scholarly journals Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus

2021 ◽  
Vol 22 (4) ◽  
pp. 1511
Author(s):  
Parul Singh ◽  
Arun Rawat ◽  
Bara Al-Jarrah ◽  
Saras Saraswathi ◽  
Hoda Gad ◽  
...  

Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (n = 19), T1DM (n = 18) and both CD and T1DM (n = 9) compared to healthy controls (n = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria Shigella and E. coli were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus Parabacteroides was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.

2021 ◽  
pp. bjophthalmol-2021-319057
Author(s):  
Hoda Gad ◽  
Bara Al-Jarrah ◽  
Saras Saraswathi ◽  
Sara Mohamed ◽  
Alise Kalteniece ◽  
...  

PurposeTo assess whether alterations in stromal keratocyte density are related to loss of corneal nerve fibres in children with type 1 diabetes mellitus (T1DM).MethodsTwenty participants with T1DM and 20 age-matched healthy controls underwent corneal confocal microscopy. Corneal sub-basal nerve morphology and corneal keratocyte density (KD) were quantified.ResultsCorneal nerve fibre density (CNFD) (p<0.001), corneal nerve branch density (p<0.001), corneal nerve fibre length (CNFL) (p<0.001) and inferior whorl length (IWL) (p<0.001) were lower in children with T1DM compared with healthy controls. Anterior (p<0.03) and mid (p=0.03) stromal KDs were lower with no difference in posterior KD (PKD) in children with T1DM compared with controls. Age, duration of diabetes, height, weight and body mass index did not correlate with anterior (AKD), mid (MKD) or PKD. Inverse correlations were found between glycated haemoglobin and PKD (r=−0.539, p=0.026), bilirubin with MKD (r=−0.540, p=0.025) and PKD (r=−0.531, p=0.028) and 25-hydroxycholecalciferol with MKD (r=−0.583, p=0.018). CNFD, CNFL and IWL did not correlate with AKD, MKD or PKD.ConclusionThis study demonstrates a reduction in corneal nerves and anterior and mid stromal KD in children with T1DM, but no correlation between corneal nerve and keratocyte cell loss.


2002 ◽  
Vol 34 ◽  
pp. A26
Author(s):  
M. Candelli ◽  
D. Rigante ◽  
E.C. Nista ◽  
A. Schiavino ◽  
I.A. Cazzato ◽  
...  

2016 ◽  
Vol 5 (11) ◽  
pp. 1485-1495 ◽  
Author(s):  
Lindsay C. Davies ◽  
Jessica J. Alm ◽  
Nina Heldring ◽  
Guido Moll ◽  
Caroline Gavin ◽  
...  

1986 ◽  
Vol 20 (11) ◽  
pp. 1205-1205
Author(s):  
S Salardi ◽  
E Cacciari ◽  
U Volta ◽  
G Biasco ◽  
S Partesotti ◽  
...  

2005 ◽  
Vol 153 (6) ◽  
pp. 895-899 ◽  
Author(s):  
Heinrich Kahles ◽  
Elizabeth Ramos-Lopez ◽  
Britta Lange ◽  
Oliver Zwermann ◽  
Martin Reincke ◽  
...  

Background: Endocrine autoimmune disorders share genetic susceptibility loci, causing a disordered T-cell activation and homeostasis (HLA class II genes, CTLA-4). Recent studies showed a genetic variation within the PTPN22 gene to be an additional risk factor. Materials and Methods: Patients with type 1 diabetes (n = 220), Hashimoto’s thyroiditis (n = 94), Addison’s disease (n = 121) and healthy controls (n = 239) were genotyped for the gene polymorphism PTPN22 1858 C/T. Results: Our study confirms a significant association between allelic variation of the PTPN22 1858 C/T polymorphism and type 1 diabetes mellitus (T1D). 1858T was observed more frequently in T1D patients (19.3% vs 11.3%, P = 0.0009; odds ratio for allele T = 1.88, 95% confidence interval [1.3–2.7]). Furthermore, we found a strong association in female patients with T1D (P = 0.0003), whereas there was no significant difference between male patients with type 1 diabetes and male controls. No significant difference was observed between the distribution of PTPN22 C/T in patients with Hashimoto’s thyroiditis or Addison’s disease and healthy controls. Conclusion: The PTPN22 polymorphism 1858 C/T may be involved in the pathogenesis of type 1 diabetes mellitus by a sex-specific mechanism that contributes to susceptibility in females.


