ED Guidebook2020_21Digital

Exploring the viruses naturally living in human intestines The human gut microbiome, made up of trillions of microorganisms such as bacteria, viruses and fungi, is known to affect how the hu- man body functions, both in health and disease. While our knowledge of the gut bacterial microbiome has grown exponentially over the past decade, there is very little known about the gut viral microbiome, or virome. A recent study published in Cell Host & Microbe set out to characterize the gut virome over time in several individuals in hopes of constructing a baseline virome for future studies. Scientists sequenced viral nucleic acids from fecal samples collected from 10 adults every month for a year. From these samples, the scien- tists determined that individual gut viromes did not change much over time. In addition, the team found that each individual had a diverse population of viruses in their gut that was different for each person. This study suggests that unlike the bacterial microbiome which is similar between individuals, there is no such thing as a core gut virome. More studies like this one need to be performed in order to establish a baseline of what a healthy human gut virome looks like for individuals living in different areas, with different ethnicities and different lifestyles. The hope is that one day the gut virome can help to diagnose and treat diseases. Approval for Ebola vaccine Vaccines are a critical asset in the fight for the prevention and control of infectious disease outbreaks. They introduce part of the infectious agent, such as a virus, into the body to train the immune system to recognize it and prepare its defenses to protect against disease if exposed. The fight against Ebola virus disease saw a major win last year with both the European Commission and the U.S. Food and Drug Administration (FDA) approving an Ebola virus vaccine called Ervebo. Ebola virus disease is a deadly and highly contagious disease caused by infection from a group of viruses within the genus Ebolavirus . Transmission occurs through direct contact with blood, bodily fluids and tissues of infected wild animals or people. Viral outbreaks occur from time to time mostly in southern African countries where scien- tists believe the virus is always present at low levels in wild animals. The Ervebo vaccine contains a live but weakened piece of the Zaire ebolavirus, the strain currently ravaging the Democratic Republic of the Congo. Starting in 2018, the World Health Organization (WHO) began using Ervebo, then an investigational vaccine, to help mitigate the outbreak. The vaccine is highly effective, with the WHO reporting that the vaccine protects 97.5 percent of people who receive it. The approval of Ervebo by multiple regulatory organizations represents a critical milestone in public health preparedness and response. REFERENCES: European Commission. Vaccine against Ebola: Commission grants first-ever market authorisation. 11 November 2019. Web. 31 August 2020. https://ec.eu- ropa.eu/commission/presscorner/detail/en/IP_19_6246. U.S. Food and Drug Administration. First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response. 19 December 2019. Web. 31 August 2020. https://www.fda.gov/news-events/ press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-dis- ease-marking-critical-milestone-public-health.

NEW FINDINGS — BACTERIA AND VIRUSES Managing microbes on masterpieces Preserving artwork is a full-time job and requires museums and collectors to employ methods such as reducing moisture, adjusting the type of lighting and preventing mold. Even with such careful

The measles vaccine protects against more than measles Measles is one of the most contagious diseases known to mankind, killing an av- erage of 2.6 million people each year before the devel- opment of a vaccine. Wide-

Deciphering the chemistry of body odor We’ve all probably walked into a crowded gym or

measures in place, the fate of timeless pieces of art from the likes of Michelangelo, Picasso and Renoir could be in the hands of a microscopic foe: bacteria. A recent study suggests that identifying and managing the communities of microbes on art could provide a more effective preservation method. Researchers swabbed the surface of centuries-old, Renais- sance-style art housed in a private art collection in Florence, Italy. They performed 16S ribosomal RNA (16S rRNA) gene sequencing to identify, classify and quantify different microbes within the sam- ples. 16S rRNA codes for part of the bacterial ribosome and can be used to identify types of bacteria in a mixed sample. A potential microbial culprit for the degradation of paintings was found in some of the samples. These “oxidase positive” microbes eat organic material in or on the art and produce water and hydro- gen peroxide which also contribute to mold and decay. Reducing the abundance of these bacteria could improve preservation and restoration methods. In addition to art preservation, identifying the microbial diversity on artwork can also help uncover counterfeit art by determining if the bacterial compositions are the same between art from a similar region. REFERENCE: Torralba, M.G. et al. Characterizing microbial signatures on sculp- tures and paintings of similar provenance. Microbial Ecology . (2020) doi: 10.1007/ s00248-02-01504-x.

