Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease

May combine two claims.

Both striatal Iba-1 and GFAP mRNA expression levels were markedly increased, while BDNF and GDNF mRNA levels were significantly reduced in the MPTP group.

“Both striatal Iba-1 (Figure 2D, T (6) = 6.405, p = 0.0007) and GFAP (Figure 2E, T (6) = 6.619, p = 0.0006) mRNA expression levels were markedly increased, while those of BDNF (Figure 2F, T (6) = 8.863, p = 0.0001) and GDNF (Figure 2G, T (6) = 6.988, p = 0.0004) were significantly reduced in the MPTP group.”

May combine two claims.

Supplementation with B. breve CCFM1067 enhanced striatal DOPA and 5-HT levels, and dramatically increased those of DA and DOPAC in mice with PD.

“Supplementation with B. breve CCFM1067 enhanced striatal DOPA (F (2,12) = 27.45, p = 0.0067) and 5-HT (F (2,12) = 15.94, p = 0.0009) levels, and dramatically increased those of DA (F (2,12) = 36.39, p < 0.0001) and DOPAC (F (2,12) = 45.03, p < 0.0001) in mice with PD (Figure 2H–K).”

May combine two claims.

B. breve CCFM1067 intervention suppresses the number of pathogenic bacteria Escherichia-Shigella and increases the number of beneficial bacteria Bifidobacterium and Akkermansia in PD mice.

“The results of fecal microbiota analysis showed that B. breve CCFM1067 intervention could act on the MPTP-induced microecological imbalance in the intestinal microbiota, suppressing the number of pathogenic bacteria (Escherichia-Shigella) while increasing the number of beneficial bacteria (Bifidobacterium and Akkermansia) in PD mice.”

• Also stated in: § 3.5. B. breve CCFM1067 Ameliorated the Dysbiosis of the Mouse Gut Microbiota of MPTP-Induced · hedged

  “Nonetheless, B. breve CCFM1067 intervention significantly restored the abundance of the above-mentioned bacterial genera, suggesting that B. breve CCFM1067 intervention could reverse MPTP-induced abnormal microbial composition in mice.”

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

Mice in the MPTP group started to lose weight on day 35 during the development of the PD model.

“Mice in the MPTP group started to lose weight on day 35, during the development of the PD model (Figure 1B).”

May combine two claims.

TH expression was reduced with L-DOPA and B. breve CCFM1067 treatment, with B. breve CCFM1067 being the most efficient.

“TH expression was reduced with L-DOPA and B. breve CCFM1067 treatment, with B. breve CCFM1067 (Figure 2B, F (2,15) = 77.15, p < 0.0001) being the most efficient (Figure 2B).”

May combine two claims.

ELISA showed that MPTP induction significantly decreased BDNF and GDNF levels, and markedly increased GFAP and Iba-1 levels in the striatum of the MPTP group compared with the control group.

“ELISA showed that MPTP induction significantly decreased the BDNF (T (6) = 9.244, p < 0.0001) and GDNF (T (6) = 8.333, p = 0.0002) levels, and markedly increased the GFAP (T (6) = 10.61, p < 0.0001) and Iba-1 (T (6) = 7.915, p = 0.0002) levels in the striatum of the MPTP group compared with that of the control group (Figure S1A–D).”

May combine two claims.

B. breve CCFM1067 markedly attenuated the mRNA expression of striatal Iba-1 and GFAP, greatly increased the mRNA expression of striatal BDNF and GDNF, and restored their normal levels.

“However, B. breve CCFM1067 markedly attenuated the mRNA expression of striatal Iba-1 (F (2,9) = 73.33, p < 0.0001) and GFAP (F (2,9) = 17.72, p = 0.0017), greatly increased the mRNA expression of striatal BDNF (F (2,9) = 143.2, p < 0.0001) and GDNF (F (2,9) = 267.2, p < 0.0001), and restored their normal levels (Figure 2D–G).”

May combine two claims.

Both L-DOPA and B. breve CCFM1067 therapies substantially reduced MPTP-induced motor impairments in the pole test, narrow-beam test, and rotarod test.

