Posts tagged Howard Hughes Medical Institute Early Career Scientist
CU: study links autism symptons to gut germs
Dec 19th
Research linking autism symptoms to
gut microbes called ‘groundbreaking’
in CU-Boulder-authored journal article
gut microbes called ‘groundbreaking’
in CU-Boulder-authored journal article
A new study showing that feeding mice a beneficial type of bacteria can ameliorate autism-like symptoms is “groundbreaking,” according to University of Colorado Boulder Professor Rob Knight, who co-authored a commentary piece about the research appearing in the current issue of the journal Cell.
The autism study, published today in the same issue of Cell, strengthens the recent scientific understanding that the microbes that live in your gut may affect what goes on in your brain. It is also the first to show that a specific probiotic may be capable of reversing autism-like behaviors in mice.
“The broader potential of this research is obviously an analogous probiotic that could treat subsets of individuals with autism spectrum disorder,” wrote the commentary authors, who also included CU-Boulder Research Associate Dorota Porazinska and doctoral student Sophie Weiss.
The study underscores the importance of the work being undertaken by the newly formed Autism Microbiome Consortium, which includes Knight as well as commentary co-authors Jack Gilbert of the University of Chicago and Rosa Krajmalnik-Brown of Arizona State University. The interdisciplinary consortium—which taps experts in a range of disciplines from psychology to epidemiology—is investigating the autism-gut microbiome link.
For the new Cell study, led by Elaine Hsiao of the California Institute of Technology, the researchers used a technique called maternal immune activation in pregnant mice to induce autism-like behavior and neurology in their offspring. The researchers found that the gut microbial community of the offspring differed markedly compared with a control group of mice. When the mice with autism-like symptoms were fed Bacteriodes fragilis, a microbe known to bolster the immune system, the aberrant behaviors were reduced.
Scientific evidence is mounting that the trillions of microbes that call the human body home can influence our gut-linked health, affecting our risk of obesity, diabetes and colon cancer, for example. But more recently, researchers are discovering that gut microbes also may affect neurology—possibly impacting a person’s cognition, emotions and mental health, said Knight, also a Howard Hughes Medical Institute Early Career Scientist and an investigator at CU-Boulder’s BioFrontiers Institute.
The Autism Microbiome Consortium hopes to broaden this understanding by further studying the microbial community of autistic people, who tend to suffer from more gastrointestinal problems than the general public.
People with autism spectrum disorder who would like to have their gut microbes sequenced can do so now through the American Gut Project, a crowdfunded research effort led by Knight.
The consortium also includes Catherine Lozupone and Kimberly Johnson of CU-Boulder, James Adams of Arizona State University, Mady Hornig of Columbia University, Sarkis Mazmanian of the California Institute of Technology, John Alverdy of the University of Chicago and Janet Jansson of Lawrence Berkeley Lab.
For more information on the American Gut Project visit http://americangut.org.
-CU-
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CU study; Death of microbes could determine time of death
Sep 27th
An intriguing study led by the University of Colorado Boulder may provide a powerful new tool in the quiver of forensic scientists attempting to determine the time of death in cases involving human corpses: a microbial clock.
The clock is essentially the lock-step succession of bacterial changes that occur postmortem as bodies move through the decay process. And while the researchers used mice for the new study, previous studies on the human microbiome – the estimated 100 trillion or so microbes that live on and in each of us – indicate there is good reason to believe similar microbial clocks are ticking away on human corpses, said Jessica Metcalf, a CU-Boulder postdoctoral researcher and first author on the study.
“While establishing time of death is a crucial piece of information for investigators in cases that involve bodies, existing techniques are not always reliable,” said Metcalf of CU-Boulder’s BioFrontiers Institute. “Our results provide a detailed understanding of the bacterial changes that occur as mouse corpses decompose, and we believe this method has the potential to be a complementary forensic tool for estimating time of death.”
Dead and dying microbes could determine time of death for forensics pathologists
Currently, investigators use tools ranging from the timing of last text messages and corpse temperatures to insect infestations on bodies and “grave soil” analyses, with varying results, she said. And the more days that elapse following a person’s demise, the more difficult it becomes to determine the time of death with any significant accuracy.
Using high-technology gene sequencing techniques on both bacteria and microbial eukaryotic organisms like fungi, nematodes and amoeba postmortem, the researchers were able to pinpoint time of mouse death after a 48-day period to within roughly four days. The results were even more accurate following an analysis at 34 days, correctly estimating the time of death within about three days, said Metcalf.
