synbiotic nebenwirkungen

Expert consensus document. Nutrients 7, 3022–3037 (2015). 2. Instead, a study including the combination, the substrate alone, the live microorganisms alone and a control should be conducted. 262, 31–37 (2015). Effects of genetic, processing, or product formulation changes on efficacy and safety of probiotics. 169, 240–247 (2018). 64 (Suppl. Microbiol. The administration of probiotics and synbiotics in immune compromised adults: is it safe? Dey, M. Toward a personalized approach in prebiotics research. The overall impression of any communication should lead consumers to understand the claim in a manner that is consistent with the evidence; any misleading use of the term constitutes misuse. Ultimately, this approach could enable better translation of clinical trial outcomes to those who are likely to benefit. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and . Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study. A complementary synbiotic is composed of a probiotic and a prebiotic that together confer one or more health benefits but do not require co-dependent function; the components must be used at doses that have been shown to be effective for the components alone. 10, 351–357 (2016). Seppo Salminen, Maria Carmen Collado, … Gabriel Vinderola, Mary Ellen Sanders, Daniel J. Merenstein, … Robert A. Rastall, Ravinder Nagpal, Shaohua Wang, … Hariom Yadav, Magali Cordaillat-Simmons, Alice Rouanet & Bruno Pot, Maria L. Marco, Mary Ellen Sanders, … Robert Hutkins, Anne-Sophie Alvarez, Julien Tap, … Muriel Derrien, Diletta Mazzantini, Marco Calvigioni, … Emilia Ghelardi, D. R. Michael, A. 141, 781–788 (2004). Food Microbiol. Modi, S. R., Collins, J. J. Exp. Scientists also face some challenges in getting them to consumers. J. Nutr. A randomized controlled clinical trial investigating the effect of synbiotic administration on markers of insulin metabolism and lipid profiles in overweight type 2 diabetic patients with coronary heart disease. Ther. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Am. The monosaccharides and disaccharides carried over from the production process that are present in prebiotic preparations are typically digested and absorbed by the host in the upper gastrointestinal tract after oral ingestion. Although the substrate might also enrich other beneficial members of the gastrointestinal microbiota, its main target is the ingested microorganism. Prior to the meeting, panellists developed a discussion outline and target questions. Ancillary analyses, which could include population subgroups, responders versus non-responders or exploratory microbiota analyses should be pre-specified. Tzortzis, G., Baillon, M. L., Gibson, G. R. & Rastall, R. A. Modulation of anti-pathogenic activity in canine-derived Lactobacillus species by carbohydrate growth substrate. A synergistic synbiotic contains a substrate that is selectively utilized by the co-administered live microorganism(s). compiled the paper, with invaluable support from G.R.G. 2017, 8130596 (2017). Digestive Disorders Health Center Reference, Digestive Disorders Health Center Slideshows, Digestive Disorders Health Center Quizzes. J. Gastroenterol. 27, 1031–1039 (2018). The population subgroups of interest should be specified. Scientists believe synbiotics may reduce gut inflammation and help relieve symptoms in people with IBD. Metabolomic analysis could also be performed using liquid chromatography–mass spectrometry, nuclear magnetic resonance or other suitable methods. Synergistic synbiotics work together (not independently) to bring about the resulting health benefits. Lipids 49, 695–701 (2014). This Consensus Statement further explores the levels. Nutr. & Canducci, F. Probiotics, prebiotics and synbiotics for weight loss and metabolic syndrome in the microbiome era. In the meantime, to ensure continued support, we are displaying the site without styles WebMD does not provide medical advice, diagnosis or treatment. & Zhang, Y. Efficacy of probiotics and synbiotics in patients with nonalcoholic fatty liver disease: a meta-analysis. Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. Immunol. Synbiotics in surgery for chronic pancreatitis: are they truly effective? This meta-analysis provides evidence that supports the use of synbiotics for the treatment of atopic dermatitis, which is thought to be associated with altered gut microbiota that promote an environment that is more susceptible to allergic disease. Sci. The Rowett Institute (K.P.S.) Depending on which microorganism is able to utilize the substrate, which antimicrobial factors are produced, and which taxa are neutralized or killed by them, such a scenario could lead to positive or negative outcomes. M.E.S. A product containing a probiotic and a prebiotic that only has evidence for each component individually, and not as a combination product, should not be called a synbiotic. Donaldson, G. P. et al. However, the absence of such substances today speaks to the difficulty of achieving the required evidence. North. A systematic review of 384 interventions involving prebiotics, probiotics and synbiotics found that no safety-related data were reported in 37% of the RCTs and 89 studies only used generic statements to describe AEs76. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. What Are Synbiotics and How Do They Help Gut Health? | livestrong 96, 552–559 (2004). Intern. A synbiotic is a term given to a combination of both prebiotics and probiotics in one product: scientists have recently defined them as " a mixture comprising live micro-organisms and substrate (s) selectively utilised by host micro-organisms that confers a health benefit on the host" 1. That's because they can't properly digest a sugar found in milk called lactose. It is incumbent on industry to follow good manufacturing practices, engage in truthful labelling and product promotion as well as adhere to appropriate use of the term ‘synbiotics’. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. The prebiotic functions by modulating the resident microbiota in a manner associated with an improved health outcome. Pharmacol. Thus, by itself, this study does not provide sufficient evidence that the tested combination was either a complementary or a synergistic synbiotic. Benef. currently receives research funding from Probi and has received presentation honoraria from Yakult. Sci. Important paper updating the probiotic concept. Gut 53, 241–245 (2004). In short, the safety, identity, purity and potency of the live microorganism should be clearly and accurately described according to the best available methods that meet applicable regulatory standards for the product category. Metabolic syndrome and synbiotic targeting of the gut microbiome Middle East J. J. Microbes 10, 121–135 (2019). Mol. This article acknowledges the importance of differentiating between two distinct types of synbiotic: the complementary synbiotic (microbial and substrate components act independently) and the synergistic synbiotic (the substrate component is chosen to support the growth of the microbial component). Food Sci. Thus, it is hoped that the definition herein is clear and widely accepted and will counter misuse of the term, including by scientists8. Childs, C. E. et al. J. Colorectal Dis. Hepatol. People with this condition have symptoms like bloating, diarrhea, stomach pain, and gas after eating or drinking dairy products. Sanders, M. E. et al. Sanders, M. E. et al. An in vitro study of the effect of probiotics, prebiotics and synbiotics on the elderly faecal microbiota. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. A synbiotic should be characterized to the extent needed to ensure safety and a consistent performance. has received presentation honoraria from Kellogg’s, PepsiCo and Nutricia North America. Enteral feeding intolerance, energy-protein malnutrition, and muscle wasting are common conditions in the critical care setting. J. Gastroenterol. Nutr. Dig. Journal of Probiotics & Health: “Synbiotics: Health benefits and dairy products.”, Journal of Food Science and Technology: “Probiotics, prebiotics and synbiotics- a review.”, Frontiers in Microbiology: “Role of Probiotic Bacilli in Developing Synbiotic Food: Challenges and Opportunities.”, American Society for Nutrition: “Synbiotic pasta found to enhance the health of obese individuals with or without hyperglycemia.”, Mayo Clinic: “Traveler’s diarrhea.”, Nutrition Journal: "Daily consumption of a synbiotic yogurt decreases energy intake but does not improve gastrointestinal transit time: a double-blind, randomized, crossover study in healthy adults. