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Journal of Neuroimmune Pharmacology :... Dec 2023Serotonergic dysfunction is related to both motor and nonmotor symptoms in Parkinson's disease (PD). As a 5-HT receptor, 5-HT4 receptor (5-HT4R) is well-studied and...
Serotonergic dysfunction is related to both motor and nonmotor symptoms in Parkinson's disease (PD). As a 5-HT receptor, 5-HT4 receptor (5-HT4R) is well-studied and already-used in clinical therapy of constipation, which is a typical non-motor symptom in PD. In this study, we investigated the role of 5-HT4R as a regulator of gut function in MPTP-induced acute PD mice model. Daily intraperitoneal injection of GR 125487 (5-HT4R antagonist) was administered 3 days before MPTP treatment until sacrifice. Seven days post-MPTP treatment, feces were collected and gastrointestinal transit time (GITT) was measured, 8 days post-MPTP treatment, behavioral tests were performed, and then animals were sacrificed for the further analysis. We found GR 125487 pretreatment not only increased GITT, but also aggravated MPTP-induced motor bradykinesia. In addition, GR 125487 pretreatment exacerbated the loss of dopaminergic neurons probably by suppressing JAK2/PKA/CREB signaling pathway and increased reactive glia and neuroinflammation in the striatum. 16 S rRNA sequencing of fecal microbiota showed that GR 125487 pretreatment altered the composition of gut microbiota, in which the abundance of Akkermansia muciniphila and Clostridium clostridioforme was increased, whereas that of Parabacteroides distasonis and Bacteroides fragilis was decreased, which are closely associated with inflammation condition. Taken together, we demonstrated that GR 125487 pretreatment exacerbates MPTP-induced striatal neurodegenerative processes possibly via the JAK2/PKA/CREB pathway and neuroinflammation by altering gut microbiota composition. In the microbiota-gut-brain axis of PD, 5-HT4R should be further explored and might serve as a target for PD diagnosis and treatment.
Topics: Mice; Animals; Parkinson Disease; Receptors, Serotonin, 5-HT4; Gastrointestinal Microbiome; Neuroinflammatory Diseases; Mice, Inbred C57BL; Disease Models, Animal; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Dopaminergic Neurons
PubMed: 37782386
DOI: 10.1007/s11481-023-10085-8 -
Aging Feb 2024Handgrip strength (HGS), which represents global muscle strength, is a powerful indicator of disability and mortality in older adults; it is also used for the diagnosis...
Handgrip strength (HGS), which represents global muscle strength, is a powerful indicator of disability and mortality in older adults; it is also used for the diagnosis of possible- or probable- sarcopenia and physical frailty. This study aimed to explore the metabolic mechanisms and potential biomarkers associated with declining HGS among older adults. We recruited 15 age- and environment-matched inpatients (age, 77-90 years) with low or normal HGS. Liquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal DNA (rDNA) gene sequencing were performed to analyze the metabolome of serum and stool samples and the gut microbiome composition of stool samples. Spearman's correlation analysis was used to identify the potential serum and fecal metabolites associated with HGS. We assessed the levels of serum and fecal metabolites belonging to the class of cinnamic acids and derivatives and reported that the levels of carboxylic acids and their derivatives decreased in the low-HGS group. Serum levels of microbial metabolites, including cinnamoylglycine, 4-methoxycinnamic acid, and (e)-3,4,5-trimethoxycinnamic acid, were positively correlated with HGS. We found that gut microbial α-diversity was significantly higher in the low-HGS group, whereas higher β-diversity was observed in the normal group. The relative abundances of the genera and increased significantly in the low-HGS group and were negatively correlated with the serum levels of cinnamoylglycine. The identified metabolites whose levels were markedly altered, and intestinal flora associated with these metabolites suggest the potential metabolic underpinnings for HGS and provide a basis for the further identification of biomarkers of muscle strength decline in older adults.
Topics: Humans; Aged; Aged, 80 and over; Gastrointestinal Microbiome; Hand Strength; Metabolome; Sarcopenia; Biomarkers
PubMed: 38305839
DOI: 10.18632/aging.205501 -
Frontiers in Endocrinology 2023To investigate the effect of short-term very-low-calorie restriction (VLCR) on metabolism in patients with type 2 diabetes (T2D), and elucidate the molecular mechanism...
BACKGROUND AND AIMS
To investigate the effect of short-term very-low-calorie restriction (VLCR) on metabolism in patients with type 2 diabetes (T2D), and elucidate the molecular mechanism through analyses on gut microbiota and small-molecule metabolites.
