2021
DOI: 10.7554/elife.59826
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Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition

Abstract: Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, the mechanisms of microbiome–brain interaction in AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice increased the Aβ plaque… Show more

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Cited by 207 publications
(155 citation statements)
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“…Some studies have also found that esterified SCFAs can exert central anti-inflammatory effect through GPR4 [ 28 ], SCFAs also play an important role in the regulation of microglia function, [ 29 ]. However, a considerable number of studies have found that SCFAs can promote the deposition of amyloid protein and the activation of microglia [ 30 ]. So, we can say that SCFAs is a double-edged sword, which plays an important role in the occurrence and development of AD.…”
Section: Discussionmentioning
confidence: 99%
“…Some studies have also found that esterified SCFAs can exert central anti-inflammatory effect through GPR4 [ 28 ], SCFAs also play an important role in the regulation of microglia function, [ 29 ]. However, a considerable number of studies have found that SCFAs can promote the deposition of amyloid protein and the activation of microglia [ 30 ]. So, we can say that SCFAs is a double-edged sword, which plays an important role in the occurrence and development of AD.…”
Section: Discussionmentioning
confidence: 99%
“…Anti-inflammatory and neuroprotective capacities of SCFAs were found mainly in animal studies or in vitro (85)(86)(87). In contrast, in one study increased Aβ plaque deposition was demonstrated in germ free AD mice fed with SCFAs (88). In human studies acetate and valerate as well as bacterial LPS were connected with an enhanced amyloid deposition in the brain.…”
Section: Short-chain Fatty Acidsmentioning
confidence: 99%
“…In addition to reporting decreased microbial richness and diversity in older mice, this study also demonstrated that 6 and 9 months old mice had increased abundances of inflammation-related bacterial taxa (Chen et al, 2020 ). Microbial products such as short chain fatty acids were also recently identified as modulators of microglial function in vivo , increasing microglial reactivity and hindering microglial phagocytosis (Colombo et al, 2021 ). Likewise, microbiome modulations in 5xFAD mice were shown to differentially control microglial Aβ clearance mechanisms and influence plaque deposition (Mezö et al, 2020 ).…”
Section: Microbiome Influences On Microglia and Astrocyte Function In Neurodegenerative Diseasementioning
confidence: 99%