate the gut microbiome and potentially lower the risks of physical and mental ill health, finds a small comparative study published in the open-access journal General Psychiatry.

The gut microbes found in a group of Tibetan Buddhist monks differed substantially from those of their secular neighbours. They have been linked to a lower risk of anxiety, depression, and cardiovascular disease.

Research shows the gut microbiome can affect mood and behaviour through the gut–brain axis. This includes the body’s immune response, hormonal signalling, stress response and the vagus nerve—the main component of the parasympathetic nervous system, which oversees an array of crucial bodily functions.

The significance of the group and specimen design is that these deep-thinking Tibetan monks can represent some more profound meditations. Although the number of samples is small, they are rare because of their location.

Meditation is increasingly being used to help treat mental health disorders, such as depression, anxiety, substance abuse, traumatic stress, and eating disorders as well as chronic pain. But it’s not clear if it might also be able to alter the composition of the gut microbiome, say the researchers.

The researchers analysed the stool and blood samples of 37 Tibetan Buddhist monks from three temples and 19 secular residents in the neighbouring areas to find out.

Tibetan Buddhist meditation originates from the ancient Indian medical system known as Ayurveda, and is a form of psychological training, say the researchers. The monks in this study had been practising it for at least 2 hours a day for 3 and 30 years.

None of the participants had used agents that can alter the volume and diversity of gut microbes: antibiotics; probiotics; prebiotics; or antifungal drugs in the preceding 3 months.

Both groups were matched for age, blood pressure, heart rate, and diet.

Stool sample analysis revealed significant differences in the diversity and volume of microbes between the monks and their neighbours. 

Bacteroidetes and Firmicutes species were dominant in both groups, as would be expected. But Bacteroidetes were significantly enriched in the monks’ stool samples (29% vs 4%), which also contained abundant Prevotella (42% vs 6%) and a high volume of Megamonas and Faecalibacterium.

“Collectively, several bacteria enriched in the meditation group [have been] associated with the alleviation of mental illness, suggesting that meditation can influence certain bacteria that may have a role in mental health,” write the researchers.

The previously published research suggests these include Prevotella, Bacteroidetes, Megamonas and Faecalibacterium species.

The researchers then applied an advanced analytical technique to predict which chemical processes the microbes might influence. This indicated that several protective anti-inflammatory pathways, in addition to metabolism—the conversion of food into energy—were enhanced in the meditation people.

Finally, blood sample analysis showed that levels of agents associated with a heightened risk of cardiovascular disease, including total cholesterol and apolipoprotein B, were significantly lower in the monks than in their secular neighbours by their functional analysis with the gut microbes.

Although a comparative study, it is observational. The numbers of participants were small, all male, and lived at high altitudes, making it difficult to draw any firm or generalisable conclusions. And the potential health implications could only be inferred from previously published research.

But based on their findings, the researchers suggest that the role of meditation in helping to prevent or treat psychosomatic illness merits further research.

And they conclude: “These results suggest that long-term deep meditation may have a beneficial effect on gut microbiota, enabling the body to maintain an optimal state of health.”

Posted on ADHD, Autism

The link between mental health and ADHD is vital – so why aren’t we paying attention?

ADHD
ADHD

Adults with high levels of attention-deficit hyperactivity disorder (ADHD) symptoms are more likely to experience anxiety and depression than adults with high levels of autistic traits, according to new research led by psychologists at the University of Bath in the UK.

This study is the first to show that ADHD predicts poor mental health outcomes in adults more than other neurodevelopmental conditions, like autism.

Until now, there has been a dearth of information on the effects of ADHD on poor mental health, with far more research focusing on the impact of autism on depression, anxiety and quality of life. As a result, people with ADHD often struggle to access the clinical care they need to cope with their symptoms.

The study’s authors hope their findings will trigger new research into ADHD and ultimately improve the mental health outcomes for people with the condition. ADHD is a neurodevelopmental condition characterised by inattention and/or hyperactivity and impulsivity. The condition is estimated to affect between 3% and 9% of the population.

