Culture

In popular culture, asteroids play the role of apocalyptic threat, get blamed for wiping out the dinosaurs - and offer an extraterrestrial source for mineral mining.

But for researcher Nicholas Hud, asteroids play an entirely different role: that of time capsules showing what molecules originally existed in our solar system. Having that information gives scientists the starting point they need to reconstruct the complex pathway that got life started on Earth.

Director of the NSF-NASA Center for Chemical Evolution at the Georgia Institute of Technology, Hud says finding molecules in asteroids provides the strongest evidence that such compounds were present on the Earth before life formed. Knowing what molecules were present helps establish the initial conditions that led to the formation of amino acids and related compounds that, in turn, came together to form peptides, small protein-like molecules that may have kicked off life on this planet.

"We can look to the asteroids to help us understand what chemistry is possible in the universe," said Hud. "It's important for us to study materials from asteroids and meteorites, the smaller versions of asteroids that fall to Earth, to test the validity of our models for how molecules in them could have helped give rise to life. We also need to catalog the molecules from asteroids and meteorites because there might be compounds there that we had not even considered important for starting life."

Hud will be a panelist at a press briefing "Asteroids for Research, Discovery, and Commerce" at 1 p.m. Central Time on February 17 at the 2018 annual meeting of the American Association for the Advancement of Science (AAAS) in Austin, Texas. He will also be part of a session on February 18 on the topic, "Seeking the Identity and Origins of the First Polymers of Life."

NASA scientists have been analyzing compounds found in asteroids and meteorites for decades, and their work provides a solid understanding for what might have been present when the Earth itself was formed, Hud says.

"If you model a prebiotic chemical reaction in the laboratory, scientists can argue about whether or not you had the right starting materials," said Hud. "Detection of a molecule in an asteroid or meteorite is about the only evidence everyone will accept for that molecule being prebiotic. It's something we can really lean on."

The Miller-Urey experiment, conducted in 1952 to simulate conditions believed to have existed on the early Earth, produced more than 20 different amino acids, organic compounds that are the building blocks for peptides. The experiment was kicked off by sparks inside a flask containing water, methane, ammonia and hydrogen, all materials believed to have existed in the atmosphere when the Earth was very young.

Since the Miller-Urey experiment, scientists have demonstrated the feasibility of other chemical pathways to amino acids and compounds necessary for life. In Hud's laboratory, for instance, researchers used cycles of alternating wet and dry conditions to create complex organic molecules over time. Under such conditions, amino acids and hydroxy acids, compounds that differ chemically by just a single atom, could have formed short peptides that led to the formation of larger and more complex molecules - ultimately exhibiting properties that we now associate with biological molecules.

"We now have a really good way to synthesize peptides with amino acids and hydroxy acids working together that could have been common on the early Earth," he said. "Even today, hydroxy acids are found with amino acids in living organisms - and in some meteorite samples that have been examined."

Hud believes there are many possible ways that the molecules of life could have formed. Life could have gotten started with molecules that are less sophisticated and less efficient than what we see today. Like life itself, these molecules could have evolved over time.

"What we find is that these compounds can form molecules that look a lot like modern peptides, except in the backbone that is holding the units together," said Hud. "The overall structure can be very similar and would be easier to make, though it doesn't have the ability to fold into as complex structures as modern proteins. There is a tradeoff between the simplicity of forming these molecules and how close these molecules are to those found in contemporary life."

Geologists believe the Earth was very different billions of years ago. Instead of continents, there were islands protruding from the oceans. Even the sun was different, producing less light but more cosmic rays - which could have helped power the protein-forming chemical reactions.

"The islands could have been potential incubators for life, with molecules raining down from the atmosphere," Hud said. "We think the key process that would have allowed these molecules to go to the next stage is a wet-dry cycling like what we are doing in the lab. That would have been perfect for an island out in the ocean."

Rather than a single spark of life, the molecules could have evolved slowly over time in gradual progression that may have taken place at different rates in different locations, perhaps simultaneously. Different components of cells, for example, may have developed separately where conditions favored them before they ultimately came together.

