Study uncovers gut microbes’ role in childhood obesity

In a recent study published in the journal Clinical Nutrition ESPEN, researchers explored causal associations between the gut microbiome and pediatric adiposity.

Childhood adiposity is a developing concern linked to several health problems in children and adults. Genetics, environment, lifestyle, and gut flora contribute significantly to juvenile obesity. Lifestyle variables such as nutrition and exercise influence childhood obesity. However, the causal link between adiposity and gut microbes is unclear. Gut microbes influence obesity by altering host metabolism. Studies have reported imbalances in gut microbes such as Clostridium and Eubacterium rectale among obesity-prone individuals. The postulated gut-brain nexus implies that fecal microbiota transplantation and prebiotic supplementation are potential anti-obesity treatments.

Study: Causal relationship between gut microbiota and childhood obesity: a Mendelian randomization study and case–control study. Image Credit: Leeferiin / Shutterstock

About the study

In the present study, researchers used Mendelian randomizations (MR) to investigate whether gut microbes are causally associated with childhood obesity. They validated the associations using sequencing information from case-control investigations.

The researchers obtained gut microbiome summary statistics from the international MiBioGen consortium data, including genome-wide genotype and 16S ribosomal ribonucleic acid (rRNA) fecal microbial information provided by 100,18,340 people. They obtained genome-wide association studies (GWAS) summary data for pediatric adiposity from European, Australian, and North American collaborative genome-level meta-analyses of 14 studies with cohort design.

The 14 studies were the North Finland 1966 Birth Cohort, Avon Children and Parents Longitudinal Study, British 1958 Birth Cohort-Welcome Trust Case Control Consortium, British 1958 Birth Cohort-Diabetes type 1 Genetic Consortium, Lifestyle Immunological System Allergy Study, French Young Study, Philadelphia Children’s Hospital study, West Australia Pregnancy Cohort Study, Helsinki Birth Cohort Study (HBCS), Essen Obesity Study, Copenhagen Prospective Study on Asthma in Childhood (COPSAC), Cardiovascular Disease Risk in Young Finns Study, Generation R Study, and CM GOYA study.

The study included 16 obese children and 16 without adiposity to assess their weight, body mass index (BMI), abdominal circumference (AC), serum lipid levels [triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), and high-density lipoproteins (HDL)], and gut microbiomes. Participants also provided fecal samples for high-throughput genetic sequencing using the whole-genome birdshot strategy.

Participants were aged nine to 12 years, without a prior history of thyroid or liver-related diseases, congenital disorders, or genetic defects, and had not attained puberty. Obese children received a three-month weight reduction intervention, including calorie restrictions and increased physical activity. To validate the changes in gut flora caused by obesity, the researchers examined the gut flora macrogenes before and after weight reduction in obese participants.

The team performed Mendelian randomization (MR) using inverse variance weighting (IWV) for analysis. They also used weighted median estimation, MR-Egger regressions, simple modes, and weighted modes. Instrumental variables (IVs) correlated with study exposure, were not associated with potential confounders and were related to the study outcome indirectly through exposure.

Results and discussion

Mendelian randomization identified 16 causal associations between gut microbes and pediatric adiposity. The case-control investigation showed five intestinal microbial differences between participants with obesity and those without. The team noted increased Romboutsia, Turicibacter, and Clostridium sensustricto abundances after weight reduction in obese children.

In the analysis, 10 gut microbes were causally associated with pediatric obesity, including Lentisphaeria species (OR, 1.1), Deltaproteobacteria species (OR, 1.2), Bacteroidaceae species (OR, 1.3), Desulfovibrionaceae species (OR, 1.2), Bacteroides species (OR, 1.2), Butyricicoccus species (OR, 1.2), Eubacterium oxidoreducens species (OR, 0.8), Rikenellaceae RC9 species (OR, 1.1), NB1n species (OR, 1.1), and Victivallales species (OR, 1.1).

The reverse MR analysis showed suggestive associations between childhood obesity and six gut microbiota, including Barnesiella (OR, 0.9), Clostridium sensustricto (OR, 0.9), Marvinbryantia (OR, 0.9), Oscillospira (OR, 0.1), Romboutsia (OR, 0.9), and Turicibacter (OR, 0.9). The findings showed that Deltaproteobacteria, Bacteroidaceae, Desulfovibrionaceae, Bacteroides, and Butyricoccus were more abundant in children with obesity than non-obese children.

Gut microbes create various compounds during digestive processes, like short-chain fatty acids (SCFAs), that impact adipogenesis and hormone synthesis. Reduced gut microbial diversity may increase insulin resistance and pro-inflammatory marker levels. Obesity-related bacteria contribute to obesity development by influencing host energy balance and central hunger through gut-brain interactions.

The study indicated that 16 gut microbiotas, including Bacteroides, Butyricicoccus, Clostridium, Romboutsia, and Turicibacter, are associated with pediatric obesity. Deltaproteobacteria, Bacteroidaceae, Desulfovibrionaceae, Bacteroides, and Butyricicoccus are the most common microbes detected in obese children. Weight loss also boosts the prevalence of Clostridium sensustricto, Romboutsia, and Turicibacter. The team also noted changes in BMI, abdominal circumference, and cholesterol levels in obese youngsters after weight reduction. These discoveries might help us understand the genetic relationship between the gut microbiota and juvenile obesity, reducing its prevalence.