Brain, behavior, and immunityAug 12, 2022

Gut bacteria chemicals called indoles may activate a brain receptor and reduce brain inflammation in Alzheimer's model mice

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 18, 2026

Abstract

Microbiota-derived indoles may alleviate neuroinflammation in Alzheimer's disease models.

Indoles derived from gut microbiota can prevent the accumulation of amyloid-beta and hyperphosphorylation of Tau, which are key features in Alzheimer's disease.
Indoles enhance synaptic plasticity and improve cognitive and behavioral abilities in APP/PS1 mice.
An imbalance in indole-producing bacteria and a deficiency in tryptophan were observed in male APP/PS1 mice.
Indoles upregulated the production of the aryl hydrocarbon receptor and inhibited the NF-κB signaling pathway.
These compounds reduced the release of inflammatory cytokines, thereby alleviating the inflammatory response associated with Alzheimer's disease.

Simplified

Gut microbiota alterations might affect the development of Alzheimer's disease (AD) through microbiota-derived metabolites. For example, microbiota-derived Indoles via tryptophan metabolism prevented Aβ accumulation and Tau hyperphosphorylation, restored synaptic plasticity, and then promoted the cognitive and behavioral ability of APP/PS1 mice. The imbalanced compositions of Indoles-producing bacteria with tryptophan deficiency were found in male APP/PS1 mice, but the molecular mechanisms remained unclear. Our current study revealed that Indoles (including indole, indole-3-acetic acid and indole-3-propionic acid) upregulated the production of aryl hydrocarbon receptor (AhR), inhibited the activation of the NF-κB signal pathway as well as the formation of the NLRP3 inflammasome, reduced the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β and IL-18, alleviating the inflammatory response of APP/PS1 mice. These findings demonstrated the roles of Indoles-producing bacteria in activating the AhR pathway to regulate neuroinflammation of AD through gut microbiota-derived Indoles, which implied a novel way for AD treatment.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Gut bacteria chemicals called indoles may activate a brain receptor and reduce brain inflammation in Alzheimer's model mice

Abstract

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Competing interests

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Abstract

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