tag:theconversation.com,2011:/us/topics/virome-52498/articlesVirome – The Conversation2022-04-07T18:01:21Ztag:theconversation.com,2011:article/1805452022-04-07T18:01:21Z2022-04-07T18:01:21ZResearchers identified over 5,500 new viruses in the ocean, including a missing link in viral evolution<figure><img src="https://images.theconversation.com/files/456226/original/file-20220404-30985-wxhz3g.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1732%2C1732&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There are even more types of viruses in the ocean than researchers once thought.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/virus-background-image-royalty-free-illustration/1017333858">newannyart/iStock via Getty Images Plus</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
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<a href="https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="From species up to kingdom, a depiction of taxonomic rank." src="https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=550&fit=crop&dpr=1 600w, https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=550&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=550&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=691&fit=crop&dpr=1 754w, https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=691&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/456726/original/file-20220406-23-4w4h4k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=691&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Diagram of the biological classification system, showing phylum is a broad grouping.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/classification-system-vector-illustration-royalty-free-illustration/1185111143">VectorMine/iStock via Getty Images Plus</a></span>
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<p>An analysis of the genetic material in the ocean has identified thousands of previously unknown RNA viruses and doubled the number of phyla, or biological groups, of viruses thought to exist, according to a new study <a href="https://scholar.google.com/citations?user=-q2s8nYAAAAJ&hl=en">our</a> <a href="https://scholar.google.com/citations?user=SO8JQsgAAAAJ&hl=en">team</a> <a href="https://scholar.google.com/citations?user=GNLkdsIAAAAJ&hl=en">of</a> <a href="https://scholar.google.com/citations?user=rYg4wbcAAAAJ&hl=en">researchers</a> has published in the journal <a href="https://science.org/doi/10.1126/science.abm5847">Science</a>.</p>
<p><a href="https://dx.doi.org/10.1016%2FB978-0-12-803109-4.00010-6">RNA viruses</a> are best known for the <a href="https://www.scientificamerican.com/article/how-coronaviruses-cause-infection-from-colds-to-deadly-pneumonia1/">diseases</a> they cause in people, ranging from the common cold to COVID-19. They also infect <a href="https://www.apsnet.org/edcenter/disandpath/viral/pdlessons/Pages/TobaccoMosaic.aspx">plants</a> and <a href="https://dx.doi.org/10.1099%2Fvir.0.2008%2F002089-0">animals</a> important to people. </p>
<p>These viruses carry their genetic information in RNA, rather than DNA. RNA viruses <a href="https://doi.org/10.1371/journal.pbio.3000003">evolve at much quicker rates</a> than DNA viruses do. While scientists have cataloged <a href="https://doi.org/10.1016/j.cell.2019.03.040">hundreds of thousands of DNA viruses</a> in their natural ecosystems, RNA viruses have been relatively unstudied.</p>
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<a href="https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Line drawing of marine RNA viruses" src="https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=488&fit=crop&dpr=1 600w, https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=488&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=488&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=613&fit=crop&dpr=1 754w, https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=613&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/456437/original/file-20220405-24-wjjhl1.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=613&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There are more RNA viruses in the oceans than researchers previously thought.</span>
<span class="attribution"><span class="source">Guillermo Domínguez Huerta</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>Unlike humans and other organisms composed of cells, however, viruses lack unique short stretches of DNA that could act as what researchers call a <a href="https://dx.doi.org/10.1073%2Fpnas.0800476105">genetic bar code</a>. Without this bar code, trying to distinguish different species of virus in the wild can be challenging. </p>
<p>To get around this limitation, we decided to identify the gene that codes for a <a href="https://dx.doi.org/10.3390%2Fv10020076">particular protein</a> that allows a virus to replicate its genetic material. It is the only protein that all RNA viruses share, because it plays an essential role in how they propagate themselves. Each RNA virus, however, has small differences in the gene that codes for the protein that can help distinguish one type of virus from another.</p>
<p>So we screened a global database of RNA sequences from plankton collected during the four-year <a href="https://fondationtaraocean.org/en/home/">Tara Oceans expeditions</a> global research project. Plankton are any aquatic organisms that are too small to swim against the current. They’re a vital part of ocean food webs and are common hosts for RNA viruses. Our screening ultimately identified over 44,000 genes that code for the virus protein.</p>
<p>Our next challenge, then, was to determine the evolutionary connections between these genes. The more similar two genes were, the more likely viruses with those genes were closely related. Because these sequences had evolved so long ago (possibly <a href="https://dx.doi.org/10.4161%2Fmge.22797">predating the first cell</a>), the genetic signposts indicating where new viruses may have split off from a common ancestor had been lost to time. A form of artificial intelligence called machine learning, however, allowed us to systematically organize these sequences and detect differences more objectively than if the task were done manually. </p>
