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

Abstract

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.

Propolis Alleviates Acute Lung Injury Induced by Heat-Inactivated Methicillin-Resistant Staphylococcus aureus via Regulating Inflammatory Mediators, Gut Microbiota and Serum Metabolites

“…SCFAs also play an important role in the immune response of the host and in metabolism. Numerous studies have shown that the gut microbiota can modulate SCFAs to alleviate acute lung injury [ 54 , 55 , 56 ]. In the present study, heat-inactivated MRSA induced a decrease in SCFAs in ALI in mice, and propolis pretreatment elevated the concentrations of acetic acid and valeric acid to reverse these changes.…”

Screening of Lipid Metabolism-Related Genes as Diagnostic Indicators in Chronic Obstructive Pulmonary Disease

“…When short-chain fatty acids are supplemented, inflammation and oxidative stress are reduced in the lungs of aging mice, as well as the increased inflammatory signal in acute lung injury in these mice. 60 A fatty acid derivative of quercetin-3-O-glucoside prevents cigarette smoke extract-induced cell death and membrane lipid peroxidation in human fetal lung fibroblasts. 61 As a result of these studies, lipids and their derivatives have been implicated as a critical pathogenic factor in COPD and other lung diseases.…”

The Role of Nutrition in the Development and Management of Chronic Obstructive Pulmonary Disease

“…Although the mechanism connecting dietary fiber and risk of COPD is unknown, the positive benefits from greater dietary fiber intake in the general population have been postulated to be related to improved gut microbiome and reduced inflammatory responses [ 64 ]. Fiber fermentation results in the formation of metabolites such as short-chain fatty acids [ 65 ], which are known to have systemic [ 66 ] and pulmonary anti-inflammatory effects [ 67 ]. Diets low in fiber can also result in gut dysbiosis and promote chronic, systemic inflammation [ 68 ].…”