Science and Research

Short chain fatty acids improve inflamm-aging and acute lung injury in old mice

A chronic pro-inflammatory milieu (inflamm-aging) is observed in the elderly and associated with poorer prognosis in acute lung injury (ALI). Gut microbiome-derived short chain fatty acids (SCFAs) are known to have immunomodulatory capabilities, but their function in the gut-lung axis in aging is poorly understood. Here we analyzed the gut microbiome and its impact on inflammatory signaling in the aging lung and tested the effects of SCFAs in young (3 months) and old (18 months) mice that received either drinking water with a mixture of each 50 mM acetate, butyrate and propionate for two weeks or water alone. ALI was induced by intranasal lipopolysaccharide (LPS; n=12/group) administration. Controls (n=8/group) received saline. Fecal pellets were sampled for gut microbiome analysis before and after LPS/saline treatment. The left lung lobe was collected for stereology and right lung lobes for cytokine and gene expression analysis, inflammatory cell activation and proteomics. Different gut microbial taxa, such as Bifidobacterium, Faecalibaculum and Lactobacillus correlated positively with pulmonary inflammation in aging, suggesting an impact on inflamm-aging in the gut-lung axis. The supplementation of SCFAs reduced inflamm-aging, oxidative stress, metabolic alteration, and enhanced activation of myeloid cells in the lungs of old mice. The enhanced inflammatory signaling in ALI of old mice was also reduced by SCFA-treatment. In summary, the study provides new evidence that SCFAs play a beneficial role in the gut-lung axis of the aging organism by reducing pulmonary inflamm-aging and ameliorating enhanced severity of ALI in old mice.

  • Hildebrand, C. B.
  • Lichatz, R.
  • Pich, A.
  • Mühlfeld, C.
  • Woltemate, S.
  • Vital, M.
  • Brandenberger, C.

Keywords

  • acute lung injury
  • gut microbiome
  • gut-lung axis
  • inflamm-aging
  • short chain fatty acid
Publication details
DOI: 10.1152/ajplung.00296.2022
Journal: Am J Physiol Lung Cell Mol Physiol
Work Type: Original
Location: Assoziierter Partner, BREATH
Disease Area: PALI
Partner / Member: BIH, MHH
Access-Number: 36802219

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