The Role of the Gut Microbiome in Autism

The Role of the Gut Microbiome in Autism
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What role do antibiotics play in the development and treatment of autism spectrum disorder?

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

“There are many examples in nature of intestinal microbes altering host behavior. One such example involves the [brain parasite] Toxoplasma”…when it infects [a] rodent [through the gut, it finds its way into the brain] and causes the animal to lose its innate fear of the odor of bobcat urine.” Why does the parasite care about what mice are afraid of? Because “by not avoiding” predators, they’re “more often caught” and eaten; so, the parasite can then go on “to infect other rodents.” If you’re a mouse-brain parasite, how are you going to spread? Mice aren’t cannibals; so, you have to make sure the mouse you’re in is eaten by something else. So, the parasite evolved a way to alter the mouse’s behavior.

Given the potential power of microbes to affect behavior, might the disruption of our gut microbiome, our good gut bacteria, be a potential factor in the causation of autism? Where’d they get that idea from? Well, kids with autism do tend to have altered gut flora, different than those of children without autism—for example, significantly less Prevotella in autistic children, which, if you remember, characterized the healthy gut enterotype that you can foster the growth of yourself with a more plant-based diet.

But, which came first? Instead of the bad gut flora leading to autism, isn’t it more likely that the autism led to the bad gut flora? Children with autism eat diets with significantly fewer servings of fruits and vegetables, “often characterized by a lack of variety, an inadequate amount of fiber-containing foods [meaning whole plant foods in general] and an increased amount of [added sugars].” So, couldn’t that explain the different gut flora right there?

There are some “perinatal risk factors” for the development of autism, including premature birth, low birth weight, and “delivery by caesarean section”—particularly the C-section. What does that have to do with the microbiome? Well, “[t]here may be a protective value offered by the maternal vaginal microbiome” that the infant misses out on when they instead come out through a surgical incision. During a C-section, the mothers are also sometimes placed under general anesthesia, and it’s possible that the anesthetics could affect the babies’ brains before the babies are disconnected from the maternal blood supply. To differentiate between the two scenarios, we’d need a study that compared autism risk between C-sections in which the moms just got an epidural or spinal block, versus C-sections under general anesthesia. But there had never been such a study…until, now.

“This study examined the incidence of autism in [infants] delivered vaginally, by C-section with [just] regional anesthesia…, and by C-section with general anesthesia.” And, only those delivered by C-section under general anesthesia had higher risk—not those in C-sections where moms just got like an epidural. So, that would suggest the C-section connection is more of an anesthesia drug exposure thing than involving the lack of vaginal flora exposure. This wasn’t an interventional trial, though, in which mothers were randomized to the various groups, just an observational study. So, it’s possible the increased autism risk had less to do with the anesthetic itself than the pregnancy complications that may have led to having to put the mother under. Either way, I’m not seeing the microbiome connection.

They’ve tried probiotics for children with autism, and so far, they don’t seem to have helped much. Some families, in desperation, have tried fecal transplants, where they like beg the neighbor kid to donate. It’s like what one fly said to the other—is this stool taken? Not FDA-approved, though; so, families are forced to go on the brown market.

It can all be traced back to this remarkable study published in the Journal of Child Neurology. “Several parents of children with regressive-onset autism”—meaning the kids started out acting normally before the autism struck—noted that it all seemed to start after their child had taken antibiotics. They had gotten “chronic diarrhea” (autism isn’t the only thing that can run in your genes *ahem*)… suggesting the antibiotics had mucked with their gut flora, and then came the “loss of language, play, and social skills.” Now, this could be a total coincidence, but it led these group of pediatric gastroenterologists to speculate that maybe there was some sort of cause-and-effect link there. Maybe by wiping out the good bugs, some bad bugs took hold, some neurotoxic bugs, and that led to the autism. If this were true, maybe they could clean the slate once again, another dose of antibiotics, but this time to try to clear out any bad bugs lurking down there. Might this reduce autism symptoms in these individuals? That would be groundbreaking.

