Mapping the ocean's microbiome

The Tara, the boat used for this 3.5 year journey
photograph by Yohann Cordelle distributed under a CC-BY 3.0 license

Today’s blog diverges a bit from our normal topics yet it may have important implications to understanding the microbiome of the human body. Like the human body, the ocean is made up of microbes that interact with one another and play a critical role in shaping the ocean’s ecosystem, just on a slightly larger scale. To map out the microbial communities, and specifically plankton, of the world’s oceans, an international team of microbiologists, scientists, and others set out on a three and a half year journey aboard the ship Tara.

The Tara Oceans Consortium resulted in five papers published recently in Science. The scientists traveled around the world and collected 579 samples from 210 locations in every major oceanic region. They sampled at any given site for about 60 hours using standardized protocols to ensure they were accurately capturing the genetic diversity of the plankton in any given region. Plankton are mostly invisible to the naked eye and largely uncharacterized, yet they are an essential to the ocean’s food web and also produce approximately half of the world’s oxygen.

One of the five papers describes a catalog of the genetic samples found in the study called The Ocean Microbial Reference Gene Catalogue. This catalog contains 40 million genes, four times the number in the human gut microbial gene catalog, from over 35,000 plankton species.  In comparison to the human gut, despite their differences, such as the gut lacking oxygen and having a stable temperature, there was a significant overlap between the two microbiomes. This led the investigators to hypothesize that it may be possible that microbiomes despite their ecosystem function in largely the same way.

The new microbial ocean catalog contains genes from mostly prokaryotic, or uni-cellular, organisms. Over 81% of the genes explored in the Tara Oceans expedition were unique to this study and did not match any previous reference genomes. This striking number highlights the fact that despite great investigation into the ocean, the ocean is still largely unknown and unexplored. The deeper the scientists went into the ocean, the novelty of the genes identified also increased. Temperature was also an important factor into the diversity of samples collected as changes in ocean temperature was the most important environmental factor that drove community composition.

This project has laid the groundwork for greater analysis of the oceans’ plankton and microbial communities and will improve models of the ocean. For example, the finding that temperature was the key driver for microbial community variation could have important implications for better understanding climate change. The information collected aboard the Tara not only helps us better understand the ocean’s microbiome but it allows scientists to compare across ecosystems and better understand microbial communities in general.  

How does the gut microbiome recover after diarrhea?

Scanning electron microscope image of Vibrio cholerae, the cause of cholera and a major cause of diarrhea-associated deaths each year.

Diarrhea is an important global health challenge that kills nearly two million people each year.  Even when it is not lethal it can have important detrimental impacts, especially on children.  For example, frequent diarrhea is associated with decreases in height, IQ, and heart health.  Diarrhea is frequently a microbiome – based disorder, and gut pathogens like enterotoxin producing Escherichia coli and Vibrio cholerae are often the culprits.  Using diarrhea caused by these pathogens as their model, scientists from Harvard University recently studied how the gut microbiome rebounds after diarrhea.  They published their results in Mbio.

The scientists measured the stools of 41 people (both children and adults) in Bangladesh that had diarrhea caused by E. coli or V. cholerae (the cause of cholera).  They measured the patients’ stools before, during, and after their diarrhea episodes and tracked the changes that occurred in all patients’ stools.  Interestingly, they identified a consistent succession of the gut microbiome that occurred in nearly all cases, regardless of the cause of diarrhea.  First, the diarrhea (or antibiotic treatment for the diarrhea) clears out much of the microbiome, and leaves both carbohydrates and oxygen to accumulate in the gut.  (Carbohydrates and oxygen would normally be metabolized by the microbiome, but in the absence of many bacteria, these things accumulate.)  Next, oxygen respiring and carbohydrate utilizing bacteria (especially those using simple carbs) colonize the gut and decrease the abundance of both of these substrates.  After, the lack of simple sugars and oxygen leads to a decline in the population of bacteria that use these, and the succession to anaerobic (i.e. do not respire oxygen), complex carb fermenting bacteria begins.  Finally, the gut microbiome resembles the complex community that existed prior to infection and the onset of diarrhea.  The entire process takes about 30 days to complete, but depends on a variety of factors such as diet, antibiotic use, and duration of diarrhea.

