Neurogastroenterol Motil. 2023 Apr 24;e14573. doi: 10.1111/nmo.14573. Online ahead of print.

Daniel F Castillo ^1 2, Lee A Denson ^1 2, David B Haslam ³, Kevin A Hommel ⁴, Nicholas J Ollberding ^2 5, Rashmi Sahay ⁵, Neha R Santucci ^1 2

Author information

¹Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

²Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

³Division of Infectious Disease, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

⁴Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

⁵Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Abstract

Background: Irritable bowel syndrome (IBS), a disorder of the gut-brain axis, is affected by the microbiome. Microbial studies in pediatric IBS, especially for centrally mediated treatments, are lacking. We compared the microbiome between pediatric IBS patients and healthy controls (HC), in relation to symptom severity, and with percutaneous electrical nerve field stimulation (PENFS), a non-invasive treatment targeting central pain pathways.

Methods: We collected a stool sample, questionnaires and a 1-2 week stool and pain diary from 11 to 18 years patients with IBS. A patient subset completed 4 weeks of PENFS and repeated data collection immediately after and/or 3 months after treatment. Stool samples were collected from HC. Samples underwent metagenomic sequencing to evaluate diversity, composition, and abundance of species and MetaCyc pathways.

Key results: We included 27 cases (15.4 ± 2.5 year) and 34 HC (14.2 ± 2.9 year). Twelve species including Firmicutes spp., and carbohydrate degradation/long-chain fatty acid (LCFA) synthesis pathways, were increased in IBS but not statistically significantly associated with symptom severity. Seventeen participants (female) who completed PENFS showed improvements in pain (p = 0.012), disability (p = 0.007), and catastrophizing (p = 0.003). Carbohydrate degradation and LCFA synthesis pathways decreased post-treatment and at follow-up (FDR p-value <0.1).

Conclusions and inferences: Firmicutes, including Clostridiaceae spp., and LCFA synthesis pathways were increased in IBS patients suggesting pain-potentiating effects. PENFS led to marked improvements in abdominal pain, functioning, and catastrophizing, while Clostridial species and LCFA microbial pathways decreased with treatment, suggesting these as potential targets for IBS centrally mediated treatments.