Date Published: April 23, 2019
Publisher: Public Library of Science
Author(s): Michelle C. Coleman, Canaan M. Whitfield-Cargile, Rodolfo G. Madrigal, Noah D. Cohen, Hauke Smidt.
Metabolic diseases such as obesity and type 2 diabetes in humans have been linked to alterations in the gastrointestinal microbiota and metabolome. Knowledge of these associations has improved our understanding of the pathophysiology of these diseases and guided development of diagnostic biomarkers and therapeutic interventions. The cellular and molecular pathophysiology of equine metabolic syndrome (EMS) and obesity in horses, however, remain ill-defined. Thus, the objectives of this study were to characterize the fecal microbiome, fecal metabolome, and circulating lipidome in obese and non-obese horses. The fecal microbiota, fecal metabolome, and serum lipidome were evaluated in obese (case) horses (n = 20) and non-obese (control) horses (n = 20) matched by farm of origin (n = 7). Significant differences in metabolites of the mitochondrial tricarboxylic acid cycle and circulating free fatty acids were identified in the obese horses compared to the non-obese horses. These results indicate that the host and bacterial metabolism should be considered important in obese horses. Further studies to determine whether these associations are causal and the mechanistic basis of the association are warranted because they might reveal diagnostic biomarkers and therapeutic interventions to mitigate obesity, EMS, and sequelae including laminitis.
Obesity is of rising concern for the health and well-being of the horse, with a reported prevalence of 31% in the United Kingdom . An obese body condition score (BCS) is associated with an increased risk of hyperinsulinemia [2–4], insulin dysregulation (ID) , and laminitis . The combination of obesity, ID, and laminitis are components of equine metabolic syndrome (EMS) . Our current understanding of EMS is based on diagnostic tests that inadequately assess the pathophysiology of the condition at the cellular and molecular levels. Consequently, our ability to diagnose, manage, and prevent this syndrome is limited.
Forty horses (20 obese and 20 non-obese) from 7 farms were included in the study (S1 Table). Of the 40 horses, 31 were geldings and 9 were mares. The mean BCS for obese horses was 7.6 (SD 0.4) and the mean BCS for non-obese horses was 4.6 (SD 0.6). Horses ranged in age from 5 to 24 years, with a mean of 14 years (SD 5.17). There was no significant difference in age between the groups (P = 0.69). Several breeds were represented including Quarter Horses (27), Thoroughbreds (3), Warmbloods (5), Drafts (4), and Arabian (1). All horses were used for pleasure riding.
Due to the complexity of bacterial and host interactions in the gastrointestinal tract, a multi-‘omics’ approach is becoming more common in the study of disease. Evaluation of the intersection of the intestinal microbiota and intestinal metabolome is still in its infancy, but it is an emerging field of inquiry using high-throughput molecular analysis platforms. These technologies have enabled considerable progress in providing system-wide insights regarding mechanisms of underlying disease processes in humans, including type 2 diabetes and obesity. These findings have led to identification of biomarkers and risk factors associated with development of disease and novel therapeutic agents for the management and prevention of disease. Despite the relative importance of the gastrointestinal tract and the impact of obesity to the equine population, similar application and progress is lacking for studying obese horses. While the present study did not identify substantial differences between obese and non-obese horses with regard to the GI microbiota, there were important and relevant differences noted in the GI metabolome and circulating lipidome.
In summary, as seen in other species, improved knowledge and understanding of the microbiome and metabolome of obese horses may elucidate information regarding the pathogenesis of disease. The present study identified an increase in fecal TCA cycle intermediates, and increased circulating FFA in obese horses compared to non-obese horses. These findings support important differences in energy metabolism between groups and warrants further investigation. Differences in fecal microbiota were not appreciated; however, further exploration into the metagenome is suggested.