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CVD and associated metabolic diseases are linked to chronic inflammation, which can be modified by diet. The objective of the present study was to determine whether there is a difference in inflammatory markers, blood metabolic and lipid panels and lymphocyte gene expression in response to a high-fat dairy food challenge with or without milk fat globule membrane (MFGM). Participants consumed a dairy product-based meal containing whipping cream (WC) high in saturated fat with or without the addition of MFGM, following a 12 h fasting blood draw. Inflammatory markers including IL-6 and C-reactive protein, lipid and metabolic panels and lymphocyte gene expression fold changes were measured using multiplex assays, clinical laboratory services and TaqMan real-time RT-PCR, respectively. Fold changes in gene expression were determined using the Pfaffl method. Response variables were converted into incremental AUC, tested for differences, and corrected for multiple comparisons. The postprandial insulin response was significantly lower following the meal containing MFGM (P < 0·01). The gene encoding soluble epoxide hydrolase (EPHX2) was shown to be more up-regulated in the absence of MFGM (P = 0·009). Secondary analyses showed that participants with higher baseline cholesterol:HDL-cholesterol ratio (Chol:HDL) had a greater reduction in gene expression of cluster of differentiation 14 (CD14) and lymphotoxin β receptor (LTBR) with the WC+MFGM meal. The protein and lipid composition of MFGM is thought to be anti-inflammatory. These exploratory analyses suggest that addition of MFGM to a high-saturated fat meal modifies postprandial insulin response and offers a protective role for those individuals with higher baseline Chol:HDL.

Individuals with anorexia nervosa (AN) restrict eating and become emaciated. They tend to have an aversion to foods rich in fat. Because epoxide hydrolase 2 (EPHX2) was identified as a novel AN susceptibility gene, and because its protein product, soluble epoxide hydrolase (sEH), converts bioactive epoxides of polyunsaturated fatty acid (PUFA) to the corresponding diols, lipidomic and metabolomic targets of EPHX2 were assessed to evaluate the biological functions of EPHX2 and their role in AN. Epoxide substrates of sEH and associated oxylipins were measured in ill AN, recovered AN and gender- and race-matched controls. PUFA and oxylipin markers were tested as potential biomarkers for AN. Oxylipin ratios were calculated as proxy markers of in vivo sEH activity. Several free- and total PUFAs were associated with AN diagnosis and with AN recovery. AN displayed elevated n-3 PUFAs and may differ from controls in PUFA elongation and desaturation processes. Cytochrome P450 pathway oxylipins from arachidonic acid, linoleic acid, alpha-linolenic acid and docosahexaenoic acid PUFAs are associated with AN diagnosis. The diol:epoxide ratios suggest the sEH activity is higher in AN compared with controls. Multivariate analysis illustrates normalization of lipidomic profiles in recovered ANs. EPHX2 influences AN risk through in vivo interaction with dietary PUFAs. PUFA composition and concentrations as well as sEH activity may contribute to the pathogenesis and prognosis of AN. Our data support the involvement of EPHX2-associated lipidomic and oxylipin dysregulations in AN, and reveal their potential as biomarkers to assess responsiveness to future intervention or treatment.

Advances in the development of bioinformatic tools continue to improve investigators' ability to interrogate, organize, and derive knowledge from large amounts of heterogeneous information. These tools often require advanced technical skills not possessed by life scientists. User-friendly, low-barrier-to-entry methods of visualizing nutrigenomics information are yet to be developed. We utilized concept mapping software from the Institute for Human and Machine Cognition to create a conceptual model of diet and health-related data that provides a foundation for future nutrigenomics ontologies describing published nutrient-gene/polymorphism-phenotype data. In this model, maps containing phenotype, nutrient, gene product, and genetic polymorphism interactions are visualized as triples of two concepts linked together by a linking phrase. These triples, or "knowledge propositions," contextualize aggregated data and information into easy-to-read knowledge maps. Maps of these triples enable visualization of genes spanning the One-Carbon Metabolism (OCM) pathway, their sequence variants, and multiple literature-mined associations including concepts relevant to nutrition, phenotypes, and health. The concept map development process documents the incongruity of information derived from pathway databases versus literature resources. This conceptual model highlights the importance of incorporating information about genes in upstream pathways that provide substrates, as well as downstream pathways that utilize products of the pathway under investigation, in this case OCM. Other genes and their polymorphisms, such as TCN2 and FUT2, although not directly involved in OCM, potentially alter OCM pathway functionality. These upstream gene products regulate substrates such as B12. Constellations of polymorphisms affecting the functionality of genes along OCM, together with substrate and cofactor availability, may impact resultant phenotypes. These conceptual maps provide a foundational framework for development of nutrient-gene/polymorphism-phenotype ontologies and systems visualization.

Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol, insulin, and adiponectin) responsiveness to acute stress (AS) were assessed in a primate model of chronic social stress (CS). Compared to controls (not exposed to CS), CS increased (P≤0.05) circulating triacylglycerol (TG) and phosphatidylethanolamine (PE) n-6/n-3 and reduced (P≤0.05) cholesterol ester (CE) 16:1n7 and phosphatidylcholine (PC) 18:1n7, suggesting lower omega-3 FA status and stearoyl-CoA desaturase activity, respectively. Cortisol responses to AS positively correlated with TG n-6/n-3 (r=0.93; P=0.007), but only in CS monkeys. The adiponectin response to AS inversely correlated with CE n-6/n3 (r=-0.89; P=0.045) and positively with TG 16:1n7 (r=0.98; P=0.004), only in CS monkeys. Our results are consistent with previously reported FA profiles in stress-related psychopathology and suggest that compositional changes of specific lipid FAs may form new functional markers of chronic psychological stress.

Genomics and bioinformatics have the vast potential to identify genes that cause disease by investigating whole-genome databases. Comparison of an individual's geno-type with a genomic database will allow the prescription of drugs to be tailored to an individual's genotype. This same bioinformatic approach, applied to the study of human metabolites, has the potential to identify and validate targets to improve personalized nutritional health and thus serve to define the added value for the next generation of foods and crops. Advances in high-throughput analytic chemistry and computing technologies make the creation of a vast database of metabolites possible for several subsets of metabolites, including lipids and organic acids. In creating integrative databases of metabolites for bioinformatic investigation, the current concept of measuring single biomarkers must be expanded to 3 dimensions to 1) include a highly comprehensive set of metabolite measurements (a profile) by multiparallel analyses, 2) measure the metabolic profile of individuals over time rather than simply in the fasted state, and 3) integrate these metabolic profiles with genomic, expression, and proteomic databases. Application of the knowledge of individual metabolism will revolutionize the ability of nutrition to deliver health benefits through food in the same way that knowledge of genomics will revolutionize individual treatment of dis-ease with pharmaceuticals. Copyright © 2001 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Epidemiologic studies from numerous disparate populations reveal that individuals with the habit of daily moderate wine consumption enjoy significant reductions in all-cause and particularly cardiovascular mortality when compared with individuals who abstain or who drink alcohol to excess. Researchers are working to explain this observation in molecular and nutritional terms. Moderate ethanol intake from any type of beverage improves lipoprotein metabolism and lowers cardiovascular mortality risk. The question now is whether wine, particularly red wine with its abundant content of phenolic acids and polyphenols, confers additional health benefits. Discovering the nutritional properties of wine is a challenging task, which requires that the biological actions and bioavailability of the >200 individual phenolic compounds be documented and interpreted within the societal factors that stratify wine consumption and the myriad effects of alcohol alone. Further challenge arises because the health benefits of wine address the prevention of slowly developing diseases for which validated biomarkers are rare. Thus, although the benefits of the polyphenols from fruits and vegetables are increasingly accepted, consensus on wine is developing more slowly. Scientific research has demonstrated that the molecules present in grapes and in wine alter cellular metabolism and signaling, which is consistent mechanistically with reducing arterial disease. Future research must address specific mechanisms both of alcohol and of polyphenolic action and develop biomarkers of their role in disease prevention in individuals. [ABSTRACT FROM AUTHOR]

