Microbiome dysbiosis in lung cancer: from composition to therapy

Abstract

The correlations between microbiota dysbiosis and cancer have gained extensive attention and been widely explored. As a leading cancer diagnosis worldwide, lung cancer poses a great threat to human health. The healthy human lungs are consistently exposed to external environment and harbor a specific pattern of microbiota, sharing many key pathological and physiological characteristics with the intestinal tract. Although previous findings uncovered the critical roles of microbiota in tumorigenesis and response to anticancer therapy, most of them were focused on the intestinal microbiota rather than lung microbiota. Notably, the considerable functions of microbiota in maintaining lung homeostasis should not be neglected as the microbiome dysbiosis may promote tumor development and progression through production of cytokines and toxins and multiple other pathways. Despite the fact that increasing studies have revealed the effect of microbiome on the induction of lung cancer and different disease status, the underlying mechanisms and potential therapeutic strategies remained unclear. Herein, we summarized the recent progresses about microbiome in lung cancer and further discussed the role of microbial communities in promoting lung cancer progression and the current status of therapeutic approaches targeting microbiome to alleviate and even cure lung cancer.

Fig. 1. Dynamic connections of microbiome inhabiting different human body sites.

Oral, lung, and gut microbiome could communicate with each other via direct manner including mucosal dispersion, respiratory and digestive activities, and indirect manner via inflammatory substances, cytokine, and metabolites in systematic circulation. Bacteria and its metabolites from intestinal tract modulate the differentiation tendency of naive T cells and Th17 release, modulating the systematic inflammation and immunity.

Fig. 2. Lung microbiome play a dual role in promoting carcinogenesis and maintaining homeostasis in different conditions.

Lung microbiome can induce carcinogenesis via causing DNA damage, inflammatory response alterations, chromosome instability, abnormal signaling pathway activations and increasing mutation load through productions of bacterial toxins and multiple cytokines. On the other side, the process of colonization and maturation lung-resident microbiome community also participates in the maturation of lung and promoting host homeostasis and tolerance, as well as conferring susceptibility to lung disorders during exposure to complex external environment.

Fig. 3. “One Health” care of lung: triple interaction among host, microbiome, and environment during lung cancer progression.

Aging, population or gene susceptibility are associated with tumorigenesis. As extrinsic factors, the microbiota produced the cytotoxicity-related components, inducing the DNA damage of host cells. The microbiota and its metabolites (e.g., short-chain fatty acids (SCFAs)) trigger downstream immune and metabolic signaling pathways, which further promote or suppress the malignant behaviors of host cells. Environment factors (ultraviolet ray, cigarette and particles) can cause altered community of microbiota and gene mutation to promote occurrence of lung cancer.