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Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease.

ABSTRACT: Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatment of bacterial infections in the context of obesity are scarce. To address this research gap, we assessed efficacy of antibiotic treatment in diet-induced obese mice infected with the Lyme disease pathogen, Borrelia burgdorferi. Diet-induced obese C3H/HeN mice and normal-weight controls were infected with B. burgdorferi, and treated during the acute phase of infection with two doses of tigecycline, adjusted to the weights of diet-induced obese and normal-weight mice. Antibiotic treatment efficacy was assessed 1 month after the treatment by cultivating bacteria from tissues, measuring severity of Lyme carditis, and quantifying bacterial DNA clearance in ten tissues. In addition, B. burgdorferi-specific IgG production was monitored throughout the experiment. Tigecycline treatment was ineffective in reducing B. burgdorferi DNA copies in brain. However, diet-induced obesity did not affect antibiotic-dependent bacterial DNA clearance in any tissues, regardless of the tigecycline dose used for treatment. Production of B. burgdorferi-specific IgGs was delayed and attenuated in mock-treated diet-induced obese mice compared to mock-treated normal-weight animals, but did not differ among experimental groups following antibiotic treatment. No carditis or cultivatable B. burgdorferi were detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses to B. burgdorferi, but did not affect efficacy of antibiotic treatment.

SUBMITTER: Petrosova H

PROVIDER: S-EPMC5323460 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease.

Pětrošová Helena H Eshghi Azad A Anjum Zoha Z Zlotnikov Nataliya N Cameron Caroline E CE Moriarty Tara J TJ

Frontiers in microbiology 20170224

Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatment of bacterial infections in the context of obesity are scarce. To address this research gap, we assessed efficacy of antibiotic treatment in diet-induced obese mice infected with the Lyme disease pa ...[more]

PMID: 28286500

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Project description:IntroductionThe biggest risk factor for obesity and its associated comorbidities is a Western diet. This Western diet induces adipose tissue (AT) inflammation, which causes an AT dysfunction. Since AT is a vital endocrine organ, its dysfunction damages other organs, thus inducing a state of chronic inflammation and causing various comorbidities. Even though it is evident a Western diet, high in fat and carbohydrates, induces obesity and its complications, it is not known yet which macronutrient plays the most important role. Therefore, the aim of this study was to investigate the effect of macronutrient composition on obesity and to reverse the Western diet-induced metabolic risk via caloric restriction (CR) or a change of diet composition.Materials and methodsMale, C57BL/6JRj mice were fed with a diet high in fat, sucrose, fructose, sucrose and fructose, starch, a Western diet, or a control diet for 15 weeks. To assess reversibility of the metabolic risk, mice were first made obese via 15 weeks of WD and then put on either a CR or switched to a sucrose-rich diet.ResultsA sucrose-rich and high-starch diet induced less obesity and a better metabolic profile than a Western diet, evidenced by less hepatic steatosis, lower plasma cholesterol, and less insulin resistance. Furthermore, these diets induced less intra-abdominal AT inflammation than a Western diet, since mRNA levels of pro-inflammatory markers were lower and there was less macrophage infiltration. Expression of tight junction markers in colon tissue was higher in the sucrose-rich and high-starch group than the Western group, indicating a better intestinal integrity upon sucrose-rich and high-starch feeding. Additionally, CR induced weight loss and decreased both metabolic abnormalities and AT inflammation, regardless of macronutrient composition. However, effects were more pronounced upon CR with sucrose-rich or high-starch diet. Even without CR, switching obese mice to a sucrose-rich diet induced weight loss and decreased AT inflammation and metabolic aberrations.DiscussionA diet high in sucrose or starch induces less obesity and obesity-associated complications. Moreover, switching obese mice to a sucrose-rich diet elicits weight loss and decreases obesity-induced metabolic complications, highlighting the potential of carbohydrates to treat obesity.

Dataset Information

Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease.

Publications

Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease.

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