Do you smell bad? Just throw on some bacteria

When you’re next to someone on the subway or on the street who smells bad, do you ever  wonder what it is on his or her body that is making him or her smell that way? I don’t. I usually just walk away and I’m done with it.  But after reading a new study out of Switzerland and published in Microbiome, the next time I’m standing next to a smelly person on the subway, I might ask him or her about the bacterial makeup of his or her armpit. While body odor has long been attributed to the degradation of bodily fluids by bacteria in armpit sweat glands, this new study sought to identify which bacteria cause body odor.

The study consisted of 24 test subjects, both male and female, of which 13 used an antiperspirant and 11 did not, as well as four trained assessors tasked with smelling and analyzing the test subjects' underarms (talk about a fun job). Unsurprisingly, the researchers found that sweat odor intensity was much higher in non-antiperspirant users.  In addition, the non-antiperspirant users' odors were more likely to be described as sulfury-cat urine, acid-spicy, and fresh onion as compared to those that used antiperspirant.  After analyzing the amount of bacteria in the armpit of all the individuals, they found that those not using an antiperspirant had 50 times more bacteria than those using one.

The researchers were able to associate specific groups of bacteria with body odor: Corynebacterium, for example, had higher abundances in the smelly pits, while Propionibacterium had higher abundances in the non-smelly pits.  Overall, bacteria from the Firmicutes and Actinobacteria phyla were the most prevalent in all the arm pits, which makes sense as they are typically the most prevalent bacteria on the skin.  Finally, some bacteria were found to be more prevalent in men than in women, evidence that lends itself to the belief that men and women have different odors.

The identification of the smelly arm-pit bacteria provides an opportunity for microbiome interventions to combat body odor, and several companies, like AOBiome, are currently trying to do this.  They have developed products that are meant to put bacteria on the body that will help control body odors.  There are people out there (some that I know!) that rarely if ever take showers or use antiperspirants…and they actually smell just fine. Talk about dedication to the microbiome!

Deciphering individual bacterial strains in the gut is important to understanding the microbiome

Phylogenetic trees go beyond just genus and species, but also to strains.

When scientists determine the bacterial population of one’s microbiome using genetic sequencing they are forced to make determinations of the populations’ phylogeny.  Some scientists will determine the abundance of each genus, like all the bacteria that belong to the Clostridium genus, while others will narrow their scope to specific species, like all the bacteria that belong to the Clostridium difficile versus Clostridium scindens species.  These distinctions can be immensely important.  For example, C difficile can cause colitis, but C. scindens can prevent colitis, so measuring the amount of Clostridium in the gut does not paint as clear a picture as measuring the amount of C. difficile (potentially harmful) and C. scindens (potentially helpful).  There is, however, a deeper level of differentiation within species: the strain (e.g. C. difficile A90 vs. C. difficile AA1).  These strains are very similar genetically, especially in the genomic regions most important to determining phylogeny, there are however, potentially important genetic differences. 

Scientists have long realized and understood that by characterizing the species population of the microbiome they were neglecting possible important strain-specific effects.  There have even been specific examples within the microbiome that differences in strains are important, like strains within the Staphylococcus aureus that differ in their antibiotic resistance (e.g. MRSA).  Just how important these strain-specific differences are is unknown, but there is mounting evidence they need to be taken into account.  Last week in the journal Cell, researchers from the University of Washington published results that showed strain-specific differences can be vast and immense, and that this is even more so true in the microbiome where genetic mutations and genetic transfers happen at a high rate.

The researchers used metagenomics data from patients with IBD from a previously published data set.  They took this data, compared it with previously published species’ genomes, and did a lot of fancy bioinformatics to measure strain-specific genetic differences within species.  I don’t mean to neglect the bioinformatics aspect of the paper, which is critically important their results, but the details of their ‘pipeline’ are beyond the scope of this short blog.  In any event, they learned that there were many examples of different strains that coded for as much as 20% more copies of specific genes.  As it turns out, these differences were prevalent in genes that coded for important functions, like transport, signaling, biosynthesis, motility, secretion, and virulence.  These are important processes in the gut environment, and each may have important impacts on the host.

Before this paper, the level of genomic resolution and bioinformatics needed to make strain specific determinations was difficult, and beyond the expertise of most labs.  Now that these researchers have published their methods, this type of strain analysis can be incorporated into many more experiments.  It does have its drawbacks, as full genomes are needed for each species that is analyzed, and inserted/deleted genes are not analyzed, but overall it is a very important paper.  As we move forward in microbiome research, this type of analysis that incorporates specific strains will become critical in associating diseases and phenotypes with the microbiome.

What exactly are antibiotics doing to our bodies?

We’ve talked a lot about antibiotics in the past as well as antibiotic resistant bacteria but it is still unknown exactly what all the effects of antibiotics are on the body and specifically our microbiome.  The increase in antibiotic resistance is a rising concern and this week President Obama and the White House announced that in their 2016 budget they would be doubling their investment in fighting antibiotic resistant bacteria to $1.2B this year. Antibiotics are essential for the treatment of bacterial infection; however, many individuals have adverse effects due to alterations of the microbiome and the increase of antibiotic resistance. These are very real concerns that are causing increasing public health issues and we are glad to see that this administration is continuing to make fighting antibiotic resistant bacteria a priority.

A study recently published in the journal Gut sought to further our understanding of the effects of antibiotics on the host. To look at the physiological effects of antibiotics, the scientists studied three groups of mice: regular germ-free mice; germ-free mice treated with antibiotics; and germ-free mice that were colonized with microbiota from antibiotic-treated normal mice. They found that the use of antibiotics influenced the host in three major ways: depletion of the overall microbiota; having a direct toxic effect on tissues in the host; and the increase of antibiotic resistant bacteria in the microbiota. The researchers also found that the antibiotic-resistant bacteria Pseudomonas aeruginosa were involved in mitochondrial damage, leading to mitochondria-dependent apoptosis (or programmed cell death) in the epithelial tissue of the intestines.

