▎WuXi AppTec content team editor
There is growing evidence that the bacteria in our gut are not as home-loving as they think, and although they work in the gut most of the time, it doesn't mean that all microbes will follow this rule.
In the past two years, papers describing the "exodus" of gut microbes have appeared in top journals, including papers in journals such as Nature and Science Immunology, which not only detect unique microorganisms in the gut in other organs and tissues, but also confirm that these microorganisms are harmless and beneficial to fight cancer.
According to the analysis of scientists at the University of Pittsburgh, probiotics can metastasize from the intestines of melanoma mice to tumors, and stimulate immune cells at tumors, thereby providing a guarantee for enhancing the anti-cancer effect of immunotherapy.
The researchers conducted this study because they found that some previous papers showed a link between probiotic supplementation and the treatment response of immune patients in melanoma patients, but there are still many questions, can probiotics work in the gut? How do they change the sensitivity of tumors to treatment?
To this end, they specially selected some common probiotics on the market, including Bifidobacterium Longum, Lactobacillus reuteri, Lactobacillus johnsonii, and added them to the daily diet of melanoma mice.
As a result, either probiotic can significantly slow down the tumor growth rate of mice, and Lactobacillus reuteri has the strongest effect, and they also focused on analyzing this microorganism.
During long-term feeding, the researchers obtained some tumor samples from mice, and the researchers clearly saw that over time, the microbial diversity in the tumor microenvironment was declining, replaced by an increasingly abundant Lactobacillus reuteri. In addition to tumors, the researchers also found Lactobacillus reuteri in liver, spleen and mesenteric lymph nodes, suggesting possible migration pathways.
▲ Probiotics in the intestine can migrate to tumors and stimulate immune responses there (Image source: Reference [1])
The researchers also additionally tested mice with fibrosarcoma and breast cancer models, and they found that Lactobacillus reuteri can also migrate to these tumors and inhibit tumor growth.
From observations, tumors invaded by Lactobacillus reuteri tend to have more CD8+ T cells, and these cells have stronger anti-cancer activity. This result is the secretion of indole-3-aldehyde (I3A) by Lactobacillus reuteri, which acts specifically on the receptors of CD8+ T cells and significantly enhances their ability to suppress tumors.
The researchers pointed out that Lactobacillus reuteri only releases I3A in tumors to enhance the anti-cancer response, and if only in the intestine, it is not enough to fight tumors. This is also consistent with past observations in melanoma patients, where higher levels of I3A in their blood levels are associated with a better response to immunotherapy.
Image source: 123RF
But as the saying goes, "It's hard for a woman to cook without rice", and the same is true for Lactobacillus reuteri. Lactobacillus reuteri without tryptophan has the ability but cannot be used, because the manufacture of I3A is inseparable from tryptophan. When melanoma mice ate tryptophan-rich foods, tumors grew more slowly and they lived longer than mice with diets deficient in tryptophan. High doses of tryptophan can significantly enhance the anti-cancer effect of immune checkpoint inhibitors.
Based on the above results, the research team believes that probiotics and a tryptophan-rich diet can be used as an adjunct to enhance anti-cancer therapy. Of course, the researchers also suggest that more clinical trials are needed to verify this in the future, and any treatment needs to consult a doctor first and not try it on your own.
Resources:
[1] Study reveals how diet and probiotics boost melanoma immunotherapy response. Retrieved April 6, 2023 from https://www.eurekalert.org/news-releases/984746?
[2] Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment. Cell (2023). DOI:https://doi.org/10.1016/j.cell.2023.03.011