Research Paper Volume 13, Issue 5 pp 6375—6405

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites

Schematic view of the experimental design. (A) Several commensals in mono-associated mice previously decontaminated by broad spectrum antibiotics (ATB) were administered by oral gavage. Akkermansia muciniphila (Akk) was administered by oral gavage to mice previously decontaminated by broad spectrum ATB and transplanted with human fecal material (FMT). Continuous ATB was administrated in the drinking water of the animals. (B) Mice previously decontaminated by broad spectrum ATB and FMT-treated, received Akk or the pasteurized form of Akk (Akk-past) by oral gavage (versus continuous FMT or ATB). PBS was administered as control (in both, (A, B) designs). (C) General methodology for metabolomics. The impact of the different treatments on the local (ileal, colon) and distal (liver, plasma) metabolome was evaluated using gas and liquid chromatography coupled to mass spectrometry allowing to detect a broad range of targeted and untargeted metabolites. Metabolite extraction was performed on the different organs collected from mice at the experiment day marked with a red arrow in (A, B). Extracts were processed and analyzed by liquid- and gas-chromatography coupled to mass spectrometry. Data was merged and analyzed using the GRmeta package in R or a built-in software, Compound Discoverer, for untargeted metabolomics. ATB, antibiotics; PBS, phosphate buffer saline; Brc, Burkholderia cepacia; Hir, Enterococcus hirae; Frg, Bacteroides fragilis; Bur, Burkholderia sp.; Mit, Catenibacterium mitsuokella; FMT, fecal microbiota transplant; Akk, Akkermansia muciniphila; Akk-past, pasteurized Akkermansia muciniphila.

Figure 1. Schematic view of the experimental design. (A) Several commensals in mono-associated mice previously decontaminated by broad spectrum antibiotics (ATB) were administered by oral gavage. Akkermansia muciniphila (Akk) was administered by oral gavage to mice previously decontaminated by broad spectrum ATB and transplanted with human fecal material (FMT). Continuous ATB was administrated in the drinking water of the animals. (B) Mice previously decontaminated by broad spectrum ATB and FMT-treated, received Akk or the pasteurized form of Akk (Akk-past) by oral gavage (versus continuous FMT or ATB). PBS was administered as control (in both, (A, B) designs). (C) General methodology for metabolomics. The impact of the different treatments on the local (ileal, colon) and distal (liver, plasma) metabolome was evaluated using gas and liquid chromatography coupled to mass spectrometry allowing to detect a broad range of targeted and untargeted metabolites. Metabolite extraction was performed on the different organs collected from mice at the experiment day marked with a red arrow in (A, B). Extracts were processed and analyzed by liquid- and gas-chromatography coupled to mass spectrometry. Data was merged and analyzed using the GRmeta package in R or a built-in software, Compound Discoverer, for untargeted metabolomics. ATB, antibiotics; PBS, phosphate buffer saline; Brc, Burkholderia cepacia; Hir, Enterococcus hirae; Frg, Bacteroides fragilis; Bur, Burkholderia sp.; Mit, Catenibacterium mitsuokella; FMT, fecal microbiota transplant; Akk, Akkermansia muciniphila; Akk-past, pasteurized Akkermansia muciniphila.