They put the kids on a powerful antibiotic called Vancomycin, and 80% of the kids got better. But, within a few weeks after the treatment, most of them slipped back towards their baseline—suggesting that perhaps the bad bugs got pushed down, but not out.

This study was performed nearly 20 years ago, and only had an “n” of 11, meaning it only looked at 11 kids. (The letter n is research-speak for the number of subjects in a study.) Surely, by now, there’s been lots larger studies done. But, in reality, there’s only been a single follow-up study published, and it had an n of 1.

“A…case report of a child with autism improving on antibiotics and a father’s quest to understand what it [all] may mean,” written by the father himself, describing a dramatic improvement in his child’s autism after taking amoxicillin. When he talked to other parents of autistic children, he was surprised to discover that many of them “routinely g[a]ve their children antibiotics” expressly for that purpose, though he also heard from other parents that felt that their children’s autism got worse after antibiotics, or that antibiotics were blamed for the emergence of the disorder in the first place. But, that all speaks to the potential role of the gut flora, just reinforcing the notion.

Other parents were talking about it, but then when he scoured the medical literature to learn more, all he was able to turn up was that 11-child study. How is it possible that there hadn’t been follow-up studies? Here it was, right before his eyes, personally witnessing evidence in his own child of what that study had shown, this seemingly intractable condition rapidly and dramatically ameliorated in response to an antibiotic—at least in some children, but surprisingly there were no attempts to repeat that study. Now, I think most parents would probably just count their blessings, that at least it worked on their child, and leave it at that, but not this parent. He started his own “Autism Research Foundation, with the mission of encouraging, sponsoring, and communicating breakthrough autism research.”

Please consider volunteering to help out on the site.

Image credit: Little Rock Air Force Base. Image has been modified.

Motion graphics by Avocado Video.

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

“There are many examples in nature of intestinal microbes altering host behavior. One such example involves the [brain parasite] Toxoplasma”…when it infects [a] rodent [through the gut, it finds its way into the brain] and causes the animal to lose its innate fear of the odor of bobcat urine.” Why does the parasite care about what mice are afraid of? Because “by not avoiding” predators, they’re “more often caught” and eaten; so, the parasite can then go on “to infect other rodents.” If you’re a mouse-brain parasite, how are you going to spread? Mice aren’t cannibals; so, you have to make sure the mouse you’re in is eaten by something else. So, the parasite evolved a way to alter the mouse’s behavior.

Given the potential power of microbes to affect behavior, might the disruption of our gut microbiome, our good gut bacteria, be a potential factor in the causation of autism? Where’d they get that idea from? Well, kids with autism do tend to have altered gut flora, different than those of children without autism—for example, significantly less Prevotella in autistic children, which, if you remember, characterized the healthy gut enterotype that you can foster the growth of yourself with a more plant-based diet.

But, which came first? Instead of the bad gut flora leading to autism, isn’t it more likely that the autism led to the bad gut flora? Children with autism eat diets with significantly fewer servings of fruits and vegetables, “often characterized by a lack of variety, an inadequate amount of fiber-containing foods [meaning whole plant foods in general] and an increased amount of [added sugars].” So, couldn’t that explain the different gut flora right there?

There are some “perinatal risk factors” for the development of autism, including premature birth, low birth weight, and “delivery by caesarean section”—particularly the C-section. What does that have to do with the microbiome? Well, “[t]here may be a protective value offered by the maternal vaginal microbiome” that the infant misses out on when they instead come out through a surgical incision. During a C-section, the mothers are also sometimes placed under general anesthesia, and it’s possible that the anesthetics could affect the babies’ brains before the babies are disconnected from the maternal blood supply. To differentiate between the two scenarios, we’d need a study that compared autism risk between C-sections in which the moms just got an epidural or spinal block, versus C-sections under general anesthesia. But there had never been such a study…until, now.

