Faecal microbiota transplantation from Alzheimer's participants induces impairments in neurogenesis and cognitive behaviours in rats

Grabrucker, S.; Marizzoni, M.; Silajdzic, E.; Lopizzo, N.; Mombelli, E.; Nicolas, S.; Dohm-Hansen, S.; Scassellati, C.; Moretti, D.; Rosa, M.; Hoffmann, K.; English, J. A.; Lavelle, A.; O'Neill, C.; Thuret, S.; Cattaneo, A.; Nolan, Y. M.

doi:10.1101/2022.11.04.515189

bioRxiv · 10.1101/2022.11.04.515189

Faecal microbiota transplantation from Alzheimer's participants induces impairments in neurogenesis and cognitive behaviours in rats

Grabrucker, S.·Marizzoni, M.·Silajdzic, E.·Lopizzo, N.·Mombelli, E.·Nicolas, S.·Dohm-Hansen, S.·Scassellati, C.·Moretti, D.·Rosa, M.·Hoffmann, K.·English, J. A.·Lavelle, A.·O'Neill, C.·Thuret, S.·Cattaneo, A.·Nolan, Y. M.

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Abstract

The gut microbiome is emerging as an important susceptibility factor in Alzheimers disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position the microbiota-gut-brain axis as a key regulator of AD. However, it is unknown whether gut microbiota alterations are the cause or consequence of AD symptoms. We transplanted faecal microbiota from AD participants and age-matched controls into microbiota-depleted naive adult rats and found impairments in AHN and associated memory tasks, which correlated with clinical cognitive scores. Discrete changes in the rat caecal and hippocampal metabolome were evident. Serum from AD participants also decreased neurogenesis in vitro and correlated with cognitive scores and pro-inflammatory genera. Our results reveal that the cognitive symptoms in AD may be due to alterations in gut microbiota, and that impaired neurogenesis may be a mechanistic link between altered gut microbiota and cognitive impairment in AD. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/515189v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@143263forg.highwire.dtl.DTLVardef@1842a23org.highwire.dtl.DTLVardef@1ea8aaborg.highwire.dtl.DTLVardef@135e5a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Grabrucker, S., Marizzoni, M., Silajdzic, E., Lopizzo, N., Mombelli, E., Nicolas, S., Dohm-Hansen, S., Scassellati, C., Moretti, D., Rosa, M., Hoffmann, K., English, J. A., Lavelle, A., O'Neill, C., Thuret, S., Cattaneo, A., Nolan, Y. M.. 2022-11-04. Faecal microbiota transplantation from Alzheimer's participants induces impairments in neurogenesis and cognitive behaviours in rats. https://doi.org/10.1101/2022.11.04.515189

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