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Agencia Nacional de Vigilancia Sanitaria. A summary of key conclusions is shown in Box 1. In addition to the synbiotic, GOS, B. adolescentis IVS-1 and placebo (lactose) controls were also included. Probiotic and synbiotic supplementation generally increased fecal levels of the bacterial strain supplemented in the formula. Gastroenterol. Srivastava, A. Effectiveness of probiotic, prebiotic, and synbiotic therapies in reducing postoperative complications: a systematic review and network meta-analysis. Surg. Adv. Anaerobe 27, 50–55 (2014). lactis Bi-07 at 109 CFU per day met criteria for a probiotic112,129. J. Ren. They also need to find a way to ensure products actually contain enough live probiotics to be helpful. When experimental trials are not feasible or ethical, observational trials, including prospective longitudinal studies, are useful; these studies must accurately capture synbiotic exposure and control for relevant confounders (such as diet or antibiotics). & Relman, D. A. Ann. Even if a given treatment fails to demonstrate an effect (that is, acceptance of the null hypothesis) in a well-conducted study, such results still warrant publication93. Define regimen de control sanitario para productors en formas farmaceutias orales, elaborados con Lactobacillus spp., Bifidobacterium spp. Cancer 67, 457–462 (2015). Although such low doses would not be expected to provide a prebiotic effect in complementary synbiotics, they could, in theory, be sufficient to stimulate a cognate microorganism in a synergistic synbiotic formulation. And study participants with high blood sugar had lower levels of a hormone linked to insulin resistance, type 2 diabetes, and obesity. van den Nieuwboer and colleagues72,77,78,79 reviewed the AEs reported in studies with probiotic and synbiotic interventions and classified them according to the Common Terminology Criteria for Adverse Events system80; they found that the incidence of AEs in each category was either no different from or often lower in the control groups than in the treatment group. Nutr. Departamento Agencia Nacional de Medicamentos, Salud Publica, Gobierno de Chile. A. Jack, … S. F. Plummer, Nature Reviews Gastroenterology & Hepatology Dermatol. Gerade bei übermäßigem Gebrauch können Fehlbesiedlungen und daraus resultierende Symptome wie Blähungen, Flatulenz und Verwirrtheitszustände die Folge sein. To summarize (Box 1), a synbiotic is a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. Nutr. This study shows a prebiotic status for XOS used at 8 g per day. Komatsu, S. et al. Despite controversy surrounding this situation, we can expect that the European Union might adopt a similar position for the use of the term ‘synbiotic’ because it also requires evidence of a health benefit. Die Einnahme von Probiotika, Präparaten mit lebensfähigen Mikroorganismen, kann auch unerwünschte Wirkungen haben. Endocrinol. Regulatory complications can result in regions that impose probiotic-specific regulations. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. Purpose: Pro- and synbiotics have been reported to ameliorate the adverse (dysbiotic) effects of antibiotics on the gut microbial architecture, but little is known how synbiotics and antibiotics interact with each other in shaping the gut microbiota. Sanders, M. E. et al. Chermesh et al., in a randomized, double-blind and placebo-controlled study, assessed Synbiotic 2000, a synbiotic consisted of four probiotics (Pediacoccus pentosecens, Lactobacillus affinolactis, Lactobacillus paracasei susp paracasei 19 and Lactobacillus plantarum 2362) and four prebiotics (β-glucan, inulin, pectin and resistant starch). To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Clinical trial on the efficacy of a new symbiotic formulation, Flortec, in patients with irritable bowel syndrome: a multicenter, randomized study. Methods Sixty-four children (3-17 years of age) were randomized to receive a synbiotic composition (n=33) comprised of mixed-chain length, prebiotic oligosaccharides and nine microbial strains or placebo (n=31) for 84 days. J. Clin. A. et al. 139, 1051–1053 (2009). Benef. NY Acad. EBioMedicine 13, 190–200 (2016). Dig. To fulfil criteria for a synergistic synbiotic, it must be demonstrated that the health benefit and selective utilization of the substrate exceed those observed for the control and for each individual component. Front. has consulted for Seed, KGK Science, Acerus Pharmaceuticals, Danone, Chris Hansen, Altmann, Kimberly Clark and Metagenics. Evidence of selective utilization of the substrate by the co-administered live microorganism must be obtained from the same trial demonstrating the