High salt diet mediates the skin immune response

Salt in our diet has been linked with all sorts of nasty side effects such as hypertension and autoimmune disease.  Researchers from Germany, though, wondered how Na+ in our diet may be affecting the skin microbiome, especially during infection.   Our skin is an important physiological barrier between our body and our microbiome, and because it is partially covered in organisms whenever we get a cut we are at risk for infection.  Fortunately our skin is actually loaded with immune cells that help destroy any of these organisms that may cause harm, and they mitigate the risk for infection.  The German researchers recently discovered that Na+ in our skin may actually be critical for our body to properly fight these infections.  The results were published in Cell Metabolism.

The scientists first infected the skin of both humans and mice with a eukaryotic organism called Leishmania major, which is a common skin pathogen primarily found in Northern Africa and the Middle East.  When they observed the infections using MRI they discovered that the local Na+ concentration around the infection increased in concentration.  They then showed that after treatment of the infection with antibiotics the local Na+ decreased.  

The scientists speculated that the Na+ was perhaps helping to fight the infections, so they designed an experiment to test this hypothesis.  They fed two groups of mice a high salt diet or a no salt diet.  Then they infected the mice with L. major.  They showed that after infection the mice that had not eaten salt struggled to clear the infection, while those that had eaten the high salt diet cleared the infection quickly.  The researchers performed a series of experiments on these mice to learn the actual mechanisms by which salt mediated the immune response, and learned that the Na+ activates and promotes certain immune cells in the skin.

This study shows an unexpected benefit to salt in the diet.  Interestingly, the salt content of our skin increases with age.  While this process has been linked to hypertension, perhaps it also helps fight bed sore infections and other types of skin infections that primarily afflict the elderly.     

Launch of The Microbiome Podcast

We are excited to announce the launch of The Microbiome Podcast. There will be a new podcast available every two weeks with new episodes becoming available on Sundays.  Our first two podcasts are available to be downloaded and subscribed to on iTunes (click here) and Stitcher (click here) or you can listen to them on our website.

In the first episode we talked with Dr. Chris Mason from Weill Cornell Medical College. Dr. Mason led the research that analyzed the bacteria and microorganisms in the New York City transit systems.  They sampled every subway station in the city and assembled the microbiome profile of the NYC subway system. We discussed the impact this research has now and what the future might look like when we can sample bacteria in the subway in real time. Read our blog post about this project here.

The second episode featured a conversation with Dr. Jonathan Eisen from University of California, Davis. We talked with Dr. Eisen about his research as well as a number of different issues pertaining to science like women in STEM fields and open access scientific publications. And if you aren’t tired by now of The Dress and whether it is blue and black or white and gold, you can hear William and David's opinion on the matter (it’s white and gold). 

We hope you will subscribe to the podcast and share it with your friends, family, and colleagues. We would love to hear any feedback you might have so feel free to email us at info@microbiomeinsitute.org.

Can gut microbes be used to diagnose and treat malnutrition?

Credit: Tanya Yatsunenko

When people think about malnutrition, they often think that not eating enough food leads to stunted growth, neurocognitive issues, weakened immune systems, and other health problems associated with malnutrition. While this is largely true, food scarcity and insecurity does lead to undernutrition, it is not the sole contributing factor to this pervasive global health problem.  Jeffrey Gordon and his group at Washington University School of Medicine in St. Louis have shown once again that gut microbes play an important role in undernutrition in a paper in Science Translational Medicine. 

To show the importance of the microbiome in undernutrition, Gordon’s team studied children in Malawi who were undernourished and others that were not. Specifically, they studied individuals with kwashiorkor, a form of severe undernutrition that occurs in children who often eat similar diets as other healthy children. They studied identical twins, one with the disease and one without the disease and sampled their gut microbes.  They transplanted the bacteria from the sick child into germ-free mice to see what effects the bacteria would have. When transplanted into the mice, the bacteria were very harmful causing weight loss as well as severe damage to the lining of the intestines and colon.

The scientists looked for bacteria that were targeted by an important molecule of the immune system called immunoglobin A (IgA). IgA is prevalent throughout the body and specifically in the gut. It plays an important role in preventing the bacteria in the gut from interacting with the human cells that line our intestines. As we saw in the paper on the blog on Monday about emulsifiers in our food, when gut bacteria in the gut interacts with the epithelial cells of the gut lining, severe health problems can arise. The scientists found that IgA and the immune system largely targeted Enterobacteriaceae, a large family of bacteria found in the gut that includes E. coli, Salmonella, and many others. The scientists were able to prevent weight loss in the mice by transplanting two strains of IgA targeted bacteria from the guts of healthy children into the mice, before they were exposed to the bacteria from the undernourished child.

This is an important study as it not only shows the significant role that gut bacteria have on malnutrition, but it shows that it may be possible to use the microbiome as a diagnostic tool to identify which children are at risk for undernutrition, and it may also be a therapeutic target for intervention. The scientists also studied 19 other groups of twins and found that higher levels of Enterobacteriaceae led to a greater risk of kwashiorkor. By sampling children at a very early age for gut bacteria, it could be possible to identify which children were at greater risk of becoming malnourished and intervening with probiotics or other therapeutic foods to alter the microbiome.

Major advance in possible bacterial treatment for cancers

Salmonella bacteria

Editor’s note: Yesterday we wrote about how microbiome bacteria may be protecting cancer cells, but today we wanted to write about how microbiome bacteria can be engineered to kill cancer cells.  Enjoy.

