scholarly journals Gut Microbiome Distinguishes Patients With Epilepsy From Healthy Individuals

2022 ◽  
Vol 12 ◽  
Author(s):  
Guangying Cui ◽  
Shanshuo Liu ◽  
Zhenguo Liu ◽  
Yuan Chen ◽  
Tianwen Wu ◽  
...  

Objective: The gut microecosystem is the largest microecosystem in the human body and has been proven to be linked to neurological diseases. The main objective of this study was to characterize the fecal microbiome, investigate the differences between epilepsy patients and healthy controls, and evaluate the potential efficacy of the fecal microbiome as a diagnostic tool for epilepsy.Design: We collected 74 fecal samples from epilepsy patients (Eps, n = 24) and healthy controls (HCs, n = 50) in the First Affiliated Hospital of Zhengzhou University and subjected the samples to 16S rRNA MiSeq sequencing and analysis. We set up a train set and a test set, identified the optimal microbial markers for epilepsy after characterizing the gut microbiome in the former and built a diagnostic model, then validated it in the validation group.Results: There were significant differences in microbial communities between the two groups. The α-diversity of the HCs was higher than that of the epilepsy group, but the Venn diagram showed that there were more unique operational taxonomic unit (OTU) in the epilepsy group. At the phylum level, Proteobacteria and Actinobacteriota increased significantly in Eps, while the relative abundance of Bacteroidota increased in HCs. Compared with HCs, Eps were enriched in 23 genera, including Faecalibacterium, Escherichia-Shigella, Subdoligranulum and Enterobacteriaceae-unclassified. In contrast, 59 genera including Bacteroides, Megamonas, Prevotella, Lachnospiraceae-unclassified and Blautia increased in the HCs. In Spearman correlation analysis, age, WBC, RBC, PLT, ALB, CREA, TBIL, Hb and Urea were positively correlated with most of the different OTUs. Seizure-type, course and frequency are negatively correlated with most of the different OTUs. In addition, twenty-two optimal microbial markers were identified by a fivefold cross-validation of the random forest model. In the established train set and test set, the area under the curve was 0.9771 and 0.993, respectively.Conclusion: Our study was the first to characterize the gut microbiome of Eps and HCs in central China and demonstrate the potential efficacy of microbial markers as a noninvasive biological diagnostic tool for epilepsy.

2020 ◽  
Vol 9 (8) ◽  
pp. 2403
Author(s):  
Hirokazu Fukui ◽  
Akifumi Nishida ◽  
Satoshi Matsuda ◽  
Fumitaka Kira ◽  
Satoshi Watanabe ◽  
...  

Irritable bowel syndrome (IBS) is diagnosed by subjective clinical symptoms. We aimed to establish an objective IBS prediction model based on gut microbiome analyses employing machine learning. We collected fecal samples and clinical data from 85 adult patients who met the Rome III criteria for IBS, as well as from 26 healthy controls. The fecal gut microbiome profiles were analyzed by 16S ribosomal RNA sequencing, and the determination of short-chain fatty acids was performed by gas chromatography–mass spectrometry. The IBS prediction model based on gut microbiome data after machine learning was validated for its consistency for clinical diagnosis. The fecal microbiome alpha-diversity indices were significantly smaller in the IBS group than in the healthy controls. The amount of propionic acid and the difference between butyric acid and valerate were significantly higher in the IBS group than in the healthy controls (p < 0.05). Using LASSO logistic regression, we extracted a featured group of bacteria to distinguish IBS patients from healthy controls. Using the data for these featured bacteria, we established a prediction model for identifying IBS patients by machine learning (sensitivity >80%; specificity >90%). Gut microbiome analysis using machine learning is useful for identifying patients with IBS.


2019 ◽  
Vol 5 (2) ◽  
pp. eaau8317 ◽  
Author(s):  
Peng Zheng ◽  
Benhua Zeng ◽  
Meiling Liu ◽  
Jianjun Chen ◽  
Junxi Pan ◽  
...  

Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that the SCZ microbiome itself can alter neurochemistry and neurologic function in ways that may be relevant to SCZ pathology.


2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Du ◽  
Wei Dong ◽  
Qing Yang ◽  
Xueying Yu ◽  
Jinghong Ma ◽  
...  

Emerging evidence indicates that gut dysbiosis may play a regulatory role in the onset and progression of Huntington’s disease (HD). However, any alterations in the fecal microbiome of HD patients and its relation to the host cytokine response remain unknown. The present study investigated alterations and host cytokine responses in patients with HD. We enrolled 33 HD patients and 33 sex- and age- matched healthy controls. Fecal microbiota communities were determined through 16S ribosomal DNA gene sequencing, from which we analyzed fecal microbial richness, evenness, structure, and differential abundance of individual taxa between HD patients and healthy controls. HD patients were evaluated for their clinical characteristics, and the relationships of fecal microbiota with these clinical characteristics were analyzed. Plasma concentrations of interferon gamma (IFN-γ), interleukin 1 beta (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor alpha were measured by Meso Scale Discovery (MSD) assays, and relationships between microbiota and cytokine levels were analyzed in the HD group. HD patients showed increased α-diversity (richness), β-diversity (structure), and altered relative abundances of several taxa compared to those in healthy controls. HD-associated clinical characteristics correlated with the abundances of components of fecal microbiota at the genus level. Genus Intestinimonas was correlated with total functional capacity scores and IL-4 levels. Our present study also revealed that genus Bilophila were negatively correlated with proinflammatory IL-6 levels. Taken together, our present study represents the first to demonstrate alterations in fecal microbiota and inflammatory cytokine responses in HD patients. Further elucidation of interactions between microbial and host immune responses may help to better understand the pathogenesis of HD.


2020 ◽  
Vol 4 (1) ◽  
pp. 23-30
Author(s):  
Margit Juhasz ◽  
Siwei Chen ◽  
Arash Khosrovi-Eghbal ◽  
Chloe Ekelem ◽  
Yessica Landaverde ◽  
...  

Background: Alopecia areata (AA) is caused by autoimmune attack of the hair follicle. The exact pathogenesis is unknown, but hypotheses include innate immunity imbalance, environmental exposures, genetic predisposition, and possibly the microbiome. The objective of this study was to characterize the skin and gut microbiome of AA patients, and compare microbial composition to healthy individuals. Methods: This was a pilot, case-control study. Scalp and fecal microbiome samples were collected from 25 AA patients, and 25 age, gender, and race-matched healthy controls in Southern California with no significant difference in demographic characteristics. After library preparation and identification of bacterial and fungal taxonomy, multivariant analysis was performed to compare AA and healthy microbiomes. Results: The AA scalp microbiome was significant for decreased Clostridia and Malasseziomycetes, and the gut microbiome was significant for decreased Bacteroidia and increased Bacilli (p<0.05) compared to healthy controls. Conclusions: The composition of the AA bacterial and fungal, scalp and gut microbiome is significantly different than healthy individuals. Future directions include using this data to characterize microbial changes associated with AA patient diet, relating to disease severity, and predicting disease progression, prognosis and/or therapeutic response.


2021 ◽  
Vol 51 (4) ◽  
Author(s):  
Giada De Palma ◽  
Premysl Bercik

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting up to 9% individuals globally. Although the etiology of this syndrome is likely heterogenous, it presents with its hallmark symptoms of abdominal pain and altered intestinal motility. Moreover, it is considered to be a disorder of the gut-brain interaction, and the microbiome has often been implicated as a central player in its pathophysiology. Patients with irritable bowel syndrome display altered composition and function of the gut microbiota compared to healthy controls. Microbiome directed therapies, such as probiotics, antibiotics and fecal microbiome transplantation, appear to be beneficial for both gut symptoms and psychiatric comorbidities. This review aims to recapitulate the available literature on the microbiome contribution to the pathophysiology and symptoms presentation of irritable bowel syndrome, as well as the current literature on microbiome-targeted treatments for this disease.


