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Neurology International Jun 2023(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is... (Review)
Review
(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is related to the pathophysiology of numerous diseases. This systematic review aims to gather existing data on the occidental hemisphere, compare it, and search for any significant association between Parkinson's disease and gut microbiota dysbiosis. (2) Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocols were used for this systematic review. PubMed was used as the database search engine. Of the 166 studies found, only 10 were used, as they met our inclusion criteria: case-control studies, studies that assessed the correlation of PD and gut microbiome, studies that took place in occidental regions, and studies that were performed on humans and were written in English. The Newcastle-Ottawa Scale was used as the assessment tool for overall risk of bias in this systematic review. (3) Results: The studies analyzed were divided into three geographic areas: Region 1: United States of America and Canada; Region 2: Germany, Ireland, and Finland; and Region 3: Italy; based on geographical similarities among these populations. The following statistically significant results were described in PD patients, compared with non-PD controls. In the first region, a significant increase in the following bacteria was seen: 1. Phylum: Actinobacteriota and its Genus: ; 2. Phylum: Verrucomicrobiota and its Genus: ; 3. Genus: , , , and of the Phylum: Firmicutes; 4. Family: of Phylum: Firmicutes; 5. Phylum: Bacteroidetes and its Genus: ; 6. Phylum: Proteobacteria. A significant decrease was described in the Family: and its Genus: , , and , which belong to the Phylum: Firmicutes. In the second region, a raised number of: 1. Phylum: Verrucomicrobiota, its Genus: , and its Species: ; 2. Family: of the Phylum: Verrucomicrobiota; 3. Genus: and of the Phylum: Firmicutes; 4. Family: of the Phylum: Firmicutes; 5. Family: of the Phylum: Bacteroidetes; 6. Genus: of the Phylum: Actinobacteriota; 7. Species: of the Phylum: Thermodesulfobacteriota, was identified. Only one Genus: of the Phylum: Bacteroidetes was decreased. In the third and last region, an augmented number of these bacteria were found: 1. Phylum: Verrucomicrobiota and its Genus: ; 2. Family: and of the Phylum: Actinobacteriota; 3. Phylum: Firmicutes and its Family: and ; 4. Family: and its Genus: , of the Phylum: Firmicutes; 5. Genus: and , of the Phylum: Firmicutes; 6. Phylum: Proteobacteria, its Family: , and the Genus: , , , and ; 7. Genus: of the Phylum: Bacteroidetes. In contrast, a significant decrease in 1. Phylum: Firmicutes, its Family: , and its Genus: and 2. Genus: of the Phylum: Firmicutes, was described. (4) Conclusion: A significant gut dysbiosis, involving multiple bacterial taxa, was found in PD patients compared to healthy people in the occidental regions. However, more studies are needed to find the precise pathophysiologic involvement of other groups of pathogens, such as fungi and parasites, in the development and progression of PD.
PubMed: 37368331
DOI: 10.3390/neurolint15020047 -
Frontiers in Cellular and Infection... 2020Increasing evidence suggests that features of the gut microbiota correlate with ischemic stroke. However, the specific characteristics of the gut microbiota in patients...
Increasing evidence suggests that features of the gut microbiota correlate with ischemic stroke. However, the specific characteristics of the gut microbiota in patients suffering different types of ischemic stroke, or recovering from such strokes, have rarely been studied, and potential microbiotic predictors of different types of stroke have seldom been analyzed. We subjected fecal specimens from patients with lacunar or non-lacunar acute ischemic infarctions, and those recovering from such strokes, to bacterial 16S rRNA sequencing and compared the results to those of healthy volunteers. We identified microbial markers of different types of ischemic stroke and verified that these were of diagnostic utility. Patients with two types of ischemic stroke, and those recovering from ischemic stroke, exhibited significant shifts in microbiotic diversities compared to healthy subjects. Cluster of Orthologous Groups of Proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed reduced metabolic and transport-related pathway activities in ischemic stroke patients. We performed fivefold cross-validation using a Random Forest model to identify two optimal bacterial species (operational taxonomic units; OTUs) serving as markers of lacunar infarction; these were (OTU_45) and (OTU_4), and the areas under the receiver operating characteristic curves (AUCs under the ROCs) were 0.881 and 0.872 respectively. In terms of non-lacunar acute ischemic infarction detection, the two optimal species were (OTU_330) and (OTU_338); the AUCs under the ROCs were 0.985 and 0.929 respectively. In post-ischemic stroke patients, the three optimal species were (OTU_35), (OTU_303), and (OTU_9); the AUCs under the ROCs were 1, 0.897, and 0.846 respectively. Notably, the gut microbial markers were of considerable value for utility when diagnosing lacunar infarction, non-lacunar acute ischemic infarction, and post-ischemic stroke. This study is the first to characterize the gut microbiotic profiles of patients with lacunar or non-lacunar, acute ischemic strokes, and those recovering from stroke, and to identify microbiotic predictors of such strokes.