In 2003 a group at the Harvard Medical School discovered that nonpathogenic Salmonella (a microbiome bacterium) that was injected into mice would preferentially accumulate in the tumors of those mice, sometimes by a factor of 10,000.  Soon after, the researchers tried to apply these findings to target and destroy cancer cells.  They began incorporating cancer-fighting proteins into the Salmonella with the hopes that the bacteria would accumulate in tumors and destroy them.  This was effective in killing the cancer, but the Salmonella was not specific enough to tumors, and the low levels that existed in healthy tissues still expressed anticancer proteins which killed the healthy tissues.  Recently though, this problem may have been solved.  One of the original scientists from Harvard Med, who now has his own group at UMass Amherst, developed a clever way to only trigger the anticancer proteins in Salmonella that are on cancer cells.  His group published their results in the Proceedings of the National Academy of Sciences on Wednesday.

The scientists incorporated a genetic switch in the Salmonella which would only trigger the production of anticancer proteins around cancer cells.  In order to do this they took advantage of the fact that the Salmonella accumulates to higher concentrations on cancer cells.  Many bacteria have proteins called quorum sensing proteins.  They are used by individuals and communities to sense what is around them, and to communicate with other bacteria.  Some of these quorum sensing proteins are only activated by their genes when there are enough other bacteria around them.  The scientists from UMass utilized this fact to incorporate a quorum sensing gene into Salmonella that would only activate a specific protein when it was around a high concentration of other Salmonella (e.g. in cancer cells). 

The scientists incorporated this quorum sensing gene into Salmonella so that, when triggered, it would express a fluorescent protein (which could be easily visualized).  They then injected these Salmonella into mice with various tumors.  They discovered, as they had hoped, that the fluorescing protein was predominantly expressed in cancer cells, and at very low levels elsewhere.  Moreover, the fluorescent protein was expressed for at least 24 days, and it did not appear to be expressed in other tissues (such as the liver) at all.

These experiments provide a partial proof of concept for a unique bacterial treatment to cancer.  The next step is to test anticancer proteins instead of fluorescing proteins, but the results using the fluorescing proteins are promising.  The scientists mentioned that the Salmonella used is non-pathogenic and can be eliminated from the body through natural processes.  This is a rather innovative potential cancer treatment, and we are excited to see what its future holds.

Microbiome bacteria help cancer cells evade the immune system

Optical microscope image of bacteria from the genus Fusobacteria.

A few weeks ago Kris Campbell wrote about the microbiome’s association with colorectal cancer.  This association is complex, but perhaps critically important, and last week a new study reinforced this connection.  Researchers, primarily from Israel, published results in Cell Immunity that showed common microbiome bacteria are protecting cancer cells by helping the cancer cells evade the immune system.

The researchers noticed that a type of bacteria, Fusobacterium nucleatum, which is normally found in the oral microbiome and is a cause of periodontal disease, can be found in high concentrations around colorectal tumors.  In addition, these same bacteria had been linked to various microbiome associated diseases, such as preterm birth and rheumatoid arthritis.  They suspected that these bacteria may somehow be protecting the cancer cells from the immune system, so they performed a series of experiments to find out.

The scientists grew cancer cells in the presence and absence of the F. nucleatum and then exposed these cancers to immune system cells that are designed to attack cancers.  They noticed that those cancer cells that had been grown with the bacteria were naturally protected from these immune cells.  Through a series of tests they discovered that the bacteria produce a protein called Fap2 that naturally bound with the immune cells and essentially deactivated them (technically speaking, Fap2 bound to the Natural Killer cells’ TIGIT inhibitory receptors).  Interestingly, this TIGIT receptor is nearly ubiquitous across many types of immune system cells, which means that this bacteria, and others like it, may be especially good at protecting themselves and other cancer cells from our bodies’ natural defenses.

It may be surprising for our readers to hear that bacteria are sometimes used to destroy cancer cells, like in the case of bladder cancer, but this paper shows a more dichotomous relationship between the microbiome and cancer.  While some bacteria may be helpful in killing cancers others may be helping them grow.  Either way, one thing is clear, the microbiome and cancers are intimately related, and learning about the microbiome should lead to advanced therapies for treating cancers.

Sewage accurately represents a city’s inhabitants’ microbiomes

An individual’s microbiome is sometimes indicative of his or her health, but what about the entirety of a population.  Can a city’s microbiome be indicative of the health of that city’s population?  In an article published in MBio, researchers collected sewage samples from 71 U.S. cities in the hopes that it would accurately reflect the microbiomes of that city’s citizens.

Researchers collected and sampled sewage from 71 cities and 78 waste water treatment plants across the United States, and compared it to publicly available data from the human microbiome project.  They discovered that the sewage samples were representative of the human stool samples, and that they captured 97% of the bacteria found in the typical stool. In addition, they noted that sewage samples had a greater bacterial diversity than stool samples.  The researchers also identified 27 “core” gut bacteria among all the sewage samples that they suspect are ubiquitous across the American population.

 Interestingly, the researchers were also able to use their data to predict, with 81-88% accuracy, whether the sample came from a lean or obese population. The relationship was driven mainly by an increased abundance of Bacteroides and a decreased abundance of Faecalibacterium. While Faecalibacterium are more present in high-diversity anti-inflammatory gut communities, Bacteroides are found more commonly in gut communities of human consume a diet high in animal fat.

 This study demonstrates that sampling sewage may be a practical way to attain large samples of human fecal microbiome, in order to compare populations without bias.  It must be unpleasant to work with fecal samples to begin with, so attaining samples from sewage may be an easier alternative, especially in studying populations, as opposed to individuals.