2019 ◽  
Author(s):  
Petar Scepanovic ◽  
Flavia Hodel ◽  
Stanislas Mondot ◽  
Valentin Partula ◽  
Allyson Byrd ◽  
...  

ABSTRACTBackgroundThe gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1,000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20 – 69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.ResultsAmong 110 demographic, clinical and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between >5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics.ConclusionIn a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals.


2021 ◽  
Author(s):  
Jin Shang ◽  
Yiding Zhang ◽  
Ruixue Guo ◽  
Wenli Liu ◽  
Jun Zhang ◽  
...  

Abstract OBJECTIVE: Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. Here we aim to establish a non-invasive diagnostic model using differential gut microbiome and to explore the relationship between gut microbiome and the pathogenesis of MN in animal experiment.DESIGN: A total of 825 fecal samples including MN patients and healthy controls (HC) were collected from Central, East and South China. We obtained crucial operational taxonomic units (OTUs) by 16S rRNA sequencing and then established a diagnostic model using five-fold cross-validation on random forest model. We subsequently validated its efficiency in cross regional cohort. MN rat model was induced by Sheep Anti-Rat Fx1A Serum and was used to explore the relationship between gut microbiome and the pathogenesis of MN.RESULTS: The diversity and richness of gut microbiome was significantly decreased in MN patients. The diagnostic model based on 7 operational OTUs achieved excellent efficiency with an area under curve (AUC) of 98.36% in training group. The different disease states and cross regional cohort validated high diagnostic efficiency. In rat model, urinary protein was significantly relieved by intestine cleaning, while increased again by fecal microbiome transplant (FMT). Interestingly, fecal microbiome from MN patients seems to play a protective role when compared with that from healthy people.CONCLUSION: Gut microbiome can be used as a non-invasive tool for MN diagnosis. The onset of MN depends partially on the existence of naturally colonized microbiome. Adaptive changes of gut microbiome during MN may help relieve urinary protein.


2021 ◽  
Author(s):  
Thomas Weber ◽  
Eva Tatzl ◽  
Karl Kashofer ◽  
Magdalena Holter ◽  
Slave Trajanoski ◽  
...  

Abstract Fibromyalgia-syndrome (FMS) is a complex disease characterized by chronic widespread pain and additional symptoms including depression, cognitive dysfunction (“fibro-fog”) and maldigestion. We examined whether FMS-related pain parameters assessed by quantitative sensory testing (QST) are related to changes of microbial diversity.We recruited 25 patients with FMS and 26 age- and sex-matched healthy controls. Medical background, food habits, psychopathology and quality of life were assessed with questionnaires. Stool samples were analyzed by 16S rRNA gene amplification and sequencing. QST was performed according to the protocol of the German Network for Neuropathic Pain.QST showed that both lemniscal and spinothalamic afferent pathways are altered in FMS patients relative to healthy controls and that peripheral as well as central pain sensitization processes are manifest. Psychometric assessment revealed enhanced scores of depression, anxiety and stress. In contrast, neither the composition nor the alpha- and beta-diversity of the fecal microbiome was changed in FMS patients.FMS patients segregate from healthy controls in various parameters of QST and psychopathology, but not in terms of composition and diversity of the fecal microbiome. Despite consideration of several confounding factors we conclude that the impact of the gut microbiome on the pathophysiology of FMS is limited.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S39-S40
Author(s):  
Jessica Breton ◽  
Vincent Tu ◽  
Ceylan Tanes ◽  
Ryan Quinn ◽  
Maire Conrad ◽  
...  