Topics: Brain Ischemia; Humans; Ischemic Stroke; RNA, Ribosomal, 16S; Stroke; Stroke, Lacunar
PubMed: 33409158
DOI: 10.3389/fcimb.2020.587284 -
Gut Pathogens 2017is a major member of sulfidogenic bacteria in human gut, it was originally recovered from different clinical specimens of intra-abdominal infections and recently was...
BACKGROUND
is a major member of sulfidogenic bacteria in human gut, it was originally recovered from different clinical specimens of intra-abdominal infections and recently was reported potentially linked to different chronic metabolic disorders. However, there is still insufficient understanding on its detailed function and mechanism to date.
METHODS
A strain was isolated from fresh feces of a latent autoimmune diabetes in adults patient and we investigated its pathogenicity by oral administration to specific-pathogen-free mice. Tissue samples and serum were collected after sacrifice. Stool samples were collected at different time points to profile the gut microbiota.
RESULTS
infection resulted in the reduction of body weight and fat mass, apparent hepatosplenomegaly and elevated serum inflammatory factors, including serum amyloid A and interleukin-6, while without significant change of the overall gut microbiota structure.
CONCLUSIONS
These results demonstrated that higher amount of caused systemic inflammatory response in SPF mice, which adds new evidence to the pathogenicity of this bacterium and implied its potential role to the chronic inflammation related metabolic diseases like diabetes.
PubMed: 29090023
DOI: 10.1186/s13099-017-0208-7 -
Genes May 2022The influence of the microbiome on neurological diseases has been studied for years. Recent findings have shown a different composition of gut microbiota detected in...
BACKGROUND
The influence of the microbiome on neurological diseases has been studied for years. Recent findings have shown a different composition of gut microbiota detected in patients with multiple sclerosis (MS). The role of this dysbiosis is still unknown.
OBJECTIVE
We analyzed the gut microbiota of 15 patients with active relapsing-remitting multiple sclerosis (RRMS), comparing with diet-matched healthy controls.
METHOD
To determine the composition of the gut microbiota, we performed high-throughput sequencing of the 16S ribosomal RNA gene. The specific amplified sequences were in the V3 and V4 regions of the 16S ribosomal RNA gene.
RESULTS
The gut microbiota of RRMS patients differed from healthy controls in the levels of the , , , , , , , , and genera. All these genera were included in a logistic regression analysis to determine the sensitivity and the specificity of the test. Finally, the ROC (receiver operating characteristic) and AUC with a 95% CI were calculated and best-matched for (AUC of 75.0 and CI from 60.6 to 89.4) and (AUC of 70.2 and CI from 50.1 to 90.4).
CONCLUSIONS
There is a dysbiosis in the gut microbiota of RRMS patients. An analysis of the components of the microbiota suggests the role of some genera as a predictive factor of RRMS prognosis and diagnosis.
Topics: Biomarkers; Dysbiosis; Gastrointestinal Microbiome; Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; RNA, Ribosomal, 16S
PubMed: 35627315
DOI: 10.3390/genes13050930 -
International Journal of Molecular... May 2023The gut-liver axis may provide a new perspective for treating anti-tuberculosis drug-induced liver injury (ATDILI). Herein, the protective effect of (Lc) was...