“Both L-DOPA and B. breve CCFM1067 therapies substantially reduced MPTP-induced motor impairments in the PT (Figure 1D, F (2,21) = 56.94, p < 0.0001), NBT (Figure 1E, F (2,21) = 33.72, p < 0.0001), and RTR (Figure 1F, F (2,18) = 21.99, p < 0.0001).”

May combine two claims.

B. breve CCFM1067 treatment greatly enhanced the expression of ZO-1, occludin, and claudin-1 genes in the striatum and colon compared to the MPTP group, and at even higher levels than in the control group.

“In contrast, B. breve CCFM1067 treatment greatly enhanced the expression of these genes in the striatum and colon compared to that in the MPTP group, and at even higher levels than that in the control group.”

May combine two claims.

The microbiota of PD mice exhibited a lower Observed index, and lower Shannon and Simpson index values compared to control.

“According to the α-diversity analysis, the microbiota of PD mice exhibited a lower Observed index (Figure 4C, T (10) = 5.147, p = 0.0004), which is closely linked to microbial richness, and lower Shannon and Simpson index values (Figure 4D, T (10) = 3.468, p = 0.006; Figure 4E, T (10) = 4.738, p = 0.0008), which are closely correlated with microbial diversity (vs. control).”

May combine two claims.

The phyla Patescibacteria, Proteobacteria, and Tenericutes showed a considerably increased abundance in PD mice, while the phyla Verrucomicrobia, Cyanobacteria, and Deferribacteres had a significantly decreased abundance compared to control.

“As shown in Figure 4B, the phyla Patescibacteria, Proteobacteria, and Tenericutes showed a considerably increased abundance in PD mice, while the phyla Verrucomicrobia, Cyanobacteria, and Deferribacteres had a significantly decreased abundance (vs. control).”

May combine two claims.

The gut microbial community of the MPTP group was considerably different from that of the control group, whereas that of the B. breve CCFM1067 and L-DOPA groups was similar to that of the control.

“Moreover, the β-diversity analysis indicated that the gut microbial community of the MPTP group was considerably different from that of the control group, whereas that of the B. breve CCFM1067 and L-DOPA groups was similar to that of the control (Figure 4F, PERMANOVA: F = 5.382, p = 0.001).”

May combine two claims.

ELISA analysis validated reduced expression of ZO-1, occludin, and claudin-1 in the MPTP group and increased expression in the B. breve CCFM1067 group in striatum and colon.

“Moreover, the ELISA analysis of these three proteins validated its reduced expression in the MPTP group (striatum, ZO-1, T (6) = 9.204, p < 0.0001; occludin, T (6) = 9.419, p < 0.0001; claudin-1, T (6) = 6.328, p = 0.0007; colon, ZO-1, T (6) = 4.383, p = 0.0047; occludin, T (6) = 4.755, p < 0.0001; claudin-1, T (6) = 6.913, p = 0.0005) and its increased expression in the B. breve CCFM1067 group”

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

Nine bacterial phyla dominated the gut microbiota in all four groups.

“Nine bacterial phyla dominated the gut microbiota in all four groups (Figure 4A).”

May combine two claims.

MPTP-induced mice exhibited a lower relative abundance of Akkermansia and a higher relative abundance of Bacteroides, Escherichia-Shigella, and Dubosiella compared to the control group.

“MPTP-induced mice exhibited a lower relative abundance of Akkermansia (Figure 5F, T (10) = 3.082, p = 0.0116) and a higher relative abundance of Bacteroides (Figure 5C, T (10) = 2.796, p = 0.0189), Escherichia-Shigella (Figure 5D, T (10) = 5.165, p = 0.0004), and Dubosiella (Figure 5E, T (9) = 8.641, p < 0.0001) compared to those in the control group.”

May combine two claims.

In mice with PD, IL-10 production was drastically reduced, while IL-6, IL-1β, and TNF-α expression levels were markedly elevated.

“According to our findings, the amount of IL-10 produced in mice with PD was drastically reduced, but the expression levels of IL-6, IL-1β, and TNF-α were markedly elevated (Figure 3).”

May combine two claims.

