scholarly journals Disturbance of Gut Bacteria and Metabolites Are Associated with Disease Severity and Predict Outcome of NMDAR Encephalitis: A Prospective Case–Control Study

2022 ◽  
Vol 12 ◽  
Author(s):  
Xue Gong ◽  
Yue Liu ◽  
Xu Liu ◽  
Aiqing Li ◽  
Kundian Guo ◽  
...  

ObjectiveWe aimed to investigate the associations between the intestinal microbiota, metabolites, cytokines, and clinical severity in anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and to further determine the predictive value of the intestinal microbiota or metabolites in clinical prognosis.MethodsIn this prospective observational cohort study of 58 NMDAR encephalitis patients and 49 healthy controls, fecal microbiota, metabolites, and cytokines were quantified and characterized by16S rRNA gene sequencing, liquid chromatography–mass spectrometry, and the Luminex assay, respectively.ResultsThere were marked variations in the gut microbiota composition and metabolites in critically ill patients. We identified 8 metabolite modules (mainly characterized by fatty acid, glycerophosphoethanolamines, and glycerophosphocholines) that were distinctly classified as negatively or positively associated with bacterial co-abundance groups (CAGs). These CAGs were mainly composed of Bacteroides, Eubacterium_hallii_group, Anaerostipes, Ruminococcus, Butyricicoccus, and Faecalibacterium, which were substantially altered in patients. In addition, these fecal and serum metabolic modules were further correlated with the serum cytokines. Additionally, the combination of clinical features, microbial marker (Granulicatella), and a panel of metabolic markers could further enhance the performance of prognosis discrimination significantly, which yielded an area under the receiver operating characteristic curve of (AUC) of 0.94 (95%CI = 0.7–0.9). Patients with low bacterial diversity are more likely to develop relapse than those with higher bacterial diversity (log-rank p = 0.04, HR = 2.7, 95%CI = 1.0–7.0).InterpretationThe associations between the multi-omics data suggested that certain bacteria might affect the pathogenesis of NMDAR encephalitis by modulating the metabolic pathways of the host and affecting the production of pro-inflammatory cytokines. Furthermore, the disturbance of fecal bacteria may predict the long-term outcome and relapse in NMDAR encephalitis.

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S382-S382
Author(s):  
Charles Burdet ◽  
Thu Thuy Nguyen ◽  
Nathalie Saint-Lu ◽  
Sakina Sayah-Jeanne ◽  
Perrine Hugon ◽  
...  

Abstract Background C. difficile (C diff) infection results from antibiotic-induced changes in colonic microbiota. DAV131A, an oral adsorbent-based product, can sequester antibiotic (AB) residues in the gut and reduce mortality in a hamster model of moxifloxacin (MXF) or clindamycin (CM) induced C diffcolitis. We studied the link between changes of the bacterial diversity within the fecal microbiota and mortality in this model. Methods Male Syrian hamsters were administered 30 mg/kg MXF or 5 mg/kg CM subcutaneously once a day for 5 days (D1 to D5) and orally infected at D3 with 104C diffspores. They were orally administered various doses of DAV131A (0, and 200 to 900 mg/kg twice a day), from D1 to D8. Survival was monitored up to D16 and feces were collected (D1 and D3) to characterize the microbiota by 16S rRNA gene profiling. Changes of various α- (Shannon, Observed OTUs and Chao1) and β- (Bray-Curtis dissimilarity and [un]weighted UniFrac) diversity indices between D1 and D3 were obtained for each animal. We analyzed links between (i) DAV131A dose and changes of bacterial diversity and (ii) changes of bacterial diversity and mortality using non parametric tests and logistic regression. Results Data from 70 and 60 animals were available in the MXF and CM studies, among which 10 and 28 died, respectively. Increasing doses of DAV131A reduced mortality from 100% to 0% and reduced changes in bacterial diversity of the fecal microbiota. Very strong predictors of mortality were changes in Shannon and unweighted UniFrac indices, which were markedly less affected in hamsters who survived (see table below median (min; max) according to vital status and area under the ROC curve, AUROC). Conclusion The extent of AB-induced changes in gut bacterial diversity correlated with increased mortality in a hamster model of C diff colitis. Higher doses of DAV131A protected fecal microbiota disruption and hence mortality. Disclosures C. Burdet, Da Volterra: Consultant and Research Contractor, Consulting fee; N. Saint-Lu, Da Volterra: Employee, Salary; S. Sayah-Jeanne, Da Volterra: Employee, Salary; P. Hugon, Da Volterra: Employee, Salary; F. Sablier-Gallis, Da Volterra: Employee, Salary; S. Ferreira, Genoscreen: Employee, Salary; A. Andremont, Da Volterra: Consultant, Consulting fee; F. Mentré, Da Volterra: Consultant and Research Contractor, Consulting fee; J. De Gunzburg, Da Volterra: Consultant and Shareholder, Consulting fee