"There is something very special about peptides, nucleic acids, polysaccharides and lipids and their ability to work together to do something they couldn't have done separately," he said. "And there could have been any number of chemical processes on the early Earth that never led to life."

Knowing what conditions were like on the early Earth therefore gives scientists a stronger foundation for hypothesizing what could have taken place, and could offer hints to other pathways that may not have been considered yet.

"There are probably a lot more clues in the asteroids about what molecules were really there," said Hud. "We may not even know what we should be looking for in these asteroids, but by looking at what molecules we find, we can ask different and more questions about how they could have helped get life started."

AUSTIN, Texas - The debate in sleep science has gone on for a generation. People and other animals sicken and die if they are deprived of sleep, but why is sleep so essential?

Psychiatrists Chiara Cirelli and Giulio Tononi of the Wisconsin Center for Sleep and Consciousness proposed the "synaptic homeostasis hypothesis" (SHY) in 2003. This hypothesis holds that sleep is the price we pay for brains that are plastic and able to keep learning new things.

A few years ago, they went all in on a four-year research effort that could show direct evidence for their theory.

The result, published in February 2017 in Science, offered direct visual proof of SHY. Cirelli, a professor in the University of Wisconsin's School of Medicine and Public Health, expanded on the research today (Feb. 17, 2018) at the annual meeting of the American Association for the Advancement of Science.

Striking electron-microscope pictures from inside the brains of mice suggest what happens in our own brain every day: Our synapses - the junctions between nerve cells - grow strong and large during the stimulation of daytime, then shrink by nearly 20 percent while we sleep, creating room for more growth and learning the next day.

A large team of researchers sectioned the brains of mice and then used a scanning electron microscope to photograph, reconstruct, and analyze two areas of cerebral cortex. They were able to reconstruct 6,920 synapses and measure their size.

The team deliberately did not know whether they were analyzing the brain cells of a well-rested mouse or one that had been awake. When they finally "broke the code" and correlated the measurements with the amount of sleep the mice had during the six to eight hours before the image was taken, they found that a few hours of sleep led on average to an 18 percent decrease in the size of the synapses. These changes occurred in both areas of the cerebral cortex and were proportional to the size of the synapses.

The study was big news, picked up by outlets including The New York Times and National Public Radio. It was bolstered by a companion Johns Hopkins University study that analyzed brain proteins to also confirm SHY's prediction that the purpose of sleep is to scale back synapses.

For Cirelli, the study was a big gamble that paid off. But she's not resting on her laurels. Her lab is now looking at new brain areas, and at the brains of young mice to understand the role sleep plays in brain development.

Focusing science education on students through genetic and genealogical studies may be the way to increase minorities in the pipeline and engage students who would otherwise deem science too hard or too uninteresting, according to a Penn State anthropologist.

"Henry Louis Gates (Jr.) and I talked about using personalized genetics and genealogy in classrooms as a way to help get kids to understand their heritage and be proud," said Nina Jablonski, Evan Pugh University Professor of Anthropology, Penn State. "And especially for African-American kids to connect with their heritage. Then also, equally, as a way to create interest in science."

Gates is the Alphonse Fletcher University Professor and Director of the Hutchins Center for African and African American Research at Harvard University. He has also produced a variety of documentary films and is currently host and expert on the Public Broadcasting System's "Finding Your Roots," which is in its fourth season.

A working group of about 30 people explored the various approaches to this goal. Eventually, the group was whittled down to only a few and an informal approach centered on the "study of me" developed.

"What we wanted to see was if the genetic 'study of me' influences the feelings about science and aspirations about wanting to be a scientist," said Jablonski. "Does it impact understanding?"

The researchers felt it was critical to work with middle school children because that is when children are figuring out who they are and what they are going to do in life. They wanted to influence the middle schoolers before they got to high school to see if this intervention approach was effective. The program and curriculum they developed were for a two-week summer camp which was eventually orchestrated by Penn State's Science U, an outreach program of the Eberly College of Science.

In the process, the group realized that this curriculum and approach would work just as well for high school and introductory undergraduate students. A program was also begun at Spelman College and Morehouse College to incorporate the material as a module in an introductory biology class.

