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Could A Gut-Brain Connection Help Explain Autism?

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What is Your Big Idea?
Diego Bohórquez/Credit: Duke University, Durham, NC

You might think nutrient-sensing cells in the human gastrointestinal (GI) tract would have no connection whatsoever to autism spectrum disorder (ASD). But if Diego Bohórquez’s “big idea” is correct, these GI cells, called neuropods, could one day help to provide a direct link into understanding and treating some aspects of autism and other brain disorders.

Bohórquez, a researcher at Duke University, Durham, NC, recently discovered that cells in the intestine, previously known for their hormone-releasing ability, form extensions similar to neurons. He also found that those extensions connect to nerve fibers in the gut, which relay signals to the vagus nerve and onward to the brain. In fact, he found that those signals reach the brain in milliseconds [1].

Bohórquez has dedicated his lab to studying this direct, high-speed hookup between gut and brain and its impact on nutrient sensing, eating, and other essential behaviors. Now, with support from a 2019 NIH Director’s New Innovator Award, he will also explore the potential for treating autism and other brain disorders with drugs that act on the gut.

Bohórquez became interested in autism and its possible link to the gut-brain connection after a chance encounter with Geraldine Dawson, director of the Duke Center for Autism and Brain Development. Dawson mentioned that autism typically affects multiple organ systems.

With further reading, he discovered that kids with autism frequently cope with GI issues, including bowel inflammation, abdominal pain, constipation, and/or diarrhea [2]. They often also show unusual food-related behaviors, such as being extremely picky eaters. But his curiosity was especially piqued by evidence that certain gut microbes can influence abnormal behaviors in mice that model autism.

With his New Innovator Award, Bohórquez will study neuropods and the gut-brain connection in a mouse model of autism. Using the tools of optogenetics, which make it possible to activate cells with light, he’ll also see whether autism-like symptoms in mice can be altered or alleviated by controlling neuropods in the gut. Those symptoms include anxiety, repetitive behaviors, and lack of interest in interacting with other mice. He’ll also explore changes in the animals’ eating habits.

In another line of study, he will take advantage of intestinal tissue samples collected from people with autism. He’ll use those tissues to grow and then examine miniature intestinal “organoids,” looking for possible evidence that those from people with autism are different from others.

For the millions of people now living with autism, no truly effective drug therapies are available to help to manage the condition and its many behavioral and bodily symptoms. Bohórquez hopes one day to change that with drugs that act safely on the gut. In the meantime, he and his fellow “GASTRONAUTS” look forward to making some important and fascinating discoveries in the relatively uncharted territory where the gut meets the brain.

References:

[1] A gut-brain neural circuit for nutrient sensory transduction. Kaelberer MM, Buchanan KL, Klein ME, Barth BB, Montoya MM, Shen X, Bohórquez DV. Science. 2018 Sep 21;361(6408).

[2] Association of maternal report of infant and toddler gastrointestinal symptoms with autism: evidence from a prospective birth cohort. Bresnahan M, Hornig M, Schultz AF, Gunnes N, Hirtz D, Lie KK, Magnus P, Reichborn-Kjennerud T, Roth C, Schjølberg S, Stoltenberg C, Surén P, Susser E, Lipkin WI. JAMA Psychiatry. 2015 May;72(5):466-474.

Links:

Autism Spectrum Disorder (National Institute of Mental Health/NIH)

Bohórquez Lab (Duke University, Durham, NC)

Bohórquez Project Information (NIH RePORTER)

NIH Director’s New Innovator Award (Common Fund)

NIH Support: Common Fund; National Institute of Mental Health

7 Comments

  • carla3214 says:

    then you need to study the dirty vaccines and see how these heavy metals and toxins are destroying good bacteria. the rise of Autism with the increased forced vaccination of our children is obvious.

  • Patricia Chieffo says:

    Ideas like that are promoting a Measles Epidemic! Can we assume this opinion is being offered by
    a Scientist? Where is the proof that vaccines cause Autism? That theory has been debunked!

  • Rodrigo S. says:

    I recently started taking medicines that caused all those GI symptoms and behavioral symptoms to the letter (depakote + zyprexa). In my case, except for the GI discomfort, it has been a very effective drug for controlling my bipolar 1 disorder. I have previously come across research that hypothesizes autism and bipolar/schizophrenia lie on opposite ends of the same spectrum of neurodevelopment and behavior. Could giving me a slightly “more autistic” gut have helped my illness? Would it be possible to give someone a slightly “more bipolar” gut?

    Also lol at the person shoehorning vaccines in the comments, get a life 🙂 I literally see things that aren’t real and I know better.

  • DR. SAUMYA PANDEY PH.D. says:

    A spectacular innovative research endeavor deserving an applause!
    Indeed, immunomodulation including the complex gut-brain axis interactions at cellular, molecular, genetic level are intriguing; the receptor(s)-heterogeneity and differential binding affinities and subsequent regulation of downstream kinases, intermediary second messengers, altered Calcium-spikes, transcriptional activation and target gene activation with post-translational modifications in the interrelated biochemical/metabolic signaling including Toll-like-receptors-Friizled-Wnt-Necrosis-Apoptosis-Autophagy signaling cascades should be precisely dissected for deciphering the pathogenesis of GI-ASD disorders in genetically heterogeneous susceptible cohorts.

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