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<a href="https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Swarm plot of the 5 phyla of RNA viruses" src="https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=319&fit=crop&dpr=1 600w, https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=319&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=319&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=401&fit=crop&dpr=1 754w, https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=401&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/456441/original/file-20220405-18-se1ghx.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=401&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This diagram shows the five previously known phyla of RNA viruses automatically organized by our methods.</span>
<span class="attribution"><a class="source" href="https://science.org/doi/10.1126/science.abm5847">Reprinted with permission from Zayed et al., Science Volume 376:156(2022).</a></span>
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<p>We identified a total of 5,504 new marine RNA viruses and doubled the number of known RNA virus phyla from five to 10. Mapping these new sequences geographically revealed that two of the new phyla were particularly abundant across vast oceanic regions, with regional preferences in either temperate and tropical waters (the <em>Taraviricota</em>, named after the Tara Oceans expeditions) or the Arctic Ocean (the <em>Arctiviricota</em>).</p>
<p>We believe that <em>Taraviricota</em> might be the missing link in the evolution of RNA viruses that researchers have long sought, connecting two different known branches of RNA viruses that diverged in how they replicate.</p>
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<a href="https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="World map showing distribution and abundance of RNA virus phyla." src="https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=382&fit=crop&dpr=1 600w, https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=382&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=382&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=480&fit=crop&dpr=1 754w, https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=480&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/456438/original/file-20220405-19-uq5khy.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=480&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This map shows the distribution of RNA viruses across the ocean. Wedge size is proportional to the average abundance of viruses present in that area, and wedge color indicates virus phyla.</span>
<span class="attribution"><a class="source" href="https://science.org/doi/10.1126/science.abm5847">Reprinted with permission from Zayed et al., Science Volume 376:156(2022).</a></span>
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<h2>Why it matters</h2>
<p>These new sequences help scientists better understand not only the evolutionary history of RNA viruses but also the evolution of early life on Earth.</p>
<p>As the COVID-19 pandemic has shown, RNA viruses can cause deadly diseases. But RNA viruses also play a <a href="https://doi.org/10.1111/j.1462-2920.2009.02101.x">vital role in ecosystems</a> because they can infect a wide array of organisms, including <a href="https://doi.org/10.1073/pnas.1908291116">microbes</a> that influence environments and food webs at the chemical level.</p>
<p>Mapping out where in the world these RNA viruses live can help clarify how they affect the organisms driving many of the ecological processes that run our planet. Our study also provides improved tools that can help researchers catalog new viruses as genetic databases grow. </p>
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<figcaption><span class="caption">Viruses do more than just cause disease.</span></figcaption>
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<h2>What still isn’t known</h2>
<p>Despite identifying so many new RNA viruses, it remains challenging to pinpoint what organisms they infect. Researchers are also currently <a href="https://doi.org/10.3390/v14040702">limited to mostly fragments</a> of incomplete RNA virus genomes, partly because of their genetic complexity and technological limitations.</p>
<p>Our next steps would be to figure out what kinds of genes might be missing and how they changed over time. Uncovering these genes could help scientists better understand how these viruses work.</p>
<p>[<em><a href="https://memberservices.theconversation.com/newsletters?nl=science&source=inline-science-corona-important">Get The Conversation’s most important coronavirus headlines, weekly in a science newsletter</a></em>]</p><img src="https://counter.theconversation.com/content/180545/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Guillermo Dominguez Huerta receives funding from U.S. National Science Foundation (DBI# 2022070). He was also supported by a Ramon-Areces Foundation postdoctoral fellowship.</span></em></p><p class="fine-print"><em><span>Ahmed Zayed receives funding from the U.S. National Science Foundation (DBI# 2022070)</span></em></p><p class="fine-print"><em><span>James Wainaina receives funding from the U.S. National Science Foundation (DBI# 2022070)</span></em></p><p class="fine-print"><em><span>Matthew Sullivan received funding for this research from the U.S. National Science Foundation and the Gordon and Betty Moore Foundation.</span></em></p>Viruses do more than just cause disease – they also influence ecosystems and the processes that shape the planet. Tracing their evolution could help researchers better understand how viruses work.Guillermo Dominguez Huerta, Science Consultant in Microbiology, The Ohio State UniversityAhmed Zayed, Research Scientist in Microbiology, The Ohio State UniversityJames Wainaina, Postdoctoral Research Associate in Microbiology, The Ohio State UniversityMatthew Sullivan, Professor of Microbiology, The Ohio State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1465212020-09-23T18:03:18Z2020-09-23T18:03:18ZHow a pregnant mouse’s microbes influence offspring’s brain development – new study offers clues<figure><img src="https://images.theconversation.com/files/359413/original/file-20200922-14-1lthrvj.jpg?ixlib=rb-1.1.0&rect=5%2C35%2C3958%2C3886&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The microbes in the mother's gut can alter the number of neurons in the baby's brain and the connections they make.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/brain-cells-pattern-royalty-free-image/1263379467?adppopup=true">bestdesigns/Getty Images</a></span></figcaption></figure><p>When a fetus is developing in the mother’s womb, it is essential that the fetus receives the correct nutrients and protection during this critical developmental window. One element of this environment includes the maternal microbiota, which are the collection of bacteria and other microorganisms that inhabit the mother’s body. </p>
