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

Wu, Shaochang; Liu, Xia; Jiang, Ruilai; Yan, Xiumei; Ling, Zongxin

doi:10.3389/fnagi.2021.650047

Cited by 91 publications

(67 citation statements)

References 221 publications

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“…Recent advances in gut microbiota studies have expanded beyond simply profiling microbiota compositions and have been increasingly characterizing microbial functions by using functional meta-omics approaches and deciphering the cross-talk between the gut microbiota and host in detail Ling et al, 2022 . With these developed omics techniques, our previous studies have found that the gut microbiota dysbiosis leading to changes in the bidirectional relationship between gut microbiota and the nervous system is linked to the pathogenesis of several neuropsychiatric diseases, such as major depressive disorder, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and so on ( Jiang et al., 2015 ; Ling et al., 2020a ; Ling et al., 2020c ; Ling et al., 2020d ; Sun et al., 2020 ; Sun et al., 2021 ; Wu et al., 2021 ). Different from previous genetic and environmental findings, the alterations of the gut microbiota provide novel insights into the pathogenesis of these neuropsychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

Fecal Dysbiosis and Immune Dysfunction in Chinese Elderly Patients With Schizophrenia: An Observational Study

Ling

Jin

Yan

et al. 2022

Front. Cell. Infect. Microbiol.

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Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3–V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial β-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium, Roseburia, Actinomyces, Butyricicoccus, Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1β were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients.

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Section: Discussionmentioning

confidence: 99%

Fecal Dysbiosis and Immune Dysfunction in Chinese Elderly Patients With Schizophrenia: An Observational Study

Ling

Jin

Yan

et al. 2022

Front. Cell. Infect. Microbiol.

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“…This improvement could also be related to the interactions between gut microbiota and mitochondrial oxidative stress, which participates in cardiac fibrosis in the context of obesity [ 23 ]. In fact, the role of microbiota dysbiosis has been reported not only in obesity but also in other pathological scenarios, including neurodegenerative diseases [ 50 , 51 , 52 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats

et al. 2021

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We have evaluated the role of mitochondrial oxidative stress and its association with endoplasmic reticulum (ER) stress activation in the progression of obesity-related cardiovascular fibrosis. MitoQ (200 µM) was orally administered for 7 weeks to male Wistar rats that were fed a high-fat diet (HFD, 35% fat) or a control diet (CT, 3.5% fat). Obese animals presented cardiovascular fibrosis accompanied by increased levels of extracellular matrix proteins and profibrotic mediators. These alterations were associated with ER stress activation characterized by enhanced levels (in heart and aorta vs. CT group, respectively) of immunoglobulin binding protein (BiP; 2.1-and 2.6-fold, respectively), protein disulfide-isomerase A6 (PDIA6; 1.9-fold) and CCAAT-enhancer-binding homologous protein (CHOP; 1.5- and 1.8-fold, respectively). MitoQ treatment was able to prevent (p < 0.05) these modifications at cardiac and aortic levels. MitoQ (5 nM) and the ER stress inhibitor, 4-phenyl butyric acid (4 µM), were able to block the prooxidant and profibrotic effects of angiotensin II (Ang II, 10−6 M) in cardiac and vascular cells. Therefore, the data show a crosstalk between mitochondrial oxidative stress and ER stress activation, which mediates the development of cardiovascular fibrosis in the context of obesity and in which Ang II can play a relevant role.

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“…Increased abundance of Gram-negative intestinal bacteria such as Bacteroides in AD patients may result in increased LPS translocation from the gut to the systemic circulation, which may contribute to AD pathology through the stimulation of systemic inflammation. Additional studies have confirmed AD-related decreases in microbiota richness and diversity and clearly evidence of different compositions in patients when compared to cognitively normal controls or MCI (reviewed in [ 91 ]). Yet, since the two pioneering clinical studies of microbiota in AD, performed in USA [ 88 ] and Italy [ 92 ] in 2017, an additional study from USA [ 93 ] and six studies from China [ 94 – 99 ] have been published.…”

Section: Cognitive Dysfunction and Microbiota In Alzheimer’s Diseasementioning

confidence: 93%

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

Bairamian

Sha

Rolhion

et al. 2022

Mol Neurodegeneration

130

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

Cited by 91 publications

References 221 publications

Fecal Dysbiosis and Immune Dysfunction in Chinese Elderly Patients With Schizophrenia: An Observational Study

Fecal Dysbiosis and Immune Dysfunction in Chinese Elderly Patients With Schizophrenia: An Observational Study

The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats

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

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