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Cited by 70Probiotics and Fermented FoodsAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease

Open access
Fang, Xin, Zhou, Xiaoting, Miao, Yuqing, Han, Yiwen, Wei, Jing, Chen, Tingtao·2020·AMB Express
DOI 10.1186/s13568-020-01014-6PMC PMC7182653
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Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative diseases (NDD) characterized by progressive degeneration of the central nervous system, and few medications are available to halt the progression of AD and PD. In the present study, an engineered strain MG136-pMG36e-GLP-1 was used to evaluate its neuroprotective effect on AD and PD mice, via the probiotics effects of Lactococcus lactis MG1363 and the constantly produced Glucagon-like peptide-1 (GLP-1) by the engineered strain. Our results indicated that oral administration of MG136-pMG36e-GLP-1 significantly reduced lipopolysaccharide (LPS)-induced memory impairment and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunction through the toll-like receptor4 (TLR4)/nuclear factor-kappa B (NFκB) and protein kinase B (AKT)/Glycogen synthase kinase-3β (GSK3β) signaling pathway. High-throughput sequencing results showed that MG1363-pMG36e-GLP-1 reduced the abundance of the pathogens Enterococcus, Proteus, and increased the abundance of the probiotics Akkermansia muciniphila. These results suggest that the engineered strain may be a new intervention for treating AD and PD by reducing the occurrence of neuroinflammation.

AI snapshot

Written from the paper’s full text.

TL;DR

Oral administration of the engineered strain MG1363-pMG36e-GLP-1 improved memory impairment in LPS-induced AD mice and motor dysfunction in MPTP-induced PD mice. The effects were associated with reduced neuroinflammation via TLR4/NF-κB and AKT/GSK3β signaling and with changes in gut microbiota.

Key findings

  • In AD mice, MG1363-pMG36e-GLP-1 reduced Barnes maze escape latency on the last day to 17.13 s versus 31.25 s in the AD group (p < 0.05).
  • In PD mice, pole descent time was 13.35 s in MPTP mice versus 7.67 s in controls, and improved to 10.11 s with treatment (p < 0.001); open-field measures also improved (p < 0.001).
  • LPS/MPTP increased TLR4, p-IκBα, and p-p65 and decreased p-AKT, p-GSK3β, and β-catenin in brain tissue; treatment reversed these trends (p < 0.05). Treatment also reduced Aβ deposition in AD mice and partially rescued TH-positive dopaminergic neurons in PD mice (p < 0.05).
  • MG1363-pMG36e-GLP-1 reduced pathogens such as Enterococcus and Proteus in PD mice and Fusobacterium in AD mice, and the abstract reports increased abundance of Akkermansia muciniphila.

Methods

  • Male C57BL/6 mice (25–30 g) were divided into five groups: control, LPS-induced AD, AD pretreated with MG1363-pMG36e-GLP-1, MPTP-induced PD, and PD pretreated with MG1363-pMG36e-GLP-1. LPS was given intraperitoneally at 0.25 mg/kg/day for 7 days; MPTP at 20 mg/kg/day for 7 days; the strain was given in drinking water at 10^9 CFU daily for 7 days before injection and for another 2 weeks.
  • Behavioral tests included Barnes maze, pole test, and open-field test. Brain tissues were analyzed by immunohistochemistry and immunofluorescence for inflammatory, apoptotic, Aβ, and TH markers.
  • Fecal microbiota was analyzed by high-throughput 16S rDNA V4 region sequencing; statistical analysis used one-way ANOVA with Tukey’s multiple comparison tests, with p < 0.05 considered significant.

Limitations

  • The authors state that a control group treated with Lactococcus lactis MG1363 alone would provide more convincing evidence for the engineered strain’s effects.
  • Evident from the text: group sizes were small and uneven in the reported analyses (n = 5 for AD and AD-G; n = 8 for C, PD, and PD-G), and Shannon diversity differences were not statistically significant.
  • Evident from the text: some microbiota effects were limited to specific taxa, and the study does not establish whether microbiota changes are causal for the behavioral or neuropathological improvements.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s13568-020-01014-6

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Oral administration of MG1363-pMG36e-GLP-1 significantly reduced LPS-induced memory impairment in AD mice.

