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BMC Medicine Jul 2021Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG...
BACKGROUND
Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients.
METHODS
Our study recruited 53 pediatric MG patients and 46 age- and gender-matched healthy controls (HC). We sequenced the fecal samples of recruited individuals using whole-genome shotgun sequencing and analyzed the data with in-house bioinformatics pipeline.
RESULTS
We built an MG disease classifier based on the abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale. The classifier obtained 94% area under the curve (AUC) in cross-validation and 84% AUC in the independent validation cohort. Gut microbiome analysis revealed the presence of human adenovirus F/D in 10 MG patients. Significantly different pathways and gene families between MG patients and HC belonged to P. copri, Clostridium bartlettii, and Bacteroides massiliensis. Based on functional annotation, we found that the gut microbiome affects the production of short-chain fatty acids (SCFAs), and we confirmed the decrease in SCFA levels in pediatric MG patients via serum tests.
CONCLUSIONS
The study indicated that altered fecal microbiota might play vital roles in pediatric MG's pathogenesis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric MG.
Topics: Adult; Bacteroides; Child; Clostridiales; Feces; Firmicutes; Fusobacterium; Gastrointestinal Microbiome; Humans; Metagenome; Myasthenia Gravis; Prevotella; RNA, Ribosomal, 16S
PubMed: 34233671
DOI: 10.1186/s12916-021-02034-0 -
Biomedicine & Pharmacotherapy =... Jan 2022Metformin modifies the gut microbiome in type 2 diabetes and gastrointestinal tolerance to metformin could be mediated by the gut microbiome.
OBJECTIVE
Metformin modifies the gut microbiome in type 2 diabetes and gastrointestinal tolerance to metformin could be mediated by the gut microbiome.
METHODS
We enrolled 35 patients with type 2 diabetes not receiving treatment with metformin due to suspected gastrointestinal intolerance. Metformin was reintroduced at 425 mg, increasing 425 mg every two weeks until reaching 1700 mg per day. According to the occurrence of metformin-related gastrointestinal symptoms, patients were classified into three groups: early intolerance, non-tolerant, and tolerant. Gut microbiota was profiled with 16 S rRNA. This sequencing aimed to determine the differences in the baseline gut microbiota in all groups and prospectively in the tolerant and non-tolerant groups.
RESULTS
The classification resulted in 15 early intolerant, 10 tolerant, and 10 non-tolerant subjects. Early tolerance was characterized by a higher abundance of Subdoligranulum; while Veillonella and Serratia were higher in the non-tolerant group. The tolerant group showed enrichment of Megamonas, Megamonas rupellensis, and Phascolarctobacterium spp; Ruminococcus gnavus was lower in the longitudinal analysis. At the end point Prevotellaceae, Prevotella stercorea, Megamonas funiformis, Bacteroides xylanisolvens, and Blautia producta had a higher relative abundance in the tolerant group compared to the non-tolerant group. Subdoligranulum, Ruminococcus torques_1, Phascolarctobacterium faecium, and Eubacterium were higher in the non-tolerant group. The PICRUSt analysis showed a lower activity of the amino acid biosynthesis pathways and a higher sugar degradation pathway in the intolerant groups.
CONCLUSIONS
Gut microbiota of subjects with gastrointestinal intolerance depicted taxonomic and functional differences compared to tolerant patients, and this changed differently after metformin administration.
Topics: Aged; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prospective Studies
PubMed: 34844104
DOI: 10.1016/j.biopha.2021.112448 -
Annals of Palliative Medicine Oct 2021Type 2 diabetes mellitus (T2DM) is a major social and public health problem which may be induced by intestinal flora imbalance through inflammatory response, and the...
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a major social and public health problem which may be induced by intestinal flora imbalance through inflammatory response, and the specific mechanism remains unclear. In this study, we aim to explore the interaction network of intestinal flora and cell inflammation in T2DM.
