Obesity Reshapes the Microbial Population Structure along the Gut-Liver-Lung Axis in Mice

Abstract

The microbiome is emerging as a major player in tissue homeostasis in health and disease. Gut microbiome dysbiosis correlates with several autoimmune and metabolic diseases, while high-fat diets and ensuing obesity are known to affect the complexity and diversity of the microbiome, thus modulating pathophysiology. Moreover, the existence of a gut-liver microbial axis has been proposed, which may extend to the lung. In this context, we systematically compared the microbiomes of the gut, liver, and lung of mice fed a high-fat diet to those of littermates fed a matched control diet. We carried out deep sequencing of seven hypervariable regions of the 16S rRNA microbial gene to examine microbial diversity in the tissues of interest. Comparison of the local microbiomes indicated that lung tissue has the least diverse microbiome under healthy conditions, while microbial diversity in the healthy liver clustered closer to the gut. Obesity increased microbial complexity in all three tissues, with lung microbial diversity being the most modified. Obesity promoted the expansion of Firmicutes along the gut-liver-lung axis, highlighting staphylococcus as a possible pathologic link between obesity and systemic pathophysiology, especially in the lungs.

Anti-Obesity Effect of Chlorin e6-Mediated Photodynamic Therapy on Mice with High-Fat-Diet-Induced Obesity

“…Adipose tissue is the primary organ responsible for storing fat in the body, and an abnormal amount of fat deposits leads to obesity [ 4 ]. Adipose tissue plays an important role in metabolic regulation and physiological homeostasis through the secretion of multiple hormones, including adipokines such as leptin and adiponectin [ 5 , 6 ]. The adipocytokine leptin is related to energy storage in both white adipose tissue and plasma [ 7 ].…”

Increased lipocalin-2 expression in pulmonary inflammation and fibrosis

“…Given the suggested role of Lcn2 in metabolic disorders and obesity ( 36 ) and the correlation between IPF and obesity in patients ( 37 ), the effect of obesity-driven microbiome changes in the lungs ( 38 ), as well as the suggested role of Lcn2 in iron sequestration and microbiome regulation, we next investigated the role of Lcn2 in the pathogenesis of pulmonary fibrosis in obese mice, following the high-fat diet (HFD) feeding for 13 weeks, in comparison with mice fed a matched control diet. No statistically significant changes in disease severity were observed either, although a clear trend of disease attenuation was observed ( Supplementary Figures S3A – D ), as opposed to lean mice.…”

“…Moreover, it is also possible that a pathogenic role for Lcn2 cannot be efficiently dissected in animal models, as has been shown for many other genes ( 4 ). In this context, a very possible role of Lcn2 in iron sequestration and microbiome regulation ( 18 ) cannot be likely examined in modeled mice, given their sterile and controlled living conditions, as well as due to the species populating the lung that are not amenable to the suggested bacteriostatic functions of Lcn2 ( 38 , 40 ). However, a role for LCN2 in microbiome regulation in humans remains likely and should be pursued in future clinical studies, especially since increased airway microbiota has been associated with a more rapid disease progression and a higher risk of mortality across different patient cohorts and quantification platforms ( 20 , 41 , 42 ).…”

Obesity, but not high-fat diet, is associated with bone loss that is reversed via CD4+CD25+Foxp3+ Tregs-mediated gut microbiome of non-obese mice

“…2i) revealed an HIO microbiota signature associated with an increase in families of Erysipelotrichaceae, Enterococcaceae, Peptostreptococcaceae and Corynebacteriaceae (Fig. S2b) which are negatively related with obesity [49][50][51][52] . HIO microbiota were also associated with increases in diseaseassociated families Saccharimonadaceae, Aerococcaceae, and Eggerthellaceae (Fig.…”