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.

Different types of dietary fat affect obesity through changes to the microbiome

A triglyceride molecule, the main constituent of lard.

Dietary fat comes in many in many different forms, such as saturated fats that come from foods like lard, and polyunsaturated fats that come from foods like fish oil.  It is generally believed that saturated fats lead to inflammation and obesity, but that polyunsaturated fats are healthier, and can counteract inflammation and promote healthy metabolism.  The role of the microbiome in mediating these effects is still unknown, but is beginning to be elucidated.  A team of researchers from Sweden, Belgium and Denmark showed that the lipids themselves alter the microbiome, which induces the characteristic inflammation associated with ingesting saturated fats.  Their results were published in the journal Cell Metabolism.

The scientists fed groups of mice identical diets that only differed in the type of fat that was consumed: lard composed of saturated fats, and fish oil composed of polyunsaturated fat.  As expected, the group that ate the saturated fat gained weight and had higher fasting glucose than those eating unsaturated fat.  When they measured the gut microbiomes of these mice, they discovered that the overall diversity of bacteria were much lower in the mice eating the saturated fat diet.  Next, the scientists measured the contents of the blood of the mice and discovered that there were higher levels of bacterial metabolites and bacterial components in the blood of mice eating the saturated fat diet.  Using complicated techniques that are beyond the scope of this blog, the researchers were able to trace the inflammation to an increase in specific receptors in the gut that are activated by bacteria from the saturated fat diet, including some specific toll like receptors (TLRs).  The scientists conducted a final experiment to show the importance of the microbiota, rather than the diet, in inducing these effects.  They transplanted the feces of both groups of mice into new, healthy mice.  The mice given the feces of the saturated fat group gained weight, whereas the ones given the microbiomes of the polyunsaturated fat group tended to lose weight.

The scientists believe that diets high in saturated fats upregulate specific immune system receptors that are activated by factors derived from the gut microbiome.  Moreover, these factors find their way into the blood much more easily after consuming saturated fat, as opposed to unsaturated fat, so they can easily activate these receptors.  After activation the factors lead to inflammation and obesity.  Overall, this research explains one of the reasons why polyunsaturated fats are healthier than saturated ones.  We know It’s not often anyone is faced with the choice between fish and lard, but after reading this study we recommend our readers go with the fish.

Diet and microbiome may influence cognitive flexibility

There has been a lot of press recently about the microbiome’s impact on mood and behavior, the so-called ‘gut-brain axis’, and it appears now more than ever that the gut microbiome has a substantial impact on the brain.  A new paper out of Oregon State University, published in the journal Neuroscience, furthers this research by showing that different diets affect mice’s cognition and memory via changes in the microbiome.

Scientists fed groups of mice a normal chow and then switched their food to either high fat, or high diets, along with continuing some on the normal diet.   The researchers then put them through a battery of cognitive tests, all the while measuring their microbiomes using stool samples.  The mice on the high sucrose and high fat diets each had similar alterations of their microbiomes, such as an increase in Clostridiales and a decrease in Bacteroidales.  Mice on the high sucrose diet had decreased scores in their cognition tests, including memory and spatial reasoning tests, which corresponded to changes in the microbiome. For example, an increase in Lactobacilli was associated with a decrease in spatial reasoning.  Mice on the high fat diet, on the other hand, showed impaired working memory, which was associated with an increase in bacteroidales.

Some of these bacteria, such as Lactobacillus are used in probiotics to increase cognitive function, and there is some scientific basis for these effects, even though this study observes a somewhat different results.  The changes in this study though, were a diet intervention, which is more complex than a simple probiotic intervention.  That being said, we must remember that microbiome science is still developing, so each of these studies should be considered in the broader context of the field before any real conclusions can be made.

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!”

An obese-type gut microbiome can lead to neurobehavioral pathology

Squirrel on high fat diet. (close enough to a mouse!)

Obesity is a complex condition with an extensive range of health complications.  Among many other issues, neurobehavioral deficits in learning, memory, and executive function are observed in this disorder.  However, the cause behind the manifestations of these deficits remains unclear, and new data suggest that obesity by itself may not be the origin of these neurobehavioral complications.  In other words, neurobehavioral deficits may not be caused by obesity, but rather by the microbiome that develops from the high-fat diet that leads to obesity.  A recent study supports this supposition, demonstrating that an “obese-specific” gut microbiome may be the driving force behind these neurobehavioral complications.