METHODS
Fourteen T2D patients were hospitalized to receive VLCR (300-600 kcal/d) for 9 days. BMI, BP, and HR were taken before and after VLCR. Levels of blood lipids, fasting insulin, FBG, and 2h PBG were assessed. The microbial diversity in feces was detected by 16S rDNA high-throughput sequencing technology, and small-molecule metabolites in plasma and feces by untargeted metabolomics technology.
RESULTS
After VLCR, BW, BMI, WC, BP, and levels of FBG and 2h PBG, insulin, HOMA-IR, and triglyceride decreased significantly in T2D patients (<0.05). There was no significant change in the α-diversity of fecal microbiota, but the abundance of increased significantly, and the ratio decreased significantly from 11.79 to 4.20. showed an abundance having increased most prominently after VLCR treatment. Plasma level of amino acid metabolite L-arginine increased significantly. Plasma levels of three lipid metabolites, PC (14:0/20:4 [8Z, 11Z, 14Z, 17Z]), LysoPC (16:1 [9Z]) and LysoPC (18:1 [11Z]), were significantly reduced. Fecal levels of lipid metabolite LysoPC (18:1 [11Z]) and bile acid metabolite glycholic acid were significantly decreased.
CONCLUSION
In T2DM patients, VLCR can considerably reduce body weight and improve glucose and lipid metabolism without causing severe side effects. LysoPC (18:1 [11Z]) and showed the most obvious difference after VLCR, which could be the indicators for VLCR in T2D.
Topics: Humans; Caloric Restriction; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Insulin; Lipids; Bacteroidetes
PubMed: 38269247
DOI: 10.3389/fendo.2023.1289571 -
Journal of Zhejiang University.... Jul 2023The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has...
Modulating effects of polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency.
The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. , used as both medicine and food, exerts the effects of tonifying spleen and qi. polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of , which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of and , and increasing that of , , , , , and . APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.
Topics: Rats; Animals; NF-kappa B; Spleen; Gastrointestinal Microbiome; Toll-Like Receptor 4; Polysaccharides; Astragalus Plant; Immune System Diseases; Body Weight
PubMed: 37455140
DOI: 10.1631/jzus.B2200491 -
Biomedical Journal Jun 2024The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides...
BACKGROUND
The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet.
METHODS
We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus.
RESULTS
The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not influence gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues.
CONCLUSIONS
Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases.
PubMed: 38901796
DOI: 10.1016/j.bj.2024.100754 -
Frontiers in Nutrition 2024The intricate interplay between dietary habits and the development of Parkinson's Disease (PD) has long been a subject of scientific inquiry. Mendelian Randomization...
BACKGROUND
The intricate interplay between dietary habits and the development of Parkinson's Disease (PD) has long been a subject of scientific inquiry. Mendelian Randomization (MR) emerges as a potent tool, harnessing genetic variants to infer causality in observational data. While evidence links diet to Parkinson's Disease (PD) etiology, a thorough MR exploration of dietary impacts on PD, particularly involving gut microbiota, is still emerging.
METHODS
This research leverages the IEU Open GWAS project's vast GWAS database to address the knowledge gap in understanding diet's influence on PD, employing a diverse range of dietary variables. Our holistic dataset includes various foods like processed fava beans, bap, red wine, to cheese, reflecting a commitment to untangling dietary complexities in PD etiology. Advancing from initial dietary-PD associations, we innovatively explore the gut microbiota, focusing on in relation to bap intake and PD, employing MR. Utilizing weighted median, MR-Egger, and inverse variance weighting methods, we ensure rigorous causality assessments, meticulously mitigating pleiotropy and heterogeneity biases to uphold finding validity.
RESULTS
Our findings indicate red wine (OR: 1.031; 95% CI 1.001-1.062; = 0.044) and dried fruit consumption (OR: 2.019; 95% CI 1.052-3.875; = 0.035) correlate with increased PD risk, whereas broad beans (OR: 0.967; 95% CI 0.939-0.996; = 0.024) and bap intake (OR: 0.922; 95% CI 0.860-0.989; = 0.023) show protective effects against PD. Employing MR, specifically the IVW method, revealed a significant inverse association between bap intake and gut microbiota, marked by an 8.010-fold decrease in per standard deviation increase in bap intake (95% CI 1.005-63.818, = 0.049). Furthermore, a connection between PD and was observed (OR: 0.810; 95% CI 0.768-0.999; = 0.049), suggesting a potential microbiota-mediated pathway in PD etiology.