Blue Monday

Speaking on Blue Monday (January 16) – the third Monday of January, described by some as the gloomiest day of the year – lead researcher, Luca Hargitai, said: “Scientists have long known that autism is linked to anxiety and depression, but ADHD has been somewhat neglected.

“Researchers have also struggled to statistically separate the importance of ADHD and autism for mental health outcomes because of how frequently they occur together.”

Ms Hargitai, a PhD Researcher at Bath, added: “Our aim was to precisely measure how strongly ADHD personality traits were linked to poor mental health while statistically accounting for autistic traits.”

The new research – a collaborative effort between the Universities of Bath, Bristol and Cardiff, and King’s College London – is published this week in the prestigious journal Scientific Reports. It comes in the same month that two British TV personalities – Johnny Vegas and Sue Perkins – have opened up about their recent diagnoses of ADHD.

“The condition affects many people – both children and adults – and the fact that more people are willing to talk about it is to be welcomed,” said Ms Hargitai. “The hope is that with greater awareness will come more research in this area and better resources to support individuals in better managing their mental health.”

Overly active, as though driven by a motor

The study used a large, nationally representative sample of adults from the UK population. All participants completed gold standard questionnaires – one on autistic traits, the other on ADHD traits – responding to statements such as “I frequently get strongly absorbed in one thing” and “How often do you feel overly active and compelled to do things like a motor drove you?”

The researchers found that ADHD traits were highly predictive of the severity of anxiety and depression symptoms: the higher the levels of ADHD traits, the more likely a person is to experience severe mental health symptoms. Through innovative analytical techniques, the study authors further confirmed that having more of an ADHD personality was more strongly linked to anxiety and depression than autistic traits.

These results were replicated in computerised simulations with a 100% ‘reproducibility rate’. This showed, with great confidence, that ADHD traits are almost certainly linked to more severe anxiety and depression symptoms in adults than autistic traits.

Shifting the focus of research and clinical practice

Ms Hargitai said: “Our findings suggest that research and clinical practice must shift some of the focus from autism to ADHD. This may help to identify those most at risk of anxiety and depression so that preventative measures – such as supporting children and adults with the management of their ADHD symptoms – can be put in place earlier to have a greater impact on improving people’s wellbeing.”

According to Dr Punit Shah, senior author and associate professor of Psychology at Bath, another important aspect of the new study is that it advances scientific understanding of neurodevelopmental conditions.

“By addressing the shortcomings of previous research, our work provides fresh information about the complex links between neurodiversity and mental health in adults – an often overlooked area.

“Further research is now needed to delve deeper into understanding exactly why ADHD is linked to poor mental health, particularly in the mental processes that might drive people with ADHD traits to engage in anxious and depressive thinking.

“Currently, funding for ADHD research – particularly psychological research – is lacking. This is significantly pronounced compared to the relatively high funds directed at autism.

“As the evidence becomes clear that ADHD isn’t just a childhood condition but persists throughout life, we must adjust our research agendas to understand ADHD in adulthood better.”

Commenting on the new findings, Dr Tony Floyd, CEO of ADHD Foundation, The Neurodiversity Foundation, said: “This research demonstrates clear evidence of the increased risks of mental health comorbidities associated with adult ADHD. This is a step towards recognising the broader impact of unmanaged and untreated ADHD. We hope this research will lead to more commissioned research in this area. We also hope it will result in changes to the design and delivery of health services.

“The cost implications to the NHS of leaving ADHD untreated, and the need to better train health practitioners in primary and secondary care, are now more apparent. And of course, there are other costs too that need to be considered – to the health of UK citizens with ADHD and to their family life, employability and economic well-being. These costs are often hidden, but they are considerable.

“This research from Bath University will add to the growing national debate and the business case for a national review of health services for ADHD across a person’s lifespan.”

Posted on Patient Talk

How better planning and behaviour regulation may lead to eating less fat

New research suggests coaching overweight or obese pregnant women to improve their ability to plan and progress toward goals may be vital to helping them lower the amount of fat in their diet.

