Targeting the gut-brain axis with <i>Bifidobacterium breve</i> in neurodegeneration: A comprehensive narrative review of current evidence in Alzheimer's disease and cognitive aging.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder arising from the interplay of amyloid, tau, neuroimmune, oxidative stress, metabolic, vascular, and synaptic processes, ultimately resulting in neurodegeneration across multiple brain regions and progressive memory and cognitive impairment. Gut dysfunction may contribute to the initiation and progression of AD-related processes through the gut-brain axis, whereby alterations in the gut microbiota can influence brain function through chemical, neuronal, immune, and metabolic pathways. Growing interest in the microbiota-gut-brain axis has consequently prompted investigation of strain-specific probiotics as potential adjunctive approaches to restoring gut microbial homeostasis. This comprehensive narrative review critically integrates preclinical and human evidence on <i>Bifidobacterium breve</i> in AD-related pathology and age-associated cognitive impairment. Targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were conducted through April 2026 and supplemented by reference-list searching. The evidence base comprised 13 preclinical publications and five human publications representing four independent clinical cohorts. Preclinical studies, predominantly conducted in rodent models, reported strain-dependent effects on cognition, amyloid- and tau-related measures, synaptic proteins, neuroinflammation, oxidative stress, microbial composition, and metabolite profiles. Human evidence was limited to <i>B. breve</i> MCC1274 (A1) and primarily involved Japanese adults with memory complaints or suspected mild cognitive impairment. Overall, current evidence supports a mechanistic rationale for the potential role of <i>B. breve</i> as a gut-brain modulator; however, the heterogeneity of preclinical findings and the small, geographically concentrated clinical evidence base highlight the need for further well-designed studies to more clearly define clinical efficacy and long-term safety.