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.

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.

New research helps determine what is healthy and unhealthy in the vaginal microbiome

Editor’s note: This blog about the vaginal microbiome is a good primer for this coming Monday’s Microbiome Podcast with Jacques Ravel, where we will discuss the vaginal microbiome and women’s health at length.  There will also be a special announcement during this podcast, so anyone interested should be sure to download it Monday, June 1.

The typical ‘healthy’ vaginal microbiome is dominated by a Lactobacillus.  However many women, especially those of African descent, are not dominated by this genus, and instead have a high diversity of bacteria in their vaginal tract.  This low lactobacilli, high diversity phenotype has been associated with many disease states, such as bacterial vaginosis (BV), preterm birth, and higher rates of sexually transmitted disease (STD) transmission.  (We have written about some of these diseases before, and encourage any interested reader to click the ‘vaginal microbiome’ below this story to learn more.)  Vaginal microbiome research is still in its early days though, and it is not clear why vaginal microbiome not dominated by Lactobacillus should lead to these diseases, and if this phenotype, if asymptomatic, should even be considered unhealthy.  New research though, out of Harvard University, shows that this phenotype does lead to inflammation, and that these inflammatory response can affect reproductive health and STD transmission.  They published their study in the journal Immunity last week.

The scientists studied the vaginal microbiomes of a cohort of 146 HIV negative, asymptomatic, black, South African women.  They discovered that 63% of them were not dominated by Lactobacillus, an extremely high percentage, especially compared to their counterparts in developed countries (38% of black women and 10% of white women).  Nearly half of those women were dominated by Gardneralla vaginalis, which is most commonly associated with BV, and a large percentage of the other half were diagnosed with BV after investigation.  This is especially interesting because, as stated before, all of the women in the cohort claimed to be asymptomatic, but as we are learning, many women are unaware that there is anything wrong.  Overall, the women were able to be grouped into 4 specific phenotypes, those dominated by Lactobacillus iners, those dominated by other Lactobacillus crispatus, those dominated by Gardnerella vaginalis, and those with a high diversity including Gardnerella vaginalis, Fusobacterium gonidiaformans, Prevotella bivia, and Atopobium vaginae (note the lack of Lacotbacillus in this high diversity group). 

The scientists discovered that there were no associations between each vaginal microbiome group and the rate of STDs, contraceptive use, or sexual behavior.  This is important in showing that, at least on first pass, these bacterial communities were not the result of these exogenous factors (nor did they cause them, for that matter).  They also discovered that there was only a loose association between inflammatory cells in the vaginas of these women, and whether or not they had an STD.  The loose association was only observed in women with Chlamydia, and the women with the highest levels of inflammation had no apparent STDs.

The fact that STDs were not strongly associated with inflammation led the researchers to hypothesize that the vaginal microbiome community, rather than STDs, were responsible for vaginal inflammation.  Indeed, when they compared the amount of inflammatory cells in each vagina with the different microbiome groups described earlier, they found a strong association between inflammation and the highly diverse microbiome group.   Moreover, when they tracked individual women over time, those women whose vaginal microbiomes shifted to the high diversity group also increased inflammatory responses.  The researchers then took this work a step further, and identified specific bacteria that were associated with the inflammatory response:  Prevotella amnii, Mobiluncus mulieris, Sneathia amnii, and Sneathia sanguinegens.

Finally, the researchers measured genes for specific receptors in the vagina that are known to trigger an immune response.  They discovered that those women with the high diversity vaginal microbiomes upregulated genes for these receptors, which are known to be activated by bacteria.  Making matters worse, specific immune cells that are triggered by these receptors, which are thought to be critically important to HIV transmission, were found in higher abundances in women in the high diversity vaginal microbiome group.

This paper did a really great job showing that a vaginal microbiome that lacks Lactobacillus is indeed an unhealthy state, because it creates a highly inflammatory vaginal microbiome which likely causes or contributes to many other ailments, beyond just the higher rates of HIV transmission that was demonstrated.  Unfortunately, at the moment, there are no easy ways for women to check which vaginal microbiome they have, but that should be changing soon, and we recommend that all of our readers tune into the Microbiome Podcast this coming Monday to hear a big announcement in this area. 

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!

Traditional societies’ and modern societies’ microbiomes differ

Traditional people of the Andes mountains.

There is a prevailing thought amongst some in the microbiome field that the 'Westernized' diet and lifestyle is responsible for many diseases that are not observed in traditional societies, which are afflicting a growing population.  Unfortunately, it is somewhat difficult to study how the 'Western' microbiome has changed because most of the world’s population could be considered to have this microbiome.  Fortunately, there are still some societies that forage for their own food and have had a consistent diet for much of their history.  The belief is that these 'traditional' societies have microbiomes that better resemble those of ancient peoples, and by unlocking the mysteries of these people’s microbiomes we can better understand these 'Western' diseases.

With this in mind, scientists from the University of Oklahoma studied the microbiomes of three groups of people with three different dietary habits: the Matsés hunter gatherers from Peru, the Tunapuco agriculturists from the Andes, and the residents of Norman, Oklahoma.  The Matsés ate primarily fish and meat along with many vegetables, the Tunapuco ate primarily potatoes and other roots along with small game, and the Oklahomans followed a typical Western diet.    The researchers found that both traditional societies had much higher microbiome diversities than the Oklahomans.  While each society had different comprised of different species of bacteria, interestingly, both traditional societies had higher levels of the genus Prevotella and Treponema than Oklahomans, who themselves were richer in Bacteroides.

Interestingly, Treponema are rarely seen in the microbiomes of Westerners, which may lead to the belief that these were important symbionts to our ancestors.  Nevertheless, there were many similarities between the all the microbiomes as well.  According to this study there is little doubt that our microbiomes have changed immensely in modern history.  How these changes may be related to so-called ‘diseases of wealth’, though, is still an open question. 

Asthma, COPD, and the Microbiome

Asthma and chronic obstructive pulmonary disease (COPD) are both illnesses that are caused by chronic inflammation of the respiratory tract, and recent research suggests that the microbiota of the lower respiratory tract may influence the development of these two diseases.  The upper respiratory tract, though, remained unstudied, until a new article was recently published in PLoS ONE.  This article characterized the microbiome of the oropharynx (in the upper respiratory tract) to discover the association between these problems and the microbiome.

Samples were swabbed from the oropharynx of patients who were recently diagnosed with asthma and COPD, as well as from a healthy control group.  Researchers performed 16S rRNA gene sequencing of the bacteria collected from the patients, in order to determine which bacteria were present. They found that there are few differences in microbiome diversity between asthma and COPD patients, however there was a prevalent presence of the bacteria Lactobacillus (phylum Firmicutes) and Pseudomonas (phylum Proteobacteria) in both, which were identified in only very small amounts in healthy patients. On the contrary, the upper respiratory tract of healthy individuals was found to be dominated by Streptococcus, Veillonella, Prevotella, and Neisseria, from the phylum Bacteroidetes, compared to individuals with asthma and COPD.

This study showed distinct differences in the microbiomes of diseased and healthy individuals.  The researchers also note that the low abundance of Neisseria they observed in this study has also been seen in studies of smokers, meaning that this bacteria may be important to respiratory health.  Further work is still needed, though, to determine if the bacteria identified in this study are contributing to the diseased individuals.  Even if they are not, they could still potentially be used in diagnosis.