Gut microbiome-derived LPS aggravated cognitive impairment by promoting systemic inflammation via the TLR4/MyD88/NF-κB signaling pathway in hypoxic-ischemic neonatal rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE271722 | GEO | 2025/07/01
REPOSITORIES: GEO
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Project description:Background: The long-term high-fat, high-sugar diet exacerbates type 2 diabetes mellitus (T2DM)-related cognitive impairments. The negative impact of poor dietary patterns on brain development and neurological function may be related to gut microbiota disturbance. The role of phlorizin in mitigating glucose and lipid metabolism disorders is well documented. However, the protective effect of phlorizin on diabetes-related cognitive dysfunction is unclear. Therefore, the present study aimed to investigate the effect of dietary supplementation of phlorizin on high-fat and high-fructose diet (HFFD)-induced cognitive dysfunction and evaluate the crucial role of the microbiota-gut-brain axis. Results: Dietary supplementation of phlorizin for 14 weeks effectively prevented glucolipid metabolism disorder, spatial learning impairment, and memory impairment in HFFD mice. In addition, phlorizin improved the HFFD-induced decrease in synaptic plasticity, neuroinflammation, and excessive activation of microglia in the hippocampus. Transcriptomics analysis shows that the protective effect of phlorizin on cognitive impairment was associated with increased expression of neurotransmitters and synapse-related genes in the hippocampus. Phlorizin treatment alleviated colon microbiota disturbance, mainly manifested by an increase in gut microbiota diversity and the abundance of short-chain fatty acid (SCFA)-producing bacteria. The level of microbial metabolites, including SCFA, inosine 5'-monophosphate (IMP), and D (-)-beta-hydroxybutyric acid (BHB) were also significantly increased after phlorizin treatment. Moreover, integrating multiomics analysis observed tight connections between phlorizin-regulated genes, microbiota, and metabolites. Furthermore, removal of the gut microbiota via antibiotics treatment diminished the protective effect of phlorizin against HFFD-induced cognitive impairment, underscoring the critical role of the gut microbiota in mediating cognitive behavior. Importantly, supplementation with SCFA and BHB alone mimicked the regulatory effects of phlorizin on cognitive function. Conclusions: These results indicate that gut microbiota and their metabolites mediate the ameliorative effect of phlorizin on HFFD-induced cognitive impairment. Therefore, phlorizin can be used as an easy-to-implement nutritional therapy to prevent and alleviate metabolism-related neurodegenerative diseases by targeting the regulation of the microbiome-gut-brain axis.
2024-03-20 | GSE261887 | GEO
Project description:Intracerebral hemorrhage (ICH) induces alterations in the gut microbiota composition, significantly impacting neuroinflammation post-ICH. However, the impact of gut microbiota absence on neuroinflammation following ICH-induced brain injury remain unexplored. Here, we observed that the gut microbiota absence was associated with reduced neuroinflammation, alleviated neurological dysfunction, and mitigated gut barrier dysfunction post-ICH. In contrast, recolonization of microbiota from ICH-induced SPF mice by transplantation of fecal microbiota (FMT) exacerbated brain injury and gut impairment post-ICH. Additionally, microglia with transcriptional changes mediated the protective effects of gut microbiota absence on brain injury, with Apoe emerging as a hub gene. Subsequently, Apoe deficiency in peri-hematomal microglia was associated with improved brain injury. Finally, we revealed that gut microbiota influence brain injury and gut impairment via gut-derived short-chain fatty acids (SCFA).
