JOURNAL OF HAZARDOUS MATERIALS
·
2025
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IF 11.3
Qiuhui Qian,Qian Pu,Lihang Li,Ji Wu,Guanchen Cheng,Ying Cheng,Xuedong Wang,Huili Wang
Polylactic acid (PLA) is a biodegradable alternative to traditional plastics due to its excellent biocompatibility. However, PLA is challenging to fully degrade and can easily become microplastics (MPs) in surface water, a process accompanied by aging. This study found that aged PLA (APLA) MPs exhibited increased surface roughness, decreased surface potential, and more oxygen-containing functional groups compared to PLA. Acute exposure to PLA/APLA in zebrafish larvae resulted in sluggish behavior and inhibited neuronal development. Chronic exposure to PLA/APLA in adult zebrafish led to reduced exploratory behavior, poor memory, increased aggression, and neuron loss. Overall, PLA/APLA induced dose-dependent neurotoxicity, with APLA exhibiting greater toxicity than PLA, potentially due to its higher rate of uptake. Additionally, exposure to PLA/APLA led to thinning of the intestinal wall, shortening of villi, and suppression of intestinal neurotransmitter levels, accompanied by alterations in microbial abundance and gut dysbiosis. Meanwhile, supplementation with bile acid, considered as the key regulator in the gut-brain axis, significantly mitigated the neurotoxicity induced by PLA/APLA. These findings confirm that PLA/APLA MPs indeed elicit neurotoxicity via the gut-brain axis and provide scientific evidence for targeted environmental interventions to minimize the adverse ecological impacts of biodegradable MPs.
研究领域:
环境科学
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毒理学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Xiaoying Lin,Jiating Zhao,Wei Zhang,Lina He,Liming Wang,Dunhu Chang,Liwei Cui,Yuxi Gao,Bai Li,Chunying Chen,Yu-Feng Li
Environmental pollutants like methylmercury (MeHg) can bring devastating neurotoxicity to animals and human beings. Gut microbiota has been found to demethylate MeHg and promote the excretion of Hg through feces. However, the impacts of MeHg on gut microbiota and metabolites related to gut-brain interactions were less studied in mammals. The object of this study was to investigate the impacts of acute MeHg exposure on gut microbiome and metabolites together with its impact on gut integrity and related biological responses in rats. Rats were exposed to MeHg through oral administration and were sacrificed after 24 h 16 S rRNA gene sequencing was used to study the perturbance to gut microbiome and liquid chromatography mass spectrometry (LC-MS) was used for metabolomics profiling. It was found that gut was one of the target tissues of MeHg. MeHg induce the changes of intestinal microbial community structure and induce the regulating neuron activity change of intestinal neurotransmitters and metabolites on intestinal neurotransmitters and metabolites regulating the neuron activity. This was supported by the increased BDNF level. These findings may suggest a potential new mechanism regarding the neurotoxicity of MeHg. The protocols used in this study may also be applied to understand the neurotoxicity of other environmental neurotoxins like Pb, Mn, polychlorinated biphenyls, and pesticides, etc and to screen the neurotoxicity of emerging environmental contaminants.
研究领域:
环境科学
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毒理学
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微生物学
✓ 已验证
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Wenting Lin,Kan Li,Yingjun Qin,Xing Han,Xiaohui Chen,Yuan Ren
The abuse of psychoactive substances has led to their frequent detection in the environment, with unknown effects on the nervous system. In this study, zebrafish were exposed to benzodiazepine drug flunitrazepam (FLZ, 0.2 and 5 μg/L) for 30 days to assess its neurotoxicity. Results revealed that FLZ disrupted the balance of gut microbiota and caused an increase in pathogenic bacteria, such as Paracoccus and Aeromonas , leading to pathological damage to the intestine. The upregulation of intestinal pro-inflammatory factors, IL-1β and TNF-α , by 2.4 and 6.3 times, respectively, along with the downregulation of tight junction proteins, Occludin and zonula occludens 1 ( ZO-1 ), by 80 % and 50 %, increased in intestinal permeability. Moreover, untargeted metabolomics demonstrated that FLZ interfered with intestinal nucleotide metabolism and amino acid biosynthesis. FLZ could also increase the levels of lipopolysaccharide (LPS) and malondialdehyde (MDA) in the brain by 0.9 and 3.4 times, respectively, leading to pathological changes in brain tissue. Furthermore, FLZ significantly disturbed nucleotide metabolism and amino acid biosynthesis and metabolism pathways in the brain. Correlation analysis between gut microbiota and neurochemicals confirmed that FLZ can induce neurotoxicity through the microbiota-gut-brain axis. These findings elucidate the molecular mechanisms of psychoactive drugs on microbiota-gut-brain axis and provide a theoretical basis for the ecological environmental risk assessment of various psychoactive substances.
