scholarly journals Uremia causes dysbiosis-mediated periodontal disease

Author(s):  
David Randall ◽  
Asil Alsam ◽  
Julius Kieswich ◽  
Susan Joseph ◽  
Joseph Aduse-Opoku ◽  
...  

Abstract It is presently unclear why there is a high prevalence of periodontal disease (PD) in individuals living with chronic kidney disease (CKD). By employing three different models in rats and mice, we demonstrate that experimental uremia causes periodontal bone loss. Uremia alters the biochemical composition of saliva and induces progressive dysbiosis of the oral microbiota, with microbial samples from uremic animals displaying reduced overall bacterial growth, increased alpha diversity, reduced abundance of key components of the healthy oral microbiota such as Streptococcus and Rothia, and an increase in minor taxa including those from gram-negative phyla Proteobacteria and Bacteroidetes. We show that transfer of oral microbiota from uremic mice induces PD in germ-free animals, whilst co-housing with healthy animals ameliorates the PD phenotype in rats. Thus, we advocate that periodontal disease should be regarded as a bacterially mediated complication of chronic uremia.

2021 ◽  
Author(s):  
Philippa M Wells ◽  
Daniel D Sprockett ◽  
Ruth CE Bowyer ◽  
Yuko Kurushima ◽  
Frances MK Williams ◽  
...  

Background: The oral microbiota is emerging as an influential factor of host physiology and disease state. Factors influencing oral microbiota composition have not been well characterised. In particular, there is a lack of population-based studies. We undertook a large hypothesis-free study of the saliva microbiota, considering potential influential factors of host health (frailty; diet; periodontal disease), demographics (age; sex; BMI) and sample processing (storage time), in a sample (n=679) of the TwinsUK cohort of adult twins. Results: Alpha and beta diversity of the saliva microbiota was associated most strongly with frailty (alpha diversity: Q = 0.003, Observed; Q=0.002, Shannon; Q=0.003, Simpson; Beta diversity: Q = 0.002, Bray Curtis dissimilarity ) and age (alpha diversity: Q=0.006, Shannon; Q=0.003, Simpson; beta diversity: Q=0.002, Bray Curtis dissimilarity; Q= 0.032, Weighted UniFrac) in multivariate models including age, frailty, sex, BMI, frailty and diet, and adjustment for multiple testing. Those with a more advanced age were more likely to be dissimilar in the saliva microbiota composition than younger participants (P = 5.125e-06, ANOVA). In subsample analyses, including consideration of periodontal disease (total n=138, periodontal disease n=66), the association with frailty remained for alpha diversity (Q=0.002, Observed ASVs; Q= 0.04 Shannon Index), but not beta diversity, whilst age was not demonstrated to associate with alpha or beta diversity in this subsample, potentially due to insufficient statistical power. Length of time that samples were stored prior to sequencing was associated with beta diversity (Q = 0.002, Bray Curtis dissimilarity). Six bacterial taxa were associated with age after adjustment for frailty and diet. Conclusions: Frailty and age emerged as the most influential factors of saliva microbiota composition. Whilst frailty and age are correlates, the associations were independent of each other, suggesting that both biological and chronological ageing are key drivers of saliva microbiota composition.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Liza K. McDonough ◽  
Karina T. Meredith ◽  
Chandima Nikagolla ◽  
Richard B. Banati

AbstractPoor drinking water quality in household wells is hypothesised as being a potential contributor to the high prevalence of chronic kidney disease of uncertain aetiology (CKDu) among the farming communities of the Medawachchiya area, Anuradhapura, Sri Lanka. One of the natural processes that can affect water quality is the dissolution of minerals contained within an aquifer by water–rock interactions (WRIs). Here we present a comprehensive assessment of WRIs and their influence on the water chemistry in household wells and spring waters in the Medawachchiya area by combining measurements of environmental isotopes, such as strontium, lithium and stable carbon isotopes and inorganic chemistry parameters, and modelling geochemical mass balance reactions between rainfall and groundwater samples. Our results reveal the presence of strontium, dissolved from both silicate and carbonate minerals, with high isotopic (87Sr/86Sr) ratios of up to 0.7316. Geochemical mass balance modelling and prior 87Sr/86Sr studies on the Wanni Complex bedrock suggest these strontium values may be the result of biotite dissolution. We also identify lithium and uranium contributed from the dissolution of silicates, albeit at concentrations too low to constitute a known health risk. In contrast, the levels of magnesium and calcium in our samples are high and demonstrate that, despite the felsic bedrock, well water chemistry in the Medawachchiya area is dominated by carbonate dissolution.


