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Specific pathobionts are enriched during flares in patients with severe CD


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Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn’s disease

2024 Feb 23

Department of Biotechnology and Biomedicine, Technical University of Denmark

Objective Patients with Crohn’s disease (CD) exhibit great heterogeneity in disease presentation and treatment responses, where distinct gut bacteria and immune interactions may play part in the yet unresolved disease aetiology. Given the role of antibodies in the barrier defence against microbes, we hypothesised that gut bacterial antibody-coating patterns may influence underlying disease-mediated processes.

Design Absolute and relative single and multicoating of gut bacteria with IgA, IgG1, IgG2, IgG3 and IgG4 in patients with CD and healthy controls were characterised and compared with disease activity. IgG2-coated and non-coated taxa from patients with severe CD were identified, profiled for pathogenic characteristics and monitored for enrichment during active disease across cohorts.

Results Patients with severe CD exhibited higher gut bacterial IgG2-coating. Supervised clustering identified 25 bacteria to be enriched in CD patients with high IgG2-coating. Sorting, sequencing and in silico-based assessments of the virulent potential of IgG2-coated and bulk stool bacteria were performed to evaluate the nature and pathogenicity of IgG2-coated and non-coated bacteria. The analyses demonstrated IgG2-coating of both known pathogenic and non-pathogenic bacteria that co-occurred with two non-coated pathobionts, Campylobacter and Mannheimia. The two non-coated pathobionts exhibited low prevalence, rarely coincided and were strongly enriched during disease flares in patients with CD across independent and geographically distant cohorts.

Conclusion Distinct gut bacterial IgG2-coating was demonstrated in patients with severe CD and during disease flares. Co-occurrence of non-coated pathobionts with IgG2-coated bacteria points to an uncontrolled inflammatory condition in severe CD mediated via escape from antibody coating by two gut pathobionts.


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"Pathobionts" is an awful recently invented term. Pathobionts are just pathogens, every pathogen is conditionally invasive. The term if often used to shield microbiome research when it turns out the microbiome is not as harmless as initially assumed, and includes a lot of unknown and invasive species.

"oops, there's a whole host of bacillota with pathogenic behavior, oops, they're actually in some probiotics. let's rename a bunch of stuff and invent a new term to cover our tracks."

The large large majority of the microbiome is completely unknown. The term "pathobiont" is not properly defined, and it allows you limitless freedom to classify any microorganism under the same umbrella, even by mere sequencing association. Evidence will increasingly show that the many gut bacteria are not as harmless as initially assumed and a lot of those "pathobionts" are very invasive, and very harmful pathogens for people with crohn's disease.

It would have been easier to just define the microbiome as gut bacteria that live in homeostasis with the host and have no feature that would make them tissue invasive or adherent to the gut wall. The immune reaction in crohn's disease is not directed at the microbiome, but it is directed at pathogens, which are gut bacteria all too often assumed to be harmless microbiome species.
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