The microbiome in adolescents with irritable bowel syndrome and changes with percutaneous electrical nerve field stimulation

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.

A multicenter registry study on percutaneous electrical nerve field stimulation for pediatric disorders of gut–brain interaction

“…Although speculative, it is conceivable that altered brain connectivity may be responsible for the long‐term improvements. Other proposed PENFS mechanisms to some degree supported by data include: (1) restoration of inefficient cardiac vagal regulation or autonomic control, (2) alterations in intestinal microbial pathways, and (3) neuromodulation of the limbic system, previously demonstrated in a preclinical study 16,17,39,40 . Multiple, conjoined mechanisms may also be at play and more studies of pathophysiology and long‐term effects of PENFS are needed.…”

“…Other proposed PENFS mechanisms to some degree supported by data include: (1) restoration of inefficient cardiac vagal regulation or autonomic control, (2) alterations in intestinal microbial pathways, and (3) neuromodulation of the limbic system, previously demonstrated in a preclinical study. 16,17,39,40 Multiple, conjoined mechanisms may also be at play and more studies of pathophysiology and long-term effects of PENFS are needed. These data are suggestive that PENFS at least in part targets the gut-brain axis dysregulation of DGBI.…”

Percutaneous electrical nerve field stimulation compared to standard medical therapy in adolescents with functional abdominal pain disorders

“…PENFS also improved these outcomes at 3 weeks and 3 months in children with functional dyspepsia ( 9 ). Another proposed mechanism for PENFS includes microbiome changes after treatment, which may also reflect changes in vagal anti-inflammatory pathways ( 39 ). In a recent study, patients with IBS, post-PENFS treatment, were found to have decreased Clostridial species and long chain fatty acid microbial pathways that have been implicated in the pathophysiology of IBS ( 39 ).…”

“…Another proposed mechanism for PENFS includes microbiome changes after treatment, which may also reflect changes in vagal anti-inflammatory pathways ( 39 ). In a recent study, patients with IBS, post-PENFS treatment, were found to have decreased Clostridial species and long chain fatty acid microbial pathways that have been implicated in the pathophysiology of IBS ( 39 ). In that study, improvements in abdominal pain, functioning, and catastrophizing were noted as well.…”

Prospective study of the effect of auricular percutaneous electrical nerve field stimulation on quality of life in children with pain related disorders of gut-brain interaction

“…Furthermore, there has been increasing interest in examining the microbiome of patients with various pain disorders, However, there is a lack of studies in the pediatric population. A recent study evaluated changes in the microbiome of adolescents with IBS after PENFS treatment, The microbiome showed decreased Clostridial species and long chain fatty acid (LCFA) microbial pathways post treatment (25). A future goal could be to examine the microbiome of children with other DBGIs besides IBS and changes in the microbiota secondary to PENFS.…”