Operating room bacteria colonize infants’ guts after C-sections

Newborns are a great study subject in the field of microbiology, because scientists are still discovering how the microbiome develops and what factors affect it. In human infants, it has been proven that vaginal birth exposes infants to bacteria that are different from those received by the mother through C-section. Babies born by vaginal delivery have gut bacteria correlated with vaginal bacteria, while babies born by C-section have gut bacteria correlated with human skin bacteria. For babies born by C-section, the sources of the human skin microbes that are acquired are still unknown.  In a study published by Microbiome, a group of scientists tested the hypothesis that the operating room environment contains human skin bacteria that could be seeding the gut microbiome of C-section born babies.

To test their hypothesis, the researchers collected samples from 11 sites in four operating rooms from three hospitals in New York City, NY and San Juan, PR. Of the 44 operating room samples that were collected, 68% of the samples contained a sufficient number of bacterial DNA samples for sequence analysis. After analyzing the bacteria collected, it was found that all samples contained human skin bacteria, with Staphylococcus and Corynebacterium being the greatest in quantity. Lamps on the operating bed and baby crib showed higher abundances of these bacteria relative to the other sampling sites. The scientists confirmed that the samples collected were more similar to human skin microbiota than other body sites, by comparing the samples to oral, fecal, and vaginal database samples.       

Even though operating rooms are supposed to be spotlessly clean and germ-free, this study shows that there are still dust particles containing human skin, and therefore human skin microbiota, samples. These samples could be from people moving in and out of the operating room during a C-section, or it could come from the people cleaning the OR. Either way, the human skin bacteria in the operating room most-likely are what influences the infant’s developing gut microbiome. 

Regulatory T cells help tolerate commensal bacteria on the skin during first few weeks of life

The human skin is the body’s first line of defense against pathogens that your body comes in contact with. Just like the gut and mouth, the skin lives in communion with bacteria. One important unanswered question that many scientists have is why commensal bacteria do not trigger an inflammatory immune response when they come in contact with the skin. An article published by Cell Press explores exactly this question, looking specifically at regulatory T cells (treg, a type of white blood cell that plays a major role in establishing homeostasis of the immune system).

Researchers engineered the genes of Staphylococcus epidermidis to produce a specific protein antigen that can be fluorescently viewed. To test whether the immune system plays a role in tolerance of skin commensal bacteria the researchers colonized the skin of 6-week-old mice with this fluorescent protein. Three weeks later the mice were compared to a group of control mice and it was found that pre-colonization with the protein was not enough to establish immune tolerance of the bacterial antigens. 

The researchers were curious as to what affect this bacterial antigen on the skin of infant mice had, so the same experiment was done with 7-day-old mice. After 3-4 weeks, when the mice were adult, a significantly diminished immune response to the commensal bacteria could be seen. This shows that exposure during the neonatal period promotes tolerance to commensal bacteria.

After examining adult vs. neonatal skin, this study concludes that there is a difference between the two in terms of immune response and windows of tolerance build-up. Specifically, the period of neonatal skin development seems to be essential in mice for the immune tolerance of commensal bacteria. The implications of this study are important for understanding of the human immune system and bacteria tolerance. Because the skin is our body’s first defense system, it is important to have an understanding as to what mediates its immune response.           

Emidermolysis bullosa, a severe skin disorder, may be influenced by skin microbiome

Epidermolysis bullosa (EB) is a terrible hereditary disease that results in blistering skin and can become so severe that the skin falls off the body (I highly recommend that you do not search for images of the disease, really). Severity levels vary but this disease can be lethal and the age of death is often very young. While recently many stem cell research advancements have been made bringing new treatments to young patients, treatments for the disease are lacking and a full understanding of the disease is not complete.

EB is a disease that is characterized by antibodies that target type VII collagen (COL7), an important part of the skin. In previous experiments, when mice are immunized for COL7, skin blisters result in 80% of the mice however 20% of mice remain healthy. To look at why this happened, scientists in Germany looked at the innate and adaptive immune response of mice that were healthy and compared this to the mice that became sick after immunization and published the results in the Journal of Autoimmunity.

They studied the skin microbiome of the mice by taking a biopsy prior to immunization because the skin microbiome has been shown to influence cutaneous inflammation. One of the major findings was that in the mice that did not develop the clinical symptoms of EB, there was greater richness and diversity of the skin microbiome before immunization. This showed that the results of the experiment could have been predicted prior to experimentation and therefore is an important factor in future studies looking at the transition from autoimmunity to the onset of autoimmune disease.

These results also lead us to the conclusion that it may be possible to prevent or reduce clinical inflammation in autoimmune disease by influencing the skin microbiome. 

Episode 9 of The Microbiome Podcast: The skin microbiome and AOBiome with Dr. Larry Weiss

On the ninth episode of The Microbiome Podcast, we talked with Dr. Larry Weiss, Chief Medical Officer of AOBiome.  AOBiome is a leading company based in Cambridge, MA that is developing treatments for inflammatory skin conditions. They also have a cosmetic product on the market that consists of Ammonia Oxidizing Bacteria that the user applies to the skin twice a day. We discuss both the cosmetic product as well as AOBiome’s approach to treating skin conditions with Dr. Weiss. 

AOBiome is offering listeners of The Microbiome Podcast a 25% discount if you order their product before June 29th. The discount code is ami25. Click here to learn more about the product.

Also, as we discussed on last week’s podcast, the AMI is sponsoring a citizen science project where individuals can sequence their vaginal or penile microbiome. To be entered to win a free sampling, enter your information here. 

Remember to call in to ask any questions about the microbiome that you would like answered on future podcasts. The number is 518-945-8583. 

Listen to the podcast on our website, on iTunes, or on Stitcher. 

