BioQuakes

AP Biology class blog for discussing current research in Biology

Author: helenogenous

Gut Microbes Help to Advance Flu Vaccines

Beneficial Gut Bacteria

This September, a potentially monumental study was published in the scientific journal, Cell, reporting that researchers have confirmed that microbes present in the gut can change, lower, or jumpstart our immune response.  Previously research has only been done with other mammals such as mice, and this was the first study that linked the results to human subjects. Since most previous trials were conducted on other animals, researchers such as Dan Littman who studies microbiota at NYU School Of Medicine, emphasized there are likely to be large differences in the results for humans versus other animals.   

Specifically, researchers found that people who have not received a flu shot or had the flu within the past 3 years and then were administered broad spectrum antibiotics, produced lower levels of antibodies to the influenza virus. Those subjects who did not receive the antibiotics produced more antibodies to the flu virus. This publication is so noteworthy because previously so little actual human clinical trials were performed to understand the role of the human gut microbiome and its relationship to the strength of our immune response.  

Previous research on how the flu vaccine works and its varying efficiency among many people has been done.  In 2011, Bali Pulendran, an immunologist at Stanford University, found that increased activity in the gene receptor that recognizes the bacterial protein flagellin, the core part flagella, seemed to stand out as the one major change among how well the flu shot was working in varying groups of people.  This underscores the connection between the immune system’s recognition of bacteria (especially gut microbes) and  how well people may respond to the flu vaccine.  

In 2014, this research was followed by gene knockouts being given to mice for the receptor for bacterial flagellin in the flu shot.  The results showed that the mice who received the knockouts made were antibodies than the control mice in the trial.  The researchers suspected this reduction was controlled by the absence or presence of gut microbes and their ability to sense flagellin.  To confirm this, researchers followed up with separate trial in which mice’s microbiota were reduced by the administration of antibiotics before receiving the flu vaccine and control mice who did not receive the antibiotics so their microbiomes remained present.  The results again showed a link that gut microbiota play a role in levels of antibodies produced against their flu shot.  Because of these results, it seemed obvious to test the same situation with humans. 

The current study did just that and was designed as a Phase 1 clinical trial to determine if gut microbes are connected to the efficiency of flu vaccine immunity.   11 adults received broad spectrum antibiotics for 5 days and 11 served as the control and did not receive antibodies.  All subjects receive the influenza vaccine on day 4. The people who received the antibiotics had reduced levels of gut microbes.  However, no major difference was observed in response to the vaccine. These results prompted researchers to dig deeper and they next investigated people who had not had the flu shot or suffered from the flu virus within the last 3 years.  They wanted subjects that would be relatively clear of flu antibodies to begin with. They repeat a very similar study with 11 people, 5 receiving the antibiotics and 6 serving as controls. Everyone got the flu vaccine, but this time the results showed a marked difference in vaccine induced immunity.  Subjects who received antibiotics and had fewer microbes presents, made far fewer flu-specific antibodies.   

This research is very promising not only in the field of flu vaccination, but could reveal that changes to microbiota can have profound impacts on future vaccine development for a variety of pathogens.  Because the results were so tiring, Pulendran is continuing to research deeper into the relationship between gut bacteria and vaccines, for viruses that may affect us in the future. This holds promise for development of vaccines for a wide range of pathogens that attack the human race.  

 

Why Healthy People are Dying from Vaping

 

 

 

 

 

 

This article explores the new phenomenon of deaths that have arisen in relatively healthy people linked to vaping or e-cigarette use. Despite the title referring to the victims as “healthy”, there is an inherent contradiction as the people being studied in fact are using vaping as part of the daily lifestyle.  As such, they are exposing themselves to harmful contaminates and toxins including both viscous oils and chemical contaminants present in the vaping liquids that are potentially toxic to the lungs.  The vaping outbreak has led to almost 1,300 lung injuries and 26 deaths as of October 2019.

While the cause of the vaping related illnesses remains a mystery to investigators, numerous potential causes have been proposed.  Two of the major culprits, according to Dr. Michael Siegel a professor at BU School of Public Health, are thought to be either the oils or chemicals found in vaping products.  Regardless of which is the cause, both place an excessive burden on the lungs, resulting in difficulty pulping oxygen to the body tissues. As a result of the reduced oxygen, a variety of symptoms have emerged in the victims, and overall these symptoms have been coined EVALI: E-cigarette or vaping product use associated lung injury.