    “Our results indicated that oral administration of MG136-pMG36e-GLP-1 significantly reduced lipopolysaccharide (LPS)-induced memory impairment and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunction through the toll-like receptor4 (TLR4)/nuclear factor-kappa B (NFκB) and protein kinase B (AKT)/Glycogen synthase kinase-3β (GSK3β) signaling pathway.”
    • Also stated in: § MG1363-pMG36e-GLP-1 improved cognitive ability in AD mice and motor function in PD mice · plain
      “However, taking of MG1363-pMG36e-GLP-1 had greatly reduced the escape latency (p < 0.05; Fig. 1b).”
    • Also stated in: § MG1363-pMG36e-GLP-1 improved cognitive ability in AD mice and motor function in PD mice · plain
      “On the last day, the latency time of AD-G group was shorter than that in AD group (17.13 s vs 31.25 s) (p < 0.05; Fig. 1c).”
    Quote in the paperSubstantial claim
  • Findingown data

    Intraperitoneal injection of LPS or MPTP increased the positive cells for TLR4, p-IκBα and p-p65 in brain tissue compared to the C group.

    “As shown in Figs. 2 and 3, intraperitoneal injection of LPS or MPTP had obviously increased the positive cells for TLR4, p-IκBαand p-p65, while decreased the nmbers of positive cells for p-AKT, p-GSK3βand β-catenin in brain tissue contrast to the C group, while treatment with MG1363-pMG36e-GLP-1 had reversed this trend (Figs. 2a–d and 3a–d) (p < 0.05).”
    Quote in the paperSubstantial claim
  • Findingnone given

    Injection of LPS and MPTP causes imbalance of intestinal microbiota in AD and PD mice.

    “Injection of LPS and MPTP can cause the imbalance of intestinal microbiota in AD and PD mice, therefore high-throughput sequencing was used to evaluate the effect of MG1363-pMG36e-GLP-1 on balance of intestinal microbiota.”
    Quote in the paperSubstantial claim
  • Findingown data

    MG1363-pMG36e-GLP-1 reduced the abundance of the pathogens Enterococcus and Proteus.

    “High-throughput sequencing results showed that MG1363-pMG36e-GLP-1 reduced the abundance of the pathogens Enterococcus, Proteus, and increased the abundance of the probiotics Akkermansia muciniphila.”
    Quote in the paperSubstantial claim
  • Findingown data

    Compared with the C group, mice in AD group exhibited cognitive impairment which notably prolonged the time for mice to find the platform.

    “Compared with the C group, mice in AD group exhibited cognitive impairment which notably prolonged the time for mice to find the platform (p < 0.05).”
    Quote in the paperSubstantial claim
  • May combine two claims. 31
  • Classified as probably not a substantial claim. 19

  • May combine two claims.

    Findingown data

    PD mice had reduced average movement speed, distance in the central area, and duration of movement in the central area versus the control group.

    “In the open field assessment, PD mice had reduced the average movement speed (1.16 s vs. 4.5 s), the distance in the central area (95.73 cm vs. 343.1 cm) and the duration of movement in the central area (4.67 s vs. 17.1 s) versus the control group (p < 0.001; Fig. 1e–g)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Shannon index of gut microbiota was higher in control (8.334) and AD-G (7.836) groups than in AD group (7.798), but the difference was not significant.

    “The shannon index was used to reflect the diversity of microbial communities, which was higher in C group (8.334) and AD-G (7.836) group, compared with AD group (7.798), and the engineered strain could increase the diversity of intestinal microbial in PD group (8.434 vs. 8.569), too (Fig. 4a), but no significant difference was shown.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MG1363-pMG36e-GLP-1 increased the Shannon index in PD group (8.434 vs. 8.569), but the difference was not significant.

    “the engineered strain could increase the diversity of intestinal microbial in PD group (8.434 vs. 8.569), too (Fig. 4a), but no significant difference was shown.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Immunohistochemistry results indicated that toxin injection greatly promoted the expressions of TLR4, p-IκBα and p-p65 in brain of AD and PD mice, and decreased the expression of p-AKT, p-GSK3β and β-catenin.

    “The immunohistochemistry results indicated that toxin injection greatly promoted the expressions of TLR4, p-IκBαand p-p65 in brain of AD and PD mice, and decreased the expression of p-AKT, p-GSK3βand β-catenin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Injection of LPS and MPTP significantly affected the behavioral ability of mice, and oral administration of MG1363-pMG36e-GLP-1 significantly improved the behavior of mice.

    “Similarly, our results indicated that the injection of LPS and MPTP significantly affected the behavioral ability of mice, and the oral administration of MG1363-pMG36e-GLP-1 significantly improved the behavior of mice.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    GLP-1 drugs have been used in AD and PD patients in clinical trials and have shown efficacy.

