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Journal of Molecular Medicine (Berlin,... Oct 2021A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of...
A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). The anti-microbial ELISA assays follow on prior human brain tissue RNA sequencing studies that established multiple sclerosis (MS) microbial candidates. Lysates included in the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans. CSF responses from patients with demyelinating diseases (DD, N = 14) were compared to those with other neurological diseases (OND, N = 8) and controls (N = 13). Commercial positive and negative control CSF specimens were run with each assay. ELISA index values were derived for each specimen against each of the 10 bacterial lysates. CSF reactivity was significantly higher in the DD group compared to the controls against Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Four of the 11 tested DD group subjects had elevated antibody indexes against at least one of the 10 bacterial species, suggesting intrathecal antibody production. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. KEY MESSAGES: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases, including multiple sclerosis and acute disseminated encephalomyelitis. CSF reactivity was significantly higher in the demyelination group compared to the controls against the bacteria Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Several of the demyelination subjects had elevated antibody indexes against at least one of the 10 antigens, suggesting at least limited intrathecal production of anti-bacterial antibodies. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients.
Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Autoantibodies; Bacteria; Cerebrospinal Fluid; Female; Humans; Immunoglobulin G; Male; Middle Aged; Multiple Sclerosis; Polyradiculoneuropathy; Young Adult
PubMed: 34100959
DOI: 10.1007/s00109-021-02085-z -
Journal of Translational Medicine May 2021The fecal microbiota in pancreatic ductal adenocarcinoma (PDAC) and in autoimmune pancreatitis (AIP) patients remains largely unknown. We aimed to characterize the fecal...
BACKGROUND
The fecal microbiota in pancreatic ductal adenocarcinoma (PDAC) and in autoimmune pancreatitis (AIP) patients remains largely unknown. We aimed to characterize the fecal microbiota in patients with PDAC and AIP, and explore the possibility of fecal microbial biomarkers for distinguishing PDAC and AIP.
METHODS
32 patients with PDAC, 32 patients with AIP and 32 age- and sex-matched healthy controls (HC) were recruited and the fecal microbiotas were analyzed through high-throughput metagenomic sequencing. Alterations of fecal short-chain fatty acids were measured using gas chromatographic method.
RESULTS
Principal coordinate analysis (PCoA) revealed that microbial compositions differed significantly between PDAC and HC samples; whereas, AIP and HC individuals tended to cluster together. Significant reduction of phylum Firmicutes (especially butyrate-producing bacteria, including Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis) and significant increase of phylum Proteobacteria (especially Gammaproteobacteria) were observed only among PDAC samples. At species level, when compared with HC samples, we revealed 24 and 12 differently enriched bacteria in PDAC and AIP, respectively. Functional analysis showed a depletion of short-chain fatty acids synthesis associated KO modules (e.g. Wood-Ljungdahl pathway) and an increase of KO modules associated with bacterial virulence (e.g. type II general secretion pathway). Consistent with the downregulation of butyrate-producing bacteria, gas chromatographic analysis showed fecal butyrate content was significantly decreased in PDAC group. Eubacterium rectale, Eubacterium ventrisum and Odoribacter splanchnicus were among the most important biomarkers in distinguishing PDAC from HC and from AIP individuals. Receiver Operating Characteristic analysis showed areas under the curve of 90.74% (95% confidence interval [CI] 86.47-100%), 88.89% (95% CI 73.49-100%), and 76.54% (95% CI 52.5-100%) for PDAC/HC, PDAC/AIP and AIP/HC, respectively.
CONCLUSIONS
In conclusion, alterations in fecal microbiota and butyrate of patients with PDAC suggest an underlying role of gut microbiota for the pathogenesis of PDAC. Fecal microbial and butyrate as potential biomarkers may facilitate to distinguish patients with PDAC from patients with AIP and HCs which worth further validation.
