Air Pollution Linked to Alzheimer's and Parkinson’s Damage in Young Brains

While it is well known that air pollution negatively harms lungs and hearts, it could also be affecting the brains of young people.
Tiny air pollution particles make their way up to the brainstems of young people where they accumulate, new research published in the journal Environmental Research showed. These same nanoparticles have been "intimately associated" with the molecular damage that serves as a hallmark for neurodegenerative diseases like Alzheimer's and Parkinson's, The Guardian reported. That linkage could have global implications if confirmed because 90% of people currently live with toxic outdoor air, another Guardian article reported.
Alzheimer's Society defines air pollution as being made up of several different components including gases, chemical compounds, metals and tiny particles known as particulate matter. When we breathe and eat, these nanoparticles enter our bodies and circulate through our bloodstream to the brain, where they can accumulate in the brain stem, The Guardian reported.
The researchers found abundant pollution nanoparticles and evidence of nerve cell growths, plaque and tangles that are linked to neurological disease in the brainstems of 186 young people (ages 11 months to 27 years) from Mexico City who died suddenly, reported First Post.
"The iron-and aluminum-rich nanoparticles found in the brainstem are strikingly similar to those which occur as combustion- and friction-derived particles in air pollution (from engines and braking systems)," said Barbara Maher, part of the research team, reported Science Alert.
In addition to the high presence of particulate matter, the brainstems also showed signs of early and progressive neurovascular nerve damage, First Post reported. The way these particles reacted with brain cells could increase oxidative stress and eventually lead to death of neurons, the report said.
The participants had all experienced lifelong exposure to particulate pollution, Study Finds reported. Brains of similarly-aged people from less-polluted areas did not display the same disease markers, The Guardian reported.
According to CNN, Mexico City has struggled with dangerous air pollution levels for decades. Statista found that the capital city reported an average particulate matter concentration in 2019 more than double the World Health Organization's recommended maximum average concentration. Air pollution rates in the majority of major cities exceed the same safe level of pollution, Alzheimer's Society reported.
Other studies have linked higher pollution levels to increased rates of different mental health diseases and wellness issues. One study similarly found that living in cities with high air pollution put children at higher risk of Alzheimer's and suicide. The researchers in that study also found that Alzheimer's disease started in the brainstem of young urbanites who'd been exposed to high levels of particulate matter and called high pollution levels "a serious health crisis."
Another study linked rising air pollution with increased rates of children's psychiatric diseases.
This latest study takes the correlation one step further. According to The Guardian, it's the first time a physical mechanism, namely the accumulation of nanoparticles in the brain stem, has been observed that can possibly explain why brain damage increases as rates of air pollution go up.
"(O)ur new findings indicate that what air pollutants you are exposed to, what you are inhaling and swallowing, are really significant in development of neurological damage," Maher told Science Alert.
The next step for researchers is to show whether the nanoparticles cause the damage and whether that damage leads to disease later in life.
"We can't prove causality so far, but how could you expect these nanoparticles containing those metal species to sit inert and harmless inside critical cells of the brain?" Maher told The Guardian. "That's the smoking gun – it seriously looks as if those nanoparticles are firing the bullets that are causing the observed neurodegenerative damage."
Maher said that the findings provide a hypothesis that now can be tested by further research. This can be done, for example, by observing whether increased exposure to pollution nanoparticles correlates with brain stem damage that affects movement control and the gait of young people.
According to The Guardian, other experts are cautious about the findings, citing that many other factors can contribute to neurodegenerative diseases. While the scientists say it is still premature to say that the brain damage caused by air pollution directly leads to the development of these diseases, the findings provide a pathway for future research to confirm causation.
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A Healthy Microbiome Builds a Strong Immune System That Could Help Defeat COVID-19
By Ana Maldonado-Contreras
Takeaways
- Your gut is home to trillions of bacteria that are vital for keeping you healthy.
- Some of these microbes help to regulate the immune system.
- New research, which has not yet been peer-reviewed, shows the presence of certain bacteria in the gut may reveal which people are more vulnerable to a more severe case of COVID-19.
You may not know it, but you have an army of microbes living inside of you that are essential for fighting off threats, including the virus that causes COVID-19.
How Do Resident Bacteria Keep You Healthy?
