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This week, we are joined by Kevin Mitchell, who has committed the unforgivable sin of pointing out that an entire academic and media hype cycle might be built on… well, very little actually. His new co-authored paper in Neuron politely dismantles the highly promoted link between the gut microbiome and autism, which turns out to rest on flawed studies, contradictory findings, creative statistics, and a touching faith in mice burying marbles.

Kevin walks us through the joys of observational studies that don’t replicate, mouse experiments that don't make sense, and clinical trials where there is no blinding and no control wing, and shockingly, everyone reports feeling better. Meanwhile, journalists and wellness gurus eagerly report each new “breakthrough” unburdened by any concerns about the strength of evidence or methodological robustness.

In the end, the microbiome–autism connection looks less like a sturdy scientific stool and more like three damp twigs taped together by optimism and marketing departments.

We finish, naturally, by dragging Matt back out of his panpsychism phase and asking whether consciousness is really fundamental to the universe or just something that happens in podcasters who haven’t slept enough.

Links

Mitchell, K. J., Dahly, D. L., & Bishop, D. V. (2025). Conceptual and methodological flaws undermine claims of a link between the gut microbiome and autism. Neuron.

Kevin Mitchell's Website

Comments

Linda Sears

Yay! This sounds like fun!

DJM

Thou shall not undermine optimism in the gut microbiome! You’ll tank the microbiome economy!

Erland Hvittfeldt

Very nice, your last interview is probably my favorite interview episode of yours, havelistened to it at least three times.

Erland Hvittfeldt

Totally OT, could anyone link to the episode where Lex F hold his insufferable monologue about what a lone wolf he is, used in the Galaxy brain montage? I want to send it to a fan of his 🙂.

Colin

"an entire academic and media hype cycle might be built on… well, very little actually" Media, academic and commercial hype are built on the same thing: attracting investors. If you want viewers, you need to hype it. If you wanna get a grant, you need to hype it. If you want investment in your company: hype it. Hype is seen as bad. And it is, but at the same time, it's good to tell a simple compelling story about what you are offering and what you plan. When does that just become hype and bullshit? I don't really know. It's a balancing act. In academic science we're all operating just below the threshold level where telling a compelling story becomes telling a hyped one, or a simplifying a complicated result becomes misrepresenting it. I'm finding it increasingly easy to forgive those who step over the line. They get fired, but they are not necessarily uniquely corrupt people, many are just people under pressure to produce an "impactful" result from very expensive experiments, whose outcome is inherently uncertain. Is it reasonable to put people under that pressure? Is there an alternative? It's often said "The incentives are wrong". But what should they be? Do we expect funders to back people who produce uninteresting, low impact science? Do we expect that science to get the same attention as more significant results? It won't ever happen, and it might not be so great if it did. I did write a well received paper that knocked down previous results. My most well received paper in fact. It's harder to build something new. And it involves quite a bit of salesmanship, no doubt about it. It is a tough one, and really quite a pressured position for us simple nerds to be in. I'm going to listen while I write a talk. I say it's a tough one, which it is, but Dorothy Bishop who's an author on this paper seemed to navigate it with no problem whatsoever. I'd be interested to know whether it really was easy for her, particularly in her early or mid career stages when she was trying to power forwards.

RareTripleBait

some of us are also rather obsessed with what goes in‘n‘out of us

Linda Sears

I can certainly see how linking the microbiome with autism serves the MAHA agenda.

Carina S.

I really hope you didn't really reconcile your disagreement about consciousness, it's way too good as a subject of banter.

Joe Euro

Basic question but can someone explain what preregistration of a study is? Is it saying publically what you are testing and what criteria you are using before you do the research so you can't blag it after collecting the data?

Maytree

AI maybe not going to be a panacea for finding cause and effect (eg diagnostic use) bc it’s made to find meaningless patterns. Interesting insight.

Maytree

Will this be public. I’d like to share with non Patreon members if possible. Very useful episode to share esp on the diagnostic stuff.

Grignard Girlie

Omg amazing episode. I love the analysis on the microbiome research and the sketchy mouse models- as someone who does biomedical research it was so refreshing to hear these takes. Animal models are awesome for so many things (you can get a mouse addicted to a substance, you can model some disease states super well)- but for something like autism those models are really sketchy. All models are of course wrong but some are useful and others seem like wishful thinking

Stoyo

Very good episode! Would be happy to hear more like this from other research fields. “AI” is given a slightly rougher treatment than it deserves, implying that anything more flexible than a regression is a black box and that people don’t know to split their data into train, test, validations sets… but overall the problems identified are worth talking about whenever possible.

Stoyo

I also think Kevin and his coauthors understate the validity and overall credibility (not to mention level of evidence) behind the mouse models of traits related to ASD. In a highly polygenic disorder single gene knockouts create heterogeneous outcomes - no surprise there. Nevertheless, a substantial number of such models do produce consistent phenotypes with repetitive behaviors and disturbances of social interaction (as well as physiological, not just behavioral signatures of neurodevelopmental pathology). The argument that we can model epilepsy, but not social disturbance in a social animal doesn’t seem strong. It implies that epilepsy is somehow more “biological” than social behavior. The more parsimonious assumption seems to be that affiliative/bonding/parental behaviors have conserved neurobiological underpinnings, as do most things

Joe Euro

Great episode. Thanks! Can Kevin do this same analysis for every health claim out there? Would be v helpful. Cheers

Ema

Great episode! You should get Mitchell on more often. Also glad that gut biome autism things been debunked. The whole theory didnt make much sense. Giving autistic children fecal transplants feels abusive, and particularly bad when they didnt even have a control. Please do a decoding academia on this. I am involved in a couple of low replicate plant/animal microbiome studies and am in continual fear of creating this kind of misinformation. Its a hard balance when you are in a really underfunded or new research area. Also I agree with Chris on the whole conciousness thing.

