Modifying progression of aging and reducing the risk of neurodegenerative diseases by probiotics and synbiotics

Lye, Huey Shi; Lee, Yee Teng; Ooi, Shao Yin; Teh, Lai Kuan; Lim, Lay Ngor; Wei, Loo Keat

doi:10.2741/e826

Cited by 16 publications

(6 citation statements)

References 30 publications

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“…Aging affects most of the multi-cellular organisms, constraining longevity and lead to neurodegenerative diseases including stroke. Probiotics, or preferably a combination of probiotics and prebiotics, can modify the composition of the gut microbiome and reduce the impact of aging and the risk of neurodegenerative diseases (47, 48). Tree nuts, as a good source of prebiotics, have been suggested to exert anti-aging effect (49).…”

Section: Discussionmentioning

confidence: 99%

Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke

et al. 2019

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Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome. Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0–2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome. Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17 + γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05). Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.

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Section: Discussionmentioning

confidence: 99%

Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke

et al. 2019

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“…Human microbiota may strongly influence the pathology of AD, the deposition of Ab, and formation of neurofibrillary tangles in the hippocampus (Kohler et al, 2016). The effects of aging and the risk of neurodegenerative diseases can be reduced by probiotics, or by combining probiotics and prebiotics known as synbiotics, which can significantly modify the composition of the gut microbiome (Lye et al, 2018). Long-term (6 months) antibiotic treatment of 2-week-old AD mice induced shifts in gut microbial composition and diversity, a decrease in Ab plaque deposition, but an increase in soluble Ab in the brain of AD mice, suggesting that gut microbiota diversity could regulate host innate immunity mechanisms that are related to Ab amyloidosis (Minter et al, 2016).…”

Section: Gut Microbiota and Hippocampal Alzheimer's Disease Pathologiesmentioning

confidence: 99%

Roles of Gut Microbiota in the Regulation of Hippocampal Plasticity, Inflammation, and Hippocampus-Dependent Behaviors

Tang

Meng

et al. 2021

Front. Cell. Infect. Microbiol.

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The study of the gut microbiota-brain axis has become an intriguing field, attracting attention from both gastroenterologists and neurobiologists. The hippocampus is the center of learning and memory, and plays a pivotal role in neurodegenerative diseases, such as Alzheimer’s disease (AD). Previous studies using diet administration, antibiotics, probiotics, prebiotics, germ-free mice, and fecal analysis of normal and specific pathogen-free animals have shown that the structure and function of the hippocampus are affected by the gut microbiota. Furthermore, hippocampal pathologies in AD are positively correlated with changes in specific microbiota. Genomic and neurochemical analyses revealed significant alterations in genes and amino acids in the hippocampus of AD subjects following a remarkable shift in the gut microbiota. In a recent study, when young animals were transplanted with fecal microbiota derived from AD patients, the recipients showed significant impairment of cognitive behaviors, AD pathologies, and changes in neuronal plasticity and cytokines. Other studies have demonstrated the side effects of antibiotic administration along with the beneficial effects of probiotics, prebiotics, and specific diets on the composition of the gut microbiota and hippocampal functions, but these have been mostly preliminary with unclear mechanisms. Since some specific gut bacteria are positively or negatively correlated to the structure and function of the hippocampus, it is expected that specific gut bacteria administration and other microbiota-based interventions could be potentially applied to prevent or treat hippocampus-based memory impairment and neuropsychiatric disorders such as AD.

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“…In comparison, FMT studies are more heterogeneous methodologically despite the limited data available on PD models [44]; some short-term studies attest to its effectiveness in treating gastrointestinal dysfunction and improving motor symptoms [45,46,67,68]. Human studies on prebiotic and synbiotic interventions in neurodegenerative diseases are even more scarce [69][70][71] Finally, solid preclinical evidence must precede the design of large RCTs on the efficacy and safety of these interventions. Hence, preclinical PD research disposes of a wide variety of induction methods and prospective therapies with advantages and limitations in replicating PD pathogenesis.…”

Section: Clinical Translation Of Rodent Studies On Microbiota-targete...mentioning

confidence: 99%

The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson’s Disease Animal Models—A Systematic Review

Panaitescu,

Răzniceanu,

Mocrei-Rebrean

et al. 2024

CIMB

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Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson’s disease by rebalancing the gut microbiome in the context of the gut–brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson’s disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson’s disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.

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Modifying progression of aging and reducing the risk of neurodegenerative diseases by probiotics and synbiotics

Cited by 16 publications

References 30 publications

Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke

Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke

Roles of Gut Microbiota in the Regulation of Hippocampal Plasticity, Inflammation, and Hippocampus-Dependent Behaviors

The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson’s Disease Animal Models—A Systematic Review

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