Perhaps you’ve seen some of the headlines from trash news or news release aggregator sites: Researchers claim to have developed a urine-based panel of gut microbe metabolites that never returns a false positive.

I can’t say urine for a treat with this paper. But what you will get is three installments of my urine paper analysis.

Today is installment one: A Crumbly Foundation

The authors of this Flynn et al. study say that they measured the urine of 52 autistic children and 47 non-autistic children ages 2 to 11 years and developed a metabolite profile that unerringly identifies autistic children as autistic.

Let’s take a look at the foundations that Flynn et al. attempted to construct for their work.

The foundation?

The introduction to a scientific paper is intended to give context and rationale – the justification – for addressing a research question. In their intro, Flynn et al. begin by citing autism prevalence in the United States and then telling the reader how costly it is for a person to be autistic, emphasizing that high-support people cost oh-so-much more.

The second paragraph goes into the usual line about how early identification allows for early intervention and again, a mention of cost – savings this time — of “hundreds of billions of dollars per year.” But there’s a lil Easter egg in the form of a citation to a 2009 publication by none other than father and son grifter team David and Mark Geier, among others. To be clear, the “others” with the Geiers include a key author on this current study, James B. Adams. This is not a good sign!

Reaching back even further, Flynn et al. cite a 2003 paper as support for their statement that autism arises from genetic and environmental factors. The age of this citation (23 years!) suggests that the authors perhaps have not exactly stayed abreast of the literature.

And then we get into it.

Autism, you see, involves gastric (GI) symptoms, affecting “approximately 40%” of autistic people. For this assertion, Flynn et al. cite two studies – this one and this one — neither of which offers a value of “approximately 40%.” The first study, from 2023, reports 33% as the prevalence, with a wide range in the studies included in its meta-analysis, from 0% to 69%. Not surprisingly, the meta-analysis results also suggested a lot of variation in factors involving these studies. The second study, from 2014 (!), is a meta-analysis that reports odds ratios, not prevalence.

So far, the foundation for this work is about as stable as loose sand and gravel.

Then we learn that GI symptoms correlate in intensity with “severity of [autistic] traits.” The two citations for this claim are both from publications by several of the same authors on this study. I’ll name those authors now, as they come up again — and again: James B. Adams, Juergen Hahn, and Rosa Krajmalnik-Brown.

Then come the assertions that disrupted gut microbiota (the microscopic organisms living with us in our GI tracts) must be at the root of these symptoms because (trademark attempt alert!) “Microbiota Transplant Therapy” (a.k.a., MTT) yields “substantial improvement” in both gut and autism “symptoms.” There are five citations to support these assertions. Three again are self-citations, one is a trial of fecal microbiota transplantation (FMT; transplanting actual poop) and not MTT (transplanting selected microbes), and the fifth is a systematic review of five studies, one of them a single case report. That systematic review did not distinguish between FMT and MTT and included only one MTT study — by the current authors. With all of this self-citation, we have to take Flynn et al.’s word for it about “substantial improvement.” Gotta say, the citation track record so far does not inspire confidence.

Flynn et al. close this paragraph of their foundation-building intro with a citation for a publication uploaded to a preprint server in 2022. They apparently couldn’t be arsed to find the actual, peer-reviewed version of it published in 2023. This paragraph is a key pillar of the rationale for this study, and every citation is self-citing, irrelevant, or out of date. These features do not build trust in the rigor of this work.

The Flynn et al. team then go on to claim that unhelpful shifts in gut microbial communities in autistic people influence production of molecules involved in things like inflammation and “xenobiotic detoxification.” The citations for this? There are three (1, 2, 3). Not one mentions autism.

They then try to say that some gut metabolites “may affect human health at high concentrations” as a lead-in to effects on neurodevelopment. Of two citations for this statement, they recycle one that doesn’t address neurodevelopment at all (it’s about kidney dialysis patients) and another that at best could be considered to address mouse, rather than human, health (yes, an “autistic mouse” study). Then we get five citations, one for an in vitro study, one for a narrative review with no new data, another narrative review, one a book chapter from 2008, and another in vitro study focused on the kidney (a lot of this work focuses on the kidney). Of these, only one (one of the narrative reviews) contains even a single citation related to autism (from 2013 and extremely out of date in terms of study groups).

Finally, Flynn et al. take a big swing with a big claim about one single metabolite (why this one? More later). They write: “P-cresol is … processed … into p-cresol sulfate (pCS), which is higher in the urine of children with autism vs. controls in 17 of 17 studies.” The studies are actually a mix of findings related to this metabolite and the microbiota that produce it, with at least one not confirming the claim at all. I am not going to tediously go through all 17 (here’s a look at some of the literature), but the metabolite in question, p-cresol (or para-cresol or 4-cresol) comes to us in part by way of consumption of two amino acids, tyrosine (which we also can make ourselves and convert into neurotransmitters) and its precursor phenylalanine (which we must get from diet, such as Jell-O, cheese, eggs), and by way of environmental exposures (tobacco smoke! Essential oils!). It is associated with chronic kidney disease and C. diff infections but, like many molecules our bodies use, it may have beneficial effects, as well. Its presence does not indicate a clear-cut negative, although this metabolite does seem to go hard on the kidneys [NB: There are not a lot of signals in the literature linking these kidney issues to being autistic.]

So that’s the foundation of this work, such as it is, and that’s the first installment of three.

Keep an eye out for the second installment, “The company they keep,” next week, and the third and final entry, “Confounders, damned confounders, and statistics” the week after that.

