Manal Ali Ahmad

Obesity is a complex chronic disease driven by the interaction of genetic, hormonal, and microbial factors. In the Middle East—particularly the Gulf region—its prevalence has risen rapidly, placing considerable strain on healthcare systems and increasing the burden of cardiometabolic disease. Despite growing global research on gut microbiota and gut-derived peptides as regulators of metabolic health, Arab populations remain underrepresented. Ethnicity, cultural dietary patterns, lifestyle practices, and genetic background may shape gut microbial composition and hormonal responses in ways that differ from Western cohorts. This thesis, therefore, investigated obesity through a multi-dimensional lens, examining gut microbiota, gut-derived peptide hormones, and metabolic health among Emirati and Lebanese adults, while also evaluating how bariatric surgery is associated with changes in host–microbiota interactions. By integrating cross-sectional, prospective, and comparative approaches, this work provides a regionally specific perspective on biological pathways underlying obesity in Arab populations.

Emirati adults with obesity demonstrated characteristic hormonal dysregulation, including elevated fasting GLP-1, GLP-2, leptin, insulin, and CCK, along with significantly lower ghrelin. Among these peptides, GLP-1 showed the strongest association with insulin resistance, independent of BMI, indicating potential relevance as a marker of metabolic dysfunction in this population. Leptin correlated with adiposity measures, while lower ghrelin and higher CCK suggested altered appetite and satiety signalling. These findings provide novel hormone–phenotype data for an understudied Arab population and suggest that physiological adaptations to energy balance and metabolic regulation may differ from those observed in Western cohorts.

Fecal microbiota profiling revealed that the commonly cited Firmicutes/Bacteroidota ratio did not differ between lean and obese participants, supporting the growing body of evidence that this phylum-level marker lacks universality. Instead, genus-level composition proved more informative: Acidaminococcus and Lachnospira were enriched in individuals with obesity and positively associated with adiposity and central fat accumulation, whereas several genera enriched in lean individuals correlated inversely with adiposity measures. These results highlight that microbial signatures of obesity are context-dependent and shaped by diet, lifestyle, and population-specific factors, reinforcing the need for high-resolution taxonomic analyses in microbiome research.

Three months after sleeve gastrectomy, participants exhibited substantial weight loss and improvements in insulin sensitivity. These metabolic gains were accompanied by marked restructuring of the gut microbiota: microbial β-diversity increased, lean-associated genera (e.g., Christensenella, Ruminococcus, Alistipes) gained in relative abundance, and phylum-level shifts included increases in Proteobacteria and Saccharibacteria. Simultaneously, hormonal adaptations occurred: fasting PYY increased, while GLP-1 and insulin decreased; ghrelin showed a modest rise. Collectively, these changes suggest early recalibration of enteroendocrine signalling, occurring alongside microbial restructuring. While causal relationships cannot be established, this chapter presents the first evidence in an Emirati cohort that bariatric surgery may trigger synchronous microbial and hormonal adaptations associated with metabolic improvement.

Comparison between obese Lebanese and Emirati individuals revealed significant inter-population differences. Lebanese participants showed higher microbial α-diversity and greater abundance of fibre-associated genera (Alloprevotella, Paraprevotella), consistent with higher reported dietary fibre intake. Emiratis, in contrast, were enriched in Bacteroides and Parabacteroides, taxa typically associated with high-fat, low-fibre diets. These differences persisted after age adjustment, underscoring the strong influence of cultural dietary habits and environmental factors on gut microbial communities. Notably, the Firmicutes/Bacteroidota ratio remained similar between countries, reinforcing the limited utility of such phylum-based metrics and highlighting the need for context-specific, higher-resolution analyses. These results demonstrate that even within the Middle East, gut microbiota composition varies significantly between populations, shaped by diet, lifestyle, and ethnic background — with important implications for designing culturally adapted interventions.

Across all chapters, this thesis reveals that obesity in Arab populations is characterized by interconnected alterations in gut-derived peptide hormones, gut microbial composition, and metabolic parameters — shaped by ethnicity, diet, lifestyle, and surgical intervention. Gut peptides, including GLP-1, GLP-2, insulin, leptin, ghrelin, PYY, and CCK, collectively reflect a hormonal milieu associated with insulin resistance, altered appetite regulation, and metabolic dysregulation. Microbial genera such as Acidaminococcus, Lachnospira, Christensenella, Alloprevotella, and others emerge as population-specific markers associated with adiposity, dietary patterns, and metabolic health. Bariatric surgery further underscores the dynamic nature of the host–microbiota–hormone axis, acting as a system-level metabolic change that triggers coordinated—but non-causal microbial and hormonal shifts accompanying metabolic improvement. Overall, the thesis indicates that universal microbial or hormonal biomarkers are insufficient; instead, context-specific, culturally grounded, and high-resolution approaches are required to understand and manage obesity in Arab populations.

This thesis advances understanding of obesity pathophysiology in underrepresented Arab populations by providing one of the first integrated datasets, combining gut-derived peptides, gut microbiota composition, and metabolic health in Emirati and Lebanese adults. Its findings provide a basis for future investigation of personalized, microbiota-aware, and culturally adapted strategies for obesity prevention and treatment. Future research should build on these findings by conducting larger, multi-ethnic, and well-phenotyped cohort studies; employing functional microbiome analyses (metagenomics, metabolomics) to assess microbial metabolic capacity; integrating detailed dietary, lifestyle, and environmental data; evaluating long-term trajectories after interventions such as bariatric surgery or nutritional modulation; and investigating microbiota or hormone-targeted interventions in randomized controlled trials. By doing so, this body of work lays the foundation for evidence-based, context-sensitive, and equitable obesity management strategies in the Middle East, while contributing to closing gabs in global microbiome and metabolic health research. Importantly, these findings emphasize that effective obesity management in the Middle East requires moving beyond one-size-fits-all models toward culturally and biologically informed approaches.