sporting facility and caught a whiff of the generally unpleasant, characteristic smell of body odor. To avoid being the culprit, many of us rely on deodorant to keep our body odor at bay. And now scientists believe they are one step closer to making a more effective deodorant. When bacteria that reside on the skin break down acids from sweat, they produce body odor molecules such as thioalcohols and volatile fatty acids. Researchers from the University of York, in collaboration with Unilever ® , previously reported that only a small subset of the bacteria living on our skin actually contributes to body odor. Although the researchers identified the odor produc- ing bacterial species (a group of Staphylococcus) , the manner in which they produce body odor molecules was still unknown. In a continuation of their previous work, the researchers recently reported the discovery of a unique enzyme within these bacteria that produce thioalcohol. The enzyme, called PatB, cuts thioal- cohol away from a larger precursor molecule, Cys-3M3SH. The researchers inserted PatB into a species of bacteria not involved in body odor production, and the bacteria were able to produce odor molecules. Now that the research group has identified key molecular path- ways in the production of odor molecules, they hope to develop targeted inhibitors to stop body odor production without disrupting the armpit microbiome. REFERENCE: Rudden, M. et al. The molecular basis of thioalcohol production in human body odor. Scientific Reports. (2020) 10:12500 doi: 10.1038/s41598-020- 68860-z. compounds that affect the immune system and other physiologi- cal processes in the body. Dysregulation of the number or type of microbes in the gut has been shown to be involved in autoimmunity, cancer and other diseases. A recent study published in Cell also implicates the gut microbiome in immunity developed after receiving a vaccine. For the study, research- ers recruited people who had not received a flu shot or been infected by the flu in the previous three years. All were given a flu shot, but half were given antibiotics beforehand. Not surprisingly, gut bacterial di- versity and number were decreased in people treated with antibiotics, because some of the bacteria in the gut were killed by the antibiotic. Along with this alteration in gut microbes, the people treated with an- tibiotics produced fewer flu-specific antibodies, the proteins that help prevent future infection with the flu, than those who did not receive an antibiotic treatment. The study suggests that the microbial community in the gut influ- ences vaccine immunity, although the exact mechanism is unknown. In the future, the scientists involved in the study want to understand more about the mechanism by which the microbes control immune responses to vaccination in the hopes of increasing the effectiveness of vaccines. REFERENCE: Hagan, T. et al. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell ( 2019) 178:1313-1328 doi: 10.1016/j. cell.2019.08.010.

spread vaccination in the early 2000’s led to a sharp decline in the number of deaths attributable to measles. However, lack of access to vaccinations and the refusal to vaccinate has led to an increased rate of cases, with almost three times as many cases reported worldwide in 2019 compared to the previous year. This decline in vaccination rate is especially concerning to many in the medical field because there is strong evidence that by preventing measles, the vaccine also preserves the body’s immunity to other infectious diseases. It has long been observed that survivors of the measles often have a diminished immunity that leaves them vulnerable to infection by other pathogens, although the reason behind this phenomenon is poorly understood. Two research groups set out to determine why measles survivors lose immunity to patho- gens they had previously acquired through illness or through vaccination. Scientists at Harvard University examined blood samples from 77 unvaccinated children before and after natural measles infections. The scientists were looking at the children’s antibody repertoire, or the presence of antibodies against more than 400 viral and bacterial pathogens. They found that after measles in- fection, antibody diversity drastically decreased. In some cases, infected children lost between 11 percent and 73 percent of the antibodies they had prior to infection. A second, independent study

published in Science Immunology also supports the importance of the measles vaccine to a child’s overall immunity. Using mea- sles-like virus in ferrets, the researchers showed that resistance to the flu was lost in ferrets as a result of the measles-like infection. Both studies point to the impor- tance of the measles vaccine not only to avoid a potentially deadly in- fection with measles virus, but also to prevent the loss of immunity to other pathogens that a child has built up throughout their lifetime.

The link between gut bacteria and vaccine effectiveness Did you know the inner space of your gastrointestinal (GI) tract is actually outside of the body? Food, pathogens and other potentially damaging material pass through the GI tract on a daily basis. The intestinal barrier system keeps harmful things out of the body and allows good nutrients and substances to enter through cells in the intestinal lining. The intestinal barrier system includes the physical barrier of a mucus layer and intestinal epithelial cells, along with a heavy immune system presence. In fact, about 70-80 percent of the human immune system resides in the GI tract. The GI tract is also home to trillions of microbes, called the gut mi- crobiome. The immune system co-exists with the “friendly” microbes to maintain health and protect against colonization by unwanted microbes. Resident microbes in the gut produce many products and

REFERENCES: Mina, M.J. et al. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science . (2019) 366:599- 606 doi: 10.1126/science.aay6485. Petrova, V.N. et al. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. (2019) Science Immunology . 4:eaay6125 doi: 10.1126/sciimmunol.aay6125.

REFERENCE: Shkoporov, A.N. et al. The human gut virome is highly diverse, stable, and individual specific. Cell Host & Microbe . (2019) 26:527-541 doi: 10.1016/j.chom.2019.09.009.

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