Thirteen KEGG (level 3) pathways were differentially enriched between B. breve CCFM1067 and MPTP (p < 0.05, Q value < 0.05), and B. breve CCFM1067 increased pathways involved in the biosynthesis of carotenoids, terpenoids and steroids, sesquiterpenoids and triterpenoids, steroids, and insulin resistance.

“Thirteen KEGG (level 3) pathways were differentially enriched between B. breve CCFM1067 and MPTP (p < 0.05, Q value < 0.05) (Figure 6B), and B. breve CCFM1067 increased pathways involved in the biosynthesis of carotenoids, terpenoids and steroids, sesquiterpenoids and triterpenoids, steroids, and insulin resistance (Figure 6B).”

The quote only partly states this claim.

B. breve CCFM1067 intake reversed the MPTP-induced decrease in catalase and GSH levels.

“Catalase levels were substantially decreased by MPTP treatment (Figure 3A, T (12) = 7.080, p < 0.0001; Figure 3B, T (12) = 11.55, p < 0.0001), whereas B. breve CCFM1067 intake reversed these effects (Figure 3A, F (2,18) = 18.09, p = 0.0003; Figure 3B, F (2,18) = 13.05, p = 0.0012).”

May combine two claims.

Twenty-four KEGG (level 3) pathways were differentially enriched between the control and MPTP groups (p < 0.01, Q value < 0.01), and MPTP increased the pathways involved in benzoate degradation, human papillomavirus infection, viral carcinogenesis, drug-metabolizing enzymes, butanoate metabolism, pentose phosphate, renal cell carcinoma, Cushing syndrome, carbon metabolism, and ribosome biogenesis.

“Twenty-four KEGG (level 3) pathways were differentially enriched between the control and MPTP groups (p < 0.01, with Q value < 0.01) (Figure 6A), and MPTP increased the pathways involved in benzoate degradation, human papillomavirus infection, viral carcinogenesis, drug-metabolizing enzymes, butanoate metabolism, pentose phosphate, renal cell carcinoma, Cushing syndrome, carbon metabolism, and rib”

May combine two claims.

B. breve CCFM1067 greatly increased the concentration of SCFAs (acetic acid, butyric acid, isobutyric acid, isovaleric acid) with the exception of propionic acid, the level of which was not affected by any of the treatments.

“In contrast, B. breve CCFM1067 greatly increased the concentration of SCFAs (Figure 6C: acetic acid, F (2, 21) = 87.78, p < 0.0001; butyric acid, F (2, 24) = 11.08, p = 0.0002; isobutyric acid, F (2, 24) = 26.18, p < 0.0001; isovaleric acid, F (2, 24) = 159.0, p < 0.0001) with the exception of propionic acid, the level of which was not affected by any of the treatments (Figure 6C).”

May combine two claims.

B. breve CCFM1067 treatment significantly increased IL-10 levels, which were significantly decreased by MPTP induction.

“B. breve CCFM1067 treatment also significantly increased IL-10 levels (Figure 3F, F (2,9) = 28.76, p = 0.0001), which were significantly decreased by MPTP induction.”

May combine two claims.

MPTP-induced PD animals exhibited intestinal inflammation with changes in inflammatory factor gene expression, consistent with brain tissues.

“We found that MPTP-induced PD animals exhibited intestinal inflammation with changes in inflammatory factor gene expression, consistent with the results in brain tissues (Figure 3).”

May combine two claims.

B. breve CCFM1067 improved dyskinesia, death of dopaminergic neurons, and decrease in neurotransmitters caused by MPTP in mice.

“We also showed that B. breve CCFM1067 improved the dyskinesia, death of dopaminergic neurons, and decrease in neurotransmitters caused by MPTP in mice.”

May combine two claims.

Intestinal epidermal mucosa in the colon of MPTP-induced PD animals had enhanced permeability, and B. breve CCFM1067 significantly alleviated this change.

“Our findings further demonstrate that the intestinal epidermal mucosa in the colon of MPTP-induced PD animals had an enhanced permeability, and that intervention with B. breve CCFM1067 significantly alleviated this change (Figure 3).”

May combine two claims.

Ingestion of B. breve CCFM1067 after MPTP treatment led to variations in microbial function and restored MPTP-induced alterations on multiple metabolic levels.