For more detailed shownotes, read below:

On this week’s podcast we discussed:

• (2:00) Ritter Pharmaceuticals, a microbiome pharmaceutical company that is working on an oral therapy for reducing lactose intolerance symptoms, filed for a $17 million IPO and is becoming a public company. Read more. 
• (2:30) Seres Health, a microbiome company working on a therapeutic for treating Clostridium difficile infection, also filed for an IPO for $100 million and received Breakthrough status from the FDA. Read more.
• (4:55) A study out of NYU found that wearing contact lenses altered the eye microbiome compared to non-contact wearers. Read the abstract. 
• (9:31) We talked a bit about AOBiome. Learn more about AOBiome. www.aobiome.com
• (11:17) Dr. Larry Weiss gave an overview of the skin microbiome and ammonia oxidizing bacteria.
• (13:22) An article out of NYU (led the same scientist who led the contact lens study) that studied a group of aboriginal Amerindians and found that they had perfect skin and still contained ammonia oxidizing bacteria on the skin. Read our blog post about the study. 
• (16:34) Dr. Weiss discussed the goals of AOBiome and how they are approaching the skin microbiome.
• (18:55) AOBiome’s cosmetic product that applies ammonia oxidizing bacteria to the skin. Learn more about the product. There is a discount code for our listeners for 25% off - ami25. 
• (26:00) Larry mentioned a Ted Talk about combatting smelly armpits. Watch the TED Talk. 
• (29:18) AOBiome’s therapeutic research areas and specifically acne.
• (32:25) Eczema and how the microbiome could be used to treat the condition.
• (39:15) Bacterial vaginosis and AOBiome’s approach to this infection.
• (42:51) Larry’s career going from a company called CleanWell, an antimicrobial company, to AOBiome, a company that administers bacteria to the body.
• (45:25) Hang hygiene and hand washing and Larry mentioned a study from the US Navy that found washing hands lowered the risk for getting a respiratory illness. Read the study.
• (50:16) On the aftershow, we discussed hand washing, whether we wear glasses or contacts, and Lebron James and the NBA finals.

The maturation of the microbiome during the first year of life

Dr. Jeffrey Gordon recently published a review article describing the importance of the proper development of the microbiome in the early stages of life.  One paper that certainly would have made it into the review if it was published in time is a new paper published last week out of Sweden and China that studied the developing microbiome of children over the course of their first year of life.

The team of scientists studied 98 women and their newborn babies. They sequenced the mother’s stool, the newborns stool, and again the child’s stool at 4 and 12 months. Throughout the study, because they used a technique called shotgun sequencing, they identified 4,000 new microbial genomes.

The infants in the study were breastfed for varying amounts of time with some never being breastfed at all. The researchers found that breastfeeding and the timeline of cessation of breastfeeding was critical to driving microbiome development. Many had previously hypothesized that it was the time at which solid foods were introduced was most important for microbiome development, however this study found that it was the time at which breastfeeding was stopped. Children that stopped breastfeeding earlier had microbiomes more similar to adults at 12 months while children who were breastfed for the duration of the study continued to have microbiomes dominated by Bifidobacterium and Lactobacillus.

The scientists also found that the 15 babies born via C-section had different microbiomes than the other 83 babies studied.  The infants born via C-section had microbiomes that more closely resembled skin and mouth microbial communities while the babies born vaginally had microbiomes more closely resembling the bacteria in their mother’s stool.

We still don’t know exactly what a “healthy” microbiome looks like and which microbial profile is best for the child. This study provides a very solid experimental design to study the development of the microbiome and allows for the continued monitoring of these children’s microbial development over the course of their lives. 

Using microbiome bacteria for cosmetics

Topical cosmetics are widely used for skin care, maintenance, and beauty.  There are entire industries dedicated to providing skin care products to a wide range of consumers, because for the most part, everyone desires healthy skin.  Scientifically speaking, skin is considered healthy if it effectively retains moisture, has a low surface acidity, and has good texture.  Many topical cosmetics act to augment or support these features.  Interestingly, researchers in Japan demonstrated that a microbiome bacterium can also provide these benefits to the skin, introducing the possibility of developing novel skin care therapy.

Staphylococcus epidermis has recently gained attention as a beneficial topical agent due its demonstrated skin care benefits.  Specifically, its metabolic products have been shown to enhance moisture retention and reduce surface acid levels.  Researchers investigated this by creating their own S. epidermidis topic gel and testing it on human subjects in a double-blind randomized study.  Skin was collected from the foreheads of 21 patients enrolled in this clinical trial.  Genetic analysis confirmed that S. epidermidis was removed from the skin.  Once isolated from other cells and bacteria, the S. epidermidis bacteria were cultured and lyophilized – or freeze dried – to preserve bacterial integrity.  The lyophilized S. epidermidis was then mixed in with a gel and continuously applied to patients’ faces in a double blind randomized clinical trial study that included a control population just receiving the gel, no bacteria. 

Patients who received the S. epidermidis had 1.4 times the amount of water in their skin after the trial was completed compared to before they started.  Additionally, a suppression of water evaporation on the skin surface was shown, concomitant to an increase in lipid content.  The increased lipid content was hypothesized to be a direct result of S. epidermidis metabolism, as the lipid metabolites provided an ample surface coat to keep moisture trapped on the skin surface.  Moreover, the S. epidermidis regiment also maintained a low acidic environment on the skin surface.

This study demonstrates S. epidermidis’s efficacy to support healthy skin.  Using certain microbiota as a topical agent is already being seen in practice, as Cambridge-based AOBiome are developing skin therapies using bacteria.  This unique approach has a lot of potential, and it will be interesting to see how bacteria can be used in this health arena.