The gut-liver axis may provide a new perspective for treating anti-tuberculosis drug-induced liver injury (ATDILI). Herein, the protective effect of (Lc) was investigated by modulating gut microflora (GM) and the toll like receptor 4 (TLR4)-nuclear factor (NF)-κB-myeloiddifferentiationfactor 88 (MyD88) pathway. C57BL/6J mice were given three levels of Lc intragastrically for 2 h before administering isoniazid and rifampicin for 8 weeks. Blood, liver, and colon tissues, as well as cecal contents, were collected for biochemical and histological examination, as well as Western blot, quantitative real time polymerase chain reaction (qRT-PCR), and 16S rRNA analyses. Lc intervention decreased alkaline phosphatase (ALP), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor (TNF)-α levels ( < 0.05), recovered hepatic lobules, and reduced hepatocyte necrosis to alleviate liver injury induced by anti-tuberculosis drugs. Moreover, Lc also increased the abundance of and and decreased abundance, while enhancing zona occludens (ZO)-1 and claudin-1 protein expression compared with the model group ( < 0.05). Furthermore, Lc pretreatment reduced the lipopolysaccharide (LPS) level and downregulated NF-κB and MyD88 protein expression ( < 0.05), thus restraining pathway activation. Spearman correlation analysis indicated that and were positively correlated with ZO-1 or occludin protein expression and negatively correlated with pathway protein expression. had significant negative relationships with alanine aminotransferase (ALT) and LPS levels. In contrast, had negative associations with ZO-1, occludin, and claudin-1 protein expressions and positive correlations with LPS and pathway proteins. The results prove that can enhance the intestinal barrier and change the composition of the gut microflora. Moreover, may also inhibit TLR4-NF-κB-MyD88 pathway activation and alleviate ATDILI.
Topics: Mice; Animals; NF-kappa B; Lipopolysaccharides; Lacticaseibacillus casei; Toll-Like Receptor 4; Signal Transduction; Antitubercular Agents; Gastrointestinal Microbiome; Myeloid Differentiation Factor 88; Occludin; Claudin-1; RNA, Ribosomal, 16S; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Chemical and Drug Induced Liver Injury; Glutathione
PubMed: 37298396
DOI: 10.3390/ijms24119444 -
Journal of Physiology and Pharmacology... Apr 2022This study aims to investigate the effect of resveratrol on intrahepatic cholestasis of pregnancy (ICP) and its effect on the gut microbiome profiles, thus contributing...
This study aims to investigate the effect of resveratrol on intrahepatic cholestasis of pregnancy (ICP) and its effect on the gut microbiome profiles, thus contributing to the potential therapeutic strategies for ICP. ICP rat models were established by injecting 17α-ethinylestradiol (EE) subcutaneously from the thirteenth day of gestation for four days and then treated with EE (D group, n=5), resveratrol (R group, n=5), or ursodeoxycholic acid (UDCA; U group, n=5) from the seventeenth to the twentieth day of gestation. Fecal samples were analyzed with 16S ribosomal RNA (rRNA) sequencing. In results: the gut microbiota of pregnant rats was characterized with reduced alpha diversity (Chao1 index), and significant variation in the microbiota structure (ANOSIM) was also observed after being treated with EE. The richness of four phyla and ten genera was upregulated, and five phyla and ten genera were downregulated by EE treatment. The dysbiosis of Bilophila, Ruminococcus, and Actinobacteria caused by EE treatment was reversed by resveratrol administration. There was a correlation between total bile acid and alanine aminotransferase in ICP rats. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results suggested that the secondary bile acid biosynthesis was decreased, and the alanine, aspartate, and glutamate metabolism was increased after being treated with EE in pregnant rats. In conclusion, EE treatment could lead to gut microbiome dysbiosis and bile acid metabolism dysregulation in pregnant rats. Resveratrol could partially rescue gut microbiota dysbiosis and improve the biochemical characteristics caused by EE treatment.