    “Currently, GLP-1 drugs have been used in AD and PD patients in clinical trials and have shown efficacy (Aviles-Olmos et al. 2013; Gejl et al. 2016).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Aviles-Olmos et al. 2013 source

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    • cites Gejl et al. 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Probiotics are active microorganisms that can colonize the body, remove or reduce the adhesion of pathogenic bacteria and regulate the body's immunity, thereby protecting the host.

    “Probiotics are a kind of active microorganisms that can colonize the body, remove or reduce the adhesion of pathogenic bacteria and regulate the body’s immunity, thereby protecting the host (Liu et al. 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Liu et al. 2015 source

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  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    MG1363-pMG36e-GLP-1 can be developed as oral GLP-1 drugs with few side effects, low cost, and no need for repeated injections.

    “MG1363-pMG36e-GLP-1 can be developed as oral GLP-1 drugs with few side effects, low cost, and no need for repeated injections.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the faecal samples of PD patients, the abundance of Escherichia-Shigella, Proteus, and Enterococcus is increased, and the abundance of Blautia and Ruminococcus is decreased.

    “Similarly, the abundance of Escherichia-Shigella, Proteus, and Enterococcus was increased, and the abundance of Blautia and Ruminococcus was decreased in the faecal samples of PD patients (Sampson et al. 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sampson et al. 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    GLP-1 is an enterogenous hormone that promotes insulin secretion and reduces glucagon secretion to reduce blood glucose in a glucose concentration-dependent manner.

    “GLP-1 is an enterogenous hormone that promotes insulin secretion and reduces glucagon secretion to reduce blood glucose in a glucose concentration-dependent manner (Athauda and Foltynie 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Athauda and Foltynie 2016 source

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  • May combine two claims.

    Premisecitation

    Diabetes drugs such as GLP-1 are used to treat AD and PD, and have shown good efficacy.

    “Therefore, diabetes drugs such as GLP-1 are used to treat AD and PD, and have shown good efficacy (Aviles-Olmos et al. 2013; Gejl et al. 2016).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Aviles-Olmos et al. 2013 source

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    • cites Gejl et al. 2016 source

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  • May combine two claims.

    Premisecitation

    Toxins in the brain can specifically recognize and combine with TLR4, activate microglia and eventually lead to neuroinflammation.

    “Toxins in the brain can specifically recognize and combine with TLR4, activate the microglia and eventually lead to neuroinflammation (Jia et al. 2017).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jia et al. 2017 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    GLP-1 is an endogenous hormone secreted by ileal endocrine cells, which promotes insulin secretion in a hyperglycemic environment.

    “Glucagon-like peptide-1 (GLP-1) is an endogenous hormone secreted by ileal endocrine cells, which promotes insulin secretion in a hyperglycemic environment (Athauda and Foltynie 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Athauda and Foltynie 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Probiotics in milk could improve cognitive function in healthy elderly people.

    “Researches indicated that probiotics containing in milk could improve cognitive function in healthy elderly people (Chung et al. 2014)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chung et al. 2014 source

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  • May combine two claims.

    Premisecitation

    Intestinal flora of NDD patients is characterized by excessive growth of pathogenic bacteria, which increases the release of LPS, and activates microglia to cause neuroinflammation.

    “The intestinal flora of NDD patients is characterized by excessive growth of pathogenic bacteria, which increases the release of LPS, and activates microglia to cause neuroinflammation (Spielman et al. 2018).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Spielman et al. 2018 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    TLR4 is a unique pattern recognition receptor, and TLR4 in the brain is mainly expressed in microglia.

    “As we know, toll-like receptor 4 (TLR4) is a unique pattern recognition receptor (PRR), and TLR4 in the brain is mainly expressed in microglia (Seija Lehnardt et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Seija Lehnardt et al. 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An engineered strain MG1363-pMG36e-GLP-1 was constructed that continuously expresses GLP-1 and overcomes the short half-life of GLP-1.

    “An engineered strain MG1363-pMG36e-GLP-1 is constructed which continuously express GLP-1, and overcome the problem of the short half-life of GLP-1.”
    • Also stated in: § Introduction · hedged
      “In our previous work, an engineered Lactococcus lactis strain MG1363-pMG36e-GLP-1 was constructed, which could continuously express GLP-1.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Chen et al. 2018 source

      Not checked in the free run.

    • cites Fang et al. 2019 source

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    • Rests on an assumption: GLP-1 is recognized and degraded by DPP-IV, and its plasma half-life is less than 2 min.

