Fecal microbiota transplant as a treatment for MRSA enterocolitis

Fecal microbiota transplants (FMTs) are most commonly used for treating Clostridium difficile infection, an often lethal bacterial infection of the gut. However, there have been many hypotheses that FMTs could be used to treat other conditions that result in a dysbiosis of the microbiota. A new study published in BMC Infectious Diseases suggests that FMTs could be used to treat enterocolitis, infection of the gut, that is a result of Methicillin-resistant Staphylococcus aureus (MRSA).

The most common treatment for this to date has been antibiotic treatment, specifically vanomycin, but the results of how this impacted the microbiota were not measured. In this new study, 5 patients with enterocolitis as a result of MRSA were given FMTs, the infusion of fecal preparation into the GI tract of the patient from a healthy donor. After administration of the FMT, all 5 patients were cured of the MRSA enterocolitis showing no symptoms. MRSA in the feces was also eliminated after FMT.

They also measured the microbiome of patients undergoing the treatment. They found that prior to treatment, patients with MRSA enterocolitis had decreased numbers of species in the gut and S. aureus reached almost half of all intestinal flora.  After the FMT, the microbiome of the recipient trended closer to the microbiome of the donor and alleviated symptoms. 

While there remain concerns with the use of FMTs, there are certain instances where there are few options for treatment and the administration of a new microbiome from a donor fecal sample remain the most promising. While this was only a study of 5 patients at one hospital in Singapore, the investigators suggest FMT as a first-line measure treatment for enterocolitis resulting from MRSA. 

New study suggests S. aureus and skin dysbioses cause eczema

Atopic dermatitis, also known as eczema, is a skin inflammation and rash that has an enigmatic cause.  There are many genetic and environmental risk factors involved, but to date the exact triggers and mechanisms that cause this autoimmune response are unknown.  Importantly, a growing percentage of infants and toddlers are developing this disease, which itself is a known risk factor for other autoimmune diseases like asthma and allergies.  Discovering the cause of atopic dermatitis is an important endeavor, because it may lead to a cure for a number of other diseases.

Staphylococcus aureus has long been associated with atopic dermatitis.  It appears to occur at relatively high abundances in the areas of skin that are affected.  Then again, S. aureus is a one of the most common skin microbiome bacteria (it is ubiquitous around the world), and it has yet to be definitively connected to the disease.  In addition, mouse models for many skin diseases, including this one, do not exist or are insufficient, so controllably studying the atopic dermatitis is difficult.  Recently though, a team of scientists from Japan and the NIH developed a mouse model for atopic dermatitis, and made a new discovery that showed S. aureus can indeed drive skin inflammation.  They published their results in Cell immunity.

The scientists were studying how a specific genetic mutation in mice affected bones and hair follicles when they serendipitously realized that it was causing eczema in the mice after around three weeks.  When they investigated the skin microbiomes of these mice, as well as normal mice, they realized that right around the time that the eczema was appearing in the mice, these mice’s skin microbiomes drastically shifted.  First, a bacterium called Corynebacterium mastitidis emerged, followed by S. aureus a few weeks later, which was coincident with the presentation of the worst symptoms.  Of note, species of Corynebacteria are associated with eczema in humans, much like S. aureus.

Next, the researchers then performed a series of experiments by providing mice with antibiotics in an effort to combat the dysbiosis.  When newborn mice with the genetic modification were treated with antibiotics they never developed eczema at all.  Moreover, genetically modified mice that were in the midst of the rash that were treated with antibiotics had their eczema subside soon after.  In addition, genetically modified mice that were taken off of antibiotics had eczema emerge shortly thereafter.  Strikingly, in all of the above situations changes in the skin microbiome corresponded with the disease state: a lack of S. aureus and high diversity were associated with healthy skin, and the emergence of S. aureus and a lack of diversity were associated with the disease.  Finally, when S. aureus was inoculated onto the skin of genetically modified mice, they developed eczema rapidly.

The researchers performed a number of other experiments to try and tease out the mechanism by which S. aureus causes atopic dermatitis.  Their results show that it appears a combination of genetic and environmental factors that affect the skin may be important in defining an individual’s risk for the disease.  Regardless, it appears that S. aureus is a major culprit in causing eczema, so future therapies that eradicate the bacteria, or at least decrease its abundance should be considered.

New antibiotic discovered that may not lead to resistance

iChip - the device used to identify the new antibiotic (image by Slava Epstein/Northeastern University)

Antibiotic resistance is a topic that we’ve written about extensively in the blog and a major public health concern in today’s society. In the US alone, over 20,000 deaths are caused by antibiotic resistant bacteria every year and several million illnesses can also be attributed annually to antibiotic resistant bacteria. Research led by Dr. Kim Lewis at Northeastern University resulted in the identification of a new antibiotic called teixobactin that looks as if it may not cause antibiotic resistanace. This discovery is being hailed as groundbreaking and a promising avenue to treat previously untreatable chronic infections.