<p>How the maternal microbiota directs fetal development, or modifies risk factors that could harm the fetus’s development, are major areas of research. </p>
<p>My training in <a href="https://www.helenvuongphd.com/">neurobiology and microbiome biology</a> led me to wonder how different microbiomes – from the mother during pregnancy or the infant’s early-life gut microbes – can shape brain development and behavior later in life, which is an active area of research. </p>
<p><a href="https://www.nature.com/articles/s41586-020-2745-3">My recent research paper</a> describes a fundamental role of the maternal gut microbes in development of the fetal brain. Specifically, my study identified how a mouse mother’s microbiome influences the formation of axons – long nerve fibers that project from a neuron – in her offspring, affecting its ability to sense its environment. </p>
<h2>What is the maternal microbiota?</h2>
<p>The maternal microbiota in pregnancy and during early life of the newborn includes microbes that inhabit the intestine, vagina, skin and breast milk and have important physiological consequences for the health of the mother and offspring. </p>
<p>There is a mounting evidence supporting the important role the maternal microbiome plays in fetal growth and development. For example, in a study of pregnant women, the <a href="https://doi.org/10.1016/j.cell.2012.07.008">gut microbiome was shown to change between the first and third trimester of pregnancy</a>. These changes are associated with the need to transfer energy and nutrients to the fetus. </p>
<p><a href="https://dx.doi.org/10.1038%2Fsrep08988">The vaginal microbiome of healthy pregnant women</a> inhibits the growth of bad bacteria by secreting antibacterial molecules and producing lactic acid, which protects the offspring from pathogenic microbes during pregnancy and birth. </p>
<p>The maternal <a href="https://doi.org/10.1073/pnas.1002601107">vaginal, fecal or skin microbes</a> are transmitted from the mother to the offspring during and after birth. The types of microbes that the offspring inherits depend on whether the baby was born through <a href="https://doi.org/10.1038/nm.4039">cesarean section or vaginal delivery</a>. </p>
<p>But this collection of microbes isn’t static. As the <a href="https://doi.org/10.1038/nm.4272">offspring develops, the microbiota</a> continues to evolve depending on whether the infant is breast-fed or given formula, as well as other environmental factors. Thus the maternal microbiota is important for the health of the fetus and the microbes the offspring will carry after birth.</p>
<h2>Interactions between the microbiota and nervous system</h2>
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<a href="https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1039&fit=crop&dpr=1 600w, https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1039&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1039&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1305&fit=crop&dpr=1 754w, https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1305&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/359412/original/file-20200922-14-xdpxjv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1305&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Microbes in the mother’s gut alter the brain development of the fetus.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/gut-brain-connection-or-gut-brain-axis-concept-art-royalty-free-image/686292062?adppopup=true">ChrisChrisW/Getty Images</a></span>
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<p>Research over the past two decades shows the microbiota is important for development and function of the nervous system. </p>
<p>In animal studies, adult mice that were raised in a sterile, germ-free environment, or depleted of the microbiota through treatment with antibiotics, had <a href="https://doi.org/10.1113/jphysiol.2004.063388">reduced levels of a protein that is important for the formation of new neurons</a>. </p>
<p>Other brain changes in these microbe-free animals included changes to the <a href="https://doi.org/10.1111/ejn.13291">parts of the neuron</a>, <a href="https://doi.org/10.3402/mehd.v26.29719">essential for communication</a>. There were also shifts in the levels of chemicals – <a href="https://doi.org/10.1073/pnas.1010529108">serotonin, dopamine, noradrenaline and nerve growth factor-inducible protein A</a> – that allow nerve cells to talk to each other. </p>
<p>Studies done in a number of different species, like zebra fish, fruit flies and pigs, show that the microbes that an organism carries affects <a href="https://doi.org/10.1146/annurev-neuro-072116-031347">social, communication, stress-related and learning and memory behaviors</a>. </p>
<p>This inspired me and <a href="https://doi.org/10.1016/S1474-4422(19)30356-4">many others</a> to investigate how microbes in the mother’s gut influence brain development and behavior of the offspring later in life. </p>
<h2>Maternal microbes influence offspring neurodevelopment and behavior</h2>
<p>The structure of a functioning brain begins while the fetus is developing in the womb. <a href="https://doi.org/10.1016/j.tins.2020.02.003">That includes the formation</a> of new nerve cells, migration of nerve cells to their correct location, formation of axons and communication between nerve cells. Environmental risk factors encountered during pregnancy can drastically impact brain development and manifest as neurodevelopmental disorders.</p>
<p><a href="https://www.nature.com/articles/s41586-020-2745-3">In my recent study in mice,</a> we focused on how the natural, unaltered mother’s gut microbes influence brain development and behavior. We compared the offspring from mothers with a full set of gut microbes to those from mothers lacking them.</p>