The goal of this investigation was to determine whether participation in an atherosclerosis treatment program would reduce the oxidative susceptibility of LDL from patients with coronary artery disease. The treatment program included intensive exercise therapy, stress management, and consumption of a diet containing 10% fat. The size and antioxidant and lipid contents of LDL particles from 25 patients were analyzed at baseline and after 3 mo of therapy. The susceptibility of LDL to copper-mediated oxidation was measured by a conjugated diene assay and headspace gas chromatography (HSGC). Atherosclerosis treatment significantly reduced plasma total cholesterol and apolipoprotein B concentrations and the molar ratio of LDL cholesterol ester to apolipoprotein B (P < 0.01). The LDL content of alpha-tocopherol and beta-carotene was increased (27% and 17%, respectively, P < 0.04) and the molar ratio of LDL cholesterol ester the sum of LDL alpha-tocopherol and LDL beta-carotene decreased from 159 at baseline to 122 at 3 mo (P < 0.01). The lag phase of LDL conjugated diene formation increased 24%, whereas the maximum rate of oxidation slowed 29% (P < 0.01). As assessed by HSGC, copper-catalyzed formation of volatile lipid oxidation products was reduced 15% (P < 0.007); the reduction in volatiles was correlated with an increase in the alpha-tocopherol content of LDL (r=-0.48, P < 0.01). The principal determinants of reduced LDL oxidative susceptibility were the particle contents of alpha-tocopherol and beta-carotene. To our knowledge, this is the first report to document a reduction in LDL oxidation in coronary artery disease patients undergoing atherosclerosis-reversal therapy. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) has a multifactorial aetiology and many potential risk markers are known. As it was not feasible to discuss all markers and their possible interactions in relation to all aspects of CVD, selections had to be made in this paper. In the context of claims and functional foods, emphasis was placed on those aetiological processes and risk markers that have been shown previously to be modified by diet: lipid and lipoprotein metabolism, haemostatic function, oxidative damage, homocysteine metabolism, and blood pressure. Except for methodological and biological characteristics of these biomarkers, their relationships with the risk of CVD are discussed.For LDL and HDL cholesterol, fasting triacylglycerol, homocysteine, and blood pressure well-validated, easy applicable, and generally accepted biomarkers exist. For haemostatic function and oxidative damage validation of markers with respect to CVD or intermediate clinical markers is recommended. For diet-related CVD, however, the ultimate question is whether changes in the biomarker are truly related to changes in risk. Only for LDL cholesterol and blood pressure does consensus exist among scientists for a possible application as enhanced function claims. For HDL, triacylglycerol, and homocysteine, and in particular for haemostatic function and oxidative damage, however, formal proof is lacking that diet-induced changes in these biomarkers alter the risk of CVD. At the same time, it should be emphasised that CVD is multifactorial. Therefore it does not seem justified that a change in one particular biomarker is enough evidence to substantiate a claim. There are examples of food components or drugs that one biomarker is changed in a favourable way, but at the same time another biomarker is changed in an unfavourable way. Therefore, studies to further validate generic predictors for the CVD risk should be initiated. [ABSTRACT FROM AUTHOR]

Carbohydrates comprise the largest fraction of most diets and exert a profound impact on health. Components such as simple sugars and starch supply energy, while indigestible components, deemed dietary fiber, reach the colon to provide food for the tens of trillions of microbes that make up the gut microbiota. The interactions between dietary carbohydrates, our gastrointestinal tracts, the gut microbiome and host health are dictated by their structures. However, current methods for analysis of food glycans lack the sensitivity, specificity and throughput needed to quantify and elucidate these myriad structures. This protocol describes a multi-glycomic approach to food carbohydrate analysis in which the analyte might be any food item or biological material such as fecal and cecal samples. The carbohydrates are extracted by ethanol precipitation, and the resulting samples are subjected to rapid-throughput liquid chromatography (LC)-tandem mass spectrometry (LC-MS/MS) methods. Quantitative analyses of monosaccharides, glycosidic linkages, polysaccharides and alcohol-soluble carbohydrates are performed in 96-well plates at the milligram scale to reduce the biomass of sample required and enhance throughput. Detailed stepwise processes for sample preparation, LC-MS/MS and data analysis are provided. We illustrate the application of the protocol to a diverse set of foods as well as different apple cultivars and various fermented foods. Furthermore, we show the utility of these methods in elucidating glycan-microbe interactions in germ-free and colonized mice. These methods provide a framework for elucidating relationships between dietary fiber, the gut microbiome and human physiology. These structures will further guide nutritional and clinical feeding studies that enhance our understanding of the role of diet in nutrition and health., (© 2024. Springer Nature Limited.)