A paper on the subject was published Sept. 23 in the new online science and biomedical journal, eLIFE, a joint initiative of the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust Fund. The study was funded by the National Institutes of Justice.
The researchers tracked microbial changes on the heads, torsos, body cavities and associated grave soil of 40 mice at eight different time points over the 48-day study. The stages after death include the “fresh” stage before decomposition, followed by “active decay” that includes bloating and subsequent body cavity rupture, followed by “advanced decay,” said Chaminade University forensic scientist David Carter, a co-author on the study.
“At each time point that we sampled, we saw similar microbiome patterns on the individual mice and similar biochemical changes in the grave soil,” said Laura Parfrey, a former CU-Boulder postdoctoral fellow and now a faculty member at the University of British Columbia who is a microbial and eukaryotic expert. “And although there were dramatic changes in the abundance and distribution of bacteria over the course of the study, we saw a surprising amount of consistency between individual mice microbes between the time points — something we were hoping for.”
As part of the project, the researchers also charted “blooms” of a common soil-dwelling nematode well known for consuming bacterial biomass that occurred at roughly the same time on individual mice during the decay period. “The nematodes seem to be responding to increases in bacterial biomass during the early decomposition process, an interesting finding from a community ecology standpoint,” said Metcalf.
“This work shows that your microbiome is not just important while you’re alive,” said CU-Boulder Associate Professor Rob Knight, the corresponding study author who runs the lab where the experiments took place. “It might also be important after you’re dead.”
The research team is working closely with assistant professors Sibyl Bucheli and Aaron Linne of Sam Houston State University in Huntsville, Texas, home of the Southeast Texas Applied Forensic Science Facility, an outdoor human decomposition facility known popularly as a “body farm.” The researchers are testing bacterial signatures of human cadavers over time to learn more about the process of human decomposition and how it is influenced by weather, seasons, animal scavenging and insect infestations.
The new study is one of more than a dozen papers authored or co-authored by CU-Boulder researchers published in the past several years on human microbiomes. One of the studies, led by Professor Noah Fierer, a co-author on the new study, brought to light another potential forensic tool — microbial signatures left on computer keys and computer mice, an idea enthralling enough it was featured on a “CSI: Crime Scene Investigation” television episode.
“This study establishes that a body’s collection of microbial genomes provides a store of information about its history,” said Knight, also an associate professor of chemistry and biochemistry and a Howard Hughes Medical Institute Early Career Scientist. “Future studies will let us understand how much of this information, both about events before death — like diet, lifestyle and travel — and after death can be recovered.”
In addition to Metcalf, Fierer, Knight, Carter and Parfrey, other study authors included Antonio Gonzalez, Gail Ackerman, Greg Humphrey, Mathew Gebert, Will Van Treuren, Donna Berg Lyons and Kyle Keepers from CU-Boulder, former BioFrontiers doctoral student Dan Knights from the University of Minnesota, and Yan Go and James Bullard from Pacific Biosciences in Menlo Park, Calif. Keepers participated in the study as an undergraduate while Gonzalez, now a postdoctoral researcher, was a graduate student during the study.
“There is no single forensic tool that is useful in all scenarios, as all have some degree of uncertainty,” said Metcalf. “But given our results and our experience with microbiomes, there is reason to believe we can get past some of this uncertainty and look toward this technique as a complementary method to better estimate time of death in humans.”
Gene sequencing equipment for the study included machines from Illumina of San Diego and Pacific Biosciences of Menlo Park, Calif. The Illumina data were generated at CU-Boulder in the BioFrontiers Next Generation Sequencing Facility.
To access a copy of the paper visit http://dx.doi.org/10.7554/eLife.01104. For more information on the BioFrontiers Institute visit http://biofrontiers.colorado.edu.
-CU-
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CU study: New public gut bacteria study expected to reach around world
Nov 25th
Ever wondered who is living in your gut, and what they’re doing? The trillions of microbial partners in and on our bodies outnumber our own cells by as many as 10 to 1 and do all sorts of important jobs, from helping digest the food we eat this Thanksgiving to building up our immune systems.
In association with the Human Food Project, researchers at the University of Colorado Boulder along with researchers at other institutions around the world are launching a new open-access project known as “American Gut” in which participants can get involved in finding out what microbes are in their own guts and what they are doing in there.