<p>Our immune defense is part of a complex biological response against harmful pathogens, such as viruses or bacteria. However, because our bodies are inhabited by trillions of mostly beneficial bacteria, virus and fungi, activation of our immune response is tightly regulated to distinguish between harmful and helpful microbes.</p><p>Our bacteria are spectacular companions diligently helping prime our immune system defenses to combat infections. A seminal study found that mice treated with antibiotics that eliminate bacteria in the gut exhibited an impaired immune response. These animals had low counts of virus-fighting white blood cells, weak antibody responses and poor production of a protein that is vital for <a href="https://doi.org/10.1073/pnas.1019378108" target="_blank">combating viral infection and modulating the immune response</a>.</p><p><a href="https://doi.org/10.1371/journal.pone.0184976" target="_blank" rel="noopener noreferrer">In another study</a>, mice were fed <em>Lactobacillus</em> bacteria, commonly used as probiotic in fermented food. These microbes reduced the severity of influenza infection. The <em>Lactobacillus</em>-treated mice did not lose weight and had only mild lung damage compared with untreated mice. Similarly, others have found that treatment of mice with <em>Lactobacillus</em> protects against different <a href="https://doi.org/10.1038/srep04638" target="_blank" rel="noopener noreferrer">subtypes of</a> <a href="https://doi.org/10.1038/s41598-017-17487-8" target="_blank" rel="noopener noreferrer">influenza</a> <a href="https://doi.org/10.1371/journal.ppat.1008072" target="_blank" rel="noopener noreferrer">virus</a> and human respiratory syncytial virus – the <a href="https://doi.org/10.1038/s41598-019-39602-7" target="_blank" rel="noopener noreferrer">major cause of viral bronchiolitis and pneumonia in children</a>.</p>Chronic Disease and Microbes
<p>Patients with chronic illnesses including Type 2 diabetes, obesity and cardiovascular disease exhibit a hyperactive immune system that fails to recognize a harmless stimulus and is linked to an altered gut microbiome.</p><p>In these chronic diseases, the gut microbiome lacks bacteria that activate <a href="https://doi.org/10.1126/science.1198469" target="_blank" rel="noopener noreferrer">immune cells</a> that block the response against harmless bacteria in our guts. Such alteration of the gut microbiome is also observed in <a href="https://doi.org/10.1073/pnas.1002601107" target="_blank" rel="noopener noreferrer">babies delivered by cesarean section</a>, individuals consuming a poor <a href="https://doi.org/10.1038/nature12820" target="_blank" rel="noopener noreferrer">diet</a> and the <a href="https://doi.org/10.1038/nature11053" target="_blank" rel="noopener noreferrer">elderly</a>.</p><p>In the U.S., 117 million individuals – about half the adult population – <a href="https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/" target="_blank" rel="noopener noreferrer">suffer from Type 2 diabetes, obesity, cardiovascular disease or a combination of them</a>. That suggests that half of American adults carry a faulty microbiome army.</p><p>Research in my laboratory focuses on identifying gut bacteria that are critical for creating a balanced immune system, which fights life-threatening bacterial and viral infections, while tolerating the beneficial bacteria in and on us.</p><p>Given that diet affects the diversity of bacteria in the gut, <a href="https://www.umassmed.edu/nutrition/melody-trial-info/" target="_blank" rel="noopener noreferrer">my lab studies show how diet can be used</a> as a therapy for chronic diseases. Using different foods, people can shift their gut microbiome to one that boosts a healthy immune response.</p><p>A fraction of patients infected with SARS-CoV-2, the virus that causes COVID-19 disease, develop severe complications that require hospitalization in intensive care units. What do many of those patients have in common? <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm" target="_blank" rel="noopener noreferrer">Old age</a> and chronic diet-related diseases like obesity, Type 2 diabetes and cardiovascular disease.</p><p><a href="http://doi.org/10.1016/j.jada.2008.12.019" target="_blank" rel="noopener noreferrer">Black and Latinx people are disproportionately affected by obesity, Type 2 diabetes and cardiovascular disease</a>, all of which are linked to poor nutrition. Thus, it is not a coincidence that <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6933e1.htm" target="_blank" rel="noopener noreferrer">these groups have suffered more deaths from COVID-19</a> compared with whites. This is the case not only in the U.S. but also <a href="https://www.washingtonpost.com/world/europe/blacks-in-britain-are-four-times-as-likely-to-die-of-coronavirus-as-whites-data-show/2020/05/07/2dc76710-9067-11ea-9322-a29e75effc93_story.html" target="_blank" rel="noopener noreferrer">in Britain</a>.</p>Discovering Microbes That Predict COVID-19 Severity
