Role of lung and gut microbiota on lung cancer pathogenesis

Abstract

Background Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359–386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004–3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. Purpose The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut–lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. Conclusion Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.

Gut Microbiota in Lung Cancer: Where Do We Stand?

“…Apart from gastroesophageal content inhalation and sputum swallowing, which can partially explain this inter-organ connection, the GLA also involves indirect communications: gut and lung microbes show similar colonization characteristics in the early stages of life, and the gut and lungs have a strong mucosal defense system against microbes [ 3 ]. It is reported that short-chain fatty acids (SCFAs), which are the major metabolic products of the GM from dietary fiber (especially in case of a high-fiber diet), act in the lungs as signaling molecules on resident antigen-presenting cells to attenuate the inflammatory and allergic responses [ 57 ].…”

“…In summary, the GLA immune interplay is a bidirectional two-way process resulting from multifaceted interactions among the different microbial components of both the gut and lung microbiota, together with local and distal immune effects. Changes in this axis may lead to harmful outcomes, such as cancer development, pathogen colonization, damage of tissue, and increased susceptibility to infections [ 3 ].…”

“…The characteristics of the GM in lung cancer patients vary widely, suggesting that the gut microbiota may affect lung cancer prognosis and therapy [ 3 ].…”

“…The GM in lung cancer patients responding to treatment with ICIs significantly differs when compared with that of patients who do not respond to immunotherapy. Furthermore, it was found that a significantly higher response to anti-PD1 therapy in lung cancer patients was positively correlated with the abundance of Akkermansia muciniphila species [ 3 ].…”

“…Although the gastrointestinal and the respiratory tracts are physically distant, they have the same embryonic origin, and they have a high similarity in their structure [ 3 ]. Additionally, numerous pathways involving their respective microbiota have reinforced the existence of a gut–lung axis (GLA) [ 4 ].…”