The microbiome may affect a child’s temperament

A new study was recently published that highlights the gut-brain axis once again.  The study, out of Ohio State University and published in Brain, Behavior, and Immunity, compares the microbiomes of toddlers and compares it to their overall behaviors.  The results show an association between temperament and the microbiome may exist.

In the study 77 toddlers were recruited to take food questionnaires, behavioral tests, and have their stools sampled.  They discovered that certain microbiome differences, which were not attributable to differences in diet, were directly associated with behavioral traits.  Chief among them was the discovery that higher microbiome diversity was correlated to more extraversion in children.  Whether or not this microbiome difference is the cause, or an effect, of these children being more active and engaged with their environments is still unknown.  Another connection was that Rickenellaceae was associated with fearful female toddlers and high intensity male toddlers.   This was interesting because bacteria from this genus have been associated with depression.

We note that the researchers’ testing methods were hardly rigorous due to the lack of controls, but the gut-brain axis has been well established, so this work still fits into an existing framework.  In addition, some may be skeptical that the microbiome could be influencing children’s behavior, but remember that the bacteria within us have been evolving along with us for so long that nothing should surprise us.  The next time the parents out there are dealing with their unruly children, you can kill two birds with one stone by punishing them by making them eat sauerkraut or kimchi!

Probiotics and a healthy heart

Major signs and symptoms of heart failure.

Chronic heart failure, also known as congestive heart failure, is a condition in which the heart has difficulty pumping blood throughout the body.  This sometimes fatal disease affects around 2% of all adults in the United States and symptoms include shortness of breath, tiredness, and swelling.  Patients of heart failure present many signs of low grade heart inflammation which leads scientists to believe that the immune system is an important cause in many cases.  For this reason scientists in Brazil conducted a clinical trial on the effect of probiotics in treating heart failure.  Their results were published last month in the International Journal of Cardiology.

The researchers recruited twenty heart failure patients and gave half of them a placebo and half of them the bacteria Saccharomyces boulardii every day for 3 months.  At the end of the three months the scientists examined the patients’  heart health and discovered that those people taking the probiotic had a decrease in cholesterol, uric acid, left ventricle diameter, and an improvement in heart strength (as measured by ejection fraction’), with many of these improvements far exceeding the placebo group. 

The study was small, but important.   Simply taking a daily probiotic, which had no adverse side effects, helps improve heart health.  It is probably only a matter of time before the recommended food pyramid includes an entire section devoted to fermented edibles. 

Changes in the microbiome may affect how we age

Betty White has aged so well because of her microbiome.  Photo by David Shankbone, 2010

Many people have researched the microbiome shift between infancy and adolescence, but very few have researched the changes in the microbiome that occur in the elderly.  A new study out of Canada, published in the Journal Microbiome, did just that.  Their results show that the frailty associated with old-age may be related to the bacteria in our guts.

The study used groups of mice that were either young, middle aged, or old.  They then measured the frailty of these mice which, as one would expect, was tied closely with age.  The researchers then studied the microbiome of these mice, as well as the genes expressed by the bacteria, so as to gain an understanding of what the bacteria are actually doing.

The scientists discovered that, when compared to young and middle aged mice, the old mice were abundant in bacteria that could break down simple sugars, but were underrepresented in bacteria that could break down more complex sugars, as well as lactate.  This is important because increased lactate in the stool has been associated with ulcerative colitis and other inflammatory bowel diseases in older humans.  The old age mice also consisted of less bacteria that could produce vitamins B12 and B7.  Both are important vitamins and the lack of B7 has been linked to colon cancer.  Finally, the old-age mice had bacteria that would rapidly degade creatine.  Creatine is known to build muscle, so constantly breaking it down may cause the decrease in muscle mass observed in the elderly.

Clearly there are changes in the microbiome as we age, and these changes must come with some consequences.  As the authors of this paper suggest, perhaps the microbiome holds to key to the difference between aging like a fine wine and aging like moldy cheese.

How is the microbiome associated with Parkinson's disease?

Michael J. Fox, before he was diagnosed with Parkinson's disease (photo by Alan Light)

We’ve talked before about what we call the gut-brain axis, the crosstalk between the gut and brain, and it’s effects on autism  and depression. But scientists in Finland have now shown that there is a relationship between bacteria in the gut and Parkinson’s disease. While Parkinson’s disease is a neurodegenerative disease caused by the loss of dopamine producing neurons in the brain that results in the loss of motor functions and tremors, gastrointestinal dysfunction, specifically constipation, is another symptom of the disease and often precedes the loss of motor function in patients.

Even though Parkinson’s disease was first described in 1817 and has been studied for many years, we still do not know what causes the majority of cases of the disease (approximately 5% of cases are a result of genetic mutations).  Because gastrointestinal dysfunction is implicated in the disease, scientists have hypothesized that the microbiome and bacteria in the gut may play a contributing role in the disease. 

