Background
Recently there has been a trend in increasing health and a significant portion of this has been tied to gut health. When it comes to gut health the gut microbiome is typically one of the first topics brought up; along with this comes the topic of maintaining and improving the bacteria in our gut. This is done in two fashions: diets and supplements. Within supplements, the ever more popular probiotics play an extremely important role in our gut health. Not only are probiotics beneficial in aiding digestion and other dietary benefits, but a recent study has shown that they may even suppress the formation of tumors, reduce colon inflammation, and cause the death of tumor cells related to colorectal cancer (CRC) (Zhou et al, 2024).
Colorectal cancer is the second most deadly cancer worldwide and it is occurring at an increasing rate, therefore it is of great importance that we continue to research the disease and find treatment options that may increase the outcomes for patients diagnosed with the disease (Patel et al, 2022). It is known that CRC patients may have altered gut microbiomes and that it may play a role in some of the symptoms of the disease as well as its progression (Cheng et al, 2020)(Yu et al, 2023). It’s also known that some probiotics can help restore a healthy balance of bacteria in the gut but can also reduce some of the harmful molecules that are produced by CRC (Amara et al, 2015)(Bender et al , 2023).
Ok so what?
So now we know a lot about probiotics and cancer but why does this matter? Well, in the recent study by Zhou et al., researchers found that a probiotic L. fermentum GR-3, has many positive benefits including antioxidant properties, immune regulation, intestinal barrier maintenance, and gut micro-ecological modulation (the structure of the gut microbiome). The current treatment options for colorectal cancer are surgery, radiotherapy, or chemotherapy, all of which have their own drawbacks. If adopted into medicine formally upon further research in humans, GR-3 could provide a much less invasive alternative or supplement to the existing treatment options.
So where’s the proof?
To examine the effect the treatments had on CRC the researchers used a treatment called azoxymethane/dextran sulfate sodium (AOM/DSS) to cause CRC in mice. They then gave groups of mice different compounds to test the effect they had on CRC. The probiotics and vitamin C were given orally and the Anti-cancer drug group, 5-fluorouracil (5-FU) was injected into the abdominal cavity. The L. fermentum (GR-3) and P.acidilactici (GR-6) groups both showed a 30% higher survival rate than the model group. Additionally, 5-FU showed a 50% lower survival rate than the model group. The model group showed shortening of the colon, all other treatment groups showed reduced shortening in comparison. The GR-3 and 5-FU groups both reduced the appearance of tumors by about 50% compared to the model group. The CR-3 and the antioxidant Vitamin C groups also stopped changes from occurring in the cells and the structure of the colon.
The next part of the study looked at whether or not GR-3 caused cancer cells to be destroyed and/or kept tumors from multiplying. The researchers were able to determine that the GR-3 bacteria was actually present in the distal colon, a place where tumors tend to form, and in tumor tissues. This was different from the GR-6 group which had similar amounts of its respective bacteria in tumors as the control group. Due to this finding, the researchers suggested that GR-3 may act directly on the tumors and promote their destruction. The researchers also tested for three markers in the colon that are related to anti tumor destruction and tumor multiplication. GR-3 decreased the amount of all 3 markers, meaning it is likely helpful in suppressing and destroying tumors. It was shown that GR-3 promotes the destruction of tumor cells in the distal colon.
In the third part of the study the researchers investigated how GR-3 affected gut inflammation and amount of stress caused by harmful molecules in the CRC models. It was found that the GR-3 group decreased the amount of molecules that cause inflammation compared to all other groups. It was also found that GR-3 reduces the amount of harmful molecules which cause stress by reducing the rate at which they were made in the body.
Next, the researchers decided to look at how GR-3 changed the community of bacteria in the gut. To do this the researchers took samples from the poop of each mouse and analyzed the kinds and amounts of bacteria in the samples. All of the treatments except for GR-3 caused a change in the community of bacteria in the mice compared to the CK group. Further analysis showed that the CK and GR-3 groups both had very similar communities of bacteria in their guts. A lot of the bacteria found in the GR-3 mice were bacteria which can destroy harmful molecules that can cause stress on the body. From their finding the researchers determined that GR-3 was able to help maintain a healthy and balanced microbial community.
