Particle Radiation Side-Effects: Intestinal Microbiota Composition Shapes Interferon-γ-Induced Osteo-Immunogenicity

2021 ◽  
Author(s):  
Irene Maier ◽  
Paul M Ruegger ◽  
Julia Deutschmann ◽  
Thomas H. Helbich ◽  
Peter Pietschmann ◽  
...  

Microbiota can both negatively and positively impact radiation-induced bone loss. Our prior research showed that compared to mice with conventional gut microbiota (CM), mice with restricted gut microbiota (RM) reduced inflammatory tumor necrosis factor (TNF) in bone marrow, interleukin (IL)-17 in blood, and chemokine (C-C motif) ligand 20 (CCL20) in bone marrow under anti-IL-17 treatment. We showed that Muribaculum intestinale was more abundant in intestinal epithelial cells (IECs) from the small intestine of female RM mice and positively associated with augmented skeletal bone structure. Female C57BL/6J pun RM mice, which were injected with anti-IL-17 antibody one day before exposure to 1.5 Gy 28Si ions of 850 MeV/u, showed high trabecular numbers in tibiae at 6 weeks postirradiation. Irradiated CM mice were investigated for lower interferon-γ and IL-17 levels in the small intestine than RM mice. IL-17 blockage resulted in bacterial indicator phylotypes being different between both microbiota groups before and after irradiation. Analysis of the fecal bacteria were performed in relation to bone quality and body weight, showing reduced tibia cortical thickness in irradiated CM mice (–15%) vs. irradiated RM mice (–9.2%). Correlation analyses identified relationships among trabecular bone parameters (TRI-BV/TV, Tb.N, Tb.Th, Tb.Sp) and Bacteroides massiliensis, Muribaculum sp. and Prevotella denticola. Turicibacter sp. was found directly correlated with trabecular separation in anti-IL-17 treated mice, whereas an unidentified Bacteroidetes correlated with trabecular thickness in anti-IL-17 neutralized and radiation-exposed mice. We demonstrated radiation-induced osteolytic damage to correlate with bacterial indicator phylotypes of the intestinal microbiota composition, and these relationships were determined from the previously discovered dose-dependent particle radiation effects on cell proliferation in bone tissue. New translational approaches were designed to investigate dynamic changes of gut microbiota in correlation with conditions of treatment and disease as well as mechanisms of systemic side-effects in radiotherapy.

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 324 ◽  
Author(s):  
Sheila Estruel-Amades ◽  
Malén Massot-Cladera ◽  
Francisco Pérez-Cano ◽  
Àngels Franch ◽  
Margarida Castell ◽  
...  

Hesperidin, found in citrus fruits, has shown a wide range of biological properties. Nonetheless, a more in-depth investigation is required on the effects on the immune system, and in particular, on the gut-associated lymphoid tissue, together with its relationship with the gut microbiota. Therefore, we aimed to establish the influence of oral hesperidin administration on the intestinal lymphoid tissue and on the gut microbiota composition in healthy animals. Lewis rats were orally administrated 100 or 200 mg/kg hesperidin three times per week for four weeks. Microbiota composition and IgA-coated bacteria were determined in caecal content. Mesenteric lymph node lymphocyte (MLNL) composition and functionality were assessed. IgA, cytokines, and gene expression in the small intestine were quantified. Hesperidin administration resulted in a higher number of bacteria and IgA-coated bacteria, with changes in microbiota composition such as higher Lactobacillus proportion. Hesperidin was also able to increase the small intestine IgA content. These changes in the small intestine were accompanied by a decrease in interferon-γ and monocyte chemotactic protein-1 concentration. In addition, hesperidin increased the relative proportion of TCRαβ+ lymphocytes in MLNL. These results show the immunomodulatory actions of hesperidin on the gut-associated lymphoid tissue and reinforce its role as a prebiotic.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e038933
Author(s):  
Rita Salvado ◽  
Sandra Santos-Minguez ◽  
Cristina Agudo-Conde ◽  
Cristina Lugones-Sanchez ◽  
Angela Cabo-Laso ◽  
...  

IntroductionIntestinal microbiota is arising as a new element in the physiopathology of cardiovascular diseases. A healthy microbiota includes a balanced representation of bacteria with health promotion functions (symbiotes). The aim of this study is to analyse the relationship between intestinal microbiota composition and arterial stiffness.Methods and analysisAn observational case—control study will be developed. Cases will be defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), Cardio-Ankle Vascular Index (CAVI), brachial ankle pulse wave velocity (ba or ba-PWV) above the 90th percentile, for age and sex, of the reference population. Controls will be selected from the same population as cases. The study will be developed in Primary Healthcare Centres. We will select 500 subjects (250 cases and 250 controls), between 45 and 74 years of age. Cases will be selected from a database that combines data from EVA study (Spain) and Guimarães/Vizela study (Portugal). Measurements: cf-PWV will be measured using the SphygmoCor system, CAVI, ba-PWV and Ankle-Brachial Index will be determined using VaSera device. Gut microbiome composition in faecal samples will be determined by 16S ribosomal RNA sequencing. Lifestyle will be assessed by food frequency questionnaire, adherence to the Mediterranean diet and IPAQ (International Physical Activity Questionnaire). Body composition will be evaluated by bioimpedance.Ethics and disseminationThe study has been approved by ‘Committee of ethics of research with medicines of the health area of Salamanca’ on 14 December 2018 (cod. 2018-11-136) and the ’Ethics committee for health of Guimaraes’ (Portugal) on 15 October 2019 (ref: 67/2019). All study participants will sign an informed consent form agreeing to participate in the study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow a better description of gut microbiota in patients with arterial stiffness.Trial registration detailsClinicalTrials.gov, identifier NCT03900338