The researchers involved in both projects will present the results of their work at a session, "Understanding Your Roots: STEM Diversity and an Evidence-Based Curriculum," organized by Jablonski today (Feb. 17) at the annual meeting of the American Association for the Advancement of Science in Austin, Texas.

"We are trying to give students the impactful personal message that history is related to what they are studying," said Jablonski.

By focusing on genealogy and genetics, the curriculum ranges from DNA and inheritance to evolution and the origins of humanity.

"The students become more literate in science, but they also see themselves as part of the genealogy of humanity, that is, ultimately all people united," said Jablonski.

During the summer camp, African-American students were often able to trace their ancestry back to their ancestors' original entry into the new world. This was possible through family oral histories that still exist. Some students of European descent had more trouble getting that far back in their ancestry.

The summer camp includes two days of independent study where kids were able to choose the direction of their studies. Projects ranged from bacteria, to further DNA studies, to genealogical trees of anime characters complete with inherited traits.

"We took the risk to empower these kids," said Jablonski. "The risk paid off in the creative thinking they showed."

Aurora, Colo. (Feb. 16, 2018) - Researchers at Children's Hospital Colorado (Children's Colorado) have completed the first-ever EXIT (Ex Utero Intrapartum Treatment) to ventricular pacing procedure. The patient, a 36-week fetus, who suffered from complete atrioventricular block (CAVB) and cardiac dysfunction, was at high risk of dying before delivery. While still attached to its mother via the umbilical cord, the baby received a temporary pacemaker, which stabilized its dangerously low and irregular heart rate and ensured enough blood flow from the heart to the rest of its body for delivery.

"In essence, this procedure gave the fetus the gift of time," said Bettina Cuneo, MD, fetal cardiologist. "Not only were we able to expose the heart and attach the pacing leads to make the heart rate faster, we were able to make sure the heart was functioning effectively before cutting the umbilical cord."

A team of experts led by Dr. Cuneo and Henry Galan, MD, maternal fetal medicine at the hospital's Colorado Fetal Care Center, worked with a multi-disciplinary team including Max Mitchell, MD, cardiothoracic surgery, to perform the procedure, and the infant was successfully delivered. Their research was recently published in Fetal Diagnosis and Therapy.

The risk of perinatal death in the first day of life is six-to-eleven times higher if a fetus:

- Develops CAVB at less than 20 weeks of gestation

- Has a fetal heart rate less than 55 beats per minute

- Develops heart failure

This approach should significantly lower this increase in mortality for a preterm fetus with these conditions.

"With the mother's body acting as a heart and lung bypass machine, the EXIT procedure allows life-saving fetal interventions while maintaining in-utero circulation," said Dr. Galan. "Although careful selection of patients is necessary, this 'rescue' pacing not only provides an option for the most fragile patients with CAVB, but also for fetuses who are at high risk for in-utero loss of life but are too premature for delivery."

AUSTIN, Texas - Our own unique experiences shape how we view the world and respond to the events in our lives. But experience is highly subjective. What's distressing or joyful to one person may be very different to another.

These differences can matter, especially as a growing body of research shows that what happens in our inner landscapes - our thoughts about and interpretations of our experiences - can have physical consequences in our brains and bodies.

This was the subject of a talk given Feb. 16 by University of Wisconsin-Madison Center for Healthy Minds founder and director Richard Davidson at the 2018 Annual Meeting of the American Association for the Advancement of Science, titled: How the Mind Informs the Brain: Depression and Well-Being.

"How we experience the world affects us in more ways than we previously thought," says Davidson, William James and Vilas Professor of Psychology and Psychiatry at UW-Madison. "We're finding that emotions and thoughts can alter neural pathways in the brain in relatively short amounts of time and even affect processes like gene expression and aging."

Davidson says tapping into the role experience plays in mental health could help scientists and clinicians design better interventions to treat disorders such as anxiety and depression.

This framework stands in contrast to the tendency of neuroscientists to place more value on behavior in lieu of studying experience. In his talk, Davidson made the case for more fully integrating emerging scientific knowledge of the mind-body connection with neuroscience study design.

Not only should individual experience be more fully accounted for and measured in neuroscience studies, Davidson argues, efforts to do so are revealing previously unknown neural networks that are implicated in well-being and mental health disorders.

