The Key to Reversing Autism May Be in the Microbiome
Part of the rise in autism is due to better diagnosis, but Dr. Emeran Mayer thinks it's something in our environment, and within us, that has played a role in causing this increase.
Dr Emeran Mayer is a world-renowned gastroenterologist and neuroscientist with 35 years of experience in the study of clinical and neurobiological aspects of how the digestive system and the nervous system interact in health and disease. His current research focus is on the role of the gut microbiota brain interactions in emotion regulation, chronic visceral pain, and in obesity. His research has been continuously supported by the National Institutes of Health.
Dr Mayer is a professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, executive director of the G Oppenheimer Center for Neurobiology of Stress and Resilience, and co-director of the CURE: Digestive Diseases Research Center at UCLA.
Emeran Mayer: Autism is both a devastating problem and it’s still a puzzle largely what causes or what has been causing the dramatic increase in the prevalence of this disease in the last 40 years or so. So it’s almost like an exponential increase. Part of that is really due to better diagnosis and the diagnostic criteria. But a lot of people think that something in our environment has played a role in causing this increase. And it’s worldwide. It’s not just in North America. It’s in Asia, it’s in Europe. So something environmental. The genes, the genetic risk factors for autism have obviously always been there but something else must have triggered it. So some people think it’s something in the diet and that is possible. It could also be something what we do to our gut microbes. So the use of antibiotics, the obsession with keeping things more and more sterile from the day we’re born, you know, throughout our lifetime.
So people have thought about this as potentially a change in microbial composition, diversity inside of us are a cause of this. There’s many observations that link the brain and the gut in autism. Clinically the majority of autistic children have digestive problems – constipation, abdominal pain, discomfort. Part of that is most likely due to the diet, the unique diet that autistic children self-select for. Many things are excluded from the diet that we normally would like fiber, fermented foods. And so it’s very possible that that plays a role. And there are people that have thought about this why do kids select such a diet. It seems to have to do a lot with the texture of foods. So very unique disturbance in the sensitivity for the texture, not so much for the content. So things that are soft are much preferred over crunchy and chewy things. And then, you know, people have started to look at the microbial composition. So they looked at the gut microbes in fecal samples from patients with autism and have found abnormalities.
The problem is most of those studies are small. They’re often not well controlled. We now understand that autism is a spectrum, autism spectrum disorder. And it probably contains several different subsets of patients. So if you just take a small number of patients, measure their gut microbes it’s, you’re likely to pick up variable patterns because it’s not a homogeneous group of patients. And the last thing that’s happened which has really drawn a lot of attention to it has been a study published a couple of years ago by a group at Cal Tech in California which showed that in an animal model of what’s called maternal immune activation – so where the mother undergoes an infection or immune activation during pregnancy. And then the offspring, the mother’s offspring shows altered social behavior. And there’s various tests that have been taken as animal behavior equivalents to human autism. Always, you know, a big chunk from something, from animal behaviors to something as complex as all the disturbances in autism. But that has received a lot of attention because in these animals that have these behaviors they have an altered gut microbial composition, produce different metabolites, particularly one metabolite that’s also been found in human patients. And they have a leaky gut. So they have immune activation in the gut and by treating these animals with – that’s the most intriguing. By treating them with a probiotic which is called B. fragilis, the investigators were able to reverse many of those behavioral changes and the gut abnormalities in these mice.
So this has triggered a tremendous interest now. There’s efforts underway to produce this probiotic and make it acceptable for human use. So it’s not a probiotic that you currently can get in your yogurt or cheese. It has to be approved. It has to be cultured. But clinical trials will happen in the next couple of years that will test this hypothesis. Can you actually by influencing the microbial composition reverse some of the changes either in terms of the gut dysfunction or cognitive and social interaction of these patients. One would assume that in humans the earlier you could start that therapy after delivery – this is clearly a developmental disorder that starts initially almost with imperceptible changes in the newborn and then gradually becomes clinically obvious. The earlier you could start this treatment, the more likely it would be beneficial. So autism in many ways is the prototypic brain-gut microbiome disorder. So this model is almost certainly going to lead to a better understanding and breakthroughs and diagnosis and therapy. But there’s still a ways to go.
