The Impact of a High-Fibre Diet and Gut Microbiota on Lung Injury and Fibrosis

Idiopathic pulmonary fibrosis is a chronic, progressive interstitial lung disease characterised by excessive extracellular matrix deposition in the lung. Current treatment options for IPF are limited; therefore, the disease is associated with high morbidity and mortality. In humans, consuming a high-soluble fibre diet has been associated with a reduced risk of respiratory diseases, including allergic airway disease. While evidence suggests that gut microbiota dysbiosis is linked to fibrotic processes in various organs, the link between the gut microbiota, high soluble fibre diet and pulmonary fibrosis remains unclear. This thesis aimed to assess the impact of a high soluble fibre diet on the composition of the gut microbiota and the development of lung injury and fibrosis in a murine model of bleomycin-induced pulmonary fibrosis. Male and female C57BL/6J mice were randomly assigned to one of 4 groups: low-soluble fibre diet control, high soluble fibre diet control, low-soluble fibre diet bleomycin or high soluble fibre diet bleomycin. Following four weeks of diet, Bleomycin (or saline control) was administered by oropharyngeal aspiration. Following 21 days of treatment, lung injury was assessed, and gut microbiota composition was determined using 16s rRNA sequencing. In a follow-up study, lung lymphocyte populations previously recognised as essential players in the pathogenesis of the disease were analysed after seven days of treatment to determine the impact of diet on the acute inflammatory phase. The results showed that a high soluble fibre diet was protective against bleomycin-induced pulmonary fibrosis. Mice fed a high-fibre diet had improved survival, reduced weight loss, reduced lung elastance and less collagen deposition in the lungs compared to their low-fibre diet-fed counterparts. The gut microbiomes of mice fed a diet low in fibre were distinct from high-fibre diet-fed mice as determined by principle component analysis based on the Bray-Curtis distance. Moreover, LEFse analysis showed that these changes were associated with an increased abundance of short-chain fatty acid-producing bacteria in the gut. Furthermore, flow cytometry analysis showed that a high fibre reduced the number of CD4+IL17+ Th17 cells following seven days of bleomycin treatment. This study is the first to establish a link between a high-fibre diet, gut microbiota, lung injury, and fibrosis.