Dietary fiber combinations to mitigate the metabolic, microbial, and cognitive imbalances resulting from diet-induced obesity in rats.

Dietary fiber promotes a healthy gut microbiome and shows promise in attenuating the unfavorable microbial changes resulting from a high-fat/sucrose (HFS) diet. High-fiber diets consisting of oligofructose alone (HFS/O) or in combination with ß-glucan (HFS/OB), resistant starch (HFS/OR), or ß-glucan and resistant starch (HFS/OBR) were fed to diet-induced obese rats for 8 weeks to determine if these fibers could attenuate the obese phenotype. Only the HFS/O group displayed a decrease in body weight and body fat, but all fiber interventions improved insulin sensitivity and cognitive function. The HFS/O diet was the least effective at improving cognitive function and only the HFS/OB group showed improvements in glucose tolerance, thus highlighting the differential effects of fiber types. Hippocampal cytokines (IL-6, IL-10) were more pronounced in the HFS/OB group which coincided with the most time spend in the open arms of the elevated plus maze. All fiber groups showed an increase in beneficial Bifidobacterium and Lactobacillus abundance while the HFS group showed higher abundance of Clostridium. Fecal microbiota transplant from fiber-treated rats into germ-free mice did not alter body composition in the mice but did result in a higher abundance of Bacteroides in the HFS/O and HFS/OB groups compared to HFS. The HFS/OB recipient mice also had higher insulin sensitivity compared to the other groups. This study highlights the influence of dietary fiber type on metabolic and cognitive outcomes suggesting that the type of supplementation (single or combined fibers) could be tailored to specific targeted outcomes.

Paternal high protein diet modulates body composition, insulin sensitivity, epigenetics, and gut microbiota intergenerationally in rats.

Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre-conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP diet improved body composition and insulin sensitivity and improved circulating satiety hormones and cecal short-chain fatty acids compared to HF/S and control diet (P < .05). Further, using 16S rRNA gene sequencing to assess gut microbial composition, we observed increased alpha diversity, distinct bacterial clustering, and increased abundance of Bifidobacterium, Akkermansia, Bacteroides, and Marvinbryantia in HP fathers and/or male and female adult offspring. At the epigenetic level, DNMT1and 3b expression was altered intergenerationally. Our study identifies paternal HP diet as a modulator of gut microbial composition, epigenetic markers, and metabolic function intergenerationally.

Effect of supplementation with select human milk oligosaccharides on artificially reared newborn rats.

Early life nutrition fundamentally influences neonatal development and health. Human milk oligosaccharides (HMO) are key components of breast milk but not standard infant formula that support the establishment of the newborn gut microbiota. Using an artificial rearing system, our objective was to test the effect of two HMO on the whole body and organ growth, adiposity, glucose tolerance and faecal microbiota in young rat pups. From postnatal days 4 to 21, Sprague-Dawley rats were randomised to receive one of: (1) CTR (rat milk substitute); (2) 2'FL (CTR + 1·2 g/l 2'-fucosyllactose); (3) 3'SL (CTR + 1·2 g/l 3'-sialyllactose) and (4) 2'FL + 3'SL (CTR + 0·6 g/l 2'-FL + 0·6 g/l 3'-SL). Body weight (BW), bowel movements and food intake were monitored daily, faecal samples collected each week and oral glucose tolerance, body composition and organ weight measured at weaning. No significant differences were observed between groups in growth performance, body composition, organ weight and abundance of dominant faecal microbes. A decreased relative abundance of genus Proteus in week 1 faecal samples and Terrisporobacter in week 3 faecal samples (P < 0·05) was suggestive of a potential pathogen inhibitory effect of 3'SL. Longitudinal changes in the faecal microbiota of artificially reared suckling rats were primarily governed by age (P = 0·001) and not affected by the presence of 2'-FL and/or 3'-SL in rat milk substitutes (P = 0·479). Considering the known protective effects of HMO, further investigation of supplementation with these and other HMO in models of premature birth, extremely low BW or malnutrition may show more pronounced outcomes.

Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet.