Maternal diet quality affects prenatal development and long-term child health outcomes. Still, the stress that typically increases during pregnancy – often heightened by concern for fetal health and anxiety over impending parenthood – may derail efforts to focus on healthful eating, previous research has shown.  

In this new study, researchers at The Ohio State University set out to identify the pathway between stress and total fat consumption, with a broader goal to evaluate an intervention designed to improve the diets of pregnant women who are overweight or obese.

Through a series of questionnaires and statistical analysis, the team found that two thinking-related skills – planning and execution of those plans – were weakened in women whose stress was high, and those skill gaps were associated with higher total fat intake.

These two skills are executive functions, a set of multiple thinking processes that enable people to plan, monitor behavior and execute their goals.

“People with a higher stress level tend to have a higher fat intake, too. If stress is high, we’re so stressed out that we’re not thinking about anything – and we don’t care what we eat,” said lead author Mei-Wei Chang, associate professor of nursing at Ohio State.

“That’s why we focused on executive functions as a mediator between stress and diet. And with this baseline data, we have reasons to believe that designing an intervention around executive functions could improve dietary outcomes,” she said. “I would anticipate the results could be similar for nonpregnant women because it’s all about how people behave.”

The study was published recently in the Journal of Pediatrics, Perinatology and Child Health.

The 70 women enrolled in the study had a pre-pregnancy body mass index of between 25 (scores between 25 and 29.9 are categorized as overweight) and 45 (scores of 30 and higher are categorized as obese).

The participants completed questionnaires assessing both overall perceived stress and pregnancy-related stress, as well as executive functions – specifically focusing on metacognition, the ability to plan, and behaviour regulation, the ability to execute those plans. They also completed two 24-hour dietary recalls of their calorie intake and consumption of total fat, added sugar, and fruits and vegetables.

“We were interested in the mediation role of executive functions. The mediator is what makes everything happen,” Chang said. “We wanted to know: If we focus intervention on executive functions, would that carry through to behaviour change in dietary intake?

“Weight loss interventions often involve a prescribed diet or meal plan, and you are told to follow it. But that doesn’t lead to behaviour change in the long term.”

Statistical modelling showed that higher perceived stress was associated with a worsened ability to plan and monitor behaviour, and that pathway was linked to higher total fat intake. Similarly, higher levels of pregnancy-related stress were associated with a lower ability to plan, which in turn was associated with the worsened ability to monitor behaviours related to carrying out the plan – and these factors were linked to higher fat consumption.

These pathways suggested that an intervention designed to lower stress would function as a starting point to improve the diet and enhancing skills through coaching – emphasizing the ability to plan, including being flexible with planning, and behaviour monitoring, particularly when making food choices – would be key to changing eating patterns.

“You need to improve executive functions, and you also need to lower stress,” Chang said. She and colleagues are now analyzing data on the effectiveness of an intervention for the study participants that emphasized stress management and boosting executive function to promote healthy eating.

A specific region of the brain regulates executive functions, and strengths or weaknesses in these skill areas are thought to be affected by various physiological factors. Previous research has found that executive function deficits are more likely to occur in women who are overweight or obese than in women whose weight is average.

“Executive function is not well-studied, and it is not related to intelligence. But people with low executive function cannot make detailed plans and stick to them, and that’s how they get into trouble,” Chang said. “Metacognition and behaviour regulation must go hand in hand – that way you have a much better chance to control your behaviours, and then you will eat better.”

Posted on Diabetes

Type 1 diabetes: Maintaining the enzyme ACE2 in the gut prevents diabetic blindness

Maria Grant


Maria Grant

 The leading cause of blindness in American adults is diabetic retinopathy, progressive damage to blood vessels in the light-sensitive tissue at the back of the eye. Yet the source of this damage appears to lie in the belly — mainly a leaky small intestine that weakens the barrier between gut bacteria and the blood system, according to a study published in the journal Circulation Research.

