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Dear Aventine Readers,
It has become well established that the gut microbiome is strongly associated with our physical and mental health. Now research shows a connection between the gut and atypical brain conditions like ADHD and autism. Of course correlation is not causation, but the connection is opening up new avenues of research, especially around autism. We speak to five experts about what they think of the findings and what they mean for future treatment.
Also in this issue: Noninvasive brain stimulation is helping combat depression; BYD is on its way to becoming the dominant force in global EV adoption; and the race to grow food on Mars begins by figuring out how to create fertile soil there.
Thanks for your time!
Danielle Mattoon
Editorial Director, Aventine
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Neurodiversity and the Microbiome
It is well established that the human gut microbiome — the collection of 100 trillion microorganisms that live inside our intestines — is connected to our health and behavior. Most neurotransmitters, the chemical molecules that enable communication throughout the nervous system, are produced in the gut. And the nervous system that lines the human digestive tract has more neurons than the spinal cord, earning it the nickname “the body’s second brain.”
Now multiple studies are showing links between the microbiome and conditions like attention deficit/hyperactivity disorder(ADHD) and autism spectrum disorder (ASD).
A systematic review of research into the microbiome and ADHD published in Nature in 2022 reported that there were “associations between gut microbiome features and ADHD.” But those results showed less consistency than findings from a study published last year on the connection between the microbiome and ASD. In it, a large team of researchers, led by Gaspar Taroncher-Oldenburg of New York University’s school of medicine and collaborators at the Simons Foundation Autism Research Initiative, analyzed data from what Taroncher-Oldenburg said were 1,298 children with and without ASD based on 25 prior studies from around the world. They found a strong correlation between people’s gut microbiome and autism or, as they described it, “a clear ASD–microbiome signal.”
What is not clear is what that correlation means, or how important it is. A 2015 meta-analysis of twin studies by researchers from King's College London showed that 60 to 90 percent of the risk for autism comes from one’s genome. Other factors — such as older parents, birth complications, environmental factors and potentially the microbiome — make up the difference, though it is unclear what role the microorganisms in our gut might play. And so far, no study has drawn a clear causal link between conditions in the gut and ASD, meaning that it’s possible differences in the microbiome could be a result of ASD-related dietary behavior or some other external cause.
Nevertheless, many researchers remain interested in the possibility of a causal link, as it would introduce possible avenues of treatment such as fecal transplantation, which early studies suggest could help reduce or prevent some of the symptoms of ASD. A systematic review of five studies looking at fecal transplantation in children with ASD showed that the process “significantly improved symptoms of autism,” though it conceded that “rigorously designed randomized controlled clinical trials are needed” to establish the safety and efficacy of the treatment. At the same time, there are efforts underway to develop a simple, noninvasive test using a stool sample to help guide diagnosis.
It is clear that there are plenty of open questions around the links between the microbiome, ADHD and ASD. Aventine spoke with five experts about the research that exists today, what we can understand from the available data and what kinds of trials are required to advance our understanding in the future.
No single factor, including genetic changes, has been shown to cause autism in every case, indicating that a combination of risk factors likely contributes to its development. There are many risk factors that people have identified. I think the microbiome could be one of those risk factors — maybe to a similar degree as the contribution from a single genetic mutation. So if you ask me if there’s causality from the microbiome, I don’t know. But if you ask me if it might be a risk factor, I’d say yes. As for how significant it could be as a risk factor, I’d say that studying the microbiome is as important as studying the role of individual genetic mutations.”
— Jun Huh, associate professor of immunology at Harvard Medical School
The next step for us involves looking at how the microbiome develops in young children over time, and applying a deeper sequencing — metagenomics — to see what they might be doing. We are pretty far from an actual intervention, but we’re hoping that gives us a better indicator of whether there is something that’s common across kids who go on to develop autism. For instance, could factors like diet, repeated infections or significant life stressors be viable targets for intervention, if they are closely aligned with bacterial changes? And does the data across time suggest exploring a new probiotic application to test? Although it would be a multi-step, long-term process, we’re interested in whether a probiotic — or even a prebiotic, including certain amino acids — might help to stabilize or strengthen the microbiome. Additionally, we want to investigate at what developmental stage might we see the most significant impact.”