Topics: Alanine; Alanine Transaminase; Animals; Aspartic Acid; Bile Acids and Salts; Cholestasis; Cholestasis, Intrahepatic; Dysbiosis; Ethinyl Estradiol; Female; Gastrointestinal Microbiome; Glutamates; Pregnancy; Pregnancy Complications; RNA, Ribosomal, 16S; Rats; Resveratrol; Ursodeoxycholic Acid
PubMed: 36193965
DOI: 10.26402/jpp.2022.2.09 -
Nature and Science of Sleep 2021To explore the characteristics of gut microbiota and its relationship between clinical manifestations in patients with type 1 narcolepsy (NT1).
PURPOSE
To explore the characteristics of gut microbiota and its relationship between clinical manifestations in patients with type 1 narcolepsy (NT1).
PATIENTS AND METHODS
Scale and polysomnography were performed in 20 NT1 patients and 16 healthy controls (HC group) to evaluate the clinical characteristics of NT1. Illumina sequencing was performed on bacterial 16S ribosomal RNA gene using V3-V4 regions to compare the fecal microbiota in all subjects. Associations between clinical characteristics and gut microbiota were analyzed using partial correlation analysis.
RESULTS
Compared with the HC group, the NT1 group had a significantly higher ESS score, longer total sleep time, increased wakefulness, decreased sleep efficiency, disturbance of sleep structure, shorter mean sleep latency, and increased sleep-onset REM periods (all P < 0.05). No differences in alpha and beta diversity were observed between the two groups. In contrast, there were significant differences at the level of class, order, family, and genus (all P < 0.05). LEfSe analysis showed that the relative abundance of in the NT1 group was higher than that in the HC group (P < 0.05), while the relative abundance of , and were lower (all P < 0.05). Partial correlation analysis revealed that partial differential bacteria in the NT1 group were correlated with total sleep time, sleep efficiency, stage 1 sleep, arousal index, and sleep latency (all P < 0.05).
CONCLUSION
Our data revealed differences in intestinal flora structure between NT1 patients and the normal population, thus providing a theoretical basis for future microecological therapy for narcolepsy. However, future larger sample size studies and different study designs are needed to further clarify the possible pathogenesis and potential causality of intestinal flora in NT1 patients and explore the new treatment strategies.
PubMed: 34785965
DOI: 10.2147/NSS.S330022 -
Frontiers in Nutrition 2021The aim of this study was to determine the effects of long-term Nicotinamide mononucleotide (NMN) treatment on modulating gut microbiota diversity and composition, as...
The aim of this study was to determine the effects of long-term Nicotinamide mononucleotide (NMN) treatment on modulating gut microbiota diversity and composition, as well as its association with intestinal barrier function. In this study, C57BL/6J mice were fed different concentrations of NMN, and their feces were collected for detection of 16S rDNA and non-targeted metabolites to explore the effects of NMN on intestinal microbiota and metabolites. The results revealed that NMN increased the abundance of butyric acid-producing bacteria (Ruminococcae_UCG-014 and Prevotellaceae_NK3B31_group) and other probiotics (Akkermansia muciniphila), while the abundance of several harmful bacteria (Bilophila and Oscillibacter) were decreased after NMN treatment. Meanwhile, the level of bile acid-related metabolites in feces from the G1 group (0.1 mg/ml) was significantly increased compared to the control group, including cholic acid, taurodeoxycholic acid, taurocholic acid, glycocholic acid, and tauro-β-muricholic acid. In addition, long-term NMN treatment affected the permeability of the intestinal mucosa. The number of goblet cells and mucus thickness increased, as well as expression of tight junction protein. These results demonstrate that NMN reduced intestinal mucosal permeability and exerts a protective effect on the intestinal tract. This study lays the foundation for exploring NMN's utility in clinical research.
PubMed: 34395502
DOI: 10.3389/fnut.2021.714604 -
MSystems Oct 2020Cardiovascular disease (CVD) has been linked to animal-based diets, which are a major source of trimethylamine (TMA), a precursor of the proatherogenic compound...
