Objective We examined the impact of maternal low-dose aspartame and stevia consumption on adiposity, glucose tolerance, gut microbiota and mesolimbic pathway in obese dams and their offspring. Design Following obesity induction, female Sprague-Dawley rats were allocated during pregnancy and lactation to: (1) high fat/sucrose diet (HFS) +water (obese-WTR); (2) HFS +aspartame (obese-APM; 5–7 mg/kg/day); (3) HFS +stevia (obese-STV; 2–3 mg/kg/day). Offspring were weaned onto control diet and water and followed until 18 weeks. Gut microbiota and metabolic outcomes were measured in dams and offspring. Cecal matter from offspring at weaning was used for faecal microbiota transplant (FMT) into germ-free (GF) mice. Results Maternal APM and STV intake with a HFS diet increased body fat in offspring at weaning and body weight long-term with APM. Maternal APM/HFS consumption impaired glucose tolerance in male offspring at age 8 weeks and both APM and STV altered faecal microbiota in dams and offspring. Maternal obesity/HFS diet affected offspring adiposity and glucose tolerance more so than maternal LCS consumption at age 12 and 18 weeks. APM and STV altered expression of genes in the mesolimbic reward system that may promote consumption of a palatable diet. GF mice receiving an FMT from obese-APM and obese-STV offspring had greater weight gain and body fat and impaired glucose tolerance compared with obese-WTR. Conclusion Maternal low-calorie sweetener consumption alongside HFS may disrupt weight regulation, glucose control and gut microbiota in dams and their offspring most notably in early life despite no direct low-calorie sweetener consumption by offspring.

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.

Human milk oligosaccharides (HMOs) are chief maternal milk constituents that feed the intestinal microbiota and drive maturation of the infant gut. Our objective was to determine whether supplementing individual HMOs to a weanling diet alters growth and gut health in rats. Healthy three-week-old Sprague Dawley rat pups were randomized to control, 2′-O-fucosyllactose (2′FL)- and 3′sialyllactose (3′SL)-fortified diets alone or in combination at physiological doses for eight weeks. Body composition, intestinal permeability, serum cytokines, fecal microbiota composition, and messenger RNA (mRNA) expression in the gastrointestinal tract were assessed. Males fed a control diet were 10% heavier and displayed elevated interleukin (IL-18) (p = 0.01) in serum compared to all HMO-fortified groups at week 11. No differences in body composition were detected between groups. In females, HMOs did not affect body weight but 2′FL + 3′SL significantly increased cecum weight. All female HMO-fortified groups displayed significant reductions in intestinal permeability compared to controls (p = 0.02). All HMO-fortified diets altered gut microbiota composition and mRNA expression in the gastrointestinal tract, albeit differently according to sex. Supplementation with a fraction of the HMOs found in breast milk has a complex sex-dependent risk/benefit profile. Further long-term investigation of gut microbial profiles and supplementation with other HMOs during early development is warranted.

Obesity is a complex disease with multiple contributing factors. One of the most intensely studied factors during the past decade has been the gut microbiota, which is the community of all microbes in the intestinal tract. The gut microbiota, via energy extraction, inflammation, and other actions, is now recognized as an important player in the pathogenesis of obesity. Dysbiosis, or an imbalance in the microbial community, can initiate a cascade of metabolic disturbances in the host. Early life is a particularly important period for the development of the gut microbiota, and perturbations such as with antibiotic exposure can have long-lasting consequences for host health. In early life and throughout the life span, diet is one of the most important factors that shape the gut microbiota. Although diets high in fat and sugar have been shown to contribute to dysbiosis and disease, dietary fiber is recognized as an important fermentative fuel for the gut microbiota and results in the production of short-chain fatty acids that can act as signaling molecules in the host. One particular type of fiber, prebiotic fiber, contributes to changes in the gut microbiota, the most notable of which is an increase in the abundance of Bifidobacterium. This review highlights our current understanding of the role of gut microbiota in obesity development and the ways in which manipulating the microbiota through dietary means, specifically prebiotics, could contribute to improved health in the host, including musculoskeletal health.

Given that prebiotics have been shown to improve gut microbiota composition, gastrointestinal symptoms and select behaviors in autism spectrum disorder (ASD), we hypothesized that prebiotic supplementation would improve sociability, communication, and repetitive behaviors in a murine model of ASD. We also examined the effect of a synbiotic (probiotic + prebiotic). Juvenile male BTBR mice were randomized to: (1) control; (2) probiotic (1 × 10¹⁰ CFU/d Lactobacillus reuteri RC-14^®; now known as Limosilactobacillus reuteri); (3) prebiotic (10% oligofructose-enriched inulin); (4) prebiotic + probiotic (n = 12/group) administered through food for 3 weeks. Sociability, communication, repetitive behavior, intestinal permeability and gut microbiota were assessed. Probiotic and symbiotic treatments improved sociability (92 s and 70 s longer in stranger than empty chamber) and repetitive behaviors (50% lower frequency), whereas prebiotic intake worsened sociability (82 s less in stranger chamber) and increased the total time spent self-grooming (96 s vs. 80 s CTR), but improved communication variables (4.6 ms longer call duration and 4 s higher total syllable activity). Mice consuming probiotics or synbiotics had lower intestinal permeability (30% and 15% lower than CTR). Prebiotic, probiotic, and symbiotic treatments shifted gut microbiota to taxa associated with improved gut health. L.reuteri may help alleviate ASD behavioral symptom severity and improve gut health. The potential use of prebiotics in an ASD population warrants further research.