Starch rich diets can influence the gut-microbiome and subsequently behavior

The microbiome’s role in modulating the gut-brain axis has been well-supported by a large body of evidence.  Many experiments in the past have demonstrated this in preclinical models by administering probiotics with specific bacterial strains or by fecal microbiome transplant in rodent models, which were then associated with changes in behavior.  Diet has also been implicated in these modulations, as food intake can influence species diversity and composition.  Low-digestible carbohydrates, or resistant starch, have received attention as being beneficial toward health, as these components are not digested but rather fermented by resident microbiota to produce an array of beneficial metabolites.  In a recent study, researchers from Texas Tech University investigated whether a diet rich in resistant starches were also associated with changes in behavior.

48 mice were randomly assigned to 3 different treatment groups, with each group either fed normal corn starch diet, a resistance starch rich diet, or an octenyl-succinate diet for 6 weeks.  The animals were monitored for weight, were subject to robust behavioral tests, and fecal samples were examined for microbiota composition.  The animals on the resistant starch diet exhibited similar weight gains as compared to the normal corn starch diet, and the octenyl-succinate group demonstrated lower weight gain.  Fecal microbiota analysis revealed diet correspondence to specific diet, and that resistant starch diet groups displayed increases in Verrucomicrobia and Actinobacteria as compared to octenyl-succinate and normal corn starch group, respectively.  In all groups, mice displayed significant anxiety-like-behavior in an elevated plus maze, and in open-field tests the mice fed resistance starch rich and octenyl-succinate diet mice exhibited high-anxiety-like behaviors. 

This data again supports that diet manipulation can have marked influence on behavior, and that starch rich diets could perhaps induce undesirable behavioral effect via modulation of the gut-brain axis.  This could be an important drawback to the beneficial components provided for microbial fermentation.  

The microbiome’s response to the flu and its treatment

In 2013 there was an avian flu (H7N9) outbreak in China that affected 140 people, killing 46 of them.  During the outbreak doctors from one of the major hospitals in China treated 40 of these patients by giving them antivirals and antibiotics, amongst other first line treatments.  In addition, they gave probiotics along with the antibiotics to restore the gut microbiome.  All the while, they measured the patients’ microbiomes to track how they changed throughout the course of treatment.  The results of this study were published last week in the journal Nature Scientific Reports.

Twenty six patients were enrolled in the study, and each of them was given antibiotics within 6 hours of admission to the hospital.  In addition, each one was given Clostridia probiotic capsules along with the antibiotics.  Thirty one healthy control stool samples that represented the demographics of those undergoing flu treatment were also measured as a part of the study.  Before the antibiotics were taken, the patients with the flu already had altered microbiomes that were low in diversity and had lower abundances of Bacteroidetes and higher levels of Proteobacteria.  After antibiotics were given there was a dramatic shift in the microbiomes, that was characterized by a relative increase in the abundance of Escherichia coli.  In addition, the scientists noted that the probiotics were in fact increasing the amounts of Clostridia in the guts of patients who took them, and that the probiotics may have led to better clinical outcomes.  In their hospital only 20% of patients died of the flu, whereas 40% died in the rest of China.

The major takeaway from this study is the changes that the flu has on the microbiome, decreasing diversity and altering the levels of certain phyla.  The fact that the probiotics did appear to take hold and improve clinical outcomes is interesting, but the study was extremely small and limited in its scope to reach any statistically significant conclusions.  Overall though, this study suggests that if you come down with a flu that it may be wise to feed and nourish your microbiome because it is ‘getting sick’ right alongside you.

Gut bacteria may help prevent asthma in children

The world has seen an explosive rise in asthma over the past three decades. Such a rise in prevalence cannot be only a result of genetic variation and leads us to believe that environmental factors play an important role in this change. There are several possible explanations for this including what we call the “hygiene hypothesis”, or the idea that we now live in an environment that is too clean and we are no longer exposed to the bacteria and germs that earlier generations were exposed to. Another possible explanation is as the world changes and becomes more modern, these environmental changes are affecting our microbiome and the “normal” microbiome is shifting to a new normal.

To better understand why some children are at high risk for becoming asthmatic, scientists in Canada studied the microbiome of 319 children in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. They sequenced fecal samples from the children and found that 4 groups of bacteria that were decreased in prevalence compared to the children without asthma. Bacteria from the genus Lachnospira, Veillonella, Faecalibacterium, and Rothia (FLVR) were at lower levels after 3 months for the children at high risk for asthma however over time, this leveled out and was similar to the children not at risk for asthma.

The study did not identify what exactly caused these differences as there could be several reasons for these differences including antibiotic use, the method in which the child was delivered either vaginally or by C-section, and if the child was breastfed or not. It is also possible and maybe even likely that some of the mother’s behaviors during the pregnancy such as diet could play an important role in the early development of the child’s microbiome.

The next obvious question is what can we do about this? Does this mean that we can now treat children that are deficient of these bacteria and they won’t get asthma? While it sounds simple, we don’t yet know too much about these bacteria and it will be important to better understand the impact his would have on the rest of development. Promising results from this study did show that when mice with low levels of FLVR were treated with probiotic samples of the bacteria, it protected them from getting asthma.

This is a very exciting study that may lead to new diagnostics for asthma and with more research and understanding, allow us to prevent the disease from developing. 

