Over the past two decades, gut microbiota has emerged as a central regulator of host metabolism and immune homeostasis, leading to extensive clinical and translational exploration of probiotic interventions. However, despite increasing recognition of microbiota complexity, clinical and translational research has remained disproportionately focused on a limited set of taxa, primarily Lactobacillus and Bifidobacterium. Meta-analyses published between 2012 and 2025 report modest benefits by these taxa and substantial heterogeneity across dysbiosis-associated and allergic conditions. This indicates limited and context-dependent efficacy, along with scarce and inconsistent impact on objective immunological endpoints. Here, we examine the prevailing probiotic paradigm in terms of ecological relevance and functional targeting, arguing that historical, technological, and regulatory biases have contributed to a misalignment between microbial selection and dominant metabolic and immunological functions in the adult gut ecosystem. Using dysbiosis and allergic disease as illustrative case studies, we integrate clinical evidence and mechanistic insights to evaluate emerging microbiota-based strategies, including next-generation probiotics, live biotherapeutic products, and non-viable microbial preparations. We suggest that future interventions should move beyond empirical taxonomic supplementation toward function-driven, context-aware approaches grounded in defined microbial activities and biologically informative clinical endpoints, enabling more precise and durable modulation of host-microbiota interactions.

Rethinking probiotics: breaking the Lactobacillus-Bifidobacterium duopoly in the management of dysbiosis and allergies.

Cappella C.
Writing – Review & Editing
;
Scarcia P.
Writing – Original Draft Preparation
;
Agrimi G.
Writing – Review & Editing
;
Bettiga M.
Supervision
2026-01-01

Abstract

Over the past two decades, gut microbiota has emerged as a central regulator of host metabolism and immune homeostasis, leading to extensive clinical and translational exploration of probiotic interventions. However, despite increasing recognition of microbiota complexity, clinical and translational research has remained disproportionately focused on a limited set of taxa, primarily Lactobacillus and Bifidobacterium. Meta-analyses published between 2012 and 2025 report modest benefits by these taxa and substantial heterogeneity across dysbiosis-associated and allergic conditions. This indicates limited and context-dependent efficacy, along with scarce and inconsistent impact on objective immunological endpoints. Here, we examine the prevailing probiotic paradigm in terms of ecological relevance and functional targeting, arguing that historical, technological, and regulatory biases have contributed to a misalignment between microbial selection and dominant metabolic and immunological functions in the adult gut ecosystem. Using dysbiosis and allergic disease as illustrative case studies, we integrate clinical evidence and mechanistic insights to evaluate emerging microbiota-based strategies, including next-generation probiotics, live biotherapeutic products, and non-viable microbial preparations. We suggest that future interventions should move beyond empirical taxonomic supplementation toward function-driven, context-aware approaches grounded in defined microbial activities and biologically informative clinical endpoints, enabling more precise and durable modulation of host-microbiota interactions.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/588740
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