Human gut microbiota Agathobaculum butyriciproducens improves cognitive impairment in LPS-induced and APP/PS1 mouse models of Alzheimer's disease

Go, Jun; Chang, Dong-Ho; Ryu, Young‐Kyoung; Park, Hye-Yeon; Lee, In-Bok; Noh, Jung‐Ran; Hwang, Dae Youn; Kim, Byoung-Chan; Kim, Kyoung‐Shim; Lee, Chul‐Ho

doi:10.1016/j.nutres.2020.12.010

Cited by 46 publications

(45 citation statements)

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“…Agathobaculum butyriciproducens, which was also positively associated with childhood blood Cd, was found to improve cognitive impairment of Alzheimer's disease in mouse models (Go et al 2021). Parabacteroides distasonis, which can alleviate obesity and metabolic dysfunctions and tumor formation associated with a high-fat diet in mice (Koh et al 2018;Wang et al 2019), was also positively associated with childhood blood Cd.…”

Section: Discussionmentioning

confidence: 95%

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Associations of Childhood and Perinatal Blood Metals with Children’s Gut Microbiomes in a Canadian Gestation Cohort

Shen

Laue

Shrubsole

et al. 2022

Environ Health Perspect

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Background: The gut microbiome is important in modulating health in childhood. Metal exposures affect multiple health outcomes, but their ability to modify bacterial communities in children is poorly understood. Objectives: We assessed the associations of childhood and perinatal blood metal levels with childhood gut microbiome diversity, structure, species, gene family-inferred species, and potential pathway alterations. Methods: We assessed the gut microbiome using 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing in stools collected from 6- to 7-year-old children participating in the GESTation and Environment (GESTE) cohort study. We assessed blood metal concentrations [cadmium (Cd), manganese (Mn), mercury (Hg), lead (Pb), selenium (Se)] at two time points, namely, perinatal exposures at delivery ( ) and childhood exposures at the 6- to 7-y follow-up ( ). We used multiple covariate-adjusted statistical models to determine microbiome associations with continuous blood metal levels, including linear regression (Shannon and Pielou alpha diversity indexes), permutational multivariate analysis of variance (adonis; beta diversity distance matrices), and multivariable association model (MaAsLin2; phylum, family, species, gene family-inferred species, and pathways). Results: Children’s blood Mn and Se significantly associated with microbiome phylum [e.g., Verrucomicrobiota ( , ; , , respectively)] and children’s blood Mn significantly associated with family [e.g., Eggerthellaceae ( , )]-level differences. Higher relative abundance of potential pathogens (e.g., Flavonifractor plautii ), beneficial species (e.g., Bifidobacterium longum , Faecalibacterium prausnitzii ), and both potentially pathogenic and beneficial species (e.g., Bacteriodes vulgatus , Eubacterium rectale ) inferred from gene families were associated with higher childhood or perinatal blood Cd, Hg, and Pb ( ). We found significant negative associations between childhood blood Pb and acetylene degradation pathway abundance ( ). Finally, neither perinatal nor childhood metal concentrations were associated with children’s gut microbial inter- and intrasubject diversity. Discussion: Our findings suggest both long- and short-term associations between metal exposure and the childhood gut microbiome, with stronger associations observed with more recent exposure. Future epidemiologic analyses may elucidate whether the observed changes in the microbiome relate to children’s health. https://doi.org/10.1289/EHP9674

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Section: Discussionmentioning

confidence: 95%

“…2002 ). Agathobaculum butyriciproducens , which was also positively associated with childhood blood Cd, was found to improve cognitive impairment of Alzheimer’s disease in mouse models ( Go et al. 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Associations of Childhood and Perinatal Blood Metals with Children’s Gut Microbiomes in a Canadian Gestation Cohort

Shen

Laue

Shrubsole

et al. 2022

Environ Health Perspect

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“…In a similar, more recent study using APP/PS1 model, 8 weeks administration of Agathobaculum butyriciproducens (SR79) significantly improved cognitive performance in the novel object recognition test and Y-maze at the overt stage of AD-like pathology, together with decreased Aβ plaque deposition and microglia activation. Of utmost importance, SR79 treatment significantly decreased the expression of IL-1β and complement component C1QB genes in the cortex of APP/PS1-treated mice [ 151 ].…”