Randomized clinical trial shows probiotic may not be an effective treatment for colic

Many families have experienced colicky infants who have excessive and inconsolable crying.  The cause of this behavior is largely unknown, however it is beginning to be linked to a variety of diseases, including allergies and gastrointestinal disorders.  Many remedies have been suggested to help assuage these infants, including probiotic therapies, but thus far the evidence of their efficacy is unknown.  Researchers in Finland put one of the probiotic therapies, using Lactobacillus rhamnosus GG (LGG), to the test and conducted a double blind randomized clinical trial to discover whether it decreased colic.  They published their results last week in Nature Pediatric Research. 

The scientists studied 30 colicky infants in the study, who were split evenly into a probiotic group and a control group.  The mothers of the probiotic group orally administered LGG to their children once a day for 28 days, while the mothers of the control group orally administered a placebo.  During this time the mothers kept diaries of how long the child cried, as well as collected stool samples for microbiome testing.  The results showed that the probiotics did not alter the amount of crying for each infant when compared to the placebo group.  In addition there was no statistical difference in the microbiome’s of both groups.

Unfortunately for the families of colicky infants, this study did not show that LGG was an effective colic therapy.  There are other studies that conflict with this one though, so perhaps different types of bacteria, or larger doses could improve efficacy.  The relationship between the microbiome and colic is unclear, however, given the recent advances in gut-brain axis research, we would not be surprised if the two are connected.

Yogurt may help combat colitis

Editor's note:  The following work comes out of Wendy Garrett's lab at Harvard.  Wendy will be an upcoming guest on the podcast.  If you have questions for her, feel free to email or call, and we will ask her on the show. 

A key signature of colitis is the build-up of reactive oxygen species (ROS) in the colon due to chronic inflammation.  One of major functions of ROS is actually to act as an antibiotic, and destroy any foreign bacteria that may exist at the site of inflammation.  However, ROS are known to be toxic to the host as well, and their high concentrations in colitis are likely a major contributor to the disease.  With this in mind, researchers at Harvard studied how probiotics from yogurt could ameliorate the disease by disposing the excess ROS.  They published their results last month in the Proceedings of the National Academy of Sciences.

The researchers had previously determined that a common yogurt that contained 5 strains of bacteria was helpful in decreasing symptoms in multiple mouse models of colitis.  In this study though, they identified Lactococcus lactis as being the most important of these strains in treating colitis symptoms.  They then compared the genome of L. lactis with the other strains in the yogurt and determined that a specific gene that codes for the enzyme, superoxide dismutase (SOD), which is capable of breaking down superoxide, an ROS, may be imparting L. lactis’ beneficial effects.  In order to support this hypothesis, the scientists showed that when this gene was removed from L. lactis the bacteria no longer reduced colitis.  They took this notion a step further and showed that superoxide levels were in fact decreased in vitro when combined with lysed L. lactis.  Finally, the scientists showed that the L. lactis must actually be lysed in the colons in order to release its SOD, destroy superoxide, and reduce colitis: when the scientists attempted to deliver SOD on its own to mice with colitis it was not as effective, and caused diarrhea.

This study is really interesting for two reasons.  The first is that it shows yogurt, like Activia, may be very helpful in dealing with colitis.  The second reason though, is that it shows a new system for deliverying SOD to a site of inflammation: via bacteria.  As they showed in the paper, simply using SOD was not effective, but using the bacteria as a vehicle for SOD, and then lysing it at the site was an effective means of drug delivery.  This has many important implications because ROS are important contributors to a variety of diseases.  

Probiotic shows effectiveness against skin allergy in mice

We’ve talked about atopic dermatitis on the blog before, because more and more evidence is linking this autoimmune disease with the microbiome.  In fact, a few weeks ago we wrote about a strong connection between Staphylococcus aureus and atopic dermatitis, which suggests this bug is the culprit behind the disease.  If atopic dermatitis does have a microbiome cause, then it makes sense that shifting the microbiome could help alleviate the disease.  This past week researchers investigated whether probiotics, specifically Lactobacillus casei, could help treat this disease in mice.  They published their results in the Journal of Applied Microbiology.

Scientists induced groups of mice to have atopic dermatitis by shaving their skin and challenging them with a molecule called trimellitic anhydride (TMA) on various days over the course of two weeks.  During that time, the scientists orally administered the probiotic to some of the groups of mice.  Over the course of the study the scientists measured various things like the changes in the microbiome and the amount of various immune-activated molecules, as well as dermatitis indicators, such as skin lesions and the amount of itching.  They discovered that the mice that took the probiotic had less severe symptoms than those that did not.  What’s more, is that this reduction of symptoms occurred in a probiotic dose-dependent manner, i.e. the more probiotic administered, the better the symptoms.  These symptoms included a reduction in the inflammatory response, as well as a desensitization of the TMA, as evidenced by less itching.  As for the microbiome, treatment with TMA decreased abundance of Bifidobacterium and Lactobacilli, and an increased abundance of Clostridia.  Probiotics on the other hand, increased the abundance of Lactobacilli and Bacteroides and decreased the abundance of Clostridia. 

This study is not the first to show in a health improvement through the administration of Lactobacillus, which we have written about before.  It seems this bug is almost always associated with health, except in the case of respiratory diseases.  Overall, it seems that you can’t get enough Lactobacilli, so the next time you are considering having a second serving of yogurt for breakfast, go right ahead.