health benefit. Klurfeld, D. M. et al. At times, overextended or inflated representations of research findings can be communicated through official academic or journal press releases. Debate ensued until a consensus was achieved. J. The other type of synbiotic previously envisioned is a synergistic synbiotic, which is a synbiotic in which the substrate is designed to be selectively utilized by the co-administered microorganisms. Wellness Nutrition Are Synbiotics the New Probiotics? This entails an adequate description of substrate and live microorganism dosages, specification of the microbial strain, the structure and purity of the substrate, and the timing and route of administration of the intervention. Previous evidence supports that Bifidobacterium animalis subsp. Google Scholar. Turk. However, whether the product is a synergistic or complementary synbiotic, the panel says testing the ingredients together is crucial. Synbiotics for prevention and treatment of a dermatitis: a meta-analysis of randomized clinical trials. In a hypothetical study, a substrate (not an established prebiotic) at 1 g per dose is combined with 106 CFU of a live microorganism (not an established probiotic). Pisano, A., D’Arrigo, G., Coppolino, G. & Bolignano, D. Biotic supplements for renal patients: a systematic review and meta-analysis. A consecutive of 42 patients admitted to the Edalatian . Hepatol. 110, 139–149 (2019). Food Sci. BMJ Evid. Prebiotics and probiotics tested to date have a strong safety record69,70,71,72,73,74, and synbiotics formulated with them might also be presumed safe for the same intended uses. Dethlefsen, L. & Relman, D. A. Table 3 is designed to clearly lay out the criteria for synbiotics in comparison to probiotics and prebiotics. The complementary approach combines a prebiotic and a probiotic that work independently to elicit one or more health benefits. Rogha, M., Esfahani, M. Z. The wash-out period length should be based on the primary outcome with consideration for secondary outcomes; a 2-week wash-out between conditions is generally adequate for gut microbiota outcomes, although longer times might be necessary for some populations (for example, the elderly or for those with constipation or functional bowel disorders). 10, 28–55 (2012). The effects of synbiotic supplementation on enteral feeding tolerance ... The synbiotic concept was first introduced as "mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the gastrointestinal tract, by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promo. Government of Canada. https://doi.org/10.1093/advances/nmaa003 (2020). They outline testing protocols for humans, pets, and livestock. Functional response to a microbial synbiotic in the ... - medRxiv Collado, M. C., Vinderola, G. & Salminen, S. Postbiotics: facts and open questions. Nutr. J. Surg. After 3 weeks of consumption, genus-specific and strain-specific quantitative real-time PCR were performed to assess changes in absolute abundances of bifidobacteria. Pharmacol. Microbes 10, 711–719 (2019). All authors participated in the panel from which the ideas for this paper were generated. 69, 75–86 (2013). J. Med. Through its Industry Advisory Committee, ISAPP incorporates industry scientists in its activities and raises funds. ‘Host’ microorganisms in this context include both autochthonous microorganisms (resident or colonizing the host) and allochthonous microorganisms (externally applied, such as probiotics), which, even if transiently present, do constitute a component of the host microbiota. Am. Jackson, S. A. et al. What are Synbiotics? | Probiotics Learning Lab World Health Organization. To explore this mutual interaction we examined, first, the effect of a multi-strain synbiotic on antibiotic-induced dysbiosis and, second, the . This issue highlights that studies should communicate the content of the active ingredient being tested in addition to the quantity of the overall product. Unless appropriate experimental methods of verification are used, the product under assessment should not be referred to as ‘synbiotic’. Natl Acad. BMC Endocr. After the meeting, individual panellists wrote sections of the summary, which were compiled by K.S.S., G.R.G., R.H. and M.E.S. J. Clin. A synbiotic is defined as a "mixture of probiotics and prebiotics that beneficially affects the host by improving the survival and activity of beneficial microorganisms in the gut." From: Dietary Interventions in Gastrointestinal Diseases, 2019 Lactobacillus Probiotic Microbiome Bifidobacterium Infectious Agent Microflora Microorganism Communication of the tested health benefit must accurately reflect what was reported in the clinical trial; results should not be extrapolated to health conditions, populations or synbiotics that have not been studied. 