The microbiome of the international space station

Characterization of the microbial composition of the International Space Station (ISS) is a topic that currently interests the National Aeronautics and Space Administration (NASA). The ISS is an interesting environment because it is a built environment that experiences constant human contact, microgravity and space radiation. Understanding the ISS microbial community would help with help and safety concerns as well as proper maintenance of the ISS. Scientists across the United States combined their efforts to properly characterize the microbial community of the ISS, and compared it to cleanrooms on Earth. The results were published by Microbiome.

         Samples were collected from ISS high-efficiently particulate arrestance (HEPA, vacuum cleaner bag components from the ISS, and two cleanrooms at the Jet Propulsion Laboratory (JPL) in Pasadena, CA. Cleanrooms are closed rooms with little human traffic and filtered air. Bacterial and fungal samples were cultured and sequenced using next generation sequencing techniques in order to determine identities. Sixteen fungal strains were isolated from the ISS samples compared to the three strains from JPL samples, with most strains being associated with the phylum Ascomycota. Bacterial samples from the ISS were dominated by Actinobacteria, Bacilli, and Clostridia, while samples from the JPL were dominated by Alphaproteobacteria and Gammaproteobacteria. On a genus level, the two sample environments were completely distinct as well.

         This study shows that the International Space Station has a very distinct microbial community that must be monitored. As we know that the microbiome is so influential on health, it is important that the ISS bacteria are characterized in order to ensure the health and safety of those on board. This is just another important example that the microbiome has a great influence on humans, even from out in space.         

Microbiome metabolite in urine predicts severity of graft versus host disease

Molecular structure of indoxyl-sulfate

People that suffer from blood cancers, such as acute myeloid leukemia, often times receive hematopoietic stem cell transplants (HSCT) as part of their therapy.  This procedure typically replaces the sick person’s white blood cells with those of a healthy donor.  While this is a life-saving procedure it does carry a type of transplant ‘rejection’ risk.  While in a normal organ transplant a person’s own white blood cells will attack the foreign organ, in this case the new, donor white blood cells begin attacking parts of the recipient’s body.  This is called graft versus host disease (GvHD), and can often times be fatal.  One of the primary areas that are attacked by the new blood cells is the gut microbiome.  This is not surprising because the ‘replacement’ immune system is not programmed to tolerate and accept the bacteria in the gut, because they are so different from the bacteria it was originally adapted for.  Therefore, GvHD, is often considered a microbiome disease, and there have even been studies to investigate whether matching microbiomes decreases risk for the disease. 

An important area of research is focused on detecting GvHD before it begins so that it can be treated early.  While normally GvHD is diagnosed by symptoms, it may be possible to use the microbiome itself for early detection of the disease.  A group out of Germany recently showed that by monitoring a specific metabolite produced in the gut, indoxyl sulfate, one could predict the severity of GvHD.  This molecule is only produced by bacteria, mostly in the gut, by breaking down the amino acid tryptophan.  Moreover, indoxyl sulfate is an important signaling molecule that is thought to modulate the gut epithelial function, and may cause inflammation.  They published the results of their study in the journal Blood last week. 

The scientists measured the indoxyl sulfate concentration in the urine of 131 individuals undergoing HSCT over the course of 28 days following the treatment.  After, the ranked the patients in terms of indoxyl sulfate level during the first ten days after transplant, and compared their outcomes.  Remarkably, the people that had the lowest levels of indoxyl sulfate had a statistically significant higher risk of dying of GvHD after 12 months.  Next, the scientists attempted to relate the gut microbiome composition of the patients with the indoxyl sulfate levels.  They realized higher diversity microbiomes were related to higher indoxyl sulfate levels, and healthier outcomes.  In addition, higher levels of Clostridia and lower levels of Bacilli led to higher indoxyl sulfate.

This study may go a long way in informing clinicians about GvHD risk in their patients.  Not only does it show that monitoring indoxyl sulfate may predict GvHD severity, but it also points to specific bacteria that may be important in controlling its levels.  HSCTs are a highly effective treatment for blood cancer, that often times have a higher efficacy/safety profile compared with traditional cancer therapies.  Understanding the microbiome’s role in GvHD, one of the most important risks of HSCT, will hopefully lead to improved therapies and better overall cancer outcomes.

Helminths may provide therapeutic benefit to treat brain disorder

We’ve recently talked about a few articles that have studied helminth infection with respect to the microbiome, and how these infections could possibly confer some therapeutic benefits.  Another recent study conducted by researchers at Duke University reinforces these findings.  Autoimmune and inflammatory disorders appear to be more common in developed societies, and many have suggested that the microbiome is a major driver of these changes to our immunity.  These investigators wanted to assess whether or not helminths – which have a lot of influence on the immune system – had any effect in modulating the brain immune system in the context of living conditions and early-life infection, as this has been shown to result in neurodevelopment disorders. 

