Microbiome-Based Immunological Calibration Theory (MICT): Early-Life Microbial Programming of Immune Tolerance, Responsiveness, and Neuroimmune Balance

This preprint introduces the Microbiome-Based Immunological Calibration Theory (MICT), a conceptual framework proposing that immune function is not solely developed or activated, but calibrated through early-life microbial signaling. MICT distinguishes immunological calibration from immune development and immune activation, framing calibration as a systems-level process that establishes immune tolerance thresholds, response proportionality, and neuroimmune balance. The theory integrates evidence from microbiome research, immunology, developmental physiology, lactation science, extracellular matrix (ECM) biology, and neuroimmune signaling. It proposes temporally ordered calibration phases spanning prenatal life, birth, lactation, and early infancy, during which microbial metabolites and host–microbe interfaces shape long-term immune behavior. MICT reframes immune-mediated disorders—including allergy, autoimmunity, chronic inflammation, and neurodevelopmental vulnerability—as potential consequences of immune miscalibration rather than isolated immune defects. This paper is presented as a conceptual and systems-level theory, intended to guide future empirical research and inform preventive approaches in early-life health.