Small intestinal metabolomics analysis reveals differentially regulated metabolite profiles in obese rats and with prebiotic supplementation.

INTRODUCTION: Obesity occurs partly due to consumption of a high-fat, high-sugar and low fiber diet and is associated with an altered gut microbiome. Prebiotic supplementation can reverse obesity and beneficially alter the gut microbiome, evidenced by previous studies in rodents. However, the role of the small intestinal metabolome in obese and prebiotic supplemented rodents has never been investigated. OBJECTIVES: To investigate and compare the small intestinal metabolome of healthy and obese rats, as well as obese rats supplemented with the prebiotic oligofructose (OFS). METHODS: Untargeted metabolomics was performed on small intestinal contents of healthy chow-fed, high fat diet-induced obese, and obese rats supplemented with oligofructose using UPLC-MS/MS. Quantification of enterohepatic bile acids was performed with UPLC-MS to determine specific effects of obesity and fiber supplementation on the bile acid pool composition. RESULTS: The small intestinal metabolome of obese rats was distinct from healthy rats. OFS supplementation did not significantly alter the small intestinal metabolome but did alter levels of several metabolites compared to obese rats, including bile acid metabolites, amino acid metabolites, and metabolites related to the gut microbiota. Further, obese rats had lower total bile acids and increased taurine-conjugated bile acid species in enterohepatic circulation; this effect was reversed with OFS supplementation in high fat-feeding. CONCLUSION: Obesity is associated with a distinct small intestinal metabolome, and OFS supplementation reverses some metabolite levels that were altered in obese rats. Future research into the effects of specific metabolites identified in this study will provide deeper insight into the mechanism of fiber supplementation on improved body weight.

Impact of maternal obesity and prebiotic supplementation on select maternal milk microRNA levels and correlation with offspring outcomes.

Breast milk composition varies with maternal factors including diet and confers health benefits to the neonate; however, the mechanisms mediating this protection remain incompletely understood. Our aim was to investigate the effects of supplementing a maternal high-fat/sucrose (HFS) diet with prebiotic oligofructose (OFS) on milk composition in rats and associations with offspring body composition and gut microbiota. Obese Sprague-Dawley dams consumed a control, HFS, HFS + OFS (10 % wt/wt) or HFS diet weight-matched to the HFS + OFS group (HFS-WM) during pregnancy and lactation. Pups were weaned onto a HFS diet on day 21. Milk was collected at weaning and analysed for protein, leptin and microRNA (miRNA) levels. Milk produced by HFS dams contained less protein than milk from lean controls which was normalised by OFS. Six miRNA (miR-222, miR-203a, miR-200a, miR-26a, miR-27a and miR-103) were differentially expressed in milk according to maternal diet. Milk leptin content was positively correlated with maternal body fat and faecal Enterobacteriaceae in male offspring at 24 weeks of age. Milk protein content was inversely associated with maternal body fat and body weight. miR-200a was positively associated with maternal body fat and Enterobacteriaceae in female offspring at 24 weeks of age. Correlations between milk protein and multiple milk miRNA and offspring body composition and gut microbiota differed by sex. Overall, our results suggest that obesogenic diets and prebiotic supplementation can alter the protein and miRNA levels in breast milk in rats and these milk components may explain, in part, the influence of these maternal diets on offspring body composition.

Effects of Fructose and Oligofructose Addition on Milk Fermentation Using Novel Lactobacillus Cultures to Obtain High-Quality Yogurt-like Products.

The incorporation of prebiotics in fermented milk products is one of the best ways to promote health benefits while improving their sensory characteristics at the same time. The aim of this study was to evaluate the effects of the addition of fructose and oligofructose (1% and 2%) on the physicochemical, rheological, sensory, and microbiological quality attributes of fermented milk products inoculated with indigenous probiotic starter cultures of Lactobacillus isolated from Polish traditional fermented foods. The samples were evaluated during 35 days of refrigerated storage. The oligofructose and fructose caused increases in the populations of bacteria in comparison to the control fermented milk products without the addition of saccharides. The degrees of acidification in different fermented milk samples, as well as their viscosity, firmness, syneresis, and color attributes, changed during storage. The highest overall sensory quality levels were observed for the samples supplemented with L. brevis B1 and oligofructose. This study is the first attempt to compare the influences of different sugar sources on the physicochemical, rheological, sensory, and microbiological quality attributes of fermented milk products.

Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats.

