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Bioinformatics Analysis of Gut Microbiota and CNS Transcriptome in Virus-Induced Acute Myelitis and Chronic Inflammatory Demyelination; Potential Association of Distinct Bacteria With CNS IgA Upregulation.

ABSTRACT: Virus infections have been associated with acute and chronic inflammatory central nervous system (CNS) diseases, e.g., acute flaccid myelitis (AFM) and multiple sclerosis (MS), where animal models support the pathogenic roles of viruses. In the spinal cord, Theiler's murine encephalomyelitis virus (TMEV) induces an AFM-like disease with gray matter inflammation during the acute phase, 1 week post infection (p.i.), and an MS-like disease with white matter inflammation during the chronic phase, 1 month p.i. Although gut microbiota has been proposed to affect immune responses contributing to pathological conditions in remote organs, including the brain pathophysiology, its precise role in neuroinflammatory diseases is unclear. We infected SJL/J mice with TMEV; harvested feces and spinal cords on days 4 (before onset), 7 (acute phase), and 35 (chronic phase) p.i.; and examined fecal microbiota by 16S rRNA sequencing and CNS transcriptome by RNA sequencing. Although TMEV infection neither decreased microbial diversity nor changed overall microbiome patterns, it increased abundance of individual bacterial genera Marvinbryantia on days 7 and 35 p.i. and Coprococcus on day 35 p.i., whose pattern-matching with CNS transcriptome showed strong correlations: Marvinbryantia with eight T-cell receptor (TCR) genes on day 7 and with seven immunoglobulin (Ig) genes on day 35 p.i.; and Coprococcus with gene expressions of not only TCRs and IgG/IgA, but also major histocompatibility complex (MHC) and complements. The high gene expression of IgA, a component of mucosal immunity, in the CNS was unexpected. However, we observed substantial IgA positive cells and deposition in the CNS, as well as a strong correlation between CNS IgA gene expression and serum anti-TMEV IgA titers. Here, changes in a small number of distinct gut bacteria, but not overall gut microbiota, could affect acute and chronic immune responses, causing AFM- and MS-like lesions in the CNS. Alternatively, activated immune responses would alter the composition of gut microbiota.

SUBMITTER: Omura S

PROVIDER: S-EPMC7358278 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Bioinformatics Analysis of Gut Microbiota and CNS Transcriptome in Virus-Induced Acute Myelitis and Chronic Inflammatory Demyelination; Potential Association of Distinct Bacteria With CNS IgA Upregulation.

Omura Seiichi S Sato Fumitaka F Park Ah-Mee AM Fujita Mitsugu M Khadka Sundar S Nakamura Yumina Y Katsuki Aoshi A Nishio Kazuto K Gavins Felicity N E FNE Tsunoda Ikuo I

Frontiers in immunology 20200707

Virus infections have been associated with acute and chronic inflammatory central nervous system (CNS) diseases, e.g., acute flaccid myelitis (AFM) and multiple sclerosis (MS), where animal models support the pathogenic roles of viruses. In the spinal cord, Theiler's murine encephalomyelitis virus (TMEV) induces an AFM-like disease with gray matter inflammation during the acute phase, 1 week post infection (p.i.), and an MS-like disease with white matter inflammation during the chronic phase, 1 ...[more]