研究领域:
毒理学
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神经科学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Lifang Wei,Changhui Li,Daozheng Fang,Chi Zhang,Haipiao Huang,Jinru Wu,Lin Zheng,Yinghao Yin,Qiugu Chen,Shiying Huang,Jihang Chen,Jianping Chen
Background Tourette syndrome (TS) is a neuropsychiatric disorder that typically manifests in childhood. Currently, anti-psychotic drugs that aim to reduce dopaminergic hyperinnervation in the brain are recommended for TS. These drugs have been proven to increase the risk of extrapyramidal symptoms, which hinder their use. Gut microbiota has been shown to modulate dopamine (Da) metabolism along gut-brain axis and be relevant to the development of TS, and which may be a novel strategy for TS therapy. Xiao-Er-An-Shen Granule (XEASG) is a clinically prescribed herbal mixture that has demonstrated clinical efficacy in treating TS. The detailed mechanism of XEASG in alleviating TS symptoms through the gut-brain axis however remains incompletely understood. Purpose This study aimed to investigate the effect of XEASG on TS through regulating Da synthesis both in the brain and gut microbiota. Methods XEASG at doses of 2 and 4 g/kg/d was administered orally to 3,3’-iminodipropionitrile (IDPN)-induced TS model mice. Behavioral assessments, targeted metabolomics analysis, 16S rRNA sequencing and ELISA were employed to elucidate the therapeutic effects and mechanisms of XEASG for TS treatment. Results Data showed that XEASG treatment significantly alleviated IDPN-induced tic-like behavior in mice. XEASG significantly reduced Da level in the brain tissues of TS mice, resulting from down-regulated Da synthesis but up-regulated Da degradation. Aberrant Da metabolism was also found in serum and colon contents of TS mice, which was restored by XEASG treatment. Furthermore,16S rRNA sequence revealed that XEASG altered the microbial community composition. Finally, experimental validation confirmed that XEASG suppressed Da synthesis pathway by reducing tyrosine hydroxylase level in the gut microbiota. Conclusion Our findings reveal that XEASG alleviates TS via inhibiting Da synthesis in the brain and gut, which suggests that the regulation of Da through gut microbiota by XEASG could be a therapeutic strategy for TS treatment.
研究领域:
神经药理学
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神经精神病学
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代谢组学
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微生物学
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中医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ALZHEIMERS DISEASE
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2025
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IF 3.1
Yanfei Wei,Yining Huang,Shiao Wang,Kuan Liu,Qi Zhong,Weidong Fan,Bifei Cao,Haowen Chen,Yongqi Liang,Qiurong Li,Zhengyun Xu,Kaiyue Liao,Xianbo Wu
BackgroundCognitive impairment (CI) is a complex condition, and older adults with CI are several times more likely to develop Alzheimer's disease (AD) than their cognitively normal peers. The gut–brain axis plays a crucial role in neurodegeneration, with gut microbiota potentially affecting cognition via autophagy regulation.ObjectiveThis study aims to elucidate the association between Ruminococcus gnavus and CI in older adults, dissect the autophagy-related mechanisms potentially involved in this association and provide new insights and evidence for the role of R. gnavus in AD-related CI.MethodsFecal 16S rRNA profiles from 30 elders with CI and 30 matched controls were compared, then pseudo-germ-free aged mice were monocolonized with R. gnavus. Cognitive performance (Morris water maze), autophagy markers (quantitative PCR, western blot analysis, histology and ELISA) and untargeted metabolomics were evaluated to identify autophagy-related pathways.ResultsR. gnavus was enriched in patients with CI and inversely correlated with Mini-Mental State Examination scores. In aged pseudo-germ-free mice monocolonized with R. gnavus, learning and memory declined and autophagy was suppressed: the mRNA levels of Atg2a, Atg5, Atg7, Atg9a, Atg14, Atg16, Beclin-1, Lc3b and Ulk1 decreased, whereas P62 increased. Consistent protein changes, decreased LC3B and Beclin-1 levels with elevated P62 and immunohistochemistry indicated reduced LC3B-positive plaques in the CA1, CA3 and cortex. Metabolomics revealed disrupted glycerophospholipid metabolism and enriched autophagy-related pathways.ConclusionsThe enrichment of R. gnavus is associated with CI, with autophagy potentially mediating its effects on cognition via the gut–brain axis. Causality remains to be established through longitudinal studies.