  • May combine two claims.

    Premisecitation

    GLP-1 is easily degraded, requiring continuous intravenous drip or continuous subcutaneous injection to produce therapeutic effects, which limits its clinical usage.

    “However, as GLP-1 is easily degraded, continuous intravenous drip or continuous subcutaneous injection is required to produce therapeutic effects, which limits its clinical usage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Athauda and Foltynie 2016 source

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  • May combine two claims.

    Premisecitation

    In the stools of patients with AD, the abundance of pro-inflammatory bacteria (Escherichia/Shigella) increases and the abundance of anti-inflammatory bacteria (Eubacterium rectale) and Bacteroides fragilis decreases.

    “In the stools of patients with AD, the abundance of pro-inflammatory bacteria (Escherichia/Shigella) increases and the abundance of anti-inflammatory bacteria (Eubacterium rectale) and Bacteroides fragilis decreases (Mancuso and Santangelo 2018).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mancuso and Santangelo 2018 source

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  • May combine two claims.

    Premisecitation

    GV-971 treats AD by targeting intestinal microbiota, opening new avenues for AD treatment by remodeling intestinal microorganisms.

    “More importantly, GV-971 treats AD by targeting to intestinal microbiota, which opens up new avenues for AD treatment by remodeling intestinal microorganisms (Wang et al. 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang et al. 2019 source

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  • May combine two claims.

    Premisecitation

    TLR4 expression is significantly elevated in brain tissue of AD and PD patients and mice, and the aggregation of α-syn and Aβ is related to the activation of TLR4.

    “Studies also indicate that TLR4 expression is significantly elevated in brain tissue of AD and PD patients and mice, and the aggregation of α-syn and Aβ is related to the activation of TLR4 (Seija Lehnardt et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Seija Lehnardt et al. 2003 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Probiotics capsule (L. acidophilus, L. casei, B. bifidum and L. fermentum) could improve mental health and metabolic status in patients with multiple sclerosis.

    “probiotics capsule (L. acidophilus, L. casei, B. bifidum and L. fermentum) could improve mental health and metabolic status in patients with multiple sclerosis (MS) (Kouchaki et al. 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kouchaki et al. 2017 source

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    Premisecitation

    GLP-1 has a neuroprotective effect in the CNS, affecting proliferation and apoptosis of neural cells, improving learning, memory and motor dysfunction, reducing Aβ plaque deposition, decreasing loss of dopaminergic neurons, and promoting nerve regeneration.

    “There are studies indicate that GLP-1 has a neuroprotective effect in the central nervous system (CNS), which affects the proliferation and apoptosis of neural cells, improves learning, memory and motor dysfunction, reduces the deposition of Aβ plaques in the brain, decreases the loss of dopaminergic neurons and promotes nerve regeneration (Kim et al. 2017).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kim et al. 2017 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Probiotics could improve cognitive, sensory and emotional function in AD patients.

    “and could improve cognitive, sensory and emotional function in AD patients (Akbari et al. 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Akbari et al. 2016 source

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  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All mice were divided into 5 groups randomly.

    “All mice were divided into 5 groups randomly (n = 12 per group).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    PCoA indicated that microbial diversity changed after LPS injection in AD group, and a new microbial balance was formed by treatment with MG1363-pMG36e-GLP-1.

    “The principal co-ordinates analysis (PCoA) indicated that the microbial diversity changed after the injection of LPS in AD group, while a new microbial balance was formed by the treatment of MG1363-pMG36e-GLP-1 when treated with engineered bacteria (Fig. 4c).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Probiotics mixture (L. acidophilus, L. casei, and Bifidobacterium bifidum) reduced the overall score of the Baker Depression Scale in patients with major depression.

    “probiotics mixture (L. acidophilus, L. casei, and Bifidobacterium bifidum) reduced the overall score of the Baker Depression Scale in patients with major depression (Akkasheh et al. 2016)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Akkasheh et al. 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Only a few drugs are available for AD and PD, and they can only relieve symptoms but fail to halt the progression of the diseases.

    “With the advent of an aging population, more and more people are suffering from AD and PD, but only a few drugs are available for the two diseases mentioned above, and they can only relieve symptoms but fail to halt the progression of the diseases (Du et al. 2018; Grimes et al. 2019).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Du et al. 2018

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    • cites Grimes et al. 2019 source

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    Premisecitation

    The neuroprotective effect of GLP-1 is effective in AD and PD, and also in other NDD such as HD, ALS, and MS.

