Journal of Traditional Chinese Medicine >
Gut microbiota-mediated short-chain fatty acids contribute to the protective effects of Xiaoxuming decoction (小续命汤) against lipopolysaccharide-induced acute lung injury
Received date: 2024-09-26
Accepted date: 2025-06-24
Online published: 2026-04-04
OBJECTIVE: To investigate the mechanisms underlying the protective effects of Xiaoxuming decoction (小续命汤, XXMD) against lipopolysaccharide (LPS)-induced acute lung injury (ALI).
METHODS: LPS was used to construct an ALI model in mice and human pulmonary alveolar epithelial cells (HPAEpiCs). Acetate and acetate-producing bacteria, including Blautia hydrotrophica, Bacteroides thetaiotaomicron, Akkermansia muciniphila, and Bacteroides vulgatus, were detected after XXMD treatment. Zonula occludens-1 (ZO-1), occludin, phosphorylated nuclear factor-kappa B p65 (p-NF-κBp65), and NF-κBp65 levels were measured by Western blotting, and an enzyme-linked immunosorbent assay was performed to detect tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6 secretion. Transepithelial electrical resistance, fluorescein isothiocyanate-dextran, and cell counting kit-8 assays were used to detect the cell’s monolayer integrity, permeability, and viability.
RESULTS: XXMD alleviated the LPS-induced downregulation of acetate and acetate-producing bacteria in feces. Furthermore, XXMD suppressed the LPS-induced downregulation of ZO-1 and occludin expression in lung tissues, LPS-induced upregulation of TNF-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid, and p-NF-κBp65 levels in lung tissues. Acetate had similar effects in LPS-induced mice. Meanwhile, the seven-day survival probability was improved by XXMD or acetate treatment. Furthermore, acetate could alleviate LPS-mediated cell viability, inflammation, and permeability in HPAEpiCs, while acetate-induced effects could be abrogated by GLPG0974, a short-chain fatty acid (SCFA) receptor G-protein coupled receptor 43 antagonist.
CONCLUSION: XXMD’s therapeutic effect may be related to gut microbiota-mediated SCFAs, which alleviated LPS-induced ALI.
XIANG Yijin , YANG Zhigang , GONG Shaomin , LI Xiangting , CAI Min . Gut microbiota-mediated short-chain fatty acids contribute to the protective effects of Xiaoxuming decoction (小续命汤) against lipopolysaccharide-induced acute lung injury[J]. Journal of Traditional Chinese Medicine, 2026 , 46(2) : 285 -293 . DOI: 10.19852/j.cnki.jtcm.2026.02.002
| 1. | Parveen S, Khan KUR, Iqbal SM, et al. Exploration of the anti-inflammatory potential of Polygonum bistorta L.: protection against LPS-induced acute lung injury in rats via NF-?β pathway inhibition. Front Pharmacol 2024; 15: 1500085. |
| 2. | Jian YJ, Lü Q, Du L, Lei CC, Zhi LP, Liu XH. Discovery of a novel pyrimidine derivative for treatment of acute lung injury through reducing oxidative stress and inflammatory response. RSC Med Chem 2025; 16: 1441-58. |
| 3. | Ren L, Hai Y, Yang X, Luo XQ. Yemazhui (Herba Eupatorii Lindleyani) ameliorates lipopolysaccharide-induced acute lung injury modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flora in rats. J Tradit Chin Med 2024; 44: 303-14. |
| 4. | Guo J, Zhu J, Wang Q, Wang J, Jia Y. Comparative efficacy of seven kinds of Chinese Medicine injections in acute lung injury and acute respiratory distress syndrome: a network Meta-analysis of randomized controlled trials. Front Pharmacol 2021; 12: 627751. |
| 5. | Chen YP, Wang KX, Cai JQ, et al. Detecting key functional components group and speculating the potential mechanism of Xiao-xu-ming decoction in treating stroke. Front Cell Dev Biol 2022; 10: 753425. |