<p><a href="https://hsiao.science/">My colleagues and I in the lab of Elaine Hsiao</a> found that there were fewer and shorter axons projecting from a region of the brain called the thalamus to the cortex – the outer layer of the brain – in the offspring from mothers lacking gut microbes during pregnancy. These axons are important for relaying sensory information from the environment. </p>
<p>This suggests that the normal maternal gut microbiota is necessary for axon formation in the embryonic brain and sensory behaviors in the adult offspring. </p>
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<figcaption><span class="caption">What roles do microbes play in your body?</span></figcaption>
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<h2>Gut microbes produce small molecules that regulate social behavior</h2>
<p>While digesting food, gut microbes can produce <a href="https://doi.org/10.1126/science.1254766">thousands of small molecules called metabolites</a> that influence an animal’s physiology. These metabolites play countless roles in maintaining health and triggering disease throughout the body. As such, we hypothesized that the microbes in the mother’s gut produce these essential metabolites that are delivered to the developing fetus along with other nutrients.</p>
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<p>To test this hypothesis, we measured the types and levels of these small molecules in the maternal blood and the fetal brain. We discovered several key metabolites in maternal blood and the fetal brain that were reduced when the mother lacked gut microbes during pregnancy. </p>
<p>To test whether these chemicals are important for fetal brain development, we gave these key metabolites to pregnant mice that lacked a gut microbiome. These chemical supplements restored the levels found naturally in the healthy fetal brain and promoted normal brain development and offspring behaviors. </p>
<p>Together, these findings demonstrate how distinct maternal gut microbiota can affect fetal brain development through the delivery of essential molecules. This study also provide insights into which molecules are important for healthy brain development.</p><img src="https://counter.theconversation.com/content/146521/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Helen Vuong receives funding from NICHD. </span></em></p>Microbes in the gut aren’t just important for digesting your food. In pregnant women, these gut microbes are producing chemicals that are essential for proper brain development of the fetus.Helen Vuong, Postdoctoral Scholar of Integrative Biology and Physiology, University of California, Los AngelesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1119082019-03-06T11:40:41Z2019-03-06T11:40:41ZAre viruses the best weapon for fighting superbugs?<figure><img src="https://images.theconversation.com/files/261720/original/file-20190301-110134-1u7yr0g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">These are viruses called bacteriophages that infect only bacterial cells. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-render-bacteriophage-viruses-infecting-bacterial-479306521">Ewa Parylak/shutterstock.com</a></span></figcaption></figure><p>Antibiotics won the battle against resistant bacteria, but they may not win the war.</p>
<p>You probably know that antibiotic-resistant bacteria, also known as superbugs, have hampered physicians’ ability to treat infections. You may also be aware that there has been a steep <a href="https://www.cdc.gov/drugresistance/pdf/11-2013-508.pdf">decline in the number of new antibiotics</a> coming to market. Some headlines suggest humanity is doomed by antimicrobial resistance; <a href="https://www.cnn.com/2019/01/24/health/antibiotic-resistance-climate-change-gbr-scli-intl/index.html?no-st=1551070126">even politicians and governments have weighed in</a>, comparing rising antimicrobial resistance to other popular crises such as climate change. Although I believe these assertions are exaggerated, antimicrobial resistance is a serious problem. </p>
<p><a href="http://www.thepridelaboratory.org">I am a physician scientist</a> with a <a href="http://www.thepridelaboratory.org/publications.html">specialty in infectious diseases</a>. I have been fascinated by the role that bacteria play in human health, and the potential for using viruses to treat bacterial infections. </p>
<h2>What causes antimicrobial resistance?</h2>
<p>One significant factor contributing to antimicrobial resistance is the <a href="https://www.ncbi.nlm.nih.gov/pubmed/25859123">excessive use of antibiotics</a>. In the U.S., where antibiotics are widely available, some patients demand these drugs for many different illnesses. Many physicians appease their patients because they <a href="https://www.pewtrusts.org/en/research-and-analysis/articles/2017/06/30/why-doctors-prescribe-antibiotics-even-when-they-shouldnt">don’t understand when and when not</a> to use them and because there is <a href="https://www.cddep.org/wp-content/uploads/2017/06/antibiotic_legislation_timeline.pdf">no regulatory structure to limit their use</a>. Anyone with a prescription pad can prescribe any antibiotic to treat any condition and rarely, if ever, face any consequences. There are some <a href="https://www.cdc.gov/antibiotic-use/stewardship-report/outpatient.html">efforts to reduce antibiotic</a> use, but the scope of the problem in the U.S. remains large.</p>
<p>Some countries, <a href="https://www.who.int/bulletin/volumes/95/11/16-184374/en/">such as Sweden</a>, use incentives to encourage doctors to improve antibiotic uses. But there is no counterpart for this system in U.S. hospitals and clinics. </p>
<p>The problem goes beyond humans; 70 percent of all antibiotics <a href="http://www.cidrap.umn.edu/news-perspective/2016/12/fda-antibiotic-use-food-animals-continues-rise">are actually used on animals</a>. This means that humans can be exposed to antibiotics by <a href="http://doi.org/10.3390/antibiotics6040034">just handling animal products</a>. The drumstick you are preparing for dinner might also have <a href="https://doi.org/10.1093/jac/dkg483">antibiotic-resistant bacteria</a> <a href="http://doi.org/10.1177/003335491212700103">tagging along</a>. </p>
