Cigarette smoke changes the gut microbiome

When we talk about smoking cigarettes, we usually discuss the harmful effects that it has on our lungs, mouth, skin, and other parts of the body. However, we don't often talk about the gut even though cigarette smoke is the best-known environmental risk factor for Inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis.  While the exact mechanism for why people get these diseases is not yet known, it is recognized that a dysbiosis of the gut plays a contributing role to the onset of these conditions. A research team in Germany investigated the effects that cigarette smoke exposure had on the mucus layer and the microbes in the gut.

The scientists exposed mice to cigarette smoke or air for a period of 24 weeks. They found there was a shift in the microbial community in the caecum and distal colon after exposure to smoke. Specifically, there was an increase in Lachnospiraceae in the colon however it remained the same in the ileum, the last part of the small intestine.

They also found that smoke exposure led to changes in mucin exposure. Mucin is a type of protein that is known for producing gels that act to lubricate and protect parts of the body, both internal and external. The most common mucins are Muc2, Muc3, and Muc4. Muc2 for example is a protein that is secreted onto the mucosal surfaces of the large intestine and serves as a protective barrier for the epithelium. In this study, they found that Muc2, Muc3, and Muc4 gene expression was altered after cigarette smoke exposure.

The authors hypothesize that cigarette smoke affects the immune system in the ileum and may lead to the inflammation associated with Crohn’s disease. Overall, this study found that exposure to cigarette smoke had a profound effect on the gut bacteria and mucin composition in the mouse. While this was not done in humans, the same effects would likely be seen.

Decreased bladder microbiome diversity associated with urinary tract infections

A catheter

Urinary tract infection is one of the top healthcare-associated infections along with pneumonia and gastrointestinal illness, according to the Centers for Disease Control and Prevention. In nursing homes, UTIs are the most common type of infection and are often caused by catheters. Catheters are used to collect urine in both male and female patients. Older patients tend to need catheters for a longer period of time, putting them at higher risk for infections as it allows for the greater colonization of infectious bacteria. In an article published in the Journal of Infection, researchers in Houston, Texas experimented with a catheter coated in a specific strain of Escherichia coli to see if it would prevent catheter-associated urinary tract infections (CAUTIs) in older patients.

Eight men and two women, with a mean age of 70.9, were enrolled in the study. All but one subject received antibiotics prior to the insertion of the catheter. This antibiotic regime most likely caused a significant disruption to the existing microbial balance in the bladder. Despite the antibiotic use, the subjects’ urine still showed the presence of microorganisms after antibiotic treatment and immediately prior to catheter insertion. The study catheters that each patient received were previously colonized in the lab by E. coli strain HU2117, which is a strain that is missing an essential infection-allowing gene. By using the benign strain without this papG gene, the patients were safe from any harm. The hypothesis was that this E. coli strain would be delivered to the bladder and compete with infectious bacteria, not allowing the pathogens to colonize the bladder.

Urine samples were collected from the subjects on days 0, 1, 3, 7, 14, 21, and 28 after catheter insertion. After that, samples were collected monthly until no E. coli was detected. Three of the subjects suffered from febrile UTI, and two from urosepsis/bacteremia, another form of UTI. In these five subjects E. coli was not the predominant bacteria and was not even detected during infection in some cases. From the results of this study we can conclude that E. coli HU2117 is most-likely not effective enough in preventing other pathogenic bacteria from infecting the bladder.  

The researchers explain that the reason why their experiment had a negative result was that the E. coli did not increase bacterial diversity in the bladder. Diversity in colonization is usually what protects from infection and in this study, decreased diversity led to UTIs. This is a theme we have seen over and over again on the blog. Further informative studies could include those that help us understand the healthy and diverse microbiome of the bladder, and subsequently use that information to decrease UTI occurrence.  

Understanding the nasal microbiome

Electron micrography of Staphylococcus aureus.

The nasal microbiome remains largely unstudied despite its potential importance to many diseases, such as rhinosinusitis, allergies, and staph infection (incuding MRSA).  Staphylococcus aureus is probably the most well-known nasal resident, but simple questions, such as which species of bacteria are most prevalent in the nose, are still not answered.  Understanding all the residents of the nasal microbiome, the influence of our genetics and the environment on defining their populations, and the influence each one has on others may be critically important to preventing diseases such as staph infection, and more research is needed.  Fortunately, a new study out of Johns Hopkins that investigated sets of twins shed light on many of these questions, and was published in Science Advances last week.

