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.

Chronic kidney disease and its effect on microbiome metabolism

Patient receiving dialysis

A substantial body of evidence points to the importance of renal filtration and the elimination of microbiome-derived metabolites.  Chronic kidney disease can lead to renal failure, which can have detrimental consequences for the elimination of microbiome metabolites.  Specifically, p­­-cresyl sulfate and indoxyl sulfate are cometabolites between human metabolism and microbiome fermentation.  Kidney failure or loss of renal function can lead to retention of these metabolites, and they can induce toxic harm by remaining in systemic circulation.  While there has been significant interest in this field, much is unknown regarding CKD’s influence on microbiota function and metabolism.  Researchers in Belgium sought to address this and identify what role CKD would have on the microbiota metabolism in the colon in patients on hemodialysis. 

The experimenters examined 20 patients on hemodialysis.  These fecal metabolites profiles of these patients were compared to 20 healthy controls using gas chromatography-mass spectrometry.  Initial observations revealed that healthy controls had a significantly higher number of volatile organic compounds (VOCs) – an indicator of microbiota metabolism - as compared to the patients on hemodialysis.  After adjusting the data for statistical confounders and discriminating VOCs between groups, the researchers determined that 81 individual VOCs were significantly different between hemodialysis patients and healthy controls.  Consistent with previous findings and known clinical conditions, both p-cresol and indole were significantly upregulated in hemodialysis patients.  A major confounder in this study is diet, as hemodialysis patients are on a very restricted diet, and as we know, dietary intake impacts microbiome composition and metabolism.  The researchers conducted the same analysis with the hemodialysis patients with household contacts who were on the same diets.  Interestingly, no significant difference in VOCs was observed between groups. 

The researchers demonstrated that CKD patients on hemodialysis experience an altered microbiota metabolism; however, dietary influence may be driving this effect rather than loss of renal function.  It was good to see the researchers included the household controls, as this evidence suggests renal function by itself may not have direct impacts on gut microbiota function.  Regardless, much of the CKD-microbiome research to this date has focused on the microbiome’s role in CKD or CKD-mediated downstream maladies.  It was interesting to see a study that took the opposite approach, as we know microbiome health is important for homeostatic mechanisms that maintain a healthy body.  

New research shows that Bifidobacteria transfer from mother to child

Both natural birth (as opposed to birth by C-section) and breastfeeding are topics that stir up a lot of conversation among mothers and the scientific community. For example, there is the question of whether breastfeeding rather than formula feeding has some specific benefit to an infant’s health. Well, what about the infant’s gut microbial health? A new article published by Applied and Environmental Microbiology takes a look at whether natural birth and breastfeeding coincides with an exchange of bacteria from mother to child.

Four mother and infant pairs were included in the study that was meant to discover whether the mother transfers any bacterial strains to the infant during vaginal birth and breastfeeding. In particular, the scientists were looking at the genus Bifidobacterium because this group has been known to be early colonizers of the infant gut. In addition, this genus has specific ways of digesting a human mother’s milk. Mother-infant pairs 2 and 4 exclusively breastfed, while pairs 1 and 3 supplemented with formula. Milk samples were collected from the mothers and fecal samples were collected from the mothers and children.

After sequencing the bacteria, B. adolescentis, B. angulatum, B. breve, B. dentitum, B. pseudolongum and B. thermacidophilum were found to be common between all of the mother and the infant fecal samples. The scientists then looked to see which bacteria were in both the mother’s milk and the infant’s fecal sample. The results suggest that the milk may be responsible for transferring B. adolescentis, B. angulatum, B. breve, B. longum and B. pseudolongum to the infant. Interestingly, there were also some bifidobacteria strains that were unique to the infant, suggesting that either they went undetected in the mother or that the infant was exposed to this bacteria from somewhere else.