2021 ◽  
Vol 22 (9) ◽  
pp. 4480
Author(s):  
Maria Tziastoudi ◽  
Georgios Pissas ◽  
Georgios Raptis ◽  
Christos Cholevas ◽  
Theodoros Eleftheriadis ◽  
...  

Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the ABCB1, IL-10, ITPA, MIF, and TNF genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.


Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1346 ◽  
Author(s):  
Nuria Jiménez-Hernández ◽  
Sergio Serrano-Villar ◽  
Alba Domingo ◽  
Xavier Pons ◽  
Alejandro Artacho ◽  
...  

Human immunodeficiency virus (HIV) infection is characterized by an early depletion of the mucosal associated T helper (CD4+) cells that impair the host immunity and impact the oral and gut microbiomes. Although, the HIV-associated gut microbiota was studied in depth, few works addressed the dysbiosis of oral microbiota in HIV infection and, to our knowledge, no studies on intervention with prebiotics were performed. We studied the effect of a six-week-long prebiotic administration on the salivary microbiota in HIV patients and healthy subjects. Also, the co-occurrence of saliva microorganisms in the fecal bacteria community was explored. We assessed salivary and feces microbiota composition using deep 16S ribosomal RNA (rRNA) gene sequencing with Illumina methodology. At baseline, the different groups shared the same most abundant genera, but the HIV status had an impact on the saliva microbiota composition and diversity parameters. After the intervention with prebiotics, we found a drastic decrease in alpha diversity parameters, as well as a change of beta diversity, without a clear directionality toward a healthy microbiota. Interestingly, we found a differential response to the prebiotics, depending on the initial microbiota. On the basis of 100% identity clustering, we detected saliva sequences in the feces datasets, suggesting a drag of microorganisms from the upper to the lower gastrointestinal tract.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Nora S. Wolff ◽  
Max C. Jacobs ◽  
W. Joost Wiersinga ◽  
Floor Hugenholtz

Abstract Background The gut microbiome plays a protective role in the host defense against pneumonia. The composition of the lung microbiota has been shown to be predictive of clinical outcome in critically ill patients. However, the dynamics of the lung and gut microbiota composition over time during severe pneumonia remains ill defined. We used a mouse model of pneumonia-derived sepsis caused by Klebsiella pneumoniae in order to follow the pathogen burden as well as the composition of the lung, tongue and fecal microbiota from local infection towards systemic spread. Results Already at 6 h post-inoculation with K. pneumoniae, marked changes in the lung microbiota were seen. The alpha diversity of the lung microbiota did not change throughout the infection, whereas the beta diversity did. A shift between the prominent lung microbiota members of Streptococcus and Klebsiella was seen from 12 h onwards and was most pronounced at 18 h post-inoculation (PI) which was also reflected in the release of pro-inflammatory cytokines indicating severe pulmonary inflammation. Around 18 h PI, K. pneumoniae bacteremia was observed together with a systemic inflammatory response. The composition of the tongue microbiota was not affected during infection, even at 18–30 h PI when K. pneumoniae had become the dominant bacterium in the lung. Moreover, we observed differences in the gut microbiota during pulmonary infection. The gut microbiota contributed to the lung microbiota at 12 h PI, however, this decreased at a later stage of the infection. Conclusions At 18 h PI, K. pneumoniae was the dominant member in the lung microbiota. The lung microbiota profiles were significantly explained by the lung K. pneumoniae bacterial counts and Klebsiella and Streptococcus were correlating with the measured cytokine levels in the lung and/or blood. The oral microbiota in mice, however, was not influenced by the severity of murine pneumonia, whereas the gut microbiota was affected. This study is of significance for future studies investigating the role of the lung microbiota during pneumonia and sepsis.