News you can use

• In case it isn’t already clear, the Autistic Self Advocacy Network reminds us all that ABA hurts autistic people. Their statement is in response to a New York Times piece describing how a large chain of ABA centers countenances horrible mistreatment of children at the centers.

• New research: Although autistic people often face challenges navigating their social worlds, autism can also be associated with more generosity. From a study just published in the journal Autism:

  … compared with non-autistic people, autistic people give more money to people they feel less close to, like strangers. In this study, we replicated this finding. … this increased generosity in autism was not the result of autistic participants responding more repetitively in the task. … some autistic people could be more generous because they show differences in how they think about fairness. While autistic people often face challenges navigating their social worlds, autism can also be associated with more generosity.

• The head of an ABA consultancy gained an audience with California’s attorney general, Rob Bonta, and based on the company’s news release, the meeting probably was (thankfully) kind of a nothingburger. If AG Bonta does, indeed, have a “longstanding concern for and support of the disability community,” he will hopefully be aware that this mode of “intervention” is a racket.

• The Transmitter has a piece highlighting the thoughts of Christine Wu Nordahl, the scientific chair of the International Society for Autism Research (INSAR) meeting in Prague, about bringing “basic science” to the fore in these gatherings [NB: basic science means the earliest kind of hypothesis-generating, discovery-oriented research with findings that could take us in unpredictable directions]. Nordahl told The Transmitter that “One of the charges to me as the scientific program chair this year was to try to bring more biologists back.”

  In a Q&A with the outlet, Nordahl, who is professor of psychiatry and behavioral sciences at the University of California, Davis MIND Institute, said:

  Some of the geneticists we had invited to come speak at the meeting had concern about the kinds of questions they might get, and whether some would be very antagonistic, having heard experiences from colleagues in prior years. … And I think that’s what moves the field forward — it’s talking about these issues in a nonconfrontational or less confrontational way.

  You know, heaven forefend that autistic people don’t sit with quiet hands and listen while nonautistic researchers talk about targeting genes with the implicit aim of erasing autistic people. Quite the dilemma to have, whether to include those who seek to erase versus those who do not want to be erased.

  In case the slant on Nordahl’s comments wasn’t entirely clear, she also told The Transmitter:

  Talking to autistic people and their families has really changed how I view autism research. Not just people who can advocate for themselves, but also families of children with profound autism.

  As though “profound autism” truly delineates a distinct population of autistic people, and autistic advocates who don’t fit the constrained framing of the term have nothing useful to say about it. Meanwhile, as another TGPA editor notes, not a word about the real threat to basic research, which is the current executive branch of the US government. - “Screens” are such a lightning rod for the scolds of the world, and, it turns out, so are autistic people and autistic behaviors. So it’s no surprise that there’s a lot of handwringing about screen time by autistic people. And it is thus great to see this personal experience essay published in Autism in Adulthood, in which autistic author Alvin van Asselt talks about why screens are so important for him. Van Asselt calls for a “neurodiversity-affirming research agenda” when it comes to screen use among autistic people. For him, he writes:

  … screen use has enabled me to fulfill my core needs—particularly predictability, safety, autonomy, and meaningful belonging—which in turn facilitated my stress and sensory regulation, social development, executive functioning, and overall mental health across the lifespan.”

  I concur and was just cogitating this past week about how much time I spend on screens and almost always have one with me for exactly the same reason I used to spend just as much time carrying around books, magazines, pens, and writing paper – to read, write, and learn at every possible opportunity. - Just about every correlational study carries the baggage of whether the chicken or egg came first – in other words, which direction an apparent relationship goes. It is “interesting” to see the reactions to a study showing that parent mental health issues, rather than pharmaceutical treatment for these issues, are linked to having autistic children. To some people, the obvious interpretation is some genetic link between depression and autism – commonalities between pathways that cause the two. But an obvious confounder is simply the genetics of autism itself, and the distinct possiblity that parents of autistic children themselves have overlapping autistic traits that went unrecognized and unaddressed, potentially leading to mental health issues. - One of our other TPGA editors highlights a potential takeaway from yet another study of mothers and autistic children. In this case, a child was likelier to be autistic if the mother bad been in the military a year before the pregnancy and until after delivery or involved in the “judicial sector” or “ground transportation.” Y’all: routine, fairness, and trains. Wonder if genetics and autistic traits in the parent play a role. - Good golly, look at this, a study focused on improving constipation treatments for autistic children by homing in on real sensory issues they may have with the flavors and textures of common GI medications. - Autistic people don’t hear better, or hear worse, necessarily. They just hear differently, which could be in part what underlies some of their differences in receiving and expressing words. - It’s hard for young college graduates to find jobs right now, thanks to billionaires and bigots setting the world and the future on fire, but it’s even harder for autistic grads.

New at TPGA

Black Spectrum Scholar on Ethics In Online Autism Diagnoses — THINKING PERSON'S GUIDE TO AUTISM

Why did Black Spectrum Scholar have their advocacy and motives challenged, after asking if an autism diagnosis business behaved unethically?

Kaligirwa is a noted autistic autism scholar and advocate. They recently had their advocacy and motives challenged after they asked an autism diagnosis and resources company, Embrace Autism, whether it was behaving unethically in coaching people on how to take an online autism screening test. We wanted to know more, and so we talked with Kaligirwa about the incident and its repercussions both for them and for the already-questioned validity of autistic self-diagnosis.

Thanks for reading, and here’s to neurodiversity-affirming research agendas.

Got something autism-related to share with us? Send it along to editorial@thinkingautism.com.

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