Microbiome Dysbiosis in Obese Adolescents: A Potential Contributor to Inflammation

Abstract

Introduction Adolescent obesity remains a public health concern, as the CDC estimates that 1 in 5 adolescents is obese. The development of obesity during childhood not only increases the chance of obesity-related death, but also increases the risk of obesity-related chronic diseases such as type 2 diabetes mellitus, hypertension, and dyslipidemia. Increased inflammation is associated with adipose tissue in obesity and is a main contributor to the development of obesity-related disease. Dysbiosis of the gut microbiome may also contribute to obesity-related systemic inflammation. In this study, patients were educated on dietary habits and exercise in an effort to understand the effect of lifestyle changes on inflammatory markers in the urine. Furthermore, we investigated the gut microbiome profiles of obese adolescents to determine if differences existed from that of healthy adolescents. Methods The study was performed at the Department of Pediatrics at TTUHSC, Amarillo. IRB approval was obtained, and informed consent/assent were signed by the parents and adolescents. Twenty-two obese adolescents ages 8-18 (BMI >25) and 16 healthy adolescents (BMI <25) were recruited into the study. At the start of the study, patients were educated on dietary changes and exercise. Urine samples were collected at enrollment, and at 3- and 6-months post-enrollment visits. Urine samples were analyzed for the presence of pro-inflammatory cytokines TNF-a and IL-6, as well as the marker for endothelial dysfunction, ET-1. Stool samples were procured at the time of enrollment and 16s metagenome sequencing was performed to determine microbiome composition. Results Adolescents with obesity exhibited higher levels of pro-inflammatory TNF-α and IL-6 (3.4 and 1.6-fold increase, respectively) in urine compared to healthy controls. Furthermore, we noted a 1.4-fold increase in urinary ET-1 of obese adolescents. Interestingly, TNF-a, IL-6, and ET-1 levels in the urine decreased in obese adolescents over a period of 6 months, suggesting that changes in diet and exercise may have contributed to these changes. Analysis of the 16s metagenome indicated a difference in the presence of 80 bacterial species between the gut microbiomes of healthy and obese adolescents, as healthy adolescents had 63 bacterial species that exhibited at least a 2-fold higher amount than obese adolescents. Conclusions Obesity is a preventable condition that can result in systemic inflammation and chronic disease. In this study, we found that obese adolescents exhibited higher levels of urinary inflammatory cytokines and altered gut microbiome composition compared to healthy controls. Furthermore, we noted that lifestyle changes over 6 months resulted in decreased urinary inflammatory markers in obese adolescents. The results of this study suggest that the altered gut microbiomes of obese adolescents may be responsible for increased urinary inflammatory cytokine levels and that lifestyle changes may attenuate urinary inflammatory cytokines.