The researchers started this study trying to determine the effects of probiotics on CRC. They determined that GR-3 was a potentially beneficial probiotic in the treatment of CRC and its symptoms. After further investigation it was shown that GR-3 had many beneficial effects which helped in the treatment of CRC, including suppressing the formation of tumors, reducing colon inflammation, and causing the death of CRC tumor cells. This study showed a promising step towards developing an alternative or supplement to traditional CRC treatments. Hopefully, with future, larger scale research, and eventually human trials we can develop more effective treatments for a disease that is deadly and an ever increasing threat.
What should we consider?
While the study is very exciting and shows some promise it does leave us with some questions and concerns. I think it will be important to further examine the mechanisms by which the probiotic causes the effects shown in this study. This could include studying how GR-3 causes a reduction in the appearance of new tumors. I think this would be an important step in establishing the causal relationship between GR-3 and the effects described. I would also like to see other cultures of L. fermentum from other locations tested to show reproducibility. This study was done on a small scale with only 10 mice per group. Some of the figures only had data from 4 mice per treatment, which provides a very modestly sized data set. This leads one to wonder if the results would remain the same if there were more mice used in each group. It is also important to replicate the experiment and show that this was not was not a result of chance, this is especially true given the small sample size. Further research should also be done to examine the effects of these probiotics on humans.
Further reading
Probiotics : Probiotics are an area of great interest among the microbiology community. These are definitely worth checking out with many probiotics, like the one in this study, showing benefits like improving your gut health.
Colorectal cancer : CRC is the second leading cause of cancer deaths and it’s occurring at an increasing rate globally (Patel et al, 2022). It would be worth learning more about this disease and how to screen for it.
Gut microbiome : The gut microbiome is a fascinating topic. There are many different associations between our gut and our overall health. This is a complex topic with tons of information available on it. Look into it and see what you can do to improve your own health! Check out this video on the importance of gut health!
References
- Amara, A. A., & Shibl, A. (2015). Role of probiotics in health improvement, infection control and disease treatment and management. Saudi Pharmaceutical Journal, 23(2), 107–114. https://doi.org/10.1016/j.jsps.2013.07.001
- Angle, E. (2019). Your Gut Microbiome: The Most Important Organ You’ve Never Heard Of | Erika Ebbel Angle | TEDxFargo. https://www.youtube.com/watch?v=B9RruLkAUm8
- Bender, M. J., McPherson, A. C., Phelps, C. M., Pandey, S. P., Laughlin, C. R., Shapira, J. H., Medina Sanchez, L., Rana, M., Richie, T. G., Mims, T. S., Gocher-Demske, A. M., Cervantes-Barragan, L., Mullett, S. J., Gelhaus, S. L., Bruno, T. C., Cannon, N., McCulloch, J. A., Vignali, D. A. A., Hinterleitner, R., … Meisel, M. (2023). Dietary tryptophan metabolite released by intratumoral lactobacillus reuteri facilitates immune checkpoint inhibitor treatment. Cell, 186(9). https://doi.org/10.1016/j.cell.2023.03.011
- Cheng, Y., Ling, Z., & Li, L. (2020). The intestinal microbiota and colorectal cancer. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.615056
- Patel, S. G., Karlitz, J. J., Yen, T., Lieu, C. H., & Boland, C. R. (2022). The rising tide of early-onset colorectal cancer: A comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. The Lancet Gastroenterology & Hepatology, 7(3), 262–274. https://doi.org/10.1016/s2468-1253(21)00426-x
- Yu, H., Li, X.-X., Han, X., Chen, B.-X., Zhang, X.-H., Gao, S., Xu, D.-Q., Wang, Y., Gao, Z.-K., Yu, L., Zhu, S.-L., Yao, L.-C., Liu, G.-R., Liu, S.-L., & Mu, X.-Q. (2023). Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses. Frontiers in Microbiology, 14. https://doi.org/10.3389/fmicb.2023.1126808
- Zhou, T., Wu, J., Khan, A., Hu, T., Wang, Y., Salama, E.-S., Su, S., Han, H., Jin, W., & Li, X. (2024). A probiotic limosilactobacillus fermentum GR-3 mitigates colitis-associated tumorigenesis in mice via Modulating Gut Microbiome. Npj Science of Food, 8(1). https://doi.org/10.1038/s41538-024-00307-5