Could the human microbiome improve cancer radiotherapy?

The human body is far more complex than the sterile array of genetically identical, specialized, and cooperating human cells suggested by textbook anatomy and physiology schemas. It is a Byzantine and interacting ecosystem of diverse and thriving communities of bacteria, fungi, protozoa, and viruses. The human genome also contains “fossil” endogenous retroviruses. This is a gene from ancestral transmission that was incorporated into the genetic lineage of humans long ago.¹

The non-human living components of our body’s ecosystem are microbiomeis sometimes referred to as the “second genome” of humans. The emerging field of metagenomics seeks to sequence microbial DNA simultaneously with the human genome of patients.²

In reality, however, microbial ecosystems vary dramatically by organ system, so each of us contains a multitude of different microbiomes. They play an important role in the composition, permeability, and repair of the intestinal mucus layer. digestion of food and absorption of nutrients; behavior of the immune system; resistance or propensity to disease.^2-6

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Species composition of the microbiome and patient biology are related in highly complex ways. For example, the circadian sleep/wake cycle appears to influence the gut bacterial community.⁷ Gut bacteria also release neuropeptides into the patient’s bloodstream that affect appetite and mood.^8,9

Microbiome oncology is a young field of research. Researchers have identified myriad connections between the microbiome and individual microbial species, cancer, and cancer treatments. So far, little is known about most of the causative molecular mechanisms underlying these associations.² However, researchers are already investigating whether the microbiome can help explain the association between smoking and diet and cancer risk. and non-smokers.^Four)

Invasion by pathogenic microorganisms or other disruption of the microbiome — collectively intestinal flora — Associated with metabolic disorders, autoimmune conditions, and cancer.^3,10 Although there is evidence that some microbiomes are associated with reduced cancer risk, the gut microbiota and certain microbial species may be carcinogenic.²

Dysbiosis promotes tumor formation, progression, and metastasis. the immune system’s response to tumor cells; and the tumor’s response to various cancer treatments, including chemotherapy, radiation therapy, and immunotherapy.^11,12 (host microenvironment within the tumor microenvironment, microbiota within the tumor, or Intratumoral microbiomehas been poorly studied, but can reasonably be expected to be equally important in understanding tumor behavior and therapeutic response.¹³)

The oropharynx, gastrointestinal, intestinal epithelium, urinary tract, and breast tissue microbiomes are key components of the tumor microenvironment. They can disrupt communication between tumor cells and influence host and tumor cell production of inflammatory cytokines. Alternatively, it may promote tumorigenesis, progression, and therapeutic response in tumors of the head and neck, colon, stomach, breast, and prostate.³ Less is known about the lung microbiome and its role in lung cancer.¹⁴

The relationship between the gut microbiome and cancer is one of the most studied. For example, there is an established role for bacteria. Helicobacter pylori In peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma.² Fusobacterium It may also promote tumorigenesis.¹⁵

Other bacteria appear to slow tumor growth or reduce side effects of treatment. Lactic acid bacteria and bifodacteriumFor example, it appears to increase apoptosis (“cell suicide”) in cancer cells and protect DNA from oxidative damage.^7,15 bifodacterium Inhibiting tumor cell growth factors and blocking inflammatory cytokines in a manner that helps explain the association with lower risk of adverse treatment effects such as radiation-related gastrointestinal mucositis and diarrhea and ipilimumab-associated colitis can.^7,15

Scientists have explored dietary changes, probiotics, fecal transplants between patients, as well as the targeted delivery of anti-cancer bacteria to tumor tissue and the use of tumor-seeking bacteria to deliver anti-cancer drug payloads. We are already investigating whether managing a patient’s gut microbiota, through e.g. It is an adjuvant component in cancer therapy, enhancing therapeutic efficacy and reducing toxicity.^4,16

Microbiome and metagenomics research for chemotherapy and cancer immunotherapy is more advanced than radiotherapy research, but microbes also appear to have implications for radiotherapy and chemoradiotherapy. .⁷