<p>Once antimicrobial resistance develops in a bacterium, it doesn’t always go away. For example, methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) evolved resistance to multiple different antibiotics; yet, despite efforts to reduce its spread by <a href="https://doi.org/10.1086/500664">limiting the use of antibiotics</a> that led to its emergence, <a href="https://doi.org/10.1086/597296">MRSA still persists</a> in hospitals and the community.</p>
<h2>An alternative to antibiotics</h2>
<p>Another reason for finding alternatives to antibiotics is that <a href="http://doi.org/10.7554/eLife.00458">we share our microbes with the people and pets who live around us</a>; thus, others can acquire one of these superbugs without ever taking an antibiotic.</p>
<p>A not-so-obvious reason for developing new therapies is that our bodies are home to a large community of microorganisms, including bacteria, called our microbiome. These microorganisms are necessary to maintain our health. Those same antibiotics that kill harmful bacteria also kill the good ones. </p>
<p>There is an alternative to antibiotics, but it was dismissed by medicine years ago. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=307&fit=crop&dpr=1 600w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=307&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=307&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=386&fit=crop&dpr=1 754w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=386&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=386&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Antibiotics or wrong diet damage the good and bad bacteria flora living in the gut.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antibiotics-wrong-diet-damage-good-bad-1225328413">Soleil Nordic/Shutterstockcom</a></span>
</figcaption>
</figure>
<h2>The original phage therapy story</h2>
<p>That alternative was something called phage therapy, which uses viruses that infect bacteria, called bacteriophages, to kill disease-causing bacteria. Bacteriophages, or phages, were used frequently in the <a href="http://doi.org/10.4161/viru.25991">early- and pre- antibiotic eras</a> between the 1920s and ‘40s to treat life-threatening infections. </p>
<p>But phage therapy had many disadvantages. The first was that phages were unpredictable. One type of phage might wipe out the bad bacteria in one individual but not another’s. So hospitals had to keep a broad collection of phages to kill disease-causing bacteria from all their patients. An antibiotic such as vancomycin, by comparison, predictably kills entire groups of bacteria. </p>
<p>Another downside is that phage collections require maintenance. So not only did hospitals have to keep a large variety of phages on hand, but they had to keep them in shape. So medicine chose antibiotics for convenience, and hadn’t looked back in any meaningful way, until recently.</p>
<h2>Making a comeback?</h2>
<p>So, why is phage therapy making a comeback? Antibiotic resistance is an obvious answer, but doesn’t explain the full story. </p>
<p>As a specialist in infectious diseases, I have been interested in phage therapy as long as I can remember, but only recently have I felt comfortable saying this out loud. Why? A physician might be considered a “quack” just for mentioning phage therapy because the early attempts were neither a rousing success or a colossal failure. Like any therapeutic, it had its strengths and weaknesses. </p>
<p>However, now scientific advances can guide us toward which phage is best for destroying a particular microbe. With the rising antimicrobial resistance crisis, physicians and scientists have a well-timed opportunity to work together to develop effective phage therapies. </p>
<p>The proof of this comes from recent landmark phage therapy cases. The successful treatment of a <a href="http://doi.org/10.1128/AAC.00954-17">physician with a life-threatening infection and a grave prognosis caused by a multi-drug resistant bacterium</a> at my institution serves as a great example. Another pivotal case <a href="https://www.buzzfeednews.com/article/azeenghorayshi/phage-therapy-follow-this">circulating in popular media</a> has kept this trend going. We physicians may be able to treat just about any disease-causing bacterium; it is just a matter of finding a suitable phage. </p>
<p>A big part of phage therapy research is devoted to “<a href="https://seaphages.org/">phage hunting</a>,” where we microbiologists scour the soil, the oceans and the human body to identify phages with the potential to kill the bacteria that ail us. While the pace of these studies has been slow, the new research is revealing the therapeutic potential of phages in medicine.</p>
<p>You might think that with all the phage hunting and landmark cases that we would start using phage therapy all the time, but we don’t. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Bacteriophages target only specific stains of bacteria.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-bacteriophage-infecting-bacterium-1126283543">Design_Cells/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>The case for using phages</h2>
<p>One advantage of antibiotics is that since they have been used for decades, we know a lot about their safety. Physicians make simple calculations every day about the risk-benefit ratio of using antibiotics, but aren’t equipped to make the same calculations about phages. Does anyone really want a doctor injecting them with a virus to cure a bacterial infection? I doubt that would be anyone’s choice when the question is posed that way. </p>
<p>But, remember that phages are natural. They’re on every surface of your body. They are in the ocean and soil, and in your toilet and sink. They are literally everywhere. Thus, putting a phage into your body to kill a bacterium quite frankly is something that nature does to us every single day, and as far as we know, we are no worse for the wear. </p>
