Microbiome affects blood glucose levels after eating, can help predict glycemic response to foods

Postprandial (post-meal) glycemic response (PPGR) is the effect that food has on blood glucose levels.   Eating a sugary candy, for example, will raise blood glucose levels, whereas drinking water will not.  PPGR remains an important predictor for metabolic syndrome and type II diabetes, so it has an important role the obesity epidemic.  Unfortunately, PPGR is difficult to predict, and efforts that are based on individual foods themselves have failed.  New research shows that there are many factors, including the microbiome, that are important to predicting blood glucose after a meal.  The research out of Israel and published in the journal Cell presents a new model that can more accurately predict PPGR that is based on personalized factors.

The researchers catalogued 800 peoples’ meals over 7 days while continuously measuring their blood glucose levels.  In addition they monitored their gut microbiota, weight, sleep, and various other lifestyle factors.  After evaluating the data, the scientists realized that identical foods had vastly different PPGRs.  For example, bread could have a 8 fold variation in glycemic response depending on the individual.  In order to explain these differences, the scientists identified several significant associations between the microbiome and the PPGR from specific foods.  For example, on the phyla level high abundances of Proteobacteria and Enterobacteriaceae were associated with poor glycemic controls.  On the species level Eubacterium rectale, which is known to ferment fiber, was correlated with low glycemic response, and Parabacteroides distasonis, which had previously been associated with obesity, was correlated with hight glycemic response.  The scientists then aggregated all of their data, including microbiome data, and created a predictive algorithm for the PPGR from foods for individuals.  This algorithm accurately predicted the glycemic response from foods on a personalized level, and was more informative than general food based predictions.

This study speaks to the power of personalized medicine that is based on the microbiome.  Knowledge of our own microbiome could be used to advise our dietary choices in order to choose foods that will lead to low PPGR, and decrease our risk for metabolic syndrome.  Overall, the scientists determined that of all foods, eating fiber was most beneficial because it lowers glycemic response over the long term.

Gut microbiome depletion promotes healthier brown fat and reduces obesity in mice

The white and brown turkey meat from a Thanksgiving dinner

An interesting article from Switzerland was published last week in Nature Medicine.  The scientists reported on a new connection between the gut microbiome and metabolic syndrome (i.e. insulin sensitivity, obesity, etc.)  Whereas most papers observe microbiome disruption and depletion is associated with obesity, this paper describes a different phenomenon: that mice with depleted microbiomes are metabolically healthier than their untouched microbiome counterparts.  As part of the basis for the paper it is important to understand that mammals have two types of fat, brown fat and white fat.  Brown fat is associated with exercise, insulin sensitivity, and health, and white fat is associated with insulin resistance and diabetes.  Brown fat can actually repopulate white fat in a process called browning, and this transition is healthy.  

In the study, the scientists started with either normal mice, germ free mice, or mice that had antibiotics administered to them. They challenged each group of mice with glucose, and noted that antibiotic administration led to improved insulin sensitivity.  When they investigated where the glucose was going, they discovered that it was uptaken by white adipose tissue under the skin.  Then, they compared the normal mice and antibiotic mice, and observed that the antibiotic mice actually had smaller volumes of fat after the glucose uptake.  Interestingly, the fat cells in the germ free and antibiotic mice were smaller and more dense, whereas the normal mice had fewer, larger cells.  The researchers then confirmed that browning of fat was occurring in the germ free and antibiotic mice.  Finally, when the scientists transplanted the microbiome of normal mice into the germ free mice a reversal of many the above described characteristics occurred.  In these mice the fat stopped browning, insulin resistance decreased, and the mice gained weight.

The scientists were able to attribute some of the above phenomena to the release of specific cytokines (molecules that regulate the immune system).  This paper, then, adds to the wealth of research that describes the complex but critical interaction between the gut microbiome, the immune system, and metabolic syndrome.  Although the relationships between these things is yet to be fully understood, this paper may at least change the way you think about the dark and white meat during Thanksgiving dinner this Thursday.

Probiotic does not restore gut microbiota function in patients with metabolic syndrome

Insulin resistance may increase the risk for metabolic syndrome

Metabolic syndrome is a condition that often leads to diabetes, heart disease, and even stroke and obesity, a chronic worldwide epidemic is a leading cause of metabolic syndrome (MetS).  It has also been shown that the microbiome may be an important factor in the development of obesity and subsequently, MetS, possibly due to its impact on gut barrier integrity and inflammation. While probiotics have been used as an intervention in several animal studies on obesity and MetS, there have not been sufficient results in humans to show it is having a positive effect.

Despite significant amounts of research, the question still remains if probiotics are having a lasting effect on the gut when administered. It is not clear if taking a probiotic is colonizing in the gut or if it is only providing an acute response during the timeframe it is being administered. A team of scientists published their work showing the effect that Lactobacillus casei Shirota (LcS) had on patients with MetS. The researchers administered LcS to 13 patients with MetS and 15 individuals received no LcS. They sequenced their microbiota composition from stool samples and compared it to healthy controls.

They found that LcS did not have an impact on Bacteroidetes/Firmicutes ratio and that it was slightly higher in the healthy controls. Serum bile acids were similarly not affected by LcS administration. While they did see small microbiota changes, LcS was not able to change the Bacteroidetes/Firmicutes ratio or gut barrier dysfunction, two important staples of metabolic syndrome.

While the small sample size of the patient cohorts may have been a factor in the failure to observe microbiota changes after probiotic administration, it was still important to see that probiotics may not always have the intended consequences we are seeking. In this study, probiotic administration did not provide a benefit to the Metabolic syndrome patients and further studies will be needed to better understand the microbiome implications of probiotics.