| 6. | Li DH, Su YF, Sun CX, Fan HF, Gao WJ. A network pharmacology-based identification study on the mechanism of Xiao-xu-ming decoction for cerebral ischemic stroke. Evid Based Complement Alternat Med 2020; 2020: 2507074. |
| 7. | Xiang Y, Cai M, Li X, Bao X, Cai D. Protective effect of Xiao-xu-ming decoction-mediated inhibition of ROS/NLRP3 axis on lipopolysaccharide-induced acute lung injury in vitro and in vivo. Evid Based Complement Alternat Med 2021; 2021: 8257495. |
| 8. | Wang J, Xue X, Zhao X, et al. Forsythiaside A alleviates acute lung injury by inhibiting inflammation and epithelial barrier damages in lung and colon through PPAR-γ/RXR-α complex. J Adv Res 2024; 60: 183-200. |
| 9. | Xie L, Wang L, Liao Y, et al. Therapeutic potential of short-chain fatty acids for acute lung injury: a systematic review and Meta-analysis of preclinical animal studies. Front Nutr 2024; 11: 1528200. |
| 10. | Hung KY, Wu SY, Pao HP, Liao WI, Chu SJ. Acetate, a gut bacterial product, ameliorates ischemia-reperfusion induced acute lung injury in rats. Int Immunopharmacol 2022; 111: 109136. |
| 11. | Shao S, Wang D, Zheng W, et al. A unique polysaccharide from Hericium erinaceus mycelium ameliorates acetic acid-induced ulcerative colitis rats by modulating the composition of the gut microbiota, short chain fatty acids levels and GPR41/43 respectors. Int Immunopharmacol 2019; 71: 411-22. |
| 12. | Wu Z, Qian S, Zhao L, et al. Metabolomics-based study of the potential interventional effects of Xiao-xu-ming decoction on cerebral ischemia/reperfusion rats. J Ethnopharmacol 2022; 295: 115379. |
| 13. | Wang Z, Liu J, Li F, et al. The gut-lung axis in severe acute pancreatitis-associated lung injury: the protection by the gut microbiota through short-chain fatty acids. Pharmacol Res 2022; 182: 106321. |
| 14. | Liu S, Su X, Pan P, et al. Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury. Sci Rep 2016; 6: 37252. |
| 15. | Yehya N, Smith L, Thomas NJ, et al. Definition, incidence, and epidemiology of pediatric acute respiratory distress syndrome: from the second pediatric acute lung injury consensus conference. Pediatr Crit Care Med 2023; 24: S87-98. |
| 16. | Lee J, d'Aigle J, Atadja L, et al. Gut microbiota-derived short-chain fatty acids promote poststroke recovery in aged mice. Circ Res 2020; 127: 453-65. |
| 17. | Ashley SL, Sjoding MW, Popova AP, et al. Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice. Sci Transl Med 2020; 12: eaau9959. |
| 18. | Ye J, Guan M, Lu Y, Zhang D, Li C, Zhou C. Arbutin attenuates LPS-induced lung injury via Sirt1/ Nrf2/ NF-kappaBp65 pathway. Pulm Pharmacol Ther 2019; 54: 53-9. |
| 19. | Hildebrand CB, Lichatz R, Pich A, et al. Short-chain fatty acids improve inflamm-aging and acute lung injury in old mice. Am J Physiol Lung Cell Mol Physiol 2023; 324: L480-92. |
| 20. | Wu Z, Shen J, Xu Q, et al. Epigallocatechin-3-gallate improves intestinal gut microbiota homeostasis and ameliorates clostridioides difficile infection. Nutrients 2022; 14: 3756. |
| 21. | Xiong RG, Zhou DD, Wu SX, et al. Health benefits and side effects of short-chain fatty acids. Foods 2022; 11: 2863. |
| 22. | Kibbie JJ, Dillon SM, Thompson TA, Purba CM, McCarter MD, Wilson CC. Butyrate directly decreases human gut lamina propria CD4 T cell function through histone deacetylase (HDAC) inhibition and GPR43 signaling. Immunobiology 2021; 226: 152126. |
| 23. | Wen C, Xie T, Pan K, et al. Acetate attenuates perioperative neurocognitive disorders in aged mice. Aging 2020; 12: 3862-79. |
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