The problem, he says, is that experience has long been thought of as synonymous with behavior, when in fact the two are separate and can influence each other.

Davidson and other scientists in the field have used imaging tools like functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to measure activity and structures in the brain while observing relationships between specific neural networks and behaviors.

"What's exciting about these findings is that when we take experience into account, certain neural mechanisms are implicated that would not otherwise be identified," he says. "The findings underscore the importance of taking both experience and behavior into account when building neural accounts of emotion, well-being and psychopathology.

Studies of mindfulness and meditation serve as examples of interventions that focus on experience. These forms of mental training hold the potential to influence how people notice sensations and form emotional responses to the events around them in ways that can affect their biology and actually drive behavior.

Previous research related to emotional well-being and depression can act as helpful models, Davidson says, because there is evidence that psychological interventions that include mental training practices to increase positive qualities of mind such as attention, kindness and compassion can leave lasting effects on the brain and physiological aspects of health.

In theory, scientists can take this information and begin looking at other interventions that influence experience to see what kind of impact on the brain and body they may have.

Davidson is excited for new study methods enabled by smartphones because they can gather critical data about a person's experience at specific intervals during the day - outside of the lab - in more natural, everyday environments. Called "experience sampling," the idea is to deliberately gather information about a person's mental state and experiences to create a larger picture of how his or her brain, behavior and experiences interact.

Austin, Tex., Feb. 16, 2018 - Are we alone in the universe? Few questions have captured the public imagination more than this. Yet to date we know of just one sample of life, that which exists here on Earth.

Although there is plenty of habitable real estate out there, "habitable" is not the same as "inhabited," says Arizona State University Regents Professor and noted cosmologist Paul Davies. Because nobody knows how non-life transitioned to life on Earth, it is impossible to estimate the odds of it springing forth elsewhere in the universe.

Davies presented his findings during a press briefing Feb. 16 at the annual meeting of the American Association for the Advancement of Science in Austin, Texas.

"During my career, opinion has shifted from life's origin being a bizarre fluke unique in the universe ('almost a miracle' in the words of Francis Crick), to the belief that the universe is teeming with life ('a cosmic imperative' in the words of Christian de Duve)," Davies said. "How can we settle the matter? For several decades astronomers have been sweeping the skies with radio telescopes hoping to stumble across a message from ET. So far they have been met by an 'eerie silence.'"

"Meanwhile, astrobiologists have considered how signatures of microbial life might be detectable in the solar system or in the atmospheres of extra-solar planets," Davies added. "If life really does form readily in Earth-like conditions, it should have started many times right here on Earth, so we should look for a 'shadow biosphere' of life, but not as we know it, under our very noses.'"

Davies is a cosmologist, theoretical physicist, astrobiologist and best-selling author. His latest book 'The Eerie Silence" is a celebration and critique of the search for cosmic company.

Davies is a member of the Breakthrough Listen Committee and formerly chaired the SETI Post-Detection Task group of the International Academy of Astronautics. He was the first person to champion the idea that life on Earth may have originated on Mars and transferred here in impact ejecta. Davies is director of the Beyond Center at ASU that researches how life began in terms of the organization of information in complex networks - the software of life. His forthcoming book "The Demon in the Machine," is a penetrating look at the power of information to explain the physics of living matter.

Davies will detail his research in the presentation, "The search for life beyond Earth," as part of the "Is There a Future for Humanity in Space?" session, 10 a.m. CT on Feb. 17.

COLUMBUS, OHIO - A clinically relevant "liquid biopsy" test can be used to profile cancer genomes from blood and predict survival outcomes for patients with metastatic triple negative breast cancer (TNBC), according to new research published by a multi-institutional team of researchers with The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard.

Although TNBC represents just 10-15 percent of all breast cancer diagnoses, the disease is responsible for 35 percent of all breast cancer-related deaths. While significant advances in understanding the genomic drivers of primary TNBC have been made in the past decade, relatively little is known about metastatic disease because surgical tumor biopsies are rarely obtained from these patients.