Topics: Autoimmune Diseases; Autoimmune Pancreatitis; Bacteroidetes; Clostridiales; Diagnosis, Differential; Feces; Humans; Pancreatic Neoplasms
PubMed: 34006295
DOI: 10.1186/s12967-021-02882-7 -
BMC Microbiology May 2021Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an...
BACKGROUND
Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis.
RESULTS
In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect.
CONCLUSIONS
Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.
Topics: Bacteria; Biodiversity; China; Colitis, Ulcerative; DNA, Bacterial; Dysbiosis; Gastrointestinal Microbiome; Humans; Intestinal Mucosa
PubMed: 33947329
DOI: 10.1186/s12866-021-02201-6 -
Cell Host & Microbe Jun 2021Microbiota play critical roles in regulating colitis and colorectal cancer (CRC). However, it is unclear how the microbiota generate protective immunity against these...
Microbiota play critical roles in regulating colitis and colorectal cancer (CRC). However, it is unclear how the microbiota generate protective immunity against these disease states. Here, we find that loss of the innate and adaptive immune signaling molecule, TAK1, in myeloid cells (Tak1) yields complete resistance to chemical-induced colitis and CRC through microbiome alterations that drive protective immunity. Tak1 mice exhibit altered microbiota that are critical for resistance, with antibiotic-mediated disruption ablating protection and Tak1 microbiota transfer conferring protection against colitis or CRC. The altered microbiota of Tak1 mice promote IL-1β and IL-6 signaling pathways, which are required for induction of protective intestinal Th17 cells and resistance. Specifically, Odoribacter splanchnicus is abundant in Tak1 mice and sufficient to induce intestinal Th17 cell development and confer resistance against colitis and CRC in wild-type mice. These findings identify specific microbiota strains and immune mechanisms that protect against colitis and CRC.
Topics: Animals; Bacteroidetes; Colitis; Colorectal Neoplasms; Cytokines; Disease Models, Animal; Feces; Female; Gastrointestinal Microbiome; Host Microbial Interactions; Immunity, Innate; Interleukin-1beta; Interleukin-6; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells; Signal Transduction; Th17 Cells
PubMed: 33894128
DOI: 10.1016/j.chom.2021.03.016 -
Frontiers in Microbiology 2020, belonging to the order Bacteroidales, is a common, short-chain fatty acid producing member of the human intestinal microbiota. A decreased abundance of has been...
, belonging to the order Bacteroidales, is a common, short-chain fatty acid producing member of the human intestinal microbiota. A decreased abundance of has been linked to different microbiota-associated diseases, such as non-alcoholic fatty liver disease, cystic fibrosis and inflammatory bowel disease (IBD). The type strain of has been genome-sequenced, but otherwise very little is known about this anaerobic bacterium. The species surfaces in many microbiota studies and, consequently, comprehension on its interactions with the host is needed. In this study, we isolated a novel strain of from a healthy fecal donor, identified it by genome sequencing and addressed its adhesive, epithelium reinforcing and immunoregulatory properties. Our results show that strain 57 is non-adherent to enterocytes or mucus, does not reinforce nor compromise Caco-2 monolayer integrity and most likely harbors penta-acylated, less endotoxic lipid A as part of its lipopolysaccharide (LPS) structure based on the lack of gene and results on low-level NF-κB activity. The studies by transmission electron microscopy revealed that produces outer membrane vesicles (OMV). cells, culture supernatant i.e., spent medium or OMVs did not induce interleukin-8 (IL-8) response in HT-29 enterocyte cells suggesting a very low proinflammatory capacity. On the contrary, the treatment of HT-29 cells with cells, spent medium or OMVs prior to exposure to LPS elicited a significant decrease in IL-8 production as compared to LPS treatment alone. Moreover, spent supernatant induced IL-10 production by immune cells, suggesting anti-inflammatory activity. Our findings indicate that and its effector molecules transported in OMVs could potentially exert anti-inflammatory action in the gut epithelium. Taken together, seems to be a commensal with a primarily beneficial interaction with the host.
