Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn's disease
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Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn's disease. / Eriksen, Carsten; Danneskiold-Samsøe, Niels Banhos; Moll, Janne Marie; Myers, Pernille Neve; Bondegaard, Pi W.; Vejrum, Simone; Hansen, Tine Brodka; Rosholm, Lisbeth Buus; Rausch, Philipp; Allin, Kristine Højgaard; Jess, Tine; Kristiansen, Karsten; Penders, John; Jonkers, Daisy; Brix, Susanne.
In: Gut, Vol. 73, No. 3, e330677, 2023, p. 448-458.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn's disease
AU - Eriksen, Carsten
AU - Danneskiold-Samsøe, Niels Banhos
AU - Moll, Janne Marie
AU - Myers, Pernille Neve
AU - Bondegaard, Pi W.
AU - Vejrum, Simone
AU - Hansen, Tine Brodka
AU - Rosholm, Lisbeth Buus
AU - Rausch, Philipp
AU - Allin, Kristine Højgaard
AU - Jess, Tine
AU - Kristiansen, Karsten
AU - Penders, John
AU - Jonkers, Daisy
AU - Brix, Susanne
N1 - Publisher Copyright: © 2023 Author(s) (or their employer(s)).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Gut Microbiota
KW - IgA-coating
KW - IgG-coating
KW - Intestinal bowel disease
KW - Mucosal immunity
U2 - 10.1136/gutjnl-2023-330677
DO - 10.1136/gutjnl-2023-330677
M3 - Journal article
C2 - 38123984
AN - SCOPUS:85180499127
VL - 73
SP - 448
EP - 458
JO - Gut
JF - Gut
SN - 0017-5749
IS - 3
M1 - e330677
ER -
ID: 377989148