. Previous studies have shown an association between the altered gut microbiome and cancer has been shown in mice. The disruption of gut microbiota due to treatment with strong antibiotics accelerated breast cancer growth, whereas supplementation with specific bacteria had a protective effect (
).
The anticancer effects of the gut microbiome are exerted through different mechanisms like enhancing innate (inborn) immunity by facilitating immune cell development and maturation and enhancing adaptive (acquired) immunity by increasing the ability of immune cells to infiltrate and kill cancer. Another mechanism is the production of short-chain fatty acids (SCFA) from dietary fibers. By serving as an energy source, SCFAs activate immune cells (
).
Conversely, the overgrowth of harmful bacteria may promote cancer development by increasing the permeability of the gut lining, which in turn leads to chronic inflammation – a well-recognized cancer-predisposing state.
Another cancer-promoting mechanism could be the production of toxic substances that damage the DNA of the gut cells, contributing to their cancerous transformation. Additionally, helping cancer cells weaken the immune response.
Can Gut Microbiome be a Cancer Biomarker
Changes in the gut microbiome have been associated with gastric, pancreatic, liver, and colorectal cancer. The association between the gut microbiome and cancer is not limited to the digestive system – it has also been seen in lung and breast cancer.
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However, with the millions of gut bacteria present, it is not easy to examine its complexity.
Bacterial culture tests which earlier were used as a standard method to identify bacteria have been replaced by next-generation sequencing (NGS) – a genetic test to determine the order in which the building blocks of bacterial nucleic acids are arranged. This technique allows testing for numerous genes at the same time, and various bioinformatics methods are used to organize the complex data. Although the composition of the microbiome slightly differs in the lining and the contents of the gut, stool samples are usually tested for convenience.
The changes in gut microbiome include a decrease or increase in species diversity, the presence of specific bacteria, or a higher number of certain bacteria compared with healthy individuals.
For instance, reduced microbiome diversity and the presence of Fusobacterium nucleatum, Bacteroides fragilis, Enterococcus faecalis, Escherichia coli, and others are characteristic of colorectal cancer.
Gut microbiome testing could be an excellent application for the early detection of cancer. By analyzing 27 species of bacteria, researchers have identified a specific microbiome “signature” for pancreatic cancer (e.g., the presence of Veillonella, Streptococcus, Akkermansia, and change in the amount of Bacteroides, Lactobacillus, Bifidobacterium). This could be a real breakthrough as pancreatic cancer is one of the most lethal cancer types and does not have any conventional screening tests.
Gut Microbiome and its Use in Cancer Therapies
The gut microbiome has been associated both with the response to cancer treatment (chemotherapy, radiotherapy, and targeted therapy) and the severity of treatment-related side effects.
Checkpoint inhibitors have made a tremendous improvement in the treatment of many cancers, but the response to these agents varies considerably between different cancer types as well as between individuals. The gut microbiome is considered to be one of the main factors that impact the response to checkpoint inhibitors. Studies in humans showed that patients with higher amounts of bacteria belonging to Ruminococcus, Faecalibacterium, and Akkermansia species responded better to checkpoint inhibitors, whereas non-responsiveness was associated with the presence of Streptococcaceae, Bacteroidaceae, etc.
As the levels of SCFAs correlate with the response to checkpoint inhibitors in patients with various solid cancers, the production of these substances by bacteria probably mediates this effect.
In animal experiments, tumor-bearing mice raised in special conditions to be free of any germs or those with gut bacteria eradicated by strong antibiotics did not respond to checkpoint inhibitors but feeding mice with certain bacteria (e.g., Bacteroides fragilis) overruled this resistance. Furthermore, bacteria ameliorated the immune system-related side effects, (e.g checkpoint-inhibitor-induced colitis) which remain a major challenge with checkpoint inhibitors.
Gut Bacteria May Assist Chemotherapy Drugs
The gut microbiome may enhance the response to conventional cancer chemotherapy drugs. Gut bacteria produce butyrate which is used as an energy source, reduces inflammation and increases programmed cancer cell death which in turn enhances the effects of oxaliplatin.
Some other bacteria promote the activation of T lymphocytes and thus enhance cyclophosphamide effects. Furthermore, the gut microbiome has been suggested to improve chemotherapy-induced neurological side effects, e.g., damage to nerves, cognitive impairment, and psychological sequelae.
How can we Optimize Gut Microbiome
There are several ways to boost gut microbiome: dietary modification, administration of probiotics, and fecal microbiome transplant (FMT). Eating foods high in fiber, inulin, and fructo-oligosaccharides (FOS) can help maintain a healthy gut microbiome.
Fermented foods such as yogurt, sauerkraut, and kombucha supplement the gut with beneficial bacteria. Various medicinal products containing live bacteria may help support the gut microbiome after its disruption by various factors, e.g., the use of antibiotics and other prescription medicines, restricted diet, or stress.
While probiotics replenish the gut with just several types of bacteria, fecal microbiome transplantation restores the microbiome as a whole. Fecal transplants may be prepared from healthy young individuals or patients responding well to certain therapies and instilled through a tube directly into the gastrointestinal tract with minimal inconvenience for the recipient. Clinical trials are currently studying whether fecal transplants could help modify the effects of cancer therapy. However, a serious concern about fecal transplants is the possibility of transplanting harmful bacteria (3✔ ✔Trusted Source
A faecal microbiota signature with high specificity for pancreatic cancer
Go to source).
Increasing evidence suggests the multifaceted association between the gut microbiome and cancer. Gut microbiome-targeted therapy for cancer patients is still in the early stages of development.
Besides, most current evidence is gained in experiments with mice, which have significant differences in microbiomes compared with humans. Currently, many clinical trials are aiming to identify microorganisms that could be helpful in protection against cancer, enhancement of cancer treatment efficacy, or alleviation of side effects.
References :
- The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes – (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885097/)
- Association of Short-Chain Fatty Acids in the Gut Microbiome With Clinical Response to Treatment With Nivolumab or Pembrolizumab in Patients With Solid Cancer Tumors – (https://pubmed.ncbi.nlm.nih.gov/32297948/)
- A faecal microbiota signature with high specificity for pancreatic cancer – (https://pubmed.ncbi.nlm.nih.gov/35260444/)
Source: Medindia