研究领域:
神经退行性疾病
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微生物学
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老年医学
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生物信息学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2025
·
IF 2.7
Ru Cheng,Aoqi Song,Jingjing Jiang,Xijier Qiaolongbatu,Zhenghua Wu,Feng Qian,Shuyu Shen,Liwen Zhang,Zhiyu Wang,Wenjuan Zhao,Yuefen Lou
The exact mechanism by which berberine alleviates depression remains unclear. In this study, we explored the relationship between the antidepressant effect of berberine and the microbiota–brain–gut axis. The levels of IL-1β, TNF-α, IL-6, corticosterone, serotonin, and brain-derived neurotrophic factor (BDNF) were quantified using enzyme-linked immunosorbent assays (ELISA) and Western blotting. Variations in the composition of the gut microbiota were examined using 16S rRNA gene sequencing. Berberine significantly mitigated depressive behaviors in mice with CRS, as manifested by increased total distance traveled and central zone duration in the open-field examination, increased time and number of entries into the outstretched arms during the elevated and maze tests, and an increase in the exercise time during the tail suspension and forced swimming tests. Histopathological analysis indicated that berberine ameliorated CRS-induced hippocampal and colonic damage in mice. Additionally, berberine substantially restrained the generation of proinflammatory cytokines and corticosterone in mice with CRS, while increasing the levels of BDNF and serotonin. Importantly, berberine significantly ameliorated CRS-induced depression-like behaviors ( p < 0.01) and restored gut microbial diversity and short-chain fatty acid (SCFA) levels (fold-change: acetate 1.8-fold, butyrate 2.2-fold; p < 0.05). Furthermore, berberine restored the CRS-induced alterations in SCFA production. Our results indicate that berberine may exert antidepressant effects via a pleiotropic mechanism that modulates the microbiome–brain–gut axis.
研究领域:
神经生物学
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精神病学
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微生物组学
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免疫学
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分子药理学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·
IF 7.5
Xiaoying Ma,Weibo Shi,Zhen Wang,Shujin Li,Rufei Ma,Weihao Zhu,Lin Wu,Xiaowei Feng,Bin Cong,Yingmin Li
Background Depression is closely associated with stress-induced hippocampal damage and dysfunction. Emerging evidence demonstrates that the gut microbiota and its metabolites, acting as probiotics or prebiotics, can modulate brain structure and function via the gut-brain axis, thereby offering therapeutic potential for ameliorating related neurological and psychiatric disorders. This study delves into the contribution of the gut microbiota and its metabolites to stress-induced ferroptosis of hippocampal neurons and the associated molecular pathways. Methods This study used time-course stress paradigms combined with ferroptosis inhibitors to identify hippocampal neuronal ferroptosis. Fecal microbiota transplantation were conducted to analyze the role of gut microbiota in this process. Subsequently, 16 S rDNA sequencing and metabolomics techniques were applied to identify key gut microbiota and metabolites. Metabolites intervention were performed to examine their causal relationship with neuronal ferroptosis. Finally, we used histochemical and molecular assays to assess both intestinal and blood-brain barrier integrity as well as inflammation in peripheral blood and hippocampal tissue, along with GPR41/RhoA/Rock1 pathway changes, to preliminarily investigate the molecular mechanisms underlying stress-induced hippocampal neuronal ferroptosis. Results We demonstrated that stress triggered hippocampal neuronal ferroptosis and subsequent depressive-like behaviors in mice. Fecal microbiota transplantation successfully replicated the ferroptosis phenotype. Butyric acid and valeric acid were identified as key metabolites significantly reduced in the serum of acutely and chronically stressed mice, respectively. Intervention with these metabolites markedly alleviated ferroptosis. Furthermore, valerate intervention increased hippocampal GPR41 expression and significantly suppressed the pro-inflammatory RhoA/Rock1 pathway in chronically stressed mice, thereby reducing neuroinflammation and ameliorating neuronal ferroptosis. However, butyrate intervention showed no significant effect on the GPR41/RhoA/Rock1 pathway. Conclusion Stress induces ferroptosis in hippocampal neurons, where reduced abundance of short-chain fatty acid-producing bacteria plays a key role. Key metabolites butyric acid and valeric acid alleviate neuroinflammation to improve ferroptosis via the gut-brain axis in acute and chronic stress, respectively. Specifically, valeric acid exerts neuroprotective effect through the GPR41/RhoA/Rock1 pathway, whereas butyric acid-mediated protection likely operates through alternative mechanisms. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12967-025-06950-0.