METHODS
This a case-control study. Patients with T2DM was the case group and healthy people as control. The differences of cytokine expression levels between patients with T2DM and healthy controls were assessed by using flow cytometry. The diversity and abundance of intestinal flora were evaluated by using 16S rRNA three-generation full-length sequencing technology.
RESULTS
A total of 29 patients with T2DM and 28 healthy controls were included for analysis. Compared with the healthy control group, the expression levels of plasma cytokine interleukin-2 (IL-2) (P=0.0000006), IL-6 (P=0.000193), tumor necrosis factor α (TNF-α) (P=0.016), interferon-γ (IFN-γ) (P=0.000036) and interleukin-17 (IL-17) (P=0.004) were significantly up-regulated in T2DM patients, and the abundance of Megamonas_funiformis (P=0.0016) and Escherichia (P=0.049) in the intestine were significantly increased. In contrast, the abundance of Bacteroides_stercoris (P=0.0068), Bacteroides_uniformis (P=0.033), and Phascolarctobacterium_faecium (P=0.033) were decreased in T2DM patients. Further, differentially expressed Escherichia had a positive correlation with IFN-γ (r=0.73) by Pearson correlation analysis.
CONCLUSIONS
The interaction network between the intestinal bacteria Escherichia and the cytokine IFN-γ may drive inflammation in visceral adipose tissue (VAT), indicating insulin signal transduction can be inhibited in adipocytes to induce insulin resistance.
Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Escherichia; Humans; Interferon-gamma; Intestines; RNA, Ribosomal, 16S
PubMed: 34763485
DOI: 10.21037/apm-21-2318 -
Veterinary Sciences Nov 2022The gut microbiome exerts important functions on host health maintenance, whereas excessive antibiotic use may cause gut flora dysfunction resulting in serious disease...
The gut microbiome exerts important functions on host health maintenance, whereas excessive antibiotic use may cause gut flora dysfunction resulting in serious disease and dysbiosis. Colistin is a broad-spectrum antibiotic with serious resistance phenomena. However, it is unclear whether colistin alters the gastrointestinal tract microbiome in piglets. In this study, 16s rDNA-based metagenome analyses were used to assess the effects of colistin on the modification of the piglet microbiome in the stomach, duodenum, jejunum, cecum, and feces. Both α- and β-diversity indices showed that colistin modified microbiome composition in these gastrointestinal areas. In addition, colistin influenced microbiome composition at the phylum and genus levels. At the species level, colistin upregulated , , , , and abundance, but downregulated , , , , , , and abundance in stomachs. Colistin-fed piglets showed an increased abundance of , , , and , but , , , , and abundance was decreased in the cecum. In feces, colistin promoted , , , , and abundance when compared with controls. Taken together, colistin modified the microbiome composition of gastrointestinal areas in piglets. This study provides new clinical rationalization strategies for colistin on the maintenance of animal gut balance and human public health.
PubMed: 36548827
DOI: 10.3390/vetsci9120666 -
Frontiers in Neuroscience 2019Multiple system atrophy (MSA) is a fatal neurodegenerative disease, and the pathogenesis is still quite challenging. Emerging evidence has shown that the...
Multiple system atrophy (MSA) is a fatal neurodegenerative disease, and the pathogenesis is still quite challenging. Emerging evidence has shown that the brain-gut-microbiota axis served a pivotal role in neurological diseases; however, researches utilizing metagenomic sequencing to analyze the alteration in gut microbiota of MSA patients were quite rare. Here, we carried out metagenomic sequencing in feces of 15 MSA patients and 15 healthy controls, to characterize the alterations in gut microbial composition and function of MSA patients in mainland China. The results showed that gut microbial community of MSA patients was significantly different from healthy controls, characterized by increased genus and species , , , , and , while decreased genera , , , and and species , , , , , and . Further, functional analysis based on the KEGG database revealed aberrant functional pathways in fecal microbiome of MSA patients. In conclusion, our findings provided evidence for dysbiosis in gut microbiota of Chinese MSA cohorts and helped develop new testable hypotheses on pathophysiology of MSA.