    “The neuroprotective effect of GLP-1 is not only effective in AD and PD, but also in other NDD such as HD (Duarte et al. 2018), ALS (Li et al. 2012), and MS (DellaValle et al. 2016).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Duarte et al. 2018 source

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    • cites Li et al. 2012

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    • cites DellaValle et al. 2016 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    L. casei strain significantly reduced anxiety symptoms in patients with chronic fatigue syndrome.

    “Furthermore, L. casei strain significantly reduced anxiety symptoms in patients with chronic fatigue syndrome (Rao et al. 2009)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rao et al. 2009 source

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  • May combine two claims.

    Premisecitation

    The deposition of Aβ and α-syn activates microglia in the brain and triggers neuroinflammation, which leads to memory and cognitive impairment in AD patients and motor and non-motor symptoms in PD patients.

    “The deposition of Aβ and α-syn activates microglia in the brain and triggers neuroinflammation, which leads to memory and cognitive impairment in AD patients and motor and non-motor symptoms in PD patients (Rogers et al. 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rogers et al. 2007 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mice injected with Nocardia astroides can cause Parkinson's like symptoms and respond to dopamine therapy, and N. astroides strain GUH-2 can cause apoptosis of dopamine neurons.

    “Mice injected with Nocardia astroides (N. astroides, a human pathogen of the phylum Actinobacteria) can cause Parkinson’s like symptoms and respond to dopamine therapy, and N. astroides strain GUH-2 can cause apoptosis of dopamine neurons (Tam et al. 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tam et al. 2002 source

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    Premisecitation

    Proteus mirabilis can cause motor dyskinesia, produce neuroinflammation and cause dopaminergic neuronal damage by producing LPS.

    “Proteus mirabilis can cause motor dyskinesia, produce neuroinflammation and cause dopaminergic neuronal damage by producing LPS (Choi et al. 2018).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Choi et al. 2018 source

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  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    This study provides a strong basis for the engineering strain MG1363-pMG36e-GLP-1 in future clinical treatment of NDD.

    “This study provides a strong basis for the engineering strain MG1363-pMG36e-GLP-1 in the future clinical treatment of NDD.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The gut microbiota changes observed in mice are relevant to human AD and PD.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lower expression of AKT in dopaminergic neurons of PD patients than in normal people.

    “Previous results indicated that a lower expression of AKT in dopaminergic neurons of PD patients than that in normal people (Malagelada et al. 2008)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Malagelada et al. 2008 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increase in Fusobacterium nucleatum promotes the production of inflammatory factors IL-8, IL-1β and TNF-α, ultimately leading to intestinal epithelial inflammation.

    “As we know, an increase in Fusobacterium nucleatum (F. nucleatum) promotes the production of the inflammatory factors IL-8, IL-1β and TNF-α, ultimately leads to intestinal epithelial inflammation (Jia et al. 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jia et al. 2017 source

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  • May combine two claims.

    Interpretationown data

    MG1363-pMG36e-GLP-1 attenuates neuroinflammation via down-regulating the TLR4/NF-κB pathway, up-regulates the AKT/GSK3β signaling pathway, and restores the disturbed microbiota to normal level, thereby reducing spatial learning and memory disorders of AD mice and the ability of movement and exploration of PD mice.

    “Based on the data presented herein, we conclude that MG1363-pMG36e-GLP-1 attenuates neuroinflammation via down-regulating TLR4/NF-κB pathway, up-regulated the AKT/GSK3β signaling pathway, and restore the disturbed microbiota to normal level, so as to reduce the spatial learning and memory disorders of AD mice and the ability of movement and exploration of PD mice.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The LPS-induced AD model and MPTP-induced PD model are valid models of human AD and PD.
    • Rests on an assumption: The gut microbiota changes observed in mice are relevant to human AD and PD.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A. muciniphila can produce secretory IgA and antibacterial peptides by immunological rejection to resist pathogen damage to the intestines, and has anti-inflammatory, barrier-improving properties; it can also regulate intestinal microbial balance, and improve the situation of PD, aging, pediatric autism, MS and ALS.

    “For probiotics strains, A. muciniphila can produce secretory immunoglobulin A (IgA) and antibacterial peptides by immunological rejection to resist pathogen damage to the intestines, and has anti-inflammatory, barrier-improving properties. It can also regulate intestinal microbial balance, and improve the situation of PD, aging, pediatric autism, MS and ALS (Derrien et al. 2017; Hidalgo-Cantabrana”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Derrien et al. 2017 source

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    • cites Hidalgo-Cantabrana et al. 2017 source

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    P-AKT is a major anti-apoptotic kinase, so AKT/GSK3β signaling abnormalities are associated with many neurological diseases.

