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CBT for IBS induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement, 2021,Jacobs et al

Discussion in 'Other psychosomatic news and research' started by Sly Saint, Dec 21, 2021.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement

    Abstract
    Background
    There is growing recognition that bidirectional signaling between the digestive tract and the brain contributes to irritable bowel syndrome (IBS). We recently showed in a large randomized controlled trial that cognitive behavioral therapy (CBT) reduces IBS symptom severity. This study investigated whether baseline brain and gut microbiome parameters predict CBT response and whether response is associated with changes in the brain-gut-microbiome (BGM) axis.

    Methods
    Eighty-four Rome III-diagnosed IBS patients receiving CBT were drawn from the Irritable Bowel Syndrome Outcome Study (IBSOS; ClinicalTrials.gov NCT00738920) for multimodal brain imaging and psychological assessments at baseline and after study completion. Fecal samples were collected at baseline and post-treatment from 34 CBT recipients for 16S rRNA gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acids. Clinical measures, brain functional connectivity and microstructure, and microbiome features associated with CBT response were identified by multivariate linear and negative binomial models.

    Results
    At baseline, CBT responders had increased fecal serotonin levels, and increased Clostridiales and decreased Bacteroides compared to non-responders. A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy (AUROC 0.96). Following treatment, CBT responders demonstrated reduced functional connectivity in regions of the sensorimotor, brainstem, salience, and default mode networks and changes in white matter in the basal ganglia and other structures. Brain changes correlated with microbiome shifts including Bacteroides expansion in responders.

    Conclusions
    Pre-treatment intestinal microbiota and serotonin levels were associated with CBT response, suggesting that peripheral signals from the microbiota can modulate central processes affected by CBT that generate abdominal symptoms in IBS. CBT response is characterized by co-correlated shifts in brain networks and gut microbiome that may reflect top-down effects of the brain on the microbiome during CBT.

    https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01188-6#Sec2
     
  2. rvallee

    rvallee Senior Member (Voting Rights)

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    Since they did not bother to provide a reference for the other trial mentioned in the abstract: Improvement in Gastrointestinal Symptoms After Cognitive Behavior Therapy for Refractory Irritable Bowel Syndrome.

    This study is a roll-over from the other trial, which obviously was not controlled but whatever, details, details:
    I am trying to decrypt what this means, it's very muddled, but it seems that they found different microbiota in some people, and tried to correlate that with "CBT responders", whatever that means.
    They really do appear to suggest that CBT changes gut microbes. Amazing.

    This is kind of funny, as it's a common assertion:
    Something tells me this will be entirely forgotten already.

    Yes, they really are saying that thoughts can alter the gut microbiome:
    Even though it's the microbiota that is the only predictor:
    Differences, such as noted, in the microbiota:
    But, hey, human-microbial telepathy is so much more exciting!

    Breaking: hammer found nails, stomped them flat.
     
  3. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    I am curious to know what exactly the CBT consisted of as I seem to remember in another trial (different research group, I think it was the moss-morris lot) they gave the recipients advice on diet.
     
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  4. strategist

    strategist Senior Member (Voting Rights)

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    This is the clinical trial and these were the treatment arms

    1) standard-CBT (S-CBT, n = 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training)

    2) 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n = 145), in which patients received home-study materials covering the same procedures as S-CBT)

    3) 4 sessions of IBS education (EDU, n = 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise.

    They emphasize that MC-CBT was better than EDU. I suspect this means that S-CBT didn't work as well.

    https://pubmed.ncbi.nlm.nih.gov/29702118/

    Also despite the grandiose claims of being a controlled clinical trial I can see huge holes for bias to affect results.

    Since the CBT involves so many things it's a bit hard to say what actually helped. Less therapist contact seemed to be better so it's probably not what the therapists think is good (this is an assumption based on how they emphasize the results of the low intensity treatment, I'm too lazy to actually go and find out).
     
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  5. Ariel

    Ariel Senior Member (Voting Rights)

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    "Bidirectional signalling", "bidirectional alterations in the brain-gut-microbiome axis"

    Who is to say there aren't more directions? Does this actually mean anything?
     
