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.

Stool consistency should be considered during microbiome research

Stool sampling remains the most common method of measuring the microbiome of the GI tract.  Researchers are well aware of its limitations, but its ease and convenience for both scientists and donors makes it nearly irreplaceable at the moment.  The most common issue regarding stool samples that is often pointed out is that it is not representative of the GI tract, and that it only samples the lower colon and not the more proximal GI tract.  In addition, it does not account for bugs that are attached to the mucous linings of the intestine rather than those that transiently pass with our feces.  Related to this point, last week Jack Gilbert and John Alverdy, professors from the University of Chicago, published a piece in the journal Gut regarding stool microbiome sampling and stool consistency.

Professors Gilbert and Alverdy argue that stool consistency greatly affects the stool microbiome populations.  The stool consistency is normally a function of intestinal transit time, with the shorter the duration between eating and passing stool being associated with watery stool, while a longer duration is associated with a more solid stool.  They point to studies that that show different bacteria have evolved to either grow rapidly when the stool is quickly moving through the lumen, in order to proliferate with the shorter duration access to nutrients, or to grow slowly and more completely utilize the available nutrients when the stool is accessible for longer periods.  Measurements of stool consistency are hardly ever performed during normal sampling, and these same studies tend to make generalizations about different phyla, like Bacteroides and Ruminococcacea, when in fact these different can be explained by stool consistency. 

In a time where microbiome diagnostics are starting to be considered as helpful indications for varous diseases, this type of quality control needs to be established.  Stool sampling is not perfect, but it is necessary, and for that reason steps should be taken now to improve and control its usefulness, especially in a clinical setting. 

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.

The giant panda’s microbiome isn’t doing it any favors

Panda bears are quite unique in the animal kingdom because they are nearly strictly herbivores yet they are descended from omnivores.  In fact, scientists aren’t quite sure why panda’s made the transition to eating bamboo, because it is a relatively inefficient energy source.  Making matters worse for the panda, its gastrointestinal tract is rather short, and resembles other carnivores, whereas most herbivores have very long gastrointestinal tracts that allow for long retention times for the microbiome to do its work.  This microbiome, of course, breaks down plant material into usable sources of energy for the host and it is critical in all herbivores.  Scientists from China recently investigated the panda’s microbiome, and to their surprise discovered that it too, resembled carnivores’ microbiomes, rather than herbivores’ as one might expect.  They published their results last week in MBio.

The scientists measured the fecal microbiomes of 45 captive pandas over the course of one year, including cubs, juveniles, and adults.  They then compared these microbiome samples with previously reported microbiomes of 54 other species, and wild, rather than captive pandas.  Their first discovery was that the panda’s microbiome was not as diverse as many of these other species, and as our regular readers know, low diversity has been implicated in many diseases in humans.  Next, they found that the panda’s microbiome was actually much more similar to other carnivorous species, especially other bears and tigers, than herbivorous species, and was dominated in Escherichia/Shigella, and Streptococcus, rather than bacteria that are known to degrade cellulose from plant matter, such as Ruminococcaceae, and Bacteroides.  Finally, of particular interest in light of the recent research on the importance of diurnal changes in the microbiome, the scientists noted that the panda microbiome undergoes huge shifts in accordance with the seasons, although they do not speculate as to the effects these shifts may be having.

These discoveries are quite surprising, but they help explain why pandas must eat around 25 lbs. of bamboo every day.  Their microbiomes are just not well equipped to digest this food.  In fact, the lack of cellulose degrading bacteria in pandas’ guts has led some scientists to speculate that pandas are merely living off the cellular contents of each plant cell, rather than the energy dense cellulytic plant cell wall.  Whichever the case, their inefficient digestion certainly is not helping them thrive as a species.

The fate of the gut microbiome following stem cell transplant

Bone marrow prior to transplant

Hematopoietic stem cell transplant (HSCT) is a difficult procedure that is usually administered to patients suffering from bone marrow or blood cancers such as multiple myeloma or leukemia.  Unfortunately, many patients who receive this treatment develop acute graft-versus-host disease (aGvHD), a multi-organ system immunologic disorder that is particularly detrimental to the gastrointestinal tract. 

In light of increasing evidence highlighting the importance of the symbiosis between the microbiome and human hosts, researchers set out to explore the fate of gut microbiota in pediatric patients who had undergone HSCT.  Specifically, phylogenetic profiles and functional properties were examined in a longitudinal analysis to develop a better understanding of the specific role the gut microbiome plays in patients who develop aGvHD following a HSTC procedure. 

