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1.
Effect of low-and non-calorie sweeteners on the gut microbiota: A review of clinical trials and cross-sectional studies.
Gauthier, E, Milagro, FI, Navas-Carretero, S
Nutrition (Burbank, Los Angeles County, Calif.). 2024;:112237
Abstract
Use of non-nutritive sweeteners (NNSs) has increased worldwide in recent decades. However, evidence from preclinical studies shows that sweetener consumption may induce glucose intolerance through changes in the gut microbiota, which raises public health concerns. As studies conducted on humans are lacking, the aim of this review was to gather and summarize the current evidence on the effects of NNSs on human gut microbiota. Only clinical trials and cross-sectional studies were included in the review. Regarding NNSs (i.e, saccharin, sucralose, aspartame, and stevia), only two of five clinical trials showed significant changes in gut microbiota composition after the intervention protocol. These studies concluded that saccharin and sucralose impair glycemic tolerance. In three of the four cross-sectional studies an association between NNSs and the microbial composition was observed. All three clinical trials on polyols (i.e, xylitol) showed prebiotic effects on gut microbiota, but these studies had multiple limitations (publication date, dosage, duration) that jeopardize their validity. The microbial response to NNSs consumption could be strongly mediated by the gut microbial composition at baseline. Further studies in which the potential personalized microbial response to NNSs consumption is acknowledged, and that include longer intervention protocols, larger cohorts, and more realistic sweetener dosage are needed to broaden these findings.
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2.
Application of Gut Bacterial Profiling Information in Precision Nutrition for Obesity and Weight Loss Management.
Ramos-Lopez, O, Aranaz, P, Riezu-Boj, JI, Milagro, FI
Lifestyle genomics. 2024;(1):22-30
Abstract
BACKGROUND It has been suggested that the dysfunction of the gut microbiome can have deleterious effects on the regulation of body weight and adiposity by affecting energy metabolism. In this context, gut bacterial profiling studies have contributed to characterize specific bacteria associated with obesity. This review covers the information driven by gut bacterial profiling analyses and emphasizes the potential application of this knowledge in precision nutrition strategies for obesity understanding and weight loss management. SUMMARY Gut bacterial profiling studies have identified bacterial families that are more abundant in obese than in nonobese individuals (i.e., Prevotellaeae, Ruminococcaceae, and Veillonellaceae) as well as other families that have been repeatedly found more abundant in nonobese people (i.e., Christensenellaceae and Coriobacteriaceae), suggesting that an increase in their relative amount could be an interesting target in weight-loss treatments. Also, some gut-derived metabolites have been related to the regulation of body weight, including short-chain fatty acids, trimethylamine-N-oxide, and branched-chain and aromatic amino acids. Moreover, gut microbiota profiles may play a role in determining weight loss responses to specific nutritional treatments for the precise management of obesity. Thus, incorporating gut microbiota features may improve the performance of integrative models to predict weight loss outcomes. KEY MESSAGES The application of gut bacterial profiling information is of great value for precision nutrition in metabolic diseases since it contributes to the understanding of the role of the gut microbiota in obesity onset and progression, facilitates the identification of potential microorganism targets, and allows the personalization of tailored weight loss diets as well as the prediction of adiposity outcomes based on the gut bacterial profiling of each individual. Integrating microbiota information with other omics knowledge (genetics, epigenetics, transcriptomics, proteomics, and metabolomics) may provide a more comprehensive understanding of the molecular and physiological events underlying obesity and adiposity outcomes for precision nutrition.
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3.
A Predictive Tool Based on DNA Methylation Data for Personalized Weight Loss through Different Dietary Strategies: A Pilot Study.