Members of the mammalian gut microbiota metabolize diverse complex carbohydrates that are not digested by the host, which are collectively labeled "dietary fiber." While the enzymes and transporters that each strain uses to establish a nutrient niche in the gut are often exquisitely specific, the relationship between carbohydrate structure and microbial ecology is imperfectly understood. The present study takes advantage of recent advances in complex carbohydrate structure determination to test the effects of fiber monosaccharide composition on microbial fermentation. Fifty-five fibers with varied monosaccharide composition were fermented by a pooled feline fecal inoculum in a modified MiniBioReactor array system over a period of 72 hours. The content of the monosaccharides glucose and xylose was significantly associated with the reduction of pH during fermentation, which was also predictable from the concentrations of the short-chain fatty acids lactic acid, propionic acid, and the signaling molecule indole-3-acetic acid. Microbiome diversity and composition were also predictable from monosaccharide content and SCFA concentration. In particular, the concentrations of lactic acid and propionic acid correlated with final alpha diversity and were significantly associated with the relative abundance of several of the genera, including Lactobacillus and Dubosiella . Our results suggest that monosaccharide composition offers a generalizable method to compare any dietary fiber of interest and uncover links between diet, gut microbiota, and metabolite production., Importance: The survival of a microbial species in the gut depends on the availability of the nutrients necessary for that species to survive. Carbohydrates in the form of non-host digestible fiber are of particular importance, and the set of genes possessed by each species for carbohydrate consumption can vary considerably. Here, differences in the monosaccharides that are the building blocks of fiber are considered for their impact on both the survival of different species of microbes and on the levels of microbial fermentation products produced. This work demonstrates that foods with similar monosaccharide content will have consistent effects on the survival of microbial species and on the production of microbial fermentation products., Competing Interests: D.A.M., J.B.G., and C.B.L. are cofounders of Infinant Health, a probiotic company, and One.Bio, a company advancing novel bioactive glycans. None of these companies had any role in the conceptualization, design, analysis, or preparation of the manuscript.

Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint ( p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R ( p = 0.035) but was linked to lower anxiety in AN-BP ( p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN.

Introduction: Historically, prioritizing abundant food production often resulted in overlooking nutrient quality and bioavailability, however, environmental concerns have now propelled sustainable nutrition and health efficacy to the forefront of global attention. In fact, increasing demand for protein is the major challenge facing the food system in the 21st century with an estimation that 70% more food is needed by 2050. This shift has spurred interest in plant-based proteins for their sustainability and health benefits, but most alternative sources of protein are poorly digestible. There are two approaches to solve digestibility: improve the digestibility of food proteins or improve the digestive capacity of consumers. Enhancing nutrient digestibility and bioavailability across diverse protein sources is crucial, with proteases presenting a promising avenue. Research, inspired by the proteases of human breast milk, has demonstrated that exogenous microbial proteases can activate within the human digestive tract and substantially increase the digestion of targeted proteins that are otherwise difficult to fully digest., Methods: Here, we introduce the use of an acid-active family of bacterial proteases (S53) to improve the digestibility and nutritional quality of a variety of protein sources, evaluated using the INFOGEST 2.0 protocol., Results: Results from in vitro digestibility indicate that the most effective protease in the S53 family substantially improves the digestibility of an array of animal and plant-derived proteins-soy, pea, chickpea, rice, casein, and whey. On average, this protease elevated protein digestibility by 115% during the gastric phase and by 15% in the intestinal phase, based on the degree of hydrolysis., Discussion: The widespread adoption of these proteases has the potential to enhance nutritional value and contribute to food security and sustainability. This approach would complement ongoing efforts to improve proteins in the food supply, increase the quality of more sustainable protein sources and aid in the nourishment of patients with clinically compromised, fragile intestines and individuals like older adults and high-performance athletes who have elevated protein needs., Competing Interests: WM, CJ, KM, and JH are employed by Digestiva, Inc. This study was funded in part by Mars Inc. and Digestiva, Inc. The funder, Mars Inc. was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication the funder, Digestiva, Inc. paid for the time and effort of researchers to collect data published herein. EF has ownership in Empowered Science, LLC. JG and JS are employees of University of California, Davis and scientific advisors to Digestiva, Inc. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Mak, Jones, McBride, Fritz, Hirsch, German and Siegel.)