PubMed: 33281770
DOI: 10.3389/fmicb.2020.575455 -
Frontiers in Neuroscience 2020Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition that may be related to an imbalance of neural transmitters. The gut microbiota is the...
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition that may be related to an imbalance of neural transmitters. The gut microbiota is the largest ecosystem in the human body, and the brain-gut axis theory proposes that the gut microbiome can affect brain function in multiple ways. The purpose of this study was to explore the gut microbiota in children with ADHD and assess the possible role of the gut microbiota in disease pathogenesis to open new avenues for ADHD treatment.
METHODS
A case-control design was used. We enrolled 17 children aged 6-12 years with ADHD who were treated in the Pediatric Outpatient Department of the First Medical Center of the Chinese PLA General Hospital from January to June, 2019. Seventeen children aged 6-12 years were selected as the healthy control (HC) group. Fecal samples of cases and controls were analyzed by shotgun metagenomics sequencing. Alpha diversity and the differences in the relative abundances of bacteria were compared between the two groups. Functional annotations were performed for the microbiota genes and metabolic pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG).
RESULTS
There was no significant difference in the alpha diversity of gut microbiota between the ADHD and HC groups. Compared with HCs, and were significantly reduced in children with ADHD ( < 0.05), and were significantly increased [linear discriminant analysis (LDA) > 2]. At the species level, , , and were significantly reduced in the ADHD group ( < 0.05), while , , , and were increased ( < 0.05). Metabolic pathway analysis revealed significant between-group differences in the metabolic pathways of neurotransmitters (e.g., serotonin and dopamine) ( < 0.05).
CONCLUSION
Composition differences of gut microbiota in subjects with ADHD may contribute to brain-gut axis alterations and affect neurotransmitter levels, which could contribute to ADHD symptoms.
PubMed: 32132899
DOI: 10.3389/fnins.2020.00127 -
British Journal of Haematology Jun 2020We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against...
We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against acute graft-versus-host disease (aGVHD). Because dysbiosis has been associated with aGVHD, we hypothesized that these SNPs may have a gut microbiota signature. In Lasso regression analysis of 248 healthy individuals, rs4415345G was associated with a higher abundance of Odoribacter splanchnicus, an anaerobic butyrogenic commensal. In multivariable analysis of data from 613 allogeneic haematopoietic cell transplant recipients, peri-engraftment presence of O. splanchnicus was associated with ~50% lower risk for grade II-IV aGVHD (hazard ratio 0·53, 95% confidence interval 0·28-1·00, P = 0·05). O. splanchnicus may protect rs4415345G individuals against aGVHD.
Topics: Acute Disease; Adolescent; Adult; Allografts; Bacteroidetes; Bone Marrow Transplantation; Cord Blood Stem Cell Transplantation; Dysbiosis; Female; Gastrointestinal Microbiome; Graft vs Host Disease; Humans; Male; Metagenome; Paneth Cells; Peripheral Blood Stem Cell Transplantation; Polymorphism, Single Nucleotide; Risk; Symbiosis; Young Adult; alpha-Defensins
PubMed: 32086815
DOI: 10.1111/bjh.16458 -
Frontiers in Microbiology 2018The characteristics of flora in the intestine of an animal, including the number and abundance of different microbial species and their functions, are closely related to...
