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Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice
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ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis , Lactobacillus casei , Bifidobacterium bifidum , and Lactobacillus acidophilus . This study aims to investigate the effects of ProBiotic-4 on the microbiota–gut–brain axis and cognitive deficits , and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits , cerebral neuronal and synaptic injuries , glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood–brain barrier, decreased interleukin-6 and tumor necrosis factor- α at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor- κ B (NF- κ B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of γ -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota–gut–brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF- κ B signaling pathway and inflammatory responses.
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“Probiotic-4 (which contains Lactobacillus, Bifidobacterium, Typhimurium, and Eosinophilus) has been shown to attenuate aging-related disruptions in the integrity of the blood–brain barrier and the intestinal barrier; in plasma and brain LPS levels; and in IL-6, TNF-α, TLR4, and NF-κB translocation in the brains of aged mice (104).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [104]
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“In addition, treatment of aged senescence-accelerated mice P8 (SAMP8) mice with ProBiotic-4, a probiotic preparation composed of Bifido-bacterium lactis , Lactobacillus casei , B. bifidum , and Lactobacillus acidophilus , significantly decreased Firmicutes / Bacteroidetes (F:B) ratio, Proteobacteria, Pseudomonas (genus),…”
BackgroundLu, L., Li, F., Gao, Y., Kang, S., Li, J., & Guo, J. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00873-0 · Cited by 60
“Interestingly, Xueqin and colleagues [199] demonstrated that the probiotic combination ProBiotic-4 alleviates cognitive deficits in geriatric Senescence Accelerated Mouse-Prone 8 (SAMP8) mice by modulating the microbiota-gut-brain axis, suggesting that studying the gut microbiota may be beneficial…”
BackgroundAyed, L., M’hir, S., Nuzzolese, D., Cagno, R. D., & Filannino, P. (2024) · Foods · doi:10.3390/foods13101538 · Cited by 56
The Roles of the Gut Microbiota and Chronic Low-Grade Inflammation in Older Adults With Frailty
Xu, Y., Liu, X., Liu, X., Chen, D., Wang, M., Jiang, X., & Xiong, Z. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.675414 · Cited by 60
“Moreover, probiotics supplementation may delay the onset of aging-related cognitive deficits (Yang et al., 2020).”
BackgroundAlterations in gut microbiota are related to metabolite profiles in spinal cord injury
Jiang, J.-H., Ning, B., Kang, J.-N., Sun, Z.-F., Li, X., Zhang, X., Jin, Z., Zhang, C., Zhang, Y., Wang, H., et al. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.355769 · Cited by 54
“In previous studies, an increased F/B ratio has been associated with several neurological disorders, such as neuropathic pain, cognitive impairment, and stroke (Park et al., 2020; Yang et al., 2020).”
BackgroundMao, J., Zhan, H., Meng, F., Wang, G., Huang, D. Y., Liao, Z., & Chen, M. (2022) · Phytotherapy Research · doi:10.1002/ptr.7383 · Cited by 51
Effects of gut microbiota on neurodegenerative diseases
Khatoon, S., Kalam, N., Rashid, S., & Bano, G. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1145241 · Cited by 55
Microbiome-based therapeutics towards healthier aging and longevity
Kadyan, S., Park, G., Singh, T. P., Patoine, C., Singar, S., Heise, T., Domeier, C., Ray, C. A., Kumar, M., Behare, P. V., et al. (2025) · Genome Medicine · doi:10.1186/s13073-025-01493-x · Cited by 56
Mechanistic new insights of flavonols on neurodegenerative diseases
Tahir, M. S., Almezgagi, M., Zhang, Y., Bashir, A., Abdullah, H. M., Gamah, M., Wang, X., Zhu, Q., Shen, X., Ma, Q., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111253 · Cited by 51
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“demonstrated that probiotic-4 (Bifidobacterium lactis, Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus casei) attenuated aging-related disruption of IEB and BBB, reduced LPS in plasma and cerebral, characterized by inhibition of the NF-κB inflammatory signaling pathway [98].”
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Fan, T., Du, Y., Zhang, M., Zhu, A. R., & Zhang, J. (2022) · Gerontology · doi:10.1159/000522656 · Cited by 51
Stroke and Vascular Cognitive Impairment: The Role of Intestinal Microbiota Metabolite TMAO
Tu, R., & Xia, J. (2024) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527322666230203140805 · Cited by 47
Li, T., Yang, S., Liu, X., Li, Y., Gu, Z., & Jiang, Z. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.04.014 · Cited by 48
Gut microbiome and Alzheimer’s disease: What we know and what remains to be explored
Kapoor, B., Biswas, P., Gulati, M., Rani, P., & Gupta, R. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102570 · Cited by 46
Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions
Shen, W., He, J., Hou, T., Si, J., & Chen, S. (2022) · Aging and Disease · doi:10.14336/ad.2021.1208 · Cited by 45
Lista, S., Munafò, A., Caraci, F., Imbimbo, C., Emanuele, E., Minoretti, P., Pinto-Fraga, J., Merino-País, M., Crespo‐Escobar, P., López‐Ortiz, S., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102659 · Cited by 50
Gut microbiota-derived metabolites in inflammatory diseases based on targeted metabolomics
Xu, H., Pan, L., Yu, H., Han, P., Fu, J., Zhang, Z., Hu, J.-C., Yang, X., Keranmu, A., Zhang, H.-J., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.919181 · Cited by 45
Self-citationSoriano, S., Curry, K. D., Wang, Q., Chow, E., Treangen, T. J., & Villapol, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094476 · Cited by 42
Hashim, H. M., & Makpol, S. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.1007166 · Cited by 47
“The involvement of segmented filamentous bacteria (SFB) such as Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria phyla in the gut has been linked to the induction of Th17-mediated autoimmune disorders (Yi et al., 2010; Lee et al., 2011).”