PubMed: 31680836
DOI: 10.3389/fnins.2019.01102 -
NPJ Biofilms and Microbiomes Jan 2024
PubMed: 38287023
DOI: 10.1038/s41522-024-00480-1 -
Frontiers in Physiology 2022The nutrient availability and supplementation of dietary phosphorus (P) and calcium (Ca) in avian feed, especially in laying hens, plays a vital role in phytase...
The nutrient availability and supplementation of dietary phosphorus (P) and calcium (Ca) in avian feed, especially in laying hens, plays a vital role in phytase degradation and mineral utilization during the laying phase. The required concentration of P and Ca peaks during the laying phase, and the direct interaction between Ca and P concentration shrinks the availability of both supplements in the feed. Our goal was to characterize the active microbiota of the entire gastrointestinal tract (GIT) (crop, gizzard, duodenum, ileum, caeca), including digesta- and mucosa-associated communities of two contrasting high-yielding breeds of laying hens (Lohmann Brown Classic, LB; Lohmann LSL-Classic, LSL) under different P and Ca supplementation levels. Statistical significances were observed for breed, GIT section, Ca, and the interaction of GIT section x breed, P x Ca, Ca x breed and P x Ca x breed ( < 0.05). A core microbiota of five species was detected in more than 97% of all samples. They were represented by an uncl. (average relative abundance (av. abu.) 12.1%), (av. abu. 10.8%), (av. abu. 6.8%), (av. abu. 4.5%), and an uncl. (av. abu. 1.1%). Our findings indicated that Ca and P supplementation levels 20% below the recommendation have a minor effect on the microbiota compared to the strong impact of the bird's genetic background. Moreover, a core active microbiota across the GIT of two high-yielding laying hen breeds was revealed for the first time.
PubMed: 36213242
DOI: 10.3389/fphys.2022.951350 -
Ecotoxicology and Environmental Safety Jan 2024Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) has been reported to be linked to a series of adverse health outcomes in mothers and their children. As...
Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) has been reported to be linked to a series of adverse health outcomes in mothers and their children. As the gut microbiota is a sensitive biomarker for assessing the toxicity of environmental contaminants, this study attempted to investigate whether prenatal PFASs exposure was associated with the gut microbiota of infants. Based on the Shanghai-Minhang Birth Cohort Study, this prospective cohort study included 69 mother-infant pairs. Fasting blood samples were collected from pregnant women for the PFASs assay. We collected fecal samples of infants at 1 year of age and analyzed the V3-V4 hypervariable region of the bacterial 16 S rRNA gene by high-throughput sequencing. Among the detected 11 PFASs, the concentration of perfluorooctanoic acid (22.19 ng/mL) was the highest, followed by perfluorooctane sulfonic acid (12.08 ng/mL). Compared with infants whose mothers' total PFASs concentrations during pregnancy were at the 40th percentile or lower (reference group), the species richness and diversity of microbiota were lower in infants prenatally exposed to a high level of PFASs (the sum of PFASs concentrations above the 60th percentile). Prenatal exposure to PFASs was associated with a higher proportion of Acidaminococcaceae, Acidaminococcus, Megamonas, Megasphaera micronuciformis and Megamonas funiformis in infants. The changes of the species have been suggested to be associated with immune and metabolic dysfunction in humans. Functional alterations of gut microbiota due to PFASs exposure were dominated by an enrichment of butanoate metabolism. Our preliminary findings may shed light on the potential role of the microbiota underlying the well-known impact of prenatal PFASs exposure on health outcomes of humans in later life.
Topics: Female; Humans; Infant; Pregnancy; Alkanesulfonic Acids; China; Cohort Studies; Environmental Pollutants; Fluorocarbons; Gastrointestinal Microbiome; Prenatal Exposure Delayed Effects; Prospective Studies; Vitamins
PubMed: 38159339
DOI: 10.1016/j.ecoenv.2023.115891