Title: Obesity and Comorbid Diseases as a Host Determinants of Staphylococcus aureus Colonization
Description: The etiology of obesity is heterogeneous as are the cardio-metabolic complications, associated with it. The cardio-metabolic profile of obese individuals places them at risk of a range of chronic metabolic diseases including diabetes. Paradoxically, a subset of the population classified as obese based on established methods present with few metabolic abnormalities, whereas a subset classified as non-obese present with a wide range of abnormalities. The observed heterogeneity suggests not only that excess adiposity is likely one of many determinant of metabolic complications, but also that our methods of measuring obesity might not be fully capturing the underlying biological mechanisms at play. The heterogeneity by which obesity presents itself in the general population is becoming more pertinent to the field of infectious diseases as findings increasingly implicate obesity in impaired host defenses and increased susceptibility to a range of different infectious organisms, one of which is Staphylococcus aureus.

S. aureus is an opportunistic pathogen with significant infectious burdens in clinical, community as well as incarcerated settings. The organism also asymptomatically colonizes human mucosal surfaces, particularly the anterior nares. The anterior nares of approximately 25-30% of US adults are colonized at any given time, and prior colonization serves as a strong predictor of subsequent infection. Obese females have been consistently shown to be at elevated risk of S. aureus colonization, however, findings amongst obese males have been inconsistent. The mechanism by which obesity increases risk of colonization remain unclear, however, many cite the underlying metabolic dysfunction that frequently accompanies obesity. Given the global burden of obesity and increasing evidence that it impairs host defenses, understanding how obesity increases host colonization with S. aureus is imperative. The overall objective of this dissertation was therefore to evaluate the influence of obesity and metabolic abnormalities on S. aureus colonization among New York State Maximum-Security prison inmates.

The objective of the dissertation was met using three aims. First a systematic review was conducted to assess the different definitions used to define persistent S. aureus colonization in community dwelling adults, as well as the reported prevalence estimates associated with those definitions. The study demonstrated that a considerable amount of variation existed in the way persistent colonization was defined in the extant literature. Despite the variation however, the prevalence of persistent S. aureus carriage remained relatively consistent after categorizing the different definitions into four general groups. The review also demonstrated that two groups of persistent carriers might exist. Therefore, differentiating strain persistence carriers from species persistence carriers may reconcile some of the inconsistencies with regard to length of strain carriage reported in the literature. Second, the influence of metabolic heath (a measure incorporating both body mass index (BMI) and metabolic abnormalities) was assessed.

A significantly higher probability of S. aureus colonization of the anterior nares and/or oropharynx was observed among metabolically abnormal normal weight (BMI < 25 kg/m²) as well metabolically abnormal obese (BMI ≥ 30 kg/m²) females when compared to metabolically healthy females. No significant association was observed between the categories of metabolic health and the prevalence of S. aureus colonization among males. We did, however observe a significant decline in exclusive oropharyngeal colonization among obese male inmates with metabolic abnormalities. Lastly, factors associated with persistent S. aureus carriage were evaluated in the third aim. Approximately 27% of the population was persistent carriers at the species level and 17% were persistent carriers at the strain level. Obesity was independently associated with species persistent carriage but not strain persistent carriage. Correspondence analysis evaluating strain compositional differences between exclusive persistent anterior nares carriers, exclusive persistent oropharynx carriers, exclusive persistent carriers at both the anterior nares and oropharynx and intermittent carriers suggested compositional differences existed between the different groups.

More specifically, the relative abundance of certain S. aureus strains appeared more prominent among exclusive nasal carriers as compared to all other carriage/mucosal site types (exclusive oropharynx, both nasal and oropharynx.