So probiotic is a microbe with a demonstrated health benefit. So lots of microbes would qualify for this. We have 100 trillion of these microbes inside of our gut so many of those are potential probiotics that if you isolate them, culture them and then give them to humans – and that’s like with this B. fragilis. It’s produced in the context of infections and abscesses strangely. But it has been shown to have many beneficial effects also stimulating the immune system. That effect on autism appears to be different from the one that has been demonstrated earlier from its anti-inflammatory effect on the gut’s immune system. So it does exist. It just doesn’t exist in a form that is currently commercially available or that would be allowed by the FDA that you could put this into humans. So the trial was left to demonstrate the safety which most likely will be shown. But the FDA is fairly strict. Anytime you use a probiotic even the ones that are in commercially available products if you want to prove that a particular yogurt with its microbes is probiotic is beneficial for a disease condition you need to get FDA approval just like for any other drug which is a complex process, a time consuming process. And it’s kind of slowed the progress in this field of identifying microbes with potential health. So new microbes with potential health benefits.
The genetic risk for autism has always existed, but in the last 40 years the prevalence has risen dramatically – and not in any one location, but across all developed nations. Many researchers are looking to identify the trigger and, as a gastroenterologist and neurologist, Dr. Emeran Mayer is following the trail of evidence that points to the microbial composition of the digestive system and its relationship to the brain. The gut microbes of those with autism differs from people who aren’t on the autism spectrum, but so far many of the studies have not been sufficient to draw solid results. Dr. Mayer runs through one of the more compelling studies and explains how a yet unapproved strain of probiotic may be the answer to the decreasing the incidence of autism in the future. Dr. Emeran Mayer's most recent book is The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health.
Dr Emeran Mayer's most recent book is The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health
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What makes some people more likely to shiver than others?
Some people just aren't bothered by the cold, no matter how low the temperature dips. And the reason for this may be in a person's genes.
Eating veggies is good for you. Now we can stop debating how much we should eat.
- A massive new study confirms that five servings of fruit and veggies a day can lower the risk of death.
- The maximum benefit is found at two servings of fruit and three of veggies—anything more offers no extra benefit according to the researchers.
- Not all fruits and veggies are equal. Leafy greens are better for you than starchy corn and potatoes.
An open letter predicts that a massive wall of rock is about to plunge into Barry Arm Fjord in Alaska.
- A remote area visited by tourists and cruises, and home to fishing villages, is about to be visited by a devastating tsunami.
- A wall of rock exposed by a receding glacier is about crash into the waters below.
- Glaciers hold such areas together — and when they're gone, bad stuff can be left behind.
The Barry Glacier gives its name to Alaska's Barry Arm Fjord, and a new open letter forecasts trouble ahead.
Thanks to global warming, the glacier has been retreating, so far removing two-thirds of its support for a steep mile-long slope, or scarp, containing perhaps 500 million cubic meters of material. (Think the Hoover Dam times several hundred.) The slope has been moving slowly since 1957, but scientists say it's become an avalanche waiting to happen, maybe within the next year, and likely within 20. When it does come crashing down into the fjord, it could set in motion a frightening tsunami overwhelming the fjord's normally peaceful waters .
The Barry Arm Fjord
Camping on the fjord's Black Sand Beach
Image source: Matt Zimmerman
The Barry Arm Fjord is a stretch of water between the Harriman Fjord and the Port Wills Fjord, located at the northwest corner of the well-known Prince William Sound. It's a beautiful area, home to a few hundred people supporting the local fishing industry, and it's also a popular destination for tourists — its Black Sand Beach is one of Alaska's most scenic — and cruise ships.
Not Alaska’s first watery rodeo, but likely the biggest
Image source: whrc.org
There have been at least two similar events in the state's recent history, though not on such a massive scale. On July 9, 1958, an earthquake nearby caused 40 million cubic yards of rock to suddenly slide 2,000 feet down into Lituya Bay, producing a tsunami whose peak waves reportedly reached 1,720 feet in height. By the time the wall of water reached the mouth of the bay, it was still 75 feet high. At Taan Fjord in 2015, a landslide caused a tsunami that crested at 600 feet. Both of these events thankfully occurred in sparsely populated areas, so few fatalities occurred.