CONCLUSION
Our study links dietary habits to PD risk, showing higher PD risk with red wine and dried fruit consumption, and a protective effect from broad beans and bap. Using MR, we found bap intake inversely correlates with in the gut, suggesting bap influences microbiota. Further, higher levels correlate with lower PD risk, highlighting a complex interplay of diet, gut microbiome, and neurological health. These insights shed light on potential dietary interventions for PD.
PubMed: 38840699
DOI: 10.3389/fnut.2024.1273874 -
Microbiology Spectrum Sep 2023Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and...
Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in developing and treating acute pancreatitis by affecting the host's metabolism. In this study, we followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease (before treatment, on the third day of treatment, and 1 month after discharge). We analyzed species composition and metabolic pathways' changes across the treatment phase, severity, and etiology. The diversity of the gut microbiome of patients with AP did not show much variation with treatment. In contrast, the metabolic functions of the gut microbiota, such as the essential chemical reactions that produce energy and maintain life, were partially reinstated after treatment. The severe AP (SAP) patients contained less beneficial bacteria (i.e., , and ) and weaker sugar degradation function than mild AP patients before treatment. Moreover, etiology was one of the drivers of gut microbiome composition and explained the 3.54% variation in species' relative abundance. The relative abundance of pathways related to lipid synthesis was higher in the gut of hyperlipidemia AP patients than in biliary AP patients. The composition and functional profiles of the gut microbiota reflect the severity and etiology of AP. Otherwise, we also identified bacterial species associated with SAP, i.e., sp 57_20 and , which have the potential to identify the SAP at an early stage. IMPORTANCE Acute pancreatitis (AP) is a type of digestive system disease with high mortality. Previous studies have shown that gut microbiota can participate in the development and treatment of acute pancreatitis by affecting the host's metabolism. However, fewer studies acquired metagenomic sequencing data to associate species to functions intuitively and performed longitudinal analysis to explore how gut microbiota influences the development of AP. We followed 20 AP patients to generate longitudinal gut microbiota profiles and activity during disease and studied the differences in intestinal flora under different severities and etiologies. We have two findings. First, the gut microbiota profile has the potential to identify the severity and etiology of AP at an early stage. Second, gut microbiota likely acts synergistically in the development of AP. This study provides a reference for characterizing the driver flora of severe AP to identify the severity of acute pancreatitis at an early stage.
PubMed: 37698429
DOI: 10.1128/spectrum.00829-23 -
Food & Function Oct 2023Trimethylamine--oxide (TMAO), originating from dietary trimethylamine-containing nutrients such as choline, has been recognized as a risk factor for atherosclerosis....
Trimethylamine--oxide (TMAO), originating from dietary trimethylamine-containing nutrients such as choline, has been recognized as a risk factor for atherosclerosis. Mangiferin is a bioactive xanthone initially extracted from mango (). The present study aimed to investigate the effect of mangiferin on TMAO-induced atherogenesis in mice fed a high-choline diet. Female ApoE mice were randomly divided into three groups and fed either a control diet, a high-choline diet with 1% free choline, or an experimental diet with 1% free choline plus 0.5% mangiferin for 15 weeks. Our results showed that a high-choline diet elevated plasma TMAO levels, accelerated atherogenesis, promoted cholesterol accumulation, and reduced the generation of short-chain fatty acids (SCFAs) by gut microbes. Mangiferin alleviated inflammation, and lowered plasma total cholesterol levels by facilitating the elimination of neutral and acidic sterols in feces, resulting in a 16.7-29.0% reduction in aortic atherosclerotic lesions. Notably, mangiferin could favorably remodel the composition of the gut microbiota by fostering the growth of the beneficial taxa , , and , while reducing the relative abundance of the pathogenic genus . This modulation led to a decrease in plasma lipopolysaccharide levels, enhanced the production of total SCFAs by gut microbes, and reduced susceptibility to atherosclerosis. In conclusion, mangiferin exhibited its ability to alleviate TMAO-induced atherosclerosis through its anti-inflammatory, cholesterol-lowering, and gut microbial modulatory activities.
Topics: Animals; Female; Mice; Atherosclerosis; Cholesterol; Choline; Gastrointestinal Microbiome; Methylamines; Oxides; Xanthones
PubMed: 37781894
DOI: 10.1039/d3fo02791k -
Food & Function Sep 2023Type 2 diabetes mellitus (T2DM) is typically accompanied by sudden weight loss, dyslipidemia-related indicators, decreased insulin sensitivity, and altered gut microbial...