“In conclusion, we found that the ingestion of B. breve CCFM1067 after MPTP treatment led to variations in microbial function and restored the MPTP-induced alterations on multiple metabolic levels.”

May combine two claims.

MPTP intervention drastically changed the intestinal microbiota of PD mice, increasing Bacteroides, Escherichia-Shigella, and Dubosiella, and decreasing Akkermansia.

“According to our research, MPTP intervention drastically changed the intestinal microbiota of PD mice (Figure 5), increasing Bacteroides, Escherichia-Shigella, and Dubosiella, and decreasing Akkermansia (Figure 5), which is consistent with the findings of previous studies [47,66,67].”

• cites [47] Sun, 2018, Neuroprotective Effects of Fecal Microbiota Transplantation on MPTP-Induced Parkinson’s Disease Mice: Gut Microbiota, Glial Reaction and TLR4/TNF-α Signaling Pathway, Brain Behav. Immun. sourceNot checked yet

  Not checked in the free run.

• cites [66] Xie, 2020, Twice Subacute MPTP Administrations Induced Time-Dependent Dopaminergic Neurodegeneration and Inflammation in Midbrain and Ileum, as Well as Gut Microbiota Disorders in PD Mice, Neurotoxicology sourceNot checked yet

  Not checked in the free run.

• cites [67] Sun, 2021, Probiotic Clostridium Butyricum Ameliorated Motor Deficits in a Mouse Model of Parkinson’s Disease via Gut Microbiota-GLP-1 Pathway, Brain Behav. Immun. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Predicted metagenomic study showed MPTP-induced modifications in intestinal microbiota functions, specifically lowered "Biosynthesis of terpenoids and steroids," "Sesquiterpenoid and triterpenoid biosynthesis," "Steroid biosynthesis," and "Carotenoid biosynthesis," but these alterations were reversed by B. breve CCFM1067.

“Meanwhile, our predicted metagenomic study showed MPTP-induced modifications in intestinal microbiota functions, specifically lowered “Biosynthesis of terpenoids and steroids,” “Sesquiterpenoid and triterpenoid biosynthesis,” “Steroid biosynthesis,” and “Carotenoid biosynthesis” (Figure 6), but these alterations were reversed by B. breve CCFM1067.”

May combine two claims.

In MPTP-challenged mice, pro-inflammatory cytokine levels were increased in the striatum and colon but decreased after B. breve CCFM1067 administration.

“In the current study, pro-inflammatory cytokine levels were increased in the striatum and colon of MPTP-challenged mice but decreased after B. breve CCFM1067 administration.”

May combine two claims.

Abundance of Bifidobacterium genus increased after B. breve CCFM1067 administration, but no discernible variation in the genus after MPTP therapy.

“Interestingly, we discovered that the abundance of the Bifidobacterium genus increased after B. breve CCFM1067 administration, but there was no discernible variation in the genus after MPTP therapy.”

May combine two claims.

PD mice treated with B. breve CCFM1067 exhibited substantial alterations in gut microbial composition and a considerable increase in fecal SCFA content.

“The present results also show that PD mice treated with B. breve CCFM1067 exhibited substantial alterations in the gut microbial composition and a considerable increase in fecal SCFA content.”

May combine two claims.

Treatment with B. breve CCFM1067 restored the altered levels of these bacteria; however, MPTP-induced alteration of several taxa, most Bacteroidetes, was irreversible.

“In addition, treatment with B. breve CCFM1067 restored the altered levels of these bacteria; nevertheless, the MPTP-induced alteration of several taxa, most of which were members of the Bacteroidetes phylum, was irreversible.”

May combine two claims.

Escherichia-Shigella genus was negatively correlated with DA, 5-HT, and DOPAC levels in the striatum, and positively correlated with movement disorder-related indicators.

“In our study, the Escherichia-Shigella genus was negatively correlated with DA, 5-HT, and DOPAC levels in the striatum, and positively correlated with movement disorder-related indicators.”

May combine two claims. The quote only partly states this claim.

B. breve CCFM1067 can prevent or treat PD by modulating the gut-brain axis.

“Therefore, we herein demonstrate that a particular strain of Bifidobacterium breve CCFM1067, may ameliorate PD-related symptoms through the MGBA.”