The Barry Arm event will be larger than either of these by far.
"This is an enormous slope — the mass that could fail weighs over a billion tonnes," said geologist Dave Petley, speaking to Earther. "The internal structure of that rock mass, which will determine whether it collapses, is very complex. At the moment we don't know enough about it to be able to forecast its future behavior."
Outside of Alaska, on the west coast of Greenland, a landslide-produced tsunami towered 300 feet high, obliterating a fishing village in its path.
What the letter predicts for Barry Arm Fjord
Moving slowly at first...
Image source: whrc.org
"The effects would be especially severe near where the landslide enters the water at the head of Barry Arm. Additionally, areas of shallow water, or low-lying land near the shore, would be in danger even further from the source. A minor failure may not produce significant impacts beyond the inner parts of the fiord, while a complete failure could be destructive throughout Barry Arm, Harriman Fiord, and parts of Port Wells. Our initial results show complex impacts further from the landslide than Barry Arm, with over 30 foot waves in some distant bays, including Whittier."
The discovery of the impeding landslide began with an observation by the sister of geologist Hig Higman of Ground Truth, an organization in Seldovia, Alaska. Artist Valisa Higman was vacationing in the area and sent her brother some photos of worrying fractures she noticed in the slope, taken while she was on a boat cruising the fjord.
Higman confirmed his sister's hunch via available satellite imagery and, digging deeper, found that between 2009 and 2015 the slope had moved 600 feet downhill, leaving a prominent scar.
Ohio State's Chunli Dai unearthed a connection between the movement and the receding of the Barry Glacier. Comparison of the Barry Arm slope with other similar areas, combined with computer modeling of the possible resulting tsunamis, led to the publication of the group's letter.
While the full group of signatories from 14 organizations and institutions has only been working on the situation for a month, the implications were immediately clear. The signers include experts from Ohio State University, the University of Southern California, and the Anchorage and Fairbanks campuses of the University of Alaska.
Once informed of the open letter's contents, the Alaska's Department of Natural Resources immediately released a warning that "an increasingly likely landslide could generate a wave with devastating effects on fishermen and recreationalists."
How do you prepare for something like this?
Image source: whrc.org
The obvious question is what can be done to prepare for the landslide and tsunami? For one thing, there's more to understand about the upcoming event, and the researchers lay out their plan in the letter:
"To inform and refine hazard mitigation efforts, we would like to pursue several lines of investigation: Detect changes in the slope that might forewarn of a landslide, better understand what could trigger a landslide, and refine tsunami model projections. By mapping the landslide and nearby terrain, both above and below sea level, we can more accurately determine the basic physical dimensions of the landslide. This can be paired with GPS and seismic measurements made over time to see how the slope responds to changes in the glacier and to events like rainstorms and earthquakes. Field and satellite data can support near-real time hazard monitoring, while computer models of landslide and tsunami scenarios can help identify specific places that are most at risk."
In the letter, the authors reached out to those living in and visiting the area, asking, "What specific questions are most important to you?" and "What could be done to reduce the danger to people who want to visit or work in Barry Arm?" They also invited locals to let them know about any changes, including even small rock-falls and landslides.
The famous cognition test was reworked for cuttlefish. They did better than expected.
- Scientists recently ran the Stanford marshmallow experiment on cuttlefish and found they were pretty good at it.
- The test subjects could wait up to two minutes for a better tasting treat.
- The study suggests cuttlefish are smarter than you think but isn't the final word on how bright they are.