2014 ◽  
Vol 80 (8) ◽  
pp. 2546-2554 ◽  
Author(s):  
Zongxin Ling ◽  
Zailing Li ◽  
Xia Liu ◽  
Yiwen Cheng ◽  
Yueqiu Luo ◽  
...  

ABSTRACTIncreasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundantBacteroidetes,Proteobacteria, andActinobacteriaphyla were significantly reduced, while theFirmicutesphylum was highly enriched in the FA group (P< 0.05). AbundantClostridiaceae1 organisms were prevalent in infants with FA at the family level (P= 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the generaEnterococcusandStaphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P< 0.05). Infants with IgE-mediated FA had increased levels ofClostridium sensu strictoandAnaerobacterand decreased levels ofBacteroidesandClostridiumXVIII (P< 0.05). A positive correlation was observed betweenClostridium sensu strictoand serum-specific IgE (R= 0.655,P< 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.


2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Gao C ◽  
Zhang H ◽  
Fu J

Idiopathic Intracranial Hypertension (IIH) or Pseudotumor Cerebri (PTC) is a disorder of young obese females and characterized by headache, papilledema and raised intracranial pressure. However, it is in the absence of known pathological cause. Due to the uncertainty of etiology, it may lead to misdiagnosis and grave clinical prognosis. IIH is typically treated with Lumboperitoneal Shunting (LPS) and Ventriculoperitoneal Shunting (VPS), but shunts are prone to dysfunctions and infection, resulting in recurrent headaches in many patients after this treatment. We report a case of 41-year-old obese female (BMI: 30.9) with IIH, who has a history of hypertension (Blood pressure: 150/100 mmHg) and elevated intracranial pressure (Open pressure: 450 mmH2 O). After the failure of several medical treatments, the patient was offered LPS because of vision loss and headache, but the postoperative symptoms (intermittent headache, mainly total craniocerebral prickling pain with neck and shoulder pain) were not significantly relieved for 11 years. Therefore, considering the blockage of the primary shunt tube and the small ventricle in the patient, it has difficulty in puncture ventricle puncture. We have to treat with the stereotactic VPS (SVPS) for her exacerbation symptoms. More surprisingly, the hypertension was in the normal range (<115/80 mmHg) after the surgery (without taking antihypertensive medication). To compare the surgical therapeutic effects and complications of LPS and the SVPS in the treatment of idiopathic intracranial hypertension. Cerebrospinal Fluid (CSF) diversion with VPS or LPS is usually performed when the main symptom is vision loss; it also stabilizes headache and papilledema. LPS significantly alleviates symptoms in the short term, but due to excessive shunt of LPS for a long time, it is easy to be complicated with Chiari malformation and slit ventricle syndrome. Therefore, we encourage operating the SVPS on our patients for the favorable long-term outcome.


2019 ◽  
Vol 52 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Huan Zhong ◽  
Yuefan Shen ◽  
Zixiang Yao ◽  
Xiaonong Chen ◽  
Jianguo Gao ◽  
...  

