The effect of various treatments for juvenile Crohn’s disease on the microbiome

CT scan showing Crohn's disease in the fundus of the stomach

Crohn’s disease is a type of inflammatory bowel disease that is characterized by an autoimmune response in the colon.  It is generally thought that the bacteria in the gut elicit this immune response and cause the disease.  In otherwords, Crohn’s is caused by a shift in the microbiome from a healthy state, to a dysbiotic one, although the ultimate cause of the disease is still unknown.  The standard of care for Crohn’s in adults is combinations of immunosuppressive drugs, although in children this is not normally recommended.  Instead, children take either a prescribed diet, normally something like Soylent that involves only essential nutrients, or antibiotics.  Scientists from UPenn recently monitored the microbiomes of children with Crohn’s that were put on various courses of treatment, as well as the progression of the disease.  They discovered the changes that occurred in the microbiome that yielded a therapeutic response, and many new associations between the microbiome and Crohn’s disease.  They published their results in Cell Host and Microbe.

The scientists measured the microbiomes and inflammatory markers of 90 children before and after entering therapy for Crohn’s: 52 taking anti-TNF (an immunosuppressant), 22 taking the enteral nutrition exclusively (i.e. something like soylent), and 16 taking the enteral nutrition along with any other food they wanted.  The scientists also took samples from 26 healthy children.  They discovered that of the 45 most abundant bacteria in each child, 14 were different between the Crohn’s children and the healthy children.  These included bacteria such as Prevotella and Odoribacter that were largely absent from the Crohn’s group, and Streptococcus, Klebsiella, and Lactobacillus that were in higher abundances in the diseased group.  Overall diversity was also higher in healthy patients compared to those with Crohn’s.  The researchers also discovered that high levels of fungi, such as Saccharomyces cerevisiae, in the stool were high associated with Crohn’s.  When the researchers monitored the response of Crohn’s patients to treatment they saw that in many patients the microbiome shifted rapidly to a healthier state, with less inflammation, within a week of treatment for all three therapies involved.

This study helped further define the dysbiosis that is associated with Crohn’s disease, as well as demonstrate how this dysbiosis is altered using treatment.  It was especially useful that treatment naïve children were used in the study, as many adult studies are unable to remove confounding variables of various previous courses of treatments.  IBD is a difficult disease to study because of its complexity, but this study supports the hypothesis that a dysbiosis is at the root of the problem.

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.

Vaginal microbiome once again tied to preterm birth

Preterm birth is major global health challenge.  Today, around 11% of all babies are born prior to 37 weeks, and are considered preterm.  Many of the causes of these preterm births are still unknown, but it is thought that around 25% of them may be related to a bacterial infection that comes from somewhere in the mother’s own body, i.e. her microbiome.  Many studies are now linking specific vaginal bacteria to risk of preterm birth, and other studies have even shown a connection between other microbiome sites, such as the gut and oral microbiome.  Unfortunately, studies on the microbiome and preterm birth are extremely difficult to conduct, so there are just not enough to have any sort of scientific consensus on the topic.  Last week though, a very rigorous study out f Stanford University was published in the Proceedings of the National Academy of Sciences that monitored expectant mothers vagina, gut, and oral microbiome throughout the course of her pregnancy and then for one year after.  Among many interesting findings, which are discussed below, the most important one was yet another connection between bacterial vaginosis and preterm birth.

The researchers monitored the vaginal, distal gut, salivary, and tooth/gum microbiomes of 49 women, 15 of which ended up delivering preterm, over the course of their pregnancy and for one year after.  Interestingly, the non-vaginal sites’ microbiomes remained relatively stable over the duration of the pregnancy, and even for the one year after.  The vaginal microbiome, however, did show some differences during and after pregnancy.

As many of our readers already know, a healthy vaginal flora is dominated by Lactobacilli, but around 20% of American women are dominated by other species, such as Gardnerella vaginalis, and have an overall increased vaginal diversity.  These women have what is known as community state type four, or CST4, and these women could be diagnosed with bacterial vaginosis (BV), though the clinical diagnosis is not so specific.  The other community state types, CST1, 2, 3, and 5, are dominated by different strains of Lactobacilli, and are generally regarded as healthy.  This current research showed that many of the women’s vaginal microbiomes actually shifted between various CST’s during pregnancy, most often shifting to and from CST4.  These transitions had no association with preterm birth, though.  After giving birth the vaginal microbiome became more diverse, and had greater abundances in anaerobic bacteria, such as Peptoniphilus, Prevotella, and Anaerococcus.  In addition, this usually coincided with a decrease in Lactobacilli.  Surprisingly, these changes did not seem to relate to mode of delivery (C-section of vaginal).

CST4 has been linked to preterm birth before, and this was reinforced in this study.  The scientists found that the longer a women’s vaginal microbiome was within CST4, the greater risk she had for preterm birth.  In addition, the abundance of Gardnerella and Ureaplasma, specifically, were linked to preterm birth.