Ten pediatric patients who had undergone HSTC, 5 of which had developed aGvHD, were selected for analysis.  The trajectory of the microbiota ecosystem was monitored using gene pyrosequencing of fecal samples, which were collected before, during, and after the HSTC procedure.  Collection and observation continued for 3 to 4 months.  Additionally, researchers examined short-chain fatty acid (SCFA) production samples in the patients as a measurement of microbiota metabolic activity.  Short-chain fatty acids are critical metabolites that microbiota require in order to maintain healthy physiology.  Healthy microbiota are critical toward educating the immune system and maintaining homeostasis.

Marked changes were observed in the gut microbiome populations of all 10 patients immediately following the HSTC procedure.  There was a massive invasion of new bacterial species following the procedure, with less than 10% of the original microbiota being conserved.  In particular, there was a significant loss in health-promoting bacterial species such as Faecalibacterium and Ruminococcus.  Two months after the procedures, the species richness and metabolic activities in the patients’ guts was restored. 

The patients who developed aGvHD experienced a major drop in health-promoting bacteria and higher abundances of invading bacteria as compared to non-aGvHD patients.  Interestingly, the gut microbiomes of the non- aGvHD patients contained significantly higher populations of Bacteroides phylum.  On top of this, Bacteriodes were the most abundant species observed among the original 10% of microbiota conserved through the HSTC operation. 

This study points to the importance of the gut microbiome in helping maintain healthy integrity of the gut immune system following a HSTC procedure.  The finding that having low Bacteriodes populations may be an unrecognized consequence that could lead to the development of aGvHD is particularly interesting.  Should these bacteria be as important as this data suggests, preventative microbiome-driven therapies could be explored with the aim of preventing post-HSTC procedural aGvHD onset.  A therapy that could maintain healthy Bacteriodes populations prior to HSTC operations could perhaps present a viable solution.  

Eating fiber alters our microbiome

Pig getting its daily dose of fiber!

Editor’s Note: Our latest podcast discussing diet and the microbiome, with Erica and Justin Sonnenburg, will be released tomorrow to coincide with the release of their new book.  In the spirit of discussing how diet affects the microbiome, today’s blog will be on that topic.  Enjoy.

Doctors always say to eat your fiber, and that it will make you healthy.  Why though?  Fiber, which broadly describes the complex polysaccharides derived from plant matter, are indigestible by a human’s normal metabolic processes.  Instead, the fiber traverses the digestive tract and is broken down by bacteria along the way.  It can be broken down into important metabolites like short chained fatty acids (SCFAs), which are thought to positively influence our health, among other metabolites.  Therefore, as Erica Sonnenburg says on our podcast to be released tomorrow, it is important to feed your microbiome with every meal.  By this, she means to include foods that are not meant to be digested by our native enzymes, but rather ones that are destined to provide nutrition for the bacteria that live inside us.

On that note, a paper out of Norway, Denmark, and the Netherlands was published last week in the Journal Microbiome that discussed how different fibers modulated the microbiomes of pigs that ate them.  Six pigs were split into two groups.  One of the groups ate a control diet, consisting of limited fiber, and the second group ate a diet that included indigestible tapioca starch.  The groups were fed these diets for 12 weeks and had their feces collected and sampled periodically during this time.

The researchers discovered that the pigs’ microbiomes did in fact change over time dependent on their diets.  The pigs that ate the tapioca starch showed a large change in their gut flora, but surprisingly it decreased its diversity relative controls.  There was also a notable increase in the abundance of Ruminococcus and Prevotella in these fiber-fed pigs compared to controls, while bacteria from other genera, like Blautia and Clostridia had decreased abundances.  The scientists then measured the differences in expressed metabolic pathways between the microbiomes of the groups, and noted that there was some evidence that the starch-fed pigs shifted their microbiomes to become more efficient at degrading starch.

We still do not know in great details how specific foods alter the microbiome, and this study is one of the first in many that are attempting to answer that question.  As you can hear in the podcast tomorrow, Justin and Erica Sonnenburg have devoted their lab at Stanford to answer this question.  They hope to someday controllably modulate the microbiome using dietary fiber in order to improve health and treat disease.    If you are interested in this topic and want to learn more about how diet can affect the microbiome, subscribe to the podcast on Itunes or wherever you get your podcasts and check back in tomorrow.