2024-05-13 | GSE266602 | GEO
Project description:The gut microbiota modulates environmental risk for cognitive impairment
| PRJNA684902 | ENA
Project description:<p><strong>BACKGROUND:</strong> Ochratoxin A (OTA) have made it a serious hazard to food safety worldwide that poses a serious health risk to humans. Our previous research showed that Walnut green husk polysaccharides (WGP) can effectively alleviate intestinal inflammation and intestinal microbiota disturbances caused by OTA. The present study further explored whether WGP can prevents OTA-induced cognitive impairments and elucidate its neuroprotective mechanism. Here, we established fecal microbiota transplantation, Lactobacillus johnsonii (L.john) and Akkermansia muciniphila (AKK) colonization, L.john and AKK-derived extracellular vesicles (EVs), as well as 5-HT and short-chain fatty acid (SCFA) supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in WGP in alleviating OTA-induced cognitive impairment. </p><p><strong>RESULTS:</strong> OTA exposure induced cognitive impairments and inhibition of hippocampal neurogenesis, which was reversed by WGP supplementation. Meanwhile, WGP supplementation significantly reversed OTA-induced gut dysbacteriosis and low abundance of L.john and AKK, high proinflammation factor levels and low neurotransmitter levels in serum, intestine and hippocampus, as well as low SCFA levels in fecal. Antibiotic cocktail treatment eliminates the neuroprotective effect of WGP on OTA-treated mice. In addition, transplantation of the OTA-gut microbiota into normal mice causing similar results to OTA treatment, and these changes were alleviated with the transplantation of OTA+WGP-gut microbiota. Furthermore, colonization with L.john and AKK markedly reversed OTA-induced cognitive impairments and inhibition of hippocampal neurogenesis, as well as increased 5-HT and SCFA levels. EVs derived from L.john and AKK exhibit consistent performance with colonized L.john and AKK, and also have superior abilities in alleviating OTA-induced cognitive impairment and inhibiting hippocampal neurogenesis. Moreover, as a key regulatory factor of microbiota-gut-brain axis, 5-HT and SCFA supplementation significantly alleviated OTA-induced cognitive impairment and inhibition of hippocampal neurogenesis. </p><p><strong>CONCLUSIONS:</strong> Taken together, this work provides new evidence for microbiota-gut-brain axis involved in the neuroprotective effects of WGP on OTA-induced cognitive dysfunction. L.john, AKK and its derived EVs mediate the ameliorative effects of WGP on OTA-induced cognitive impairment. A feasible mechanism is that WGP increased the content of L.john, AKK and its derived EVs, which improve 5-HT and SCFA production in colon to ameliorate cognitive impairment and enhance hippocampal neurogenesis.</p>
2024-10-10 | MTBLS10673 | MetaboLights
Project description:<p>Parkinson's disease (PD) is a common neurodegenerative disorder. It is marked by motor dysfunction and cognitive decline. In recent years, scientific studies have found that PD's pathogenesis may be tied to an imbalance in the gut microbiota. This offers new perspectives for PD treatment. Modulating the gut microbiota is recognized as a potential way to enhance PD symptoms. While aerobic exercise can positively influence the gut microbiota, research on how the gut microbiota mediates aerobic exercise's effects on PD cognitive impairment is still limited. Thus, this study aimed to explore the potential mechanisms by which aerobic exercise improves cognitive impairment in PD patients. It does so by modulating the gut microbiota's structure and, in turn, improving cognitive function. Through this study, we hope to offer new strategies and a theoretical basis for treating PD cognitive impairment.</p>
2025-10-12 | MTBLS13123 | MetaboLights
Project description:Hypertension Promotes Neuroinflammation, Brain Injury and Cognitive Impairment
| PRJNA1087309 | ENA
Project description:Gut microbiome-derived LPS aggravated cognitive impairment by promoting systemic inflammation via the TLR4/MyD88/NF-κB signaling pathway in hypoxic-ischemic neonatal rats
| PRJNA1132994 | ENA
Project description:CurrentNeonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.
2022-09-27 | GSE205143 | GEO
Project description:Neonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.
2022-09-27 | GSE205142 | GEO
Project description:Hypertension is a major risk factor for both stroke and cognitive impairment, but it is unclear whether it may specifically affect post-stroke cognitive impairment. We assessed the effect of hypertension and/or stroke on brain injury, cognitive outcome, and the brain transcriptomic profile. C57BL/6J mice (n=117; 3-5 mo.) received s.c. infusion of either saline or angiotensin II (for 14 d or 28 d) followed by sham surgery or photothrombotic stroke targeting the prefrontal cortex seven days later. Cognitive function was assessed with the Barnes maze. RNA sequencing was used to quantify transcriptomic changes in the brain. Angiotensin II treatment produced spontaneous hemorrhaging on the stroke brain. In the Barnes maze, hypertensive mice that received stroke surgery had an increased escape latency compared to other groups (day 3: hypertensive + stroke=166.6±6.0 s vs. hypertensive + sham=122.8±13.8 s vs. normotensive + stroke=139.9±10.1 s vs. normotensive + sham=101.9±16.7 s), consistent with a greater learning impairment. RNA sequencing revealed >800 differentially expressed genes related to neuroinflammation in hypertensive + stroke vs. hypertensive + sham, which included genes associated with apoptosis, microRNAs, autophagy, anti-cognitive biomarkers and Wnt signaling. The combination of hypertension and stroke resulted in greater learning impairment and brain injury.
2024-11-27 | GSE247789 | GEO