2019 ◽  
Vol 30 (6) ◽  
pp. 1467-1472
Author(s):  
Serdar Ozates ◽  
Mert Simsek ◽  
Ufuk Elgin ◽  
Melikşah Keskin ◽  
Zehra Aycan

Purpose: To assess the visual field sensitivity changes and investigate the association between visual field sensitivity and retinal nerve fiber layer thickness in patients with type 1 diabetes mellitus. Materials and methods: In this cross-sectional and observational study, 46 patients (22 males, 24 females) with type 1 diabetes mellitus and no diabetic retinopathy formed the diabetes mellitus group and 50 age-matched healthy subjects (32 males, 18 females) formed the control group. Retinal nerve fiber layer thickness, full-threshold standard automated perimetry, and short-wavelength automated perimetry were performed. Main outcomes were retinal nerve fiber layer thickness, mean deviation, pattern standard deviation, and short fluctuation. Results: Average retinal nerve fiber layer thickness was significantly thinner in the diabetes mellitus group (p < 0.001). The mean values of mean deviation and pattern standard deviation of the full-threshold standard automated perimetry did not differ between the groups (p = 0.179, p = 0.139, respectively). Mean short fluctuation was significantly greater in the diabetes mellitus group (p < 0.001). Both mean deviation and pattern standard deviation of the short-wavelength automated perimetry were significantly greater in the diabetes mellitus group (p < 0.001, p < 0.001, respectively). Pattern standard deviation of short-wavelength automated perimetry equal or higher than 1.57 dB had 91% sensitivity and 90% specificity (area under the curve = 0.969, p < 0.001) and short fluctuations of full-threshold standard automated perimetry equal or higher than 0.80 dB had 80% sensitivity and 76% specificity over detecting early retinal nerve fiber layer loss in patients with type 1 diabetes mellitus (area under the curve = 0.855, p < 0.001). Conclusion: This study showed that thinner retinal nerve fiber layer in patients with type 1 diabetes mellitus may be associated with abnormal retinal sensitivity to short-wavelength stimulations in short-wavelength automated perimetry; however, retinal sensitivity to white stimulus was similar to that in healthy subjects in full-threshold standard automated perimetry.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Phillip Trefz ◽  
Juliane Obermeier ◽  
Ruth Lehbrink ◽  
Jochen K. Schubert ◽  
Wolfram Miekisch ◽  
...  

Abstract Monitoring metabolic adaptation to type 1 diabetes mellitus in children is challenging. Analysis of volatile organic compounds (VOCs) in exhaled breath is non-invasive and appears as a promising tool. However, data on breath VOC profiles in pediatric patients are limited. We conducted a cross-sectional study and applied quantitative analysis of exhaled VOCs in children suffering from type 1 diabetes mellitus (T1DM) (n = 53) and healthy controls (n = 60). Both groups were matched for sex and age. For breath gas analysis, a very sensitive direct mass spectrometric technique (PTR-TOF) was applied. The duration of disease, the mode of insulin application (continuous subcutaneous insulin infusion vs. multiple daily insulin injection) and long-term metabolic control were considered as classifiers in patients. The concentration of exhaled VOCs differed between T1DM patients and healthy children. In particular, T1DM patients exhaled significantly higher amounts of ethanol, isopropanol, dimethylsulfid, isoprene and pentanal compared to healthy controls (171, 1223, 19.6, 112 and 13.5 ppbV vs. 82.4, 784, 11.3, 49.6, and 5.30 ppbV). The most remarkable differences in concentrations were found in patients with poor metabolic control, i.e. those with a mean HbA1c above 8%. In conclusion, non-invasive breath testing may support the discovery of basic metabolic mechanisms and adaptation early in the progress of T1DM.


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