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Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.
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Barrera Hematoencefálica , Disfunción Cognitiva , Disbiosis , Emulsionantes , Microbioma Gastrointestinal , Polisorbatos , Animales , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Polisorbatos/farmacología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/inducido químicamente , Emulsionantes/metabolismo , Emulsionantes/farmacología , Disbiosis/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Envejecimiento/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Masculino , Microglía/metabolismo , Microglía/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Cognición/efectos de los fármacos , Ácidos y Sales Biliares/metabolismoRESUMEN
Evidence reveals that gut dysbiosis is involved in bidirectional interactions in gut-brain axis and participates in the progress of multiple disorders like anxiety. Gut microbes in early life are crucial for establishment of host health. We aimed to investigate whether early life probiotics Lactobacillus rhamnosus GG (LGG) colonization could relieve anxiety in adulthood through regulation of gut-brain axis. Live or fixed LGG was gavaged to C57BL/6 female mice from day 18 of pregnancy until natural birth, and newborn mice from day 1 to day 5 respectively. In this study, we found that live LGG could be effectively colonized in the intestine of offspring. LGG colonization increased intestinal villus length and colonic crypt depth, accompanied with barrier function protection before weaning. Microbiota composition by 16S rRNA sequencing showed that some beneficial bacteria, such as Akkermansia and Bifidobacteria, were abundant in LGG colonization group. The protective effect of LGG on gut microbiota persisted from weaning to adulthood. Intriguingly, behavioral results assessed by elevated plus mazed test and open field test demonstrated relief of anxiety-like behavior in adult LGG-colonized offspring. Mechanically, LGG colonization activated epithelial growth factor receptor (EGFR) and enhanced serotonin transporter (SERT) expression and modulated serotonergic system in the intestine, and increased brain-derived neurotrophic factor and γ-aminobutyric acid receptor levels in the hippocampus and amygdala. Blocking EGFR blunted LGG-induced the increased SERT and zonula occludens-1 expression. Collectively, early life LGG colonization could protect intestinal barrier of offspring and modulate gut-brain axis in association with relief of anxiety-like behavior in adulthood.
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Lacticaseibacillus rhamnosus , Probióticos , Animales , Ansiedad , Eje Cerebro-Intestino , Receptores ErbB/metabolismo , Femenino , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Embarazo , Probióticos/uso terapéutico , ARN Ribosómico 16S/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismoRESUMEN
PURPOSE: The aim of the study is to explore interhemispheric homotopic functional connectivity alterations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric lupus (NPSLE and non-NPSLE, respectively) and their potential correlations with clinical characteristics and neuropsychological performance. METHODS: Based on resting-state functional MRI (rs-fMRI) data collected from SLE patients and matched healthy controls (HCs), the voxel-mirrored homotopic connectivity (VMHC) analysis was conducted to measure functional homotopy. Subsequently, correlations between altered functional homotopy and clinical/neuropsychological data were analyzed. RESULTS: Compared with the HC group, both NPSLE and non-NPSLE groups showed attenuated homotopic connectivity in middle temporal gyrus (MTG), cuneus (CUN), middle occipital gyrus (MOG), angular gyrus (ANG), and postcentral gyrus (PoCG). NPSLE patients also exhibited decreased homotopic connectivity in inferior parietal gyrus (IPG) and middle frontal gyrus (MFG). Compared with non-NPSLE patients, NPSLE patients showed weaker interhemispheric homotopic functional connectivity in MOG. Decreased homotopic functional connectivity in PoCG, IPG, and MOG were associated with the anxiety state of SLE patients. CONCLUSIONS: Our findings revealed attenuated functional homotopy in both NPSLE and non-NPSLE groups compared to the HC group, which appeared to be more severe in patients with comorbid neuropsychiatric lupus. Interhemispheric homotopy dysconnectivity may participate in the neuropathology of anxiety symptoms in SLE.
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Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Humanos , Lupus Eritematoso Sistémico/diagnóstico por imagen , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Consuming probiotic products is a solution that people are willing to choose to augment health. As a global health hazard, sleep deprivation (SD) can cause both physical and mental diseases. The present study investigated the protective effects of Lacticaseibacillus rhamnosus GG (LGG), a widely used probiotic, on a SD mouse model. Here, it has been shown that SD induced intestinal damage in mice, while LGG supplementation attenuated disruption of the intestinal barrier and enhanced the antioxidant capacity. Microbiome analysis revealed that SD caused dysbiosis in the gut microbiota, characterized by increased levels of Clostridium XlVa, Alistipes, and Desulfovibrio, as well as decreased levels of Ruminococcus, which were partially ameliorated by LGG. Moreover, SD resulted in elevated pro-inflammatory cytokine concentrations in both the intestine and the brain, while LGG provided protection in both organs. LGG supplementation significantly improved locomotor activity in SD mice. Although heat-killed LGG showed some protective effects in SD mice, its overall efficacy was inferior to that of live LGG. In terms of mechanism, it was found that AG1478, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, could diminish the protective effects of LGG. In conclusion, LGG demonstrated the ability to alleviate SD-induced intestinal barrier dysfunction through EGFR activation and alleviate neuroinflammation.