“This study examined the incidence of autism in [infants] delivered vaginally, by C-section with [just] regional anesthesia…, and by C-section with general anesthesia.” And, only those delivered by C-section under general anesthesia had higher risk—not those in C-sections where moms just got like an epidural. So, that would suggest the C-section connection is more of an anesthesia drug exposure thing than involving the lack of vaginal flora exposure. This wasn’t an interventional trial, though, in which mothers were randomized to the various groups, just an observational study. So, it’s possible the increased autism risk had less to do with the anesthetic itself than the pregnancy complications that may have led to having to put the mother under. Either way, I’m not seeing the microbiome connection.

They’ve tried probiotics for children with autism, and so far, they don’t seem to have helped much. Some families, in desperation, have tried fecal transplants, where they like beg the neighbor kid to donate. It’s like what one fly said to the other—is this stool taken? Not FDA-approved, though; so, families are forced to go on the brown market.

It can all be traced back to this remarkable study published in the Journal of Child Neurology. “Several parents of children with regressive-onset autism”—meaning the kids started out acting normally before the autism struck—noted that it all seemed to start after their child had taken antibiotics. They had gotten “chronic diarrhea” (autism isn’t the only thing that can run in your genes *ahem*)… suggesting the antibiotics had mucked with their gut flora, and then came the “loss of language, play, and social skills.” Now, this could be a total coincidence, but it led these group of pediatric gastroenterologists to speculate that maybe there was some sort of cause-and-effect link there. Maybe by wiping out the good bugs, some bad bugs took hold, some neurotoxic bugs, and that led to the autism. If this were true, maybe they could clean the slate once again, another dose of antibiotics, but this time to try to clear out any bad bugs lurking down there. Might this reduce autism symptoms in these individuals? That would be groundbreaking.

They put the kids on a powerful antibiotic called Vancomycin, and 80% of the kids got better. But, within a few weeks after the treatment, most of them slipped back towards their baseline—suggesting that perhaps the bad bugs got pushed down, but not out.

This study was performed nearly 20 years ago, and only had an “n” of 11, meaning it only looked at 11 kids. (The letter n is research-speak for the number of subjects in a study.) Surely, by now, there’s been lots larger studies done. But, in reality, there’s only been a single follow-up study published, and it had an n of 1.

“A…case report of a child with autism improving on antibiotics and a father’s quest to understand what it [all] may mean,” written by the father himself, describing a dramatic improvement in his child’s autism after taking amoxicillin. When he talked to other parents of autistic children, he was surprised to discover that many of them “routinely g[a]ve their children antibiotics” expressly for that purpose, though he also heard from other parents that felt that their children’s autism got worse after antibiotics, or that antibiotics were blamed for the emergence of the disorder in the first place. But, that all speaks to the potential role of the gut flora, just reinforcing the notion.

Other parents were talking about it, but then when he scoured the medical literature to learn more, all he was able to turn up was that 11-child study. How is it possible that there hadn’t been follow-up studies? Here it was, right before his eyes, personally witnessing evidence in his own child of what that study had shown, this seemingly intractable condition rapidly and dramatically ameliorated in response to an antibiotic—at least in some children, but surprisingly there were no attempts to repeat that study. Now, I think most parents would probably just count their blessings, that at least it worked on their child, and leave it at that, but not this parent. He started his own “Autism Research Foundation, with the mission of encouraging, sponsoring, and communicating breakthrough autism research.”

Please consider volunteering to help out on the site.

Image credit: Little Rock Air Force Base. Image has been modified.

Motion graphics by Avocado Video.

Doctor's Note

I referred to my video What’s Your Gut Microbiome Enterotype?, which you may want to check out. The more important one, however, is How to Change Your Enterotype.

For more on sprucing up your friendly flora, see:

If you’re interested in trying to prevent or treat autism—which I completely respect not everyone is—you may want to check out:

If you haven’t yet, you can subscribe to my videos for free by clicking here.

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