Increased consumption of high fat/sucrose (HF/S) diets has contributed to rising rates of obesity and its co-morbidities globally, while also negatively impacting male reproductive health. Our objective was to examine whether adding a methyl donor cocktail to paternal HF/S diet (HF/S+M) improves health status in fathers and offspring. From 3-12 weeks of age, male Sprague Dawley rats consumed a HF/S or HF/S+M diet. Offspring were followed until 16 weeks of age. Body composition, metabolic markers, gut microbiota, DNA methyltransferase (DNMT) and microRNA expression were measured in fathers and offspring. Compared to HF/S, paternal HF/S+M diet reduced fat mass in offspring (p < 0.005). HF/S+M fathers consumed 16% fewer kcal/day, which persisted in HF/S+M female offspring and was explained in part by changes in serum glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels. Compared to HF/S, HF/S+M fathers had a 33% improvement in days until conception and 300% fewer stillbirths. In fathers, adipose tissue DNMT3a and hepatic miR-34a expression were reduced with HF/S+M. Adult male offspring showed upregulated miR-24, -33, -122a and -143 expression while females exhibited downregulated miR-33 expression. Fathers and offspring presented differences in gut microbial signatures. Supplementing a paternal HF/S diet with methyl-donors improved fertility, physiological outcomes, epigenetic and gut microbial signatures intergenerationally.

Maternal low-dose aspartame and stevia consumption with an obesogenic diet alters metabolism, gut microbiota and mesolimbic reward system in rat dams and their offspring.

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.

The chemo-gut study: investigating the long-term effects of chemotherapy on gut microbiota, metabolic, immune, psychological and cognitive parameters in young adult Cancer survivors; study protocol.

BACKGROUND: The gut microbiota is an important modulator of immune, metabolic, psychological and cognitive mechanisms. Chemotherapy adversely affects the gut microbiota, inducing acute dysbiosis, and alters physiological and psychological function. Cancer among young adults has risen 38% in recent decades. Understanding chemotherapy's long-term effects on gut microbiota and psycho-physiological function is critical to improve survivors' physical and mental health, but remains unexamined. Restoration of the gut microbiota via targeted therapies (e.g. probiotics) could potentially prevent or reverse the psycho-physiological deficits often found in young survivors following chemotherapy, ultimately leading to reduced symptom burden and improved health. METHODS: This longitudinal study investigates chemotherapy induced long-term gut dysbiosis, and associations between gut microbiota, and immune, metabolic, cognitive and psychological parameters using data collected at < 2 month (T1), 3-4 months (T2), and 5-6 months (T3) post-chemotherapy. Participants will be 18-39 year old blood or solid tumor cancer survivors (n = 50), and a healthy sibling, partner or friend as a control (n = 50). Gut microbiota composition will be measured from fecal samples using 16 s RNA sequencing. Psychological and cognitive patient reported outcome measures will include depression, anxiety, post-traumatic stress disorder symptoms, pain, fatigue, and social and cognitive function. Dual-energy X-ray Absorptiometry (DXA) will be used to measure fat and lean mass, and bone mineral concentration. Pro-inflammatory cytokines, C-reactive protein (CRP), lipopolysaccharide (LPS), serotonin, and brain derived neurotrophic factor (BDNF) will be measured in serum, and long-term cortisol will be assayed from hair. Regression and linear mixed model (LMM) analyses will examine associations across time points (T1 - T3), between groups, and covariates with gut microbiota, cognitive, psychological, and physiological parameters. CONCLUSION: Knowing what bacterial species are depleted after chemotherapy, how long these effects last, and the physiological mechanisms that may drive psychological and cognitive issues among survivors will allow for targeted, integrative interventions to be developed, helping to prevent or reverse some of the late-effects of treatment that many young cancer survivors face. This protocol has been approved by the Health Research Ethics Board of Alberta Cancer Committee (ID: HREBA.CC-19-0018).

Short-chain fatty acids propionate and butyrate control growth and differentiation linked to cellular metabolism.