Published in the journal Movement Disorders, the researchers in Helsinki have shown that there are variations in specific bacteria in Parkinson’s patients compared to control subjects without the disease. They recruited 72 Parkinson’s patients and the same number of control subjects and compared the bacteria in their fecal samples. They found that specific bacteria, specifically in the Prevotellaceae family, were less abundant in patients who had Parkinson’s disease. Patients who had high levels of Prevotellaceae were unlikely to have the disease. They also found that patients who had higher levels of bacteria in the Enterobacteriaceae family had greater severity of balance impairment and difficulties with their gait. 

While low levels of Prevotellaceae cannot yet be used as an identifier for Parkinson’s disease because it has also been correlated in other conditions like autism and type 1 diabetes, this study shows us that a better understanding of the bacteria in our guts may provide insight into the cause of the disease.  It is important to further investigate the microbiome in association with Parkinson’s as the identification of a biomarker for the disease is critically important. Understanding the role that bacteria in the gut may have in the disease may not only allow us to better identify and diagnose patients, but manipulation of the microbiome prior to the onset of the disease may help prevent or slow disease progression. Countless diseases and conditions are thought to be caused by environmental factors and as we discussed in yesterday's blog, the microbiome may play an important role in these environmental causes of disease.  

Microbiota biofilms and colorectal cancer

Colorectal cancer is the 4th most deadly cancer in the world, and over 1 million people are diagnosed with it each year.  It has very few genetic indicators and it is rapidly growing in prevalence, thus researchers believe it is very likely associated with environmental causes.  An obvious environmental cause would be the microbiome, and researchers from John’s Hopkins helped establish this link with their recent publication in PNAS.  In their article they show that biofilm formation in the colon is tightly correlated with colorectal cancer.

The researchers studied a cohort of people that had colorectal cancer along with healthy people as controls.  In those people with tumors they studied the microbiome of the tumors themselves along with other, distal parts of their colons.  They discovered that the majority of people with tumors, whether benign or malignant, had thick biofilms growing on and even in the tumor.  What’s more, is that the researchers noticed that biofilms were forming all along the colon, even in the distal parts.  Biofilms were not seen in healthy patients, and in some of the patients with tumors. 

Interestingly, the bacteria in the biofilms between different patients did not necessarily correlate, and so it appeared the presence of biofilms, rather than the composition of the biofilm was critical.  Moreover, the biofilms studied decreased the gut permeability, leading to ‘leaky guts’, which we have covered on this blog before.

A normal colon has a mucous layer to prevent any bacteria from infiltrating the underlying epithelial cells.  It is possible that people with decreased mucosal integrity are at risk for bacteria to invade and form these biofilms which may eventually lead to cancer.  In fact, according to this small study, people with biofilm formation in their colon have a 5-fold increase in their likelihood to get colorectal cancer, much higher than any other known indicator.  More research on a larger scale still needs to be performed.  Still though, biofilm detection could be a useful diagnostic for colorectal cancer, and biofilm management could be a target for drugs or probiotics. 

Gut bacteria protect against malaria transmission

Malaria is a deadly disease transmitted through mosquitoes and most widespread in tropical and subtropical regions around the world, especially in Africa. According to the Center for Disease Control and Prevention (CDC), 627,000 people died in 2012 and there were a total of 207 million cases worldwide. Through studying the microbiome, scientists last week published a major discovery in Cell that may lead to better vaccinations for malaria that could help prevent the disease from being transmitted.

Scientists in Portugal, collaborating with colleagues in the United States, Australia, and Mali, found that the parasite the causes malaria, Plasmodium, expresses the same sugar molecule that is seen in a type of Escherichia coli (E. coli).  This sugar molecule from the E. coli called alpha-gal (a-gal) results in the body’s immune system producing antibodies against this molecule and therefore also protecting against the malaria parasite. It is known that adults who are exposed to malaria are at lower risk of contracting the disease than children under the age of 5 and the researchers hypothesized that this was due to the children lacking this specific E. coli in their body and therefore unable to fight back against Plasmodium exposure.   

The scientists studied the gut bacteria of a group of individuals in Mali who had very high rates of malaria transmission. They found that those who had higher levels of anti-a-gal antibodies had lower risk of transmitting malaria and those with low levels of these antibodies had greater risk of transmitting the disease.  This showed that children are at greater risk for the disease because they do not produce enough anti-a-gal antibodies to prevent the parasite from infecting the body.

The scientists also found that the transmission of the parasite is blocked almost immediately following its introduction into the body through the skin. The antibodies against a-gal attach to the Plasmodium as soon as it is exposed to the body, and a part of the immune system called the component cascade is activated, killing the parasite before it can leave the skin and reach the blood stream.   

They found that by vaccinating mice against a kind of a-gal, the mice produced enough anti-a-gal antibodies that were highly efficient in protecting the mice from malaria transmission.  The scientists believe that it may now be possible to translate this work to humans and develop vaccines that would increase anti-a-gal antibodies and prevent malaria transmission. If successful, vaccinations could be given to children who are at high risk for the disease and could prevent hundreds of thousands of deaths every year.  These findings also illustrate the protective aspects of the microbiome in regulating immunity, and the potential treasure-trove of molecules produced by the microbiome that could be used in therapeutics.