In this study, male and female rats were infected with a H. diminuta cystercircoid rat tapeworm a few weeks prior to breeding.  The rats were segregated by living conditions, housed in either dirty colonies (or “farm-like” environments), where no water or air filtration was provided) or standard clean pathogen-free laboratory conditions.  The offspring in both environments were delivered helminths, and the males were infected with E. coli early in life. 

Later in adulthood, the immune systems of the progeny animals were challenged by lipopolysaccharide (LPS) inductions in learning tests, and brains were collected shortly after to examine changes in molecular immune responses.  Exaggerated immune responses were observed in rats that were infected with E.coli early in life in the standard clean lab conditions.  Alternatively, the cohort that lived in the farm-like conditions did not experience an increase.  Both groups were infected with helminths.

To narrow down further, the researchers examined the impact of helminths alone in rats housed under clean pathogen-free laboratory conditions.  Indeed, cytokine responses in rats infected with E.coli were reduced in the animals whose mothers were infected with helminths before giving birth.  In addition to immunologic modulation, helminth infections in adult rats where shown to reduce memory deficits that are common following E. coli infection, suggesting helminth infection played a role in modulating developmental disorders due to bacterial infection. 

The helminths also had an effect on the microbiomes of the rodents.  16s rRNA sequencing revealed an average 25% shift in microbiome composition of animals infected with helminths (with a predominant shift of Bacilli to Clostridia).  Rats that were infected with E. coli early in life experienced a microbiome composition shift in adulthood, as more harmful Bacteroidetes species were found in adults.  Interestingly, this observation was not found in those who were E.coli infected but also infected with helminths, suggesting helminths prevented this composition shift. 

Overall, these findings suggest that helminths could provide therapeutic benefit, especially after infection early in life.  It will be interesting to see how this research can translate to human models, especially by narrowing down bacterial infections that could harm or benefit development.  Understanding what drives these developmental complications could have immense health benefits for the public. 

New info on fecal microbiota transplants for C. difficile and ulcerative colitis

"Fecal bacterial communities of recurrent [C. diff]  patients shift towards [healthy] fecal bacterial communities after FMT. Pre-FMT patient samples (red circle); post-FMT patient samples (green circles); trajectory of patient fecal communities after FMT (blue line)."
Image and caption from the C. diff paper: Weingarden et al. Microbiome 2015 3:10   doi:10.1186/s40168-015-0070-0

Two important papers regarding fecal microbiota transplants (FMTs) were published last week.  The first was an examination of a patient’s microbiome over time after he or she undergoes an FMT to treat C. difficile.  The second showed the results of clinical trials that used FMTs in an attempt to treat ulcerative colitis.   The FMT papers, which are described below, improve our understanding of this procedure, which holds promise to treat various microbiome-based diseases.

The C. diff paper, published in the journal Microbiome, attempted to answer the question: Do the microbiome changes that occur after FMT remain long after the procedure?  We know that FMTs are highly effective in treating C. diff because they install a healthy microbiome that can crowd out the infection.  However, it is unknown if these new bugs that take hold are transient, or if they become permanent members of the gut.  The researchers sampled the microbiomes of FMT donors and recipient patients before and up to 84 days after an FMT procedure to treat C. diff.  They discovered that the recipients’ dysbiotic microbiomes stabilized quickly, and after just one day they closely resembled the donors’ microbiomes.  Continued measurements showed that the microbiomes deviated over the next few weeks, but that they remained healthy.

The colitis clinical trial, published in the journal Gastroenterology, attempted to discover if FMTs could treat ulcerative colitis.  Ulcerative colitis is widely considered to somehow be related to a dysbiosis in the microbiome, so can FMTs from healthy donors treat this disease?  The study was a double blind randomized clinical in which 48 people suffering from ulcerative colitis either received stool from healthy donors (treatment) or just an FMT of their own stool (control).  7/23 patients who received stool from a healthy donor were in remission after 12 weeks, while 5/25 patients who received their own stool were in remission at that time.  Unfortunately, this is not a clinically significant result based on the number of patients involved.  The researchers measured the bacterial abundance in all of the patients microbiomes before and after treatment.  Before treatment the microbiomes all had some baseline similarity.  After treatment, though, the patients who responded to treatment from a healthy donor all had an increase in certain Clostridia, and the patients who responded to treatment from their own stool all had in increase in certain Bacilli, Proteobacteria and Bacteriodetes.  The researchers feel that this information warrants further study.

FMTs are an exciting new therapy that may be important in treating some really nasty diseases.  We do want to remind people, though, that it is still an unproven technique that should only be performed under the guidance of a doctor.  As we have written about before, the promise of the microbiome is what makes FMTs both attractive, but potentially dangerous at the same time.