The short-chain fatty acids (SCFA) propionate and butyrate are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. In order to better understand the function of these modifications we used ChIP-seq to map the genome-wide location of four short-chain acyl histone marks H3K18pr/bu and H4K12pr/bu in treated and untreated colorectal cancer (CRC) and normal cells, as well as in mouse intestines in vivo. We correlate these marks with open chromatin regions along with gene expression to access the function of the target regions. Our data demonstrate that propionate and butyrate act as promoters of growth, differentiation as well as ion transport. We propose a mechanism involving direct modification of specific genomic regions, resulting in increased chromatin accessibility, and in case of butyrate, opposing effects on the proliferation of normal versus CRC cells.

Short-chain fatty acids propionate and butyrate control growth and differentiation linked to cellular metabolism.

The short-chain fatty acids (SCFA) propionate and butyrate are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. In order to better understand the function of these modifications we used ChIP-seq to map the genome-wide location of four short-chain acyl histone marks H3K18pr/bu and H4K12pr/bu in treated and untreated colorectal cancer (CRC) and normal cells, as well as in mouse intestines in vivo . We correlate these marks with open chromatin regions along with gene expression to access the function of the target regions. Our data demonstrate that propionate and butyrate act as promoters of growth, differentiation as well as ion transport. We propose a mechanism involving direct modification of specific genomic regions, resulting in increased chromatin accessibility, and in case of butyrate, opposing effects on the proliferation of normal versus CRC cells.

Associations Between Health Behaviors, Gastrointestinal Symptoms, and Gut Microbiota in a Cross-Sectional Sample of Cancer Survivors: Secondary Analysis from the Chemo-Gut Study.

BACKGROUND: Health behaviors, such as diet and exercise, are actions individuals take that can potentially impact gastrointestinal (GI) symptoms and the gut microbiota. Little is known about how health behaviors impact GI symptoms and the gut microbiota after anti-cancer therapies. METHODS: This is a secondary analysis of a cross-sectional study that investigated relationships between GI symptoms, gut microbiota, and patient-reported outcomes in adult cancer survivors. Gut microbiota was assessed from stool samples using 16 S rRNA gene sequencing. GI symptoms and health behaviors were measured via self-report. Descriptive statistics, multiple regression, and correlation analyses are reported. RESULTS: A total of 334 cancer survivors participated, and a subsample of 17 provided stool samples. Most survivors rated their diet as moderately healthy (55.7%) and reported engaging in low intensity exercise (53.9%) for ≤5 h/week (69.1%). Antibiotic use was associated with more belly pain, constipation, and diarrhea (P < .05). Survivors consuming a healthier diet had fewer symptoms of belly pain (P = .03), gas/bloating (P = .01), while higher protein consumption was associated with less belly pain (P = .03). Better diet health was positively correlated with Lachnospiraceae abundance, and negatively with Bacteroides abundance (P < .05). Greater exercise frequency positively correlated with abundance of Lachnospiraceae, Faecalibacterium, Bacteroides, Anaerostipes, Alistipes, and Subdoligranulum (P < .05). CONCLUSION: Results provide evidence for associations between antibiotic use, probiotic use, dietary health behaviors, and GI symptoms. Diet and exercise behaviors are related to certain types of bacteria, but the direction of causality is unknown. Dietary-based interventions may be optimally suited to address survivors' GI symptoms by influencing the gut microbiota. Larger trials are needed.

Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.

To understand dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune and clinical markers of microbiomes from four body sites in 86 participants over six years. We found that microbiome stability and individuality are body-site-specific and heavily influenced by the host. The stool and oral microbiome were more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. Also, we identified individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlated across body sites, suggesting systemic coordination influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals showed altered microbial stability and associations between microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease. Study Highlights: The stability of the human microbiome varies among individuals and body sites.Highly individualized microbial genera are more stable over time.At each of the four body sites, systematic interactions between the environment, the host and bacteria can be detected.Individuals with insulin resistance have lower microbiome stability, a more diversified skin microbiome, and significantly altered host-microbiome interactions.

Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.

To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.

