Ruimin Chen

Gut dysbiosis has been linked to type 1 diabetes (T1D); however, microbial capacity in T1D remains unclear. Here, we integratively profiled gut microbial functional and metabolic alterations in children with new-onset T1D in independent cohorts and investigated the underlying mechanisms. In T1D, the microbiota was characterized by decreased butyrate production and bile acid metabolism and increased lipopolysaccharide biosynthesis at the species, gene, and metabolite levels. The combination of 18 bacterial species and fecal metabolites provided excellently discriminatory power for T1D. Gut microbiota from children with T1D induced elevated fasting glucose levels and declined insulin sensitivity in antibiotic-treated mice. In streptozotocin-induced T1D mice, butyrate and lipopolysaccharide exerted protective and destructive effects on islet structure and function, respectively. Lipopolysaccharide aggravated the pancreatic inflammatory response, while butyrate activated Insulin1 and Insulin2 gene expression. Our study revealed perturbed microbial functional and metabolic traits in T1D, providing potential avenues for microbiome-based prevention and intervention for T1D.

OBJECTIVES: To determine the current prevalence and mean ages of onset of pubertal characteristics in healthy urban Chinese girls. METHODS: A cross-sectional study of sexual maturation of healthy Chinese girls was conducted in 9 representative cities of the eastern, western, southern, and northern parts and central region of China between 2003 and 2005. At examination, stages of breast and pubic hair development were rated on girls 3 through 19.83 years of age, and height and weight were also recorded. Data on menses were collected by the status quo method. Probit analysis was used to calculate the median age and 95% confidence interval (CI) for onset of breast and pubic hair development and menarche. RESULTS: Data were analyzed for 20654 apparently healthy girls. At age 8 years, 19.57% of these girls had evidence of breast development. The median ages of onset of Tanner stages 2 and 3 for breast development were 9.20 (95% CI: 9.06-9.32) years and 10.37 (95% CI: 10.28-10.45) years, respectively. The median ages of onset of Tanner stages 2 and 3 for pubic hair development were 11.16 (95% CI: 11.03-11.29) years and 12.40 (95% CI: 12.25-12.55) years, respectively. Menses occurred at 12.27 years (95% CI: 12.16-12.39). CONCLUSIONS: These data suggest that urban Chinese girls are actually experiencing earlier breast development than currently used norms. The up-to-date reference for normal pubertal development in urban Chinese girls needs to be established for the purpose of determining precocious puberty or pubertal delay.

BACKGROUND: Accumulating evidence infer that gut microbiome-host relations are key mediators or modulators driving the observed sexual dimorphism in some disease onset and progression. To date, the sex-differences of gut microbiota at different pubertal status have not been reported. OBJECTIVE: To determine the characteristics of gut microbiota of both genders at different pubertal status. METHODS: Gut microbiota was analyzed in 89 Chinese participants aged 5-15 years. Participants were divided into pre-puberty and puberty groups for both male and female. The composition of gut microbiota was investigated by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed. The prediction of metagenomic functional content from 16S rRNA gene surveys was conducted. RESULTS: There were 49 males (9.76 ± 2.15 years) and 40 females (9.74 ± 1.63 years); 21 males and 26 females were at puberty. At genus level, Alistipes, Megamonas, Oscillospira and Parabacteroides were more prevalent in girls than in boys (p < 0.05). There were no significantly differences of alpha-diversity between genders, which was independent of pubertal status. The beta-diversity was significantly different in pubertal subjects between genders. Using statistical analyses, we assigned genera Dorea, Megamonas, Bilophila, Parabacteroides and Phascolarctobacterium as microbial markers for pubertal subjects. The predicted metabolic profiles differ in both pubertal and pre-pubertal groups between genders. CONCLUSION: This cross-sectional study revealed that sex differences in the gut microbiota composition and predicted metabolic profiles exist before puberty, which become more significant at puberty. The identification of novel puberty bacterial markers may disclose a potential effects of gender-related microbiota profiles on puberty onset.

BACKGROUND: The make-up of gut microbiota at different puberty stages has not been reported. This cross-sectional study analyzed the bio-diversity of gut microbiota at different puberty stages. RESULT: The subjects (aged 5-15 years) were divided into non-pubertal (n = 42, male%: 66.7%) or pubertal groups (n = 47, male%:44.68); in both groups, Firmicutes, Bacteroidetes and Proteobacteria were the dominant phylum. There was no difference of alpha- and beta-diversity among disparate puberty stages. Non-pubertal subjects had members of the order Clostridiales, family Clostridiaceae, genus Coprobacillus which were significantly more prevalent than puberty subjects. Also, the pubertal subjects had members of class Betaproteobacteria, order Burkholderiales which were significantly more prevalent than the non-pubertal subjects. Their relative abundance was independent of BMI-Z. In the pubertal subjects, the abundance of genus Adlercreutzia, Ruminococcus, Dorea, Clostridium and Parabacteroides was associated with the level of testosterone. CONCLUSIONS: This is the first report of the diversity of gut microbiota at different puberty stages. The various species of gut microbiota changed gradually associated with puberty stages. Differences in gut microflora at different pubertal status may be related to androgen levels.

BACKGROUND: The term "metabolically healthy obese (MHO)" denotes a hale and salutary status, yet this connotation has not been validated in children, and may, in fact, be a misnomer. As pertains to obesity, the gut microbiota has garnered attention as conceivably a nosogenic or, on the other hand, protective participator. OBJECTIVE: This study explored the characteristics of the fecal microbiota of obese Chinese children and adolescents of disparate metabolic statuses, and the associations between their gut microbiota and circulating proinflammatory factors, such as IL-6, TNF-α, lipopolysaccharide-binding protein (LBP), and a cytokine up-regulator and mediator, leptin. RESULTS: Based on weight and metabolic status, the 86 Chinese children (ages 5-15 years) were divided into three groups: metabolically healthy obese (MHO, n = 42), metabolic unhealthy obese (MUO, n = 23), and healthy normal weight controls (Con, n = 21). In the MUO subjects, the phylum Tenericutes, as well as the alpha and beta diversity, were significantly reduced compared with the controls. Furthermore, Phylum Synergistetes and genus Bacteroides were more prevalent in the MHO population compared with controls. For the MHO group, Spearman's correlation analysis revealed that serum IL-6 positively correlated with genus Paraprevotella, LBP was positively correlated with genus Roseburia and Faecalibacterium, and negatively correlated with genus Lactobacillus, and leptin correlated positively with genus Phascolarctobacterium and negatively with genus Dialister (all p < 0.05). CONCLUSION: Although there are distinct differences in the characteristic gut microbiota of the MUO population versus MHO, dysbiosis of gut microsystem is already extant in the MHO cohort. The abundance of some metabolism-related bacteria associates with the degree of circulating inflammatory compounds, suggesting that dysbiosis of gut microbiota, present in the MHO children, conceivably serves as a compensatory or remedial response to a surfeit of nutrients.