This study reinforces what many microbiome scientists already suspect, and that is the importance of the vaginal flora in preterm birth.  It is unclear at this point if manipulating the vaginal flora prior to, or during pregnancy would help prevent preterm birth, but it is certainly worthy of discussion and clinical testing.  If you are reading this and wondering what your vaginal microbiome is, then we recommend you participate in the citizen science project, YourPrivateBiome, to find out.  You can learn more about it by following this link on our site, or just click the link above.

Study suggests penile microbiome can transmit bacterial vaginosis by sexual intercourse

Bacterial vaginosis (BV) is a microbiome-based disease characterized by a lack of Lactobacillus in the vagina.  We have covered this disease with multiple blog posts and encourage any interested readers to search for these blogs to learn more.  One outstanding question regarding BV is how sexual intercourse affects the disease.  One prevailing thought is that the penis can actually be colonized by BV-associated bacteria, and that through sexual intercourse it can be spread between partners.  A new paper published last week in mBio suggests this is true.

The researchers measured the penile microbiomes of 165 uncircumcised, black men from Uganda, as well as diagnosing BV status in their female partners.  The BV status was measured by Nugent score, which is a bacterial staining technique that basically measures the amount of anaerobic bacteria in the vagina (non-Lactobacilli).  The stain produces a score between 1-7 with 1 being healthiest and 7 being least healthy (mostly anaerobic bacteria).  After measuring the penile microbiomes, the scientists were able to be categorize them into 7 different community state types (CST1-7).  These community state types varied from 1 to 7 in terms of both overall abundance and composition, with CST1 having the lowest density of bacteria and the lowest diversity while CST7 had the highest density and the highest diversity of bacteria.

The scientists compared the female partner’s BV status with the men’s community state type, and noted that having a CST1-7 on the penile microbiome corresponded with a higher likelihood of the female partner being diagnosed with BV.  Two genera of bacteria, Corynebacterium and Staphylococcus, on the penile microbiome were associated with healthy vaginal flora, whereas Dialister, Mobiluncus, Prevotella, and Porphyromonas were associated with BV.  Interestingly penises that included Lactobacillus and Gardnerella, genera associated with healthy vaginas and BV vaginas, respectively, were not statistically associated with BV status.  Overall, men with CST4-7 were significantly more likely to have a sexual partner with BV, and had more BV associated bacteria colonizing their penises.  In addition, men with more than one sexual partner were more likely to have CST4-7, and again, their partners more likely to have BV.

It appears that men’s penises, especially uncircumcised ones, can be vectors for bacterial transmission.  This simple fact should make us reconsider BV as an STD, and actually fits in well with another that has shown promiscuity is a risk for BV.  It is likely that circumcision and condom would decrease BV transmission rate, as they do other STDs, but until a paper comes out that studies this connection no one can say for sure.

Schisandra chinensis fruit modulates microbiome in obese women

Flower from Schisandra chinensis fruit plant

A search for the blog posts on our site about obesity will result in a list of posts discussing correlations between obesity and bacteria in the gut. People have hypothesized that by modulating the microbiome, you may be able to alter obesity levels in humans. Many studies have looked at how probiotics and prebiotics can modulate bacterial structure to control obesity and metabolic diseases, however little has been done to look at how herbs and fruits could modulate bacterial composition.

A recent study from Korea looked at Schisandra chinensis fruit (SCF), a fruit found most commonly in northern China, that has a long history of being used in East Asian culture as a therapeutic for conditions such as diabetes, obesity, cough, and other conditions.  Previous studies of SCF in mice have shown that it modulates the microbiome, however no human trials had been previously conducted. To analyze this in humans, a clinical trial was conducted in Korea to look at the impact that SCF had on gut bacteria, body composition, and blood chemistry.

At the Dongguk University Ilsan Hospital in Korea, scientists recruited women who were obese (BMI over 25) who met other specific medical conditions. 28 women ended up participating in the study, 13 in the SCF treatment group and 15 in the placebo group. The study participants each took either SCF or placebo twice a day for twelve weeks and blood and fecal samples were taken before and after the treatment as well as a physical examination including heart rate, waist circumference, body weight, and blood pressure.

After twelve weeks, both the placebo and experimental group saw a decrease in waist circumference and fat mass, thought the SCF group saw a greater decrease in fat mass, blood glucose and other parameters. An analysis of the fecal samples before and after the twelve weeks saw greater clustering in the SCF group than the placebo group. At the genus level, there was significant differences between the two groups and the SCF group saw a greater abundance of genus levels (both groups saw similar levels of phyla changes). They saw specific clustering between patients in the SCF group despite dissimilar clustering prior to treatment. This showed that SCF had an influence on gut microbiota that was dependent on gut bacteria prior to treatment.

This study found differences between bacterial composition in patients who were given the Schisandra chinensis fruit and those in the placebo group. Many of the bacteria that saw an increase in the SCF group, including Akkaermansia, Roseburia, Prevotella, Bifidobacterium, and Bacteroides, had shown an association with reduced obesity levels in previous studies. While decreased waist circumference, body mass, and other weight loss parameters were seen in the SCF group, the results were not statistically significant. Much research has been done to look at ways of altering the microbiome and this study shows us that we should continue to investigate the effects of herbs and fruits on our microbiome.  

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!”