Yogurt is a drink for all ages, and we love to drink yogurt not only because of its sweet and sour taste, but also because of its health benefits. Indeed, the probiotics contained in yogurt – mainly lactic acid bacteria and bifidobacteria – have a wide range of effects on human health, including stimulating mucosal immunity, inhibiting the growth of harmful bacteria, supporting intestinal vitamin production, strengthening immunity, and so on [1]. In recent years, the relationship between probiotics and cancer prevention and treatment has attracted more and more attention.
Drink more yogurt to prevent cancer
In 2018, mainland researchers collected all available studies as of July 2018 on the relationship between fermented dairy intake and cancer risk, and finally included 61 eligible studies into a meta-analysis, combining data from more than 1.9 million study subjects and nearly 40,000 cancer patients, and found that yogurt intake significantly reduced bladder cancer (OR = 0.68; 95% confidence interval: 0.62 to 0.75) and colorectal cancer (OR= 0.83; 95% Confidence interval: 0.79 to 0.88) risk [2].
Another study, which separately assessed the relationship between dietary fiber intake and yogurt consumption and lung cancer risk, included a pooled analysis of 10 prospective cohorts of 1 445 850 adults, conducted across the United States, Europe and Asia, with a median follow-up of 8.6 years, during which a total of 18 822 people developed lung cancer. The results of the study showed that both dietary fiber and yogurt intake were inversely correlated with lung cancer risk, and that the two had a synergistic effect, that is, people who consumed more dietary fiber and drank more yogurt had a more than 30% lower incidence of lung cancer than people who consumed less fiber and did not drink yogurt at all [3].
Gut microbes affect the efficacy of immunotherapy
In addition to reducing the risk of cancer, drinking yogurt may improve the efficacy of tumor immunotherapy.
Primary resistance to immune checkpoint inhibitors has been shown to be attributable to abnormalities in the composition of the gut microbiome. The researchers treated sarcomas and melanoma mouse models treated with the broad-spectrum antibiotic ampicillin plus colistin plus streptomycin, and found that broad-spectrum antibiotics significantly affected the efficacy of immune checkpoint inhibitors [4].
Figure 1 Antibiotics affect the efficacy of immune checkpoint inhibitors
The next study evaluated the effect of broad-spectrum antibiotics on the efficacy of anti-PD-1/PD-1 antibody therapy in patients with clinical tumors, and found that the use of broad-spectrum antibiotics significantly shortened progression-free survival (PFS) and overall survival (OS) in treated patients, suggesting that dysbacteriosis may affect the therapeutic efficacy of immune checkpoint inhibitors. Transplanting the fecal microbiota of patients who respond to immune checkpoint inhibitors into germ-free mice or antibiotic-treated mice significantly improved the antitumor effect of PD-1 blockers, while the stool of non-responders did not.
Drinking yogurt may improve the efficacy of immunotherapy
Since changing the gut microbiota can affect the effect of immunotherapy, can the probiotics in yogurt reach the intestine improve the efficacy of immunotherapy?
Recently, a study led by American scientists pointed out that CBM588, a live bacterium product, can regulate the efficacy of immunotherapy for advanced renal cell carcinoma through the gut microbiome, which was based on Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a Randomized phase 1 trial was published in the authoritative medical journal Nature Medicine[5].
Dual immune checkpoint inhibitor therapy with nivolumab (PD-1 inhibitor) and ipilimumab (CTLA-4 inhibitor) has become a first-line solution for the clinical treatment of metastatic renal cell carcinoma, however, the therapy has no effect on the vast majority of patients, and even about 20% of patients will have an immediate worsening of the disease after treatment with this therapy, so it is necessary to take some methods to enhance the efficacy of immunotherapy, this time, The researchers turned their attention to the gut microbiome.
The live product CBM588 contains Clostridium butyrate, an anaerobic Bacillus capable of producing butyric acid. In this study, investigators designed a randomized study that prospectively tested the role of CBM588 in patients with metastatic renal cell carcinoma treated with navulisumab and ipilimumab. The study included a total of 30 patients, with a median age of 66 years, 72% of whom were male, and patients were randomized in a 2:1 ratio who received CBM588 + navuliyu-ipilizumab combination therapy and only navuliyu-ipilizumab.
As of April 15, 2021, the average follow-up time for patients was 12.2 months, at which point 12 patients were still being treated and 24 patients were still alive. The results showed that the PFS in the combined CBM588 group was significantly longer than in the control group (12.7 months vs. 5 months). Of these, 11 patients (58%) who received combination therapy achieved partial response (PR), while only 2 patients (20%) in the control group achieved partial response, with significant differences between the two groups. A total of 74% of patients in the CBM588 group observed a decrease in tumor-targeted lesions, and 79% of patients with controlled disease (PR + SD), while only 50% of patients in the control group had a reduction in target lesions and 40% of patients were controlled.
In terms of safety, the data in the two groups were similar, and 50% of the control patients and 52% of the CBM588 group had grade 3 or 4 adverse reactions, including fatigue, rash, adrenal insufficiency, etc., and no treatment-related deaths occurred.
Figure 2 CBM588 prolongs survival in patients with advanced renal cell carcinoma
Analysis of the gut microbiome found a significant increase in bifidobacteria in stool samples from patients treated with CBM588 and responding to treatment.
Interestingly, in the control group, one patient mentioned that he had been taking yogurt containing Bifidobacterium for a long time, and in the study, this patient showed the strongest response to immunotherapy, with the tumor shrinking by 82%.
This study suggests that CBM588 can improve the response to immunotherapy by increasing the abundance of Bifidobacterium, although this study has shortcomings such as small sample size, lack of placebo control, lack of long-term follow-up data, etc., the results of the study are still of great significance, proving that live bacteria products may increase the activity of immune checkpoint inhibitors, and there is no obvious safety hazard, laying the foundation for future related research on more probiotics and more cancer species.
In short, combined with the results of multiple studies, drinking yogurt supplements with certain specific probiotics does have certain positive significance for anti-cancer and anti-cancer, but drinking should be moderate.
bibliography:
1.Vinusha KS, Deepika K, Johnson TS, Agrawal GK, Rakwal R. Proteomic studies on lactic acid bacteria: A review. Biochem Biophys Rep 2018;14:140-8.
2.Zhang K, Dai H, Liang W, Zhang L, Deng Z. Fermented dairy foods intake and risk of cancer. International journal of cancer 2019;144:2099-108.
3.Yang JJ, Yu D, Xiang YB, et al. Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk: A Pooled Analysis. JAMA oncology 2020;6:e194107.
4.Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science (New York, NY) 2018;359:91-7.
5.Dizman N, Meza L, Bergerot P, et al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature medicine 2022.
Author | Yin Qilei
Source | The frontline of tumors in the health world