For over a century, physicians have witnessed a common enrichment of bifidobacteria in the feces of breast-fed infants that was readily associated with infant health status. Recent advances in bacterial genomics, metagenomics, and glycomics have helped explain the nature of this unique enrichment and enabled the tailored use of probiotic supplementation to restore missing bifidobacterial functions in at-risk infants. This review documents a 20-year span of discoveries that set the stage for the current use of human milk oligosaccharide-consuming bifidobacteria to beneficially colonize, modulate, and protect the intestines of at-risk, human milk-fed, neonates. This review also presents a model for probiotic applications wherein bifidobacterial functions , in the form of colonization and HMO-related catabolic activity in situ , represent measurable metabolic outcomes by which probiotic efficacy can be scored toward improving infant health.

Objectives: Protein overfeeding in infants can have negative effects, such as diabetes and childhood obesity; key to reducing protein intake from formula is improving protein quality. The impact of a new infant formula [study formula (SF)] containing alpha-lactalbumin, lactoferrin, partially hydrolyzed whey, and whole milk on growth and tolerance compared to a commercial formula (CF) and a human milk reference arm was evaluated., Methods: This randomized, double-blind trial included healthy, singleton, term infants, enrollment age ≤14 days. Primary outcome was mean daily weight gain. Secondary outcomes were anthropometrics, formula intake, serum amino acids, adverse events, gastrointestinal characteristics, and general disposition., Results: Non-inferiority was demonstrated. There were no differences between the formula groups for z scores over time. Formula intake [-0.33 oz/kg/day, 95% confidence interval (CI): -0.66 to -0.01, P = 0.05] and mean protein intake (-0.13 g/kg/day, 95% CI: -0.26 to 0.00, P = 0.05) were lower in the SF infants, with higher serum essential amino acid concentrations (including tryptophan) compared to the CF infants. Energetic efficiency was 14.0% (95% CI: 8.3%, 19.7%), 13.0% (95% CI: 6.0%, 20.0%), and 18.1% (95% CI: 9.4%, 26.8%) higher for weight, length, and head circumference, respectively, in SF infants compared to the CF infants. SF infants had significantly fewer spit-ups and softer stool consistency than CF infants., Conclusions: The SF resulted in improved parent-reported gastrointestinal tolerance and more efficient growth with less daily formula and protein intake supporting that this novel formula may potentially reduce the metabolic burden of protein overfeeding associated with infant formula., Competing Interests: S.Z. receives an honorarium as part of the ByHeart Scientific Advisory Board. Bruce German receives an honorarium as part of the ByHeart Scientific Advisory Board. C.F. receives an honorarium as part of the ByHeart Scientific Advisory Board. S.D. receives an honorarium as part of the ByHeart Scientific Advisory Board and has received research grants from ByHeart. In addition, S.D. serves on Scientific Advisory Boards for Austnutria, Danone North America, Danone Institute International, and the National Dairy Council. She currently receives grant funding from General Mills, International Foods and Fragrances, Kyowa Hakka Bio, the National Dairy Council, National Institutes of Health (NIH), and the U.S. Department of Agriculture. B.L. receives an honorarium as part of the ByHeart Scientific Advisory Board and has received research grants from ByHeart. The remaining authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

The origin of lactation and the composition, structures and functions of milk's biopolymers highlight the Darwinian pressure on lactation as a complete, nourishing and protective diet. Lactation, under the driving pressure to be a sustainable bioreactor, was under selection pressure of its biopolymers with diverse functions acting from the mammary gland through the digestive system of the infant. For example, milk is extensively glycosylated and the glycan structures and their functions are now emerging. Milk contains free oligosaccharides; complex polymers of sugars whose stereospecific linkages are not matched by glycosidic enzymes within the mammalian infant gut. These glycan polymers reach the lower intestine undigested. In this microbe-rich environment, bacteria compete to release and ferment the sugars via different hydrolytic strategies. One specific type of bacteria, Bifidobacterium longum subsp. infantis , ( B. infantis ) is uniquely equipped with a repertoire of genes encoding enzymes capable of taking up, hydrolyzing and metabolizing the complex glycans of human milk. This combination of a distinct food supply and unique genetic capability shapes the composition and metabolic products of the entire microbial community within the lower intestine of breast fed infants. The intestinal microbiome dominated by B. infantis , shields the infant from the growth of gram negative enteropathogens and their endotoxins as a clear health benefit. The world is facing unprecedented challenges to produce a food supply that is both nourishing, safe and sustainable. Scientists need to guide the future of agriculture and food in response to these 21st century challenges. Lactation provides an inspiring model of what that future research strategy could be., Competing Interests: The authors co-founded the company Evolve Biosystems., (Copyright © 2022 German, Lebrilla and Mills.)

