Episode 5 of The Microbiome Podcast: Diet and its impact on our microbiota and health with Drs. Erica and Justin Sonnenburg

As we read on yesterday's blog post, dietary fibers alter the microbiome. On this week's episode of The Microbiome Podcast we talked in depth with Drs. Erica and Justin Sonnenburg from Stanford University about dietary fibers and their impact on our microbiota and our health.  Erica and Justin wrote a book that was published today called The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-term Health. You can buy it here on Amazon and it's a highly recommended read for anyone interested in the microbiome. 

Check out the newest episode on iTunes, Stitcher, or listen on our website. 

We will continue answering your questions on the podcast so please call 518-945-8583 with any questions for us or for next week's guest, Dr. Elaine Hsiao.

See below for more detailed show notes from today's episode: 

(1:17) Dr. Rob Knight received a Creative Promise in Biomedical Science Prize from the Vilcek Foundation. Read more.
(3:09) Rob Knight also published a book called Follow Your Gut: The Enormous Impact of Tiny Microbes. Click here to buy it on Amazon. 
(3:33) uBiome recently began a pregnancy microbiome study to better understand how the bacteria in our bodies change during and after pregnancy. Find out more on the uBiome website. 
(4:56) Microbiome Therapeutics performed a clinical study with an investigational drug in type 2 diabetics taking metformin and found that the drug resulted in more tolerability for patients and fewer side effects than metformin without the drug. Read more.  

In the (9:40) conversation with Erica and Justin Sonnenburg (read more about their research), we talked about several topics pertaining to diet and dietary fiber and its impact on our microbiota and health. We also discussed: 

(11:49) Why they decided to write the book.
(16:05) Their personal experiences having children and the importance of nurturing their health and its impact on their lives.
(17:55) Dietary fibers and differences among various types of fibers in our diets.
(26:15) How fast does diet change the microbiota?
(32:05) Bacteroides thetaiotaomicron and why it is Erica and Justin's favorite microbe and a study Justin published in 2005 while he was in Jeff Gordon's lab. Read the paper here.  
(37:35) How microbiome therapies are going to look in the future. 
(41:00) How eating better can make an impact now on our overall health. Read the seminal obesity and microbiome paper Erica mentions from the Gordon laboratory. 

We also answered two other (44:00) listener questions about phage therapy and organic vs. non-organic baby and adult foods. 

Next week we will be talking with Dr. Elaine Hsiao from Cal Tech so please call 518-945-8583 with your questions about autism and the microbiome as well as the microbiome's ability to regulate serotonin levels. 

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.

Probiotics may be able to prevent depression

Clinical studies have shown that probiotics can decrease anxiety, improve mental outlook, and induce positive mood changes and outlook.  In fact, some bacteria strains have been shown to reduce anxiety and depression in mice by directly modulating nerve firings associated with these cognitive maladies.  A recent study conducted by Leiden University in The Netherlands explored further in human subjects to assess whether or not probiotics, composed of various strains of Bifidobacteria and Lactobacilli could specifically modulate cognitive reactivity to sad mood, a well-characterized indicator for vulnerability to depression. 

In brief, cognitive reactivity is defined as a series of dysfunctional patterns of thinking prompted by subtle mood changes, such as rumination, aggression, and hopelessness.  It is thought that cognitive reactivity is central in the development, maintenance, and recurrence of depression episodes.  This behavioral reaction is considered to have significant predictive value in detecting vulnerability to developing clinical depression.  Due to this implication, cognitive reactivity is considered a target for therapeutic intervention to prevent depression onset, and was thus analyzed in this study. 

40 healthy, non-depressed adults were selected and split into two groups, each receiving a 4-week regiment of a probiotic or a placebo.  The participants filled out questionnaires before and after the regiment to assess cognitive reactivity and depression symptoms.  Of the several behavioral indicators of cognitive reactivity that were assessed, aggression and rumination were significantly modified according to the behavioral questionnaires.  Specifically, post-regiment scores in the probiotic group were significantly lowered from pre-regiment scores, and this was not observed in the placebo group.  All told, this suggests that a probiotic regiment eased cognitive reactivity to aggressive and ruminative thoughts.

This study is the first to show that probiotics can modulate an important cognitive process that determines vulnerability to clinically diagnosed depression.  These findings are additionally enlightening with respect to the gut microbiome’s role in overall cognitive health.  As is often the case however, there were some limitations.  Specifically, it would have been interesting to investigate biological underpinnings of these interactions in complementary animal models, especially in light of previous findings that indicate probiotics can facilitate microbiota to synthesize and release serotonin.  On Monday we highlighted work done by Professor Diane Hsiao’s group at Cal Tech that stressed the gut microbiome’s role in serotonin production.  As we mentioned, serotonin is implicated in many bodily functions, including a vast range of cognitive mechanisms.  Indeed, serotonin systems have been primary target for therapeutic treatment of depression.  Zoloft, one of the most highly prescribed antidepressants in the world, blocks serotonin metabolism to facilitate its endogenous mode of action in the brain. 

Not only do the current findings complement those from the Cal Tech lab, but they also highlight an exciting new potential toward therapeutic approach.  Conventional therapies that directly target serotonin systems can be ineffective and have many undesired side-effects and limitations.  Understanding the microbiome’s role in serotonin production can give us more insight and perhaps pave a way toward a more organic therapeutic approach aimed at preventing and/or treating depression.  

Probiotic lozenge fights periodontitis

Periodontitis is a complicated bacterial infection in the gums generally caused by a dysbiosis in the oral microbiome. It results is an immune response which inflames the gums, and after a long time causes pockets to develop in the gums that can be further infected by harmful bacteria. The usual treatment for this problem is the physical removal, or scraping away of the accumulated bacteria in these sensitive pockets. A team of researchers in Istanbul, Turkey did a study published by the Journal of Clinical Periodontology in which they tested the effects of a probiotic lozenge, Prodentis®, on the periodontitis condition.

