Therapeutic potential of short-chain fatty acid production by gut microbiota in neurodegenerative disorders

Yadav, Sarika; Tripathi, Anurag; Tripathi, Anurag; Tripathi, Amit Kumar

doi:10.1016/j.nutres.2022.07.007

Cited by 24 publications

(8 citation statements)

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“…Several studies have provided facts that acts as a biological antioxidant and plays a leading function in cellular growth due to its ability to scavenge reactive oxygen species and renew endogenous antioxidants (Attia et al 2020 ), contributing to α-lipoic acid-dependent cell death in various types of cancer like breast cancer, lung cancer, and colorectal cancer intimating that the mitochondrial apoptotic pathway is triggered by α-lipoic acid, also various researches show that α-lipoic acid plays a significant role in cancers related to metabolism (Dozio et al 2010 ; Choi et al 2012 ; Trivedi and Jena 2013 ; Omran and Omer 2015 ; Attia et al 2020 ; Yadav et al 2022a , b ).…”

Section: Discussionmentioning

confidence: 99%

“…α-Lipoic acid is a short-chain fatty acids (SCFAs) derived from the fermentation of vegetables and meat and modulates the gut microbiota without reducing the microbial diversity (Tripathi et al 2022 ; Yadav et al 2022a , b ). A recent study showed that α-lipoic acid and the SCFAs produced by Ruminococcaceae rejuvenated aged intestinal stem cells by preventing the age-associated endosome reduction (Du et al 2020 ; Xiong et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

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Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention

Tripathi

Ray

Mishra

et al. 2023

Rev. Bras. Farmacogn.

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Alpha-lipoic acid is an organic, sulfate-based compound produced by plants, humans, and animals. As a potent antioxidant and a natural dithiol compound, it performs a crucial role in mitochondrial bioenergetic reactions. A healthy human body, on the other hand, can synthesize enough α-lipoic acid to scavenge reactive oxygen species and increase endogenous antioxidants; however, the amount of α-lipoic acid inside the body decreases significantly with age, resulting in endothelial dysfunction. Molecular orbital energy and spin density analysis indicate that the sulfhydryl (-SH) group of molecules has the greatest electron donating activity, which would be responsible for the antioxidant potential and free radical scavenging activity. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties. α-Lipoic acid has cytotoxic and antiproliferative effects on several cancers, including polycystic ovarian syndrome. It also has usefulness in the context of female and male infertility. Although α-lipoic acid has numerous clinical applications, the majority of them stem from its antioxidant properties; however, its bioavailability in its pure form is low (approximately 30%). However, nanoformulations have shown promise in this regard. The proton affinity and electron donating activity, as a redox-active agent, would be responsible for the antioxidant potential and free radical scavenging activity of the molecule. This review discusses the most recent clinical data on α-lipoic acid in the prevention, management, and treatment of a variety of diseases, including coronavirus disease 2019. Based on current evidence, the preclinical and clinical potential of this molecule is discussed. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s43450-023-00370-1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention

Tripathi

Ray

Mishra

et al. 2023

Rev. Bras. Farmacogn.

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“…SCFAs are the fundamental gut microbial byproducts that are related to microbiome-gut-brain axis function. SCFAs mainly include acetic acid (AA), propionic acid (PPA), butyrate (BTA), and valeric acid (VA) 37 . Growing evidence also shows that higher concentrations of SCFAs may be plausible environmental agents that are related to altered GI function and overall health status in children with ASD.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analyses demonstrate the modulating role of gut microbiota on the associations of unbalanced dietary intake with gastrointestinal symptoms in children with autism spectrum disorder

Li,

Liu,

Huang

et al. 2023

Gut Microbes

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Our previous work revealed that unbalanced dietary intake was an important independent factor associated with constipation and gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD). Growing evidence has shown the alterations in the gut microbiota and gut microbiota-derived metabolites in ASD. However, how the altered microbiota might affect the associations between unbalanced diets and GI symptoms in ASD remains unknown. We analyzed microbiome and metabolomics data in 90 ASD and 90 typically developing (TD) children based on 16S rRNA and untargeted metabolomics, together with dietary intake and GI symptoms assessment. We found that there existed 11 altered gut microbiota (FDR-corrected P-value <0.05) and 397 altered metabolites (P-value <0.05) in children with ASD compared with TD children. Among the 11 altered microbiota, the Turicibacter , Coprococcus 1 , and Lachnospiraceae FCS020 group were positively correlated with constipation (FDR-corrected P-value <0.25). The Eggerthellaceae was positively correlated with total GI symptoms (FDR-corrected P-value <0.25). More importantly, three increased microbiota including Turicibacter , Coprococcus 1 , and Eggerthellaceae positively modulated the associations of unbalanced dietary intake with constipation and total GI symptoms, and the decreased Clostridium sp. BR31 negatively modulated their associations in ASD children (P-value <0.05). Together, the altered microbiota strengthens the relationship between unbalanced dietary intake and GI symptoms. Among the altered metabolites, ten metabolites derived from microbiota ( Turicibacter , Coprococcus 1 , Eggerthellaceae, and Clostridium sp. BR31 ) were screened out, enriched in eight metabolic pathways, and were identified to correlate with constipation and total GI symptoms in ASD children (FDR-corrected P-value <0.25). These metabolomics findings further support the modulating role of gut microbiota on the associations of unbalanced dietary intake with GI symptoms. Collectively, our research provides insights into the relationship between diet, the gut microbiota, and GI symptoms in children with ASD.

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“…These drugs have also shown promise as potential treatments for other neurological pathologies including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (Kim et al., 2022). SCFAs maintain healthy mitochondrial function and stimulate the maturation of microglia, consequently suppressing the progression of neurodegenerative diseases by regulating inflammation and oxidative stress (Yadav et al., 2022). However, SCFAs such as butyric acid and propionic acid may play a part in the acquisition of ASD (Lei et al., 2016).…”

Section: Therapeutic Potential Of Manipulating Glucose and Ketone Met...mentioning

confidence: 99%

The interplay between glucose and ketone bodies in neural stem cell metabolism

Molloy,

Barry

2024

J of Neuroscience Research

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Glucose is the primary energy source for neural stem cells (NSCs), supporting their proliferation, differentiation, and quiescence. However, the high demand for glucose during brain development often exceeds its supply, leading to the utilization of alternative energy sources including ketone bodies. Ketone bodies, including β‐hydroxybutyrate, are short‐chain fatty acids produced through hepatic ketogenesis and play a crucial role in providing energy and the biosynthetic components for NSCs when required. The interplay between glucose and ketone metabolism influences NSC behavior and fate decisions, and disruptions in these metabolic pathways have been linked to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Additionally, ketone bodies exert neuroprotective effects on NSCs and modulate cellular responses to oxidative stress, energy maintenance, deacetylation, and inflammation. As such, understanding the interdependence of glucose and ketone metabolism in NSCs is crucial to understanding their roles in NSC function and their implications for neurological conditions. This article reviews the mechanisms of glucose and ketone utilization in NSCs, their impact on NSC function, and the therapeutic potential of targeting these metabolic pathways in neurological disorders.

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Therapeutic potential of short-chain fatty acid production by gut microbiota in neurodegenerative disorders

Cited by 24 publications

References 131 publications

Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention

Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention

Multi-omics analyses demonstrate the modulating role of gut microbiota on the associations of unbalanced dietary intake with gastrointestinal symptoms in children with autism spectrum disorder

The interplay between glucose and ketone bodies in neural stem cell metabolism

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