Researchers hypothesized that microbiome communities that develop from a sustained high-fat diet could by themselves induce neurobehavioral maladies, independent of diet, adipose fat accumulation, and/or metabolic dysfunction.  To test this theory, the researchers developed a paradigm in which microbiota taken from the gut of obese mice were recolonized in the gut of non-obese mice.  Specifically, mice were split into two groups, and members from each cohort were administered either a standard chow diet or a high-fat chow diet (to induce obesity).  After 10 weeks on their respective diets, the animals were sacrificed and their microbiota bacteria were harvested from cecal and colonic contents.  A third group of mice were administered an intense antibiotic regimen to wipe out their intestinal microbiota populations.  Microbiotas from either the normal chow diet mice or high-fat chow diet mice were subsequently implanted in the microbial-free guts of third group.  These mice were then subject to behavioral examinations and eventually sacrificed for biochemical analysis to characterize disease markers and pathology indications in the brain and gut. 

Behavioral assessments revealed significant increases in anxiety and anxiety-like behaviors concomitant to decreases in memory in mice administered the high-fat diet-associated microbiota.  To validate that differences in gut microbiomes were the root cause, analysis of cecal and fecal samples from mice indicated that the gut microbiomes in both high fat diet and normal diet groups had distinct phylogenetic profiles, demonstrating that microbiota populations from each group were indeed distinct. 

Researchers next analyzed biological protein markers associated endotoxins and inflammation in the gut, as well as markers for injury and inflammation in the brain.  Several inflammatory-associated markers were significantly upregulated in the high-fat diet group, indicating disruption to intestinal permeability and inflammation.  Furthermore, expression of inflammatory protein markers in the brain was significantly increased in the mice with the high-fat diet microbiota, and two proteins known to maintain integrity of brain vasculature were significantly reduced.  Additionally, a protein known to be present during normal synaptic function was significantly reduced. 

Collectively, these data link disturbances in gut and brain physiology resulting in behavioral dysfunction with obese-specific microbiota rather than the state of obesity.  Importantly, however, this study reveals a potential therapeutic target to remedy behavioral disorders that many have previously perceived as a consequence of simply being obese.  

Diet plays a more important role than genetics in shaping the microbiome in mice

Today is December 31st which means it’s time to make our New Years Resolutions! Luckily for all of us, a new paper by Peter Turnbaugh’s laboratory gives us good reason to make improving our diet an important goal for the New Year. Dr. Turnbaugh and colleagues at Harvard University and University of California, San Francisco have shown that diet plays the dominant role over genetics in shaping the gut microbiome in mammals. 

Published in Cell Host and Microbe, the team of scientists used several strains of mice to investigate whether diet or the genetics of the mice played a more important role in what bacteria colonized the gut.  They exposed the mice to a low-fat, plant-based (LFPP) diet and a high-fat, high-sugar (HFHS) diet. When mice were given the HFHS, an increase in Firmicutes bacteria and a decrease in Bacteroidetes bacteria was seen, regardless as to what their genetic background was.  When the LFPP diet was given, the shift went in the other direction.  Further investigation needs to be done to better understand whether diet plays a direct role in shaping the bacterial communities in the gut or if it is due to an indirect role that the food has on the entire body of the host.

Another important takeaway from the study was that most changes to the microbiome are reversible. This means that once you shift to a new diet, the microbiome changes with the new diet and the new microbial communities are established within 3 days of exposure to the new diet.  However, the microbiome does remember past dietary patterns.  They leave an imprint on the microbial communities in the gut and some bacterial species are dependent on prior consumption.  

Dr. Turnbaugh suggests that in the future it may be possible to design diets that shape the microbiome in ways that are therapeutically beneficial.  He also states that due to this finding that diet plays a more important role than genetics on establishing gut bacteria, diets won’t need to be tailored to every individual person and specific diets may be useful for most people. 

So while you make your New Years Resolution to eat better and have a healthier diet, know that you are not only impacting your nutritional intake but you are also shaping your microbiome.

We wish all of our readers a happy and healthy New Year. This has been a particularly exciting first year for us and we look forward to another great year ahead.