A Systematic Review on the Effects of Different Types of Probiotics in Animal Alzheimer's Disease Studies

Rijke, Tanja J. de; Doting, M. H. E.; Hemert, Saskia van; Deyn, Peter Paul De; Munster, Barbara C. Van; Harmsen, Hermie J. M.; Sommer, Iris

doi:10.3389/fpsyt.2022.879491

Cited by 24 publications

(15 citation statements)

References 101 publications

(253 reference statements)

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“…Intestinal microbiota imbalance is common in AD patients ( van Olst et al, 2021 ) and has been reported in APP/PS1 transgenic mice and 5✕FAD transgenic mice ( Zhang et al, 2017 ; Liu et al, 2021 ). Studies have shown that restoring the intestinal microbiota is effective in improving AD ( de Rijke et al, 2022 ; Snigdha et al, 2022 ). Therefore, the mechanism of improving AD by modulating insulin signaling in the brain may be related to restoring the intestinal microbiota.…”

Section: Discussionmentioning

confidence: 99%

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Liu²,

Sun³

et al. 2023

Front. Pharmacol.

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Radix Rehmanniae Praeparata (RRP, Shu Dihuang in Cinese) is widely used as primal medicine in Chinese herbal formula for the treatment of Alzheimer’s disease (AD). However, the underlying mechanism of RRP for AD remains unclear. The aim of this study was to investigate the therapeutic effect of RRP on intracerebroventricular injection of streptozotocin (ICV-STZ)-induced AD model mice and its potential mechanism. ICV-STZ mice were continuously gavaged with RRP for 21 days. The pharmacological effects of RRP were evaluated by behavioral tests, brain tissue H&E staining and hippocampal tau protein phosphorylation levels. The expression levels of insulin receptor (INSR), IRS-1, pSer473-AKT/AKT and pSer9-GSK-3β/GSK-3β proteins in hippocampal and cortical tissues were detected by Western-blot method. The 16S rRNA gene sequencing was used to analyze the changes of intestinal microbiota in mice. The compounds in RRP were analyzed by mass spectrometry and their binding ability to INSR proteins was detected by molecular docking. The results showed that RRP ameliorated cognitive dysfunction and neuronal pathological changes of brain tissue in ICV-STZ mice, reduced tau protein hyperphosphorylation, INSR, IRS-1, pSer473-AKT/AKT, and pSer9-GSK-3β/GSK-3β levels in hippocampal and cortical tissues. Meanwhile, RRP reversed ICV-STZ-induced dysregulation of intestinal microbiota in AD mice. Mass spectrometry analysis showed that the RRP consisted mainly of seven compounds, namely Acteoside (Verbascoside), 5-Hydroxymethyl-2-furaldehyde (5-HMF), Apigenin7-O-glucuronide, Icariin, Gallic acid, Quercetin-3β-D-glucoside, and Geniposide. Molecular docking results further indicated that the compounds in RRP have binding ability to INSR protein and potential multiple synergistic effects. RRP ameliorates cognitive dysfunction and brain histopathological changes in AD mice. The mechanism of RRP ameliorating AD may be related to the regulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota. This study supports the potential anti-AD efficacy of RRP and initially reveals the pharmacological mechanism of RRP, providing a theoretical basis for further clinical application of RRP.

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Section: Discussionmentioning

confidence: 99%

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Liu²,

Sun³

et al. 2023

Front. Pharmacol.

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“…Given that AD pathology and neuropsychiatric disorders are associated with dysbiosis in gut microbiota, treatments with different compositions of probiotics have been explored in therapeutic trials. There are several systematic reviews of these interventions in human patients [49,50] as well as in experiments with AD mice [51]. Briefly, it has been commonly observed that probiotic treatments are able to improve cognitive functions in both MCI and AD patients.…”

Section: Microbiota Gut-brain Axis In Ad Pathogenesismentioning

confidence: 99%

Activation of aryl hydrocarbon receptor (AhR) in Alzheimer’s disease: role of tryptophan metabolites generated by gut host-microbiota