15, 126 (2017). Gut 67, 1716–1725 (2018). J. Nutr. A randomized synbiotic trial to prevent sepsis among infants in rural India. The supplementation with synbiotic preparations carried out for 42 days caused a significant increase in the level of lactic acid in the excreta of chickens, ranging between 22.61 ± 2.35 and 27. . Thus, the probiotic strain(s) is chosen based on the benefits that it provides to the host, while the prebiotic is designed to promote the growth and activities of beneficial members of the indigenous microbiota and provide a health benefit14. The exact cause of CD is unknown, but genetics, diet, and the gut microbiome are all thought to play a major role. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Earle, K. A. et al. 15, 15–22 (2003). 29, 209–220 (2019). Thus, the combination exerted certain benefits that were not afforded by the probiotic or prebiotic alone. Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. In a blinded four-arm study, 41 healthy volunteers received either Bifidobacterium animalis subsp. Moher, D. et al. Synbiotics present challenges for researchers, including deciphering mechanisms underlying the health benefit and proving that the microbiota are modulated via complementary or synergistic means. Krumbeck, J. Clarke, M. & Chalmers, I. Reflections on the history of systematic reviews. Mahboobi, S., Rahimi, F. & Jafarnejad, S. Effects of prebiotic and synbiotic supplementation on glycaemia and lipid profile in type 2 diabetes: a meta-analysis of randomized controlled trials. Studies have shown that synbiotics could reduce these symptoms. Microbes 5, 45–60 (2014). R.A.R. Probiotika und Nebenwirkungen: Was Sie wissen müssen 8, 565–574 (2018). For interventions composed of a food or beverage, the control group must be carefully considered, including differences in flavour, texture and nutrient content. As synbiotic products are being used more frequently in clinical trials, it is incumbent upon scientists to clarify the appropriate use of this term as has been done for the terms ‘probiotic’12 and ‘prebiotic’13. In a hypothetical study, an established prebiotic substrate (for example, GOS or inulin) at the dose shown to be both selectively utilized and have a health benefit (primary outcome showing improved probably of response) is combined with an established probiotic at the dose shown to have a health benefit in the same target host. has received presentation honoraria from Beneo and research funding from General Mills and Sensus. Rev. Funding food science and nutrition research: financial conflicts and scientific integrity. Although many scenarios of formulations for synbiotics can be conceived, we provide both actual and hypothetical examples to illustrate the concept (Box 2). Implied in the definition is that safety of the synbiotic for the intended use is established. A synbiotic must contain a live microorganism and a selectively utilized substrate. Finally, as with all trials, funding sources should be transparently reported, AEs must be carefully recorded and reported, and study design, execution and reporting should comply with CONSORT guidelines48 to minimize study bias. To be a synergistic synbiotic, the live microorganism is selected based on its ability to provide a health benefit and the substrate is chosen to primarily support the growth or activity of that selected microorganism14. Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA, Department of Food and Nutritional Sciences, The University of Reading, Reading, UK, Department of Food Science and Technology, University of Nebraska – Lincoln, Lincoln, NE, USA, Faculty of Kinesiology and Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada, Translational Research in Gastrointestinal Disorders, KU Leuven, Targid, Leuven, Belgium, Leuven Food Science and Nutrition Research Centre, Leuven, Belgium, Rowett Institute, University of Aberdeen, Aberdeen, UK, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA, Children’s Hospital Research Institute of Manitoba, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada, Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium, International Scientific Association for Probiotics and Prebiotics, Centennial, CO, USA, You can also search for this author in Because the word refers to synergism, hence it must be reserved for products in which the prebiotic component selectively favours the probiotic compound (Mishra et al. & Zargarzadeh, A. H. The efficacy of a synbiotic containing Bacillus coagulans in treatment of irritable bowel syndrome: a randomized placebo-controlled trial. Fecal pH was lower with some prebiotic and synbiotic supplementation; however, no difference was . declares no competing interests. 