Background: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome., Objectives: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries., Methods: LC-MS-based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations., Results: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations., Conclusions: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The molecular complexity of the carbohydrates consumed by humans has been deceptively oversimplified due to a lack of analytical methods that possess the throughput, sensitivity, and resolution required to provide quantitative structural information. However, such information is becoming an integral part of understanding how specific glycan structures impact health through their interaction with the gut microbiome and host physiology. This work presents a detailed catalogue of the glycans present in complementary foods commonly consumed by toddlers during weaning and foods commonly consumed by American adults. The monosaccharide compositions of over 800 foods from diverse food groups including Fruits, Vegetables, Grain Products, Beans, Peas, Other Legumes, Nuts, Seeds; Sugars, Sweets and Beverages; Animal Products, and more were obtained and used to construct the "Davis Food Glycopedia" (DFG), an open-access database that provides quantitative structural information on the carbohydrates in food. While many foods within the same group possessed similar compositions, hierarchical clustering analysis revealed similarities between different groups as well. Such a Glycopedia can be used to formulate diets rich in specific monosaccharide residues to provide a more targeted modulation of the gut microbiome, thereby opening the door for a new class of prophylactic or therapeutic diets.

Bifidobacterium species are beneficial and dominant members of the breastfed infant gut microbiome; however, their health benefits are partially species-dependent. Here, we characterize the species and subspecies of Bifidobacterium in breastfed infants around the world to consider the potential impact of a historic dietary shift on the disappearance of B. longum subsp. infantis in some populations. Across populations, three distinct patterns of Bifidobacterium colonization emerged: (1) The dominance of Bifidobacterium longum subspecies infantis , (2) prevalent Bifidobacterium of multiple species, and (3) the frequent absence of any Bifidobacterium. These patterns appear related to a country's history of breastfeeding, with infants in countries with historically high rates of long-duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter-duration breastfeeding. In addition, the timing of infant colonization with B. longum subsp. infantis is consistent with horizontal transmission of this subspecies, rather than the vertical transmission previously reported for other Bifidobacterium species. These findings highlight the need to consider historical and cultural influences on the prevalence of gut commensals and the need to understand epidemiological transmission patterns of Bifidobacterium and other major commensals.

Evolutionary selective pressure on lactation has resulted in milk that provides far more than simply essential nutrients, delivering a complex repertoire of agents from hormones to intact cells. Human infants are born with low barrier integrity of their gut, which means that many of the complex biopolymer components of milk enter and circulate in lymph and blood, reaching organs throughout the body. Due to this state of gut maturation, all components of milk are potentially part of the crosstalk between mother and infants. This article highlights the functions of milk's complex biopolymers, more specifically the potential role of microRNAs (miRNAs) contained in extracellular vesicles in human milk. miRNAs are key effectors in the regulation of many biological processes during early-age development, and consequently milk-sourced miRNAs must be considered to provide unique biological assets to the infant during breastfeeding. This article interprets the evidence of the potential action of human milk miRNAs on infant development, taking into account their abundance in milk based on the literature and current knowledge. Human milk miRNAs appear to influence lipid and glucose metabolism, gut maturation, neurogenesis, and immunity. We also show growing evidence that human milk miRNAs are epigenetic modulators that play a pivotal role in the regulation of tissue-specific gene expression throughout life. Furthermore, this article addresses the ongoing debate regarding the potential influence of human milk miRNAs on viral infection as a new research area. This article highlights that these bioactive molecules are now being incorporated into our overall understanding of nutrient needs for healthy infant development, preparing each individual infant to succeed as a healthy and protected adult throughout its life. In essence, miRNAs are a new language in the Rosetta stone of health that is mammalian lactation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host's immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon β (IFNβ) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life., Competing Interests: Declaration of interests P.B., A.O., J.M., and T.L. are co-founders of Cytodelics AB (Stockholm, Sweden). P.B. is an advisor to Scailyte AG (Zurich, Switzerland) and Kancera AB (Stockholm, Sweden). R.D.M., S.C., J.P., H.K.B., S.A.F., and B.M.H. are employees of Evolve BioSystems. J.T.S. received funding to conduct the IMPRINT trial and A.M.E. received funding to assist in writing the manuscript. J.B.G. is a co-founder of Evolve BioSystems. S.A.F. and B.M.H. serve as adjunct assistant professors in the Food Science and Technology Department, University of Nebraska, Lincoln. P.B. and B.M.H. are co-inventors on a patent application related to this work., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Five years ago, with the editorial board of Frontiers in Nutrition, we took a leap of faith to outline the Goals for Nutrition Science - the way we see it (1). Now, in 2020, we can put ourselves to the test and take a look back. Without a doubt we got it right with several of the key directions. To name a few, Sustainable Development Goals (SDGs) for Food and Nutrition are part of the global public agenda, and the SDGs contribute to the structuring of international science and research. Nutritional Science has become a critical element in strengthening work on the SDGs, and the development of appropriate methodologies is built on the groundwork of acquiring and analyzing big datasets. Investigation of the Human Microbiome is providing novel insight on the interrelationship between nutrition, the immune system and disease. Finally, with an advanced definition of the gut-brain-axis we are getting a glimpse into the potential for Nutrition and Brain Health. Various milestones have been achieved, and any look into the future will have to consider the lessons learned from Covid-19 and the sobering awareness about the frailty of our food systems in ensuring global food security. With a view into the coming 5 years from 2020 to 2025, the editorial board has taken a slightly different approach as compared to the previous Goals article. A mind map has been created to outline the key topics in nutrition science. Not surprisingly, when looking ahead, the majority of scientific investigation required will be in the areas of health and sustainability. Johannes le Coutre, Field Chief Editor, Frontiers in Nutrition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bassaganya-Riera, Berry, Blaak, Burlingame, le Coutre, van Eden, El-Sohemy, German, Knorr, Lacroix, Muscaritoli, Nieman, Rychlik, Scholey and Serafini.)

