scholarly journals The relationship between mucosal microbiota, colitis and systemic inflammation in Chronic Granulomatous Disorder

2021 ◽  
Author(s):  
Mehmet Davrandi ◽  
Stephanie Harris ◽  
Philip J Smith ◽  
Charles D Murray ◽  
David M Lowe

Background: Chronic granulomatous disorder (CGD) is a primary immunodeficiency which is frequently complicated by an inflammatory colitis and is associated with systemic inflammation. Objective: To investigate the role of the microbiome in the pathogenesis of colitis and systemic inflammation. Methods: We performed 16S rDNA sequencing on mucosal biopsy samples from each segment of 10 CGD patients colons, and conducted compositional and functional pathway prediction analyses. Results: The microbiota in samples from colitis patients demonstrated reduced taxonomic alpha diversity compared to unaffected patients, even in apparently normal bowel segments. Functional pathway richness was similar between the colitic and non-colitic mucosa, although metabolic pathways involved in butyrate biosynthesis or utilisation were enriched in patients with colitis and correlated positively with faecal calprotectin levels. One patient with very severe colitis was dominated by Enterococcus spp., while among other patients Bacteroides spp. abundance correlated with colitis severity measured by faecal calprotectin and an endoscopic severity score. In contrast, Blautia abundance associated with low severity scores and mucosal health. Several taxa and functional pathways correlated with concentrations of inflammatory cytokines in blood but not with colitis severity. Notably, dividing patients into High and Low systemic inflammation groups demonstrated clearer separation than on the basis of colitis status in beta diversity analyses. Conclusion: The microbiome is abnormal in CGD-associated colitis and altered functional characteristics probably contribute to pathogenesis. Furthermore, the relationship between the mucosal microbiome and systemic inflammation, independent of colitis status, implies that the microbiome in CGD can influence the inflammatory phenotype of the condition.

2020 ◽  
Vol 8 (2) ◽  
pp. 254 ◽  
Author(s):  
Ke Liu ◽  
Yongling Zhang ◽  
Qinglin Li ◽  
Huan Li ◽  
Danfeng Long ◽  
...  

Although the human gut microbiome is shaped by factors such as diet, environment, and genetic background, most studies investigating the relationship between ethnicity and microbiota have compared groups living in separate geographical locations. To isolate the effects of ethnicity on microbial diversity by minimizing environmental differences, we selected 143 school children from Han, Tibetan, and Hui populations from the same town on the Qinghai–Tibetan Plateau for fecal microbiome 16S rDNA sequencing. We characterized the diversity, identified signature taxa, and performed correlation analysis between diet and community composition. Firmicutes (47.61%) and Bacteroidetes (38.05%) were dominant phyla among the three ethnic groups; seven genera showed significant differences in relative abundance. Tibetan populations had a higher relative abundance of Oscillibacter and Barnesiella, compared with Han and Hui populations. Alpha diversity analyses (observed species, ACE, and Shannon indices) showed that the Tibetan population had the highest diversity compared to the Hui and Han groups, whereas beta diversity analysis revealed no significant differences between groups. The consumption of grains, milk, eggs, and fruits were positively correlated with specific taxa. Under similar environments and diet, ethnic background significantly contributed to differences in alpha diversity but not beta diversity of gut microbiota.


2021 ◽  
Vol 190 ◽  
pp. 553-559
Author(s):  
Irina K. Malashenkova ◽  
Vadim L. Ushakov ◽  
Sergey A. Krynskiy ◽  
Daniil P. Ogurtsov ◽  
Nikita A. Khailov ◽  
...  

Author(s):  
Shien Ren ◽  
Chao Fan ◽  
Liangzhi Zhang ◽  
Xianjiang Tang ◽  
Haibo Fu ◽  
...  

