Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats

Pulsed antibiotic treatment (PAT) early in life increases risk of obesity. Prebiotics can reduce fat mass and improve metabolic health. We examined if co-administering prebiotic with PAT reduces obesity risk in rat pups weaned onto a high fat/sucrose diet. Pups were randomized to (1) control [CTR], (2) antibiotic [ABT] (azithromycin), (3) prebiotic [PRE] (10% oligofructose (OFS)), (4) antibiotic + prebiotic [ABT + PRE]. Pulses of antibiotics/prebiotics were administered at d19–21, d28–30 and d37–39. Male and female rats given antibiotics (ABT) had higher body weight than all other groups at 10 wk of age. The PAT phenotype was stronger in ABT males than females, where increased fat mass, hyperinsulinemia and insulin resistance were present and all reversible with prebiotics. Reduced hypothalamic and hepatic expression of insulin receptor substrates and ileal tight junction proteins was seen in males only, explaining their greater insulin resistance. In females, insulin resistance was improved with prebiotics and normalized to lean control. ABT reduced Lactobacillaceae and increased Bacteroidaceae in both sexes. Using a therapeutic dose of an antibiotic commonly used for acute infection in children, PAT increased body weight and impaired insulin production and insulin sensitivity. The effects were reversed with prebiotic co-administration in a sex-specific manner

High density lipoprotein and metabolic disease: Potential benefits of restoring its functional properties

Background: High density lipoproteins (HDLs) are thought to be atheroprotective and to reduce the risk of cardiovascular disease (CVD). Besides their antioxidant, antithrombotic, anti-inflammatory, anti-apoptotic properties in the vasculature, HDLs also improve glucose metabolism in skeletal muscle. Scope of the review: Herein, we review the functional role of HDLs to improve metabolic disorders, especially those involving insulin resistance and to induce regression of CVD with a particular focus on current pharmacological treatment options as well as lifestyle interventions, particularly exercise. Major conclusions: Functional properties of HDLs continue to be considered important mediators to reverse metabolic dysfunction and to regress atherosclerotic cardiovascular disease. Lifestyle changes are often recommended to reduce the risk of CVD, with exercise being one of the most important of these. Understanding how exercise improves HDL function will likely lead to new approaches to battle the expanding burden of obesity and the metabolic syndrome. Keywords: High density lipoprotein (HDL), Metabolic disease, Glucose homeostasis, Physical activity, Atherosclerotic plaque regression, HDL functio

Impaired Hypothalamic Microglial Activation in Offspring of Antibiotic-Treated Pregnant/Lactating Rats Is Attenuated by Prebiotic Oligofructose Co-Administration

Microbial colonization of the gut early in life is crucial for the development of the immune and nervous systems, as well as influencing metabolism and weight gain. While early life exposure to antibiotics can cause microbial dysbiosis, prebiotics are non-digestible substrates that selectively promote the growth of beneficial gut microbiota. Our objective was to examine the effects of dietary prebiotic administration on the consequences of maternal antibiotic intake on offspring body weight, behavior, and neuroimmune responses later in life. Sprague-Dawley rat dams were given low-dose penicillin (LDP), prebiotic fiber (10% oligofructose), or both, during the third week of pregnancy and throughout lactation. Anxiety-like behavior, weight gain, body composition, cecal microbiota composition, and microglial responses to lipopolysaccharide (LPS) were assessed in offspring. Male and female prebiotic offspring had lower body weight compared to antibiotic offspring. Maternal antibiotic exposure resulted in lasting effects on select offspring microbiota including a lower relative abundance of Streptococcus, Lactococcus, and Eubacterium at 10 weeks of age. Maternal antibiotic use impaired microglial response to LPS in the hypothalamus compared to control, and this phenotype was reversed with prebiotic. Prebiotic fiber warrants further investigation as an adjunct to antibiotic use during pregnancy

Low-Dose Stevia (Rebaudioside A) Consumption Perturbs Gut Microbiota and the Mesolimbic Dopamine Reward System

Stevia is a natural low-calorie sweetener that is growing in popularity in food and beverage products. Despite its widespread use, little is understood of its impact on the gut microbiota, an important environmental factor that can mediate metabolism and subsequent obesity and disease risk. Furthermore, given previous reports of dysbiosis with some artificial low-calorie sweeteners, we wanted to understand whether prebiotic consumption could rescue potential stevia-mediated changes in gut microbiota. Three-week old male Sprague–Dawley rats were randomized to consume: (1) Water (CTR); (2) Rebaudioside A (STV); (3) prebiotic (PRE); (4) Rebaudioside A + prebiotic (SP) (n = 8/group) for 9 weeks. Rebaudioside was added to drinking water and prebiotic oligofructose-enriched inulin added to control diet (10%). Body weight and feces were collected weekly and food and fluid intake biweekly. Oral glucose and insulin tolerance tests, gut permeability tests, dual X-ray absorptiometry, and tissue harvest were performed at age 12 weeks. Rebaudioside A consumption alone did not alter weight gain or glucose tolerance compared to CTR. Rebaudioside A did, however, alter gut microbiota composition and reduce nucleus accumbens tyrosine hydroxylase and dopamine transporter mRNA levels compared to CTR. Prebiotic animals, alone or with Rebaudioside A, had reduced fat mass, food intake, and gut permeability and cecal SCFA concentration. Adding Rebaudioside A did not interfere with the benefits of the prebiotic except for a significant reduction in cecal weight. Long-term low-dose Rebaudioside A consumption had little effect on glucose metabolism and weight gain; however, its impact on gut microbial taxa should be further examined in populations exhibiting dysbiosis such as obesity

Contractility of permeabilized rat vastus intermedius muscle fibres following high-fat, high-sucrose diet consumption

Obesity is a worldwide health concern associated with impaired physical function. It is not clear if contractile protein dysfunction contributes to the impairment of muscle function observed with obesity. The purpose of this study was to examine if diet-induced obesity affects contractile function of chemically permeabilized vastus intermedius fibres of male Sprague Dawley rats expressing fast myosin heavy chain (MHC) IIa or slow MHC I. Rats consumed either a high-fat, high-sucrose (HFHS) diet or a standard (CHOW) diet beginning as either weanlings (7-week duration: WEAN7 cohort, or 14-week duration: WEAN14 cohort) or young adults (12-week duration: ADULT12 cohort, 24-week duration: ADULT24 cohort). HFHS-fed rats had higher (PThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author