Thrombospondin-1 Modulation by Bifidobacterium spp. Mitigates Lung Damage in an Acute Lung Injury Mouse Model

Abstract

Our study shows that Bifidobacterium spp. supplementation reduces lung damage in acute lung injury by enhancing immune cell activity and restoring thrombospondin-1 levels, offering a promising therapeutic approach for the treatment of ALI/ARDS. Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions characterized by severe lung inflammation and damage, often exacerbated by mechanical ventilation. Probiotics, particularly those containing Bifidobacterium spp. (Bifidus) have shown promise in modulating immune responses and reducing inflammation. Methods: In this study, we investigated the effects of Bifidus supplementation in a mouse model of lipopolysaccharide induced ALI and ventilator-induced lung injury. Results: Our results demonstrate that Bifidus significantly ameliorates lung injury by enhancing efferocytosis and reducing pro-inflammatory cytokine levels. Single-cell RNA sequencing revealed significant changes in lung immune cell populations, particularly macrophages and monocytes, which showed increased efferocytosis activity and modulation of key signaling pathways such as TNF, MAPK and TLR. Notably, Bifidus feeding restored thrombospondin-1 levels in lung tissue, facilitating clearance of apoptotic cells and promoting resolution of inflammation. Conclusions: Overall, our study highlights the potential of Bifidus as a therapeutic strategy to mitigate lung injury in ALI/ARDS. © 2025 The Authors