Gut Bacteria and Anticancer Therapy — Chromatography Studies the Link

A new study has found that the type of bacteria in the gut of cancer patients is affected by the type of treatment. The study, Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients, was published in the journal Neoplasmia.

Fighting alien invaders

Our immune system is made of cells, tissues and organs that protects the body against alien invaders. These invaders could be bacteria or parasites — or any foreign microbe that the body thinks is attacking it. The immune system attempts to keep these invaders out or to seek and destroy them when they get into our cells, bloodstream or organs.

So, one of the key aspects of the immune system is its ability to tell the difference between foreign invaders and normal cells — and to remember which foreign invaders it has seen before. This is how our immune system responds to infections it has seen before and the basis of how vaccines work in the body. Knowing the difference between ‘good’ and ‘bad’ allows our immune system to attack the invaders and keep us safe.

Checkpoint Charlies

So how does the immune system know who to attack? Well one way is to use ‘checkpoints’. These are molecules on immune cells that need activating to start the relevant immune response. The checkpoints can be activating or inhibiting depending on the molecules. And researchers can use this fact to design medicines that either stimulate or inhibit cells.

But recent work has found a link between bacteria in our gut and the immune systems response to drugs at the checkpoints — and the work concerns drugs designed to help treat cancer. In the paper referenced above, the team carried out a prospective study designed to look at the effects of the human gut microbiota and the response to immune checkpoint inhibitor therapy (ICT) using some of the drugs designed for ICT therapy of melanoma.

Gold standard study

A prospective cohort study is considered to be the best type of epidemiological study — ruling out unwanted biases and giving the best risk estimations of disease for the population. The study was based on metastatic melanoma patients. Metastatic melanoma is also known as stage IV melanoma and is when melanoma cells have spread through the lymph nodes to other parts of the body.

The team took faecal samples from patients before they started ICT treatment and again during their treatment. Liquid chromatography with tandem mass spectrometry was used to analyse the samples. The use of HPLC in proteomics and metabolomics is discussed in the article, Enhanced Peptide Identification Using Capillary UHPLC and Orbitrap Mass Spectrometry.

The team report that although the type of ICT treatment influenced the gut microbiota of the patients, the study did not find a causal link between gut bacteria and ICT efficacy. They plan a larger scale trial.