Double-edged sword effect of Sutterella in neurological disorders: implications for the gut-brain axis and neuroimmune interactions

The genus Sutterella, a group of bile-resistant microaerophilic gram-negative bacteria, has emerged as a key player in gut-brain axis communication, with significant yet complex implications for neurological and psychiatric disorders. This study synthesizes current evidence on Sutterella's dual role in modulating immune responses and neuroinflammation, highlighting its context-dependent effects across Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), multiple sclerosis (MS), migraine, epilepsy, autoimmune encephalomyelitis (AE), and depression. While Sutterella exhibits pro-inflammatory properties, such as inducing cytokines (e.g., IL-6 and TNF-α) and degrading immunoglobulin A (IgA), it also demonstrates immunomodulatory potential, including anti-inflammatory IL-10 induction. Recent studies underscore Sutterella's direct and indirect involvement in neuropathological processes through its influence on systemic inflammation, barrier permeability, tryptophan metabolism, and glial activation. In AD and PD, its abundance correlates with disease severity and key molecular markers such as amyloid burden and oxidative stress. In ASD and depression, Sutterella has been linked to neuroinflammatory cascades and behavioral dysregulation, potentially mediated through lipopolysaccharide (LPS)-associated immune activation. Furthermore, the presence of Sutterella has shown predictive utility in migraine and schizophrenia cohorts, reinforcing its relevance as both a potential biomarker and therapeutic target. This review underscores the need for standardized methodologies, mechanistic studies, and longitudinal cohorts to clarify Sutterella's causal contributions. By integrating preclinical and clinical data, we propose Sutterella as a potential biomarker and therapeutic target, emphasizing the importance of personalized approaches in microbiota-based interventions for neurological and psychiatric disorders.