    “P-AKT is a major anti-apoptotic kinase, so AKT/GSK3β signaling abnormalities are associated with many neurological diseases (Morissette et al. 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Morissette et al. 2010 source

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    Premisecitation

    AKT can promote neuronal survival by mediating multiple neurotrophic factors.

    “as AKT can promote neuronal survival by mediating multiple neurotrophic factors (Morissette et al. 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Morissette et al. 2010 source

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40 of 40

  • The authors state this as an assumption.

    The reason why MG1363-pMG36e-GLP-1 has a sound effect both on AD and PD has not been fully elucidated.

    “However, why it has a sound effect both on AD and PD has not been fully elucidated.”

  • The paper relies on this without support.

    LPS and MPTP enhance the release of proinflammatory cytokines, which can contribute to neuroinflammation and lead to the apoptosis of brain cells.

    “LPS and MPTP could enhance the release of proinflammatory cytokines, which can contribute to neuroinflammation and lead to the apoptosis of brain cells.”

  • The paper relies on this without support.

    GLP-1 is recognized and degraded by DPP-IV, and its plasma half-life is less than 2 min.

    “However, when GLP-1 enters the body, it is recognized and degraded by dipeptidyl peptidase IV (DPP-IV), and its plasma half-life is less than 2 min.”

  • The paper relies on this without support.

    Intestinal flora imbalance occurs in the early stages of neurodegenerative diseases.

    “It is well known that intestinal flora imbalance occurs in the early stages of neurodegenerative diseases.”

  • The paper relies on this without support.

    The LPS-induced AD model and MPTP-induced PD model are valid models of human AD and PD.

    “the LPS-induced AD model and MPTP-induced PD model were developed to evaluate the treatment effect of MG1363-pMG36e-GLP-1 on AD and PD.”

  • The paper relies on this without support.

    The gut microbiota changes observed in mice are relevant to human AD and PD.

    “This study provides a strong basis for the engineering strain MG1363-pMG36e-GLP-1 in the future clinical treatment of NDD.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • An engineered GLP-1-producing probiotic strain, Lactococcus lactis MG1363-pMG36e-GLP-1, counteracts MPTP-induced neurodegeneration by inhibiting glial activation, oxidative stress, and ferroptosis.

    “An engineered GLP-1-producing probiotic strain, Lactococcus lactis MG1363-pMG36e-GLP-1, counteracts MPTP-induced neurodegeneration by inhibiting glial activation, oxidative stress, and ferroptosis.”

    From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [619]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • AD figure caption reverses the reported AKT-pathway effect

    Major

    The results say LPS decreased p-AKT, p-GSK3β and β-catenin and that treatment reversed this trend. The Fig. 2 caption instead says treatment decreased their expression.

  • PD figure caption reverses the reported AKT-pathway effect

    Major

    The results say MPTP decreased p-AKT, p-GSK3β and β-catenin and that treatment reversed this trend. The Fig. 3 caption instead says treatment decreased their expression.

2 of 2

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Fang, X., Zhou, X., Miao, Y., Han, Y., Wei, J., & Chen, T.
Affiliations
  • First Affiliated Hospital of Nanchang University (CN)
  • Nanchang University (CN)
Corresponding author
Chen, Tingtao
ORCID
Venue
AMB Express
Publisher
Springer Science and Business Media LLC
Published
2020-04-24
Volume
10
Issue
1
Pages
80-80
ISSN
2191-0855 (ISSN-L)
DOI
10.1186/s13568-020-01014-6
PMC
PMC7182653
OpenAlex
W3018058123
Semantic Scholar
88097eaf9616448927e70c0947ec115e18bb1015
Cited by
70
References
39
Citations by year
2026: 5 · 2025: 9 · 2024: 15 · 2023: 12 · 2022: 20 · 2021: 9
FWCI
6.64
Type
journal article
Language
en
Open access
Licence
Locations
  • AMB Express (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (81660203)
  • Excellent Youth Foundation of Jiangxi Scientific Committee (20171BCB23028)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, Parkinson's disease, glucagon-like peptide-1, Lactococcus lactis, neuroprotection, neuroinflammation, TLR4/NF-κB signaling, Akt/GSK-3β signaling, memory impairment, Akkermansia muciniphila, gut microbiota, oral administration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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