UCLA

ABSTRACT OF THE DISSERTATION

Finding the Gut Microbiome Connection to the Risk of Childhood Obesity Through an Examination of Gut Microbiota Among Children in Los Angeles, California: A Cross-Sectional Pilot Study

by

Cecille M. BasilioDoctor of Philosophy in Nursing University of California, Los Angeles, 2024 Professor Felicia Hodge, Chair

Background: Childhood obesity has emerged as one of the most critical public health problems in the 21st century of national and global epidemic concern. Globally, in 2020, the number of children and adolescents between the ages of 5 and 19 who were classified as obese reached 150 million, and projections suggest this number could escalate to 254 million by 2030, according to the World Health Organization (WHO) 2021. In the United States (U.S.), obesity affects approximately 14.7 million children and adolescents aged 2-19 years (Centers for Disease Control and Prevention [CDC], 2022a). Considering the accelerating incidence of childhood obesity and its related comorbidities, environmental predispositions underlying childhood obesity and associated metabolic disorders need to be further explored. The cause of obesity is multifactorial. Genetic factors may determine an individual’s susceptibility to obesity, and environmental and lifestyle factors play a crucial role in the development of obesity. Thus, the gut microbial ecosystem has emerged as a significant environmental factor involved in the pathogenesis of childhood obesity. An altered gut microbiota has been linked to adult obesity. However, very little is known about the association of altered gut microbiota with childhood obesity. Purpose: The purpose of this study was to examine the association between gut microbiota composition and child obesity. The specific aims were to: 1) evaluate the impact of child obesity status on three related outcomes to be assessed by extracting DNA from children’s stool samples using 16S rRNA gene sequencing: alpha diversity of gut microbiota composition, Firmicutes: Bacteroidetes ratio, and abundance of SCFA-generating gut microbes between obese and non-obese school children; 2) compare the dietary habits and intakes between obese and non-obese school children; and 3) evaluate the association of body mass index differences in gut microbiota composition between obese and non-obese school children. Methods: This pilot study used a cross-sectional design. Stool samples were collected and sequenced at the 16S rRNA gene in the V4 region. We recruited 27 participants, 13 in the obese and 14 in the lean groups. The outcomes are diversity of gut microbiota composition, Firmicutes: Bacteroidetes ratio, and abundance of short-chain fatty acid-generating gut microbes. We compared these outcomes between obese and non-obese school children using two sample T-tests. A logistic regression model was used to estimate the association between obese status and microbiota-related outcomes, adjusting for age, race/ethnicity, education of caregiver, and nutrition status. Results: The alpha diversity was similar between the obese and non-obese groups. The F: B ratio in the o/o group was significantly increased (99.54 ±264.52) compared with non-o/o children (31.25 ± 56.25) but not statistically significant at p = 0.38. There were no significant differences in the abundance of Firmicutes between non-o/o (0.71 ± 0.12) and o/o (0.69 ± 0.11) with p = 0.59. Overweight/obese children had an increased gut microbiota-producing SCFA (0.63 ± 0.25) compared with the non-o/o children (0.52 ± 022); however, it was not statistically significant (p = 0.25). Although o/o children consumed more calories (2021.46 ± 570.83) than non-o/o children (1744 ± (415.37), it was not significant at p = 0.16). The overweight/obese children also ate more foods rich in saturated fats (32.69 ± 21.01) than non-o/o children (24.07 ± 6.26), but it was insignificant at p = 0.18. Overweight/obese children had a higher diversity of fiber-rich foods (1.8 ± 1.77) than non-o/o children (1.39 ± 0.82). The differences were not significant (p = 0.46). There was no significant relationship between BMI z-score and Firmicutes, and BMI z-score was not a good predictor of the relative abundance of Firmicutes. Discussion: There were no significant differences in alpha diversity at the phylum level between non-o/o and o/o groups. This suggests that obesity could not be determined as a causality of an alteration or dysbiosis in the gut microbiota among the o/o children in this study. The study's results provided limited evidence to support the F: B ratio as a biomarker for obesity. This study showed that SCFA-generating gut microbes were increased in o/o children compared with non-o/o children; however, it did not reach statistical significance. The daily gut microbiota friendliness score (DGMFS) was not statistically significant when comparing dietary intakes of high-energy, saturated fats, and fiber-rich foods. The study's results did not show an association between BMI z-score and relative abundance of Firmicutes.