Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the "second human genome"

Abstract

It has been found that the composition of intestinal microbiota can indicate the risk of disease to each individual. The concepts of biodynamics as used by the Benziger Winery in California, which treats every part of an agricultural environment as a living, breathing entity, can be usefully used in the construction of a system for cancer prevention, which seeks to use the relationship of coexistence (symbiosis) shared between people and intestinal symbiosis, that is, microbiota. Changes in the incidence rate of cancer among Japanese emigrants to Hawaii demonstrate the effect of the changes in the living environment. This leads to the hypothesis that an intake of soy-derived food products and the metabolization of the isoflavones they contain by intestinal microbiota is one of the factors for the significant difference in the incidence rate of prostate cancer among Asian and European/North American populations. It is further hypothesized that isoflavones, particularly equol, are a key factor in the difference in incidence rate between Asia and the West. It is suggested that not having equol converting bacteria in the intestine (non-equol producers) can be a risk factor for prostate cancer and that one direction for future research will be to examine the possibility of improving the intestinal environment to enable equol production.

Figure 1

Electron microscopic imaging of newly identified NATTS bacteria. The human intestinal bacterium NATTS converts daidzein found in soy isoflavones to equol. It is a Gram‐positive bacillus and is classified in the family Coriobacteriacea, belonging to the Slackia genus. The NATTS bacillus was detected and identified in the course of our research, but other equol‐converting bacteria have also been reported. The NATTS bacillus is the most efficient in its equol‐converting capacity. (a) Gram staining. (b) Scanning electron microscopy.

Figure 2

Comparisons of serum isoflavone concentrations and equol producer in the controls in each country. Comparison of serum isoflavone concentrations and ratios of equol producers among adults in Japan, Korea, the United States and Germany. The serum concentrations of genistein and daidzein are extremely high in Japanese and Korean subjects, who have a daily intake of soy‐derived food products, in comparison with US and German subjects. Of special mention is the ratio of equol products (the fourth column from left in the graph). Among control groups without prostate cancer, there was a marked difference in the proportion of equol producers in each country: Japan (50%), Korea (59%), USA (14%), Germany (6%).

Figure 3

Comparisons between cases and controls in Japan and Korea. Results of case–control studies on the serum isoflavone concentrations and the proportion of equol producers for case groups with prostate cancer and control groups that tested negative for cancer. This case–control study for Japan and Korea was implemented as a joint study. The case and control groups for both countries showed high concentrations of genistein and daidzein. However, the ratio of equol producers was in statistical terms significantly lower in prostate cancer patients in the case group (χ² test; P < 0.05). In other words, equol non‐producers can be said to be a high risk group for prostate cancer. This would further suggest that the presence or absence of equol‐producing bacteria could have an effect on the risk of protracting prostate cancer. This is possibly a new function for intestinal microbiota.

Figure 4

Pattern diagram showing the antiproliferation effect of equol on prostate cancer cells. Working hypothesis of growth inhibition of PC cells by equol. AR, androgen receptor; DHT, dihydrotestosterone; E₂, estrogen; Erα, estrogen receptor α; Erβ, estrogen receptor β; T, testosterone.

Figure 5

Changes in serum equol level. Double‐blind phase II trials involving isoflavone administration for high risk prostate cancer group. Changes in serum equol concentrations before and after the administration of isoflavones. In the equol‐producer group, although 25–33 ng/mL of equol was detected, in the equol non‐producer group almost no equol was detected. It was observed that serum equol concentrations only increased in equol‐producers who were provided with an isoflavone dose, thus demonstrating the validity of the trial.