This study examined sclerostin and cytokine responses to an endurance training session in male single sculling rowers. Sixteen highly trained rowers performed a 2-h rowing exercise (distance: ...23.8 ± 0.9 km; heart rate: 138 ± 8 beats.min
-1
; intensity: 79.8 ± 2.1% of the anaerobic threshold). Rowing resulted significant increment (p < 0.05) in sclerostin (36%), interleukin (IL)-6 (345%), IL-10 (129%) and monocyte chemoattractant protein-1 (MCP-1) (132%), while increases in irisin (6%) and tumour necrosis factor-α (3%) were not significant (p > 0.05). There was a correlation between the pre-to-post-exercise increase in sclerostin and the distance covered (r = 0.67; p = 0.005) as a marker of energy expenditure, and weekly training volume (r = 0.66; p = 0.005) as a marker of training stress. Post-exercise gain in MCP-1 was the most important predictor of post-exercise gain in sclerostin (β = 0.543; p = 0.040). In conclusion, acute non-impact rowing training session with a total body mode induced increases in sclerostin and also in IL-6, IL-10 and MCP-1 concentrations, while post-exercise gain in MCP-1 was the main determinant of post-exercise gain in sclerostin. Exercise-induced increase in sclerostin could be regarded as a signal for metabolic reaction to the energy cost of acute exercise in rowers.
According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune ...maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.
Display omitted
•Finnish and Estonian infants have a distinct early gut microbiome compared to Russians•B. dorei and other Bacteroides species are highly abundant in Finland and Estonia•B. dorei LPS inhibits the immunostimulatory activity of E. coli LPS•LPS from B. dorei does not protect NOD mice from type 1 diabetes
Bacteroides species in the microbiota of children from countries with high susceptibility to autoimmunity produce a type of lipopolysaccharide (LPS) with immunoinhibitory properties. These properties may preclude early immune education and contribute to the development of type 1 diabetes.
Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 ...diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease.
Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics ...throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors.
Display omitted
•Gut microbial metabolic pathways but not taxonomies are stable throughout infancy•Strain composition of high-abundance species remains constant throughout infancy•Decreased community diversity occurs after seroconversion but before onset of T1D•T1D onset is preceded by increased inflammation-associated organisms and pathways
Kostic et al. perform a microbiome analysis of type 1 diabetes (T1D), examining the infant gut microbiome as T1D develops. Microbial metabolic pathways remain remarkably stable throughout infancy. T1D onset is preceded by a drop in community diversity and a spike in inflammation-associated species and metabolic pathways.
The potential impact of the composition of maternal breast milk is poorly known in children who develop celiac disease (CD). The aim of our study was to compare the microbiota composition and the ...concentrations of immune markers in breast milk from mothers whose offspring carried the genetic predisposition to CD, and whether they did or did not develop CD during follow-up for the first 3 years of life. Maternal breast milk samples CD children (n = 6) and healthy children (n = 18) were collected 3 months after delivery. Enzyme-linked immunosorbent assays were used to measure TGF-β1, TGF-β2, sIgA, MFG-E8 and sCD14. For microbiota analysis, next generation (Illumina) sequencing, real-time PCR and denaturing gradient gel electrophoresis were used. Phylotype abundance and the Shannon 'H' diversity index were significantly higher in breast milk samples in the CD group. There was higher prevalence of the phyla Bacteroidetes and Fusobacteria, the classes Clostridia and Fusobacteriia, and the genera Leptotrichia, Anaerococcus, Sphingomonas, Actynomyces and Akkermansia in the CD group. The immunological markers were differently associated with some Gram-negative bacterial genera and species (Chryseobacterium, Sphingobium) as well as Gram-positive species (Lactobacillus reuteri, Bifidobacterium animalis). In conclusion, the microbiota in breast milk from mothers of genetically predisposed offspring who presented CD showed a higher bacterial phylotype abundance and diversity, as well as a different bacterial composition, as compared with the mothers of unaffected offspring. These immune markers showed some associations with bacterial composition and may influence the risk for development of CD beyond early childhood.
Very few studies have analyzed how the composition of mother's microbiota affects the development of infant's gut and oral microbiota during the first months of life. Here, microbiota present in the ...mothers' gut, vagina, breast milk, oral cavity, and mammary areola were compared with the gut and oral microbiota of their infants over the first six months following birth. Samples were collected from the aforementioned body sites from seven mothers and nine infants at three different time points over a 6-month period. Each sample was analyzed with 16S rRNA gene sequencing. The gut microbiota of the infants harbored distinct microbial communities that had low similarity with the various maternal microbiota communities. In contrast, the oral microbiota of the infants exhibited high similarity with the microbiota of the mothers' breast milk, mammary areola and mouth. These results demonstrate that constant contact between microbial communities increases their similarity. A majority of the operational taxonomic units in infant gut and oral microbiota were also shared with the mothers' gut and oral communities, respectively. The disparity between the similarity and the proportion of the OTUs shared between infants' and mothers' gut microbiota might be related to lower diversity and therefore competition in infants' gut microbiota.
Imprinting disorders (ImpDis) represent a small group of rare congenital diseases primarily affecting growth, development, and the hormonal and metabolic systems. The aim of present study was to ...identify the prevalence of the ImpDis in Estonia, to describe trends in the live birth prevalence of these disorders between 1998 and 2016, and to compare the results with previously published data. We retrospectively reviewed the records of all Estonian patients since 1998 with both molecularly and clinically diagnosed ImpDis. A prospective study was also conducted, in which all patients with clinical suspicion for an ImpDis were molecularly analyzed. Eighty-seven individuals with ImpDis were identified. Twenty-seven (31%) of them had Prader-Willi syndrome (PWS), 15 (17%) had Angelman syndrome (AS), 15 (17%) had Silver-Russell syndrome (SRS), 12 (14%) had Beckwith-Wiedemann syndrome (BWS), 10 (11%) had pseudo- or pseudopseudohypoparathyroidism, four had central precocious puberty, two had Temple syndrome, one had transient neonatal diabetes mellitus, and one had myoclonus-dystonia syndrome. One third of SRS and BWS cases fulfilled the diagnostic criteria for these disorders, but tested negative for genetic abnormalities. Seventy-six individuals were alive as of January 1, 2018, indicating the total prevalence of ImpDis in Estonia is 5.8/100,000 (95% CI 4.6/100,000-7.2/100,000). The minimum live birth prevalence of all ImpDis in Estonia in 2004-2016 was 1/3,462, PWS 1/13,599, AS 1/27,198, BWS 1/21,154, SRS 1/15,866, and PHP/PPHP 1/27,198. Our results are only partially consistent with previously published data. The worldwide prevalence of SRS and GNAS-gene-related ImpDis is likely underestimated and may be at least three times higher than expected.
PDF