Studies like this one are important to combatting diarrhea, and shortening recovery time.  For example, it is now known that oxygen accumulates after diarrhea, and that while it exists at high levels the microbiome is not fully recovered.  Perhaps introducing an agent after diarrhea that rapidly decreases the amount of oxygen in the terminal gut could hasten the microbiome recovery time and improve the patient’s wellbeing.  Next time you have diarrhea, remember that it takes almost a month for your microbiome to recover, so nurture during that time.

Episode 8 of The Microbiome Podcast: The vaginal microbiome and the announcement of a new citizen science project with Dr. Jacques Ravel

This week's episode of The Microbiome Podcast featured Dr. Jacques Ravel from the University of Maryland School of Medicine talking about the vaginal microbiome. We all also talked about a new project that Dr. Ravel helped start called Your Private Biome, an open source citizen science project designed to help researchers get a better understanding of how all the bacteria in women’s vaginas – the vaginal microbiome - affects their health. The new project launched today, June 1st, and the AMI is sponsoring free sampling for a number of women and possibly her partner or family members. If you'd like to learn more, click here. Remember to call in to ask any questions about the microbiome that you would like answered on future podcasts. The number is 518-945-8583. 

Listen to the podcast here on our website, here on iTunes, and here on Stitcher. 

For more detailed show notes, read below:

• (1:20) The White House Office of Science and Technology Policy issued a Request for Information (RFI) to solicit ideas from various stakeholders on the future needs of microbiome research. Read the RFI.
• (2:55) A recent paper out of Curtis Huttenhower’s laboratory describing how microbiome samples could be traced back to their hosts and if this could be used to track individuals related to forensics and other applications. Read the paper. Read our blog post on the paper. 
• (5:22) We begin our conversation with Dr. Jacques Ravel. Read more about Dr. Ravel’s research. 
• (5:47) Dr. Jacques Ravel gives an introduction to the vaginal microbiome. Read more about his research laboratory at the University of Maryland School of Medicine.
• (8:23) Dr. Ravel mentions a paper by Dr. Larry Forney about the vaginal microbiome of adolescent girls. Read the paper.  
• (20:10) Other health issues related the microbiome such as bacterial vaginosis and STDs.
• (30:30) A new citizen science project called Your Private Biome that offers women as well as their partners and families that allows women to sample their vaginal microbiome. Read more about Your Private Biome. 
• (34:59) A paper on circumcision and it’s influence on bacterial load on the penis. Read the paper. 
• (40:40) On the after show, David and Bill talk about their own health issues, specifically allergies.
• (46:15) During our conversation of Bill’s cat allergies, we mention the Kitty Microbiome. Learn more here.

The oral microbiome of periodontitis patients has distinct profiles dependent on disease severity

A few weeks ago we discussed periodontitis, a bacterial infection of the gums that leads to inflammation and deep pockets to develop in which harmful bacteria can colonize. Periodontitis develops in association with dramatic changes in the makeup of the oral microbiome. Smokers and diabetics are more frequently victims of the disease. The study we discussed previously was one performed by researchers in Istanbul, Turkey in which they tested whether a probiotic lozenge could improve the patients’ condition. In a different, more recently published study concerning periodontitis, researchers in Connecticut and Massachusetts looked not to change the oral microbiome of patients suffering from periodontitis, but to organize and identify the microbial characteristics of the disease.

In the study published in Plos One, seventeen subjects, 8 of whom were diabetic, with Chronic Kidney Disease (CKD) and seventeen subjects without CKD, 3 of whom were diabetic, were studied.  All 34 subjects suffered from periodontitis. Samples were taken from each participant, from the deepest pockets in two different areas of the mouth. DNA was then isolated and sequenced to identify microbial communities in each individual. After much statistical analysis, the researchers found that the microbial communities tended toward two clusters, A and B, with type B communities correlating with more severe periodontitis. Group A subjects had communities with greater health-associated bacteria and cluster B communities were dominated by Porphyromonas gingivalis and Tannerella forsythia. Additionally, the analysis showed that diabetes and CKD are not correlated with a certain periodontitis microbial makeup.

A set-back of this experiment is the low sample size, which makes for less meaningful statistical analysis. Greater sample sizes of each cluster could give stronger claim to the findings of this study. However, this study does begin to clarify the bacterial community characterization of healthy, unhealthy, and severely unhealthy oral microbiomes. In addition, the results from this study could be used to ask further questions about the disease, including questions such as: what environmental factors cause the difference in clusters A and B? Do inflammatory diseases such as CKD and diabetes have anything to do with the severity of inflammatory response of periodontitis? Further analysis may allow us to answer these tough questions.