For this new study, researchers completed what is believed to be the largest genomic characterization of metastatic TNBC derived exclusively from liquid biopsies. This was done by measuring cell-free DNA levels in the blood -- DNA that is excreted from both cancerous and normal cells into the bloodstream. The study included blood samples from 164 women with metastatic TNBC.

"Traditionally, we would need to obtain a tissue biopsy to perform the whole genome sequencing tests that could reveal potential DNA-level mutations driving a patient's specific cancer. For metastatic breast cancer patients, however, tissue biopsy can be risky or painful," says Daniel Stover, MD, co-first and co-corresponding author of the study and a breast medical oncologist/researcher with the OSUCCC - James. "Being able to do this type of genomic analysis from a simple blood draw allows us to get a picture of a patient's specific cancer genomic characteristics in a less invasive way."

Researchers then used a customized liquid biopsy technique they developed to distinguish levels of DNA from cancer cells and healthy cells (tumor fraction). Whole genome sequencing was performed to identify potential mutations associated with metastatic TNBC.

The team found that 64 percent of patients had more than 10 percent tumor DNA, and that this threshold of tumor DNA was correlated with poor survival outcomes in patients with metastatic TNBC. Additionally, researchers used genome-wide data to identify specific abnormal genes more frequently altered in metastatic TNBC compared with primary cases of the disease. These abnormal genes were associated with survival outcomes in the metastatic TNBC patient population and could serve as targets for new therapies for at-risk populations in the future, researchers say.

"The recognition that a significant fraction of patients harbor greater than 10 percent tumor DNA in blood suggests that liquid biopsies may enable routine and non-invasive profiling of cancer genomes for patients with metastatic TNBC," says Viktor Adalsteinsson, PhD, co-corresponding author and group leader of the Blood Biopsy Team at the Broad Institute.

Researchers say this study suggests that minimally invasive liquid biopsies could be used as a new predictive marker for metastatic TNBC.

"This is a very challenging disease. Our team's findings -- and others enabled by liquid biopsy --could improve how we track disease and treat our patients in the clinic," says Heather Parsons, MD, MPH, co-first author of the study and breast medical oncologist/researcher at Dana-Farber Cancer Institute and Harvard Medical School.

"These are exciting and important discoveries that could help us understand how a patient's cancer is likely to progress and, ultimately, could have the potential to guide treatment decisions based on specific genomic risk factors," adds Stover, whose plans for his laboratory at the OSUCCC - James include expanded validation studies with a goal to bring this test into the clinic and investigate new methods to study circulating DNA.

Boston, MA (February 16, 2018) - Increasing evidence has linked autism spectrum disorder (ASD) with dysfunction of the brain's cerebellum, but the details have been unclear. In a new study, researchers at Boston Children's Hospital used stem cell technology to create cerebellar cells known as Purkinje cells from patients with tuberous sclerosis complex (TSC), a genetic syndrome that often includes ASD-like features. In the lab, the cells showed several characteristics that may help explain how ASD develops at the molecular level.

The team, led by Mustafa Sahin, MD, director of the Translational Research Center at Boston Children's, reports its findings today in the journal Molecular Psychiatry.

TSC, a rare condition in which benign tumors grow in multiple organs of the body, is associated with ASD in about half of all cases. Previous brain autopsies have shown that patients with TSC, as well as patients with ASD, have reduced numbers of Purkinje cells, the main type of neuron that communicates out of the cerebellum. In a 2012 mouse study, Sahin and colleagues knocked out a TSC gene (Tsc1) in Purkinje cells and found social deficits and repetitive behaviors in the mice, together with abnormalities in the cells.

In the new paper, Sahin and colleagues took their observations to humans, studying Purkinje cells derived from three patients with TSC (two also had ASD symptoms, and all three also had epilepsy).

"Developmentally, stem-cell derived neurons are close to a fetal state, recapitulating early differentiation of cells," says Maria Sundberg, PhD, the paper's first author.

Neuronal abnormalities

To make the cells, Sundberg first created induced pluripotent stem cells from patients' blood cells or skin cells, then differentiated these into neural progenitor cells and finally Purkinje cells. The team then compared them with Purkinje cells derived from unaffected people (parents or gender-matched controls) and with cells whose TSC mutation was corrected using CRISPR-Cas9 gene editing.

