CB001 bioactive compounds mitigate intestinal immune dysregulation induced by simulated microgravity and radiation...

Gastrointestinal discomfort is a prevalent issue during spaceflight, yet targeted therapeutic strategies remain elusive. Existing research largely relies on single-factor modeling, limiting a comprehensive understanding of the underlying pathologies.

We established a composite mouse model combining simulated microgravity (hindlimb unloading) and low-dose radiation (Cobalt-60) to evaluate intestinal injury and the therapeutic potential of CB001. Mechanisms were investigated through histological analysis, in vitro co-culture assays, and flow cytometry assessment of B-cell dynamics and IgA/IgG secretion.

The dual-factor model more effectively simulated spaceflight-induced injuries than single-factor models, showing significant intestinal inflammation and homeostasis disruption. Mechanistically, dual factors promoted CCR7⁺ B cells migration into the intestine by upregulating CXCR4 expression, subsequently enhancing leukocyte activation. CB001 treatment mitigated these intestinal perturbations by restoring tight junction proteins, suppressing excessive B-cell migration, and downregulating pro-inflammatory cytokines. Furthermore, in vitro assays confirmed that CB001 directly enhanced B-cell viability and augmented IgA/IgG secretion, thereby promoting mucosal repair.

CB001 is a promising candidate for mitigating spaceflight-induced intestinal dysfunction, as identified using a novel dual-factor mouse model. These data shed light on strategies for screening protective medicines to safeguard astronaut health during space missions.