Abstract

A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome

Sci Rep. 2021 Mar 9;11(1):5521. doi: 10.1038/s41598-021-84686-9.

Annikka Polster 1, Lena Öhman 2 3, Julien Tap 4, Muriel Derrien 4, Boris Le Nevé 4, Johanna Sundin 2 3, Hans Törnblom 2, Marija Cvijovic # 5, Magnus Simrén # 2 6

 
     

Author information

  • 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, 41345, Göteborg, Sweden. a.v.polster@ncmm.uio.no.
  • 2Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg, 41345, Göteborg, Sweden.
  • 3Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
  • 4Danone Nutricia Research, Palaiseau, France.
  • 5Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Göteborg, Sweden.
  • 6Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

#Contributed equally.

Abstract

Although incompletely understood, microbiota-host interactions are assumed to be altered in irritable bowel syndrome (IBS). We, therefore, aimed to develop a novel analysis pipeline tailored for the integrative analysis of microbiota-host interactions and association to symptoms and prove its utility in a pilot cohort. A multilayer stepwise integrative analysis pipeline was developed to visualize complex variable associations. Application of the pipeline was demonstrated on a dataset of IBS patients and healthy controls (HC), using the R software package to analyze colonic host mRNA and mucosal microbiota (16S rRNA gene sequencing), as well as gastrointestinal (GI) and psychological symptoms. In total, 42 IBS patients (57% female, mean age 33.6 (range 18-58)) and 20 HC (60% female, mean age 26.8 (range 23-41)) were included. Only in IBS patients, mRNA expression of Toll-like receptor 4 and genes associated with barrier function (PAR2, OCLN, TJP1) intercorrelated closely, suggesting potential functional relationships. This host genes-based "permeability cluster" was associated to mucosa-adjacent Chlamydiae and Lentisphaerae, and furthermore associated to satiety as well as to anxiety, depression and fatigue. In both IBS patients and HC, chromogranins, secretogranins and TLRs clustered together. In IBS patients, this host genes-based "immune-enteroendocrine cluster" was associated to specific members of Firmicutes, and to depression and fatigue, whereas in HC no significant association to microbiota was identified. We have developed a stepwise integrative analysis pipeline that allowed identification of unique host-microbiota intercorrelation patterns and association to symptoms in IBS patients. This analysis pipeline may aid in advancing the understanding of complex variable associations in health and disease.

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