Type 2 diabetes mellitus (T2DM) is typically accompanied by sudden weight loss, dyslipidemia-related indicators, decreased insulin sensitivity, and altered gut microbial communities. possesses many biological activities, such as antioxidant, hypolipidemic, and hypotensive activities. However, only a few studies have attempted to elucidate the regulatory effects of ethanol extract (FTE) on intestinal microbial communities and its potential relationships with T2DM. In this study, we established a T2DM mouse model and investigated the regulatory effects of FTE on hyperglycemia symptoms and intestinal microbial communities. FTE intervention significantly improved the levels of fasting blood glucose, the area under the curve of oral glucose tolerance test (OGTT), and glycosylated serum protein, as well as pancreas islet function correlation index. In addition, FTE effectively improved hepatic and cecum injuries and insulin secretion due to T2DM. It was also revealed that the potential hypoglycemic mechanism of FTE was involved in the regulation of protein kinase B (AKT-1) and glucose transporter 2 (GLUT-2). Furthermore, compared with the Model group, the FTE-H intervention exhibited a significantly decreased ratio of to at the phylum level, reduced relative abundance of pernicious bacteria at the genus level, such as , , , , and , and ameliorated inflammatory response and insulin resistance. Moreover, the correlation between gut microbiota and hypoglycemic indicators was predicted. The results showed that , , , , and have the potential to be used as bacterial markers for T2DM. In conclusion, our research showed that FTE alleviates hyperglycemia symptoms by regulating the expression of AKT-1 and GLUT-2, as well as intestinal microbial communities in T2DM mice.
Topics: Animals; Mice; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Fagopyrum; Proto-Oncogene Proteins c-akt; Hyperglycemia; Hypoglycemic Agents; Firmicutes; Lactobacillales; Bacteroidetes; Clostridiales; Ethanol; Plant Extracts
PubMed: 37655471
DOI: 10.1039/d3fo02385k -
Journal of Ethnopharmacology Dec 2023Erchen decoction (ECD) is a traditional Chinese medicine formula comprising six distinct herbs and has been documented to possess a protective effect against obesity....
ETHNOPHARMACOLOGICAL RELEVANCE
Erchen decoction (ECD) is a traditional Chinese medicine formula comprising six distinct herbs and has been documented to possess a protective effect against obesity. The study conducted previously demonstrated that ECD has the potential to effectively modulate the composition of gut microbiota and levels of short-chain fatty acids (SCFAs) in obese rat. However, the regulatory mechanism of ECD on gut microbiota and SCFAs and further improvement of obesity have not been thoroughly explained.
AIM OF THE STUDY
The objective of this study was to examine the therapeutic effect and molecular mechanism of ECD in a rat model of high-fat diet (HFD) feeding.
MATERIALS AND METHODS
Rats with HFD-induced obesity were treated with ECD. Upon completion of the study, serum and liver samples were procured to conduct biochemical, pathological, and Western blotting analyses. The investigation of alterations in the gut microbiota subsequent to ECD treatment was conducted through the utilization of 16S rRNA sequencing. The metabolic alterations in the cecal contents were examined through the utilization of mass spectrometry-ultraperformance liquid chromatography.
RESULTS
ECD treatment improved lipid metabolic disorders and reduced hepatic steatosis in HFD-induced obese rats. Obese rat treated with ECD showed a higher abundance of SCFA-producing bacteria, including Lactobacillus, Bifidobacterium, and Butyricicoccus, and lower abundance of disease-related bacteria, such as Bacteroides, Parabacteroides, and Sediminibacterium. Additionally, ECD caused an increase in total SCFAs levels; in particular, butyric acid was dramatically increased in the HFD group. Rats treated with ECD also exhibited significantly increased butyric acid concentrations in the serum and liver. The subsequent reduction in histone deacetylase 1 expression and increase in acetyl-histone 3-lysine 9 (H3K9ac) levels contributed to the promotion of fatty acid β-oxidation (FAO) in liver by ECD.
CONCLUSION
This study demonstrates that ECD regulates the gut microbiota and promotes butyric acid production to ameliorate obesity-related hepatic steatosis. The mechanism might be related to the promotion of FAO via a butyric acid-mediated increase in H3K9ac levels in the liver.
Topics: Rats; Animals; Mice; Butyric Acid; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Obesity; Non-alcoholic Fatty Liver Disease; Fatty Acids, Volatile; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 37336336
DOI: 10.1016/j.jep.2023.116811