García-Álvarez, NC, Riezu-Boj, JI, Martínez, JA, García-Calzón, S, Milagro, FI
Nutrients. 2023;(24)
Abstract
BACKGROUND AND AIMS Obesity is a public health problem. The usual treatment is a reduction in calorie intake and an increase in energy expenditure, but not all individuals respond equally to these treatments. Epigenetics could be a factor that contributes to this heterogeneity. The aim of this research was to determine the association between DNA methylation at baseline and the percentage of BMI loss (%BMIL) after two dietary interventions, in order to design a prediction model to evaluate %BMIL based on methylation data. METHODS AND RESULTS Spanish participants with overweight or obesity (n = 306) were randomly assigned to two lifestyle interventions with hypocaloric diets: one moderately high in protein (MHP) and the other low in fat (LF) for 4 months (Obekit study; ClinicalTrials.gov ID: NCT02737267). Basal DNA methylation was analyzed in white blood cells using the Infinium MethylationEPIC array. After identifying those methylation sites associated with %BMIL (p < 0.05 and SD > 0.1), two weighted methylation sub-scores were constructed for each diet: 15 CpGs were used for the MHP diet and 11 CpGs for the LF diet. Afterwards, a total methylation score was made by subtracting the previous sub-scores. These data were used to design a prediction model for %BMIL through a linear mixed effect model with the interaction between diet and total score. CONCLUSION Overall, DNA methylation predicts the %BMIL of two 4-month hypocaloric diets and was able to determine which type of diet is the most appropriate for each individual. The results of this pioneer study confirm that epigenetic biomarkers may be further used for precision nutrition and the design of personalized dietary strategies against obesity.
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4.
Fecal microbiota relationships with childhood obesity: A scoping comprehensive review.
de Cuevillas, B, Milagro, FI, Tur, JA, Gil-Campos, M, de Miguel-Etayo, P, Martínez, JA, Navas-Carretero, S
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2022;:e13394
Abstract
Childhood obesity is a costly burden in most regions with relevant and adverse long-term health consequences in adult life. Several studies have associated excessive body weight with a specific profile of gut microbiota. Different factors related to fecal microorganism abundance seem to contribute to childhood obesity, such as gestational weight gain, perinatal diet, antibiotic administration to the mother and/or child, birth delivery, and feeding patterns, among others. This review reports and discusses diverse factors that affect the infant intestinal microbiota with putative or possible implications on the increase of the obesity childhood rates as well as microbiota shifts associated with excessive body weight in children.
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5.
A weight-loss model based on baseline microbiota and genetic scores for selection of dietary treatments in overweight and obese population.
Cuevas-Sierra, A, Milagro, FI, Guruceaga, E, Cuervo, M, Goni, L, García-Granero, M, Martinez, JA, Riezu-Boj, JI
Clinical nutrition (Edinburgh, Scotland). 2022;(8):1712-1723
Abstract
BACKGROUND & AIMS The response to weight loss depends on the interindividual variability of determinants such as gut microbiota and genetics. The aim of this investigation was to develop an integrative model using microbiota and genetic information to prescribe the most suitable diet for a successful weight loss in individuals with excess of body weight. METHODS A total of 190 Spanish overweight and obese participants were randomly assigned to two hypocaloric diets for 4 months: 61 women and 29 men followed a moderately high protein (MHP) diet, and 72 women and 28 men followed a low fat (LF) diet. Baseline fecal DNA was sequenced and used for the construction of four microbiota subscores associated with the percentage of BMI loss for each diet (MHP and LF) and for each sex. Bootstrapping techniques and multiple linear regression models were used for the selection of families, genera and species included in the subscores. Finally, two total microbiota scores were generated for each sex. Two genetic subscores previously reported to weight loss were used to generate a total genetic score. In an attempt to personalize the weight loss prescription, several linear mixed models that included interaction with diet between microbiota scores and genetic scores for both, men and women, were studied. RESULTS The microbiota subscore for the women who followed the MHP-diet included Coprococcus, Dorea, Flavonifractor, Ruminococcus albus and Clostridium bolteaea. For LF-diet women, Cytophagaceae, Catabacteriaceae, Flammeovirgaceae, Rhodobacteriaceae, Clostridium-x1vb, Bacteriodes nordiiay, Alistipes senegalensis, Blautia wexlerae and Psedoflavonifractor phocaeensis. For MHP-diet men, Cytophagaceae, Acidaminococcaceae, Marinilabiliaceae, Bacteroidaceae, Fusicatenibacter, Odoribacter and Ruminococcus faecis; and for LF-men, Porphyromanadaceae, Intestinimonas, Bacteroides finegoldii and Clostridium bartlettii. The mixed models with microbiota scores facilitated the selection of diet in 72% of women and in 84% of men. The model including genetic information allows to select the type of diet in 84% and 73%, respectively. CONCLUSIONS Decision algorithm models can help to select the most adequate type of weight loss diet according to microbiota and genetic information. CLINICAL TRIAL REGISTRY NUMBER This trial was registered at www. CLINICALTRIALS gov as NCT02737267 (https://clinicaltrials.gov/ct2/show/NCT02737267?term=NCT02737267&cond=obekit&draw=2&rank=1).
