Associations between the microbiome and blood lipids

Cholesterol molecule

It is well known that we have to be careful with what foods we eat, remembering to stay healthy and eat our fruits and vegetables. Diets high in fat can create serious health issues such as obesity, high cholesterol, and possibly Type 2 diabetes. Also on that list of related health problems is cardiovascular disease, which is characterized by blood clots, due to fat and plaque build-up in blood vessels, and can lead to a heart attack or stroke. Previous research has implied a connection between the microbiome and cardiovascular disease, due to the microbiome’s effect on production of a molecule called trimethylamine N-oxide (TMAO). As of yet, no research has been done to track the association between the microbiome and lipid (fat) build-up, so this is precisely what researchers published in Circulation Research set out to do.

The scientists located in The Netherlands, Poland, and Massachusetts, collected blood cholesterol measurements from 1500 LifeLines-DEEP subjects. LifeLines-DEEP is a collection of subjects used for assessing various health issues. Ethnic outliers and genetically related participants were removed from the study. Fecal samples were collected from 1180 participants, and sequenced. By the end of the data collection, 99 participants were excluded for reasons such as antibiotic use, or use of potentially microbiome-altering medications. In total there was a final number of 893 participants (380 men and 513 women) for which cholesterol samples, microbiome samples, and genotypic information was obtained. The participants included a wide range of age, BMI, and blood lipid levels.

The researchers found that gut microbiome species richness was significantly higher in women, and increased with age. Microbial richness was positively correlated with high density lipoproteins (HDL, the 'good cholesterol'), not correlated with low density lipoproteins (LDL, the bad cholesterol), and negatively correlated with body mass index (BMI). For example, the study confirmed that lower abundances of kingdom Archaea, families Christensenellaceae and Rikenellaceae, class Mollicutes, and genus Dehalobacterium are associated with high BMI. It was estimated that the microbiome could explain 4.57% to 65 of variation in BMI, triglyceride and HDL. No link was found between the gut microbiome and genetic predisposition to obesity of high blood lipid levels.

One hypothesis raised by the researchers is that bacteria potentially try to correct lipid imbalances, thereby helping to prevent cardiovascular disease. The strong associated between the gut microbiome and BMI and blood lipid levels – regardless of age, sex, and genetics – suggests that the microbiome does indeed play a role, if indirectly, in cardiovascular disease and other fat-related issues. 34 gut bacteria were found to be associated with BMI and blood lipids. There is a real potential for the utilization of this information in health therapies, such as blood clot and stroke prevention.

New study suggests gut microbiome directly influences BMI, triglyceride, and HDL levels

Molecular structure of cholesterol

The microbiome has long been associated with cardiovascular disease, especially after studies showing differences between the gut microbiomes of obese and slim individuals.  The mechanisms by which the microbiome may be influencing heart disease are still unknown, but there are a few mechanisms that have been identified.  For example, as has been previously discussed on this blog, trimethylamine N-oxide (TMAO) in the blood is an independent risk factor for atherosclerosis, and is produced by gut bacteria from choline and carnitine.  In addition, systemic, chronic inflammation is associated with heart disease, and our avid readers will know that the microbiome can cause chronic inflammation in the vagina, gut, and mouth.  Overall though, a direct relationship between specific bacteria and heart disease has not been shown.  A recent epidemiological study though, did just that.  The researchers, mostly from the Netherlands, were able to identify specific species that were associated with higher BMIs, as well as those that were directly correlated with HDL cholesterol levels.  They published their results in the journal Circulation Research.

The scientists measured the genomes, microbiomes, BMI, and blood lipids of 1500 adults.  Their results showed that higher overall diversity and richness of the gut microbiome was associated with a lower a lower BMI (healthier state), lower triglycerides (healthier state), and higher level of HDL cholesterol (healthier state).  The diversity was not, however, associated with total cholesterol nor LDL levels.  The researchers then identified specific bacteria associated with these health indicators.  There are too many to list in this blog, so we encourage interested readers to take a look at the article.  Some examples though: Akkermansia, Christensenellaceae, and Tenericutes were each associated with low BMI, low triglycerides, and high HDL (all healthy states), while Eggerthella was associated with high BMI and high triglycerides, and Butyricimonas was associated with high BMI, high triglycerides, and low HDL (all unhealthy states).  Finally, the researchers sought to determine just how important the microbiome was to overall BMI, triglyceride levels, and HDL levels by incorporating the host genetics, age, and gender into their calculations.  They showed the 4.5% of the variance in BMI, 6% of the variance in triglycerides, and 4% of the variance in HDL is directly attributable to the microbiome.

These study results reaffirm the importance of the microbiome to our overall health, and even quantitatively show its influence on specific health indicators.  The authors do not attempt to explain why specific bacteria would cause variation in these metrics, although as previously mentioned some mechanisms have already been demonstrated.  To check to see which other diseases these bacteria have been associated with, use the search tool, or click the tags below to see all the blog articles that mention them.

Does eating fermented foods help you lose weight?

Kimchi is a Korean food that traditionally consists of fermented cabbage and spices.  It is a staple in the South Korean diet, and is one of the most frequently consumed fermented foods.  The presence of bacteria in the kimchi has led many to speculate that it can exert a positive influence on the microbiome, and kimchi is believed to have anti-obesity effects.  In order to test this hypothesis researchers from South Korea conducted a clinical trial in which they put obese women on a kimchi diet.  The women were split into two groups, one of which consumed fermented kimchi, while the other consumed non-fermented kimchi.  A summary of the study was recently published by Molecular Nutrition and Food Research.

Surprisingly, fermentated kimchi did not appear to affect the women’s body measurements or specific health indicators when compared to the non-fermented version.  For example, women on both diets had similar decreases in weight, waist circumference, body fat, blood pressure, and cholesterol. There were some important differences though, fermented kimchi increased fasting insulin levels and fasting blood glucose.

The scientists also measured the two groups’ gut microbiomes and blood gene-expression in the study.  The group that ate fermented kimchi had higher abundances of Bacteroides and Prevotella in their microbiomes, and an increased Bacteroides/Firmicute ratio, which has been linked to weight loss.  Bifidobacterium longum, a major lactic acid bacterium that ferments kimchi, has also been linked to weight loss, and to this end, a significant correlation between an increase of this bacterium in the microbiome and decrease in waist circumference was observed.    In addition, a gene known as Acyl-CoA synthetase long-chain family member 1 was found to be significantly upregulated in subjects consuming fermented kimchi compared to those consuming fresh kimchi. This gene plays an important role in metabolism, and it is important in breaking down fatty acids. A second gene, aminopeptidase N (ANPEP) was also expressed more in subjects consuming fermented kimchi.  ANPEP is important for regulating inflammation, and has been associated with a healthy blood pressure.

Overall, this study showed fermented kimchi possibly has beneficial effects on metabolism and immunity when compared to the non-fermented variety. While this study is limited by its small sample size, among other factors, it still shows that the bacteria involved in the fermentation process could benefit us in more ways than we currently know.  These bacteria not only make kimchi taste good, but they may make us healthy too!

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.