Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease

Qian, Xiaohang; Xie, Ru-Yan; Liu, Xiaoli; Chen, Shengdi; Tang, Huidong

doi:10.14336/ad.2021.1215

Cited by 48 publications

(38 citation statements)

References 162 publications

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“…Furthermore, recent investigations on the relationship between gut microbiota and cognition, including NCDs related to age, could be reversed by gut flora transplantation. Similarly, such relationship was observed in other diseases ( Boehme et al, 2021 ; Qian et al, 2022 ; Thu Thuy Nguyen and Endres, 2022 ).…”

Section: Discussionsupporting

confidence: 74%

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Liu

Sun

et al. 2022

Front. Microbiol.

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Neurocognitive disorders (NCDs) include complex and multifactorial diseases that affect many patients. The 5-hydroxytryptamine (5-HT) neuron system plays an important role in NCDs. Existing studies have reported that para-chlorophenylalanine (PCPA), a 5-HT scavenger, has a negative effect on cognitive function. However, we believe that PCPA may result in NCDs through other pathways. To explore this possibility, behavioral tests were performed to evaluate the cognitive function of PCPA-treated mice, suggesting the appearance of cognitive dysfunction and depression-like behavior. Furthermore, 16S rRNA and metabolomic analyses revealed that dysbiosis and acetate alternation could be related to PCPA-induced NCDs. Our results suggest that not only 5-HT depletion but also dysbiosis and acetate alternation contributed to PCPA-related NCDs. Specifically, the latter promotes NCDs by reducing short-chain fatty acid levels. Together, these findings provide an alternative perspective on PCPA-induced NCDs.

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Section: Discussionsupporting

confidence: 74%

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Liu

Sun

et al. 2022

Front. Microbiol.

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“…Propionate and butyrate induce neutrophil death in the immune system by inhibiting HDAC via a pathway that does not include GPRs or MAPKs. Furthermore, n-butyrate can modulate macrophage functioning in the intestines via suppressing HDACs rather than by triggering toll-like receptor signaling and induction of GPRs [ 62 ].…”

Section: Neurodegeneration and Associated Diseasesmentioning

confidence: 99%

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Singh

Chakrabarty

Shabir

et al. 2022

Mediators of Inflammation

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Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome’s role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

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“…Second, the increase the level of SCFAs derived from gut microbiota. As the main metabolite of gut microbiota, SCFAs have been reported to ameliorate cognitive impairment mediated by a variety of etiologies, including DCI (Lee et al, 2020;Enry et al, 2021;Qian et al, 2021;Zheng et al, 2021). Our previous study also found that ZSWF increased fecal SCFAs levels in DCI mice (unpublished).…”

Section: Discussionmentioning

confidence: 74%

Zi Shen Wan Fang Attenuates Neuroinflammation and Cognitive Function Via Remodeling the Gut Microbiota in Diabetes-Induced Cognitive Impairment Mice

et al. 2022

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Background: Cognitive dysfunction is a critical complication of diabetes mellitus, and there are still no clinically approved drugs. Zi Shen Wan Fang (ZSWF) is an optimized prescription composed of Anemarrhenae Rhizoma, Phellodendri Chinensis Cortex, and Cistanches Herba. The purpose of this study is to investigate the effect of ZSWF on DCI and explore its mechanism from the perspective of maintaining intestinal microbial homeostasis in order to find an effective prescription for treating DCI.Methods: The diabetes model was established by a high-fat diet combined with intraperitoneal injections of streptozotocin (STZ, 120 mg/kg) and the DCI model was screened by Morris water maze (MWM) after 8 weeks of continuous hyperglycemic stimulation. The DCI mice were randomly divided into the model group (DCI), the low- and high-ZSWF–dose groups (9.63 g/kg, 18.72 g/kg), the mixed antibiotic group (ABs), and the ZSWF combined with mixed antibiotic group (ZSWF + ABs). ZSWF was administered orally once a day for 8 weeks. Then, cognitive function was assessed using MWM, neuroinflammation and systemic inflammation were analyzed by enzyme-linked immunosorbent assay kits, intestinal barrier integrity was assessed by hematoxylin-eosin (HE) staining and Western blot and high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Furthermore, the alteration to intestinal flora was monitored by 16S rDNA sequencing.Results: ZSWF restored cognitive function in DCI mice and reduced levels of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α. Moreover, ZSWF protected the integrity of the intestinal barrier by increasing intestinal ZO-1 and occludin protein expression and decreasing urinary lactulose to mannitol ratio. In addition, ZSWF reshaped the imbalanced gut microbiota in DCI mice by reversing the abundance changes of a wide range of intestinal bacteria at the phyla and genus levels. In contrast, removing gut microbiota with antibiotics partially eliminated the effects of ZSWF on improving cognitive function and reducing inflammation, confirming the essential role of gut microbiota in the improvement of DCI by ZSWF.Conclusion: ZSWF can reverse cognitive impairment in DCI mice by remolding the structure of destructed gut microbiota community, which is a potential Chinese medicine prescription for DCI treatment.

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Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease

Cited by 48 publications

References 162 publications

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Zi Shen Wan Fang Attenuates Neuroinflammation and Cognitive Function Via Remodeling the Gut Microbiota in Diabetes-Induced Cognitive Impairment Mice

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