"We saw changes," says Sahin. "The cells are bigger and fire less than control cells - exactly what we see in the mouse model."

Purkinje cells with the TSC genetic defect were harder to differentiate from neural progenitor cells, suggesting that TSC may impair the early development of cerebellar tissue. On examination, the patient-derived Purkinje cells showed structural abnormalities in dendrites (the projections neurons use to take in signals) and signs of impaired development of synapses (junctions with other neurons).

The TSC Purkinje cells also showed over-activation of a cell growth pathway called mTOR. Accordingly, the team treated the cells with rapamycin, an mTOR inhibitor that is already used clinically in TSC to reduce the size of TSC-related tumors and prevent TSC-related seizures.

Added to patient-derived cells in culture, rapamycin enabled the development of more Purkinje precursor cells, improved the functioning of their synapses and increased their tendency to fire.

Finally, the researchers also compared what genes were being "turned on" in Purkinje cells from TSC patients versus controls. Unexpectedly, the patient-derived cells showed reduced production of FMRP, a protein that is associated with Fragile X syndrome, a common genetic cause of ASD and intellectual disability. FMRP is known to help regulate synapse function, so it may contribute to the abnormalities seen in Purkinje cell functioning in TSC.

"These conditions may have a common downstream pathway," says Sahin.

The analysis also showed reduced production of two proteins important for neuron-to-neuron communication at synapses: synaptophysin and a glutamate receptor protein.

A platform for studying autism

The study was the first to create human Purkinje cells using TSC patients' own stem cells. In future studies, Sahin and colleagues hope to generate larger numbers of patient-derived cells to investigate differences between patients with TSC alone and those who also have ASD. Additionally, they hope to use the Purkinje cell platform to study other ASD-related genetic disorders, including Fragile X and SHANK3 mutation, and to test potential drugs. Sundberg also plans to create other types of neurons for modeling ASD.

"Looking at cell-type-specific changes is very important," Sundberg says. "In TSC, we know that in different cell types, the mutation causes different effects."

ITHACA, N.Y. - Caffeine, the widely consumed stimulant and igniter of sluggish mornings, has been found to temper taste buds temporarily, making food and drink seem less sweet, according to new Cornell University research.

Caffeine is a powerful antagonist of adenosine receptors, which promote relaxation and sleepiness. Suppressing the receptors awakens people but decreases their ability to taste sweetness -- which, ironically, may make them desire it more.

The research demonstrates taste modulation in the real world, said senior author Robin Dando, assistant professor of food science: "When you drink caffeinated coffee, it will change how you perceive taste -- for however long that effect lasts. So if you eat food directly after drinking a caffeinated coffee or other caffeinated drinks, you will likely perceive food differently."

Dando, along with lead authors Ezen Choo and Benjamin Picket published, "Caffeine May Reduce Perceived Sweet Taste in Humans, Supporting Evidence That Adenosine Receptors Modulate Taste," in the Journal of Food Science.

In the blind study, one group sampled decaffeinated coffee with 200 milligrams of caffeine added in a laboratory setting, making a strong cup of coffee. The stimulant was added to make that group's coffee consistent with real-life amounts of caffeine. The other group drank just decaffeinated coffee. Both groups had sugar added. Panelists who drank the caffeinated brew rated it as less sweet.

In a secondary part of the study, participants disclosed their level of alertness and estimated the amount of caffeine in their coffee. Further, panelists reported the same increase in alertness after drinking either the caffeinated or decaffeinated samples, all the while panelists could not predict if they had consumed the decaffeinated or the caffeinated version.

"We think there might be a placebo or a conditioning effect to the simple action of drinking coffee," said Dando. "Think Pavlov's dog. The act of drinking coffee - with the aroma and taste - is usually followed by alertness. So the panelists felt alert even if the caffeine was not there," said Dando.

"What seems to be important is the action of drinking that coffee," Dando said. "Just the action of thinking that you've done the things that make you feel more awake, makes you feel more awake."

