The Relationship Between the Gut Microbiome and Neurodegenerative Diseases

Xiao-hong, Zhu; Li, Bo; Lou, Pengcheng; Dai, Tingting; Chen, Yang; Zhuge, Aoxiang; Yuan, Yin; Li, Lanjuan

doi:10.1007/s12264-021-00730-8

Cited by 71 publications

(58 citation statements)

References 112 publications

(119 reference statements)

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“…In the present study, we deciphered the close connection between the gut microbiota and AD through the microbiota-gut-brain axis. Gut microbiota could serve as a potential new target for therapeutic intervention in AD (Zhou et al, 2019;Zhu et al, 2021). The brain-gut axis controls the interaction of biochemical molecules of brain and gut (Lu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites

Yan

Gao

Fang

et al. 2021

Front. Aging Neurosci.

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Background: Fasudil, a Rho kinase inhibitor, exerts therapeutic effects in a mouse model of Alzheimer's disease (AD), a chronic neurodegenerative disease with progressive loss of memory. However, the mechanisms remain unclear. In addition, the gut microbiota and its metabolites have been implicated in AD.Methods: We examined the effect of fasudil on learning and memory using the Morris water-maze (MWM) test in APPswe/PSEN1dE9 transgenic (APP/PS1) mice (8 months old) treated (i.p.) with fasudil (25 mg/kg/day; ADF) or saline (ADNS) and in age- and gender-matched wild-type (WT) mice. Fecal metagenomics and metabolites were performed to identify novel biomarkers of AD and elucidate the mechanisms of fasudil induced beneficial effects in AD mice.Results: The MWM test showed significant improvement of spatial memory in APP/PS1 mice treated with fasudil as compared to ADNS. The metagenomic analysis revealed the abundance of the dominant phyla in all the three groups, including Bacteroidetes (23.7–44%) and Firmicutes (6.4–26.6%), and the increased relative abundance ratio of Firmicutes/Bacteroidetes in ADNS (59.1%) compared to WT (31.7%). In contrast, the Firmicutes/Bacteroidetes ratio was decreased to the WT level in ADF (32.8%). Lefse analysis of metagenomics identified s_Prevotella_sp_CAG873 as an ADF potential biomarker, while s_Helicobacter_typhlonius and s_Helicobacter_sp_MIT_03-1616 as ADNS potential biomarkers. Metabolite analysis revealed the increment of various metabolites, including glutamate, hypoxanthine, thymine, hexanoyl-CoA, and leukotriene, which were relative to ADNS or ADF microbiota potential biomarkers and mainly involved in the metabolism of nucleotide, lipids and sugars, and the inflammatory pathway.Conclusions: Memory deficit in APP/PS1 mice was correlated with the gut microbiome and metabolite status. Fasudil reversed the abnormal gut microbiota and subsequently regulated the related metabolisms to normal in the AD mice. It is believed that fasudil can be a novel strategy for the treatment of AD via remodeling of the gut microbiota and metabolites. The novel results also provide valuable references for the use of gut microbiota and metabolites as diagnostic biomarkers and/or therapeutic targets in clinical studies of AD.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites

Yan

Gao

Fang

et al. 2021

Front. Aging Neurosci.

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“…healthy and pathological states in human beings (Zhu et al, 2021). Therefore, metaomics pipeline integrating different omics approaches is necessary to generate a holistic view of clinical samples, which is also why metaproteomics and metabolomics are needed for sample analysis.…”

Section: Drawbacks Of Standalone Omics Methodsmentioning

confidence: 99%

Metaomics in Clinical Laboratory: Potential Driving Force for Innovative Disease Diagnosis

Wang

Li²,

et al. 2022

Front. Microbiol.

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Currently, more and more studies suggested that reductionism was lack of holistic and integrative view of biological processes, leading to limited understanding of complex systems like microbiota and the associated diseases. In fact, microbes are rarely present in individuals but normally live in complex multispecies communities. With the recent development of a variety of metaomics techniques, microbes could be dissected dynamically in both temporal and spatial scales. Therefore, in-depth understanding of human microbiome from different aspects such as genomes, transcriptomes, proteomes, and metabolomes could provide novel insights into their functional roles, which also holds the potential in making them diagnostic biomarkers in many human diseases, though there is still a huge gap to fill for the purpose. In this mini-review, we went through the frontlines of the metaomics techniques and explored their potential applications in clinical diagnoses of human diseases, e.g., infectious diseases, through which we concluded that novel diagnostic methods based on human microbiomes shall be achieved in the near future, while the limitations of these techniques such as standard procedures and computational challenges for rapid and accurate analysis of metaomics data in clinical settings were also examined.

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“…The arguments about the beneficial uses of per os sodium butyrate in animal models for Parkinson's disease were already published. Moreover, it is thought that a microbiota that would generate butyrate locally could be much more efficient [147] and a careful selection of prebutyrogenic fiber (or new strategies of gut-microbiota-based) appears that it is already the subject of recent studies [148,149].…”

Section: Dietary Fibers and Neurological Impactmentioning

confidence: 99%

Therapeutic Benefits and Dietary Restrictions of Fiber Intake: A State of the Art Review

et al. 2022

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Throughout history, malnutrition and deficiency diseases have been a problem for our planet’s population. A balanced diet significantly influences everyone’s health, and fiber intake appears to play a more important role than previously thought. The natural dietary fibers are a category of carbohydrates in the constitution of plants that are not completely digested in the human intestine. High-fiber foods, such as fruits, vegetables and whole grains, have consistently been highly beneficial to health and effectively reduced the risk of disease. Although the mode of action of dietary fiber in the consumer body is not fully understood, nutritionists and health professionals unanimously recognize the therapeutic benefits. This paper presents the fiber consumption in different countries, the metabolism of fiber and the range of health benefits associated with fiber intake. In addition, the influence of fiber intake on the intestinal microbiome, metabolic diseases (obesity and diabetes), neurological aspects, cardiovascular diseases, autoimmune diseases and cancer prevention are discussed. Finally, dietary restrictions and excess fiber are addressed, which can cause episodes of diarrhea and dehydration and increase the likelihood of bloating and flatulence or even bowel obstruction. However, extensive studies are needed regarding the composition and required amount of fiber in relation to the metabolism of saprotrophic microorganisms from the enteral level and the benefits of the various pathologies with which they can be correlated.

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The Relationship Between the Gut Microbiome and Neurodegenerative Diseases

Cited by 71 publications

References 112 publications

Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites

Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites

Metaomics in Clinical Laboratory: Potential Driving Force for Innovative Disease Diagnosis

Therapeutic Benefits and Dietary Restrictions of Fiber Intake: A State of the Art Review

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