Matthew Zingarella

Interesting to hear the take on machine learning in microbiome research. I’m in grad school studying genomics right now and taking a microbial community analysis course. Making PCoA plots and using ML algorithms to assign clusters was a major component of the course.

Chris Rincón

Matt shilling for Big Panpsychism is wild

Nancy Hale

Terrific episode! As someone who had a loved one with a neurological disorder (Parkinsons disease) I’m still a bit tuned into the community of PD patients and family members. Granted, PD is different from autism in that its diagnosis is not largely behavioral but physical (tremors, rigidity, etc.) I used to hear a lot of talk about the “brain-gut connection” including the microbiome and “leaky gut.” It’s always sounded a bit thin to me, and I’ve always wanted to see some solid analyses of the studies. Kevin offered some great insights on challenges with doing research into these brain-gut hypotheses.

John Pohl

Good episode. I would like to point out one thing that may have been said incorrectly during the podcast. I am a pediatric gastroenterologist so I take care of many children with autism and other disorders. When it was discussed that children with Down syndrome have increased G.I. disorders similar to that of children with autism, that statement is not correct. Children with Down syndrome have a genetic syndrome (trisomy 21) leading to associated immune and GI neurological dysfunction that sets them up for various and very serious G.I. disorders. These disorders include Crohn disease, celiac disease, and Hirschsprung disease. Such a correlation is not seen in children with autism.

Ryan Booker

I enjoyed that. Thanks for injecting some sanity into the feed. 😆

Zendegi Leonard

Great episode. It would be helpful for any students in the sciences to listen too. Can anyone point me towards information about the issues with positive psychology that was quickly mentioned in the end? I am interested in that area but also sceptical about it as well.

Zendegi Leonard

"I have not, or ever been, a Panpsychist" belongs on a shirt.

Melinda

THANK YOU KEVIN! I don't like the "what it feels like to be a bat" explanation of consciousness either! Very nebulous indeed.

Ymirsdreams

An an autist, it's highly likely the mice were just angling for more marbles.

Martin 🇧🇻

I'm with Chris on the whole consiousness thing - I don't see the mystery or issue at all. So either I (and Chris?) am very smart (unlikely) or I don't have the understanding needed to even come up to the level of seeing the problem/mystery.

Max

Important topic and beautiful science communication!

Damien

This was really enjoyable.

Linda Sears

I agree with Kevin that consciousnesss requires the ability to feel, yet I agree with Chris that it is not mysterious and is an emergent property of agentic beings.

Trees

Great episode! Anti-establishment narratives I can get behind. Also, is consciousness caused by the gut microbiome? Maybe that's how Chris became a p-zombie. Too much sweet coffee.🤯

MoooinkForYourSupper

Great episode! Though did notice that - in isolation - some of the things said, sounded rhetorically very familiar... "The whole field is just spinning it's wheels" "What would make you change your mind? If you don't have an answer, its not an honest endeavour" "There is a shared interest to believe the thing is real" "We need to get everyone together and figure out what's going on with these journals... Something's not right" I think the difference is that you are ultimately measured and have good faith, and you are objecting to specific statistical practices. But I love to see more discussion of the nuances, just to help lay people understand why your anti-institutional critiques are more valid than e.g Eric's or Sabines!

James Smith

For someone who hates Panpsychism as much as you do, your intuition that there "is no mystery to subjective experience" is very Panpsychist (in the formal sense).

Nina J.

This was excellent! It’s fascinating that a not-insignificant chunk of the population desperately wants an environmental explanation for autism rather than the genetic one that’s far more plausible. Kevin posited that this is because the genetics involved are an inherently complicated, technical, and unsatisfying story. This makes sense to me, but given the right-wing obsession with blaming autism on anything but genetics, I wonder if there are also some subconscious motivations at play. These people often have eugenics-adjacent fixations on purity – there are whole online communities hysterical over the possible genetic ramifications of reproducing with people who’ve been vaccinated for COVID, for fuck’s sake. They also tend to sanctify reproduction and parenthood, but are often extremely harsh about the choices of mothers; it makes sense to me that they’d prefer to blame a woman for choosing to take Tylenol after conception, for being fat while pregnant, or for feeding her kid the wrong foods than to acknowledge that the raw material contributed by either the mother OR father (or both) likely predisposed their child to neurodivergence.

Nina Davies

I had to work up to this, given my exposure to 25 years of autism discourse nonsense at this point. However, it was worth it just to listen to the sentence (not an exact quote) 'if you have a restricted diet it is likely to cause problems with your gut'. What on earth would it be that would make you believe it was the other way round?

Sue Fricke

Really enjoyed this discussion. Would be keen for decoding academia on the paper.

Alex R

Great episode, love the deep dive. I did think though that Kevin's comments on machine learning were a bit off the mark. In particular I don't think he distinguished between what is generically true about ML-based analyses vs. the poor way that some/many ML analyses in the literature have been done. Any proper ML analysis should look at questions of overfitting, statistical power, etc.