Altered in Vitro Metabolomic Response of the Human Microbiota to Sweeteners.
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ABSTRACT:
SUBMITTER: Vamanu E
PROVIDER: S-EPMC6678981 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The effect of stevioside on human health is still insufficiently highlighted by recent research. The total or partial replacement of sugar with sweeteners influences the general state of health, especially the human microbiota's response as a determining factor in the onset of type 2 diabetes. The present study aimed to present the long-term (one-year) in vitro effect that regular stevioside consumption had on children's pattern microbiota. A metabolomic response was established by determining the synthesis of organic acids and a correlation with antioxidant status. An increase in the number of bacterial strains and the variation of amount of butyrate and propionate to the detriment of lactic acid was observed. The effect was evidenced by the progressive pH increasing, the reduction of acetic acid, and the proliferation of Escherichia coli strains during the simulations. Synthesis of the main short-chain fatty acids (SCFAs) was interpreted as a response (adaptation) of the microbiota to the stevioside, without a corresponding increase in antioxidant status. This study demonstrated the modulatory role of stevioside on the human microbiota and on the fermentation processes that determine the essential SCFA synthesis in maintaining homeostasis. The protection of the microbiota against oxidative stress was also an essential aspect of reducing microbial diversity.
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Project description:INTRODUCTION:Metoprolol succinate is a long-acting beta-blocker prescribed for the management of hypertension (HTN) and other cardiovascular diseases. Metabolomics, the study of end-stage metabolites of upstream biologic processes, yield insight into mechanisms of drug effectiveness and safety. Our aim was to determine metabolomic profiles associated with metoprolol effectiveness for the treatment of hypertension. METHODS:We performed a prospective pragmatic trial (NCT02293096) that enrolled patients between 30 and 80?years with uncontrolled HTN. Patients were started on metoprolol succinate at a dose based upon systolic blood pressure (SBP). Urine and blood pressure measurements were collected weekly. Individuals with a 10% decline in SBP or heart rate (HR) were considered responsive. Genotype for the CYP2D6 enzyme, the primary metabolic pathway for metoprolol, was evaluated for each subject. Unbiased metabolomic analyses were performed on urine samples using UPLC-QTOF mass spectrometry. RESULTS:Urinary metoprolol metabolite ratios are indicative of patient CYP2D6 genotypes. Patients taking metoprolol had significantly higher urinary levels of many gut microbiota-dependent metabolites including hydroxyhippuric acid, hippuric acid, and methyluric acid. Urinary metoprolol metabolite profiles of normal metabolizer (NM) patients more closely correlate to ultra-rapid metabolizer (UM) patients than NM patients. Metabolites did not predict either 10% SBP or HR decline. CONCLUSION:In summary, urinary metabolites predict CYP2D6 genotype in hypertensive patients taking metoprolol. Metoprolol succinate therapy affects the microbiome-derived metabolites.
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Project description:The consumption of sugar has become central to the Western diet. Cost and health concerns associated with sucrose spurred the development and consumption of other sugars and sweeteners, with the average American consuming 10 times more sugar than 100 y ago. In this review, we discuss how gut microbes are affected by changes in the consumption of sugars and other sweeteners through transcriptional, abundance, and genetic adaptations. We propose that these adaptations result in microbes taking on different metabolic, ecological, and genetic profiles along the intestinal tract. We suggest novel approaches to assess the consequences of these changes on host-microbe interactions to determine the safety of novel sugars and sweeteners.
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Project description:The aim of this study was to evaluate the effects of non-nutritive sweeteners (NNS) consumption on energy intake, body weight and postprandial glycemia in healthy and with altered glycemic response rats. Animals on normal diet (ND) or high-fat diet (HFD) were divided to receive NNS (sucralose, aspartame, stevia, rebaudioside A) or nutritive sweeteners (glucose, sucrose) for 8 weeks. The NNS were administered at doses equivalent to the human acceptable daily intake (ADI). A test using rapidly digestible starch was performed before and after treatments to estimate glycemic response. No effects of NNS consumption were observed on energy intake or body weight. Sucrose provoked an increased fluid consumption, however, energy intake, and weight gain were not altered. In ND, no effects of NNS on glycemic response were observed. In HFD, the glycemic response was increased after sucralose and stevia when only the final tolerance test was considered, however, after including the baseline test, these results were no longer significant compared to glucose. These findings provide further evidence suggesting that at the recommended doses, NNS do not alter feeding behavior, body weight or glycemic tolerance in healthy and with altered glycemic rats.
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Project description:Non-nutritive sweeteners (NNSs) are widely used in various food products and soft drinks. There is growing evidence that NNSs contribute to metabolic dysfunction and can affect body weight, glucose tolerance, appetite, and taste sensitivity. Several NNSs have also been shown to have major impacts on bacterial growth both in vitro and in vivo. Here we studied the effects of various NNSs on the growth of the intestinal bacterium, E. coli, as well as the gut bacterial phyla Bacteroidetes and Firmicutes, the balance between which is associated with gut health. We found that the synthetic sweeteners acesulfame potassium, saccharin and sucralose all exerted strong bacteriostatic effects. We found that rebaudioside A, the active ingredient in the natural NNS stevia, also had similar bacteriostatic properties, and the bacteriostatic effects of NNSs varied among different Escherichia coli strains. In mice fed a chow diet, sucralose increased Firmicutes, and we observed a synergistic effect on Firmicutes when sucralose was provided in the context of a high-fat diet. In summary, our data show that NNSs have direct bacteriostatic effects and can change the intestinal microbiota in vivo.
