Gut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids.

A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host-microbe interactions in the gut remain largely unknown. Here we report that the gut commensal Christensenella minuta modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of C. minuta alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for C. minuta and acylated bile acids in metabolic diseases.

[Fluoroquinolone associated myasthenia gravis exacerbation: clinical analysis of 9 cases].

OBJECTIVE: To explore the characteristics of acute exacerbations of myasthenia gravis after fluoroquinolone exposure. METHODS: Gender, age, prior type, absolute score, concurrent disease, precipitated disease, use of antibiotic, onset/symptom/degree of exacerbation, therapeutic measures and prognosis at Month 1 were retrospectively analyzed for 9 patients after fluoroquinolone systemic exposure. RESULTS: Ciprofloxacin (n = 4), levofloxacin (n = 1) and moxifloxacin (n = 4) exposure resulted in myasthenia gravis exacerbation. Myasthenia gravis exacerbations developed at 15 minutes to 4 days post-exposure. And the clinical scores of quantitative myasthenia gravis (QMG) increased by an average of 10. The main syndromes included dyspnea, diplopia, ptosis and dysphagia. All patients improved upon the withdrawal of fluoroquinolone in conjunctions with other interventions. CONCLUSION: Fluoroquinolone exposure may result in myasthenia gravis exacerbations in patients with underlying diseases. Healthcare professionals should be aware of this serious drug-disease association.

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up. CASE PRESENTATION: A 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen. CONCLUSIONS: Persistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis.

Association between HLA-DRB1 and myasthenia gravis in a northern Han Chinese population.

The cause of myasthenia gravis (MG) is unknown, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals. The human leukocyte antigen (HLA) region is considered to be the most important genetic region for MG susceptibility genes. To investigate the association between HLA-DRB1 and myasthenia gravis (MG) in a northern Han Chinese population, a polymerase chain reaction with sequence-specific oligonucleotide probe hybridization method was used to determine the HLA-DRB1 genotypes of 91 patients with MG and 171 healthy individuals. We found that the HLA-DRB1(*)09 allele was significantly more prevalent among patients with MG than among healthy controls, especially those who experienced early onset of the disease (≤40 years), those who were seronegative for acetylcholine receptor antibody, and those with ocular MG. The prevalence of the HLA-DRB1(*)08 allele was significantly lower among patients with MG than among controls. These results indicate that HLA-DRB1(*)09 might be positively associated and DRB1(*)08 negatively associated with MG in the northern Han Chinese population.