URBANA, Ill. - Gut microbes have been in the news a lot lately. Recent studies show they can influence human health, behavior, and certain neurological disorders, such as autism. But just how do they communicate with the brain? Results from a new University of Illinois study suggest a pathway of communication between certain gut bacteria and brain metabolites, by way of a compound in the blood known as cortisol. And unexpectedly, the finding provides a potential mechanism to explain the characteristics of autism.

"Changes in neurometabolites during infancy can have profound effects on brain development, and it is possible that the microbiome -- or collection of bacteria, fungi, and viruses inhabiting our gut -- plays a role in this process," says Austin Mudd, a doctoral student in the Neuroscience Program at U of I. "However, it is unclear which specific gut bacteria are most influential during brain development and what factors, if any, might influence the relationship between the gut and the brain."

The researchers studied 1-month-old piglets, which are remarkably similar to human infants in terms of their gut and brain development. They first identified the relative abundances of bacteria in the feces and ascending colon contents of the piglets, then quantified concentrations of certain compounds in the blood and in the brain.

"Using the piglet as a translatable animal model for human infants provides a unique opportunity for studying aspects of development which are sometimes more difficult or ethically challenging to collect data on in human infants," Mudd says. "For example, in this study we wanted to see if we could find bacteria in the feces of pigletsthat might predict concentrations of compounds in the blood and brain, both of which are more difficult to characterize in infants."

The researchers took a stepwise approach, first identifying predictive relationships between fecal bacteria and brain metabolites. They found that the bacterial genera Bacteroides and Clostridium predicted higher concentrations of myo-inositol, Butyricimonas positively predicted n-acetylaspartate (NAA), and Bacteroides also predicted higher levels of total creatine in the brain. However, when bacteria in the genus Ruminococcus were more abundant in the feces of the piglets, NAA concentrations in the brain were lower.

"These brain metabolites have been found in altered states in individuals diagnosed with autism spectrum disorder (ASD), yet no previous studies have identified specific links between bacterial genera and these particular metabolites," Mudd notes.

The next step was to determine if these four bacterial genera could predict compounds in the blood. "Blood biomarkers are something we can actually collect from an infant, so it's a clinically relevant sample. It would be nice to study an infant's brain directly, but imaging infants is logistically and ethically difficult. We can, however, obtain feces and blood from infants," says Ryan Dilger, associate professor in the Department of Animal Sciences, Division of Nutritional Sciences, and Neuroscience Program at U of I.

The researchers found predictive relationships between the fecal microbiota and serotonin and cortisol, two compounds in the blood known to be influenced by gut microbiota. Specifically, Bacteroides was associated with higher serotonin levels, while Ruminococcus predicted lower concentrations of both serotonin and cortisol. Clostridium and Butyricimonas were not associated strongly with either compound.

Again, Mudd says, the results supported previous findings related to ASD. "Alterations in serum serotonin and cortisol, as well as fecal Bacteroides and Ruminococcus levels, have been described in ASD individuals."

Based on their initial analyses, the researchers wanted to know if there was a three-way relationship between Ruminococcus, cortisol, and NAA. To investigate this further, they used a statistical approach known as "mediation analysis," and found that serum cortisol mediated the relationship between fecal Ruminococcus abundance and brain NAA concentration. In other words, it appears that Ruminococcus communicates with and makes changes to the brain indirectly through cortisol. "This mediation finding is interesting, in that it gives us insight into one way that the gut microbiota may be communicating with the brain. It can be used as a framework for developing future intervention studies which further support this proposed mechanism," Dilger adds.

"Initially, we set out to characterize relationships between the gut microbiota, blood biomarkers, and brain metabolites. But once we looked at the relationships identified in our study, they kept leading us to independently reported findings in the autism literature. We remain cautious and do not want to overstate our findings without support from clinical intervention trials, but we hypothesize that this could be a contributing factor to autism's heterogenous symptoms," Mudd says. Interestingly, in the time since the researchers wrote the paper, other publications have also reported relationships between Ruminococcus and measures of brain development, supporting that this might be a promising area for future research.

Dilger adds, "We admit this approach is limited by only using predictive models. Therefore, the next step is to generate empirical evidence in a clinical setting. So it's important to state that we've only generated a hypothesis here, but it's exciting to consider the progress that may be made in the future based on our evidence in the pre-clinical pig model."