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Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut-Brain Axis Dysregulation in Pediatric

Shabana M Shaik1, Gabriele Schiro1, Daniel Laubitz1

  • 1Department of Pediatrics, Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children's Research Center, University of Arizona, Tucson, AZ 85721, USA.

Microorganisms
|May 27, 2026
PubMed

Insights

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) show altered gut bacteria and metabolites, indicating disrupted gut-brain axis signaling. This research opens doors for new microbiome-based PANDAS treatments.

Area of Science:

  • Neuroscience
  • Microbiology
  • Immunology

Background:

  • Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) involve neuropsychiatric symptoms and immune dysregulation.
  • The gut-brain axis and host-microbiome interactions are implicated in neuro-immune functions, but their role in PANDAS is unclear.

Purpose of the Study:

  • To investigate the gut microbiome's role in PANDAS pathophysiology.
  • To identify potential microbiome-based biomarkers and therapeutic targets for PANDAS.

Main Methods:

  • Collected microbiome samples from nasal, throat, and stool sites of PANDAS patients and controls.
  • Performed integrated multi-omics analysis (16S rRNA, shotgun metagenomics, UPLC-MS/MS metabolomics) on stool samples.
  • Analyzed gut-brain modules (GBMs) and gut metabolic modules (GMMs).

Main Results:

  • PANDAS cases showed reduced gut microbial diversity and altered composition.
  • Key functional pathways like quorum sensing and GABA biosynthesis were diminished.
  • Perturbed GBMs, GMMs, and disrupted microbe-metabolite networks linked to gut-brain signaling were observed.
  • Metabolomic profiling revealed distinct metabolic profiles with altered neuroactive compounds.

Conclusions:

  • Significant functional shifts in gut microbiota and metabolites suggest gut-brain axis dysregulation in PANDAS.
  • Findings support the development of microbiome-based biomarkers and therapies for PANDAS.

Keywords:
16Schildrenfecalmetabolomemetagenomicsmicrobiomeneuropsychiatricnosethroat

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