A maternal high-fat/sucrose diet, in the presence of maternal obesity, can program increased susceptibility to obesity and metabolic disease in offspring. In particular, nonalcoholic fatty liver disease risk is associated with poor maternal nutrition and obesity status, which may manifest via alterations in gut microbiota. Here, we report that in a preclinical model of diet-induced maternal obesity, maternal supplementation of a high-fat/sucrose diet with the prebiotic oligofructose improves glucose tolerance, insulin sensitivity, and hepatic steatosis in offspring following a long-term high-fat/sucrose dietary challenge compared with offspring of untreated dams. These improvements are associated with alterations in gut microbial composition and serum inflammatory profiles in early life and improvements in inflammatory and fatty-acid gene expression profiles in tissues. Serum metabolomics analysis highlights potential metabolic links between the gut microbiota and the degree of steatosis, including alterations in 1-carbon metabolism. Overall, our data suggest that maternal prebiotic intake protects offspring against hepatic steatosis and insulin resistance following 21 wk of high fat/sucrose diet, which is in part due to alterations in gut microbiota.-Paul, H. A., Collins, K. H., Nicolucci, A. C., Urbanski, S. J., Hart, D. A., Vogel, H. J., Reimer, R. A. Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats.

Effects of prebiotic dietary fibers and probiotics on human health: With special focus on recent advancement in their encapsulated formulations.

BACKGROUND: Dietary fibers (DFs) are known as potential formulations in human health due to their beneficial effects in control of life-threatening chronic diseases including cardiovascular disease (CVD), diabetes mellitus, obesity and cancer. In recent decades scientists around the globe have shown tremendous interest to evaluate the interplay between DFs and gastrointestinal (GIT) microbiota. Evidences from various epidemiological and clinical trials have revealed that DFs modulate formation and metabolic activities of the microbial communities residing in the human GIT which in turn play significant roles in maintaining health and well-being. Furthermore, interestingly, a rapidly growing literature indicates success of DFs being prebiotics in immunomodulation, namely the stimulation of innate, cellular and humoral immune response, which could also be linked with their significant roles in modulation of the probiotics (live beneficial microorganisms). SCOPE AND APPROACH: The main focus of the current review is to expressively highlight the importance of DFs being prebiotics in human health in association with their influence on gut microbiota. Now in order to significantly achieve the promising health benefits from these prebiotics, it is aimed to develop novel formulations to enhance and scale up their efficacy. Therefore, finally, herein unlike previously published articles, we highlighted different kinds of prebiotic and probiotic formulations which are being regarded as hot research topics among the scientific community now a days. CONCLUSION: The information in this article will specifically provide a platform for the development of novel functional foods the demands for which has risen drastically in recent years.

Stability of camu-camu encapsulated with different prebiotic biopolymers.

BACKGROUND: A viable possibility for the best use of bioactive compounds present in camu-camu, fruit native to the Amazonian rainforest, is the preparation of microcapsules using different biopolymers by the spray-drying technique, which would increase the possibilities for innovation in the food industry, as well as facilitate the application in different food matrices. In this context, the chemical, physicochemical, and morphological properties and stability of camu-camu extract (peel and pulp) spray-dried using maltodextrin, inulin, and oligofructose as encapsulating agents were investigated, as well as lyophilized camu-camu extract (CEL). Different relative humidities (22%, 51%, and 75%) and temperatures (25 °C and 45 °C) were evaluated. RESULTS: The moisture, water activity, and solubility values varied from 18.4 to 107.9 g water per kilogram dry powder, 0.06 to 0.27, and 950.80 to 920.28 g microparticles per kilogram of water respectively. Retention of the bioactive compounds varied in the ranges 5.5-7.1 g per kilogram ascorbic acid fresh weight and 7.2-9.0 g per kilogram anthocyanins fresh weight. The increase in temperature and relative humidity during storage provided a significant decrease in the stability of the bioactive compounds for all treatments. However, the CEL presented higher water adsorption kinetics and degradation under all storage conditions, indicating the importance of the use of encapsulating agents. CONCLUSION: In general, the prebiotic biopolymers used as encapsulating agents in the microencapsulation of extracts of camu-camu by spray-drying presented satisfactory results, suggesting that this technique is an effective strategy to increase the stability of bioactive compounds contained in fruits and vegetables. © 2020 Society of Chemical Industry.

Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.

PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. METHODS: In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. RESULTS: Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. CONCLUSIONS: Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. CLINICAL TRIAL: This trial was registered at Clinicaltrials.com as NCT03184376.

Promising Prebiotic Candidate Established by Evaluation of Lactitol, Lactulose, Raffinose, and Oligofructose for Maintenance of a Lactobacillus-Dominated Vaginal Microbiota.