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The epidemic of coronavirus disease-19 (COVID-19) has grown to be a global health threat. Gastrointestinal symptoms are thought to be common clinical manifestations apart from a series of originally found respiratory symptoms. The human gut harbors trillions of microorganisms that are indispensable for complex physiological processes and homeostasis. Growing evidence demonstrate that gut microbiota alteration is associated with COVID-19 progress and severity, and post-COVID-19 syndrome, characterized by decrease of anti-inflammatory bacteria like Bifidobacterium and Faecalibacterium and enrichment of inflammation-associated microbiota including Streptococcus and Actinomyces. Therapeutic strategies such as diet, probiotics/prebiotics, herb, and fecal microbiota transplantation have shown positive effects on relieving clinical symptoms. In this article, we provide and summarize the recent evidence about the gut microbiota and their metabolites alterations during and after COVID-19 infection and focus on potential therapeutic strategies targeting gut microbiota. Understanding the connections between intestinal microbiota and COVID-19 would provide new insights into COVID-19 management in the future.
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COVID-19 , Microbioma Gastrointestinal , Probióticos , Humanos , Síndrome Post Agudo de COVID-19 , Prebióticos , Probióticos/uso terapéuticoRESUMEN
Metabolic syndrome (MetS) is a complex pathological condition that involves disrupted carbohydrate, protein, and fat metabolism in the human body, and is a major risk factor for several chronic diseases, including diabetes, cardiovascular disease, and cerebrovascular disease. While the exact pathogenesis of metabolic syndrome is not yet fully understood, there is increasing evidence linking mitochondrial dysfunction, which is closely related to the mitochondrial genome and mitochondrial dynamics, to the development of this condition. Recent advancements in genetic sequencing technologies have allowed for more accurate detection of mtDNA mutations and other mitochondrial abnormalities, leading to earlier diagnosis and intervention in patients with metabolic syndrome. Additionally, the identification of specific mechanisms by which reduced mtDNA copy number and gene mutations, as well as abnormalities in mtDNA-encoded proteins and mitochondrial dynamics, contribute to metabolic syndrome may promote the development of novel therapeutic targets and interventions, such as the restoration of mitochondrial function through the targeting of specific mitochondrial defects. Additionally, advancements in genetic sequencing technologies may allow for more accurate detection of mtDNA mutations and other mitochondrial abnormalities, leading to earlier diagnosis and intervention in patients with MetS. Therefore, strategies to promote the restoration of mitochondrial function by addressing these defects may offer new options for treating MetS. This review provides an overview of the research progress and significance of mitochondrial genome and mitochondrial dynamics in MetS.
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Crohn's disease (CD) is an inflammatory bowel disease (IBD) with complex clinical manifestations such as chronic diarrhea, weight loss and hematochezia. Despite the increasing incidence worldwide, cure of CD remains extremely difficult. The rapid development of high-throughput sequencing technology with integrated-omics analyses in recent years has provided a new means for exploring the pathogenesis, mining the biomarkers and designing targeted personalized therapeutics of CD. Host genomics and epigenomics unveil heredity-related mechanisms of susceptible individuals, while microbiome and metabolomics map host-microbe interactions in CD patients. Proteomics shows great potential in searching for promising biomarkers. Nonetheless, single omics technology cannot holistically connect the mechanisms with heterogeneity of pathological behavior in CD. The rise of multi-omics analysis integrates genetic/epigenetic profiles with protein/microbial metabolite functionality, providing new hope for comprehensive and in-depth exploration of CD. Herein, we emphasized the different omics features and applications of CD and discussed the current research and limitations of multi-omics in CD. This review will update and deepen our understanding of CD from integration of broad omics spectra and will provide new evidence for targeted individualized therapeutics.