Abstract Purpose The purpose of this study was to analyze long-term complications, urodynamics, and quality of life (QoL) of patients after orthotopic ileal neobladder with orthotopic ureteral reimplantation to enrich clinical data and provide a basis for clinical use of this surgery. Methods Between January 2007 and January 2013, 72 consecutive patients who underwent spiral ileal neobladder following radical cystectomy were enrolled. The neobladder was created using a modified Camey-II technique. Complications were reviewed and staged according to Clavien–Dindo classification and evaluated in long-term follow-up. Urodynamics were performed, and QoL was assessed by the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL) instrument. Results The total follow-up time was 60 months, and the total survival rates at 3 and 5 years after surgery were 76.4% (55/72) and 65.3% (47/72), respectively. There were 34 (47.2%) early complications in 23 (31.9%) patients and 42 (58.3%) late complications in 35 (48.6%) patients. The total satisfactory control rates were 69.1% and 66.0% at 3 and 5 years after the surgery, respectively. Urodynamic studies were performed in some patients, and the receiver operating characteristic curve analysis showed that pressure at maximum capacity, compliance, and post void residual urine had predictive value for mortality (P < 0.05). The total FACT-BL scores of patients at 1, 3, and 5 years postoperation were 125.0 ± 15.2, 127.0 ± 16.2, and 120.6 ± 13.5, respectively, and it decreased at 5 years postoperation (P < 0.05). Conclusion Spiral ileal neobladder with orthotopic ureteral reimplantation offers satisfactory long-term results, and urodynamic monitoring might have prognostic value.


2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Charles Burdet ◽  
Nathalie Grall ◽  
Morgane Linard ◽  
Antoine Bridier-Nahmias ◽  
Michèle Benhayoun ◽  
...  

ABSTRACT Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.)


Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 683 ◽  
Author(s):  
Wilbert Gutiérrez-Sarmiento ◽  
Sonia Guadalupe Sáyago-Ayerdi ◽  
Isabel Goñi ◽  
Federico Antonio Gutiérrez-Miceli ◽  
Miguel Abud-Archila ◽  
...  

Mango (Mangifera indica L.) peel and pulp are a source of dietary fiber (DF) and phenolic compounds (PCs) that constituent part of the indigestible fraction (IF). This fraction reaches the colon and acts as a carbon and energy source for intestinal microbiota. The effect of mango IF on intestinal microbiota during colonic fermentation is unknown. In this study, the isolated IF of a novel ‘Ataulfo’ mango-based bar (snack) UV-C irradiated and non-irradiated (UVMangoB and MangoB) were fermented. Colonic fermentation occurred in vitro under chemical-enzymatic, semi-anaerobic, batch culture and controlled pH colonic conditions. Changes in the structure of fecal microbiota were analyzed by 16s rRNA gene Illumina MiSeq sequencing. The community´s functional capabilities were determined in silico. The MangoB and UVMangoB increased the presence of Faecalibacterium, Roseburia, Eubacterium, Fusicatenibacter, Holdemanella, Catenibacterium, Phascolarctobacterium, Buttiauxella, Bifidobacterium, Collinsella, Prevotella and Bacteroides genera. The alpha indexes showed a decrease in microbial diversity after 6 h of colonic fermentation. The coordinates analysis indicated any differences between irradiated and non-irradiated bar. The metabolic prediction demonstrated that MangoB and UVMangoB increase the microbiota carbohydrate metabolism pathway. This study suggests that IF of mango-based bar induced beneficial changes on microbial ecology and metabolic pathway that could be promissory to prevention or treatment of metabolic dysbiosis. However, in vivo interventions are necessary to confirm the interactions between microbiota modulating and intestinal beneficial effects.


2019 ◽  
Vol 90 (e7) ◽  
pp. A35.2-A35
Author(s):  
Alana Donaldson ◽  
Abhay Venkat ◽  
Shaun Zhai ◽  
Ronak Patel ◽  
Yash Gawarikar

IntroductionAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the more common forms of autoimmune encephalitis, predominantly affecting children and women of the child-bearing age. It is characterised by memory deficit, behavioural disturbance and seizures. Dysautonomia is recognised as a feature but rarely the first symptom of the condition.1 Here we present a case of severe dysautonomia preceding the diagnosis of NMDAR encephalitis.MethodsWe conducted a retrospective review of the admissions to the neurology ward at the Calvary Hospital, Canberra in 2018 to identify patients diagnosed with NMDAR encephalitis.ResultsOne patient was identified from the registry data. A 37-year-old woman presented with a week-long history of symptomatic orthostatic hypotension. Her supine systolic blood pressure was 110mmHg with a 46mmHg postural drop. Over the first week of hospitalisation, she became increasingly disoriented and erratic in behaviour with fluctuating levels of consciousness requiring intensive unit care. Her CSF demonstrated lymphocytic pleocytosis and NMDAR antibodies were detected in both CSF and serum. She was treated with IVIG, IV steroids and subsequently Rituximab. A pelvic teratoma was found and removed. Her symptomatology including dysautonomia improved substantially by the end of her six-week hospital admission. Her modified Rankin Scale was zero at three months.ConclusionAutonomic dysfunction is not a common feature of autoimmune encephalitides. Our case highlighted the possibility that dysautonomia can be the initiating symptom of this disease entity. Physician awareness is important in the early recognition and treatment of this condition.ReferenceTitulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12(2):157–165.