BackgroundResearch progress on perioperative blood-brain barrier damage and its potential mechanism
Qiu, Y., Mo, C., Xu, S., Chen, L., Ye, W., Kang, Y., Chen, G., & Zhu, T. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1174043 · Cited by 45
Yadav, H., Jaldhi, Bhardwaj, R., Anamika, A., Bakshi, A., Gupta, S., & Maurya, S. K. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122022 · Cited by 47
Zhou, H., Zhao, J., Liu, C., Zhang, Z., Zhang, Y., & Meng, D. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.153937 · Cited by 44
The Role of Gut Microbiota—Gut—Brain Axis in Perioperative Neurocognitive Dysfunction
Lu, J. G., Hou, W., Gao, S., Zhang, Y., & Zong, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.879745 · Cited by 42
Sun, W., Zhu, J., Qin, G., Huang, Y., Cheng, S., Chen, Z., Zhang, Y., Shu, Y., Zeng, X., & Guo, R. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.125517 · Cited by 44
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“Furthermore, the study revealed a decrease in NF-κB translocation, toll-like receptor 4 (TLR4) expression, as well as a reduction in decreased plasma and brain LPS concentration[113].”
BackgroundWang, S.-S., Li, X., Liu, P., Li, J., & Liu, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.972982 · Cited by 42
“…of the flora in intestine and brain, reduce the destruction of intestinal barrier and blood-brain barrier, and reduce the level of lipopolysaccharide in plasma and brain, reduce the level of inflammatory factors in the brain and intestine at the level of messenger RNA (Yang et al., 2020).”
BackgroundLactic Acid Bacteria (LAB) and Neuroprotection, What Is New? An Up-To-Date Systematic Review
Mutalib, N. A., Mohamad, S. A. S., Jusril, N. A., Hasbullah, N. I., Amin, M. C. I. M., & Ismail, N. H. (2023) · Pharmaceuticals · doi:10.3390/ph16050712 · Cited by 53
“Its mechanism of action is associated with the inhibition of both TLR4- and RIG-I-mediated NFkB signaling pathways as well as inflammatory responses [55].”
BackgroundZhang, S., Lv, S., Li, Y., Wei, D., Zhou, X., Niu, X., Yang, Z., Song, W., Zhang, Z., & Peng, D. (2023) · European Journal of Nutrition · doi:10.1007/s00394-023-03208-7 · Cited by 42
“One study demonstrated that ProBiotic-4 alleviated the disruption of the intestinal barrier and blood–brain barrier and decreased the levels of TLR4, NF-κB and IL-6 in the brain [16].”
BackgroundImpact of Pesticide Residues on the Gut-Microbiota–Blood–Brain Barrier Axis: A Narrative Review
Diwan, M. A., Lahimer, M., Bach, V., Gosselet, F., Khorsi‐Cauet, H., & Candela, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076147 · Cited by 45
“In fact, recent research has shown that GM disorders (dysbiosis and/or bacterial translocation) are often associated with a leaky IB and BBB disruption accompanied with inflammation [101,102].”
BackgroundJiang, J. H., Liu, H., Wang, Z., Tian, H., Wang, S., Yang, J., & Ren, J. (2021) · PLoS ONE · doi:10.1371/journal.pone.0259530 · Cited by 39
“The new research found that: the molecular model of Lactobacillus Enterobacter can effectively inhibit the pathogenic infiltration of peripheral immune cells into the central nervous system [55], thus reducing neuroinflammation [56]; After supplementation with Lactobacillus and Bifidobacterium, the cognitive function…”
Hong, D., Zhang, C., Wu, W., Lu, X., & Zhang, L. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1133546 · Cited by 38
Zhang, Z., Deng, S., Chen, C., He, Q., Peng, X., Liang, Q., Zhuang, G., Wang, S., & Tang, D. (2023) · Phytotherapy Research · doi:10.1002/ptr.7827 · Cited by 40
“To explore whether there are intestinal inflammation and neuroinflammation in DCI mice, and the intervention mechanism of pterostilbene, we conducted a series of studies based on the MGBA.”
BackgroundInfluential
Metadata
- Authors
- Yang, X., Yu, D., Xue, L., Li, H., & Du, J.
- Affiliations
- Sichuan University (CN)
- Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (CN)
- Corresponding author
- Du, Junrong
- Venue
- Acta Pharmaceutica Sinica B
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 10
- Issue
- 3
- Pages
- 475-487
- ISSN
- 2211-3835 (ISSN-L)
- PMC
- PMC7049608
- OpenAlex
- W2954864461
- Cited by
- 407
- References
- 54
- Citations by year
- 2026: 45 · 2025: 82 · 2024: 91 · 2023: 69 · 2022: 65 · 2021: 41 · 2020: 14
- FWCI
- 23.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Pharmaceutica Sinica B (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81473219, 81973307)
- Sichuan Province Youth Science and Technology Innovation Team (2016TD0001)
- Higher Education Discipline Innovation Project
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Keywords
- probiotics, microbiota-gut-brain axis, memory impairment, aging, SAMP8 mice, Bifidobacterium animalis subsp. lactis, Lactobacillus casei, Lactobacillus acidophilus, Bifidobacterium bifidum, neuroinflammation, blood-brain barrier, intestinal barrier, lipopolysaccharide, TLR4, NF-κB signaling, RIG-I, oxidative stress, cognitive function
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