Forty participants with periodontitis were involved in this double-blind study and randomly placed into a placebo group or a group that would consume a probiotic lozenge twice a day for three weeks, after brushing their teeth in the morning and at night. The probiotic used in this experiment was Lactobacillus reuteri, which is a bacterium we have discussed on the blog previously because of its probiotic characterization and because it commonly resides in the gut.

Samples were taken from the participants at day 21, 90, 180, and 360 to test for bleeding on probing (BoP), plaque (PI), gingival indices (GI), and probing depth (PD). The researchers found a significant reduction in probing depth on day 360 in the patients receiving the probiotic, compared to those receiving the placebo. Also, significantly fewer patients were at high risk for periodontitis disease at day 360 if they received the probiotic. As for the presence of L. reuteri in the mouth of participants taking the probiotic, on day 21 the bacteria was detected in six patients and on day 90 it was detected in eleven. No L. reuteri was detected in patients on days 180 and 360, making the levels not statistically different from the baseline sample before the start of the trial.

So what do the results of this study tell us? The participants receiving the Prodentis® probiotic lozenge had improved clinical and microbiological states compared to the placebo group. No long-term statement about L. reuteri colonization capabilities can be said however, because the microorganism was not detected in the probiotic group at days 180 and 360. At the very least, it seems the probiotic slowed the recolonization of harmful bacteria for up to six months before the levels returned to those pre-treatment, which is a promising step toward a more long-term treatment of periodontitis. 

Can human embryonic stem cells model human nutrition?

Human embryonic stem cell colony

Scientists at Harvard University have proposed a new model for studying nutrition, human embryonic stem cells. Human embryonic stem cells are unique in their ability to turn into all the cell types in the body, including the various tissue types in the human gut.

Drs. Doug Melton and Danny Ben-Zvi propose in an essay in Cell that human embryonic stem cell derived tissues populated by gut microbiota may be an ideal system for studying the physiology of digestion and nutrition. The authors state that the mechanisms of human nutrition are largely unknown and that it is difficult to model how nutrition affects human health on a biological front. By developing systems of stem cell derived tissues, it may be possible to model the gut in the petri dish or even on a chip. Significant engineering advances have been made to model biological systems on a chip.  These chips are devices with specific cell types in chambers that are connected through microfluidic channels to better model the tissues and organs in the human body and how they interact with one another.

Chips could be developed that are made of up cells of the various organs that make up our gastrointestinal tract.  These organoids could then be populated by bacteria that make up the microbiota. Food could be passed through the chip and scientists could watch bacteria break down food that is passing through it and see how the microbiota adapts to changes in diet. Various conditions could be tested such as what bacterial strains are best at digesting complex carbohydrates? The authors state that many combinations of bacterial strains should be tested to find what bacteria conduct these tasks most efficiently. To do this in mice would require thousands of animals and this may be too restrictive to conduct such experiments. This however could be done using chips with stem cell derived tissues that make up our GI tract and connected through microfluidic channels to stem cell derived liver and pancreas cells that are important for nutrition and digestion.

Significant biological and engineering challenges still exist before this is a reality, including the ability for specific strains of bacteria to thrive in such an environment.  However, if some challenges can be overcome, the authors propose that the complexity of nutrition and digestion could be better dissected using systems of stem cell derived tissues in the dish.  This work would complement existing research using model organisms and epidemiological and other human studies to better address the questions that we ask every day about what food we should eat and the effects this has on the human body. 

Breastmilk varies between mothers – affects microbiome of infant

Chemical structure of fucose molecule

We know that breastmilk is crucial to the development of a healthy infant’s microbiome.  It contains many oligosaccharides that cannot be digested by the infant, and whose primary purpose appears to be stimulating the growth of specific microbiome bugs.  There are, however, differences between new mothers’ milk.  For instance, some mothers cannot produce 2′-fucosylated oligosaccharides, which are oligosaccharides that have a fucose sugar on the end.  David Mills and his team at UC Davis recently investigated how the microbiomes of infants differed based on the presence or absence of fucosylated glycans in the milk that they drank.  They published their work in the journal Microbiome last week.

Forty four infants who were fed breast milk had their microbiomes measured throughout the first 120 days of their lives.  Thirty two of these infants were fed milk from woman with fucosylation ability (secretors), and twelve were from women without the fucosylation ability (non-secretors).  When the researchers investigated the contents of the milk they found that it varied in many ways, besides fucosylation.  For example, those women that did not fucosylate appeared instead to increase their monosaccharide sialylation, a sugar that has been linked to C. difficile infection.  When the scientists compared the infants’ microbiomes in the two groups they discovered that secretor-fed infants achieved higher levels of Bifidobacteria and Bacteroides, and achieved these levels more quickly than non-secretor-fed infants.  Instead, the non-secretor-fed infants had relatively higher levels of Enterobacteria, Clostridia, and Streptococci.

These differences may be important to the infants’ developments.  For example, Bifidobacteria in the gut is associated with lower gut permeability and less inflammation.  Also, Bifidobacteria and Bacteroides are large contributors to the production of short chain fatty acids and lactate, which have each been associated with gut health time and time again.  A full 20% of the U.S. population is non-secretors, and it would be interesting to see if any epidemiologically significant differences exist between the two groups into adulthood.  In either case, in the future it may be worth considering supplementing infant milk with fucosylated oligosaccharides if the lack of fucosylation does turn out to be detrimental to the baby.