The research blood from human subjects with Type 1 diabetes and a mouse model of Type 1 diabetes were used to explore mechanisms underlying diabetic retinopathy. The results show a way to possibly prevent, or even reverse, eye damage.

“To our knowledge, this study represents the first time that gut barrier disruption has been implicated in the pathogenesis of diabetic retinopathy and also directly links gut leakage with retinopathy severity in human subjects with Type 1 diabetes,” said Maria Grant, M.D., leader of the research team and a professor in the University of Alabama at Birmingham Department of Ophthalmology and Visual Sciences.

Some background is useful to understand Grant’s research.

First, it is known that Type 1 diabetes dysregulates the systemic renin-angiotensin system, or RAS. RAS is a system of hormones and enzymes that regulates blood pressure and other metabolic changes. Besides systemic RAS, there are also local RAS networks that act in diverse tissues. One key RAS enzyme is ACE2, or angiotensin-converting enzyme 2. The loss of ACE2 in diabetes activates the vasodeleterious RAS axis and lessens the vasoprotective RAS axis. Intriguingly, in a mouse model of Type 1 diabetes, feeding mice with a modified gut bacterial strain of Lactobacillus paracasei, which was engineered to produce human ACE2, protects the mice against diabetic retinopathy progression. Finally, lack of ACE2 in the gut was known to increase gut permeability and systemic inflammation.

The human studies, published in Prasad, Floyd et al., Circulation Research, compared people with Type 1 diabetes versus controls. The subjects with Type 1 diabetes were further stratified into three groups: no diabetic retinopathy, non-proliferative diabetic retinopathy and the more serious disease called proliferative diabetic retinopathy. By measuring levels of certain immune cells and biomarkers in the blood, including gut microbial antigens, the researchers found that human subjects with retinopathy had a dysregulated systemic RAS and profound gut permeability defects that activated components of both the adaptive and innate immune response. Furthermore, increases in the severity of diabetic retinopathy were found to correlate with increased levels of gut permeability biomarkers and a gut microbial antigen. This included increased levels of angiotensin II, the RAS hormone that activates the vasodeleterious RAS axis.

Using the Akita mouse-Type 1 diabetes model, researchers first gave the ACE2-producing Lactobacillus paracasei, developed by Qiuhong Li, Ph.D., from the University of Florida, to the mice orally beginning at the onset of diabetes. This probiotic treatment prevented the loss of gut epithelial ACE2 typically seen in Akita mice, and importantly, it prevented intestinal epithelial and endothelial barrier damage. It also reduced the high blood sugar levels known as hyperglycemia.

When the oral ACE2-producing Lactobacillus paracasei treatment was withheld until six months after diabetes was established, that delayed treatment reversed the gut barrier dysfunction and diabetic retinopathy that had already formed in the mice, including reducing the number of damaged capillaries in the retina.

Grant and colleagues also found evidence for several mechanisms that contributed to the ACE2-reduced gut barrier damage and ACE2-lowering of blood sugar. To validate results from the Akita/ACE2-producing Lactobacillus paracasei model, they created a second model — a genetically modified Akita strain that overexpresses human ACE2 in small intestine epithelial cells.

“The significance of the work is we demonstrated that dysregulated intestinal RAS results in translocation of gut microbial antigens into the plasma,” Grant said. “These bacterial peptides activate the endothelium via toll-like receptors, creating an inflammatory endothelium that has been strongly implicated in the pathogenesis of vascular diseases, including diabetic retinopathy.

“We demonstrated loss of intestinal barrier function in human subjects with Type 1 diabetes using gut barrier biomarkers, and this increase in permeability was associated with gut-derived immune cell activation.”

Posted on Lupus

Study identifies potential new approach for treating lupus

Researchers identify new approach for treating lupus


Jeffrey Rathmell, PhD, (left), and Kelsey Voss, PhD, led a multidisciplinary team that identified iron metabolism in T cells as a potential target for treating lupus. CREDIT Vanderbilt University Medical Center

Targeting iron metabolism in immune system cells may offer a new approach for treating systemic lupus erythematosus (SLE) — the most common form of the chronic autoimmune lupus.