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6.
Holistic Integration of Omics Tools for Precision Nutrition in Health and Disease.
Ramos-Lopez, O, Martinez, JA, Milagro, FI
Nutrients. 2022;(19)
Abstract
The combination of multiple omics approaches has emerged as an innovative holistic scope to provide a more comprehensive view of the molecular and physiological events underlying human diseases (including obesity, dyslipidemias, fatty liver, insulin resistance, and inflammation), as well as for elucidating unique and specific metabolic phenotypes. These omics technologies include genomics (polymorphisms and other structural genetic variants), epigenomics (DNA methylation, histone modifications, long non-coding RNA, telomere length), metagenomics (gut microbiota composition, enterotypes), transcriptomics (RNA expression patterns), proteomics (protein quantities), and metabolomics (metabolite profiles), as well as interactions with dietary/nutritional factors. Although more evidence is still necessary, it is expected that the incorporation of integrative omics could be useful not only for risk prediction and early diagnosis but also for guiding tailored dietary treatments and prognosis schemes. Some challenges include ethical and regulatory issues, the lack of robust and reproducible results due to methodological aspects, the high cost of omics methodologies, and high-dimensional data analyses and interpretation. In this review, we provide examples of system biology studies using multi-omics methodologies to unravel novel insights into the mechanisms and pathways connecting the genotype to clinically relevant traits and therapy outcomes for precision nutrition applications in health and disease.
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7.
A nutrigenetic tool for precision dietary management of non-alcoholic fatty liver disease deeming insulin resistance markers.
Perez-Diaz-Del-Campo, N, Riezu-Boj, JI, Marin-Alejandre, BA, Monreal, JI, Elorz, M, Herrero, JI, Benito-Boillos, A, Milagro, FI, Bugianesi, E, Tur, JA, et al
Panminerva medica. 2022;(4):485-496
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) development is linked to insulin resistance and influenced by environmental factors, but it also underlined a genetic predisposition. The aim of this research was to build a predictive model based on genetic and hepatic health information, deeming insulin resistance markers in order to personalize dietary treatment in overweight/obese subjects with NAFLD. METHODS A 6-month nutritional intervention was conducted in 86 overweight/obese volunteers with NAFLD randomly assigned to 2 energy-restricted diets: the American Heart Association (AHA) diet and the Fatty Liver in Obesity (FLiO) diet. Individuals were genotyped using a predesigned panel of 95 genetic variants. A Genetic Risk Score (GRS) for each diet was computed using statistically relevant SNPs for the change on Fatty Liver Index (FLI) after 6-months of nutritional intervention. Body composition, liver injury and insulin resistance markers, as well as physical activity and dietary intake were also assessed. RESULTS Under energy restriction, both the AHA and FLiO diets induced similar significant improvements on body composition, insulin resistance markers, hepatic health and dietary and lifestyle outcomes. The calculated score included in the linear mixed regression model was able to predict the change of FLI adjusted by diet, age and sex. This model allowed to personalize the most suitable diet for 72% of the volunteers. Similar models were also able to predict the changes on Triglycerides and Glucose (TyG) Index and retinol-binding protein 4 (RBP4) levels depending on diet. CONCLUSIONS Models integrating genetic screening and insulin resistance markers can be useful for the personalization of NAFLD weight loss treatments.
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8.
Genetic and epigenetic nutritional interactions influencing obesity risk and adiposity outcomes.
Ramos-Lopez, O, Riezu-Boj, JI, Milagro, FI
Current opinion in clinical nutrition and metabolic care. 2022;(4):235-240
Abstract
PURPOSE OF REVIEW This article aims to critically overview the current interplay of genetic/epigenetic factors and several nutritional aspects influencing obesity susceptibility and adiposity outcomes for obesity management and weight status monitoring. RECENT FINDINGS Single nucleotide polymorphisms located in or near genes participating in energy homeostasis, fatty acid metabolism, appetite control, brain regulation, and thermogenesis have been associated with body composition measures (body weight, body mass index, waist circumference, body fat percentage, and visceral adipose tissue) depending on nutrient intakes, dietary patterns, and eating behaviors. Moreover, studies analyzing interactions between the epigenome and dietary intakes in relation to adiposity outcomes are reported. The main epigenetic mechanisms include methylation levels of promoter sequences, telomere length, and micro-ribonucleic acid expression profiles, whereas covalent histone modifications remain less studied. SUMMARY Exploring potential interactions between the genetic/epigenetic background and nutritional features is improving the current understanding of the obesity physiopathogenesis and the usefulness of translating this precision information in the clinical setting for weight gain prediction, the design of personalized nutrition therapies as well as individual responsiveness estimation to dietary advice. The analysis of further relationships between the genotype, the epigenotype and other precision markers including the gut microbiota and the metabolome is warranted.