Cardiovascular disease (CVD) has been linked to animal-based diets, which are a major source of trimethylamine (TMA), a precursor of the proatherogenic compound trimethylamine--oxide (TMAO). Human gut bacteria in the genus have genomic signatures for genetic code expansion that could enable them to metabolize both TMA and its precursors without production of TMAO. We uncovered evidence that the demethylation pathway is actively transcribed in gut microbiomes and that animal-based diets cause to rapidly increase in abundance. CVD occurrence and abundance in humans were significantly negatively correlated. These data lead us to propose that , which is commonly regarded as a pathobiont, may play a role in mitigating cardiovascular disease. Human gut microbiomes have been shown to affect the development of a myriad of disease states, but mechanistic connections between diet, health, and microbiota have been challenging to establish. The hypothesis that reduces cardiovascular disease by circumventing TMAO production offers a clearly defined mechanism with a potential human health impact, but investigations of cell biology and ecology will be needed to fully evaluate these ideas. Links between trimethylamine--oxide (TMAO) and cardiovascular disease (CVD) have focused attention on mechanisms by which animal-based diets have negative health consequences. In a meta-analysis of data from foundational gut microbiome studies, we found evidence that specialized bacteria have and express a metabolic pathway that circumvents TMAO production and is often misannotated because it relies on genetic code expansion. This naturally occurring mechanism for TMAO attenuation is negatively correlated with CVD. Ultimately, these findings point to new avenues of research that could increase microbiome-informed understanding of human health and hint at potential biomedical applications in which specialized bacteria are used to curtail CVD development.
PubMed: 33109749
DOI: 10.1128/mSystems.00413-20 -
Shock (Augusta, Ga.) Apr 2023Background: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is...
Background: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is evidence suggesting that in the post-TBI period, the gastrointestinal tract plays a central role in driving organ and immune dysfunction and may be the source of increased circulating proinflammatory mediators. In this study, we examined systemic inflammation and bacterial dysbiosis in patients who sustained a TBI with or without polytrauma. Using a mouse model of TBI, we further show how neuroinflammation after TBI is potentially linked to disruptions in gut homeostasis such as intestinal transit and inflammation. Methods: During a study of trauma patients performed from September 1, 2018, to September 1, 2019, at a single, level 1 trauma center, TBI patients aged 21 to 95 years were enrolled. Patients were categorized as TBI based on evidence of acute abnormal findings on head computed tomographic scan, which was a combination of isolated TBI and TBI with polytrauma. Blood and stool samples were collected between 24 h and 3 days after admission. Twelve plasma samples and 10 fecal samples were used for this study. Healthy control samples were obtained from a healthy control biobank. We examined systemic inflammation and bacterial changes in patients who sustained a TBI. In addition, TBI was induced in 9- to 10-week-old male mice; we assessed neuroinflammation, and intestine transit (motility) and bacterial changes 24 h after TBI. Results: When compared with healthy controls, TBI patients had increased systemic inflammation as evidenced by increased levels of IFN-γ and MCP-1 and a trend toward an increase of IL-6 and IL-8 ( P = 0.0551 and P = 0.0549), respectively. The anti-inflammatory cytokine, IL-4, was also decreased in TBI patients. Although there was a trend of an increase in copy number of Enterobacteriaceae and a decrease in copy number of Lactobacillus in both patients and mice after TBI, these trends were not found to be significantly different. However, TBI significantly increased the copy number of another potential pathogenic bacteria Bilophila wadsworthia in TBI patients compared with healthy controls. After a moderate TBI, mice had increased expression of TNF-α, IL-6 and IL-1β, CXCL1, s100a9, and Ly6G and decreased IL-10 in the brain lesion after TBI. This accompanied decreased transit and increased TNF-α in the small intestine of mice after TBI. Conclusions: Our findings suggest that TBI increases systemic inflammation, intestinal dysfunction, and neuroinflammation. More studies are needed to confirm whether changes in intestinal motility play a role in post-TBI neuroinflammation and cognitive deficit.
Topics: Male; Humans; Interleukin-6; Tumor Necrosis Factor-alpha; Neuroinflammatory Diseases; Brain Injuries, Traumatic; Inflammation; Multiple Trauma
PubMed: 36645886
DOI: 10.1097/SHK.0000000000002082