Immunotherapy works better with a strong gut microbiome

Immunotherapy works better with a strong gut microbiome

Cancer immunotherapy drugs are more successful of the patient has a strong gut microbiome, whether that is through diet, probiotic and prebiotic foods or even where patients have a fecal microbiome transplant from a donor who previously had good results. 

The microbiome is a 'Key Influencer' for immunotherapy success

More and more people with cancer are going to be offered immunotherapy over the coming years. But results to date have disappointed against the huge potential for these drugs. Quite rightly, scientists have been asking 'Why?'. At the 2019 European Society for Radiotherapy and Oncology (ESTRO) meeting in Milan Dr. Marianna Nuti from the University of Rome talked of the potential for the immune system to cure any cancer and immunotherapy being an excellent weapon. In her team's research on Nivolumab with NSCLC there was "a significant role of specific gut bacteria in influencing the cancer development AND the response to immunotherapy" (1).

Nuti said that the microbiome was crucial as it influenced the immune system, but a damaged microbiome, caused by antibiotics (even during the cancer treatment) could inhibit the performance of Nivolumab, which she was studying. "When we treat our children with antibiotics, we are changing their microbiota and their capacity to respond to pathogens, through the immune system. And it's the same with antibiotics and drugs with cancer". Nuti talked of the importance of keeping attacker T-cells primed by improving the microbiome so that immunotherapy drugs could work better.

Strong Microbiome essential in fighting cancer

T-cells are the attackers in your immune system. You need them if you are to beat cancer or Covid.

Researchers have previously concluded that increasing the number of T-cells through increasing good bacteria numbers (through probiotics or their favourite foods, prebiotics) aided the PD-1 drugs like Pembrolizumab (Keytruda) and Nivolumab (Opdivo), whereas decreasing T-cell numbers through antibiotics hindered the drugs, which anyway themselves seem to damage the gut microbiome further.

  • People who take antibiotics before immunotherapy have very poor success rates
  • People who take probiotics with immunotherapy get a better response in some studies
  • People who consume high levels of soluble fibre (a proven prebiotic), get a much better response

For example, a team of researchers from the Gustave Roussy Cancer Center in France found that one species with promoted gut lining health (Akkermansia muciniphila), prompted cytokine IL12 release promoting T-cell formation. The immune system has long been known to develop in the gut lining.

2019 research in the Lancet showed that there were 39 clinical trials currently studying the positive effects of increasing the diversity of gut bacteria through high fibre diets (2) and the benefits in fighting cancer. One recent study showed how just two bacteria species could improve sugar and lipid metabolism, reducing BMI and diabetes risk. Poor sugar control and diabetes are linked to a 3-fold increase in cancer risk (3).

Fecal Microbiome Transplants from survivors help 'cure' cancer!

Two different studies in their early stages were presented at the 2020 American Association for Cancer Research. The early results suggest that some patients who initially did not benefit from certain immunotherapy drugs were successful after receiving a gut microbiome transplant from patients for whom the immunotherapy drugs had worked. Their tumours stopped growing and/or shrank.

The research involved patients on PD-1 immunotherapy drugs, where the drugs block a protein on immune system T-cells, stopping them from working fully. By the drug reducing the block, the T-cell can recognise the cancer and do its job.

Initial studies showed the benefits of Fecal Transplants with immunotherapy drugs in mice. Now a number of different centres are looking at giving fecal microbiome transplants to humans.

Go to: What is a Fecal Transplant?

For example, Gal Markel and Ben Boursi at Sheba Medical Center in Ramat Gan, Israel, collected stool samples from two patients with metastatic skin cancer whose tumours completely disappeared after they had been given the PD-1 drugs. Using colonoscopy, the researchers added bacteria from the successful patients to ten others who had previously had poor results and were all terminally ill. The microbiome of all patients moved closer to that of the successful patients and side-effects were much reduced when resuming immunotherapy. The patients went back on the immunotherapy and continued to receive pills orally, which were tasteless and odourless, but contained cancer survivors faeces. In this initial trial several patients had significantly improved responses to immunotherapy and one man was 'cured'. Dr. Boursi said recently, "For the first time in the world, we have successfully fought cancerous tumours by changing the gut microbiome"

Researchers for the National Cancer Institute saw the same sort of result – a major breakthrough in one person, improved performance in another but no improvement in a third.

Early days yet, but already lessons can be learned. If you are about to have immunotherapy, do everything in your power to boost your microbiome. Although, just to confuse issues, after three studies from Chicago Medical School and Lille, France showing Probiotics had a positive benefit, MD Anderson researchers think they might not!

Go to: Your microbiome controls your immune response

Early days yet, Chris Woollams, former Oxford University Biochemist and a founder of CANCERactive said, "I am really pleased to see this research. We have long argued that antibiotics are dangerous and 50% are unnecessary. It's good to see Dr. Nuti saying the same. Even in cancer treatment, they clearly get in the way, and can prove extremely damaging to your chances of survival. In Personal Prescriptions for more than a decade we've been killing the pathogens and rebuilding the gut microbiome with probiotic and prebiotic foods. Perhaps this is why we have been getting such good results!"

Go to: Heal your Gut - Heal your Body.

*****
Reference

  1. J Clin Oncol 2018; doi:10.1200/JCO.2018.36.15_suppl.e15020
  2. https://www.canceractive.com/article/increasing-fibre%20intake%20improves%20immunotherapy%20outcomes
  3. https://www.sciencemag.org/news/2019/04/fecal-transplants-could-help-patients-cancer-immunotherapy-drugs

 


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2020 Research
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