On a related note: www.smbc-comics.com/comic/prompt...

It's out now! (15/15 😅)

www.tandfonline.com/doi/full/10....

Oops, you were on here already: @hannasimpson.bsky.social

Finally: our work wouldn't be possible without the dedication of all the participants (patients ánd healthy individuals) that contribute bodily materials (in this case: stool samples 💩) and that fill out several questionnaires covering many different topics. So: a big thanks 🙏! (14/15)

Functional follow-up studies will now have to address the infamous chicken-egg conundrum: which observed patterns are merely the consequence of the disease or the diet, and which were actually pre-existent and could play a role in disease onset or progression? (13/15)

Subsequently, we found that the disappearing E. rectale subspecies is characterised by a lack of motility genes and the presence of many glycosyltransferases, which corresponds perfectly to the European subspecies as described by Karcher et al. (DOI: 10.1186/s13059-020-02042-y). (12/15)

Lastly, we focused on observations in the bacterium Eubacterium rectale (now known as Agathobacter rectalis): besides increased interindividual variation among tCeD patients (see skeet 9/15), we also saw a cluster of strains (subspecies) being nearly absent in patients. (11/15)

In line with this, we find that a protein domain, implicated in DNA repair and associated with within-species mutation rates, was underrepresented in tCeD patients. Perhaps faster evolution (accelerated by reactive oxygen species) benefits bacterial survival during inflammation? (10/15)

Using the nucleotide-level resolution of MGS, we could also look into sub-species variation and found that several species also show an increased number of mutations in their core genome in patients, relative to controls. We speculate that inflammation may lead to elevated mutation rates. (9/15)

Interestingly, while we expected the microbiomes of tCeD patients to share a certain signature, we instead saw that they have less similar microbiome compositions (i.e. higher BC dissimilarity) than random pairs of control individuals. The same was seen for IBD, but not for IBS patients. (8/15)

We show that duration of GFD positively correlates (Spearman's Rho) with most of the overabundant species, suggesting a significant contribution of the diet to the observed patterns. (7/15)

We found several bacteria previously associated with CeD (including several Bacteroides species), but also identified novel associations, such as Roseburia hominis and Eggerthella lenta. (6/15)

First of all, as expected, there is little overlap between the microbial patterns observed in IBD, IBS, and coeliac disease, arguing against a general signature of intestinal problems. (5/15)

Microbial DNA from all stool samples was sequenced using Metagenomic Shotgun Sequencing (MGS), allowing high-resolution analysis of microbiome composition.

Now, let's dive in! 👇(4/15)

We also selected several IBD and IBS patients from Lifelines, with controls.

As virtually all CeD patients will adhere to a gluten-free diet (GFD) after having received diagnosis, the only available treatment, our study will find the combined effects of the disease and GFD. (3/15)

To set the scene: we combined data from our own Celiac Disease Northern Netherlands cohort (CeDNN; currently unpublished) with data from the population cohort Lifelines (https://www.lifelines.nl) to end up with stool samples of 152 CeD patients and 760 matched controls. (2/15)

Not E. coli, but FWIW: we resequenced S. pneumoniae D39 (several passages down the line from the Avery strain) and found differences with the original. Some of those may have been incorrect in the original assembly, others true differences.

academic.oup.com/nar/article/...

See table 1, fig. 3, S1