<p>Phages are estimated to <a href="https://daily.jstor.org/fighting-bacterial-infection-with-viruses/?utm_source=marketing&utm_medium=social&utm_campaign=twitter">kill half the world’s bacteria</a> every 48 hours and are probably the most potent antibacterial agents out there. Is there really a compelling reason to be concerned when a doctor gives us a phage instead of us acquiring that same phage from our sink at home? Only time will tell. Unfortunately, as antimicrobial resistance continues to rise, time may not be on our side.</p><img src="https://counter.theconversation.com/content/111908/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Bacteria are becoming resistant to even the most powerful antibiotics. These expensive, hard-to-treat infections are prompting physicians to reassess using viruses to destroy bacteria.David Pride, Associate Director of Microbiology, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1041052018-10-09T10:44:53Z2018-10-09T10:44:53ZMeet the trillions of viruses that make up your virome<figure><img src="https://images.theconversation.com/files/238796/original/file-20181001-195278-zxp1fb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Every surface of our body -- inside and out -- is covered in microorganisms: bacteria, viruses, fungi and many other microscopic life forms.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/microbiome-microorganisms-bacteria-viruses-microbes-crawling-714045286?src=4HMvDP6bwGcrS9t-IJGgSA-1-6">vrx/Shutterstock.com</a></span></figcaption></figure><p><a href="https://theconversation.com/conozca-los-billones-de-virus-que-constituyen-su-viroma-104813"><em>Leer en español</em></a>.</p>
<p>If you think you don’t have viruses, think again.</p>
<p>It may be hard to fathom, but the human body is occupied by large collections of microorganisms, commonly referred to as our microbiome, that have evolved with us since the early days of man. Scientists have only recently begun to quantify the microbiome, and discovered it is inhabited by at least <a href="http://doi.org/10.1371/journal.pbio.1002533">38 trillion bacteria</a>. More intriguing, perhaps, is that bacteria are not the most abundant microbes that live in and on our bodies. That award goes to viruses.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=703&fit=crop&dpr=1 600w, https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=703&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=703&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=883&fit=crop&dpr=1 754w, https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=883&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/238779/original/file-20181001-195256-6s5ayh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=883&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Transmission electron micrograph of multiple bacteriophages attached to a bacterial cell wall.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/5/52/Phage.jpg">Dr. Graham Beards</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>It has been estimated that there are over <a href="http://doi.org/10.1016/j.coviro.2011.12.004">380 trillion viruses</a> inhabiting us, a community collectively known as the human virome. But these viruses are not the dangerous ones you commonly hear about, like those that cause the flu or the common cold, or more sinister infections like Ebola or dengue. Many of these viruses infect the bacteria that live inside you and are known as bacteriophages, or phages for short. The human body is a breeding ground for phages, and despite their abundance, we have very little insight into what all they or any of the other viruses in the body are doing. </p>
<p>I am a physician-scientist studying the human microbiome by focusing on viruses, because I believe that harnessing the power of bacteria’s ultimate natural predators will teach us how to prevent and combat bacterial infections. One might rightly assume that if viruses are the most abundant microbes in the body, they would be the target of the majority of human microbiome studies. But that assumption would be horribly wrong. The study of the human virome lags so far behind the study of bacteria that we are only just now uncovering some of their most basic features. This lag is due to it having taken scientists much longer to recognize the presence of a human virome, and a lack of standardized and sophisticated tools to decipher what’s actually in your virome.</p>
<h2>The 411 on the virome</h2>
<p>Here’s a few of the things we have learned thus far. Bacteria in the human body are not in love with their many phages that live in and around them. In fact they developed CRISPR-Cas systems – which <a href="http://doi.org/10.1016/j.cell.2014.05.010">humans have now co-opted for editing genes</a> – to rid themselves of phages or to <a href="http://doi.org/10.1126/science.1138140">prevent phage infections altogether</a>. Why? Because phages kill bacteria. They take over the bacteria’s machinery and force them to make more phages rather than make more bacteria. When they are done, they burst out of the bacterium, destroying it. Finally, phages sit on our body surfaces <a href="http://doi.org/10.1073/pnas.1305923110">just waiting to cross paths with vulnerable bacteria</a>. They are basically bacteria stalkers. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=744&fit=crop&dpr=1 600w, https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=744&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=744&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=934&fit=crop&dpr=1 754w, https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=934&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/238782/original/file-20181001-195256-8oif9s.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=934&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A virus called a bacteriophage infects bacteria and inserts its genetic material into the cell. The bacterium ‘reads’ the genetic instructions and manufactures more viruses which destroy the bacterium when they exit the cell.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/b/ba/11_Hegasy_Phage_T4_Wiki_E_CCBYSA.png">Guido4</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>It’s clear that there’s a war being fought on our body surfaces every minute of every day, and we haven’t a clue who’s winning or what the consequences of this war might be. </p>
<p>Viruses may inhabit all surfaces both inside and outside of the body. Everywhere researchers have looked in the human body, viruses have been found. Viruses in the blood? Check. Viruses on the skin? Check. Viruses in the lungs? Check. Viruses in the urine? Check. And so on. To put it simply, when it comes to where viruses live in the human body, figuring out where they don’t live is a far better question than <a href="http://doi.org/10.1016/j.jmb.2014.07.002">asking where they do</a>. </p>
