Bacteria on the skin help shape immune response

The skin is the largest organ of the human body and the first line of defense against harmful microorganisms in the environment. However, it is also home to trillions of microbes that are beneficial to the host individual. In a study published in Nature, scientists found that specific bacteria on mammalian skin influence the host immune response.

To better understand this relationship, researchers chose Staphylococcus epidermidis, a bacterium commonly found on human skin, to see how the bacterium shaped the immune response. Using mice, the researchers found that the presence of S. epidermidis on mice skin caused an increase in CD8 β+ T cells, cells that are involved in immune response.  The application of other common skin bacteria to mice resulted in the increase of different T cell populations. The scientists next investigated how the skin cells detected the presence of S. epidermidis. The results suggested that a specific type of dendritic cell – located not on the exterior epidermal layer of skin cell, but within the dermal, second layer of the skin – is the cause of the unique CD8 β+ T cell response.

While mechanisms are still unclear, it is possible that S. epidermidis produce specific proteins that can trigger an immune response within the human skin when exposed to skin pathogens. What is clear from this study is that different bacteria living on the skin can elicit different immune responses. This suggests a commensal or possibly mutualistic relationship between skin cells and certain bacteria. Further investigation and knowledge of this relationship could lead to better understanding of the immune system and how the human microbiome participates in immunity as well as how this can be translated into therapy.            

Our microbiome has a taste for beer

Many humans enjoy the taste of bread, beer, soy sauce, and other yeasty treats because they taste so darn good.  As it turns out though, we may not be only ones who like these flavors.  A report published last week in Nature describes the discovery of bacteria in our guts that survive by off the yeast in our diets.

The researchers noted that many gut bacteria from the phylum bacteroidetes have genomes that contain genes for enzymes that are capable of degrading complex carbohydrates, including one called α-mannan.  Curiously, the primary source of α-mannan in the gut is on cell walls of ingested yeasts such as Saccharomyces cerevisiae.  The researchers performed a variety of experiments that confirmed that at least one of the bacteroidetes, Bacteroides thetaiotaomicron, could metabolize the yeast cell wall molecule.  The scientists also hypothesize that B. thetaiotaomicron evolved this ability as an adaptation to the changing human diet which includes yeasts from of leavened bread and fermented alcohols. The ability to break down and utilize yeast cell wall components as energy gives B. thetaiotaomicron a competitive edge in living in the gut over other bacteria with less metabolic options.

The B. thetaiotaomicron can thrive in the human intestine because of their evolved symbiotic relationship with the human host: the bacteria breaks down the yeast for the human, while at the same time gaining a source of energy.  This type of relationship is probably quite common in the gut and likely extends to other popular foods.  Who knows, but knowing what we do about the gut-brain axis, maybe these bacteria are actually causing our cravings for bread and beer.

Our beneficial relationship with our virome

X-ray crystallographic structure of a Norovirus capsid.

We have been championing the virome since the inception of the AMI.  We believe that with time, viruses will prove equally as important as bacteria within the microbiome.  To this end, a paper published last week in Nature shows evidence that a specific virus can promote a healthy gut in mice the same way that bacteria do.  The virus, murine norovirus (MNV), was able to successfully restore function to mice with compromised guts.

The authors started with two groups of mice, a control group and a germ-free group.  The control group had normal guts and immune function as measured by gut morphology, and the amount of T-cells.  The germ free mice had thin, leaky guts, and low levels of T-cells.  The scientists infected these germ free mice with MNV and allowed it to proliferate.  Upon investigation of these mice, their gut integrity and immune function resembled the control group.  A second experiment was performed on mice that had been given a course of antibiotics that wiped out the normal microbiome and resulted in an abnormal immune system and compromised gut.  When these mice were infected with MNV they too saw an improvement in health.  In a final experiment mice were given pathogenic bacteria that damaged the gut, but when infected with the virus the negative effects from the pathogens were diminished.

Viruses have a bad reputation, but that’s because we generally only care about the ones that make us sick.  There are countless viruses that exist in our guts though, many that we do not interact with at all, and many symbiotic ones which have yet to be discovered.  It is time that we appreciate the entirety of our microbiome, not just the bacteria but the eukaryotes, archaea, fungi, and viruses as well.

A new probiotic candidate to treat C. diff

Molecular structure of the antibiotic enroflaxcin.

A brief letter was recently published in Nature that identifies a bacteria that may confer resistance to C. difficile.  In addition, they discovered how three commonly prescribed antibiotics alter a patient's risk for C. diff.  

The researchers treated mice with 3 different antibiotics, enrofloxacin, ampicillin, and clindamycin. While the overall microbiome bacterial density was unchanged for each antibiotic, each one altered C. diff susceptibility differently: enrofloxacin did not increase likelihood of getting infected, ampicillin induced transient susceptibility, and clindamycin greatly increased long-term chances of getting infected.

The researchers then identified 11 bacteria that were associated with C. diff resistance.  They  tested one of these bacteria, Clostridium scindens, on humans taking antibiotics that either already had C. diff infections or were susceptible for infection.  They discovered that the probiotic conferred substantial resistance to infection.  Interestingly, this probiotic also led to weight loss.

The researchers then studied how this bacteria could be preventing C. diff infection.  They discovered that this particular bacteria had a rare ability to break down bile into secondary structures, called secondary bile acids.  They tested these secondary bile acids against C. diff and they inhibited C. diff growth.

These results, taken collectively, may be immensely important in treating d. Diff.  Specific types of antibiotics that are known to not increase infection risk, along with probiotics like C. scindens could be combined into new therapies.  This could be important in treating this disease without more rudimentary approaches like fecal microbiota transfers (FMTs).

Gender, diet, and the microbiome

A recent article in Nature Communications demonstrated that a connection between changes to the gut microbiome which occur due to diet are different for different genders.  These experiments were performed first on fish, then with humans.  The gist of the experiments was that when new diets are introduced to humans, each individual's microbiome responds differently depending on gender. 

This has interesting implications to the community moving forward.  First, it demonstrates a direct link between genetics (gender) and microbiome populations, a link that, while self-evident, has been difficult to experimentally prove.  Second, the authors suggest that links such as this may be the cause of certain diseases that are gender biased, such as IBD that appears to affect women more than men.  On a final note, it highlights the need for future research to control for gender, and future microbiome therapeutics and probiotics to consider gender as important variable.

Why does the microbiome adjust differently for men and women when a new diet is introduced?  That is currently unknown, but the authors mention gender-specific hormones and gender-specific immune functions as possible causes.