Salminen

2023

J Mol Med

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Gut microbiota in interaction with intestinal host tissues influences many brain functions and microbial dysbiosis has been linked with brain disorders, such as neuropsychiatric conditions and Alzheimer’s disease (AD). l-tryptophan metabolites and short-chained fatty acids (SCFA) are major messengers in the microbiota-brain axis. Aryl hydrocarbon receptors (AhR) are main targets of tryptophan metabolites in brain microvessels which possess an enriched expression of AhR protein. The Ah receptor is an evolutionarily conserved, ligand-activated transcription factor which is not only a sensor of xenobiotic toxins but also a pleiotropic regulator of both developmental processes and age-related tissue degeneration. Major microbiota-produced tryptophan metabolites involve indole derivatives, e.g., indole 3-pyruvic acid, indole 3-acetaldehyde, and indoxyl sulfate, whereas indoleamine and tryptophan 2,3-dioxygenases (IDO/TDO) of intestine host cells activate the kynurenine (KYN) pathway generating KYN metabolites, many of which are activators of AhR signaling. Chronic kidney disease (CKD) increases the serum level of indoxyl sulfate which promotes AD pathogenesis, e.g., it disrupts integrity of blood–brain barrier (BBB) and impairs cognitive functions. Activation of AhR signaling disturbs vascular homeostasis in brain; (i) it controls blood flow via the renin-angiotensin system, (ii) it inactivates endothelial nitric oxide synthase (eNOS), thus impairing NO production and vasodilatation, and (iii) it induces oxidative stress, stimulates inflammation, promotes cellular senescence, and enhances calcification of vascular walls. All these alterations are evident in cerebral amyloid angiopathy (CAA) in AD pathology. Moreover, AhR signaling can disturb circadian regulation and probably affect glymphatic flow. It seems plausible that dysbiosis of gut microbiota impairs the integrity of BBB via the activation of AhR signaling and thus aggravates AD pathology. Key messages Dysbiosis of gut microbiota is associated with dementia and Alzheimer’s disease. Tryptophan metabolites are major messengers from the gut host-microbiota to brain. Tryptophan metabolites activate aryl hydrocarbon receptor (AhR) signaling in brain. The expression of AhR protein is enriched in brain microvessels and blood-brain barrier. Tryptophan metabolites disturb brain vascular integrity via AhR signaling. Dysbiosis of gut microbiota promotes inflammation and AD pathology via AhR signaling.

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“…A study summarized the evidence of the relationship between the intestinal microflora, cognitive function, and dementia pathology in the elderly, and its conclusion supported the impact of intestinal microorganisms on cognitive function. In animal studies, prebiotics and probiotics had a positive effect on cognitive function ( Neta et al., 2022 ; de Rijke et al., 2022 ), but the existing evidence is insufficient to support a clinical application ( Ticinesi et al., 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Probiotics for constipation in Parkinson’s: A systematic review and meta-analysis of randomized controlled trials

Yin

Zhu

2022

Front. Cell. Infect. Microbiol.

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BackgroundParkinson’s disease (PD)-related constipation may affects both disease occurrence and disease progression. Probiotics, as a potential therapeutic intervention, have attracted the attention of researchers, but the evidence of their efficacy and safety has not been systematically reviewed.AimA systematic review and meta-analysis of randomized controlled trials of probiotics in the treatment of PD constipation was conducted to determine the efficacy and safety of probiotics in the treatment of PD constipation.MethodsFour databases (The Cochrane Central Register of Controlled Trials, Embase, PubMed, and Web of Science) were searched from their establishment to June 1, 2022. We included randomized controlled trials of probiotics for the treatment of constipation in patients with PD, with probiotics in the experimental group and a placebo, another treatment, or no treatment in the control group. The primary outcome was the number of bowel movements per week. Secondary outcomes included nonmotor symptoms (NMS), gut transit time (GTT), abdominal pain, abdominal distention, constipation, and quality of life scores. Stata15.1 was used to generate a summary of the data and perform a descriptive analysis if necessary. The GRADE tool was used to assess the quality of the evidence and the Cochrane guidelines to assess the risk of bias for each study.ResultsFinally, four qualified RCTs were included, comprising 287 participants. Compared with the control group, probiotics could effectively increase the frequency of defecation per week in PD patients (WMD = 1.02. 95%CI: 0.56–1.48, and P < 0.00001), but the heterogeneity was high, and the quality of the evidence was low. There was no significant difference in average stool consistency between patients with PD treated with probiotics and those given a placebo in (WMD = –0.08. 95%CI: –1.42–1.26, and P = 0.908). In addition, the results suggested that probiotics have no obvious effect on additional indicators of gastrointestinal dysfunction, such as GTT, abdominal pain, and abdominal distension, and there is insufficient evidence on their ability to improve NMS and Parkinson’s disease Questionnaire 39 summary indices (PDQ39-SI). Safety issues should be carefully explained.ConclusionThere is insufficient evidence supporting the use of probiotics to treat constipation in patients with PD. Taking all the results together, probiotics have potential value in the treatment of PD-related constipation.Systematic Review RegistrationPROSPERO CRD42022331325.

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A Systematic Review on the Effects of Different Types of Probiotics in Animal Alzheimer's Disease Studies

Cited by 24 publications

References 101 publications

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Activation of aryl hydrocarbon receptor (AhR) in Alzheimer’s disease: role of tryptophan metabolites generated by gut host-microbiota

Probiotics for constipation in Parkinson’s: A systematic review and meta-analysis of randomized controlled trials

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