1.5 CPEUs and 2.0 ANCC Contact Hours An Overview of Current Knowledge of the Gut Microbiota and Low-Calorie Sweeteners Riley L. Hughes, PhD 06/10/2021 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= by http://journals.lww.com/nutritiontodayonline from Downloaded Cindy D. Davis, PhD Downloaded Alexandra Lobach, PhD Hannah D. Holscher, PhD, RD from http://journals.lww.com/nutritiontodayonline This review provides an overview of the interrelationships WHAT IS THE MICROBIOME? among the diet, gut microbiota, and health status and then focuses specifically on published research assessing the rela- The human body is more than its human components. Trillions tionship of low-/no-calorie sweeteners (LNCSs) to selected of microorganisms, termed the microbiome, reside on and aspects of the gut microbiota. Microbiome research is within the human body including in the gut, oral and nasal expanding as new data on its role in health and disease vul- cavities, vagina, and on the skin (Box 1).1,2 The microbiota nerability emerge. The gut microbiome affects health, di- are comprised of bacteria, archaea, fungi, and viruses and by 1,3 BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= gestion, and susceptibility to disease. In the last 10 years, represents a diverse array of species and functional genes. investigations of LNCS effects on the gut microbiota have proliferated, although results are conflicting and are often confounded by differences in study design such as study Box 1. Definitions of the Microbiome diet, the form of the test article, dosage, and study popula- Microbiome: the collection of microbial genomes1 tion. Staying current on microbiome research and the role of Microbiota: the collection of microbial organisms1 dietary inputs, such as LNCSs, will allow healthcare and nutri- Gut microbiome: the collection of microbial genomes tion practitioners to provide evidence-based guidance to the inhabiting the gastrointestinal tract1 individuals they serve. Nutr Today. 2021;56(3):105–113 Metagenome: the collection of all of the genetic materials in asample2 Metagenomics: the study of collected genomes from an ecosystem to understand the taxonomic and functional properties of microbial communities2 Riley L. Hughes, PhD, is a postdoctoral research associate at the Univer- Metatranscriptomics: the study of RNA gene expression sity of Illinois at Urbana-Champaign. from microbial communities2 Cindy D. Davis, PhD, is the Director of Grants and Extramural Activities, Metaproteomics: the study of proteins from microbial Office of Dietary Supplements, Bethesda, MD. communities2 Alexandra Lobach, PhD, is senior manager of Toxicology, Chemistry Metabolomics: the study of small molecules (ie, metabolites) & Regulatory Affairs; Food and Nutrition, Intertek Health Sciences Inc., within a sample2 Mississauga, ON, Canada. Hannah D. Holscher, PhD, RD, is an assistant professor of Nutrition at the University of Illinois at Urbana-Champaign. The diversity of the microbiota is represented both R.L.H. and H.D.H. received funding to write the manuscript from the Insti- within and between individuals, with each person harboring tute for the Advancement of Food and Nutrition Sciences through an ILSI a unique microbial community, the majority of which reside North America Low-Calorie Sweeteners Committee grant. The Institute in the colon and are termed the “gut microbiota.”1 However, for the Advancement of Food and Nutrition Sciences is a nonprofit science on 06/10/2021 organization that pools funding from industry collaborators and advances these microbes are not passive passengers. The gut science through the in-kind and financial contributions from public and pri- microbiome can provide beneficial functions, such as metabo- vate sector participants. lism of undigested food components, vitamin production, and C.D.D. and A.L. approved the final version of the article with respect to supporting immunity. However, while certain diseases have representation of their webinar content. All authors read and approved the final manuscript. been associated with abnormal microbiota (ie, dysbiosis), it “ ” 1 The authors have no conflicts of interest to disclose. is unclear what constitutes a healthy gut microbiome. In- Correspondence: Hannah D. Holscher, PhD, RD, 1201 West Gregory Dr, deed, the composition of the gut microbiota is variable Urbana, IL 61801 ([email protected]). throughout the gastrointestinal tract (ie, stomach, ileum, de- This is an open-access article distributed under the terms of the Creative scending colon; mucosa to lumen), across geography, with Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC- age, and in relation