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Project description:Axial spondyloarthritis (axSpA) is an inflammatory arthritis involving the spine and the sacroiliac joint with extra-articular manifestations in the eye, gut, and skin. The intestinal microbiota has been implicated as a central environmental component in the pathogenesis of various types of spondyloarthritis including axSpA. Additionally, alterations in the oral microbiota have been shown in various rheumatological conditions, such as rheumatoid arthritis (RA). Therefore, the aim of this study was to investigate whether axSpA patients have an altered immunoglobulin A (IgA) response in the gut and oral microbial communities. We performed 16S rRNA gene (16S) sequencing on IgA positive (IgA+) and IgA negative (IgA-) fractions (IgA-SEQ) from feces (n=17 axSpA; n=14 healthy) and saliva (n=14 axSpA; n=12 healthy), as well as on IgA-unsorted fecal and salivary samples. PICRUSt2 was used to predict microbial metabolic potential in axSpA patients and healthy controls (HCs). IgA-SEQ analyses revealed enrichment of several microbes in the fecal (Akkermansia, Ruminococcaceae, Lachnospira) and salivary (Prevotellaceae, Actinobacillus) microbiome in axSpA patients as compared with HCs. Fecal microbiome from axSpA patients showed a tendency towards increased alpha diversity in IgA+ fraction and decreased diversity in IgA- fraction in comparison with HCs, while the salivary microbiome exhibits a significant decrease in alpha diversity in both IgA+ and IgA- fractions. Increased IgA coating of Clostridiales Family XIII in feces correlated with disease severity. Inferred metagenomic analysis suggests perturbation of metabolites and metabolic pathways for inflammation (oxidative stress, amino acid degradation) and metabolism (propanoate and butanoate) in axSpA patients. Analyses of fecal and salivary microbes from axSpA patients reveal distinct populations of immunoreactive microbes compared to HCs using the IgA-SEQ approach. These bacteria were not identified by comparing their relative abundance alone. Predictive metagenomic analysis revealed perturbation of metabolites/metabolic pathways in axSpA patients. Future studies on these immunoreactive microbes may lead to better understanding of the functional role of IgA in maintaining microbial structure and human health.
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Project description:Reduction or replacement of sucrose while maintaining sweetness in foods is challenging, but today there are many sweeteners with diverse physical and caloric compositions to choose from. The choice of sweetener can be adapted to match reformulation goals whether these are to reduce calories, lower the glycaemic response, provide bulk or meet criteria as a natural ingredient. The current study sought to describe and compare the sweetness intensity dose-response, sweetness growth rate, sweetness potency, and potential for calorie reduction across 16 different sweeteners including sucrose. Sweetness growth rate was defined as the rate of change in sweetness intensity per unit of sweetener concentration. Sweetness potency was defined as the ratio of the concentration of a sweetener to that of sucrose at equivalent sweetness intensity, whereas the potential for calorie reduction is the caloric value of a sweetener compared to sucrose at matched sweetness intensities. Sweeteners were drawn from a range of nutritive saccharide (sucrose, dextrose, fructose, allulose (d-psicose), palatinose (isomaltulose), and a sucrose?allulose mixture), nutritive polyol (maltitol, erythritol, mannitol, xylitol, sorbitol), non-nutritive synthetic (aspartame, acesulfame-K, sucralose) and non-nutritive natural sweeteners stevia (rebaudioside A), luo han guo (mogroside V). Sweetness intensities of the 16 sweeteners were compared with a sensory panel of 40 participants (n = 40; 28 females). Participants were asked to rate perceived sweetness intensity for each sweetener series across a range of concentrations using psychophysical ratings taken on a general labelled magnitude scale (gLMS). All sweeteners exhibited sigmoidal dose-response behaviours and matched the 'moderate' sweetness intensity of sucrose (10% w/v). Fructose, xylitol and sucralose had peak sweetness intensities greater than sucrose at the upper concentrations tested, while acesulfame-K and stevia (rebA) were markedly lower. Independent of sweetener concentration, the nutritive sweeteners had similar sweetness growth rates to sucrose and were greater than the non-nutritive sweeteners. Non-nutritive sweeteners on the other hand had higher potencies relative to sucrose, which decreases when matching at higher sweetness intensities. With the exception of dextrose and palatinose, all sweeteners matched the sweetness intensity of sucrose across the measured range (3.8?25% w/v sucrose) with fewer calories. Overall, the sucrose?allulose mixture, maltitol and xylitol sweeteners were most similar to sucrose in terms of dose-response behaviour, growth rate and potency, and showed the most potential for sugar replacement within the range of sweetness intensities tested.
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Project description:Sucrose, xylose, and saccharin are commonly used beverage additives and long-term consumption of these compounds inevitably affects the oral immune system and the composition of oral microbiomes. In this study, we used 24 Sprague Dawley rats divided into four groups, i.e., sucrose, saccharin, xylose, or pure water treated over an eight week period to evaluate any changes in the composition, community structure, and function of the oral microbiomes. At the end of the treatment period, we collected oral microbiome samples from each animal and subjected them to high-throughput sequencing. We also used ELISA to determine the concentration of salivary immunoglobulin in these rats to reveal the effect of sweetener on the oral immune system. Sequencing results demonstrated that Firmicutes and Proteobacteria, remained the predominant phyla, but we found that the oral microbial diversity of rats drinking sucrose water was significantly higher than that of the other groups. Our results indicate that drinking water supplemented with sweeteners may influence oral immunity as well as the composition, metabolic function, and diversity of the oral microbiota, thereby disrupting the oral microbiome.
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