How can imbalance in the gut microbiome be related to cancer?

So there are multiple ways in which this could be.

And I wanted to mention you as break it up into three parts.

So one is diversity. So if there is a change in diversity in your gut microbiome, diversity means how much of different types of species do you have, how many different species, and how much of each types of type of these species you have. So our body has a certain balance of this diversity.

If there is an alteration in this balance, it's a microbial imbalance or dysbiosis. Dysbiosis is associated with many chronic diseases such as ones related to inflammation, obesity, diabetes, even cancer.

So having a good healthy diversity in your gut microbiome is essential to good health.

In myeloma, we have seen some studies that show a decreased diversity is associated with decreased overall survival progression free survival, increased risk of diarrhea, oral ulcers and other chemotherapy toxicities as well.

The next thing would be thinking about not just the overall diversity, but looking at specific bacteria.

There are certain bacteria that are good and we want more of them and there are certain bacteria that are bad. And some of the research that has looked at this to date, one paper from Dr. Lesokhin and our group at MSK had shown that two bacteria.

Eubacterium hallii and faecalibacteriumprausnitzii were associated with MRD negativity. So better outcomes. And what's known is these are butyrate producers.

A study in mice showed that prevotella heparinolytica and other bacteria is associated with increased risk of progression by increasing changes in the immune system, an increase in an interleukin 17.

based on this, I think knowing which bacteria to increase versus decrease will be the future of research in many diseases, including myeloma.

And then the third thing I'd like to say is looking at the metabolites or the substances that these bacteria make, because that can also impact outcomes. So there are some good substances like Butyrate, like I mentioned. So Butyrate is a short chain fatty acid. It has anti-cancer and anti-inflammatory effects.

The way it works is through inhibition of the nuclear factor Kappa B pathway, which is something that bortazomib works through as well.

And then each HDAC inhibitors belinostatt has been approved for myeloma that so if butyrate has an HDAC inhibitory effect as well. So both of these reasons say it's likely that having increased butyrate levels is going to be likely associated with better outcomes, though we don't have much data in myeloma at this point for that.

And then bile acids are associated with increased risk of other cancers and considered a carcinogen in some situations like liver cancer and colon cancer, we don't have data for myeloma.