Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons

Jeanne Neuffer; Raúl González-Domínguez; Sophie Lefèvre-Arbogast; Dorrain Y. Low; Bénédicte Driollet; Catherine Helmer; Andrea Du Preez; Chiara de Lucia; Silvie R. Ruigrok; Barbara Altendorfer; Ludwig Aigner; Paul J. Lucassen; Aniko Korosi; Sandrine Thuret; Claudine Manach; Mercè Pallàs; Mireia Urpi-Sardà; Alex Sánchez-Pla; Cristina Andres-Lacueva; Cécilia Samieri

doi:10.3390/nu14214688

Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons

Jeanne Neuffer^*, Raúl González-Domínguez, Sophie Lefèvre-Arbogast, Dorrain Y. Low, Bénédicte Driollet, Catherine Helmer, Andrea Du Preez, Chiara de Lucia, Silvie R. Ruigrok, Barbara Altendorfer, Ludwig Aigner, Paul J. Lucassen, Aniko Korosi, Sandrine Thuret, Claudine Manach, Mercè Pallàs, Mireia Urpi-Sardà, Alex Sánchez-Pla, Cristina Andres-Lacueva, Cécilia Samieri

^*Corresponding author for this work

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Abstract

The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.

Original language	English
Article number	4688
Journal	Nutrients
Volume	14
Issue number	21
Early online date	5 Nov 2022
DOIs	https://doi.org/10.3390/nu14214688
Publication status	Published - 5 Nov 2022

Keywords

Alzheimer’s disease
cognitive decline
dementia
gut microbiota
gut–brain axis
metabolomics
propionic acid

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Neuffer, J., González-Domínguez, R., Lefèvre-Arbogast, S., Low, D. Y., Driollet, B., Helmer, C., Du Preez, A., de Lucia, C., Ruigrok, S. R., Altendorfer, B., Aigner, L., Lucassen, P. J., Korosi, A., Thuret, S., Manach, C., Pallàs, M., Urpi-Sardà, M., Sánchez-Pla, A., Andres-Lacueva, C., & Samieri, C. (2022). Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons. Nutrients, 14(21), Article 4688. https://doi.org/10.3390/nu14214688

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title = "Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons",

abstract = "The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.",

keywords = "Alzheimer{\textquoteright}s disease, cognitive decline, dementia, gut microbiota, gut–brain axis, metabolomics, propionic acid",

author = "Jeanne Neuffer and Ra{\'u}l Gonz{\'a}lez-Dom{\'i}nguez and Sophie Lef{\`e}vre-Arbogast and Low, {Dorrain Y.} and B{\'e}n{\'e}dicte Driollet and Catherine Helmer and {Du Preez}, Andrea and {de Lucia}, Chiara and Ruigrok, {Silvie R.} and Barbara Altendorfer and Ludwig Aigner and Lucassen, {Paul J.} and Aniko Korosi and Sandrine Thuret and Claudine Manach and Merc{\`e} Pall{\`a}s and Mireia Urpi-Sard{\`a} and Alex S{\'a}nchez-Pla and Cristina Andres-Lacueva and C{\'e}cilia Samieri",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = nov,

day = "5",

doi = "10.3390/nu14214688",

language = "English",

volume = "14",

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Neuffer, J, González-Domínguez, R, Lefèvre-Arbogast, S, Low, DY, Driollet, B, Helmer, C, Du Preez, A, de Lucia, C, Ruigrok, SR, Altendorfer, B, Aigner, L, Lucassen, PJ, Korosi, A, Thuret, S, Manach, C, Pallàs, M, Urpi-Sardà, M, Sánchez-Pla, A, Andres-Lacueva, C & Samieri, C 2022, 'Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons', Nutrients, vol. 14, no. 21, 4688. https://doi.org/10.3390/nu14214688

TY - JOUR

T1 - Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons

AU - Neuffer, Jeanne

AU - González-Domínguez, Raúl

AU - Lefèvre-Arbogast, Sophie

AU - Low, Dorrain Y.

AU - Driollet, Bénédicte

AU - Helmer, Catherine

AU - Du Preez, Andrea

AU - de Lucia, Chiara

AU - Ruigrok, Silvie R.

AU - Altendorfer, Barbara

AU - Aigner, Ludwig

AU - Lucassen, Paul J.

AU - Korosi, Aniko

AU - Thuret, Sandrine

AU - Manach, Claudine

AU - Pallàs, Mercè

AU - Urpi-Sardà, Mireia

AU - Sánchez-Pla, Alex

AU - Andres-Lacueva, Cristina

AU - Samieri, Cécilia

PY - 2022/11/5

Y1 - 2022/11/5

N2 - The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.

AB - The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut–brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case–control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.

KW - Alzheimer’s disease

KW - cognitive decline

KW - dementia

KW - gut microbiota

KW - gut–brain axis

KW - metabolomics

KW - propionic acid

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U2 - 10.3390/nu14214688

DO - 10.3390/nu14214688

M3 - Article

C2 - 36364950

AN - SCOPUS:85141623976

SN - 2072-6643

VL - 14

JO - Nutrients

JF - Nutrients

IS - 21

M1 - 4688

ER -

Exploration of the Gut–Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons

Abstract

Keywords

UN SDGs

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