• AssumptionRests on an assumption: Oral administration of B. breve CCFM1067 results in its colonization or functional activity in the gut sufficient to modulate the gut microbiota.

May combine two claims.

The reduction of glial activation and boosting of neurotrophins are the two mechanisms through which B. breve CCFM1067 protects the striatum.

“These findings show that the reduction of glial activation and boosting of neurotrophins are the two mechanisms through which B. breve CCFM1067 protects the striatum.”

May combine two claims.

B. breve CCFM1067 reduced the neuropathological changes and glial activation caused by MPTP and restored the normal levels of neurotransmitters in PD mice.

“Collectively, these results indicate that B. breve CCFM1067 reduced the neuropathological changes and glial activation caused by MPTP and restored the normal levels of neurotransmitters in PD mice.”

May combine two claims.

B. breve CCFM1067 has neuroprotective effects in MPTP-induced PD mice, protecting dopaminergic neurons and suppressing glial cell hyperactivation and neuroinflammation.

“Our study shows that supplementation with the probiotic B. breve CCFM1067 protected dopaminergic neurons and suppressed glial cell hyperactivation and neuroinflammation in PD mice.”

• Also stated in: § 4. Discussion · plain

  “Our results show that B. breve CCFM1067 intake exhibited neuroprotective effects, significantly alleviating motor deficits in PD mice (Figure 1D–J), protecting dopaminergic neurons in the midbrain (Figure 2A,B), and increasing the levels of striatal neurotransmitters (Figure 2H–M).”

May combine two claims.

B. breve CCFM1067 enhances antioxidant capacity and alleviates oxidative stress in the central nervous system of PD mice.

“In addition, the antioxidant capacity of the central nervous system was enhanced and oxidative stress was alleviated.”

• Also stated in: § 4. Discussion · plain

  “Ingestion of B. breve CCFM1067 also enhanced endogenous neuroprotective factors in the brains of mice (Figure 2F,G) and alleviated MPTP-induced neuroinflammation (Figure 3C–E) and oxidative stress (Figure 3A,B).”

May combine two claims.

B. breve CCFM1067 suppressed pro-inflammatory gene expression and protein expression, decreased inflammation in the brain and colon, and boosted anti-inflammatory capabilities in PD mice.

“Overall, B. breve CCFM1067 suppressed pro-inflammatory gene expression and protein expression, decreased inflammation in the brain and colon, and boosted anti-inflammatory capabilities in PD mice.”

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

DA synthesis is limited by the rate-limiting enzyme TH, and motor symptoms of PD emerge when TH levels drop below a particular threshold.

“DA synthesis is limited by the rate-limiting enzyme TH, and motor symptoms of PD emerge when TH levels drop below a particular threshold [28,29].”

• cites [28] Haavik, 1998, Tyrosine Hydroxylase and Parkinson’s Disease, Mol. Neurobiol. sourceNot checked yet

  Not checked in the free run.

• cites [29] Kawahata, I., and Fukunaga, K. (2020). Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease and Dopa-Responsive Dystonia. Int. J. Mol. Sci., 21. sourceNot checked yet

  Not checked in the free run.

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

BDNF may modulate the neuroinflammatory response through the m-BDNF-TrkB pathway, in addition to maintaining neuronal survival.

“BDNF may modulate the neuroinflammatory response through the m-BDNF-tropomyosin receptor kinase B (TrkB) pathway, in addition to its role in maintaining neuronal survival [33,34,35].”

• cites [33] Palasz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., and Niewiadomska, G. (2020). BDNF as a Promising Therapeutic Agent in Parkinson’s Disease. Int. J. Mol. Sci., 21. sourceNot checked yet

  Not checked in the free run.

• cites [34] Li, 2022, Anti-Depressive-like Behaviors of APN KO Mice Involve Trkb/BDNF Signaling Related Neuroinflammatory Changes, Mol. Psychiatry sourceNot checked yet

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• cites [35] Panagiotakopoulou, 2020, Anti-Neuroinflammatory, Protective Effects of the Synthetic Microneurotrophin BNN-20 in the Advanced Dopaminergic Neurodegeneration of “Weaver” Mice, Neuropharmacology sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Probiotics protect neurons by preventing a decline in TH in dopaminergic neurons and boosting DA expression.

