Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model

Abstract

An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan–Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer.

Potential mechanisms underlying inhibition of xenograft lung cancer models by kaempferol: modulation of gut microbiota in activating immune cell function

“…For example, Zhang et al 41 found in their in vivo studies that Lactobacillus casei inhibited the proliferation of A549 lung cancer cells, and Matsuzaki T et al 42 found that the same species significantly improved the antitumor activity in mouse models of lung cancer. Le Noci et al 43 demonstrated that aerosol inhalation of Lactobacillus rhamnosus inhibited lung cancer growth by promoting local immunity. Lachnospiraceae can produce a large number of short-chain fatty acids that regulate the body's immune response 44 .…”

Time-restricted feeding affects the fecal microbiome metabolome and its diurnal oscillations in lung cancer mice

“…We also found that at the genus level, Lactobacillus and Bacillus were persistently increased significantly in the TRF group, which have been proven to have effective antitumor activity [ 44 , 45 ]. Lactobacillus administration conferred a beneficial role in lung cancer and colon cancer [ 46 , 47 ]. Moreover, the relative abundances of Bifidobacterium and Corynebacterium decreased in lung cancer mice and were recovered after TRF intervention.…”

Global research trends between gut microbiota and lung cancer from 2011 to 2022: A bibliometric and visualization analysis

“…Studies have demonstrated that Lactobacillus, one of the most widely studied probiotics in lung cancer, can significantly inhibit metastasis of tumor cells to the lung, thereby improving the prognosis of patients with lung cancer (39,40). A previous study by Valentino Le Noci et al suggested that an increase in the gene encoding the joining chain (J chain) of immunoglobulins was observed by Lactobacillus aerosolization, while high levels of Jchain mRNA strongly associated with a good prognosis for patients with lung adenocarcinoma (41). In addition, intravenous and intradermal injections of Lactobacillus casei significantly increased the anti-tumor activity in lung cancer model mice (42).…”