The research published on Wednesday in Nature identified this new antibiotic by culturing bacteria that were previously difficult to grow in the laboratory.  Only about 1% of microbes can be grown in the laboratory making the identification of new antibiotics very difficult (antibiotics are generally developed using microbes).  Using a device called the iChip, they were able to successfully grow up to 50% of bacteria that were previously unable to be grown in the lab. 

Cells from different bacterium were placed individually into a chamber on the iChip that holds several hundred chambers. The device is then placed under the soil where the bacteria are able to grow in their natural environment. After they form colonies, the device was brought to the laboratory and the bacterial colonies were placed on a petri dish.  A target bacteria is then covered over the bacteria that were growing in the soil. If they see that there is no growth over a specific area, they know that the bacteria in that chamber is releasing a potential antibiotic. Through this method, the scientists identified 25 promising novel antibiotics in which teixobactin was the most promising. 

Two diseases we’ve discussed on the blog previously are MRSA (methicillin resistant Staphylococcus aureus) and Clostridium difficile infection. C. diff is a disease usually caused when the healthy bacteria in the gut are killed by an antibiotic and C. diff colonizes the gut. This can be very difficult to treat and a last resort is often a fecal microbiota transplant (FMT). An exciting development from this research is that this new antibiotic was particularly effective against both C. diff and S. aureus as well as the bacteria that causes tuberculosis. 

This is an incredibly exciting development but as an organization focused on the microbiome, we need to think about what the implications are on the microbiome.  The development of new antibiotics is incredibly important and we have seen the field move very slowly in recent times, but we still need to be careful with the overuse of antibiotics. Even if bacteria do not become resistant to this antibiotic, the same issues we’ve discussed pertaining to the overuse of antibiotics still exist.  This antibiotic seems to be quite powerful and ridding our guts of bacteria on a regular basis can cause increased levels of obesity in children among countless other public health problems. It is important that just because an antibiotic does not cause resistance, we do not overuse it. 

We look forward to the further developments with teixobactin and hope to see this move to clinical trials in the near future. This new antibiotic has only been tested so far in mice and will need to be tested further in animals and later humans.  The authors estimate that if all goes well, this new antibiotic could be on the market in about 4 or 5 years (they hope to be in clinical trials in two years with clinical trials taking an additional two to three years).  

How an antibiotic resistant bacteria is raising concerns for the 2016 Summer Olympics

About a month ago we wrote about an antibiotic resistant bacteria called MRSA, or methicillin-resistant Staphylolococcus aureus, and gave an example of an athlete who had contracted the bacteria.  There is now another antibiotic resistant bacteria making international headlines and it is once again a relationship with sports that is bringing it to the forefront of our attention.  Recent reports out of Rio De Janeiro, Brazil show that an antibiotic resistant “superbug” has been found in the Cariorca River that runs through Rio and empties into the Atlantic Ocean at the famous Flamengo Beach.

This report from scientists at the Instituto Oswaldo Cruz is particularly concerning as the bacteria have been found close to the Marina da Gloria, site of the 2016 Olympic sailing competitions. This bacterium is of the Enterobacteriaceae family and produces an enzyme called KPC that is resistant to most forms of antibiotics.  This bacterium is usually only found in hospitals, so how is that it was found in three separate sites of the Cariorca River?

Well, its not yet clear how the bacteria made its way to the river, but the scientists did note that the bacteria were not found before the river made it’s way through town. This leads to the belief that it was likely sewage and waste from hospitals that transmitted the bacteria into the environment. There are several hospitals along the river and fecal matter in the sewage very well could have been host to the bacteria. Officials in Rio had stated their goal was to reduce the sewage and waste by 80% but officials have recently acknowledged that this number was not going to be reached in preparation of the 2016 Olympic games.

Like other bacteria, it is possible that someone who comes in contact with the bacteria may not get sick from it but they could carry it and pass it on to someone else. Those who do contract this bacterium will need to be hospitalized and studies have shown that KPC producing bacteria result in a 50% mortality rate. Antibiotic resistant bacteria are a major concern in today’s society and something that we feel does not get enough attention.  A recent report out of the UK that was commissioned by Prime Minister David Cameron and supported by the Wellcome Trust found that antimicrobial resistance resulted in approximately 700,000 deaths a year and this number was going to increase to 10 million people a year by 2050.  This is a staggering figure and is one of the fastest rising figures in the cause of deaths around the world. 

Almost every two years there is some major health concern at the Olympics. At the 2002 winter games in Salt Lake City we saw influenza running rampant, in 2010 at the winter games in Vancouver, Canada there was a measles outbreak, and earlier this year in Sochi we had stray dogs running loose. Now, we have antibiotic resistant bacteria on the loose in Rio and it will be interesting to see how officials in Brazil get this under control in preparation for the 2016 Summer Olympics. 

This is our last post for the week. We hope everyone has a happy holiday season and we will be back with another post on Monday.