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.  

New research helps determine what is healthy and unhealthy in the vaginal microbiome

Editor’s note: This blog about the vaginal microbiome is a good primer for this coming Monday’s Microbiome Podcast with Jacques Ravel, where we will discuss the vaginal microbiome and women’s health at length.  There will also be a special announcement during this podcast, so anyone interested should be sure to download it Monday, June 1.

The typical ‘healthy’ vaginal microbiome is dominated by a Lactobacillus.  However many women, especially those of African descent, are not dominated by this genus, and instead have a high diversity of bacteria in their vaginal tract.  This low lactobacilli, high diversity phenotype has been associated with many disease states, such as bacterial vaginosis (BV), preterm birth, and higher rates of sexually transmitted disease (STD) transmission.  (We have written about some of these diseases before, and encourage any interested reader to click the ‘vaginal microbiome’ below this story to learn more.)  Vaginal microbiome research is still in its early days though, and it is not clear why vaginal microbiome not dominated by Lactobacillus should lead to these diseases, and if this phenotype, if asymptomatic, should even be considered unhealthy.  New research though, out of Harvard University, shows that this phenotype does lead to inflammation, and that these inflammatory response can affect reproductive health and STD transmission.  They published their study in the journal Immunity last week.

The scientists studied the vaginal microbiomes of a cohort of 146 HIV negative, asymptomatic, black, South African women.  They discovered that 63% of them were not dominated by Lactobacillus, an extremely high percentage, especially compared to their counterparts in developed countries (38% of black women and 10% of white women).  Nearly half of those women were dominated by Gardneralla vaginalis, which is most commonly associated with BV, and a large percentage of the other half were diagnosed with BV after investigation.  This is especially interesting because, as stated before, all of the women in the cohort claimed to be asymptomatic, but as we are learning, many women are unaware that there is anything wrong.  Overall, the women were able to be grouped into 4 specific phenotypes, those dominated by Lactobacillus iners, those dominated by other Lactobacillus crispatus, those dominated by Gardnerella vaginalis, and those with a high diversity including Gardnerella vaginalis, Fusobacterium gonidiaformans, Prevotella bivia, and Atopobium vaginae (note the lack of Lacotbacillus in this high diversity group). 

The scientists discovered that there were no associations between each vaginal microbiome group and the rate of STDs, contraceptive use, or sexual behavior.  This is important in showing that, at least on first pass, these bacterial communities were not the result of these exogenous factors (nor did they cause them, for that matter).  They also discovered that there was only a loose association between inflammatory cells in the vaginas of these women, and whether or not they had an STD.  The loose association was only observed in women with Chlamydia, and the women with the highest levels of inflammation had no apparent STDs.

The fact that STDs were not strongly associated with inflammation led the researchers to hypothesize that the vaginal microbiome community, rather than STDs, were responsible for vaginal inflammation.  Indeed, when they compared the amount of inflammatory cells in each vagina with the different microbiome groups described earlier, they found a strong association between inflammation and the highly diverse microbiome group.   Moreover, when they tracked individual women over time, those women whose vaginal microbiomes shifted to the high diversity group also increased inflammatory responses.  The researchers then took this work a step further, and identified specific bacteria that were associated with the inflammatory response:  Prevotella amnii, Mobiluncus mulieris, Sneathia amnii, and Sneathia sanguinegens.

Finally, the researchers measured genes for specific receptors in the vagina that are known to trigger an immune response.  They discovered that those women with the high diversity vaginal microbiomes upregulated genes for these receptors, which are known to be activated by bacteria.  Making matters worse, specific immune cells that are triggered by these receptors, which are thought to be critically important to HIV transmission, were found in higher abundances in women in the high diversity vaginal microbiome group.

This paper did a really great job showing that a vaginal microbiome that lacks Lactobacillus is indeed an unhealthy state, because it creates a highly inflammatory vaginal microbiome which likely causes or contributes to many other ailments, beyond just the higher rates of HIV transmission that was demonstrated.  Unfortunately, at the moment, there are no easy ways for women to check which vaginal microbiome they have, but that should be changing soon, and we recommend that all of our readers tune into the Microbiome Podcast this coming Monday to hear a big announcement in this area.