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  Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline

Mossad, O., Nent, E., Woltemate, S., Folschweiller, S., Büscher, J. M., Schnepf, D., et al. (2021). Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline. Nature aging, 1, 1127-1136. doi:10.1038/s43587-021-00141-4.

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 Creators:
Mossad, Omar1, Author
Nent, Elisa2, Author
Woltemate, Sabrina1, Author
Folschweiller, Shani1, Author
Büscher, Jörg Martin2, Author              
Schnepf, Daniel1, Author
Erny, Daniel1, Author
Staeheli, Peter1, Author
Bartos, Marlene1, Author
Szalay, Antal1, Author
Stecher, Bärbel1, Author
Vital, Marius1, Author
Sauer, Jonas F.1, Author
Lämmermann, Tim2, Author              
Prinz, Marco1, Author
Blank, Thomas1, Author
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1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              

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 Abstract: Understanding the physiological origins of age-related cognitive decline is of critical importance given the rising age of the world’s population. Previous work in animal models has established a strong link between cognitive performance and the microbiota, and it is known that the microbiome undergoes profound remodeling in older adults. Despite growing evidence for the association between age-related cognitive decline and changes in the gut microbiome, the mechanisms underlying such interactions between the brain and the gut are poorly understood. Here, using fecal microbiota transplantation (FMT), we demonstrate that age-related remodeling of the gut microbiota leads to decline in cognitive function in mice and that this impairment can be rescued by transplantation of microbiota from young animals. Moreover, using a metabolomic approach, we found elevated concentrations of δ-valerobetaine, a gut microbiota-derived metabolite, in the blood and brain of aged mice and older adults. We then demonstrated that δ-valerobetaine is deleterious to learning and memory processes in mice. At the neuronal level, we showed that δ-valerobetaine modulates inhibitory synaptic transmission and neuronal network activity. Finally, we identified specific bacterial taxa that significantly correlate with δ-valerobetaine levels in the brain. Based on our findings, we propose that δ-valerobetaine contributes to microbiota-driven brain aging and that the associated mechanisms represent a promising target for countering age-related cognitive decline.

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Language(s): eng - English
 Dates: 2021-12-20
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s43587-021-00141-4
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Title: Nature aging
  Abbreviation : Nat. Aging
Source Genre: Journal
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Publ. Info: London : Nature Research
Pages: - Volume / Issue: 1 Sequence Number: - Start / End Page: 1127 - 1136 Identifier: ISSN: 2662-8465
CoNE: https://pure.mpg.de/cone/journals/resource/2662-8465