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  6. Joan Crawford

    Joan Crawford Senior Member (Voting Rights)

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    "human-microbial telepathy"

    Priceless
     
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  7. rvallee

    rvallee Senior Member (Voting Rights)

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    I'd say it means pretty much whatever one wants it to say. There are no wrong answers. No right answers either but no one's counting so it's fine. That's the advantage of shapeless bags of hot air, it will fill any container you put it into.
     
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  8. Amw66

    Amw66 Senior Member (Voting Rights)

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    So given advice on diet was part of the protocol was diet even monitored?

    Changes in nutritional profiles may influence gut microbiome - potentially significantly.

    Did anyone have antibiotics for an unrelated illness with knock on effects?
     
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  9. Hutan

    Hutan Moderator Staff Member

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    84 people all got CBT.

    Over the trial period, some of these people's IBS symptoms improved.
    The study found some things were associated with improvement over the trial period - fecal serotonin levels and levels of certain high level groups of micro-organisms in the gut. Those findings are possibly interesting and could have been the basis of a useful paper. These findings are from only 34 participants (22 had improved over the trial and 12 had not).

    But yes, as @rvallee said, these people have a CBT hammer, and they are going to belt everything they see with it, logic be damned. At least from the abstract, this study tells us nothing about whether CBT has any impact on IBS symptoms - because all the participants got CBT.

    I do not understand how people can write this rubbish, and peer reviewers and journal editors can allow it to be published, and how these authors are funded to keep on producing this type of work. The problems with this paper are not subtle.
     
    Last edited: Dec 22, 2021
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  10. Hutan

    Hutan Moderator Staff Member

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    Metabolomics at baseline


    Screen Shot 2021-12-22 at 3.47.42 PM.png

    God knows how many metabolites were measured. 55 are recorded in Table S3 as being different among those who got better ("responders") and those who didn't ("non-responders") over the trial, but none of the comparisons survived adjustment for multiple comparisons. It's a real stretch to suggest that the metabolites at baseline predicted who would improve over the trial period, even for serotonin - look at the overlap in the D Serotonin chart in the picture above. The sample was not big enough, the differences were not marked enough.


    Metabolomics after the CBT treatment
    So, basically there's nothing in the metabolomics whichever way you slice it and the conclusion about serotonin isn't warranted.
     
    Last edited: Dec 22, 2021
  11. Hutan

    Hutan Moderator Staff Member

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    I really should not have gone down this rabbit hole.

    Stool consistency
    That's important because pretty much all of the other measures of improvement supposedly resulting from the CBT were subjective.

    Screen Shot 2021-12-22 at 4.36.01 PM.png

    Microbiome
    I've run out of steam, but it looks to me as though, after the CBT, the people who reported improvements actually had microbiomes that looked more similar to those of the people who didn't report improvements - that is, their microbiomes became Bacterioides predominant. I think trying to get much meaning out of microbiome compositions is mostly hopeless when you aren't getting down to species/strain level.

     
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  12. rvallee

    rvallee Senior Member (Voting Rights)

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    Only checked at baseline, at least from what the paper says. The sheer diversity of what people eat, and their provenance, makes this all a pretty useless study:
    I'm not sure how they assessed that since they only mention having checked at baseline, so it's unclear:
    I'm not sure how they can claim that, since there is no mention of having checked diet after baseline, though it may have occurred, but unless they actually recorded everything that was consumed, there is a lot of work going on behind that statement, the "CBT-associated alterations" is bizarre, as people don't eat the same thing all the time anyway, and they don't need to be told to do so:
    So different diet, different gut bacteria. But, hey, sure, CBT did a thing. Why not?!

    Now I'm kind of pissed at how the editors allowed the language of "CBT responders" when there is nothing to attribute to CBT anyway. Basically trying to attribute improvement without having to provide evidence, let's just label them this way and hope no one notices. Seems mostly out of tradition as it's common to use that term.
     
    Last edited: Dec 24, 2021

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