研究领域:
神经科学
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精神病学
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微生物学
·
代谢组学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science and Ecotechnology
·
2023
·
IF 12.6
Si-Qi Zhang,Ping Li,Shu-Wen He,Shao-Ying Xing,Zhi-Han Cao,Xue-Li Zhao,Cuici Sun,Zhi-Hua Li
Microplastics (MPs), an emerging group of pollutants, not only have direct toxic effects on aquatic organisms but also cause combined toxicity by absorbing other pollutants. Triphenyltin (TPT), one of the most widely used organotin compounds, has adverse effects on aquatic organisms. However, little is known about the combined toxicity of MPs and TPT to aquatic organisms. To investigate the individual and combined toxicity of MPs and TPT, we selected the common carp ( Cyprinus carpio ) for a 42-day exposure experiment. Based on the environmental concentrations in a heavily polluted area, the experimental concentrations of MPs and TPT were set at 0.5 mg L −1 and 1 μg L −1 , respectively. The effects of MPs combined with TPT on the carp gut–brain axis were evaluated by detecting gut physiology and biochemical parameters, gut microbial 16S rRNA, and brain transcriptome sequencing. Our results suggest that a single TPT caused lipid metabolism disorder and a single MP induced immunosuppression in carp. When MPs were combined with TPT, the involvement of TPT amplified the immunotoxic effect induced by MPs. In this study, we also explored the gut–brain axis relationship of carp immunosuppression, providing new insights for assessing the combined toxicity of MPs and TPT. At the same time, our study provides a theoretical basis for evaluating the coexistence risk of MPs and TPT in the aquatic environment.
研究领域:
环境科学
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毒理学
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水生生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Therapeutic Advances in Gastroenterology
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2021
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IF 4.409
Fenghua Xu,Yi Cheng,Guangcong Ruan,Liqin Fan,Yuting Tian,Zhifeng Xiao,Dongfeng Chen,Yanling Wei
Background: The community of gut microbes is a key factor controlling the intestinal barrier that communicates with the nervous system through the gut-brain axis. Based on our clinical data showing that populations of Roseburia intestinalis are dramatically decreased in the gut of patients with ulcerative colitis, we studied the efficacy of a strain belonging to this species in the context of colitis and stress using animal models. Methods: Dextran sulfate sodium was used to induce colitis in rats, which then underwent an enema with R. intestinalis as a treatment. The disease activity index, fecal changes and body weight of rats were recorded to evaluate colitis, while histological and immunohistochemical analyses were carried out to examine colon function, and 16S rRNA sequencing was performed to evaluate the gut microbiota change. Behavioral assays and immunohistochemical staining of brain were performed to assess the effect of R. intestinalis on the gut-brain axis. Results: Colitis-related symptoms in rats were significantly relieved after R. intestinalis enema, and the stool traits and colon length of rats were significantly recovered after treatment. The gut epithelial integrity and intestinal barrier were restored in treated rats, as evidenced by the higher expression of Zo-1 in colon tissues, accompanied by the restoration of gut microbiota. Meanwhile, depressive-like behaviors of rats were reduced after treatment, and laboratory experiments on neuronal cells also showed that IL-6, IL-7 and 5-HT were downregulated by R. intestinalis treatment in both serum and brain tissue, while Iba-1 expression was reduced in treated rats. Conclusions: The administration of R. intestinalis contributes to restoration of the gut microbiota, promoting colon repair and the recovery of gastrointestinal function. These alterations are accompanied by the relief of depressive-like behaviors through a process modulated by the neuronal network and the regulation of inflammation by the gut-brain axis.