PMID: 32733435

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Project description:Introduction: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a serious neurological autoimmune disorder caused by autoantibodies with diverse clinical manifestations, may simultaneously onset with antimyelin oligodendrocyte glycoprotein (MOG) demyelination after recurrent central nervous system (CNS) demyelination. Case Report: We present a case of anti-NMDAR encephalitis combining with anti-MOG CNS demyelination following recurrent CNS demyelination. A 38-year-old man admitted to hospital developed epileptic seizures following recurrent episodes of cross-sensory disturbance and dizziness. Magnetic resonance imaging (MRI) showed a demyelinating lesion in the right brainstem initially. Despite a good response to methylprednisolone pulse therapy at the beginning, the patient still had relapses and progression after corticosteroid reduction or withdrawal. Then brain MRI discovered new serpentine lesions involving extensive cerebral cortex on his second relapse. Repeat autoantibodies test indicated cerebrospinal fluid (CSF) NMDAR antibodies coexisted with MOG-Abs simultaneously, suggesting the diagnosis of anti-NMDAR encephalitis with anti-MOG CNS demyelination. Results: After a definite diagnosis, the patient was treated with mycophenolate mofetil (MMF) and corticosteroid. He was discharged after his symptoms ameliorated. No neurological sequels remained, and there were no effects on his activities of daily living after 6 months of immunoregulatory therapy of MMF and corticosteroid. Conclusion: For individuals with recurrent CNS demyelination, especially combining with cortical encephalitis, repeated detection of autoantibodies against AE, and demyelination in CSF/serum can be helpful to enable a definite early diagnosis. For patients who suffer from anti-NMDAR encephalitis combining with anti-MOG CNS demyelination, second-line immunotherapy is recommended when first-line treatment such as steroids, intravenous immunoglobulin G (IVIG) and plasma exchange has been proven ineffective to prevent the relapse of disease.

Project description:Simple Summary The ever-growing human population is increasingly demanding more fish. As a response, aquaculture has become the fastest growing industry in its sector. Alternatives to fish meal, an unsustainable commodity used as the main protein source for carnivorous species, are urgently needed in aquafeeds. Recently, in Europe, seven insect species have been approved as potential ingredients for animal feeds, including fish feed. However, chitin, one of the components of an insect’s exoskeleton, is indigestible for several economically valuable fish species, decreasing fish performance upon inclusion. This work aimed to isolate, from the European sea bass gastrointestinal tract, probiotic bacteria capable of producing chitinases to improve the use of diets containing high levels of insect meal. Based on the enhanced adaptability of gut microbial communities and the selective pressure of chitin-enriched diets on fish gut microbiota, bacteria were first isolated from the gastrointestinal tract of European sea bass fed chitin-enriched diets. Isolates were then comprehensively screened in vitro for important traits such as their ability to utilize chitin, gut-survival aptitude, and biosafety-related issues required to be considered eligible as probiotics by the European Food Safety Authority (EFSA). Abstract Insect meal (IM), recently authorized for use in aquafeeds, positions itself as a promising commodity for aquafeed inclusion. However, insects are also rich in chitin, a structural polysaccharide present in the exoskeleton, which is not digested by fish, resulting in lower fish performance. Through the application of a dietary pressure, this study aimed to modulate European sea bass gut microbiota towards the enrichment of chitinolytic bacteria to allow the isolation of novel probiotics capable of improving the use of IM-containing diets, overcoming chitin drawbacks. Five isoproteic (44%) and isolipidic (18%) diets were used: a fish meal (FM)-based diet (diet CTR), a chitin-supplemented diet (diet CHIT5), and three diets with either 25% of Hermetia illucens and Tenebrio molitor larvae meals (HM25 and TM25, respectively) or H. illucens exuviae meal (diet HEM25) as partial FM substitutes. After an 8-week feeding trial, the results showed a clear modulatory effect towards spore-forming bacteria by HM25 and HEM25 diets, with the latter being responsible for the majority of the chitinolytic fish isolates (FIs) obtained. Sequential evaluation of the FI hemolytic activity, antibiotic resistance, total chitinolytic activity, sporulation, and survival in gastrointestinal-like conditions identified FI645 and FI658 as the most promising chitinolytic probiotics for in vivo application.

Dataset Information

Bioinformatics Analysis of Gut Microbiota and CNS Transcriptome in Virus-Induced Acute Myelitis and Chronic Inflammatory Demyelination; Potential Association of Distinct Bacteria With CNS IgA Upregulation.

Publications

Bioinformatics Analysis of Gut Microbiota and CNS Transcriptome in Virus-Induced Acute Myelitis and Chronic Inflammatory Demyelination; Potential Association of Distinct Bacteria With CNS IgA Upregulation.

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