Peter Dobranowski

@srmbeauroy @bottomlineibd @policritic Strong disease-level conclusions, with residuals perhaps explained by e.g. diet x gene x microbiome x psych x medication interactions. I anticipate future PREdiCCt studies will leverage these interactions to cut through noise and arrive closer to individualized predictions.

@bottomlineibd @policritic I agree that diet's important but on the face of it the study diminishes its role in flares. Or am I missing something? It's certainly been my experience that my diet doesn't stop my inflammation from waxing and waning.

Although diet is only one element of the PREdiCCt study, there's a reason it's super important to me as an #IBD patient. Why? 1. Back in the year dot when I was diagnosed, most clinicians dismissed diet as irrelevant. 2. Unlike much of the misery of IBD, diet can be modified.

@IldikoMe Nonetheless, metagenomics on the removed appendices seems like low-hanging fruit to predict responders/non-responders.

@IldikoMe I was excited to read this as an indictment on the microbiome, but certainly tempered by the nuance - appendicectomy was adjunct to biologics, and 80% of the control group was given Tofa 10mg. E.g. outcomes would be different without adjunct biologics or with a 100% Upad control.

The appendectomy saga continues.

Writing this made me feel better this week. I hope reading it makes you feel better. theintrinsicperspective.com/p/we-are-not-l…

This is not a totally surprising outcome of precision medicine (and may be useful in certain contexts): patients predicted to respond to a therapy may simply fare better without the therapy to begin with.

Clinical remission was more likely in “predicted responders” (32%) than non-stratified patients (26%). But, clinical remission was also more likely in “predicted responders” randomized to the placebo group (11%) than non-stratified placebo patients (1%).

2025 @NEJM study by @bruce_sands1 et al reports efficacy and safety of anti-TL1A (Tulisokibart) in moderate-severe #UC. Notably, they evaluated patient stratification using a gene-variant machine learning algorithm. nejm.org/doi/full/10.10…

Given that gut barrier dysfunction can precede IBD diagnosis by years, the role of butyrate remains a critical part of IBD research: as a biomarker of disease, and therapeutic lever through personalized diet, next-gen probiotics, and FMT. 10.1016/j.clnu.2022.10.024

But, this vicious cycle parallels a virtuous cycle – treating these dysbiotic mice with butyrate reversed DUOX2 upregulation, epithelial permeability, and subclinical inflammation.

From 2025 @Gut_BMJ, Hazime et al @ibddocmaria untangle more of DUOX2’s role in early / subclinical #IBD, with new evidence of #butyrate’s role in maintaining gut homeostasis gut.bmj.com/content/early/…

#IBD microbiomes (generally) are depleted in primary fiber degraders, enriched in H₂S producers (but not methanogens), and lower in butyrate, suggesting a dysregulated “hydrogen economy” may be constraining butyrate production.

H₂ is a by-product of dietary #fiber fermentation, and is cross-fed by methanogens, H₂S-producers, and acetogens. Healthy participants had breath H₂ measured before and after a #resistantstarch intervention. Butyrate production was higher in participants lacking methanogens.

From 2023 @MicrobiomeJ, Campbell et al answer a fascinating question: how does hydrogen direct microbial fermentation towards acetate versus butyrate production in the gut? microbiomejournal.biomedcentral.com/articles/10.11…