Prevotella in the gut appears to improve glucose tolerance

Last week we wrote about a study that showed that the glycemic response from foods was a function of the microbiome, and alluded to the fact that the microbiome likely affects many aspects of metabolism.  Another paper was published this week, in the journal Cell Metabolism, that describes which bacteria are responsible for some of these effects.  The authors describe how Prevotella improve glucose metabolism in healthy human subjects.

The scientists gave 39 subjects white bread and barley bread for three consecutive days and measured their glucose and insulin responses to the diets.  For the most part, the barley bread was associated with an improved response over white bread, but some of the individuals’ responded with a much more stark improvement than others.  The scientists then measured the gut microbiomes of each individual and noted that the microbiome changed in the most responsive individuals, and this change was characterized by an increase in Prevotella (specifically Prevotella copri) and methanogenic archaea.  The opposite effect was seen in the individuals that responded least to the barley bread intervention.  The scientists then confirmed these results in mice.  Mice that were given fecal microbiota transplants from human responders, or P. copri probiotics had improved glycemic responses to high fiber diets than control mice.

Prevotella comes up in a lot of microbiome literature as a bug seen in ‘traditional’ societies that eat a lot of fiber.  This paper demonstrates that many of the genes from Prevotella are crucial to digest the complex fibers and that this may stimulate an improved glycemic response.  Collectively, many papers now support the idea that Prevotella is a critical bacterium to a ‘healthy’ microbiome.

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.

Dietary fiber promotes microbiome richness and stability

The richness and stability of gut bacteria play an important role in microbiome homeostasis. We’ve chronicled many ways to perturb or alter the microbiome but diet is an area that has long been studied as a way to modify the microbiome.  Specifically, dietary fiber has been shown to alter the microbiome and a recent study out of France looked at the microbiome of individuals who were given high fiber diets compared to normal diets.

19 people participated in a nutritional study and ate a normal diet for five days supplemented with 10 or 40 grams of dietary fiber per day. After the short-term intervention, there was a 15 day washout period and fecal samples were analyzed using qPCR and 16s RNA sequencing at various stages of the experiment. 

The scientists found that the increase in dietary fiber intake did have an effect on the microbiota populations however it was dependent on the richness which varied from individual to individual. They also found that for the individuals on the 10 g fiber per day diet, microboime changes were not associated with richness and therefore it may be possible that other factors are playing a role in microbiome dynamics. Higher microbiome stability was seen with increased richness as well as a higher Prevotella:Bacteroides ratio.

This study showed that microbiome richness is a key factor that needs to be analyzed when comparing individuals’ responses to dietary interventions. Microbiome richness should be studied as we look at other factors such as antibiotic intake, aging, among others. This study also proposes that subjects with low microbiome richness should undergo long-term interventions such as diets with high vegetable diversity to try and improve overall microbiome richness.

Elderly people's microbiomes may contribute to their frailty

The ELDERMET program is a microbiome project in Ireland out of the University College Cork that is attempting to define the elderly microbiome and discover any associations between the microbiome and diseases linked with frailty and old age.  The team has published multiple papers from this project, some of which we have already blogged about, and last week they published another one in the ISME Journal.  In this latest paper the researchers described in fine detail just how the microbiota changes with diet within a geriatric population, and how this is actually independent of where the elderly people live.

The researchers studied the fecal microbiota of 384 elderly subjects over the course of one year.  They noticed immediately that the microbiomes clustered dependent upon whether the person was living in a nursing home or living amongst the general community.    The researchers characterized the microbiota in 4 groups based on a certain characteristics: M1, M2, M3, and M9.  M1 is a group of genera that is present in almost all subjects sampled, so it represents a core microbiome and is composed of genera such as Bacteroides, Alistipes, Parabacteroides, Faecalibacterium and Ruminococcus.   M2 is a cluster that is composed of bacteria that are associated with high-fiber diets and health, and is comprised of Coprococcus, Prevotella and Catenibacterium.  M3 is associated with folks who lived long-term residential care facilities, and consists of Anaerotruncus, Desulfovibrio and Coprobacillus genera.  Finally, M9 consists of other bacteria that were often found, like strains of Bacteroides, Parabacteroides and Alistipes.

The scientists then compared these microbiome groups with health indicators.  They discovered that highly diverse microbiomes were associated with health, especially among those living in the general community.  However, even though living in long term care facilities often increased diversity, having an M3 microbiome was overall associated with negative health.  In addition, the researchers noted that while individual foods were not strongly correlated with any health indicators, ‘healthy diets’ characterized by high fiber intake, were associated with better health than ‘unhealthy diets’.  Finally, when looking at how the microbiome changed over time, it was apparent that entering a nursing home increased the likelihood of shifting the subjects’ microbiomes to the M3 state, which is associated with bad health.  The researchers think this is likely due to the lack of fiber in nursing home food, and the high use of antibiotics.

