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Clinical Study

Lessard-Lord, unpublished

In a human clinical trial, 39 healthy participants consumed 480 mg of Prebiocran™ daily for 4 days. A 7-day washout period preceded the intervention, with strict limitation of polyphenols-containing food. Biological samples were collected before and after the treatment. Fecal DNA has been sequenced to study the gut microbiota evolution.

Results showed that Prebiocran™:

• Modulates the basal human gut microbiota beta-diversity in a shortterm period

• Notably induces a bloom of Bifidobacterium, a bacteria associated with gut health (Chen et al., 2021)

These results highlight the short-term clinical efficacy of Prebiocran™ and have been confirmed in ex vivo and animal studies in a longer term (2 weeks and 12 weeks).

Each dot represents a unique human microbiota analyzed by 16S rRNA gene amplicon sequencing. The distance-based redundancy analysis here clearly discriminates the gut microbiota after 4 days of Prebiocran™ treatment.

M-SHIME® STUDY

Cattero, unpublished

In this study, researchers inoculated fecal material of six healthy subjects in individual M-SHIME® systems. After weeks of stabilization to allow a suitable adaptation period for the microbiome to adapt, they administrated 480 mg Prebiocran™ for two weeks of treatment and analyzed the gut microbiota composition and function in the ascendant and transverse colon.

The M-SHIME® model

The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) is one of the few gut models that mimics the entire gastrointestinal tract. It is a semi-dynamic model with multi-stage compartment reactors, each of them respectively displaying defined conditions (pH, nutritional medium etc.) according to the intestinal region they represent. The M-SHIME, i.e., Mucosal-SHIME, is an extension of this model which also mimics the mucosal microbiome. It incorporates mucin-covered microcosms, allowing better understanding of the host-microbe interaction. Molly et al., 1993 & Van de Wiele et al., 2015.

Consistent with the clinical study, Prebiocran™ significantly and gradually modulated the microbiota composition throughout the 2-week dietary treatment in all the gut compartments (lumen and mucus of the ascendant and transverse colons).

Transverse colon

More specifically, Prebiocran™ was shown to promote in both lumen and mucin, the growth of:

• Bacteria known to metabolize proanthocyanidins (PACs) into smaller bioactive metabolites: Eggerthella, Flavonifactor and Lactiplantibacillus. (Corrêa et al., 2019 ; Gaur et al., 2023)

• Bacteria associated with gut barrier protection and health: Akkermansia and Faecalibacterium (Cani et al., 2022 ; Leylabadlo et al., 2020)

Animal Models

Anhê et al., 2015 ; Rodríguez-Daza et al., 2020 ; Daoust et al. 2021 ; Medina-Larqué et al., 2022

In several male and female mouse studies, Prebiocran™ was administrated at a dose of 200 mg/kg of body weight during 8 to 12 weeks.

In all the studies, Prebiocran™ modulated the mice microbiota diversity in a long-term period, often associated with a bloom of Akkermansia

The gut microbiota was analyzed in all the compartments of the M-SHIME system. Here are selected bacteria (Akkermansia, Faecalibaterium) with a significant increase in relative abundance according to the duration of Prebiocran™ treatment.

Metataxonomic analysis of the mice fecal microbiota, with significant difference of relative abundance after 9 weeks of Prebiocran™ treatment.

Anhê, F.F. et al. (2015)