After six months, samples were collected again in order to see how/if the sample compositions change. The scientists found that, especially in the infants, the abundance of bifidobacteria decreases. This is most likely due to changes in diet – less breastfeeding and more formula feeding – and perhaps environmental exposure. All in all, the results of this experiment shows that the infant microbiome might indeed be influenced by a vertical transfer of bacteria from mother to child. With more evidence of this as a possibility, science may begin looking into more complete analyses with larger study sizes.  

Different diets can affect C. diff infection and survival

We’ve covered the topic of Clostridium difficile infection extensively on this blog. We know that infection of this bacteria (CDI) can be nasty, sometimes even leading to death. A lot of research has been done to find ways to treat the effects of C. diff infection or to find out how the infection is acquired, but few papers have investigated dietary interventions to help treat CDI.  A new study published by PLoS One examined this, studying how different diets, and specifically how protein content of those diets, affected the severity of CDI.

          7-8 week old male mice were weighed and separated into five groups, each given a different diet. One group was fed a protein-deficient 2% protein diet, and a counterpart group was fed a 20% protein diet. Another group was given a Research Diets regional basic malnutrition diet, while its counterpart was fed a matched control. A fifth group was fed a traditional (corn, wheat, soybean) diet, and acted as the positive control. Mice were fed the diets 12-14 days before being given antibiotics and then infected by C. difficile.  After infection, the mice were housed individually to prevent being affected by other mice. Stool and colon samples were collected from the mice up to two weeks after infection, and the bacterial content was sequenced.

Mice on the 20% protein diet showed delayed onset disease with a 25% survival rate over 2 weeks. Mice on the 2% diet also showed delayed disease onset and had a survival rate of 57.1% over two weeks. A significant statistically difference in survival and weigh loss was seen between the traditional diet and both the 20% and 2% diets, however the survival difference between the 20% and 2% groups was not significant.

In another part of the study done by the researchers, they chose to examine the presence of four gut microbiota groups ( Firmicutes, Bacteroides, Enterobacteriaceae, and total bacteria), after antibiotics or no antibiotics. All aspect of the experiment were the same except for this one factor. In mice not given antibiotics, the total number of bacteria was greater in the colon of mice given traditional diet. In mice given antibiotics, traditional diet-fed mice had lower levels of Bacteroidetes but higher levels of Firmicutes and Enterobacteriaceae. The most significant finding the researchers may have made however, is that traditional diet-fed and antibiotic given mice had the highest levels of C. difficile and therefore C. difficile toxins.

In the end, it can be assumed that diet does influence rates of C. diff infection. The presence of antibiotics also alters the bacterial compositions of the colon, with lower protein diets seeming to protect against or prevent full potential C. difficile infection.

Study shows different microbiomes associated with ingesting artificial sweetners

Last year a very important study showed how eating artificial sweeteners could actually increase risk of obesity and diabetes due to a microbiome-mediated response.  Based on this study, researchers from George Mason University investigated the microbiome differences between folks that eat artificial sweeteners, like aspartame and acesulfame-K, and those that do not.  They published their results in the journal Annals of Epidemiology.

The researchers surveyed 31 adults and gave them a questionnaire regarding their eating habits over the previous four days.  Then, on the 5th day the scientists measured the bacteria and the genes those bacteria expressed in each subjects stool.  The scientists learned that the microbiomes did not vary substantially between the two groups, but there were statistically significant differences in the overall diversities of the groups.  In addition, there were no significant differences in the genomes of the bacteria, again suggesting the microbiome is not considerably affected by the ingestion of these sweeteners.  Unfortunately, the authors did not comment on which differences they perceived as being important.

This article suffered from many flaws in its analysis, so we take the results with a grain of salt.  Nonetheless, epidemiological studies in humans like this one are important in supporting the conclusions of studies that demonstrate effects in mice.  The cost/benefits of eating artificial sweeteners versus regular sucrose are still being evaluated, so in the mean time we encourage our readers to eat lots of veggies.

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!”