Abstract Plants produce various plant secondary compounds (PSCs) to deter the foraging of herbivorous mammals. However, little is known about whether PSCs can reshape gut microbiota and promote gut homeostasis of hosts. Using 16S rDNA sequencing to investigate the effects of PSCs on the gut microbiota of small herbivorous mammals, we studied plateau pikas (Ochotona curzoniae) fed diets containing swainsonine (SW) extracted from Oxytropis ochrocephala. Our results showed that both long- and short-term treatment of a single artificial diet in the laboratory significantly reduced alpha diversity and significantly affected beta diversity, core bacteria abundance, and bacterial functions in pikas. After SW was added to the artificial diet, the alpha diversity significantly increased in the long-term treatment, and core bacteria (e.g., Akkermansiaceae) with altered relative abundances in the two treatments showed no significant difference compared with pikas in the wild. The complexity of the co-occurrence network structure was reduced in the artificial diet, but it increased after SW was added in both treatments. Further, the abundances of bacteria related to altered alanine, aspartate, and glutamate metabolism in the artificial diet were restored in response to SW. SW further decreased the concentration of short-chain fatty acids (SCFAs) in both treatments. Our results suggest that PSCs play a key role in regulating gut microbiota community and intestinal homeostasis, thereby maintaining host health. Key points • Swainsonine improves the intestinal bacterial diversity of plateau pikas. • Swainsonine promotes the recovery of core bacterial abundances in the gut of plateau pikas. • Swainsonine promotes the restoration of intestinal bacterial functions of plateau pikas.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Sirignano ◽  
Josef Frank ◽  
Laura Kranaster ◽  
Stephanie H. Witt ◽  
Fabian Streit ◽  
...  

AbstractElectroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10−8). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10−7). Regional analyses identified two differentially methylated regions on chromosomes 8 (Šídák’s p = 0.0031) and 20 (Šídák’s p = 4.2 × 10−5) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 407-407
Author(s):  
Ki Beom Jang ◽  
Sung Woo Kim

Abstract This study aimed to evaluate supplemental effects of milk carbohydrates in whey permeate on jejunal mucosa-associated microbiota in nursery pigs during 7 to 11 kg BW. A total of 720 pigs at 7.5 kg BW were allotted to 6 treatments (6 pens/treatment and 20 pigs/pen). Treatments were 6 levels of whey permeate supplementation (0, 3.75, 7.50, 11.25, 15.00, and 18.75%) and fed to pigs for 11 d. On d 11, 36 pigs representing median BW of each pen were euthanized to collect the jejunal mucosa to evaluate microbiota in the jejunum by 16S rDNA sequencing. Data were analyzed using contrasts in MIXED procedure of SAS. Whey permeate contained 76.3% lactose and 0.4% milk oligosaccharides. Increasing whey permeate supplementation from 0 to 18.75% did not affect the alpha-diversity estimates of microbiota. Whey permeate supplementation tended to decrease (P = 0.073, 1.59 to 1.22) Firmicutes:Bacteroidetes compared with no addition of whey permeate. Increasing whey permeate supplementation tended to linearly increase Bifidobacteriaceae (P = 0.089, 0.73 to 1.11), decrease Enterobacteriaceae (P = 0.091, 1.04 to 0.52), decrease Stretococcaceae (P = 0.094, 1.50 to 0.71), and caused quadratic changes (P &lt; 0.05) on Lactobacillaceae (maximum: 9.14% at 12.91% whey permeate). Increasing whey permeate supplementation caused a quadratic change (P &lt; 0.05) on Lactobacillus_Salivarius (maximum: 0.92% at 7.35% whey permeate) and tended to cause quadratic changes on Lactobacillus_Rogosae (P = 0.083; maximum: 0.53% at 8.45% whey permeate) and Lactobacillus_Mucosae (P = 0.092; maximum: 0.70% at 6.98% whey permeate). In conclusion, supplementation of whey permeate as sources of lactose and milk oligosaccharides at a range from 7 to 13% seems to be beneficial to nursery pigs by increasing the abundance of lactic acid-producing bacteria in the jejunal mucosa.