“Liao et al. demonstrated that probiotics protect neurons by preventing a decline in TH in dopaminergic neurons and boosting DA expression [7].”

• cites [7] Liao, 2020, Lactobacillus Plantarum PS128 Alleviates Neurodegenerative Progression in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Mouse Models of Parkinson’s Disease, Brain Behav. Immun. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The correlation data jointly suggest the participation of the MGBA in the development of the MPTP-induced PD mouse model, as well as the protective effects of B. breve CCFM1067 therapy in this model.

“These correlation data jointly suggest the participation of the MGBA in the development of the MPTP-induced PD mouse model, as well as the protective effects of B. breve CCFM1067 therapy in this model.”

May combine two claims.

B. breve CCFM1067 protects against BBB damage and intestinal barrier dysfunction in an MPTP-induced mouse model.

“These results indicate that B. breve CCFM1067 protects against BBB damage and intestinal barrier dysfunction in an MPTP-induced mouse model.”

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

Upregulated NLRP3 expression may enhance caspase-1-mediated inflammatory cascades and stimulate production of IL-1β, IL-6, and TNF-α, leading to inflammatory response in neurological diseases.

“Upregulated NLRP3 expression may enhance caspase-1-mediated inflammatory cascades and further stimulate the production of downstream inflammatory molecules, including IL-1β, IL-6, and TNF-α, all of which lead to an inflammatory response in a variety of neurological diseases [48,49].”

• cites [48] Han, 2019, Small Molecule-Driven NLRP3 Inflammation Inhibition via Interplay between Ubiquitination and Autophagy: Implications for Parkinson Disease, Autophagy sourceNot checked yet

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• cites [49] Lahooti, 2021, Therapeutic Role of Inflammasome Inhibitors in Neurodegenerative Disorders, Brain Behav. Immun. sourceNot checked yet

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May combine two claims.

In clinical studies, probiotics lower the development of α-synuclein aggregates by lowering ROS levels, thereby improving the condition of patients with PD.

“In clinical studies, probiotics have been shown to lower the development of α-synuclein aggregates by lowering ROS levels, thereby improving the condition of patients with PD [37,39].”

• cites [37] Yan, 2013, Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease, Free Radic. Biol. Med. sourceNot checked yet

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• cites [39] Wang, 2022, Lactobacillus Plantarum DP189 Reduces α-SYN Aggravation in MPTP-Induced Parkinson’s Disease Mice via Regulating Oxidative Damage, Inflammation, and Gut Microbiota Disorder, J. Agric. Food Chem. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

B. breve CCFM1067 alleviates microbiota dysbiosis in mice with PD, highlighting the importance of microbial dysbiosis in PD progression.

“These findings suggest that B. breve CCFM1067 alleviates microbiota dysbiosis in mice with PD, highlighting the importance of microbial dysbiosis in PD progression.”

May combine two claims.

Mice with PD showed significant microbial changes, which B. breve CCFM1067 was shown to correct.

“Mice with PD showed significant microbial changes, which B. breve CCFM1067 was shown to correct.”

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

GSH depletion starts before other PD symptoms, including diminished complex I activity and development of Lewy bodies, and relates with disease severity.

“Although GSH is not the sole antioxidant involved in PD, it seems to relate with disease severity because GSH depletion starts before other PD symptoms, including diminished complex I activity in the mitochondria and the development of Lewy bodies [42,43].”

• cites [42] Peana, 2021, The Glutathione System in Parkinson’s Disease and Its Progression, Neurosci. Biobehav. Rev. sourceNot checked yet

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• cites [43] Jenner, 1996, Oxidative Stress and the Pathogenesis of Parkinson’s Disease, Neurology sourceNot checked yet

  Not checked in the free run.

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

Neurotrophic factors BDNF and GDNF protect dopaminergic neurons in PD mice by preventing neuronal death.

“Neurotrophic factors, such as BDNF and GDNF, have been shown to protect dopaminergic neurons in PD mice by preventing neuronal death [31,32].”

