Heather A. Paul

Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats

Prebiotics and probiotics may be able to modify an obesity‐associated gut microbiota. The aim of this study was to examine the individual and combined effects of the prebiotic oligofructose (OFS) and the probiotic Bifidobacterium animalis subsp. lactis BB‐12 (BB‐12) on gut microbiota and host metabolism in obese rats.

Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy.

A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

The chronic low-level inflammation associated with obesity is known to deleteriously affect muscle composition. However, the manner in which obesity leads to muscle loss has not been explored in detail or in an integrated manner following a short-term metabolic challenge. In this paper, we evaluated the relationships between compromised muscle integrity, diet, systemic inflammatory mediators, adipose tissue, and gut microbiota in male Sprague-Dawley rats. We show that intramuscular fat, fibrosis, and the number of pro-inflammatory cells increased by 3-days and was sustained across 28-days of high-fat high-sugar feeding compared to control-diet animals. To understand systemic contributors to muscle damage, dynamic changes in gut microbiota and serum inflammatory markers were evaluated. Data from this study links metabolic challenge to persistent compromise in muscle integrity after just 3-days, a finding associated with altered gut microbiota and systemic inflammatory changes. These data contribute to our understanding of early consequences of metabolic challenge on multiple host systems, which are important to understand as obesity treatment options are developed. Therefore, intervention within this early period of metabolic challenge may be critical to mitigate these sustained alterations in muscle integrity.

Improvement in adiposity with oligofructose is modified by antibiotics in obese rats

Given the intimate link between gut microbiota and host physiology, there is growing interest in understanding the mechanisms by which diet influences gut microbiota and affects human metabolic health. Using antibiotics and the prebiotic oligofructose, which has been shown to counteract excess fat mass, we explored the gut microbiota‐dependent effects of oligofructose on body composition and host metabolism. Diet‐induced obese male Sprague Dawley rats, fed a background high‐fat/sucrose diet, were randomized to one of the following diets for 6 wk: 1) high‐energy control; 2) 10% oligofructose; 3) ampicillin; 4) ampicillin + 10% oligofructose; 5) ampicillin/neomycin; or 6) ampicillin/neomycin + 10% oligofructose. Combining oligofructose with ampicillin treatment blunted the decrease in adiposity seen with oligofructose. Although ampicillin did not affect total bacteria, ampicillin impeded oligofructose‐induced increases in Bifidobacterium and Lactobacillus. In contrast, the combination of ampicillin and neomycin reduced total bacteria but did not abrogate the oligofructose‐induced decrease in adiposity. Oligofructose‐mediated effects on host adiposity and metabolic health appear to be in part dependent on the presence of specific microbial species within the gut.—Bomhof, M. R., Paul, H. A., Geuking, M. B., Eller, L. K., Reimer, R. A. Improvement in adiposity with oligofructose is modified by antibiotics in obese rats. FASEB J. 30, 2720‐2732 (2016). www.fasebj.org

Potential Impact of Metabolic and Gut Microbial Response to Pregnancy and Lactation in Lean and Diet-Induced Obese Rats on Offspring Obesity Risk

SCOPE Maternal obesity programs metabolic dysfunction in offspring, increasing their susceptibility to obesity and metabolic diseases in later life. Moreover, pregnancy and lactation are associated with many metabolic adaptations, yet it is unclear how diet-induced maternal obesity may interrupt these processes. METHODS AND RESULTS 1 H NMR serum metabolomics analysis was performed on samples collected pre-pregnancy and in pregnant and lactating lean and high fat/sucrose (HFS) diet-induced obese Sprague-Dawley rats to identify maternal metabolic pathways associated with developmental programming of offspring obesity. Gut microbial composition was assessed using qPCR. Offspring of HFS dams had nearly 40% higher adiposity at weaning compared to offspring of lean dams. While pregnancy and lactation were associated with distinct maternal metabolic changes common to both lean and obese dams, we identified several metabolic differences, potentially implicating dysregulated one-carbon and mammary gland metabolism in the metabolic programming of obesity. Gut microbial composition was significantly altered with obesity, and both gestation and lactation were accompanied by changes in gut microbiota. CONCLUSION Diet-induced maternal obesity and consumption of an obesogenic maternal diet results in differential metabolic and gut microbial adaptations to pregnancy and lactation; these maladaptations may be directly involved in maternal programming of offspring susceptibility to obesity.

Impact of Food Ingredients (Aspartame, Stevia, Prebiotic Oligofructose) on Fertility and Reproductive Outcomes in Obese Rats: Food Ingredients and Reproduction in Obesity

This study aimed to investigate the interaction between obesity, low‐calorie sweeteners, and prebiotic oligofructose on reproductive parameters in rats.

Milk Collection in the Rat Using Capillary Tubes and Estimation of Milk Fat Content by Creamatocrit.

Milk, as the sole source of nutrition for the newborn mammal, provides the necessary nutrients and energy for offspring growth and development. It also contains a vast number of bioactive compounds that greatly affect the development of the neonate. The analysis of milk components will help elucidate key factors that link maternal metabolism and health with offspring growth and development. The laboratory rat represents a popular model organism for maternal studies, and rat milk can be used to examine the effect of various maternal physiological, nutritional, and pharmacological interventions on milk components, which may then impact offspring health. Here a simple method of manually collecting milk from the lactating rat that can be performed by a single investigator, does not require specialized vacuum or suction equipment, and provides sufficient milk for subsequent downstream analysis is described. A method for estimating the fat content of milk by measuring the percentage of cream within the milk sample, known as the creamatocrit, is also presented. These methods can ultimately be used to increase insight into maternal-child health and to elucidate maternal factors that are involved in proper growth and development of offspring.