There are various risks associated with exposure to both the oils and the chemicals present in most vaping products. The oils, such as vitamin E Acetate are often added as thickening agents to black market vaping products which are inherently dangerous as they are not regulated by the FDA. Furthermore, the oils are thought to coat the lungs and as Dr. Siegel points out, our lungs are not designed to handle oil exposure, as the oil coats the air sacs that are needed for gas exchange and thus limit the body’s ability to acquire oxygen. The patients may experience respiratory failure, and as a result require mechanical ventilation in order to be able to breathe sufficiently. Conversely, it is also thought that chemical contaminants may be the primary problem.  Dr. Siegel draws attention to the risks associated with them including “damage to the lungs, which triggers a severe inflammatory response“.

Building on the knowledge that vaping is causing a mysterious outbreak of illnesses and deaths, researchers have taken interest in studying the problem more in depth. Samples were taken from 17 patients throughout the US who suffered from EVALI, and researchers concluded that the lung samples did not indicate that the oils were in fact the primary cause of the disease and symptoms. Instead, the samples showed evidence of injury similar to chemical pneumonitis, which results from inhalation of chemical fumes, and the authors cited in the publication in the New England Journal of Medicine that these chemicals are most likely the cause.  This information can be very promising for future research, as with this knowledge the actual cause of EVALI can be better pinpointed.

The damage found in vaping patients included very severe symptoms, with some patients even experiencing their lung cells falling off from extreme damage. The severity of this damage also led to acute respiratory distress syndrome, which allows materials such as dead cells and blood clotting proteins to enter the lung’s air sacs. The presence of these materials are quite dangerous as they prevent efficient oxygen exchange from occurring. Shockingly, this disease has an extremely high mortality rate and no known cure. This leaves people with the prospect that they may not recover, and as of right now all that can be done is temporary treatment or more importantly prevention in those portions of the population who are not vaping.  Scientists and doctors do not yet know if EVALI and associated acute respiratory distress syndrome is reversible or permanent. Thus, education is key to warn people of these risks so that they can make educated choices when being exposed to the possibility of partaking in vaping. 

 

 

 

Migrating Cancer Invading the Brain

Glioblastoma tumor Credit: The Armed Forces Institute of Pathology [Public domain]

Recent research has unveiled the ability of cancer cells to invade and take over our brain’s neural network. Three independent studies, Monje, Winkler, and Hanahan have indicated that not only can cancer cells metastasize to parts of the body, including the brain, but once present, they have the uncanny ability to “hijack” our brain and incorporate into our neurons.  The research published in Nature discovered this unusual ability in a certain type of brain cancer called gliomas and in specific aggressive breast cancers that are known to spread to the brain, called Triple Negative Breast Cancer. This accidental discovery was “crazy stuff” according to Winkler, and researchers were not only amazed by their findings, but found it difficult to believe.  The implications of the research hold great promise for treating aggressive forms of cancer in the future.

The  first discovery was made by Winkler’s team and supported by Monje, found that synapses in the tumors themselves, specifically in glioma samples, are a type of cancer that is known to be difficult to treat.   Synapses are usually used for neural cell communication, but the discovery of them in tumor cells was novel.  The synapses seem to play a role in allowing the cancer cells to grow and thrive.  This discovery indicates that cancer’s ability to “weave into the brain’s neural network” explains why these cancers have been so difficult to detect early on and treat successfully.  Rather than disrupting the brain’s functions, the tumor incorporates itself into the brain’s normal functions, becoming a stealthy “hijacker”.

In a third study, Hanahan expanded the results from not only brain cancers but also certain types of aggressive breast cancers that are known to spread to the brain.  They found that certain breast cancer cells actually invade the brain and take on a role similar to neurons.  These triple-negative tumors had the uncanny ability to turn on genes that play a role in signaling between neurons.  They specifically found the cancer cells to have the ability in the brain to create a specialized type of synapse that can take in a large amount of Glutamate, one of our brain’s main neurotransmitters.  Glutamate not only functions as a neurotransmitter, relaying signals between neurons, but also seems to play a role in tumor growth.

Lisa Sevenich, a scientist studying brain cancer, emphasized how hostile the brain’s environment is for cancer cells, and the ability of these glioma cells to survive and even thrive in the brain highlights their adaptability and resilience.  Researchers looking forward hoping that these unusual cancer cells may hold promise for new innovative treatments for cancer in the future.

 

 

 

 

 

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