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

Abstract

Three urolithin metabotypes (UMs) have been defined in the population according to final urolithins converted by gut microbiota. Currently, it is difficult to establish the cause-and-effect relationship between urolithins and microbiota in human studies. Studies on the health effects of ellagic acid (EA) in animal models rarely consider the differences in the urolithin production. Therefore, the objective of this study is to establish human microbiota-associated (HMA) mice, imitating the microbiota composition of the three UMs. Antibiotic-induced pseudo germ-free mice were gavaged with fecal bacteria of the three UM donors for four weeks. The results showed that the ability to produce corresponding urolithins was successfully transferred from the donor of the three UMs to HMA mice. The three UM HMA mice adopted a humanized microbiota profile similar to their corresponding donor. The family Eggerthellaceae and genera Eggerthella and Gordonibacter were successfully transferred and colonized from UM-A/B donors to HMA mice. Overall, the three UM HMA mouse models were successfully established, which provide a basis for exploring the health effects of EA.

In vivo administration of gut bacterial consortia replicates urolithin metabotypes A and B in a non-urolithin-producing rat model

“…This Uros production profile has also been described recently in a different approach with a pseudo-germ-free mice model after transplanting daily the faecal microbiota of different UMs donors for 4 weeks, which could be a valuable model to explore the health effects of EA and ETs. 34 However, our study has shown that consuming the bacterial consortia A (Gordonibacter + Enterocloster) and B (Ellagibacter + Enterocloster) is enough to produce the intestinal colonization of Uro-producing bacteria in a non-Uro-producing rat model, where the continued consumption of ETs was not sufficient to modify the UM-0 towards a Uros-producing metabotype (UM-A or UM-B).…”

Ameliorative Effect of Ellagic Acid on Aging in Rats with the Potential Mechanism Relying on the Gut Microbiota and Urolithin A-Producing Ability

“…6 Urolithins have various biological activities such as considerable antioxidant and anti-inflammatory properties. Interestingly, the large interindividual differences in the types and contents of urolithins produced after EA ingestion were observed in healthy Chinese youth 7 and human microbiotaassociated mice 8 in our previous study as well as in European 9 and Brazilian 10 studies, which is possibly due to the difference in the gut microbiota composition. In addition, EA can significantly modulate the gut microbiota composition.…”

Antioxidant and Anti-Inflammatory Properties of Walnut Constituents: Focus on Personalized Cancer Prevention and the Microbiome

“…Notably, some mouse lines lack the capacity to form urolithins from ellagic acid [45]). Thus, using mouse cancer models with a defined (or humanized) microbiome [102] would be an important future direction that could applied for studying walnuts, phytochemicals, and their cancer preventive properties. Several clinical trials have made significant inroads regarding the health benefits of walnuts, particularly with respect to cardiovascular and cognitive effects [3,26,70].…”