Proof that some people are less patient than invertebrates<iframe width="730" height="430" src="https://www.youtube.com/embed/H1yhGClUJ0U" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><p> The common cuttlefish is a small cephalopod notable for producing sepia ink and relative intelligence for an invertebrate. Studies have shown them to be capable of remembering important details from previous foraging experiences, and to adjust their foraging strategies in response to changing circumstances. </p><p>In a new study, published in <a href="https://royalsocietypublishing.org/doi/10.1098/rspb.2020.3161" target="_blank" rel="noopener noreferrer">The Proceedings of the Royal Society B</a>, researchers demonstrated that the critters have mental capacities previously thought limited to vertebrates.</p><p>After determining that cuttlefish are willing to eat raw king prawns but prefer a live grass shrimp, the researchers trained them to associate certain symbols on see-through containers with a different level of accessibility. One symbol meant the cuttlefish could get into the box and eat the food inside right away, another meant there would be a delay before it opened, and the last indicated the container could not be opened.</p><p>The cephalopods were then trained to understand that upon entering one container, the food in the other would be removed. This training also introduced them to the idea of varying delay times for the boxes with the second <a href="https://www.sciencealert.com/cuttlefish-can-pass-a-cognitive-test-designed-for-children" target="_blank" rel="noopener noreferrer">symbol</a>. </p><p>Two of the cuttlefish recruited for the study "dropped out," at this point, but the remaining six—named Mica, Pinto, Demi, Franklin, Jebidiah, and Rogelio—all caught on to how things worked pretty quickly.</p><p>It was then that the actual experiment could begin. The cuttlefish were presented with two containers: one that could be opened immediately with a raw king prawn, and one that held a live grass shrimp that would only open after a delay. The subjects could always see both containers and had the ability to go to the immediate access option if they grew tired of waiting for the other. The poor control group was faced with a box that never opened and one they could get into right away.</p><p>In the end, the cuttlefish demonstrated that they would wait anywhere between 50 and 130 seconds for the better treat. This is the same length of time that some primates and birds have shown themselves to be able to wait for.</p><p>Further tests of the subject's cognitive abilities—they were tested to see how long it took them to associate a symbol with a prize and then on how long it took them to catch on when the symbols were switched—showed a relationship between how long a cuttlefish was willing to wait and how quickly it learned the associations. </p>
All of this is interesting, but what use could it possibly have?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTcxNzY2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY2MTM0MzYyMH0.lKFLPfutlflkzr_NM6WmnosKM1rU6UEIHWlyzWhYQNM/img.jpg?width=1245&coordinates=0%2C10%2C0%2C88&height=700" id="77c04" class="rm-shortcode" data-rm-shortcode-id="7eb9d5b2d890496756a69fb45ceac87c" data-rm-shortcode-name="rebelmouse-image" data-width="1245" data-height="700" />
A diagram showing the experimental set up. On the left is the control condition, on the right is the experimental condition.
Credit: Alexandra K. Schnell et al., 2021<p> As you can probably guess, the ability to delay gratification as part of a plan is not the most common thing in the animal kingdom. While humans, apes, some birds, and dogs can do it, less intelligent animals can't. </p><p>While it is reasonably simple to devise a hypothesis for why social humans, tool-making chimps, or hunting birds are able to delay gratification, the cuttlefish is neither social, a toolmaker, or is it hunting anything particularly <a href="https://gizmodo.com/cuttlefish-are-able-to-wait-for-a-reward-1846392756" target="_blank" rel="noopener noreferrer">intelligent</a>. Why they evolved this capacity is up for debate. </p><p>Lead author Alexandra Schnell of the University of Cambridge discussed their speculations on the evolutionary advantage cuttlefish might get out of this skill with <a href="https://www.eurekalert.org/pub_releases/2021-03/mbl-qc022621.php" target="_blank" rel="noopener noreferrer">Eurekalert:</a> </p><p style="margin-left: 20px;"> "Cuttlefish spend most of their time camouflaging, sitting and waiting, punctuated by brief periods of foraging. They break camouflage when they forage, so they are exposed to every predator in the ocean that wants to eat them. We speculate that delayed gratification may have evolved as a byproduct of this, so the cuttlefish can optimize foraging by waiting to choose better quality food."</p><p>Given the unique evolutionary tree of the cuttlefish, its cognitive abilities are an example of convergent evolution, in which two unrelated animals, in this case primates and cuttlefish, evolve the same trait to solve similar problems. These findings could help shed light on the evolution of the cuttlefish and its relatives. </p><p> It should be noted that this study isn't definitive; at the moment, we can't make a useful comparison between the overall intelligence of the cuttlefish and the other animals that can or cannot pass some variation of the marshmallow test.</p><p>Despite this, the results are quite exciting and will likely influence future research into animal intelligence. If the common cuttlefish can pass the marshmallow test, what else can?</p>