While antibiotics save lives and are incredibly important in fighting bacterial infection, they can also have very unpleasant effects such as local immunodeficiency and cell death. This study took an important, in depth look at the effects of antibiotics on the physiology of the host the effects on the microbiome.        

The fungal microbiome may be associated with colon cancer

We don’t write much about the fungal microbiome on this blog, but it may be every bit as important as the bacterial microbiome (and let’s not forget about the archaeal and eukaryotic microbiomes, and virome as well!).   Fungi are not as abundant in the microbiome as bacteria, which is probably why they are not as heavily researched, but they are known to cause diseases.  For example, vaginal yeast infections and oral thrush are caused by fungi belonging to the Candida genus.    

We recently wrote about a study that linked bacterial biofilm formation with colorectal cancer.  In this blog we mentioned that colorectal cancer is likely to have environmental causes.  Researchers from China hypothesized that fungi may be one of these risk factors, so they conducted an experiment to find out.  They recently published their results in Nature Scientific Reports.

The researchers first sampled the microbiomes of 27 patients with various stages of colorectal tumors, in addition to other, healthy areas of those patients’ guts adjacent to the tumors.  They then sequenced the genomes of the samples to determine which fungi existed, and where.  They discovered that fungal diversity was lower on tumors compared to other areas of the colon.  In addition, two known pathogenic fungi, Candida and Phoma existed in higher levels on tumors compared to the adjacent areas.  Finally, they found distinct differences between individuals with advanced and non-advanced tumors.  Those with advanced tumors had a higher abundance of two other known pathogenic fungi, Fusarium, which has been associated with intestinal disease in the past, and Trichoderma, which has been associated with infections of various organs. 

This study did not involve any healthy patient controls, and its sample size was somewhat limited.  Still, the results are intriguing because gut fungi that are known to cause inflammation elsewhere in the body are being found at the site of tumors.  Even if these fungi are not causing the tumors, they could at least be potentially used as a diagnostic or biomarker for tumors.  While we know that some fungi can be dangerous, we note that even specific genera are not always pathogenic, and sometimes they can exist normally in a host and only turn pathogenic at a later time.  Like other aspects of the microbiome, the story is complicated, but we would be willing to bet there is at least one beneficial fungus among us.

Walk, chew gum, and fight cavities all at the same time

Chewing gum has been suggested to have many cognitive benefits such as increasing focus and alertness, improving memory, and controlling, besides its obvious benefit of making breath smell minty fresh.  What about gum's effect on our microbiome though?  Could gum help prevent cavities in the same way as tooth brushing or flossing?  In order to find out, researchers from the Netherlands and Wrigley, the gum company, recently published the results of a study in PLoS One that set out to answer the question: how much oral bacteria is trapped and removed by chewing gum?

In order to test the hypothesis, volunteers chewed gum for various times for up to 10 minutes. The researchers then used different quantitative and qualitative analyses, such as culturing and genomic analysis, to measure the amounts of bacteria collected in the gum.  The researchers found that the chewing gum does indeed trap around 100 million bacteria, which is about the same as brushing your teeth with a new, clean toothbrush without using toothpaste. They also state that chewing gum could prevent biofilm formation, much like tooth brushing.  Finally, they concluded that the longer gum is chewed, the fewer bacteria it removes from the mouth.

This study in quantifying bacterial removal by gum was preparing the researchers for their next project, which is to intelligently design gum to prevent cavities.  As we know there are healthy and harmful bacteria in the oral cavity, but the study did not investigate which types of bacteria were removed.  If gum could be designed that preferentially adsorbs and removes acid-forming bacteria like Streptococcus mutans then it could be highly effective in eliminating cavities.  We look forward to reading more about this project, and in the meantime, if you’re going to chew gum, try and make sure it’s sugar free.

Viruses in the gut connected to inflammatory bowel disease

Drawing of a bacteriophage

A new study has shown that the composition of viruses in the gut may play an important role in inflammatory bowel diseases (IBD).  If you’ve been reading the blog for a while, you’ve seen us write about something called the virome. The virome is the collection of viruses in the body and similarly to the microbiome, it may have profound affects on human health. This study led by scientists at Washington University in St. Louis and published in Cell is the first to correlate a disease with changes in a person’s virome.

IBD, specifically Crohn’s disease and ulcerative colitis (UC), are diseases that have been characterized by decreased bacterial diversity in the gut.  However in this study, the scientists found that patients with Crohn’s and UC showed greater diversity of viruses than healthy individuals.  This suggested that viruses played a role in the disease.

The team of scientists studied individuals in Boston, Chicago, and the United Kingdom with the disease. They took stool samples from patients with UC and Crohn’s and sequenced their viral DNA. They compared this to the viruses in stool samples from healthy individuals living in the same areas and households. Patients with the disease had a higher number of viruses than those without IBD. Specifically, they found that Crohn’s and UC patients had higher levels of Caudovirales bacteriophages (viruses that infect bacteria) that were specific to each disease.

Further research is needed to better understand the relationship between the virome and the microbiome but as we see from the increase in bacteriophages, there is certainly a relationship between these two systems. While the authors state that it does not look as if changes in the virome were secondary to changes in bacterial populations, it is not yet clear if changes in the virome are the result of bacterial alterations in the gut or if it may lead to microbiome changes - or a combination of the two.  This study is the first of its kind to show a connection between disease and the virome and I think we are going to see several more studies in the coming years showing this type of correlation with disease.  While we generally think of viruses as causing infections like influenza, their impact on chronic disease may be vast.