The project builds on previous efforts, including the five-year, $173-million NIH-funded Human Microbiome Project, to characterize the microbes living in and on our bodies, said Associate Professor Rob Knight of CU-Boulder’s BioFrontiers Institute. But unlike other projects that have focused on carefully chosen test subjects with a few hundred people, this project allows the public to get involved and is encouraging tens of thousands of people to do so, Knight said.
“Galileo saw outer space through his telescope, and we want to see the inner space of your gut through modern genetics,” said Rob Dunn, a scientist at North Carolina State University and a collaborator on the project. The new project will be “crowd-funded” by individuals interested in learning more about their own gut bacteria and by others who simply want to contribute to the project, said Dunn.
“By combining the crowd-funding model with the open-access data analysis model that we pioneered with the Earth Microbiome Project, we can finally give anyone with an interest in his or her microbiome an opportunity to participate, whether by contributing samples or by looking at the data,” said Knight, also a Howard Hughes Medical Institute Early Career Scientist.
Public interest is immense, says the research team. 18,000 people have already signed up to receive more information by email about the project when it launches. “The American Gut project builds on the Human Microbiome Project by allowing anyone to participate, and will let the public join in the excitement of this new field,” said Lita Proctor, program director for the Human Microbiome Project. “We can expect this to lay the groundwork for all sorts of fascinating studies in the future, that others will in turn build on.”
The American Gut project is an opportunity for the “citizen scientists” working with team of leading researchers and labs throughout the United States to help shape a new way of understanding how diet and lifestyle may contribute to human health through each person’s suite of trillions of tiny microbes, say the researchers. A key aspect of the project is to understand how diet and lifestyle, whether by choice — like athletes or vegetarians — or by necessity, including those suffering from particular autoimmune diseases or who have food allergies, affect peoples’ microbial makeup, said Knight.
“This will be the first project of its kind that might be able to address this question at such a large scale,” said Jeff Leach, founder of the Human Food Project and co-founder of American Gut. The gut microbiome has been linked to many diseases, including obesity, cancer, and inflammatory bowel disease — all of which are much more common in Western populations, he said.
“We should start thinking about diets not only from the perspective of what we should eat, but what we should be feeding our entire gut microbial systems,” said Leach. A key aspect of the project is to integrate studies of Americans of all shapes and sizes with studies of people living more traditional lifestyles in Africa, South America and elsewhere, he said.
The steep decline in the cost of DNA sequencing and recent advances in computational techniques allow for the analysis of microbial genomes orders of magnitude cheaper than was possible only a few years ago, said Knight. Sequencing is now getting cheap enough — participants who donate $99 or more can expect to get tens of thousands of sequences from microbes in their gut — that participants can include their families and even their pets, Knight said.
Doctoral student Daniel McDonald is one of several CU-Boulder students who will be involved in the effort. “I am excited to have the opportunity to develop new computational tools in order to further explore this frontier,” said McDonald, who is in the Interdisciplinary Quantitative Biology program at the BioFrontiers Institute.
“I am pleased to participate in this pioneering effort that marries the vast interest of the public in science with questions that are worth answering about human health and nutrition,” said Martin Blaser, chair of the Department of Medicine and professor of microbiology at New York University. “Through this consortium, the technical and intellectual resources are there to lead to important new knowledge.”
The project will seek to build on a growing canine and feline database as well. “The majority of data we currently have on the dog and cat microbiomes has come from a handful of small studies in research or clinically ill animals,” said Associate Professor Kelly Swanson of the Department of Animal Sciences and Division of Nutritional Sciences at the University of Illinois at Urbana-Champaign. “This study will apply the technology to free-living pets, where diet, genetics, and living environment are quite different from household to household.
“This research may identify important trends not possible with lab-based studies, and help guide us on how to feed our pets in the future,” said Swanson.
The backdrop to the project is the radical decline in the cost of DNA sequencing, which allows analysis of microbial genomes orders of magnitude cheaper than was possible only a few years ago, and recent advances in computational techniques. Participants in the project include many of the key players in the Human Microbiome Project and research facilities around the world.
To learn more about participating in or contributing to the project visit https://www.indiegogo.com/americangut. For a list of additional collaborators on the project visithttp://humanfoodproject.com/the-people/collaborators/.
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