<p>Viruses are contagious. But we often don’t think about bacterial viruses as being easily shared. Researchers have shown that <a href="http://doi.org/10.1186/s40168-016-0212-z">just living with someone will lead to rapid sharing of the viruses in your body</a>. If we don’t know what the consequences are of the constant battle between bacteria and viruses in our body, then it gets exponentially more complicated considering the battle between your bacteria and their viruses that are then shared with everyone including your spouse, your roommate, and even your dog. </p>
<h2>Viruses keeping us healthy?</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/238804/original/file-20181001-195260-1d8xn0z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Viruses destroy the bacterium when they burst out of the cell. Here, the clear circles reveal where the bacteriophage have killed the bacteria.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/bacteriophage-activity-little-spots-on-right-175492538?src=ScqQu3941Q4d-DJ6NHxD6g-1-81">Guido4/Shutterstock.com</a></span>
</figcaption>
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<p>Ultimately, we need to know what all these viruses in the human body are doing, and figure out whether we can take advantage of our virome to promote our health. But it’s probably not clear at this point why anyone would believe that our virome may be helpful. </p>
<p>It may seem counterintuitive, <a href="http://doi.org/10.1136/bmj.j831">but harming our bacteria can be harmful to our health</a>. For example, when our healthy bacterial communities are disturbed by antibiotic use, other microbial bad guys, also called pathogens, take advantage of the opportunity to invade our body and make us sick. Thus, in a number of human conditions, our healthy bacteria play important roles in preventing pathogen intrusion. Here’s where viruses come in. They’ve already figured out how to kill bacteria. It’s all they live for. </p>
<p>So the race is on to find those viruses in our viromes that have already figured out how to protect us from the bad guys, while leaving the good bacteria intact. Indeed, there are recent anecdotal examples <a href="http://doi.org/10.1128/AAC.00954-17">utilizing phages successfully to treat life-threatening infections</a> from bacteria resistant to most if not all available antibiotics – a treatment known as phage therapy. Unfortunately, these treatments are and will continue to be hampered by inadequate information on how phages behave in the human body and the unforeseen consequences their introduction may have on the human host. Thus, phage therapy remains heavily regulated. At the current pace of research, it may be many years before phages are used routinely as anti-infective treatments. But make no mistake about it; the viruses that have evolved with us for so many years are not only part of our past, but will play a significant role in the future of human health.</p><img src="https://counter.theconversation.com/content/104105/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Just because you don’t have the flu doesn’t mean that your aren’t teeming with viruses inside and out. But what are all these viruses doing, if they aren’t making you sick?David Pride, Associate Director of Microbiology, University of California, San DiegoChandrabali Ghose, Visiting Scientist, The Rockefeller UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/913512018-05-29T19:51:17Z2018-05-29T19:51:17ZThe bugs we carry and how our immune system fights them<figure><img src="https://images.theconversation.com/files/212443/original/file-20180328-109196-1n6ey6i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The immune system has to establish which cells belong to us and which are foreign, no mean feat. </span> <span class="attribution"><span class="source">www.shutterstock.com</span></span></figcaption></figure><p><em>This article is part of a three-part package exploring immunity and infectious diseases around the world. Read the other articles <a href="https://theconversation.com/au/topics/immunity-and-infectious-diseases-around-the-world-52607">here</a>.</em></p>
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<p>Human beings are large, complex, multicellular, multi-organ systems. We reproduce slowly and rely on a breadth of mechanisms that allow us to control the myriad of rapidly replicating, simple life forms that have evolved to live in or on us. </p>
<p>The system of defence is referred to collectively as immunity. </p>
<p>The word itself comes from the Latin <em>immunis</em>, describing the status of returned soldiers (<em>Genio immunium</em>) in the Roman state who were, for a time, exempt from paying taxes. </p>
<p>Our immunity protects us from many illnesses, including some forms of cancer. <a href="https://theconversation.com/cancer-immunotherapy-drugs-like-keytruda-and-opdivo-hold-hope-for-some-but-theres-still-a-way-to-go-81320">New cancer therapeutics</a>, called immunotherapies, work by boosting our immune cells to fight cancer cells that have found ways to evade them.</p>
<p>The immune system is divided into two interactive spheres, the much older “innate” sphere, and the more recently evolved “adaptive” sphere. A primary challenge for the very specifically targeted cells that form the basis of adaptive immunity is to distinguish “self” (our own body cells and tissues) from “non-self” – the foreign invaders. When that goes wrong, we can develop autoimmune diseases such as multiple sclerosis or rheumatoid arthritis. </p>
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Read more:
<a href="https://theconversation.com/explainer-what-are-autoimmune-diseases-22577">Explainer: what are autoimmune diseases?</a>
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<h2>The organisms we carry around with us</h2>
<p>The human body is host to many organisms over a lifetime. Some are dangerous to health (pathogens), some are benign, and some are necessary for proper functioning. </p>
<p>Most of the genetic material we carry around with us is “non-self”: principally harmless bacteria (called “commensals”) that live in the gastrointestinal tract. </p>