2009 ◽  
Vol 9 (1) ◽  
Author(s):  
Farhad Hosseinpanah ◽  
Farshad Kasraei ◽  
Amir A Nassiri ◽  
Fereidoun Azizi

2021 ◽  
Author(s):  
Roser Torra ◽  
Mónica Furlano ◽  
Alberto Ortiz ◽  
Elisabet Ars

Abstract Inherited kidney diseases (IKDs) are among the leading causes of early-onset chronic kidney disease (CKD) and are responsible for at least 10–15% of cases of kidney replacement therapy (KRT) in adults. Pediatric nephrologists are very aware of the high prevalence of IKDs among their patients, but this is not the case for adult nephrologists. Recent publications have demonstrated that monogenic diseases account for a significant percentage of adult cases of CKD. A substantial number of these patients have received a non-specific/incorrect diagnosis or a diagnosis of CKD of unknown etiology, which precludes correct treatment, follow-up and genetic counseling. There are a number of reasons why genetic kidney diseases are difficult to diagnose in adulthood: a) adult nephrologists, in general, are not knowledgeable about IKDs, b) existence of atypical phenotypes, c) genetic testing is not universally available, d) family history is not always available or may be negative, e) lack of knowledge of various genotype–phenotype relationships, f) conflicting interpretation of the pathogenicity of many sequence variants.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1907.2-1907
Author(s):  
Y. Tsuji ◽  
M. Tamai ◽  
S. Morimoto ◽  
D. Sasaki ◽  
M. Nagayoshi ◽  
...  

Background:Anti-citrullinated protein antibody (ACPA) production is observed in several organs even prior to the onset of rheumatoid arthritis (RA), and oral mucosa is considered to be one of the important tissues. The presence of HLA-DRB1*SE closely associates with ACPA production. Saliva is considered to reflect the oral microbiota including periodontal disease. Alteration of oral microbiota of RA becomes to be normalized by DMARDs treatment, however, the interaction of HLA-DRB1*SE, ACPA and oral microbiota of RA patients remains to be elucidated.Objectives:The Nagasaki Island Study, which had started in 2014 collaborating with Goto City, is intended for research of the preclinical stage of RA, including ACPA/HLA genotype screening and ultrasound and magnetic resonance imaging examinations in high-risk subjects. Using the samples accumulated in this cohort, we have tried to investigate the difference of oral microbiota among RA patients and healthy subjects regarding to ACPA and HLA-DRB1*SE.Methods:Blood and salivary samples were obtained from 1422 subjects out of 4276 who have participated in the Nagasaki Island Study from 2016 to 2018. ACPA positivity was 1.7 % in total. Some of RA patients resided in Goto City participated in the Nagasaki Island Study. At this point, we selected 291 subjects, who were ACPA positive non-RA healthy subjects (n=22) and patients with RA (n=33, 11 subjects were ACPA positive and 22 ACPA negative respectively) as the case, age and gender matched ACPA negative non-RA healthy subjects (n=236) as the control. ACPA was measured by an enzyme-linked immunosorbent assay, and HLA genotyping was quantified by next-generation sequencing (Ref.1). The operational taxonomic unit (OUT) analysis using 16S rRNA gene sequencing were performed. The richness of microbial diversity within-subject (alpha diversity) was scaled via Shannon entropy. The dissimilarity between microbial community composition was calculated using Bray-Curtis distance as a scale, and differences between groups (beta diversity) were tested by permutational multivariate analysis of variance (PERMANOVA). In addition, UniFrac distance calculated in consideration of the distance on the phylogenetic tree were performed.Results:Median age 70 y.o., % Female 58.8 %. Among RA and non-RA subjects, not alpha diversity but beta diversity was statistically significance (p=0.022, small in RA). In RA subjects, both alpha and beta diversity is small (p<0.0001), especially significant in ACPA positive RA (Figure 1). Amongt RA subjects, presence of HLA-DRB1*SE did not show the difference but the tendency of being small of alpha diversity (p=0.29).Conclusion:Our study has suggested for the first time the association of oral microbiota alteration with the presence of ACPA and HLA-DRB1*SE. Oral dysbiosis may reflect the immunological status of patients with RA.References:[1]Kawaguchi S, et al. Methods Mol Biol 2018;1802: 22Disclosure of Interests:None declared


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