• cites [31] Yan, 2021, Schisandra Chinensis Protects against Dopaminergic Neuronal Oxidative Stress, Neuroinflammation and Apoptosis via the BDNF/Nrf2/NF-ΚB Pathway in 6-OHDA-Induced Parkinson’s Disease Mice, Food Funct. sourceNot checked yet

  Not checked in the free run.

• cites [32] Allen, 2013, GDNF, NGF and BDNF as Therapeutic Options for Neurodegeneration, Pharmacol. Ther. sourceNot checked yet

  Not checked in the free run.

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

Akkermansia muciniphila has a role in metabolic illnesses, including obesity and diabetes.

“It has been widely assessed that Akkermansia muciniphila, which is one of the most numerous bacteria in the gut microbiota, has a role in metabolic illnesses, including obesity [72] and diabetes [73].”

• cites [72] Plovier, 2017, A Purified Membrane Protein from Akkermansia Muciniphila or the Pasteurized Bacterium Improves Metabolism in Obese and Diabetic Mice, Nat. Med. sourceNot checked yet

  Not checked in the free run.

• cites [73] Toivonen, 2018, Akkermansia Muciniphila Induces Gut Microbiota Remodelling and Controls Islet Autoimmunity in NOD Mice, Gut sourceNot checked yet

  Not checked in the free run.

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

A. muciniphila is crucial for proper brain function and has therapeutic potential in several neuropsychiatric diseases through the gut-brain axis.

“Although its mode of action has not been completely elucidated, mounting data suggest that, through the gut–brain axis, A. muciniphila is crucial for proper brain function and has therapeutic potential in several neuropsychiatric diseases [75,76].”

• cites [75] Xu, 2022, The Role of the Probiotic Akkermansia Muciniphila in Brain Functions: Insights Underpinning Therapeutic Potential, Crit. Rev. Microbiol.Not checked yet

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• cites [76] Pascale, 2020, Targeting the Microbiota in Pharmacology of Psychiatric Disorders, Pharmacol. Res. sourceNot checked yet

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May combine two claims.

MPTP induction may increase occurrence of certain pathogenic bacteria and impair antioxidant and anti-inflammatory capabilities.

“According to previous studies, MPTP induction may increase the occurrence of certain pathogenic bacteria and significantly impair the antioxidant and anti-inflammatory capabilities of the body [7,65], corroborating our findings.”

• cites [7] Liao, 2020, Lactobacillus Plantarum PS128 Alleviates Neurodegenerative Progression in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Mouse Models of Parkinson’s Disease, Brain Behav. Immun. sourceNot checked yet

  Not checked in the free run.

• cites [65] Liu, 2022, Polymannuronic Acid Prebiotic plus Lacticaseibacillus Rhamnosus GG Probiotic as a Novel Synbiotic Promoted Their Separate Neuroprotection against Parkinson’s Disease, Food Res. Int. sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

SCFAs generated by bacterial fermentation in the colon serve as essential mediators for the gut microbiota to regulate gut-brain communication.

“According to reports, SCFAs generated by bacterial fermentation in the colon serve as essential mediators for the gut microbiota to regulate gut–brain communication [77].”

• cites [77] Scheperjans, 2015, Gut Microbiota Are Related to Parkinson’s Disease and Clinical Phenotype, Mov. Disord. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

B. breve CCFM1067 treatment may reduce inflammation and restore BBB integrity damaged by MPTP intoxication.

“This indicates that B. breve CCFM1067 treatment may reduce inflammation and restore BBB integrity damaged by MPTP intoxication.”

May combine two claims.

Treatment with B. breve CCFM1067 reduced intestinal inflammation and prevented the development of PD by improving intestinal barrier health, preventing leakage of inflammatory molecules, and reducing brain inflammation.

“However, treatment with B. breve CCFM1067 reduced intestinal inflammation and prevented the development of PD. This was accomplished by improving the health of the intestinal barrier, preventing leakage of inflammatory molecules, and reducing inflammation in the brains of mice with PD.”

May combine two claims.

SCFAs can act as neuromodulators by regulating synthesis of neurotransmitters (especially 5-HT) and expression of their receptors, thus providing neuroprotection.