The Chemo-Gut Pilot Study: Associations between Gut Microbiota, Gastrointestinal Symptoms, and Psychosocial Health Outcomes in a Cross-Sectional Sample of Young Adult Cancer Survivors.

Chemotherapy adversely affects the gut microbiota, inducing dysbiosis, and negatively impacts gastrointestinal (GI) and psychosocial health during treatment, but little is known about the long-term effects or how these factors are related. Methods: This cross-sectional pilot study investigated the effects of chemotherapy on the gut microbiota, GI symptoms, and psychosocial outcomes in cancer survivors aged 18−39 years old, compared to healthy controls. Gut microbial diversity and composition were assessed from stool samples using 16S rRNA gene sequencing. Results: Survivors (n = 17) and healthy controls (n = 18) participated. Mean age at diagnosis was 31 years (±5.3). Mean time off treatment was 16.9 months (±16.4). Survivors had more severe GI symptoms, poorer psychosocial health, and increased relative abundance of Selenomondales, Veilloneliaceae, and Intestinibacter. In survivors, Lachnospiraceae, Ruminococcaceae and Intestinibacter correlated with psychosocial symptoms, while diarrhea correlated positively with Lachnospiraceae. Results are statistically significant. Survivors ≤6 months post-treatment had lower alpha diversity than survivors >6 months post-treatment (p = 0.04) and controls (p = 0.19). Conclusion: This small exploratory study demonstrates potential long-term gut microbial dysbiosis in cancer survivors, which may be associated with psychosocial symptoms. Larger trials concurrently and longitudinally examining gut microbiota, GI symptoms, and psychosocial outcomes are needed.

Microbiota Changes in Fathers Consuming a High Prebiotic Fiber Diet Have Minimal Effects on Male and Female Offspring in Rats.

BACKGROUND: Consuming a diet high in prebiotic fiber has been associated with improved metabolic and gut microbial parameters intergenerationally, although studies have been limited to maternal intake with no studies examining this effect in a paternal model. METHOD: Male Sprague Dawley rats were allocated to either (1) control or (2) oligofructose-supplemented diet for nine weeks and then mated. Offspring consumed control diet until 16 weeks of age. Bodyweight, body composition, glycemia, hepatic triglycerides, gastrointestinal hormones, and gut microbiota composition were measured in fathers and offspring. RESULTS: Paternal energy intake was reduced, while satiety inducing peptide tyrosine tyrosine (PYY) gut hormone was increased in prebiotic versus control fathers. Increased serum PYY persisted in female prebiotic adult offspring. Hepatic triglycerides were decreased in prebiotic fathers with a similar trend (p = 0.07) seen in female offspring. Gut microbial composition showed significantly reduced alpha diversity in prebiotic fathers at 9 and 12 weeks of age (p < 0.001), as well as concurrent differences in beta diversity (p < 0.001), characterized by differences in Bifidobacteriaceae, Lactobacillaceae and Erysipelotrichaceae, and particularly Bifidobacterium animalis. Female prebiotic offspring had higher alpha diversity at 3 and 9 weeks of age (p < 0.002) and differences in beta diversity at 15 weeks of age (p = 0.04). Increases in Bacteroidetes in female offspring and Christensenellaceae in male offspring were seen at nine weeks of age. CONCLUSIONS: Although paternal prebiotic intake before conception improves metabolic and microbiota outcomes in fathers, effects on offspring were limited with increased serum satiety hormone levels and changes to only select gut bacteria.

The Effects of Human Milk Oligosaccharide Supplementation During Critical Periods of Development on the Mesolimbic Dopamine System.