The characteristics of flora in the intestine of an animal, including the number and abundance of different microbial species and their functions, are closely related to the diets of the animal and affect the physical condition of the host. The Malayan pangolin () is an endangered species that specializes in myrmecophagy. Analyzing the microbiome in the intestine of the pangolin is imperative to protect this species. By sequencing the metagenomes of the feces of four pangolins, we constructed a non-redundant catalog of 211,868 genes representing 1,811 metagenomic species. Taxonomic annotation revealed that Bacteroidetes (49.9%), Proteobacteria (32.2%), and Firmicutes (12.6%) are the three main phyla. The annotation of gene functions identified 5,044 genes from 88 different glycoside hydrolase (GH) families in the Carbohydrate-Active enZYmes database and 114 gene modules related to chitin-degrading enzymes, corresponding to the catalytic domains of GH18 family enzymes, containing chitinase genes of classes III and V in the dataset. Fourteen gene modules corresponded to the catalytic domains of GH19 family enzymes, containing chitinase genes of classes I, II, and IV. These genes were found in 37 species belonging to four phyla: Bacteroidetes, Cyanobacteria, Firmicutes, and Proteobacteria. Moreover, when the metabolic pathways of these genes were summarized, 41,711 genes were associated with 147 unique KEGG metabolic pathways, and these genes were assigned to two Gene Ontology terms: metabolic process and catalytic activity. We also found several species that likely play roles in the digestion of cellulose and may be able to degrade chitin, including , and . In addition, we identified some intestinal microflora and genes related to diseases in pangolins. Twenty-seven species were identified by STAMP analysis as differentially abundant in healthy and diseased animals: 20 species, including and , were more abundant in healthy pangolins, while seven species, including , and , were more abundant in diseased pangolins. These results will support the efforts to conserve pangolins.
PubMed: 30532742
DOI: 10.3389/fmicb.2018.02793 -
Infection and Immunity Jan 2015Capnocytophaga canimorsus, a dog mouth commensal and a member of the Bacteroidetes phylum, causes rare but often fatal septicemia in humans that have been in contact...
Capnocytophaga canimorsus, a dog mouth commensal and a member of the Bacteroidetes phylum, causes rare but often fatal septicemia in humans that have been in contact with a dog. Here, we show that C. canimorsus strains isolated from human infections grow readily in heat-inactivated human serum and that this property depends on a typical polysaccharide utilization locus (PUL), namely, PUL3 in strain Cc5. PUL are a hallmark of Bacteroidetes, and they encode various products, including surface protein complexes that capture and process polysaccharides or glycoproteins. The archetype system is the Bacteroides thetaiotaomicron Sus system, devoted to starch utilization. Unexpectedly, PUL3 conferred the capacity to acquire iron from serotransferrin (STF), and this capacity required each of the seven encoded proteins, indicating that a whole Sus-like machinery is acting as an iron capture system (ICS), a new and unexpected function for Sus-like machinery. No siderophore could be detected in the culture supernatant of C. canimorsus, suggesting that the Sus-like machinery captures iron directly from transferrin, but this could not be formally demonstrated. The seven genes of the ICS were found in the genomes of several opportunistic pathogens from the Capnocytophaga and Prevotella genera, in different isolates of the severe poultry pathogen Riemerella anatipestifer, and in strains of Bacteroides fragilis and Odoribacter splanchnicus isolated from human infections. Thus, this study describes a new type of ICS that evolved in Bacteroidetes from a polysaccharide utilization system and most likely represents an important virulence factor in this group.
Topics: Bacteroidetes; Gram-Negative Bacterial Infections; Humans; Iron; Membrane Transport Proteins; Multigene Family; Serum
PubMed: 25368114
DOI: 10.1128/IAI.02042-14 -
Standards in Genomic Sciences Apr 2011Odoribacter splanchnicus (Werner et al. 1975) Hardham et al. 2008 is the type species of the genus Odoribacter, which belongs to the family Porphyromonadaceae in the...
Odoribacter splanchnicus (Werner et al. 1975) Hardham et al. 2008 is the type species of the genus Odoribacter, which belongs to the family Porphyromonadaceae in the order 'Bacteroidales'. The species is of interest because members of the Odoribacter form an isolated cluster within the Porphyromonadaceae. This is the first completed genome sequence of a member of the genus Odoribacter and the fourth sequence from the family Porphyromonadaceae. The 4,392,288 bp long genome with its 3,672 protein-coding and 74 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.
PubMed: 21677857
DOI: 10.4056/sigs.1714269