Fecal extract from obese horses induces an inflammatory response by murine macrophages in vitro

Abstract

OBJECTIVE To compare the inflammatory response of murine macrophages exposed to the enteric microbiome of obese horses versus nonobese horses. SAMPLE Fecal samples from 12 obese horses (body condition score ≥ 7/9) and 12 nonobese horses (body condition score 4 to 5/9) with similar dietary management. PROCEDURES Fecal supernatant was prepared from frozen fecal samples. RAW 264.7 macrophage cells were exposed to the fecal extract. Inflammatory cytokine (interleukin-1β, tumor necrosis factor-α, and interleukin-6) gene expression was quantified via real-time quantitative reverse transcription PCR assay, and cytokine concentration was quantified via ELISA. Lipopolysaccharide was evaluated in fecal extract via chromo-limulus amoebocyte lysate assay. RESULTS Compared with fecal extracts from nonobese horses, fecal extracts from obese horses presented higher concentrations of lipopolysaccharide and induced a heightened expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, and interleukin-6 from macrophages. CLINICAL RELEVANCE The increased levels of inflammatory markers induced in murine macrophages by the microbiome of obese horses in vitro suggested important differences in the enteric microbial composition of these horses, compared with nonobese horses. Overall, this study showed that the microbiome may play a role in mediating an inflammatory response within the gastrointestinal tract of obese horses. Mechanisms of obesity in the horse have not been fully elucidated. Improved understanding of the pathophysiology of disease will guide future research into potential diagnostic and therapeutic interventions for equine obesity.

The Microbiota and Equine Asthma: An Integrative View of the Gut–Lung Axis

“…In a diet-controlled study with a more homogenous population, fecal microbiome diversity and Bacteroidetes abundance were increased in obese horses [70]. In addition, murine macrophages exposed to fecal extracts from obese horses exhibited increased expressions of inflammatory markers such as IL-1β, TNF-α, and IL-6 when compared to those exposed to fecal extracts from non-obese horses [71].…”

Current Understanding of Equine Gut Dysbiosis and Microbiota Manipulation Techniques: Comparison with Current Knowledge in Other Species

“…Horses with metabolic syndrome have been shown to harbor distinct intestinal microbiota and metabolites compared to healthy controls [ 92 , 103 ]. Furthermore, an in vitro study showed that macrophage cells exposed to fecal extracts obtained from obese horses induced a higher production of proinflammatory cytokines compared to extracts from non-obese horses, suggesting a potential role of the microbiota composition in obese horses [ 104 ]. The diseases associated with altered intestinal microbiota have been reviewed elsewhere [ 13 , 32 ].…”

Obesity during Pregnancy in the Horse: Effect on Term Placental Structure and Gene Expression, as Well as Colostrum and Milk Fatty Acid Concentration

“…Obesity in horses has been associated with metabolic alterations and diseases, including insulin resistance [ 22 ], alterations of adipose tissue and cardiovascular function [ 23 , 24 ], low-grade inflammation [ 25 ] and weakened immunity [ 26 ], equine metabolic syndrome [ 27 ], and laminitis [ 28 ], as well as changes in the composition [ 29 ] and function [ 30 ] of the gut microbiota. Obesity can also negatively impact sports performances [ 31 ], as well as the physiological response to exercise and locomotion symmetry [ 32 ].…”