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BackgroundIn adults, gut dysbiosis may contribute to the pathogenesis of gout. However, the characteristics of gut microbiota in children with hyperuricemia (HUA) in the absence of clinical gout have not been explored.ObjectiveThis present study analyzed the gut microbiota in children with HUA as compared to controls (Con) and explored bacterial associations that may account for differences.MethodsA total of 80 children were enrolled in this study; they were divided into HUA and Con according to the level of serum uric acid (UA). The composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing.ResultsPrincipal coordinate analysis revealed that gut microbiota of the HUA group was clustered together and separated partly from the Con group. There was no difference in alpha-diversity between the two groups. However, Spearman’s correlation analysis revealed that serum UA level positively correlated with genera Actinomyces, Morganella, and Streptococcus, and negatively associated with the producers of short-chain fatty acids (SCFAs), such as Alistipes, Faecalibacterium, and Oscillospira, and the sulfidogenic bacteria Bilophila. The members of the genera Alistipes and Bilophila in the Con group were significantly more prevalent than the HUA subjects. Compared to the Con cohort, metabolic pathway predictions found that the superpathways of purine nucleotide de novo biosynthesis were decreased in HUA subjects, whereas the superpathway of purine deoxyribonucleoside de gradation was increased.ConclusionThe composition of the gut microbiota in children with HUA differs from Con. Although causality cannot be established, modification in the microbiota that produces SCFA and sulfide may promote HUA.

Being one of the most dynamic entities in the human body, glycosylation of proteins fine-tunes the activity of the organismal machinery, including the immune system, and mediates the interaction with the human microbial consortium, typically represented by the gut microbiome. Using data from 194 healthy individuals, we conducted an associational study to uncover potential relations between the gut microbiome and the blood plasma N-glycome, including N-glycome of immunoglobulin G. While lacking strong linkages on the multivariate level, we were able to identify associations between alpha and beta microbiome diversity and the blood plasma N-glycome profile. Moreover, for two bacterial genera, namely, Bilophila and Clostridium innocuum, significant associations with specific glycans were also shown. The study’s results suggest a non-trivial, possibly weak link between the total plasma N-glycome and the gut microbiome, predominantly involving glycans related to the immune system proteins, including immunoglobulin G. Further studies of glycans linked to microbiome-related proteins in well-selected patient groups are required to conclusively establish specific associations.

Abstract Background Gankyrin (GK) is an oncoprotein which regulates inflammatory responses and its inhibition is considered as a possible anti-inflammatory therapy for inflammatory bowel disease (IBD). Methods In this study, we investigated the role of GK in epithelial cells using mice with intestinal epithelial cell-specific GK deletion in (i) the entire small intestine and colon (Villin-Cre;Gankyrin f/f ) and (ii) the distal intestine and colon (Cdx2-Cre;Gankyrin f/f ). Result Unexpectedly, GK-deficiency in the upper small bowel augmented inflammatory activity compared with control mice when colitis was induced with dextran sodium sulfate. Biochemical analyses have revealed GK-deficiency to have caused reduction in the expression of antimicrobial peptides, α-Defensin-5 and -6, in the upper small bowel. Examination of human samples have further confirmed that the reduction of GK expression in the small bowel is associated with colonic involvement in human Crohn’s disease. Through the sequencing of bacterial 16S rRNA gene amplicons, bacteria potentially deleterious to intestinal homeostasis such as Helicobacter japonicum and Bilophila were found to be over-represented in colitis induced Villin-Cre;Gankyrin f/f mice when compared to Gankyrin f/f control mice under the same condition. Conclusion These results highlight the distinct site dependence of the pro- and anti-inflammatory functions of GK and provide important insights into the pathogenesis of IBD.

In Canada and the US, the infant diet is supplemented with vitamin D via supplement drops or formula. Pregnant and nursing mothers often take vitamin D supplements. Since little is known about the impact of this supplementation on infant gut microbiota, we undertook a study to determine the association between maternal and infant vitamin D supplementation, infant gut microbiota composition and Clostridioides difficile colonization in 1,157 mother-infant pairs of the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study over 2009–2012. Logistic and MaAsLin regression were employed to assess associations between vitamin D supplementation, and C. difficile colonization, or other gut microbiota, respectively. Sixty-five percent of infants received a vitamin D supplement. Among all infants, infant vitamin D supplementation was associated with a lower abundance of genus Megamonas (q = 0.01) in gut microbiota. Among those exclusively breastfed, maternal prenatal supplementation was associated with lower abundance of Bilophila (q = 0.01) and of Lachnospiraceae (q = 0.02) but higher abundance of Haemophilus (q = 0.02). There were no differences in microbiota composition with vitamin D supplementation among partially and not breastfed infants. Neither infant nor maternal vitamin D supplementation were associated with C. difficile colonization, after adjusting for breastfeeding status and other factors. However, maternal consumption of vitamin-D fortified milk reduced the likelihood of C. difficile colonization in infants (adjustedOR: 0.40, 95% CI: 0.19–0.82). The impact of this compositional difference on later childhood health, especially defense against viral respiratory infection, may go beyond the expected effects of vitamin D supplements and remains to be ascertained.