— Angelica Ahrens, microbiologist and data scientist at the University of Florida
There’s a lot out there on the microbiome, and it’s really fascinating, but we still need to figure out how to study it well. One problem is that we still don’t know what each of the bacteria might be doing, how the compounds they produce might be influencing our body’s functioning or be related to autism. Another challenge is that most of the studies that have been done are what is called cross-sectional: You basically take one measurement in time to compare neurotypical to neurodivergent individuals. But that is very uninformative. For example, if you do an intervention, unless you know what was happening before, during and after, you can never know whether what you’re comparing is a cause of something or the effect of something. Finally, by default, most autism studies end up gravitating toward kids and people that are on the less severe end of the spectrum, because they’re easier to work with. So that creates a huge bias, because you’re missing out on most of the spectrum. Fortunately, efforts are being made to better understand the function of individual microbes in the context of the gut microbiome; rigorous, longitudinal intervention studies to determine the effect of fecal transplants in ASD are underway and improved clinical protocols are being rolled out to expand the spectrum of individuals with ASD who can participate in these studies.”
— Gaspar Taroncher-Oldenburg, director of Therapeutics Alliances, a drug discovery accelerator at New York University Grossman School of Medicine
A lot of the models right now are based on correlations, but it would be nice to actually do interventions and see how manipulating the gut microbiome can lead to differences. We would also love to understand at what time point in life interventions could be important: If there is a critical period, is it in the prenatal environment, the first year of life or afterward?”
— Lisa Aziz-Zadeh, a professor at the Brain and Creativity Institute at the University of Southern California
I think the interrelatedness of diet, the microbiome and autism phenotype is going to be critically important as we evaluate new interventions. There are a lot of anecdotal success stories of microbiome-based interventions in ASD, but if the microbiome could be used as either a pre-screening tool to determine if a specific intervention is worth considering or as an outcome measure associated with symptom improvement, that potentially objective metric would be especially useful in the less communicative individuals in the ASD community.
— Ruth Ann Luna, associate professor of pathology and immunology at Baylor College of Medicine and director of medical metagenomics at the Texas Children's Microbiome Center
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Advances That Matter
The stellerator at Princeton University. The Trustees of Princeton University, 2023
An off-the-shelf device to advance nuclear fusion. Sitting on a heavy metal table in the Princeton Plasma Physics Laboratory is an odd-looking contraption that could help advance the planet’s energy security. IEEE Spectrum reports that researchers at the university have built a device that will allow them to quickly and affordably test new ideas in the field of nuclear fusion — a technology that could one day provide almost limitless clean energy. Currently the study of fusion is dominated by so-called tokamaks, donut-shaped devices that use magnetic fields to confine superhot plasma — atoms that have been stripped of their electrons and reach temperatures as high as 150 million degrees Celsius — in a tight ring. But there is a competing device, known as a stellarator, through which the plasma circulates in a figure eight rather than a ring. This could prove more efficient and potentially make fusion a more realistic commercial prospect. These devices are less well understood because most investment has been directed toward tokamaks, but the Princeton team has built a stellarator from commercially available components for just $640,000, which could help advance research into the devices. To be clear, this kind of benchtop stellarator won’t solve our energy crisis; it is small and far from powerful enough. But it is an accessible option for research institutes and startups looking to understand how stellarators work. That, in turn, may help advance a growing number of stellarator startups — including Type One Energy, a company that has raised $82.5 million in funding — that buy into the idea that the underlying design, if scaled up correctly, could offer a path toward commercial fusion.
At-home brain stimulation can help tackle depression. A simple skullcap device that allows patients to receive gentle brain stimulation in their own homes has been shown to effectively reduce the symptoms of depression, Nature reports. So-called transcranial direct current stimulation, or tDCS, delivers weak electrical currents through electrodes placed on the scalp and was tested in a trial of 174 people. The treatment group used the device for 30 minutes, five times a week for the first three weeks, then three times a week for seven weeks; a control group did the same, but received only a brief pulse of current at the start of each session to replicate the initial sensation caused by the treatment. The results, published in Nature Medicine, showed that 45 percent of participants with the real device experienced reduction in or recovery from their symptoms, compared with almost 22 percent of the control group, and the perceived improvement among those using the real device was significantly greater. Although previous studies have suggested that tDCS may not be effective as a means of treating depression, researchers believe that tailored dosages may be required for the approach to be effective in all patients. Using real-time imaging to determine the optimal dosage might be the next step in making it a mainstream treatment.
