Doctor of Philosophy (PhD)
An increasing number of studies suggest that the complex microbial community of the human gut may have an important role in human health and disease conditions such as obesity and diabetes. However, the causal relationship among gut microbiota, obesity, weight loss, and the influence of bariatric surgery remains largely unknown. This study investigated the correlation between human gut microbiota and obesity via determining how gut microbiota is associated with obesity improvement induced by bariatric surgeries (BRS) and low-calorie diet (LCD) treatment. Specifically, we investigated the effects of various bariatric surgery (BRS) procedures and a low-calorie diet (LCD) treatment on the diversity, composition, and metabolism of the gut microbiota of obese patients using a combination of robust, high-throughput metagenomic technologies, (Illumina sequencing and HuMiChip microarray), quantitative polymerase chain reaction (qPCR), and gas chromatography. We discovered that following BRS procedures or LCD treatment the gut microbial community structure significantly altered, along with efficient, persistent obesity improvement after bariatric surgeries and, to a lesser degree, LCD treatment. First, microbial richness and diversity were significantly increased after both treatments. Second, the distribution and composition of microbial community were switched toward a healthier profile. For instance, phylum Actinobacteria was significantly reduced, while phylum Verrucomicrobia was significantly increased at week 52 after BRS. Phylum Firmicutes was significantly reduced, while phylum Bacteroidetes was significantly increased after LCD treatment. Microbial community structure at different taxonomic levels and their connectivity were significantly correlated with obesity-related physiological variables, and high-molecular-weight adiponectin (ADPHMW) seemed to be an important factor that links to the correlation. Third, microbial functional gene profile was significantly altered at week 7 post treatments, with the BRS group showing significantly higher gene richness and diversity than the LCD group. Over half of the gene categories showed significant correlations with obesity-related physiological variables, and the entire gene community significantly correlated with obesity-related hormones (adiponectin [ADP], APHMW and active Ghrelin [GHRA]), with the gene richness and diversity significantly negatively correlated with the active hunger hormone GHRA. In addition, we found that genus Akkermansia was significantly correlated with better health condition. It significantly increased after BRS treatment, and its change showed a significantly negative correlation with a change of obesity conditions following the treatments. Moreover, the concentrations of gut microbial metabolites (short-chain fatty acids [SCFAs]) were significantly altered. Total SCFAs and acetate were significantly reduced after both treatments. Following BRS, the proportion of acetate was significantly reduced, while proportions of propionate and butyrate were significantly increased. Correspondingly, the relative abundance of most butyrate-producing genera was significantly increased after BRS, and the gene communities relevant to the metabolism of SCFAs significantly correlated with obesity-related hormones (ADP, ADPHW, peptide tyrosine tyrosine [PYY] and GHRA). Using a combination of multiple approaches, this research revealed that both taxonomical and functional gut microbial communities significantly correlate with obesity-related variables. The study indicates that weight-loss treatments might induce the alteration of gut microbial community structure toward a healthier profile, which then further fosters the weight loss and better health condition and thus form a positive loop. Obesity-related hormones, including ADPHMW, ADP, glucagon-like peptide-1 (GLP-1), PYY, GHR, and GHRA, in particular, ADPHMW, might play important roles in linking gut microbiota and obesity. A pathway of gut microbiota-ADPHMW-obesity could be one of the important mechanisms that underlie the substantial and persistent weight loss following bariatric surgeries. The study suggests several potential therapeutic methods that could be developed for treatment and/or prevention of obesity and obesity-related health conditions, including (1) supplying obese people with prebiotics (materials that boost beneficial microbes) and/or probiotics (beneficial microbes, such as Akkermansia and butyrate-producing bacteria) that can improve the healthiness of gut microbial community structure, (2) supplying human subjects with beneficial gut microbial products, such as butyrate and propionate that can increase the level of GLP-1 and PYY which have been proven to signal satiety, and (3) direct use of hormones such as ADPHMW, GLP-1, and PYY with caution of other possible health effects.
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Zhang, Rui, "Human Gut Microbiota and Obesity:
How Is Gut Microbiota Associated with Obesity Improvement Induced by Bariatric Surgeries or Low-Calorie Diet Treatment?" (2017). LSU Doctoral Dissertations. 4272.
Available for download on Saturday, February 23, 2019