The fungal microbiome in obese individuals

We hear mostly about the bacterial microbiome but there are other microbiomes out there like the virome (virus microbiome) and mycobiome (fungal microbiome). The mycobiome is an important part of the gastrointestinal tract and fungal microorganisms make up between .03-2% of the total microorganisms in the gut. A recent study out of Spain characterized the mycobiome of obese individuals and compared them to non-obese individuals.

The scientists used sequencing technologies to analyze the diversity of fungal organisms in the gut of 52 Caucasian individuals who were recruited for the study. After fecal sampling and sequencing, they found that diversity was lower in obese subjects than in non-obese subjects and they could be stratified depending on their mycobiome composition. Ascomycota and Basidiomycota were not significantly different between the two groups, however, the minor phylum Zygomycota was represented less in obese patients.

Interestingly, they found that the relative abundance of fungus in the Eurotiomycetes class of the Ascomycota phylum were similar between obese individuals and non-obese individuals but obese subjects with low levels of Eurotiomycetes had worse metabolic profiles. These subjects were identified as more “unhealthy” obese subjects than those with a higher abundance of Eurotiomycetes. 

This was the first study to look at the human mycobiome in relation to obesity and associated metabolic disorders. Further knowledge of these interactions between the mycobiome, microbiome, and metabolic disorders may elucidate new methods for treating obesity and metabolic syndromes.  

Eating more vegetables appears to improve microbiome-mediated health indicators

There are many diets that have been rigorously shown to decrease metabolic syndrome (obesity, diabetes, etc.) and are generally associated with a healthy lifestyle, such as vegetarian, vegan, and Mediterranean diets.  The one thing they share in common is a high consumption of plant material, and a low consumption of meat.  There are mechanistic reasons for why high veggie - low fat diets should improve health, and many researchers now believe this is partly due to the gut microbiome that these diets create.  In order to help demonstrate the microbiome-mediated health benefits of a high vegetable – low meat diet, a team of researchers from Italy recently measured the microbiome and specific metabolites produced by the microbiome in 153 individuals.  They then compared these results with the diet that the individual had consumed prior to the measurements, and confirmed that these ‘healthy’ diets were creating ‘healthy’ microbiomes.  They published their results in the journal Gut.

The scientists asked 51 vegans, 51 vegetarians, and 51 ominivores individuals to self-declare their eating habits over the past seven days, and then sampled their stool and urine for bacteria and metabolites.  They learned that amongst the different types of diet the individuals’ overall microbiome diversities were relatively similar.  However, they did show that Bacteroidetes were more prevalent in vegetarians and vegans than in ominvores, and that a higher Firmicutes to Bacteroidetes ratio existed in the guts of ominvores than in vegans and vegetarians.  In addition, the abundance of Prevotella, which is normally associated with health, was positively correlated with overall vegetable intake, and on the contrary Ruminococcus was negatively associated with a high vegetable diet.

The scientists also measured specific metabolites in the individuals.  They discovered that short chained fatty acids (SCFAs), which are normally implicated with health, were associated with the consumption of fruits, vegetables, and legumes.  In addition, there were positive associations between SCFAs and specific populations of bacteria, such as Prevotella.  On the other hand, the metabolite trimethylamine oxide (TMAO), which is a microbiome metabolite whose concentration is directly related to atherosclerosis and other diseases, was significantly lower in vegetarian and vegan diets compared to omnivore diets. It was also directly associated with the abundance of the aforementioned Ruminococcus. 

These relationships between SCFAs and veggies are unsurprising, because SCFAs are the byproducts of bacteria breaking down the complex glycans found in fiber.  In addition, the TMAO is produced by gut bacteria from carnitine and choline, two molecules that exist in red meat and eggs, among other things.  Regardless though, this study should remind us that our diet can shape our microbiome and have lasting health effects.  This study only reinforces that a diet high in veggies that feeds the microbiome is probably a healthy choice.

Interactions of microbiome, diet, and genetics modulate predispostion to diabetes and metabolic syndrome

The human population is undergoing epidemics of metabolic syndromes, type 2 diabetes, and cardiovascular disease and the reasons for these increases in prevalence are not entirely known.  Scientists understand that this rise may be a combination of genetic risk factors as well as environmental risk factors. Scientists from Harvard, Washington University in St. Louis, and the Helmholtz Center in Germany published a paper in Cell Metabolism investigating three strains of mice and analyzing interactions between host genetics, diet, and the gut microbiota.

They used two strains of mice from the Jackson Laboratory (B6J and 129J) and one strain from Taconic Farms (129T). They Taconic strain is very similar to the 129J strain from Jax however it is given a probiotic, resulting in a difference in its gut microbiome. They also inbred the three strains for several generations to create environmentally normalized mouse groups.

They found that the Taconic 129T mice were similar to the 129J mice in their development of diet induced obesity after a high-fat diet but they only developed mild glucose intolerance in comparison to the Jax mouse strain. After inbreeding these mice for three generations in the same environment, these differences were lost. After analysis including 16s sequencing, the original differences in phenotypes and the changes following inbreeding normalization were a result of microbiome differences and microbiome differences were largely dependent on diet, host genetics, and environmental history.  They also found strong strain-dependent and strain-independent relationships between specific phenotypes and bacterial communities that indicated strong interactions between the microbiome, diet, ancestry and genetics.

This study shows that metabolic syndrome and related conditions is the result of complex interactions between genetic and environmental factors, including the gut microbial community. These interactions between diet, genetics, and the microbiome present a significant challenge in the analysis of human disease.