Section: Putative Interventions Aimed At Improving Neuronal Activity ...mentioning

confidence: 99%

Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

Bairamian

Sha

Rolhion

et al. 2022

Mol Neurodegeneration

162

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Background The implication of gut microbiota in the control of brain functions in health and disease is a novel, currently emerging concept. Accumulating data suggest that the gut microbiota exert its action at least in part by modulating neuroinflammation. Given the link between neuroinflammatory changes and neuronal activity, it is plausible that gut microbiota may affect neuronal functions indirectly by impacting microglia, a key player in neuroinflammation. Indeed, increasing evidence suggests that interplay between microglia and synaptic dysfunction may involve microbiota, among other factors. In addition to these indirect microglia-dependent actions of microbiota on neuronal activity, it has been recently recognized that microbiota could also affect neuronal activity directly by stimulation of the vagus nerve. Main messages The putative mechanisms of the indirect and direct impact of microbiota on neuronal activity are discussed by focusing on Alzheimer’s disease, one of the most studied neurodegenerative disorders and the prime cause of dementia worldwide. More specifically, the mechanisms of microbiota-mediated microglial alterations are discussed in the context of the peripheral and central inflammation cross-talk. Next, we highlight the role of microbiota in the regulation of humoral mediators of peripheral immunity and their impact on vagus nerve stimulation. Finally, we address whether and how microbiota perturbations could affect synaptic neurotransmission and downstream cognitive dysfunction. Conclusions There is strong increasing evidence supporting a role for the gut microbiome in the pathogenesis of Alzheimer’s disease, including effects on synaptic dysfunction and neuroinflammation, which contribute to cognitive decline. Putative early intervention strategies based on microbiota modulation appear therapeutically promising for Alzheimer’s disease but still require further investigation.

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“…Butyrate is beneficial for proper vagal afferent signals in patients with AD and participates in learning and memory, regulating neuronal growth and survival as well as synaptic differentiation via intracellular Ca 2+ signaling and by maintaining BDNF levels (Barichello et al, 2015;Goswami et al, 2018). Agathobaculum butyriciproducens SR79, a strict anaerobic and butyrate-producing bacterium, can improve cognitive impairment by decreasing microglial activation and reducing Aβ plaque deposition in APP/PS1 mice (Go et al, 2021). To date, most of the existing evidence has been based on in vitro and in vivo experimental studies (Wang F. et al, 2020).…”

Section: Probioticsmentioning

confidence: 99%

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

Liu

Jiang

et al. 2021

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is the most common age-related progressive neurodegenerative disease, characterized by a decline in cognitive function and neuronal loss, and is caused by several factors. Numerous clinical and experimental studies have suggested the involvement of gut microbiota dysbiosis in patients with AD. The altered gut microbiota can influence brain function and behavior through the microbiota–gut–brain axis via various pathways such as increased amyloid-β deposits and tau phosphorylation, neuroinflammation, metabolic dysfunctions, and chronic oxidative stress. With no current effective therapy to cure AD, gut microbiota modulation may be a promising therapeutic option to prevent or delay the onset of AD or counteract its progression. Our present review summarizes the alterations in the gut microbiota in patients with AD, the pathogenetic roles and mechanisms of gut microbiota in AD, and gut microbiota–targeted therapies for AD. Understanding the roles and mechanisms between gut microbiota and AD will help decipher the pathogenesis of AD from novel perspectives and shed light on novel therapeutic strategies for AD.

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Human gut microbiota Agathobaculum butyriciproducens improves cognitive impairment in LPS-induced and APP/PS1 mouse models of Alzheimer's disease

Cited by 46 publications

References 78 publications

Associations of Childhood and Perinatal Blood Metals with Children’s Gut Microbiomes in a Canadian Gestation Cohort

Associations of Childhood and Perinatal Blood Metals with Children’s Gut Microbiomes in a Canadian Gestation Cohort

Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

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