The scientists sequenced the nasal microbiomes of 46 identical and 43 fraternal pairs of twins.  First, thy learned that these people’s nasal microbiomes could be classified into 7 different phenotypes or community state types (CST) which broadly described their nasal microbiomes.  These 7 types are defined by their most abundant bacteria, and are as follows: CST1 – S. aureus, CST2 - Escherichia spp., Proteus spp., and Klebsiella spp., CST3 - Staphylococcus epidermidis, CST4 - Propionibacterium spp., CST5 - Corynebacterium spp., CST6 - Moraxella spp., and CST7 - Dolosigranulum spp.   The most common CTS was CTS4 with 29% of the sampled population having that CTS, whereas CTS4 was the least popular, coming in at 6% of the individuals tested.  The researchers noted that many of these bacteria, such as Proteus, were not considered to be important to the nasal microbiome at all, so their dominance in some noses was surprising.  The scientists learned that genetics plays nearly no role in the microbiome community composition, but does influence the overall microbiome population.  In addition, gender influenced the overall population, with women having about half as many total bacteria in their noses as men.

With regards to S. aureus, while it existed in 56% of the individuals studied, it was associated with other bacterial.   For example, the researchers discovered that Dolosigranulum, and Propionibacterium granulosum were negatively correlated to the existence of S. aureus, whereas S. epidermidis was positively correlated with S. aureus abundance.  This lends itself to the idea that specific bacteria can create colonization resistance against S. aureus, and thus could be used to prevent the disease.  The researchers suggest a probiotic should be tested for its therapeutic value in preventing S. aureus colonization, and hopefully they move forward with those trials.

New test developed that rapidly profiles the human virome

Molecular representation of an antibody (green) binding with an HIV virus (red and yellow).

The viruses that live in our body may be just as important to our health and development as their bacterial counterparts.  Unfortunately, testing which ones currently exist, or have at point infected us is expensive, time consuming, and laborious using current techniques.  Making matters worse, these techniques, which usually rely on measuring the amount of antibodies against specific viruses that exist in our blood, are often times ineffective when the antibodies are in low levels.  Recently though, scientists from Harvard University developed a new technique that can accurately, rapidly, and inexpensively (~$25) screen for the existence of over 200 viral antibodies in less than a drop of blood.  They call their technique VirScan, and they published their method last week in Science.

The scientists combined two advanced biological screening tools to create their method: DNA microarray synthesis and phage display.  In short, the scientists created libraries of peptides that represented 206 known human viruses, like HIV and influenza, and expressed them on simple bacteriophages.  They then combined these bacteriophages with a drop of blood, which itself contains antibodies that combat viruses that someone currently has, or has been infected from in the past.  The antibodies that exist specifically bind to the phages that represent a virus.  They then eliminate all the phages not bound to antibodies, and measuring what remains gives the scientist an indication of which antibodies were in the blood.  This explanation of the researchers’ technique may not satisfy our more curious readers, so those that wish to learn more should definitely check out the paper. When the scientists screened over 500 people using this method, the results showed that most people tested positive on average for 10 viruses (i.e. they had antibodies against these viruses).  Interestingly, 2 individuals tested positive for 84/206 viruses.  The most commonly detected virus was Epstein-Barr virus, followed by types of rhinovirus (common cold), and adenovirus.  Also of interest was that the viral structures differed geographically between continents.

This assay has many immediate implications in many areas.  The most obvious is its use as a diagnostic tool for easily screening people for their viruses.  In addition though, by discovering which peptides antibodies efficiently bind to, and how those differ between humans, more effective vaccines can be developed that treat more people.  Also, it should be interesting to discover how infection with certain viruses influences long term health and chronic disease.  For example, were those two individuals that tested positive for antibodies against 84 viruses more, or less healthy than those who tested positive for very few, and whether infection with certain viruses is associated with any chronic conditions.