Author(s):  
Bingquan Zhu ◽  
Shuangshuang Zheng ◽  
Kexin Lin ◽  
Xin Xu ◽  
Lina Lv ◽  
...  

Several lines of evidence suggest that the intestinal microbiota plays crucial roles in infant development, and that it is highly influenced by extrinsic and intrinsic factors. Prebiotic-containing infant formula may increase gastrointestinal tolerance and improve commensal microbiota composition. However, it remains unknown whether supplementation of milk-formulas with prebiotics and 1,3-olein-2-palmitin (OPO) can achieve feeding outcomes similar to those of breastfeeding. In the present study, we investigated the effects of two kinds of infant formula with different additives on the overall diversity and composition of the fecal microbiota, to determine which was closer to breastfeeding. A total of 108 infants were enrolled, including breastfeeding (n=59) and formula feeding group (n=49). The formula feeding infants were prospectively randomly divided into a standard formula group (n=18), and a supplemented formula group(n=31). The fecal samples were collected at 4 months after intervention. Fecal microbiota analysis targeting the V4 region of the 16S rRNA gene was performed using MiSeq sequencing. The overall bacterial diversity and composition, key functional bacteria, and predictive functional profiles in the two different formula groups were compared with breastfeeding group. We found that the alpha diversity of the gut microbiota was not significantly different between the OPO and breastfeeding groups with Chaos 1 index (p=0.346). The relative abundances of Enhydrobacter and Akkermansia in the OPO group were more similar to those of the breastfeeding group than to those of the standard formula group. The gut microbiota metabolism function prediction analysis showed that the supplemented formula group was similar to the breastfeeding group in terms of ureolysis (p=0.297). These findings suggest that, when formula supplemented with prebiotics and OPO was given, the overall bacterial diversity and parts of the composition of the fecal microbiota would be similar to that of breastfeeding infants.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4827 ◽  
Author(s):  
Katti R. Horng ◽  
Holly H. Ganz ◽  
Jonathan A. Eisen ◽  
Stanley L. Marks

Studies involving gut microbiome analysis play an increasing role in the evaluation of health and disease in humans and animals alike. Fecal sampling methods for DNA preservation in laboratory, clinical, and field settings can greatly influence inferences of microbial composition and diversity, but are often inconsistent and under-investigated between studies. Many laboratories have utilized either temperature control or preservation buffers for optimization of DNA preservation, but few studies have evaluated the effects of combining both methods to preserve fecal microbiota. To determine the optimal method for fecal DNA preservation, we collected fecal samples from one canine donor and stored aliquots in RNAlater, 70% ethanol, 50:50 glycerol:PBS, or without buffer at 25 °C, 4 °C, and −80 °C. Fecal DNA was extracted, quantified, and 16S rRNA gene analysis performed on Days 0, 7, 14, and 56 to evaluate changes in DNA concentration, purity, and bacterial diversity and composition over time. We detected overall effects on bacterial community of storage buffer (F-value = 6.87, DF = 3, P < 0.001), storage temperature (F-value=1.77, DF = 3, P = 0.037), and duration of sample storage (F-value = 3.68, DF = 3, P < 0.001). Changes in bacterial composition were observed in samples stored in −80 °C without buffer, a commonly used method for fecal DNA storage, suggesting that simply freezing samples may be suboptimal for bacterial analysis. Fecal preservation with 70% ethanol and RNAlater closely resembled that of fresh samples, though RNAlater yielded significantly lower DNA concentrations (DF = 8.57, P < 0.001). Although bacterial composition varied with temperature and buffer storage, 70% ethanol was the best method for preserving bacterial DNA in canine feces, yielding the highest DNA concentration and minimal changes in bacterial diversity and composition. The differences observed between samples highlight the need to consider optimized post-collection methods in microbiome research.


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