The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights

Abstract

The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. Methods: A total of 223 adolescents aged 10 to 18 years with BMI ≥95th percentile were enrolled, along with 71 healthy weight participants. Clinical data, fasting serum, and fecal samples were collected at repeated intervals over 6 months. Herein, the study design, data collection methods, and interim analysis-including targeted serum metabolite measurements and fecal 16S ribosomal RNA gene amplicon sequencing among adolescents with obesity (n = 27) and healthy weight controls (n = 27)-are presented. Results: Adolescents with obesity have higher serum alanine aminotransferase, C-reactive protein, and glycated hemoglobin, and they have lower high-density lipoprotein cholesterol when compared with healthy weight controls. Metabolomics revealed differences in branched-chain amino acid-related metabolites. Also observed was a differential abundance of specific microbial taxa and lower species diversity among adolescents with obesity when compared with the healthy weight group. Conclusions: The Pediatric Metabolism and Microbiome Study (POMMS) biorepository is available as a shared resource. Early findings suggest evidence of a metabolic signature of obesity unique to adolescents, along with confirmation of previously reported findings that describe metabolic and microbiome markers of obesity.

Genotypic and Phenotypic Diversity among Human Isolates of Akkermansia muciniphila

“…The relative abundance of A. muciniphila in fecal samples is highly variable in a cohort of children with obesity. To survey the diversity of A. muciniphila strains present among healthy children and those with obesity, we used fecal samples that had been collected before and after various interventions aimed at decreasing their body mass index (BMI) (18). We selected 5 lean controls (Z-score adjusted BMI, or zBMI, -0.99 to 0.41) and 36 children with extreme obesity (zBMI, -1.63 to 3.18 .…”

“…In this work, we leveraged fecal samples collected as part of the POMMS interventional study for childhood obesity (18) to isolate Akkermansia strains that reflect the diversity of phylogroups present in both healthy and diseased states in children. Importantly, the availability of cultured strains enabled the phenotyping of each isolate to identify variances in traits that may impact the health of their hosts.…”

“…Isolation of A. muciniphila from fecal samples. The recruitment criteria and composition of stool donors in the POMMS Study were previously reported (18). Approximately 75 mg of frozen stool was used to inoculate 1 ml of mucin medium supplemented with vancomycin (6 mg/ml), gentamicin (10 mg/ ml), and kanamycin (12 mg/ml) and incubated at 37°C for 48 h. After three sequential passages in mucin medium, a sample of the suspension was streaked on 1% agar mucin medium plates to isolate single colonies and was incubated for 7 days at 37°C.…”

“…Given that multiple A. muciniphila phylogroups are found in humans, we asked what is the genomic and phenotypic diversity of A. muciniphila isolated from children, with the long-term goal of determining if there are correlates between strain and phylogroup abundance and specific health outcomes. To begin to address these questions, we used fecal samples collected by the Pediatric Obesity Microbiome and Metabolome Study (POMMS) (18) to isolate 71 unique strains of A. muciniphila. Participants included adolescents with healthy weight at a single time point only and adolescents with obesity at baseline and then at 6 months following a behavioral lifestyle intervention.…”

Fecal microbiota relationships with childhood obesity: A scoping comprehensive review

“…14 Thus, there is evidence for an influence of intestinal microbiota on body metabolism in infants with obesity, 15 where increased levels of fecal butyrate may be involved as well as inflammatory phenomena. 16,17 In fact, there are some probiotics that supplies butyrate and administered orally might be key in childhood obesity. 18 Therefore, it has become essential to analyze maternal, prenatal, infant, and childhood interactions that could impact infant's health.…”