The placental microbiome

Microbiome populations have been well-characterized in many distinct body-sites.  Interestingly, there is a lack of knowledge in the microbiome of the placenta, an environment that was long thought to be sterile.  Investigating the placenta is important toward understanding the microbiome in human development, especially in light of previous evidence demonstrating that human microbiota populations fluctuate extensively in the first year(s) of life.  The placenta is the cradle of life for fetal development, leading researchers from Baylor School of Medicine to study the microbiome of this tissue.  Placenta samples were collected and analyzed to characterize the placenta microbiome, and explore links to fetal development and microbiome compositions. 

320 placenta specimens were collected, and PCR was used to characterize bacterial populations.  The Meta genome sequencing revealed that the placenta microbiome harbored unique abundances in specific bacteria compared to other body sites.  E. coli in particular had the highest species abundance.  Interestingly, the microbiota populations were most similar to the oral microbiome.  Species such as Prevotella tannerae and Neisseria, known to populate the mouth, were also abundantly present in the placenta.  Further analysis confirmed that the placenta bacteria were indeed most similar to bacteria specifically found in the tongue, tonsils, and gingival plaques. 

The researchers also demonstrated an association between placental microbiome composition and healthy births or births with complications.  Specifically, a significant association was shown between distinct placental microbiome populations and pre-term birth.  Taxa such as Durkholderia were shown to be enriched in the placentas of those who delivered their infants preterm, whereas Paenibacillus was abundant in normal terms placental specimens. 

This study reveals a couple very interesting associations between cross-site microbiome similarities and disruptions in compositions that appeared to be linked to preterm birth.  Although not definitive evidence, these findings could lead to some important research in the future.  There were a few confounding elements to this study, such as other body site samples occurred in non-pregnant subjects, or the fact that the mass of the placental microbiota was particularly low.  However, these findings certainly raise awareness of the uniqueness of the placental microbiome, and what this means in terms of the microbiome entering the developing fetus.  It will be interesting to see what further research can reveal about this relationship. 

The oral microbiome of children, and its relation to dental caries

The oral microbiome is a popular area of exploration because bacteria are a prominent part of dental health, and because it is one of the most heavily colonized and easily accessible niches in the body. Many studies have been discussed on this blog concerning adult oral microbiomes, and its relations to bodily issues such as cystic fibrosis and periodontitis. It is also very useful to investigate children and the ways that their bacterial communities first inhabit and develop. A study done in Sweden at the Umeå University, and published by Plos One, takes a look at the maturation of the oral microbiome from infants at 3 months old to children at 3 years old.

The Swedish researchers performed a longitudinal study that followed children from 3 months to 3 years of age, looking for microbial characteristics of children with dental caries (i.e. cavities) compared to those without. There were 207 original participating 3 month olds that were consented by their parents to be in the study. The parents provided information on mode of feeding, mode of delivery, use of antibiotics or probiotics, health issues like allergies, and presence of teeth. At 3 months and later at 3 years samples were taken from the buccal mucosa, tongue, and alveolar ridges. Teeth were also scraped for plaque and saliva was collected. Of the original 207 participants, 155 returned for sampling at 3 years of age, and 13 of those children had dental caries.

After sequencing the bacterial DNA samples, it was found that Escherichia coli, Staphylococcus epidermidis, and various Pseudomonas species were significantly more prevalent in 3 month olds. However, there were 23 genera that were more significantly prevalent at 3 years of age than at 3 months.

By comparing the children with and without caries, the scientists were able to make several conclusions.  The researchers identified seven taxa that appear to be associated with healthy teeth.  On the other hand, Streptococcus mutans seemed to be more prevalent in the children with caries, than in those without caries. Additionally, the colonization of this species was most prevalent in girls. This is possibly because girls develop faster, so earlier tooth eruption allows for a longer time for the colonization of these bacteria.

The results of this study show us that during the first three years of life, species richness and diversity seems to increase significantly in the mouth. While there is an increase in the type of the bacteria, there are also some taxa that are lost with age. The researchers also concluded that the oral microbial composition of the mouth at 3 months does not appear related to the development of dental caries. With this information, it might be smart to perform a related study that collects oral microbiome samples in children within the time frame of 3 months to 3 years, because it could show a clearer picture of the changes that take place in bacterial composition.