Multi-omics for biomarker approaches in the diagnostic evaluation and management of abdominal pain and irritable bowel syndrome: what lies ahead

ABSTRACT

Reliable biomarkers for common disorders of gut–brain interaction characterized by abdominal pain, including irritable bowel syndrome (IBS), are critically needed to enhance care and develop individualized therapies. The dynamic and heterogeneous nature of the pathophysiological mechanisms that underlie visceral hypersensitivity have challenged successful biomarker development. Consequently, effective therapies for pain in IBS are lacking. However, recent advances in modern omics technologies offer new opportunities to acquire deep biological insights into mechanisms of pain and nociception. Newer methods for large-scale data integration of complementary omics approaches have further expanded our ability to build a holistic understanding of complex biological networks and their co-contributions to abdominal pain. Here, we review the mechanisms of visceral hypersensitivity, focusing on IBS. We discuss candidate biomarkers for pain in IBS identified through single omics studies and summarize emerging multi-omics approaches for developing novel biomarkers that may transform clinical care for patients with IBS and abdominal pain.

KEYWORDS:

• Microbiome
• microbiota
• metabolome
• genetic
• epigenetic
• transcriptome
• proteome
• functional gastrointestinal disorder
• connectome
• disorders of gut–brain interaction

Acknowledgments

The authors would like to acknowledge Thomas Weinzerl and the Indiana University Visual Media for preparation of the Figure.

Abbreviations

CBT = cognitive behavioral therapy; CGRP = calcitonin gene-related peptide; CRH = corticotrophin-releasing hormone; DGBI = disorders of gut brain interaction; EP2 = prostaglandin E2 receptor; GABA = gamma-aminobutyric acid; GC-C= guanylate cyclase C; GRPR = Gastrin releasing peptide receptor; HPA = hypothalamic-pituitary-adrenal; IBS = irritable bowel syndrome; IBS-D = IBS with diarrhea; miRNA = microRNA; NGF = nerve growth factor; NPFF = Neuropeptide FF; PI = post-infection; SERT = serotonin transporter; RNA-seq = RNA-sequencing; SCFA = short-chain fatty acids; TRP = transient receptor potential; TRPA1 = TRP cation channel subfamily A member 1; TRPV1 = TRP vanilloid 1; TRPV3 = TRP vanilloid 3; TRPV4 = TRP vanilloid 4; WAS = water avoidance stress; 5

Disclosure statement

AS serves on Ardelyx Scientific Communications Advisory Board for irritable bowel syndrome with constipation. PCK is an ad hoc consultant for Pendulum Therapeutics, IP Group Inc., Novome Biotechnologies, and Intrinsic Medicine. PCK holds the patent US20170042860A1 “Methods and materials for using Ruminococcus gnavus or Clostridium sporogenes to treat gastrointestinal disorders” for use of tryptamine producing bacteria to treat gastrointestinal disorders. Mayo Clinic and PCK have a financial interest related to use of tryptamine-producing bacteria.

Disclosures

AS serves on Ardelyx Scientific Communications Advisory Board for irritable bowel syndrome with constipation. PCK is an ad hoc consultant for Pendulum Therapeutics, IP Group Inc., Novome Biotechnologies, and Intrinsic Medicine. PCK holds the patent US20170042860A1 “Methods and materials for using Ruminococcus gnavus or Clostridium sporogenes to treat gastrointestinal disorders” for use of tryptamine producing bacteria to treat gastrointestinal disorders. Mayo Clinic and PCK have a financial interest related to use of tryptamine-producing bacteria.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Additional information

Funding

AS is supported by NIDDK K23DK122015, R03DK132446. PCK is supported by NIH R01DK114007.