The world’s first electric hydrofoil ferry sets sail. One commute in Stockholm just got a whole lot quicker and greener. A nine-mile route between Stockholm’s City Hall and the suburb of Ekerö is now being served on a trial basis by an electric hydrofoil ferry. The vessel, called P-12 Nova and powered purely by renewable energy, uses its hydrofoils to lift itself out of the water, saving energy by reducing drag. The boat is capable of hitting 30 knots without creating a wake big enough to interfere with other boats, meaning it can complete the nine-mile journey in just 30 minutes. That’s 15 minutes faster than the diesel-powered ferries that have previously been the quickest boats on the route; their speed is limited to12 knots inside city limits because of the large wakes they create. The P-12 Nova, built by a company called Candela, has a range of 40 nautical miles at 25 knots and is expected to recharge at City Hall during lunch breaks. Unfortunately the trial, which has already faced delays, will need to pause over the winter when Sweden’s waterways freeze and resume next spring. Nevertheless, it will soon be able to prove itself in warmer climates, as Candela has received orders for similar vessels from Saudi Arabia, New Zealand and Berlin.
Magazine and Journal Articles Worthy of Your Time
BYD Is Winning the Global Race to Make Cheaper EVs, from Bloomberg Businessweek
5,900 words, or about 24 minutes
If it seemed to you like the Chinese car maker BYD appeared from nowhere, that’s because it kind of did: In 2020, it sold just under 180,000 cars; in 2023, it sold 3 million, with a roughly 50-50 split between electric and hybrid vehicles. As Bloomberg Businessweek reports in this story, that explosion in sales has funded a huge push into new markets around the world that follows a well-rehearsed playbook: “Do intensive market research; win hearts and minds on the ground; then tap BYD’s vast product portfolio to deliver whatever the locals want.” Winning hearts and minds takes many forms, from providing jobs to becoming the official E-Mobility Partner of last summer’s European football championship. And the company’s portfolio of vehicles is vast — from bargain-basement hatchbacks that can sell for less than $11,000, to midsize pickups and luxury SUVs, to an almost $240,000 supercar to rival the likes of Lamborghini and Ferrari. With new plants slated for Hungary and Turkey that would help BYD avoid European import tariffs, along with aggressive moves in Canadian and Mexican markets, the company could become a dominant force driving EV adoption around the world.
The quest to figure out farming on Mars, from MIT Technology Review
4,000 words, or about 16 minutes
In the film “The Martian,” the astronaut Mark Watney, played by Matt Damon, manages to exploit his botanical skills to grow enough potatoes on Mars so that he doesn’t starve. The truth for real-life Mars-going astronauts will not be so simple: There is no soil on the planet, just rock, sand and dust. To make matters worse, the planet is riddled with toxic salts called perchlorates. Researchers from multiple U.S. universities, backed by funding from NASA and the National Science Foundation, are focused on overcoming those issues so that if — or when — humans experiment with living on the planet, the first inhabitants will be able to sustain themselves. The secret to making that happen might be the introduction of microbial life on plots of currently infertile Martian land. Some strains of microbe, for example, might be able to ingest those toxic salts to survive and then enrich the sand and rock to form rudimentary soil when they die. It may sound like science fiction, but as MIT Technology Review points out, this is technology that must be proven long before we even contemplate life on Mars.
Can AI help Africa close the development gap? from the Financial Times
2,600 words, or about 11 minutes
Artificial intelligence holds enormous promise for the continent of Africa: It could save doctors, of which there are few, huge amounts of time, allowing them to see more patients; it could help predict where to plant crops and when to water them to optimize yields; it could create tailored educational programs for children in areas where there aren’t enough teachers. It’s a long list. Yet there is concern about how, exactly, AI will be rolled out in the continent. Done badly, some people fear, multinational tech firms will hoover up data from African consumers, roll out technology that isn’t designed with the local populations in mind, and generally take advantage of nations that aren’t prepared for the impact of artificial intelligence. This article explores all those tensions and sadly reveals that there isn’t a simple answer to the question the headline poses.