How Gut Microbiota Regulation with Chemotherapy Could Help Lung Cancer Treatment

What is Lung Cancer?

Lung cancer is one of the most common types of cancer and it is also one of the deadliest. Lung cancer can be caused by smoking, air pollution, or other things. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer.

The Present Treatment and Technology of Advanced Non-Small Cell Lung Cancer

Most NSCLCs or Non-small-cell lung carcinoma tumors have been found to be in an advanced stage when diagnosed. This means that they have spread too far to be surgically removed, and the main treatment is chemotherapy drugs. However, the current chemotherapy drugs only have a 25-30% success rate and cause many unpleasant side effects like nausea, vomiting, constipation, and others. As a result, there is still much room for improvement in the treatment of advanced NSCLC.

Relationship Between Malignant Tumors and Gut-Lung Axis Microecology

Gut-lung microecology has been found to be closely related to malignant tumors in some studies. A large number of intestinal flora is called the second-largest gene pool in humans. 

Its distribution, products, and functional metabolism have a profound impact on the patient by regulating the patient’s nutrient absorption and biochemical indicators, especially the immune system. 

US White House launched the “National Microbiome Program” in 2016. This program explored the influence of microbial community abundance in the human body, thereby helping us understand its role in human health and diseases.  

Advancement in metagenomics and high-throughput sequencing technologies has found that the microecological lung balance is linked to the patient’s immune response. In April 2017, a study published in Nature Medicine by the Dickson team at the University of Michigan revealed that microorganisms in the lungs are not the only pathogens of pneumonia, but also intestinal microorganisms can cause diseases in the lungs. Clinicians and scientists have been paying attention to studying the “intestinal-pulmonary axis” in recent years. 

In 2015, major clinical trials were conducted to verify if intestinal bacteria can cause lung pathology. Two of these trials gave beneficial probiotic bacteria to participants, while another experiment gave narrow-band antibiotics designed to change the intestinal microbial distribution.

Genetic and environmental factors can cause tumors, but 20% of human tumors are associated with microorganisms. The microbiome can cause cancer to develop through three pathways: 

  1. A shift in the balance of host cell multiplication and death

2. Regulation of the natural and adaptive immune function

3. And by impacting the metabolism of host factors

There is also a close connection between lung cancer and the microbiome. Studies have verified that the oral microbiome is associated with an increased risk of lung cancer. 

Pulmonary infection with Mycobacterium tuberculosis is noted to raise patients’ risk of lung cancer. Evidence from multiple studies confirmed that intestinal microecology can impact lung immunity and microecological stability. Epithelial cells and other immune cells can influence the inflammatory reaction from microorganisms and accompanying local cytokines. This form of immune reaction often occurs in the lungs and other organs. Therefore, there is a close connection between intestinal microecology and lung microecology.

How Probiotics Affect the Intestinal Microecology and Immunity

Probiotics are microorganisms that are beneficial to the host. They help to regulate and keep the microecological balance of the host. Some probiotics include Bifidobacterium, Lactobacillus, and Clostridium butyricum.  

Bifidobacterium is an Essential Probiotic that has been Widely Researched

It produces dynamic changes with age, diet, disease, drugs, etc. in type and quantity. As people get older, the number of Bifidobacterium decreases.  

Bifidobacterium has anti-tumor mechanisms including:  

1. Significantly increasing glutathione-S-transferase activity and reduce the metabolites and carcinogens toxicity.

2. Changes the metabolism of intestinal spoilage bacteria, like nitroreductase and azo reductase, and hinder the catalytic release of carcinogenic precursors in the intestine

3. Regulate the body’s immune response, increase the number of lymphocytes in the blood, and activate the functions of macrophages, NK cells, MHC II + cells, and other immune cells, thereby activating the body Immune Function and activating the differentiation and reproduction of T cells and B cells

4. Reduce the growth of carcinogenic potential harmful bacteria.

A Mouse Lung Cancer Model

A mouse lung cancer model showed that when the mice were fed with three mixed antibiotics, it disrupted the balance of intestinal flora. However, when they were fed with bifidobacteria, the mice which were treated with cisplatin monotherapy showed a significant reduction in tumor size. This suggests that Bifidobacterium participates in the systemic anti-lung cancer response and that the anti-tumor effect of probiotics could be manifested in lungs. 

Researchers are exploring the possibility of inhibiting the number of Th2 cells (allergic cells) in the lungs and increasing the number of Tregs (immune cells) by regulating a balance using intestinal flora. Intestinal probiotics can upregulate levels of Treg and regulatory dendritic cells, thereby promoting expression of regulatory cytokines TGF-β and IL-10 and reversing tumor process. 

This shows that intestinal probiotics have a role in inhibiting tumorigenesis through “intestinal-pulmonary axis microecological regulation”.

It is believed that the imbalance of intestinal flora may provide a pathological cause for the occurrence of microecological lung imbalances, and probiotics are vital for maintaining the balance of intestinal flora. 

Suppose this hypothesis is proven to be true. In that case, the intestinal-pulmonary micro ecological balance will become a target for lung cancer treatment, likely prolonging the survival of patients with advanced lung cancer treatment and improving their quality of life.

The Research on Microbiota Modulation

Based on the “intestinal and lung axis microecological adjustment” theory, a new therapy was studied which involved traditional platinum-containing two-drug chemotherapy. The effectiveness of the new therapy on patients with advanced NSCLC was observed. 

The study collected basic information from patients and looked at the effectiveness of chemotherapy on the intestinal flora in patients with lung cancer before and after receiving chemotherapy treatment. 

A total of 180 subjects were divided into the intervention group (platinum-containing dual-drug chemotherapy combined with Bifico) and control group (platinum-containing dual-drug chemotherapy)

Study Results Are Still Ongoing

Research on the study is still ongoing but researchers continue to recognize the importance of the “gut-lung axis” in regulating lung cancer. They believe that intestinal flora may provide a pathological basis for the occurrence of lung micro ecological imbalances, and probiotics is an important piece for maintaining the balance of intestinal flora. 

If this hypothesis is proved true, the intestinal-pulmonary micro ecological balance will become a prospect for the treatment of lung cancer, which may prolong the survival period of patients with advanced lung cancer and improve their quality of life. 

This would save patients’ financial burdens on medical bills and medical resources as a whole.


Efficacy Of “Microbiota Modulation Of The Gut-Lung Axis” Combined With Chemotherapy In Advanced NSCLC Patients

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