Single Treatment of Vitamin D3 Ameliorates LPS‐Induced Acute Lung Injury through Changing Lung Rodentibacter abundance

• Published in: Molecular nutrition & food research 2022-02, Vol.66 (3), p.e2100952-n/a
• Main Authors: Jin, Ai, Zhao, Yan, Yuan, Ye, Ma, Shulan, Chen, Jian, Yang, Xiaojun, Lu, Shemin, Sun, Qingzhu
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D; Abundance; Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Alveoli; Animals; Bronchoalveolar Lavage Fluid - chemistry; Bronchus; Calcitriol; Cholecalciferol - pharmacology; Composition; Correlation analysis; Cytokines; Cytokines - metabolism; Dietary supplements; DNA sequencing; Gene expression; Inflammation; Interleukins; Lipopolysaccharides; Lipopolysaccharides - metabolism; Lipopolysaccharides - toxicity; LPS; Lung; lung inflammation; lung microbiota; Lungs; Mice; Microbiota; NF-kappa B - metabolism; Phosphorylation; Relative abundance; Rodentibacter; SOCS-3 protein; Transcription; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vitamin D3
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202100952

Acute lung injury (ALI) is characterized by severe inflammation. Vitamin D3 is discussed to reduce inflammation in ALI, but the mechanism is not well understood. This study assesses the effect of different calcitriol administration strategies on inflammation and the lung microbiota composition in ALI. In a mouse model, the alveolus and airway pathology are assessed by immunohistology. mRNA expression is determined by Real‐Time Quantitative PCR and protein expressions is detected by Western‐blotting. The composition of microbiota is performed by 16s DNA high‐throughput sequencing. Short‐term vitamin D3 supplementation prevents lipopolysaccharide‐induced ALI by preventing pro‐inflammatory cytokines including interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor α (TNF‐α). In contrast, long‐term treatment over 3 days, 6 days, or 10 days had no such effect. Short‐term vitamin D3, but not long‐term pretreatment significantly reduces the phosphorylation of signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3, but upregulates the phosphorylation of inhibitor of nuclear factor‐κ‐gene binding. Furthermore, an increased relative abundance of Rodentibacter genus in LPS‐challenged mice bronchoalveolar lavage fluid is observed, which is sensitive to short‐term vitamin D3 treatment, effectively alleviating the Rodentibacter abundance. Correlation analysis shows that the load of Rodentibacter positively correlated with the IL‐1β, IL‐6, and TNF‐α gene expression. The data support that a single administration of vitamin D3 may work as an adjuvant therapy for acute lung inflammation. Single time vitamin D3 pretreatment significantly attenuates lipopolysaccharide (LPS) stimulated lung inflammation through reducing STAT3 phosphorylation, upregulating ACE2 protein expression, elevating Ikb‐α phosphorylation, and changing lung microbiota composition. However, long‐term vitamin D3 supplementation does not have the effect. Especially, the abundance of Rodentibacter in lung microbiota positively correlates with the Il‐1β, Il‐6, and Tnfα expressions.