Colonization Potential to Reconstitute a Microbe Community in Pseudo Germ-Free Mice After Fecal Microbe Transplant From Equol Producer

Abstract

Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.

Use of Physiologically Based Pharmacokinetic Modeling to Predict Human Gut Microbial Conversion of Daidzein to S-Equol

“…Contribution of S-equol to the overall estrogenicity in these two species can also be further compared. Rodents are reported to be S-equol producers, 51 , 52 while in human, only 20–55% of the population are S-equol producers. 8 , 9 The results of the current work, however, reveal that in spite of this species difference, rats may still reflect the human situation because the results of the PBPK modeling predict that S-equol contributes to the overall estrogenicity upon exposure to daidzein to a only limited extent in both species.…”

Production of Bovine Equol-Enriched Milk: A Review

“…About 50% of the Asian population and 70–80% of the Western population do not excrete equol, even if they have consumed soybean products or pure isoflavones [ 19 ], because, for a reason that is not known yet, they do not harbor equol-producing bacteria [ 48 ]. Several bacterial strains that possess the required enzymes (daidzein reductase, dihydrodaidzein reductase, tetrahydrodaidzein reductase, and dihydrodaidzein racemase) and are involved in the metabolism of daidzein to equol have been identified [ 49 , 50 ]. Even though the list of the identified intestinal bacteria involved in the daidzein metabolism may not be exhaustive, the majority seems to be part of the family Coriobacteriaceae [ 49 ].…”

“…Several bacterial strains that possess the required enzymes (daidzein reductase, dihydrodaidzein reductase, tetrahydrodaidzein reductase, and dihydrodaidzein racemase) and are involved in the metabolism of daidzein to equol have been identified [ 49 , 50 ]. Even though the list of the identified intestinal bacteria involved in the daidzein metabolism may not be exhaustive, the majority seems to be part of the family Coriobacteriaceae [ 49 ].…”

Potential of Establishing the Corresponding Human Microbial Community in Pseudo Germ-Free Mice through Fecal Microbe Transfer from Three Urolithin Metabotypes

“…For example, Liang et al established HMA mice for equol production using pseudo GF mice. 27 However, HMA mouse models of the three UMs based on pseudo GF mice have not yet been established. Research on the transformation mechanism of different urolithins and the health effects of EA in different UMs with humanized mice has not been reported.…”