Human milk oligosaccharides (HMO)s are a key component in human milk and represent an important dietary modulator of infant gut microbiota composition and associated gut-brain axis development and homeostasis. The brain reward system, specifically the mesolimbic dopamine (DA) projections from the ventral tegmental area (VTA) to nucleus accumbens (NAc) is involved in the motivation and preference for food. The objective of the present study was to determine if HMO fortified diets given during the critical period of reward system development (p21) could affect the structure of the reward system. At weaning (p21), Sprague-Dawley rats were randomized to one of four fortified diet groups: Control, 3'sialyllactose (3'FL), 2'-fucosyllactose (2'FL), or a combination of 3'SL and 2'FL (3'SL + 2'FL). Messenger RNA (mRNA) expression was quantified for DA and appetite associated markers in the VTA and NAc and western blots measured the immediate early gene FosB and its isoform ΔFosB. Females fed the 3'SL + 2'FL fortified diet displayed a decrease in DAT expression in the VTA and an increase in leptin expression in the NAc. Females displayed an overall lower expression of NAc D2, VTA ghrelinR, and VTA leptin. In males, VTA DAT and FosB were negatively correlated with body weight and systemic leptin. Sex differences in the expression of DA markers underscore the need to investigate this phenomenon and understand the functional significance in preventing or treating obesity. This study highlights sex differences in response to HMO supplementation and the need for further investigations into the functional significance of nutritional interventions during DA system development.

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.

Dietary Vitamin B6 Deficiency Impairs Gut Microbiota and Host and Microbial Metabolites in Rats.

Vitamin B6 plays a crucial role as a cofactor in various enzymatic reactions but bacteria-produced vitamin B6 is not sufficient to meet host requirements. Our objective was to assess the impact of diet-derived vitamin B6 on gut microbiota and host serum metabolomics. Sprague-Dawley rats (n = 47) were fed a control, low B6 (LB6) or high B6 (HB6) diet for six weeks. Serum and cecal samples were collected for biochemical, metabolomics and gut microbiota profiling. There was a significant sex effect for gut microbiota and several metabolic markers. Bodyweight and percent body fat were significantly reduced in LB6 compared to control and HB6 rats. Microbial beta-diversity differed significantly between LB6 and the control and HB6 rats in both sexes. Lachnospiraceae_NK4A136_group and Bacteroides were the primary taxa driving the difference between LB6 and control. There was a significant separation of cecal and serum metabolites of LB6 compared to control and HB6 rats. In the cecum, arginine biosynthesis was impaired, while vitamin B6 metabolism, lysine degradation and nicotinate and nicotinamide metabolism were impaired in serum metabolite profiles. Cecal propionate and butyrate were significantly reduced in LB6 rats irrespective of sex. Host vitamin B6 deficiency but not excess significantly alters gut microbial composition and its metabolites.

Human Milk Oligosaccharide Supplementation Affects Intestinal Barrier Function and Microbial Composition in the Gastrointestinal Tract of Young Sprague Dawley Rats.

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.

Prebiotic Oligofructose Prevents Antibiotic-Induced Obesity Risk and Improves Metabolic and Gut Microbiota Profiles in Rat Dams and Offspring.

SCOPE: Antibiotics in early life disrupt microbiota and increase obesity risk. Dietary agents such as prebiotics may reduce obesity risk. The authors examine how antibiotics administered with/without prebiotic oligofructose, alter metabolic and microbial outcomes in pregnant rats and their offspring. METHODS AND RESULTS: Pregnant rats are randomized to: 1) Control, 2) Antibiotic (ABT), 3) Prebiotic (PRE), 4) Antibiotic+Prebiotic (ABT+PRE) during the 3rd week of pregnancy and lactation. Offspring were fed a high fat/high sucrose (HFS) diet from 9-17 weeks of age to unmask obesity risk. ABT dams had higher body weight, body fat and leptin during lactation than all other groups. Prebiotics attenuate these outcomes and increase cecal Bifidobacterium. ABT offspring have higher body weight, fat mass, and liver triglycerides after HFS diet, with a stronger phenotype in males; prebiotics attenuate these. At weaning, male ABT offspring have lower Lactobacillus while PRE and ABT+PRE offspring had higher Bifidobacterium and Collinsella. Fecal microbiota transfer of adult offspring cecal matter could not reliably transfer the obese ABT phenotype. CONCLUSIONS: Antibiotic use during pregnancy/lactation increases adiposity and impairs post-partum weight loss in dams. Co-administering prebiotics with antibiotics in rat dams prevented obesity risk in offspring and is associated with altered gut microbiota.

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.