2015 ◽  
Vol 46 (2) ◽  
pp. 431-443 ◽  
Author(s):  
Rozenn Quarck ◽  
Marijke Wynants ◽  
Erik Verbeken ◽  
Bart Meyns ◽  
Marion Delcroix

Deficient angiogenesis and systemic inflammation could be involved in the pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to characterise the histopathology of pulmonary vascular lesions from 52 CTEPH patients who underwent a pulmonary endarterectomy (PEA) and investigate a potential link between clinical, biological and morphometric parameters.Collagen, elastin, fibrin, lipid, endothelial, smooth muscle and inflammatory cell content was investigated using immunohistochemistry. Qualitative changes were evaluated using severity scores. Circulating levels of inflammatory mediators were measured using ELISA.Neointima, thrombotic, recanalised and atherosclerotic lesions were found. Accumulation of macrophages, T-lymphocytes and neutrophils was found mainly in atherosclerotic and thrombotic lesions. Angiogenesis was observed in all kinds of lesions; low-scored angiogenesis predicted adverse outcome, including persistent pulmonary hypertension post-PEA, start of medical therapy and poor survival. C-reactive protein (CRP), interleukin-10, monocyte chemotactic protein-1, macrophage inflammatory protein-1α and matrix metalloproteinase (MMP)-9 were significantly elevated in CTEPH patients. Plasma CRP and MMP-9 levels correlated with neutrophil and macrophage accumulation, respectively.Enhanced systemic inflammation parallels local inflammatory cell infiltration in major pulmonary arteries at advanced stages of CTEPH. Impaired neovascularisation is associated with poor survival, start of medical treatment and persistent pulmonary hypertension post-PEA. These findings suggest that inflammation and impaired angiogenesis could contribute to the progression of the disease.


2017 ◽  
Author(s):  
Ryan H. Hsu ◽  
Dylan M. McCormick ◽  
Mitchell J. Seitz ◽  
Lauren M. Lui ◽  
Harneet S. Rishi ◽  
...  

AbstractOur knowledge of the relationship between the gut microbiome and health has rapidly expanded in recent years. Diet has been shown to have causative effects on microbiome composition, which can have subsequent implications on health. Soylent 2.0 is a liquid meal replacement drink that satisfies nearly 20% of all recommended daily intakes per serving. This study aims to characterize the changes in gut microbiota composition resulting from a short-term Soylent diet. Fourteen participants were separated into two groups: 5 in the regular diet group and 9 in the Soylent diet group. The regular diet group maintained a diet closely resembling self-reported regular diets. The Soylent diet group underwent three dietary phases: A) a regular diet for 2 days, B) a Soylent-only diet (five servings of Soylent daily and water as needed) for 4 days, and C) a regular diet for 4 days. Daily logs self-reporting diet, Bristol stool ratings, and any abdominal discomfort were electronically submitted. Eight fecal samples per participant were collected using fecal sampling kits, which were subsequently sent to uBiome, Inc. for sample processing and V4 16S rDNA sequencing. Reads were clustered into operational taxonomic units (OTUs) and taxonomically identified against the GreenGenes 16S database. We find that an individual’s alpha-diversity is not significantly altered during a Soylent-only diet. In addition, principal coordinate analysis using the unweighted UniFrac distance metric shows samples cluster strongly by individual and not by dietary phase. Among Soylent dieters, we find a significant increase in the ratio of Bacteroidetes to Firmicutes abundance, which is associated with several positive health outcomes, including reduced risks of obesity and intestinal inflammation.


Author(s):  
Tevfik Kalelioglu ◽  
Guler Celikel ◽  
Ozlem Devrim Balaban ◽  
Nesrin Karamustafalioglu ◽  
Jennifer Kim Penberthy

Objective: Neuroleptic malignant syndrome (NMS) is a rare but severe side effect of antipsychotic medication. Neutrophil-lymphocyte ratio (NLR) is a simple marker used to measure systemic inflammation. Method: In this case report we explore the relationship of inflammation in the etiology of NMS. In our case involving NMS, although there was no leukocytosis, the NLR was increased up to systemic infection levels. Conclusion: We hypothesized that systemic inflammation may take a role in developing NMS. If so, NLR could be a new marker of NMS that may be able to provide more sensitive results than leukocyte levels.


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