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RATIONALE AND OBJECTIVES: Neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). We assessed the white matter microstructural integrity of the visual pathway in diabetes patients vs. healthy subjects, and investigated the advantages of generalized Q-sampling imaging (GQI) in the assessment of the visual pathway. MATERIALS AND METHODS: T1-weighted, T2-weighted fluid-attenuated inversion recovery, and simultaneous multislice- diffusion sequences were acquired from 21 DR patients, 29 diabetes patients without DR (NDR group), and 28 age- and gender-matched healthy controls. Diffusion source images were reconstructed to GQI. Region of interest (ROI)-based analysis was utilized to evaluate microstructural alterations in the visual pathway. Multivariate linear regression analysis (forward stepwise method) was performed to investigate associations between clinical data and mean GQI parameters. RESULTS: ROI-based analyses indicated that the GQI parameters generalized fractional anisotropy, quantitative anisotropy (QA), and normalized QA (NQA) were significantly lower in the NDR group than in the healthy controls, and even lower in the DR group than in the NDR group. Disease duration was significantly and negatively correlated with mean generalized fractional anisotropy and mean NQA. CONCLUSION: GQI could sensitively and non-invasively evaluate the visual pathway in diabetes patients. The nerve fibers of the visual pathway were damaged before the onset of retinopathy, and this damage was aggravated after retinopathy onset, as a consequence of long exposure to hyperglycemia.
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Diabetes Mellitus Tipo 2 , Enfermedades de la Retina , Sustancia Blanca , Anisotropía , Encéfalo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Humanos , Vías Visuales/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
Inflammatory bowel disease (IBD) is an idiopathic inflammatory bowel disease. Modulation of gut microbiota with dietary and nutritional targets is a feasible strategy for the prevention and treatment of IBD. In this study, we focused on Clostridium butyricum Prazmowski (CB), a butyrate-producing potential probiotic. We found that CB feeding decreased the disease activity index, colon inflammation/injury score and cell apoptosis in an experimental colitis mouse model, as well as elevated the level of SCFAs in cecal feces. CB could also balance the inflammatory cytokines, protect tight junctions, and increase the number of goblet cells and MUC2 production in mice, accompanied by EGFR signaling activation triggered by heparin-binding epidermal growth factor (HB-EGF) and amphiregulin (AREG). From the perspective of mechanism, the CB supernatant (CBS) stimulated EGFR activation in colon epithelial cell lines in concentration-dependent and time-dependent manners. CBS reduced the damage of tight junctions induced by H2O2, and inhibition of EGFR could suppress the protective effect of CBS. In conclusion, CB could protect the gut barrier and alleviate experimental colitis through the transactivation of EGFR signaling in intestinal epithelial cells induced by ligands (HB-EGF and AREG). This study identified the potential efficacy of CB as a preventive strategy for IBD and showed the broad prospect of CB as a food supplement.
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Clostridium butyricum , Colitis , Enfermedades Inflamatorias del Intestino , Probióticos , Animales , Butiratos/metabolismo , Clostridium butyricum/fisiología , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/prevención & control , Factor de Crecimiento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Factor de Crecimiento Similar a EGF de Unión a Heparina/metabolismo , Peróxido de Hidrógeno/metabolismo , Ratones , Probióticos/metabolismoRESUMEN
Objective: This study aims to investigate the alterations in functional brain network in systemic lupus erythematosus patients without overt neuropsychiatric symptoms [neuropsychiatric systemic lupus erythematosus (non-NPSLE)] from the perspective of degree centrality (DC) and functional connectivity (FC) using resting-state functional magnetic resonance imaging (MRI) and multivariate pattern analysis (MVPA) approach. Methods: DC analysis was performed based on the resting-state functional MRI data derived from 47 non-NPSLE patients and 47 healthy controls (HCs). Nodes with abnormal DC were utilized as seeds for further FC analysis. The correlation between MRI variables and clinical or neuropsychological data was analyzed using Pearson correlation analysis. Finally, MVPA classification based on DC was performed. Results: When compared with the HCs, the non-NPSLE patients exhibited remarkably higher DC in the bilateral hippocampus (HIP), right insula (INS), and lower DC in the left superior parietal gyrus. Furthermore, the patients displayed significantly higher FC between the left HIP and the left INS/left dorsolateral middle frontal gyrus/left supramarginal gyrus and higher FC between the right HIP and the right middle temporal gyrus/right dorsolateral middle frontal gyrus/right dorsolateral inferior frontal gyrus/right supramarginal gyrus (all imaging variables mentioned earlier underwent cluster-level false discovery rate corrections, the voxel threshold was p < 0.001, cluster threshold was p < 0.05). Correlation analysis revealed significantly negative correlations between DC values of the right INS and disease activity and the DC values of the right HIP and the Montreal Cognitive Assessment scores. The accuracy, sensitivity, and specificity of MVPA classification based on DC were 72.34, 63.83, and 80.85%, respectively. The most discriminative power brain regions were chiefly located within the temporal, parietal, and frontal regions. Conclusion: Patients with non-NPSLE exhibited abnormal DC and FC in the brain network. MVPA based on DC possessed commendable classification ability. Our study may provide a novel perspective on the neuropathological mechanisms underlying subclinical brain damage in non-NPSLE.