<p>The COVID-19 pandemic has inspired me to shift my research and explore the role of the gut microbiome in the overly aggressive immune response against SARS-CoV-2 infection.</p><p>My colleagues and I have hypothesized that critically ill SARS-CoV-2 patients with conditions like obesity, Type 2 diabetes and cardiovascular disease exhibit an altered gut microbiome that aggravates <a href="https://theconversation.com/exercise-may-help-reduce-risk-of-deadly-covid-19-complication-ards-136922" target="_blank" rel="noopener noreferrer">acute respiratory distress syndrome</a>.</p><p>Acute respiratory distress syndrome, a life-threatening lung injury, in SARS-CoV-2 patients is thought to develop from a <a href="http://doi.org/10.1016/j.cytogfr.2020.05.003" target="_blank" rel="noopener noreferrer">fatal overreaction of the immune response</a> called a <a href="https://theconversation.com/blocking-the-deadly-cytokine-storm-is-a-vital-weapon-for-treating-covid-19-137690" target="_blank" rel="noopener noreferrer">cytokine storm</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2" target="_blank" rel="noopener noreferrer">that causes an uncontrolled flood</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2" target="_blank" rel="noopener noreferrer">of immune cells into the lungs</a>. In these patients, their own uncontrolled inflammatory immune response, rather than the virus itself, causes the <a href="http://doi.org/10.1007/s00134-020-05991-x" target="_blank" rel="noopener noreferrer">severe lung injury and multiorgan failures</a> that lead to death.</p><p>Several studies <a href="https://doi.org/10.1016/j.trsl.2020.08.004" target="_blank" rel="noopener noreferrer">described in one recent review</a> have identified an altered gut microbiome in patients with COVID-19. However, identification of specific bacteria within the microbiome that could predict COVID-19 severity is lacking.</p><p>To address this question, my colleagues and I recruited COVID-19 hospitalized patients with severe and moderate symptoms. We collected stool and saliva samples to determine whether bacteria within the gut and oral microbiome could predict COVID-19 severity. The identification of microbiome markers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment.</p><p><a href="https://doi.org/10.1101/2021.01.05.20249061" target="_blank" rel="noopener noreferrer">We demonstrated</a>, in a paper which has not yet been peer reviewed, that the composition of the gut microbiome is the strongest predictor of COVID-19 severity compared to patient's clinical characteristics commonly used to do so. Specifically, we identified that the presence of a bacterium in the stool – called <em>Enterococcus faecalis</em>– was a robust predictor of COVID-19 severity. Not surprisingly, <em>Enterococcus faecalis</em> has been associated with <a href="https://doi.org/10.1053/j.gastro.2011.05.035" target="_blank" rel="noopener noreferrer">chronic</a> <a href="https://doi.org/10.1016/S0002-9440(10)61172-8" target="_blank" rel="noopener noreferrer">inflammation</a>.</p><p><em>Enterococcus faecalis</em> collected from feces can be grown outside of the body in clinical laboratories. Thus, an <em>E. faecalis</em> test might be a cost-effective, rapid and relatively easy way to identify patients who are likely to require more supportive care and therapeutic interventions to improve their chances of survival.</p><p>But it is not yet clear from our research what is the contribution of the altered microbiome in the immune response to SARS-CoV-2 infection. A recent study has shown that <a href="https://doi.org/10.1101/2020.12.11.416180" target="_blank" rel="noopener noreferrer">SARS-CoV-2 infection triggers an imbalance in immune cells</a> called <a href="https://doi.org/10.1111/imr.12170" target="_blank" rel="noopener noreferrer">T regulatory cells that are critical to immune balance</a>.</p><p>Bacteria from the gut microbiome are responsible for the <a href="https://doi.org/10.7554/eLife.30916.001" target="_blank" rel="noopener noreferrer">proper activation</a> <a href="https://doi.org/10.1126/science.1198469" target="_blank" rel="noopener noreferrer">of those T-regulatory</a> <a href="https://doi.org/10.1038/nri.2016.36" target="_blank" rel="noopener noreferrer">cells</a>. Thus, researchers like me need to take repeated patient stool, saliva and blood samples over a longer time frame to learn how the altered microbiome observed in COVID-19 patients can modulate COVID-19 disease severity, perhaps by altering the development of the T-regulatory cells.</p><p>As a Latina scientist investigating interactions between diet, microbiome and immunity, I must stress the importance of better policies to improve access to healthy foods, which lead to a healthier microbiome. It is also important to design culturally sensitive dietary interventions for Black and Latinx communities. While a good-quality diet might not prevent SARS-CoV-2 infection, it can treat the underlying conditions related to its severity.</p><p><em><a href="https://theconversation.com/profiles/ana-maldonado-contreras-1152969" target="_blank">Ana Maldonado-Contreras</a> is an assistant professor of Microbiology and Physiological Systems at the University of Massachusetts Medical School.</em></p><p><em>Disclosure statement: Ana Maldonado-Contreras receives funding from The Helmsley Charitable Trust and her work has been supported by the American Gastroenterological Association. She received The Charles A. King Trust Postdoctoral Research Fellowship. She is also member of the Diversity Committee of the American Gastroenterological Association.</em></p><p><em style="">Reposted with permission from <a href="https://theconversation.com/a-healthy-microbiome-builds-a-strong-immune-system-that-could-help-defeat-covid-19-145668" target="_blank" rel="noopener noreferrer" style="">The Conversation</a>. </em></p>By Jeff Masters, Ph.D.
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