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9.
Kefir and Intestinal Microbiota Modulation: Implications in Human Health.
Peluzio, MDCG, Dias, MME, Martinez, JA, Milagro, FI
Frontiers in nutrition. 2021;:638740
Abstract
In the last decades changes in the pattern of health and disease in Latin America and in the world has been observed, with an increase in cases of chronic non-communicable diseases. Changes in intestinal microbiota composition can contribute to the development of these diseases and be useful in their management. In this context, the consumption of fermented foods with probiotic properties, such as kefir, stands out due to its gut microbiota-modulating capacity. There is an increasing interest in the commercial use of kefir since it can be marketed as a natural beverage containing health-promoting bacteria and has been gaining international popularity in Latin America. Also the consumption of these drinks in Latin America seems to be even more relevant, given the socioeconomic situation of this population, which highlights the need for disease prevention at the expense of its treatment. In this narrative review, we discuss how kefir may work against obesity, diabetes mellitus, liver disease, cardiovascular disorders, immunity, and neurological disorders. Peptides, bioactive compounds and strains occurring in kefir, can modulate gut microbiota composition, low-grade inflammation and intestinal permeability, which consequently may generate health benefits. Kefir can also impact on the regulation of organism homeostasis, with a direct effect on the gut-brain axis, being a possible strategy for the prevention of metabolic diseases. Further studies are needed to standardize these bioactive compounds and better elucidate the mechanisms linking kefir and intestinal microbiota modulation. However, due to the benefits reported, low cost and ease of preparation, kefir seems to be a promising approach to prevent and manage microbiota-related diseases in Latin America and the rest of the world.
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10.
Potential Mechanisms Linking Food-Derived MicroRNAs, Gut Microbiota and Intestinal Barrier Functions in the Context of Nutrition and Human Health.
Díez-Sainz, E, Lorente-Cebrián, S, Aranaz, P, Riezu-Boj, JI, Martínez, JA, Milagro, FI
Frontiers in nutrition. 2021;:586564
Abstract
MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules from 18 to 24 nucleotides that are produced by prokaryote and eukaryote organisms, which play a crucial role in regulating gene expression through binding to their mRNA targets. MiRNAs have acquired special attention for their potential in cross kingdom communication, notably food-derived microRNAs (xenomiRs), which could have an impact on microorganism and mammal physiology. In this review, we mainly aim to deal with new perspectives on: (1) The mechanism by which food-derived xenomiRs (mainly dietary plant xenomiRs) could be incorporated into humans through diet, in a free form, associated with proteins or encapsulated in exosome-like nanoparticles. (2) The impact of dietary plant-derived miRNAs in modulating gut microbiota composition, which in turn, could regulate intestinal barrier permeability and therefore, affect dietary metabolite, postbiotics or food-derived miRNAs uptake efficiency. Individual gut microbiota signature/composition could be also involved in xenomiR uptake efficiency through several mechanisms such us increasing the bioavailability of exosome-like nanoparticles miRNAs. (3) Gut microbiota dysbiosis has been proposed to contribute to disease development by affecting gut epithelial barrier permeability. For his reason, the availability and uptake of dietary plant xenomiRs might depend, among other factors, on this microbiota-related permeability of the intestine. We hypothesize and critically review that xenomiRs-microbiota interaction, which has been scarcely explored yet, could contribute to explain, at least in part, the current disparity of evidences found dealing with dietary miRNA uptake and function in humans. Furthermore, dietary plant xenomiRs could be involved in the establishment of the multiple gut microenvironments, in which microorganism would adapt in order to optimize the resources and thrive in them. Additionally, a particular xenomiR could preferentially accumulate in a specific region of the gastrointestinal tract and participate in the selection and functions of specific gut microbial communities.