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BACKGROUND: Hashimoto's thyroiditis (HT) may cause salivary dysfunction in patients resulting in xerostomia, but little is known about changes in salivary function in patients with no obvious dry mouth symptoms. In this study we assessed salivary function in women with HT, who had not experienced xerostomia and, for the first time, evaluated the effects of thyroid auto-antibodies on this function.: METHODS: Sixty consecutive subjects were included, comprising 32 women (mean age, 36â±â12 years) diagnosed with HT accompanied by differentiated thyroid cancer (DTC) in the study group (HT group), along with a control group (DTC group) of 28 women (mean age, 40â±â12 years) diagnosed with DTC only. Salivary gland scintigraphy was used to assess salivary function with the semi-quantitative parameters of maximum absorption ratio and maximum secretion ratio, the decrease of which indicate impaired salivary function. Moreover, the HT and DTC groups were divided into four subgroups (Anti- HT, Anti+ HT, Anti- DTC, and Anti+ DTC), based on the presence of anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Finally, salivary gland semi-quantitative parameters were correlated with levels of thyroid-stimulating hormone (TSH), TGAb, and TPOAb in the HT and DTC groups. RESULTS: None of the semi-quantitative parameters examined in parotid or submandibular glands differed significantly between the HT and DTC groups. However, the maximum secretion ratio for the parotid and submandibular glands were significantly different in the subgroup comparison (pâ<â0.05). Furthermore, the TgAb, TPOAb, and TSH values correlated significantly with salivary excretive function (p ≤â0.05). CONCLUSION: Women with HT without xerostomia may not have salivary functional impairment during hypothyroidism. Serum thyroid autoantibody and TSH levels may mainly influence salivary excretive function but not uptake function.
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Autoanticuerpos/inmunología , Enfermedad de Hashimoto/inmunología , Enfermedad de Hashimoto/fisiopatología , Glándulas Salivales/fisiopatología , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Early life events can lead to multiple diseases in adulthood. Previous studies suggested that polysorbate 80 (P80) as a widely used emulsifier in pharmaceutical formulations and food industries could impair the intestinal barrier. However, whether maternal P80 (MP80) exposure could affect the long-term health of offspring remains unknown. In this study, we found that maternal P80 intake could retard intestinal development, disrupt the intestinal barrier, and cause low-grade intestinal inflammation in 3-week-old offspring. 16S rRNA sequencing and correlation analysis revealed that Mucispirillum, Clostridium XI, and Parabacteroides, which positively correlated with intestinal proliferation and differentiation, were decreased in the maternal P80 group. Interestingly, the increase in some harmful bacteria, including Proteobacteria, Helicobacteraceae, Campylobacterales, and Desulfovibrionales, persisted from the weaning period to adulthood (3 to 8 weeks). Furthermore, a fecal microbiota transplantation assay showed that the mice gavaged with feces from 3-week-old offspring of the MP80 group presented more severe intestinal inflammation and barrier disruption than the mice that received feces from the offspring of the control group. Finally, maternal P80 intake remarkably aggravated the structural disorder of intestinal crypt, increased proinflammatory factors, and exacerbated dextran sulfate sodium (DSS)-induced colitis in adulthood. Conclusively, maternal P80 intake could induce gut dysbiosis and promote colitis susceptibility in adulthood. This study provides new insights into the prevention of inflammatory bowel disease (IBD).IMPORTANCE The main findings of this research showed that maternal P80 intake could disrupt the intestinal barrier, induce gut dysbiosis, and promote colitis susceptibility in adulthood. This study will enhance understanding of the prevention of IBD.
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With the rapidly aging human population, age-related cognitive decline and dementia are becoming increasingly prevalent worldwide. Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota, microbial metabolites, and the functions of astrocytes. The microbiota-gut-brain axis has been the focus of multiple studies and is closely associated with cognitive function. This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases. This article also summarizes the gut microbiota components that affect astrocyte function, mainly through the vagus nerve, immune responses, circadian rhythms, and microbial metabolites. Finally, this article summarizes the mechanism by which the gut microbiota-astrocyte axis plays a role in Alzheimer's and Parkinson's diseases. Our findings have revealed the critical role of the microbiota-astrocyte axis in age-related cognitive decline, aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.