“In addition, SCFAs can act as neuromodulators by regulating the synthesis of neurotransmitters (especially 5-HT) [80] as well as the expression of their receptors, thus providing neuroprotection [81].”

• cites [80] Reigstad, 2015, Gut Microbes Promote Colonic Serotonin Production through an Effect of Short-Chain Fatty Acids on Enterochromaffin Cells, FASEB J. sourceNot checked yet

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• cites [81] Wenzel, 2020, Short-Chain Fatty Acids (SCFAs) Alone or in Combination Regulate Select Immune Functions of Microglia-like Cells, Mol. Cell. Neurosci. sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Microbiota-derived SCFAs are crucial for α-synuclein-mediated neuroinflammation, glial cell hyperactivation, and motor symptoms.

“Sampson et al. showed that microbiota-derived SCFAs are crucial for α-synuclein-mediated neuroinflammation, glial cell hyperactivation, and motor symptoms [10].”

• cites [10] Sampson, 2016, Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease, Cell sourceNot checked yet

  Not checked in the free run.

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

Fisetin ameliorated the disorder by decreasing the number of Escherichia-Shigella in the intestines of PD mice.

“Chen et al. demonstrated that fisetin ameliorated the disorder by decreasing the number of Escherichia-Shigella in the intestines of PD mice [70].”

• cites [70] Chen, 2020, Fisetin Regulates Gut Microbiota and Exerts Neuroprotective Effect on Mouse Model of Parkinson’s Disease, Front. Neurosci. sourceNot checked yet

  Not checked in the free run.

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

Tight junction proteins ZO-1 and occludin contribute significantly to maintenance of the intestinal barrier.

“Tight junction proteins, such as ZO-1 and occludin, contribute significantly to the maintenance of the intestinal barrier, which aids in protecting immune cells underneath the intestinal mucosa from invading infections [54,63,64].”

• cites [54] Zhao, 2021, Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis, Microbiome sourceNot checked yet

  Not checked in the free run.

• cites [63] Dodiya, 2020, Chronic Stress-Induced Gut Dysfunction Exacerbates Parkinson’s Disease Phenotype and Pathology in a Rotenone-Induced Mouse Model of Parkinson’s Disease, Neurobiol. Dis. sourceNot checked yet

  Not checked in the free run.

• cites [64] Chelakkot, 2018, Mechanisms Regulating Intestinal Barrier Integrity and Its Pathological Implications, Exp. Mol. Med. sourceNot checked yet

  Not checked in the free run.

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

Escherichia-Shigella genus is inversely correlated with illness duration.

“The Escherichia-Shigella genus is inversely correlated with illness duration, as reported by Qian et al. [69].”

• cites [69] Qian, 2018, Alteration of the Fecal Microbiota in Chinese Patients with Parkinson’s Disease, Brain Behav. Immun. sourceNot checked yet

  Not checked in the free run.

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

Enterobacteriaceae is thought to be implicated in both PD and AD.

“Furthermore, we found that MPTP-treated mice presented elevated levels of Enterobacteriaceae (Figure 5), which is thought to be implicated in both PD and AD [68].”

• cites [68] Liu, 2019, Altered Microbiomes Distinguish Alzheimer’s Disease from Amnestic Mild Cognitive Impairment and Health in a Chinese Cohort, Brain Behav. Immun. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The possible mechanism by which B. breve CCFM1067 exerts neuroprotective effects in PD mice is through increase in neurotrophic factor and SCFA levels, and decrease in glial hyperactivation, resistance to oxidative stress injury, inflammatory response, and gut microbiota dysregulation, thus preventing dopaminergic neuron loss in the SN.

“The possible mechanism by which B. breve CCFM1067 exerts neuroprotective effects in PD mice is through the increase in neurotrophic factor and SCFA levels, and the decrease in glial hyperactivation, resistance to oxidative stress injury, inflammatory response, and gut microbiota dysregulation, thus preventing dopaminergic neuron loss in the SN.”

• AssumptionRests on an assumption: The MPTP-induced mouse model reproduces key features of human PD sufficiently to evaluate neuroprotective therapies.