Perturbations to the vaginal microbiota can lead to dysbiosis, including bacterial vaginosis (BV), which affects a large portion of the female population. In a healthy state, the vaginal microbiota is characterized by low diversity and colonization by Lactobacillus spp., whereas in BV, these species are displaced by a highly diverse population of bacteria associated with adverse vaginal health outcomes. Since prebiotic ingestion has been a highly effective approach to invigorate lactobacilli for improved intestinal health, we hypothesized that these compounds could stimulate lactobacilli at the expense of BV organisms to maintain vaginal health. Monocultures of commensal Lactobacillus crispatus, Lactobacillus vaginalis, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus jensenii, and Lactobacillus iners, in addition to BV-associated organisms and Candida albicans, were tested for their ability to utilize a representative group of prebiotics consisting of lactitol, lactulose, raffinose, and oligofructose. The disaccharide lactulose was found to most broadly and specifically stimulate vaginal lactobacilli, including the strongly health-associated species L. crispatus, and importantly, not to stimulate BV organisms or C. albicans Using freshly collected vaginal samples, we showed that exposure to lactulose promoted commensal Lactobacillus growth and dominance and resulted in healthy acidity partially through lactic acid production. This provides support for further testing of lactulose to prevent dysbiosis and potentially to reduce the need for antimicrobial agents in managing vaginal health.IMPORTANCE Bacterial vaginosis (BV) and other dysbioses of the vaginal microbiota significantly affect the quality of life of millions of women. Antimicrobial therapy is often poorly effective, causes side effects, and does not prevent recurrences. We report one of very few studies that have evaluated how prebiotics-compounds that are selectively fermented by beneficial bacteria such as Lactobacillus spp.-can modulate the vaginal microbiota. We also report use of a novel in vitro polymicrobial model to study the impact of prebiotics on the vaginal microbiota. The identification of prebiotic lactulose as enhancing Lactobacillus growth but not that of BV organisms or Candida albicans has direct application for retention of homeostasis and prevention of vaginal dysbiosis and infection.

Plasma profile and urine excretion of amino acids in children with celiac disease on gluten-free diet after oligofructose-enriched inulin intervention: results of a randomised placebo-controlled pilot study.

The circulating amino acid (AAs) concentrations are indicators of dietary protein intake and metabolic status. In celiac disease (CD), the AA imbalance is frequently observed. Prebiotics are found to alleviate nutrient deficiencies. Therefore, the aim of this study was to analyse the impact of oligrofructose-enriched inulin (Synergy 1), administered for 3 months as a gluten-free diet (GFD) supplement to children with CD, on the plasma and urine concentrations of AAs. CD children (N = 34) were randomised into two groups, receiving Synergy 1 (10 g/day) or placebo (maltodextrin) for 3 months. The AA profile and concentration was determined in plasma and urine before and after the dietary intervention by gas chromatography. 22 and 28 AAs were determined in plasma and urine samples, respectively. After the intervention, the plasma concentrations of several AAs (Ala, Pro, Asn, Glu, Tyr, Lys, His, Orn) increased significantly in both experimental groups, while Gln increased only in the Synergy 1 group. The urinary excretion of Asn, Lys and Aaa increased significantly in the Synergy 1 group, and the excretion of Asp and Met decreased (p < 0.05) in the placebo group. The Gln:Glu ratio in urine increased in both groups after the intervention. An increased urinary excretion of AAs observed in Synergy 1 group with a simultaneous increase in the content of circulating AAs could be attributed to higher absorption or intensified metabolism of AAs, and on the other hand further healing of the intestinal mucosa being the result of continuous treatment with GFD. Moreover, the observed changes in Glu concentration suggest that oligofructose-enriched inulin could improve the intestinal condition and permeability. To conclude, a prebiotic-supplemented GFD influences beneficially the overall AAs metabolism in CD children; however, further prospective cohort studies are needed to confirm the results obtained.

The efficacy of daily snack replacement with oligofructose-enriched granola bars in overweight and obese adults: a 12-week randomised controlled trial.

Oligofructose is a prebiotic dietary fibre obtained from chicory root inulin. Oligofructose supplementation may affect satiety, food intake, body weight and/or body composition. The aim was to examine the efficacy of oligofructose-supplemented granola bars on the following weight management outcomes: satiety, energy intake, body weight and body composition in overweight or obese adults. In all, fifty-five adults with overweight or obesity (thirty-six females/nineteen males; age: 41 (sd 12) years; 90·6 (sd 11·8) kg; BMI: 29·4 (sd 2·6) kg/m2) participated in a parallel, triple-blind, placebo-controlled intervention. A total of twenty-nine subjects replaced their snacks twice a day with an equienergetic granola bar supplemented with 8 g of oligofructose (OF-Bar). Subjects in the control group (n 26) replaced their snack with a control granola bar without added oligofructose (Co-Bar). Satiety, 24-h energy intake, body weight and body composition (fat mass and waist circumference) were measured at baseline, weeks 6 and 12. In addition, weekly appetite and gastrointestinal side effects were measured. During the intervention, energy intake, body weight and fat mass remained similar in the Co-Bar and OF-Bar groups (all P>0·05). Both groups lost 0·3 (sd 1·2) kg lean mass (P<0·01) and reduced their waist circumference with -2·2 (sd 3·6) cm (P<0·0001) after 12 weeks. The OF-Bar group reported decreased hunger in later weeks of the intervention (P=0·04), less prospective food consumption (P=0·03) and less thirst (P=0·003). To conclude, replacing daily snacks for 12 weeks with oligofructose-supplemented granola bars does not differentially affect energy intake, body weight and body composition compared with a control bar. However, there was an indication that appetite was lower after oligofructose bar consumption.