<p>Traditionally, studies focused on the “bad bugs” in our gut that cause diarrhoea and dysentery. But more recently, we’re learning there are also good guys. And there’s a general consensus we need to know more about the “microbiome”, the mass of bacteria in any “clinically normal” gut.</p>
<p>Gut bacteria provide essential vitamin B12 and when they die, release myriad proteins that will be broken down into amino acids, which the body needs. About 30% of our poo is comprised of dead bacteria.</p>
<p>Apart from our microbiome, normal human beings also have a substantial “virome”. Viruses differ from bacteria (which are cells in their own right) in that they are much simpler and can only replicate in living cells. </p>
<p>The greatest number of viruses we carry around are the “bacteriophages”, which infect the commensal bacteria in our gut. Not all “phages” are, however, benign. For example, the toxin that causes human diphtheria is encoded in the genome of a bacteriophage.</p>
<p>There’s also a spectrum of viruses that persistently infect our body tissues. The most familiar are herpes viruses, like those that cause cold sores (H. simplex) and shingles (H. zoster). Both viruses hide out in the nervous system and are normally under immune control. They re-emerge to cause problems as a consequence of tissue stress (such as a sunburnt lip) or as immunity declines with age (shingles). This is why a booster shingles vaccine is recommended for the elderly.</p>
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Read more:
<a href="https://theconversation.com/essays-on-health-microbes-arent-the-enemy-theyre-a-big-part-of-who-we-are-79116">Essays on health: microbes aren't the enemy, they're a big part of who we are</a>
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<h2>Our innate and adaptive immune systems</h2>
<p>The innate system ranges from processes as basic as phagocytosis (ingestion of bacteria), to molecules like the interferons produced by any virus-infected cell that can limit replication. Such innate systems are found right across the evolutionary spectrum and don’t target specific pathogens.</p>
<p>The much younger adaptive immune system is what we stimulate with vaccines. A property of small white blood cells called lymphocytes, it divides broadly into two lineages: the B cells and T cells. These bear the extraordinarily diverse and very specific immunoglobulin (Ig) and T cell receptor (TCR) recognition molecules that detect invading pathogens (bacteria, virus, fungi and so on). </p>
<p>The immunoglobulins bind to “non-self” (foreign) proteins called “antigens”, while the <a href="https://www.nobelprize.org/mediaplayer/index.php?id=1710">T cell receptors</a> are specifically targeted to “self” transplantation molecules.</p>
<p>The assassins of the immune system are then switched on; the killer T cells that eliminate virus-infected (or cancer) cells. Also activated are the “helper” T cells that secrete various molecules to “help” both the B cells and killer T cells differentiate and do their work.</p>
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Read more:
<a href="https://theconversation.com/explainer-what-is-the-immune-system-19240">Explainer: what is the immune system?</a>
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<h2>How does our immune system learn and remember?</h2>
<p>All lymphocyte responses work by massive cell division in the lymph nodes (the “glands” in our neck that swell when we get a sore throat). This process is started by small numbers of “naive” B and T cells that haven’t encountered the invader before, and only stops when the foreign invader is eliminated. </p>
<p>The B cells differentiate into large protein-secreting cells called plasma cells, which produce the protective antibodies (immunoglobulins) that circulate for years in our blood.</p>
<p>Most of the T cells die off after they’ve done their job, but some survive so they can remember how to target specific invaders. They can be rapidly recalled to their “killer” or “helper” function. </p>
<p>Prior infection or the administration of non-living or “attenuated” (to cause a very mild infection) vaccines sets up the memory so protective antibodies are immediately available to bind (and neutralise) pathogens like the polio or measles virus. While immune T cells are rapidly recalled to “assassin” status and eliminate pathogen-infected cells.</p>
<p>As you may have gathered from this very brief and far too simplified account, the immune system is extraordinarily complex. And it’s also very finely balanced with, for example, cross reactive responses to bacterial proteins sometimes setting us up for autoimmune diseases. </p>
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Read more:
<a href="https://theconversation.com/no-combination-vaccines-dont-overwhelm-kids-immune-systems-82377">No, combination vaccines don't overwhelm kids' immune systems</a>
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<p>Another example of autoimmunity is rheumatoid arthritis, which can be triggered by blood-borne chemicals from tobacco smoke that modify “self” transplantation molecules in the joints.</p>
<p>And when we talk about the possible effects of the microbiome, or the “too clean” hypothesis, we’re discussing how exposure to bacteria and viruses can modify that immune balance in ways that directly affect our wellbeing. This is a very active area of research which, given the underlying complexity, presents scientists with big challenges as we seek to reach verifiable conclusions.</p><img src="https://counter.theconversation.com/content/91351/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter C. Doherty is a Chief Investigator on an NHMRC Program grant focused on immunity to the influenza viruses. He chairs the board for the ARC Centre of Excellence for Convergent Bio-NanoScience and Technology, and is a member of advisory boards for Doctors for the Environment Australia, the Melbourne Sustainable Society Institute and the International One Health Initiative. </span></em></p>Nobel laureate Peter Doherty explains immunity.Peter C. Doherty, Laureate Professor, The Peter Doherty Institute for Infection and ImmunityLicensed as Creative Commons – attribution, no derivatives.