The authors state that older people have many differences in their eating habits as compared to a normal adult population, like number of teeth, amount of chewing, and intestinal transit time, and all of these things may be contributing to the altered microbiome.    Regardless of these exogenous factors, this study reinforces the notion that lack of diet diversity and high use of drugs in nursing homes may be creating dysbioses that contribute to frailty disease.  If you have loved ones in an extended stay facility we recommend considering supplementing their diet with some fresh vegetables, so as to keep their microbiome from turning against them.

Americans swap foods with Africans and their microbiomes follow – fiber, fat and cancer risk

Phuto pap and porridge, a traditional South African, high fiber, meal.

Despite having similar genetic backgrounds, African Americans are thirteen times more likely to develop colon cancer than rural South Africans.  Indeed, environmental factors, rather than genetics, are thought to be the major factor in developing colon cancer, because recent immigrants’ children’s risk is more similar to where they are living than to their parents’ homeland.  This environmental risk could be primarily caused by a number of factors, such as antibiotic use or drug use, but many scientists believe that diet, and its influence on the microbiome, is primarily responsible.  As it turns out, rural Africans eat much more fiber (almost 5x more) and much less fat (almost 3x less) than African Americans, and these differences have drastic effects on the microbiomes of their hosts.  Not only are the most abundant bacterial species different, but the major metabolites vary greatly as well.  Scientists from the University of Pittsburgh came up with the clever idea of swapping the foods of rural South Africans and African Americans, to investigate how this dietary intervention would affect each group’s microbiomes and risk for colon cancer.  They published the results of their study in Nature Communications last week.

The researchers studied 20 middle aged African American men and 20 middle aged rural South African men.  They each had their microbiomes and colons studied for two weeks while eating their normal diets, and then again for two weeks after swapping diets.  Initially, the Americans had microbiomes dominated by Bacteroides and the Africans by Prevotella.  After the diet though, they noticed a rapid shift in these populations, and it corresponded to an increase in colonic inflammation for the Africans and decrease in the Americans.  In addition, an increase in butyrate, the short chained fatty acid (SCFA) that is thought to be beneficial to health, followed the fiber diet as well, and a decrease was associated with eating the high fat diet; this makes sense, as butyrate is produced as a metabolite of fiber fermentation by the microbiome.  Interestingly, prior to the diet change a top-level analysis of all the metabolic end products of the microbiome showed that Africans produced more of every single one studied except for choline, which is related to heart disease.  Many of the metabolites studied, including choline, followed their diet switch, and were produced according to the food eaten, rather than the person eating it.  Perhaps most importantly, secondary bile acids, which are produced by the microbiome and may be carcinogenic and an important cause of colon cancer, followed the diet as well.  Africans, who produced much fewer secondary bile acids than Americans while consuming their regular diet, had a 400% increase in production after the diet switch, and vice versa for the Americans, who had a 70% decrease.

This study really illustrates the importance of diet on the output of the microbiome.  These metabolites can directly influence our health, and may be more important to our well-being than the bacteria that produce them.  According to this study, it appears that eating more veggies and less fat, something that parents have been saying for a long time, fits in with our understanding of the microbiome.  As Erica Sonnenburg said in our podcast 3 weeks ago, “Feed your microbiome at every meal!”

Sex, body mass index, and dietary fiber correlated with microbiome composition

On last week’s podcast, we talked with Erica and Justin Sonnenburg about how the food we eat, and specifically dietary fiber, is important for “feeding” our microbiomes. All of the variables that influence microbiome composition are not fully understood, however research is continually being conducted to better understand what factors affect the microbiome.  To this end, a team of scientists from New York University School of Medicine set out to find how sex, body mass index (BMI), and dietary fiber intake impact the microbiome.

The scientists analyzed fecal samples from 82 individuals, 51 men and 31 women. They found that the women had different microbiome composition than the men, specifically a lower abundance of Bacteroidetes. They also found that BMI impacted microbiome diversity, specifically in women. Overweight and obese women had less diverse gut bacteria than normal weight women and women with a higher BMI also had less Bacteroidetes in their guts compared to the normal weight women.

The scientists also found that various sources of dietary fiber differentially impacted the microbiome of subjects.  Fiber intake from fruits and vegetables resulted in higher levels of Clostridia and fiber intake from beans was associated with greater abundance of Actinobacteria. It is possible that dietary fiber is influencing the microbiome by reducing gut transit time and lowering the pH. It is also possible that it is influencing systemic levels of estrogen, which could alter microbiome composition.

As the microbiome continues to be implicated in diseases, the ability to identify variables that affect the microbiome are important and can potentially be used for altering microbiota composition to prevent or possibly treat disease.