Altered intestinal antibacterial gene expression response profile in irritable bowel syndrome is linked to bacterial composition and immune activation

Bennet SMP1,2, Sundin J1,2, Magnusson MK2, Strid H3, Tap J4, Derrien M4, Le Nevé B4, Doré J5, Törnblom H1,6, Simrén M1,6,7, Öhman L1,2. Neurogastroenterol Motil. 2018 Sep 17:e13468. doi: 10.1111/nmo.13468. [Epub ahead of print]

Author information

1 Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

2 Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.

3 Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden.

4 Danone Nutricia Research, Palaiseau, France.

5 French National Institute for Agricultural Research (INRA) MetaGenoPolis, Jouy-en-Josas, France.

6 Centre for Person-Centred Care, University of Gothenburg, Gothenburg, Sweden.

7 Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina.


BACKGROUND: Immune activity and gut microbiota may impact the pathophysiology of irritable bowel syndrome(IBS). We aimed to determine whether antibacterial gene expression of immune activity-defined IBS patients differed compared to healthy subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial profiles reflected gut microbiota composition and IBS symptoms.

METHODS: Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered according to immune activity (systemic and intestinal cytokines): immunonormal or immunoactive), and UC patients was assessed by Human Antibacterial Response RT2 Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and mucosal bacteria was performed and symptom pattern and severity were assessed.

KEY RESULTS: Intestinal antibacterial gene expression profiles differed between IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups based on bowel habit predominance or symptom severity. Based on previously identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune activity (n = 16) had clearly separate antibacterial gene expression profiles from active UC patients (n = 12) and differed compared to each other and to HS. The differences in antibacterial gene expression profiles between immunonormal and immunoactive IBS patients were also reflected in distinct fecal and mucosal microbiota composition profiles, but not in symptom pattern or severity.

CONCLUSIONS & INFERENCES: This study demonstrates an altered antibacterial gene expression profile in IBS patients compared to HS and UC patients. While not linked to symptoms, immune activity-defined IBS clusters showed different intestinal antibacterial gene expression and distinct fecal and mucosal bacterial profiles.

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