2017 ◽  
Vol 8 (10) ◽  
pp. 3510-3522 ◽  
Author(s):  
Laura E. Griffin ◽  
Katherine A. Witrick ◽  
Courtney Klotz ◽  
Melanie R. Dorenkott ◽  
Katheryn M. Goodrich ◽  
...  

Grape seed extract changes small intestinal gut microbiota composition.


mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Héctor Argüello ◽  
Jordi Estellé ◽  
Finola C. Leonard ◽  
Fiona Crispie ◽  
Paul D. Cotter ◽  
...  

ABSTRACT Salmonella colonization and infection in production animals such as pigs are a cause for concern from a public health perspective. Variations in susceptibility to natural infection may be influenced by the intestinal microbiota. Using 16S rRNA compositional sequencing, we characterized the fecal microbiome of 15 weaned pigs naturally infected with Salmonella at 18, 33, and 45 days postweaning. Dissimilarities in microbiota composition were analyzed in relation to Salmonella infection status (infected, not infected), serological status, and shedding pattern (nonshedders, single-point shedders, intermittent-persistent shedders). Global microbiota composition was associated with the infection outcome based on serological analysis. Greater richness within the microbiota postweaning was linked to pigs being seronegative at the end of the study at 11 weeks of age. Members of the Clostridia, such as Blautia, Roseburia, and Anaerovibrio, were more abundant and part of the core microbiome in nonshedder pigs. Cellulolytic microbiota (Ruminococcus and Prevotella) were also more abundant in noninfected pigs during the weaning and growing stages. Microbial profiling also revealed that infected pigs had a higher abundance of Lactobacillus and Oscillospira, the latter also being part of the core microbiome of intermittent-persistent shedders. These findings suggest that a lack of microbiome maturation and greater proportions of microorganisms associated with suckling increase susceptibility to infection. In addition, the persistence of Salmonella shedding may be associated with an enrichment of pathobionts such as Anaerobiospirillum. Overall, these results suggest that there may be merit in manipulating certain taxa within the porcine intestinal microbial community to increase disease resistance against Salmonella in pigs. IMPORTANCE Salmonella is a global threat for public health, and pork is one of the main sources of human salmonellosis. However, the complex epidemiology of the infection limits current control strategies aimed at reducing the prevalence of this infection in pigs. The present study analyzes for the first time the impact of the gut microbiota in Salmonella infection in pigs and its shedding pattern in naturally infected growing pigs. Microbiome (16S rRNA amplicon) analysis reveals that maturation of the gut microbiome could be a key consideration with respect to limiting the infection and shedding of Salmonella in pigs. Indeed, seronegative animals had higher richness of the gut microbiota early after weaning, and uninfected pigs had higher abundance of strict anaerobes from the class Clostridia, results which demonstrate that a fast transition from the suckling microbiota to a postweaning microbiota could be crucial with respect to protecting the animals.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Caroline Marcantonio Ferreira ◽  
Angélica Thomaz Vieira ◽  
Marco Aurelio Ramirez Vinolo ◽  
Fernando A. Oliveira ◽  
Rui Curi ◽  
...  

The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sabrine Naimi ◽  
Emilie Viennois ◽  
Andrew T. Gewirtz ◽  
Benoit Chassaing

Abstract Background Epidemiologic evidence and animal studies implicate dietary emulsifiers in contributing to the increased prevalence of diseases associated with intestinal inflammation, including inflammatory bowel diseases and metabolic syndrome. Two synthetic emulsifiers in particular, carboxymethylcellulose and polysorbate 80, profoundly impact intestinal microbiota in a manner that promotes gut inflammation and associated disease states. In contrast, the extent to which other food additives with emulsifying properties might impact intestinal microbiota composition and function is not yet known. Methods To help fill this knowledge gap, we examined here the extent to which a human microbiota, maintained ex vivo in the MiniBioReactor Array model, was impacted by 20 different commonly used dietary emulsifiers. Microbiota density, composition, gene expression, and pro-inflammatory potential (bioactive lipopolysaccharide and flagellin) were measured daily. Results In accordance with previous studies, both carboxymethylcellulose and polysorbate 80 induced a lasting seemingly detrimental impact on microbiota composition and function. While many of the other 18 additives tested had impacts of similar extent, some, such as lecithin, did not significantly impact microbiota in this model. Particularly stark detrimental impacts were observed in response to various carrageenans and gums, which altered microbiota density, composition, and expression of pro-inflammatory molecules. Conclusions These results indicate that numerous, but not all, commonly used emulsifiers can directly alter gut microbiota in a manner expected to promote intestinal inflammation. Moreover, these data suggest that clinical trials are needed to reduce the usage of the most detrimental compounds in favor of the use of emulsifying agents with no or low impact on the microbiota.