50, 196–201 (2013). The aim is to demonstrate that the combined effect is better than the estimated effects of each component separately. Synbiotics in caries prevention: A scoping review | PLOS ONE Ioannidis, J. P. et al. Sci. Hadi, A., Mohammadi, H., Miraghajani, M. & Ghaedi, E. Efficacy of synbiotic supplementation in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of clinical trials: Synbiotic supplementation and NAFLD. The synbiotic group (n = 10) was on the same diet plan, but additionally received a synbiotic (probiotic plus prebiotic) supplement daily for 3 months. Gelegentlich kommt es jedoch zu Blähungen und/oder Durchfall oder Verstopfung, During the meeting, panellists presented the perspectives and evidence regarding the core issues involved. SH-DS01 on Fecal Metagenomic Stability - Full Text View ... Skonieczna-Zydecka, K. et al. For synergistic synbiotics, methods that quantify the live microorganism should be used to show that the target strain has indeed been enriched21 and other suitable methods can be used to show that its function has been enhanced. Instead, we advocate requiring a measurable, confirmed health benefit of the synbiotic, which is conferred, at least in part, through selective utilization of the substrate(s) provided in the synbiotic. J. Clin. 32, 918–927 (2013). & Shanahan, F. Establishing or exaggerating causality for the gut microbiome: lessons from human microbiota-associated rodents. Governement of Canada. Always check with your doctor before trying a new supplement. Probiotic and prebiotic components of the complementary synbiotic must meet the minimum criteria, as stipulated previously12,13. Clin. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. ‘Symbiotic’ is not a synonym of synbiotic and is incorrect in this context. Without the use of the term probiotic or prebiotic, relevant specific regulations would not be triggered. Gastroenterol. High-quality metagenome-assembled genomes from proximal ... - Nature However, because an increase of Bifidobacterium was not observed in individuals fed the combination product, it does not meet our definition of a synergistic synbiotic. Moreover, the Synbiotic 2000 treatment reduced the restricted, repetitive and stereotyped behaviors significantly more than placebo did (95% CI: −0.166, −0.013, ƞ 2 = 0.052; mean of t 1-t 2: 0.052 for Synbiotic 2000, −0.034 for placebo), suggesting that Synbiotic 2000 had specific benefits in reducing autistic symptoms in children. Purpose The research goal is to develop dietary strategies to help address the growing incidence of inflammatory bowel diseases (IBD). Although the term ‘synbiotic’ might not be as well recognized as probiotics and prebiotics, it is nonetheless found on product labels, in popular press articles and in the scientific literature. This result does not provide evidence for either a synergistic or complementary synbiotic. Gut health experts define 'synbiotic' supplements - Medical News Today Benef. contributed written sections for the paper. & Mishra, S. Enrichment and evaluation of galacto-oligosaccharides produced by whole cell treatment of sugar reaction mixture. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Modulation of the gastrointestinal microbiome with nondigestible fermentable carbohydrates to improve human health. PubMed Central  Gerardo, N. & Hurst, G. Q&A: friends (but sometimes foes) within: the complex evolutionary ecology of symbioses between host and microbes. Synbiotics: a technological approach in food applications 22, 7588–7605 (2018). N.M.D. For example, selective utilization of a substrate could be demonstrated experimentally using well-established in vitro gut models64 that include measurement of substrates and products during a prescribed time course.

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