研究领域:
胃肠病学
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微生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NATURE MEDICINE
·
2025
·
IF 50
He Xiaolong,Hu Mengyao,Xu Yi,Xia Fangbo,Tan Yang,Wang Yuqing,Xiang Huiling,Wu Hao,Ji Tengfei,Xu Qian,Wang Lei,Huang Zhenhe,Sun Meiling,Wan Yu,Cui Peng,Liang Shaocong,Pan Yuan,Xiao Siyu,He Yan,Song Ruixin,Yan Junqing,Quan Xin,Wei Yingge,Hong Changze,Liao Weizuo,Li Fuli,El-Omar Emad,Chen Jinjun,Qi Xiaolong,Gao Jie,Zhou Hongwei
Up to 50–70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut–brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus , increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus . Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut–liver–brain axis and identify a promising therapeutic and predictive target for HE.
研究领域:
胃肠病学
·
微生物学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Psychiatry
·
2021
·Vol. 11
·期 1
·1-27
·
IF 6.222
Guo Yinrui,Zhu Xiangxiang,Zeng Miao,Qi Longkai,Tang Xiaocui,Wang Dongdong,Zhang Mei,Xie Yizhen,Li Hongye,Yang Xin,Chen Diling
Gut microbiota (GM) metabolites can modulate the physiology of the host brain through the gut–brain axis. We wished to discover connections between the GM, neurotransmitters, and brain function using direct and indirect methods. A diet with increased amounts of sugar and fat (high-sugar and high-fat (HSHF) diet) was employed to disturb the host GM. Then, we monitored the effect on pathology, neurotransmitter metabolism, transcription, and brain circularRNAs (circRNAs) profiles in mice. Administration of a HSHF diet-induced dysbacteriosis, damaged the intestinal tract, changed the neurotransmitter metabolism in the intestine and brain, and then caused changes in brain function and circRNA profiles. The GM byproduct trimethylamine-n-oxide could degrade some circRNAs. The basal level of the GM decided the conversion rate of choline to trimethylamine-n-oxide. A change in the abundance of a single bacterial strain could influence neurotransmitter secretion. These findings suggest that a new link between metabolism, brain circRNAs, and GM. Our data could enlarge the “microbiome–transcriptome” linkage library and provide more information on the gut–brain axis. Hence, our findings could provide more information on the interplay between the gut and brain to aid the identification of potential therapeutic markers and mechanistic solutions to complex problems encountered in studies of pathology, toxicology, diet, and nutrition development.
研究领域:
神经科学
·
微生物学
·
分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Dijun Zhang,Jiaojiao Han,Yanyan Li,Bei Yuan,Jun Zhou,Lingzhi Cheong,Ye Li,Chenyang Lu,Xiurong Su
To discern whether tuna oil modulates the expression of brain proteins and the gut microbiota structure during aging induced by d-galactose, we generated an aging mouse model with d-galactose treatment, and the mice showed aging and memory deterioration symptoms according to physiological and biochemical indices. Treatment with different doses of tuna oil alleviated the symptoms; the high dose showed a better effect. Subsequently, brain proteomic analysis showed the differentially expressed proteins were involved in damaged synaptic system repairment and signal transduction system enhancement. In addition, tuna oil treatment restored the diversity of gut microbiota, 27 key operational taxonomic units, which were identified using a redundancy analysis and were significantly correlated with at least one physiological index and three proteins or genes. These findings suggest that the combination of proteomics and gut microbiota is an effective strategy to gain novel insights regarding the effect of tuna oil treatment on the microbiota–gut–brain axis.
研究领域:
老年学
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神经科学
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微生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）