2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Sharath P. Sasi ◽  
Daniel Park ◽  
Sujatha Muralidharan ◽  
Justin Wage ◽  
Albert Kiladjian ◽  
...  

Bone-marrow- (BM-) derived endothelial progenitor cells (EPCs) are critical for endothelial cell maintenance and repair. During future space exploration missions astronauts will be exposed to space irradiation (IR) composed of a spectrum of low-fluence protons (1H) and high charge and energy (HZE) nuclei (e.g., iron-56Fe) for extended time. How the space-type IR affects BM-EPCs is limited. In media transfer experimentsin vitrowe studied nontargeted effects induced by1H- and56Fe-IR conditioned medium (CM), which showed significant increase in the number of p-H2AX foci in nonirradiated EPCs between 2 and 24 h. A 2–15-fold increase in the levels of various cytokines and chemokines was observed in both types of IR-CM at 24 h.Ex vivoanalysis of BM-EPCs from single, low-dose, full-body1H- and56Fe-IR mice demonstrated a cyclical (early 5–24 h and delayed 28 days) increase in apoptosis. This early increase in BM-EPC apoptosis may be the effect of direct IR exposure, whereas late increase in apoptosis could be a result of nontargeted effects (NTE) in the cells that were not traversed by IR directly. Identifying the role of specific cytokines responsible for IR-induced NTE and inhibiting such NTE may prevent long-term and cyclical loss of stem and progenitors cells in the BM milieu.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2936
Author(s):  
Maija Marttinen ◽  
Reeta Ala-Jaakkola ◽  
Arja Laitila ◽  
Markus J. Lehtinen

Among athletes, nutrition plays a key role, supporting training, performance, and post-exercise recovery. Research has primarily focused on the effects of diet in support of an athletic physique; however, the role played by intestinal microbiota has been much neglected. Emerging evidence has shown an association between the intestinal microbiota composition and physical activity, suggesting that modifications in the gut microbiota composition may contribute to physical performance of the host. Probiotics represent a potential means for beneficially influencing the gut microbiota composition/function but can also impact the overall health of the host. In this review, we provide an overview of the existing studies that have examined the reciprocal interactions between physical activity and gut microbiota. We further evaluate the clinical evidence that supports the effects of probiotics on physical performance, post-exercise recovery, and cognitive outcomes among athletes. In addition, we discuss the mechanisms of action through which probiotics affect exercise outcomes. In summary, beneficial microbes, including probiotics, may promote health in athletes and enhance physical performance and exercise capacity. Furthermore, high-quality clinical studies, with adequate power, remain necessary to uncover the roles that are played by gut microbiota populations and probiotics in physical performance and the modes of action behind their potential benefits.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3444
Author(s):  
Julia Beisner ◽  
Anita Gonzalez-Granda ◽  
Maryam Basrai ◽  
Antje Damms-Machado ◽  
Stephan C. Bischoff

High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.


2018 ◽  
Author(s):  
Fernanda L. Paganelli ◽  
Misha Luyer ◽  
C. Marijn Hazelbag ◽  
Hae-Won Uh ◽  
Malbert R.C. Rogers ◽  
...  

AbstractBackgroundBariatric surgery in patients with morbid obesity, either through gastric sleeve gastrectomy or Roux-Y gastric bypass surgery, leads to sustainable weight loss, improvement of metabolic disorders and changes in the intestinal microbiota. Yet, the relationship between changes in gut microbiota, weight loss and the surgical procedure remains incompletely understood.Subjects/MethodsWe determined temporal changes in microbiota composition in 45 obese patients undergoing a crash diet followed by gastric sleeve gastrectomy (n= 22) or Roux-Y gastric bypass (n= 23). Intestinal microbiota composition was determined before intervention (baseline, S1), 2 weeks after a crash diet (S2), and 1 week (S3), 3 months (S4) and 6 months (S5) after surgery.ResultsRelative to S1, the microbial diversity index declined at S2 and S3 (p< 0.05), and gradually returned to baseline levels at S5. The crash diet was associated with an increased abundance of Rikenellaceae and decreased abundances of Ruminococcaceae and Streptococcaceae (p< 0.05). After surgery, at S3, the relative abundance of Bifidobacteriaceae had decreased (compared to the moment directly after the crash diet), whereas those of Streptococcaceae and Enterobacteriaceae had increased (p< 0.05). Increased weight loss during the next 6 months was not associated without major changes in microbiota composition. Significant differences between both surgical procedures were not observed at any of the time points.ConclusionsIn conclusion, undergoing a crash diet and bariatric surgery were associated with an immediate but temporary decline in the microbial diversity, with immediate and permanent changes in microbiota composition, with no differences between patients undergoing gastric sleeve gastrectomy or Roux-Y gastric bypass surgery.


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