A multidisciplinary team of investigators at Vanderbilt University Medical Center has discovered that blocking an iron uptake receptor reduces disease pathology and promotes the activity of anti-inflammatory regulatory T cells in a mouse model of SLE. The findings were published Jan. 13 in the journal Science Immunology. 

Lupus, including SLE, occurs when the immune system attacks a person’s own healthy tissues, causing pain, inflammation and tissue damage. Lupus most commonly affects skin, joints, brain, lungs, kidneys and blood vessels. About 1.5 million Americans and 5 million people worldwide have a form of lupus, according to the Lupus Foundation of America. 

Treatments for lupus aim to control symptoms, reduce immune system attack of tissues, and protect organs from damage. Only one targeted biologic agent has been approved for treating SLE, belimumab in 2011. 

“It has been a real challenge to come up with new therapies for lupus,” said Jeffrey Rathmell, PhD, professor of Pathology, Microbiology and Immunology and Cornelius Vanderbilt Chair in Immunobiology. “The patient population and the disease are heterogeneous, which makes it difficult to design and conduct clinical trials.” 

Rathmell’s group has had a long-standing interest in lupus as part of a broader effort to understand mechanisms of autoimmunity. 

When postdoctoral fellow Kelsey Voss, PhD, began studying T cell metabolism in lupus, she noticed that iron appeared to be a “common denominator in many of the problems in T cells,” she said. She was also intrigued by the finding that T cells from patients with lupus have high iron levels, even though patients are often anemic. 

“It was not clear why the T cells were high in iron, or what that meant,” said Voss, first author of the Science Immunology paper. 

To explore T cell iron metabolism in lupus, Voss and Rathmell drew on the expertise of other investigators at VUMC: 

  • Eric Skaar, PhD, and his team are experienced in the study of iron and other metals; 
  • Amy Major, PhD, and her group provided a mouse model of SLE; and 
  • Michelle Ormseth, MD, MSCI, and her team recruited patients with SLE to provide blood samples. 

First, Voss used a CRISPR genome editing screen to evaluate iron-handling genes in T cells. She identified the transferrin receptor, which imports iron into cells, as critical for inflammatory T cells and inhibitory for anti-inflammatory regulatory T cells. 

The researchers found that the transferrin receptor was more highly expressed on T cells from SLE-prone mice and T cells from patients with SLE, which caused the cells to accumulate too much iron. 

“We see a lot of complications coming from that — the mitochondria don’t function properly, and other signaling pathways are altered,” Voss said. 

An antibody that blocks the transferrin receptor reduced intracellular iron levels, inhibited inflammatory T cell activity, and enhanced regulatory T cell activity. Treatment of SLE-prone mice with the antibody reduced kidney and liver pathology and increased production of the anti-inflammatory factor, IL-10. 

“It was really surprising and exciting to find different effects of the transferrin receptor in different types of T cells,” Voss said. “If you’re trying to target an autoimmune disease by affecting T cell function, you want to inhibit inflammatory T cells but not harm regulatory T cells. That’s exactly what targeting the transferrin receptor did.” 

In T cells from patients with lupus, expression of the transferrin receptor correlated with disease severity, and blocking the receptor in vitro enhanced production of IL-10. 

The researchers are interested in developing transferrin receptor antibodies that bind specifically to T cells, to avoid any potential off-target effects (the transferrin receptor mediates iron uptake in many cell types). They are also interested in studying the details of their unexpected discovery that blocking the transferrin receptor enhances regulatory T cell activity. 

Skaar is the Ernest W. Goodpasture Professor of Pathology and director of the Vanderbilt Institute for Infection, Immunology, and Inflammation. Major, associate professor of Medicine, and Ormseth, assistant professor of Medicine, are faculty members in the Division of Rheumatology and Immunology. Rathmell is the director of the Vanderbilt Center for Immunobiology.