Prebiotics in human breast milk are associated with infant weight

Human breast milk contains nutrients and compounds that are beneficial for infants. Human milk oligosaccharides (HMOs) are a group of important complex carbohydrates that are found in breast milk. These HMOs are important in the developing infant because they serve as a prebiotic, helping to shape the infant’s gut microbiome by facilitating the selection of beneficial bacteria. The link between gut microbiota composition and infant obesity has led to speculation that HMOs might affect certain bacteria that in turn lead to decreased body fat. Because HMO composition of female breast milk varies over the course of lactation, researchers in Oklahoma and California tested to see whether differences in milk HMO content are associated with infant body weight. The results of their study were published in The American Journal of Clinical Nutrition.

Twenty-five mother-infant pairs participated in this study. On average, the mothers were 29.5 years of age and overweight before conception. When the infants were 1 month and 6 months old, the mothers supplied breast milk samples to test for HMO composition. Concurrently, the infants’ body fat composition, weight, and length were measured.

The findings suggest that HMOs are associated with infant body weight, fat mass, and lean mass at both 1 month and 6 months. A diversity of HMOs, such as LNFFPI (lacto-N-fucopentaose I, a sugar), DSLNT (difucosyl-LNT, a sugar), and FDSLNH (fucosyl-disialyl-lacto-N-hexaose, a sugar) accounted for 33% of the fat mass, which was more than other variables such as gender, and mothers’ pregnancy BMI. infant fat mass than did sex, pregnancy BMI.  LNFPI was inversely associated with 1 month old infant weight, while at 6 months it was inversely associated with weight, lean mass, and fat mass. Overall, the presence of a diverse group of HMOs decreased infant body mass.  While this study has its limitations because it does not specifically test the bacterial composition of the gut, it is a first step to identifying an association between HMOs and infant BMI. As obesity remains an epidemic in the United States, perhaps the microbiome is the first place to look towards to prevent the disease. 

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.

The anorexia nervosa gut microbiome differs from healthy controls and is related to mental health

Two photographs, before and after treatment for anorexia

Anorexia nervosa is devastating condition in which an individual purposely starves themselves leading to severely low weight.  In addition, most patients with anorexia have depression, and there is a definitely mental aspect to this disease.  The disease then, has both dietary and mental components, making it extremely interesting to microbiome scientists, because the microbiome is implicated with both of these facets.  Scientists from UNC recently conducted a preliminary study on both of these aspects of the disease by comparing the microbiomes and mental state of anorexic patients before and after treatment, along with healthy controls.  They published there results last week in the journal Psychosomatic Medicine.

Sixteen patients with anorexia nervosa who sought treatment for their disease had stool samples collected at admission to the hospital as well as their mental health assessed.  Ten of these individuals that made partial recoveries (improved body mass index) were discharged from the hospital and donated stool samples and had their mental health assessed upon leaving.  The researchers discovered that the patients’ microbiomes severely lacked diversity compared to aged matched controls, and that was true for both admission and discharge from the hospital.  The scientists noted though, that the patients that left the hospital had microbiomes that more resembled the control individuals than when they entered.  For example, the anorexic patients had very little Clostridia when they entered the hospital, but these populations rebounded during treatment.  In terms of the mental health aspect of anorexia and the microbiome, the researchers found a direct association between eating disorder psychopathology and microbiome diversity, with lower diversity corresponding to worse eating disorder psychopathology.  The same was true for depression, as the degree of depression was inversely correlated with bacterial diversity.  In terms of individual families of bacteria, a lack of Ruminococcaceae had the strongest association negative mental state.

This study shows that a lack of eating decreases gut flora diversity and negatively impacts the microbiome.  While not surprising, this lack of diversity will almost certainly cause a dysbiosis that detriments many other aspects of health.  One of these, in the case of anorexia, may be mental health, but of course it is not clear which causes which, or if there is any causation or merely just correlation.  In any event, disorders that have both mental and dietary components are extremely fascinating to investigate, as it is possible the microbiome is of primary importance to these diseases.

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.

Gastric bypass surgery alters microbiome which possible contributes to weight loss

Schematic of Roux-en-Y anastomosis.

Roux-en-Y gastric bypass surgery and vertical banded gastroplasty are two types of bariatric weight loss surgeries that are highly effective in promoting weight loss.  The mechanisms for their efficacy are complex and not completely known, but both surgeries are shown to reduce caloric intake, suppress hunger and increase gastric emptying.  Little is known about how the microbiome changes during these surgeries, and how this change may effect subsequent weight loss.  A team of Swedish scientists investigated this topic and showed the gut microbiota undergo important changes.  They published their results in the journal Cell Metabolism.

The researchers compared the microbiomes of women that were obese and hadn’t had surgery with those who were of similar BMI presurgery, but had undergone surgery at least nine years earlier.  They observed some major differences in the women’s microbiomes, with the post-operative women had much higher levels of Gammaproteobacteria and lower levels of Firmicutes.  When the scientists looked at actual genetic variations they found many differences.  Some notable differences were a decrease in short chain fatty acid (SCFA) and in increase in trimethylamine N-oxide (TMAO) creation in women who had surgery.  As we have written about in this blog before, SCFAs are often associated with health, while TMAO is a risk factor for some cardiovascular diseases.  Interestingly, when they took the microbiomes from both groups of women and transferred them into germ-free mice, the mice receiving microbiomes of women that had undergone surgery gained less weight than the mice that received microbiomes of obese women.

Gastric bypass surgery is often a last resort for folks that have severe obesity.  While not normally considered, the microbiome is drastically affected by this procedure. The microbiome is certainly altered by the procedure, and it appears that it may even be helping keep the weight off.  However, there may be some negative microbiome-mediated consequences as well, derived from alterations to micrbiome metabolism, such as an increased level of TMAO.  Like all surgeries, folks undergoing this one need to balance the risks and rewards of the procedure, and hopefully after this study, the microbiome will be considered.