Abstract Introduction The microbiome has been suggested to play an important role in the pathogenesis and progression of Crohn’s disease (CD) with the components of a Western diet, in turn, potentially altering the gut microbiome. We conducted an observational study comparing dietary influences on the gut microbiota in children with active or quiescent CD with healthy controls. Method A prospective cross-sectional study including 58 children with CD (36 with clinically active disease, PCDAI&gt;10) between 6 and 21 years of age and 56 healthy controls was conducted. Dietary intake was estimated using a 3 day dietary recall. The following measurements were selected to assess diet quality based on 1) consumption measured against the American Dietary Guidelines (HEI-2015) (a higher score over 100 representing a healthier diet) and 2) inflammatory potential (DII) (a higher score representing a more pro-inflammatory diet). Compositional and functional analysis of the fecal microbiome was performed using shotgun metagenomics DNA sequencing and associations with dietary indices was modelled with linear mixed-effects models after controlling for confounding effects. Results Energy and dietary intakes between the healthy and CD cohorts were similar with the exception of fiber intake (%DRI), which was significantly lower in children with active CD than healthy controls (41.4 vs. 50.4, P=0.03). A similarly low total HEI-2015 score was found in patients with active and quiescent CD in comparison to healthy controls respectively (47.6 vs. 51.0 vs. 49.7, P= 0.41). A pro-inflammatory total DII score was found in all three groups (0.48 vs. 0.41 vs. 0.51, P=0.87). At the microbiome level, HEI-2015 (P=0.009) and DII (P= 0.024) showed significant positive and negative correlations with alpha-diversity, respectively, in children with quiescent CD only (Figure 1). In children with active CD, Proteobacteria Enterobacteriaceae displayed a significant positive correlation with DII (P= 0.006) (Figure 2), where a more pro-inflammatory DII score correlated with higher Escherichia coli relative abundances (P= 0.006). Conclusions To our knowledge, this is the largest study assessing dietary indices to evaluate the effects of diet quality on the gut microbiome in children with CD. Our results suggest important differential dietary influences on the gut microbiome according to clinical disease status in comparison to healthy children, with low quality diet and higher pro-inflammatory potential being associated with overall lower microbiome diversity in inactive CD and an enrichment in Proteobacteria, specifically E. coli, in children with active CD. Current ongoing functional analyses, including metabolomics, will shed light on the underlying diet-microbiota interactions implicated in CD and potentially assist clinical nutrition guidance and development of new dietary therapeutic trials.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anthony Patrizz ◽  
Antonio Dono ◽  
Soheil Zorofchian ◽  
Gabriella Hines ◽  
Takeshi Takayasu ◽  
...  

AbstractThe gut microbiome is fundamental in neurogenesis processes. Alterations in microbial constituents promote inflammation and immunosuppression. Recently, in immune-oncology, specific microbial taxa have been described to enhance the effects of therapeutic modalities. However, the effects of microbial dysbiosis on glioma are still unknown. The aim of this study was to explore the effects of glioma development and Temozolomide (TMZ) on fecal microbiome in mice and humans. C57BL/6 mice were implanted with GL261/Sham and given TMZ/Saline. Fecal samples were collected longitudinally and analyzed by 16S rRNA sequencing. Fecal samples were collected from healthy controls as well as glioma patients at diagnosis, before and after chemoradiation. Compared to healthy controls, mice and glioma patients demonstrated significant differences in beta diversity, Firmicutes/Bacteroides (F/B) ratio, and increase of Verrucomicrobia phylum and Akkermansia genus. These changes were not observed following TMZ in mice. TMZ treatment in the non-tumor bearing mouse-model diminished the F/B ratio, increase Muribaculaceae family and decrease Ruminococcaceae family. Nevertheless, there were no changes in Verrucomicrobia/Akkermansia. Glioma development leads to gut dysbiosis in a mouse-model, which was not observed in the setting of TMZ. These findings seem translational to humans and warrant further study.


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