to a host of other lifestyle factors among ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way healthy individuals, demonstrating that the gut microbiota or used commercially without permission from the journal. is a dynamic component of human physiology.4,5 Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. A variety of approaches are used to determine differ- DOI: 10.1097/NT.0000000000000481 ences in which microbes are present (composition), their ® Volume 56, Number 3, May/June 2021 Nutrition Today 105 genetic potential (functional potential), and what the mi- metabolites elicit concentration-dependent physiological crobes are doing (function).2,6 To generate taxonomic clas- effects, which are postulated to underlie the associated health sifications of microorganisms (eg, Bifidobacterium, benefits of dietary fibers, including improved glycemic control, Lactobacillus), DNA is isolated from the study samples, satiety, weight loss, increased mineral absorption, decreased typically fecal samples in human studies, and then a spe- inflammation, and overall improvement of digestive and cific region of the DNA known as the 16S rRNA gene is am- intestinal health.18 plified so that it can be used to classify the taxa present and Specific dietary components used to target the gut mi- characterize the relative abundances of the taxa within the crobiota include prebiotics, probiotics, and synbiotics samples. Similarly, metagenomic sequencing creates a se- (Box 2).22–24 The benefits of certain probiotics22 have been quence database of the full microbial genome so that the systematically reviewed under the auspices of different genetic potential of the microbiome can be characterized evidence-based organizations, including the American (eg, the presence of the enzyme used to metabolize a β2- Gastroenterological Association25; Journal of Family Prac- 1 linkage, which is found in inulin). A limitation of 16S tice26; World Gastroenterology Organisation27;European amplicon and metagenomic sequencing is that it is not pos- Society for Pediatric Gastroenterology, Hepatology and sible to determine if the microorganisms are alive or dead Nutrition28–31; Cochrane32; and European Food Safety Author- at the time of sequencing. To determine what the microbes ity.33 Notably, the health benefits of probiotic consumption are are actually doing at the time of measurement, RNA gene dependent on the strain(s), dose (>1 Â 109 colony-forming expression, proteins, and metabolites are measured using units/serving), and duration of consumption.22 Similarly, con- metatranscriptomics, metaproteomics, or metabolomics, sumption of certain prebiotics is associated with a range of respectively. Thus, these methods assess outputs or the health benefits, including bone, gut, heart, and mood, al- functions of the microbial community that may affect the though the associated benefits are dependent on the host. Therefore, an integrated approach may allow for a type of prebiotic.23,34,35 Currently established prebiotics more comprehensive view of host–microbe interactions include certain dietary fibers that impact the abundance and identification of dietary components that may be used and functionality of gut microorganisms, namely, to manipulate the gut microbiota to benefit health and re- Bifidobacterium and Lactobacillus.23 A synbiotic may duce the risk of developing certain diseases. be a combination of a probiotic and a prebiotic (comple- mentary synbiotic), although the individual components WHAT IS THE EVIDENCE THAT DIET do not necessarily need to meet the criteria for probiotics CAN INFLUENCE THE MICROBIOME? and prebiotics, as long as they act synergistically when coadministered (synergistic synbiotic).24 As with probiotics Given the role of the gut microbiome in metabolism of dietary and prebiotics, the potential health benefits of synbiotics components, there is robust evidence that intake of specific depend on the duration of use, the strain of microorgan- food components7–11 and broad dietary patterns12 influence ism, and the type and amount of nondigestible substrate, the gut microbiome over both short13,14 and long12 time as well as factors such as the individual's baseline mi- scales. In addition, recent research suggests that food choices crobiota, diet, medication, and potentially genetics.24 may be more important than nutrient profiles in influencing 14 microbiota composition. Indeed, specific foods have been Box 2. Definitions of Prebiotics, Probiotics, and Synbiotics shown to induce transient changes in the gut microbiota 7–11 Probiotic: live microorganisms that, when administered in composition thatmaythenbeusedtopredictintakeof