Human milk contains oxylipins involved in infant development. Although oxylipins have been identified in whole or skim milk, their localization within human milk cream, cell, and skim fractions is not known. This study determined the distribution of free and esterified oxylipins in cream, cell, and skim fractions of human milk. Out of 72 oxylipins probed by mass-spectrometry, 42, 29, and 41 oxylipins (free or bound) were detected in cream, cell, and skim fractions, respectively. Over 90% of free and bound oxylipins were derived from linoleic acid in all milk fractions. Other oxylipins were derived from n-6 arachidonic acid and dihomo-gamma-linolenic acid, and n-3 alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Free oxylipins were more abundant in skim milk (59.9% of total oxylipins) compared to cream and cell pellet, whereas esterified oxylipins were most abundant in milk cream and cell pellets (74.9-76.9%). The heterogenous distribution of oxylipins in different fractions of human milk may regulate the guided release of these bioactive signaling molecules within infants., (© 2020 AOCS.)

Polysaccharides are the most abundant biomolecules in nature, but are the least understood in terms of their chemical structures and biological functions. Polysaccharides cannot be simply sequenced because they are often highly branched and lack a uniform structure. Furthermore, large polymeric structures cannot be directly analyzed by mass spectrometry techniques, a problem that has been solved for polynucleotides and proteins. While restriction enzymes have advanced genomic analysis, and trypsin has advanced proteomic analysis, there has been no equivalent enzyme for universal polysaccharide digestion. We describe the development and application of a chemical method for producing oligosaccharides from polysaccharides. The released oligosaccharides are characterized by advanced liquid chromatography-mass spectrometry (LC-MS) methods with high sensitivity, accuracy and throughput. The technique is first used to identify polysaccharides by oligosaccharide fingerprinting. Next, the polysaccharide compositions of food and feces are determined, further illustrating the utility of technique in food and clinical studies.

Background: Wearable and mobile sensor technologies can be useful tools in precision nutrition research and practice, but few are reliable for obtaining accurate and precise measurements of diet and nutrition., Objective: This study aimed to assess the ability of wearable technology to monitor the nutritional intake of adult participants. This paper describes the development of a reference method to validate the wristband's estimation of daily nutritional intake of 25 free-living study participants and to evaluate the accuracy (kcal/day) and practical utility of the technology., Methods: Participants were asked to use a nutrition tracking wristband and an accompanying mobile app consistently for two 14-day test periods. A reference method was developed to validate the estimation of daily nutritional intake of participants by the wristband. The research team collaborated with a university dining facility to prepare and serve calibrated study meals and record the energy and macronutrient intake of each participant. A continuous glucose monitoring system was used to measure adherence with dietary reporting protocols, but these findings are not reported. Bland-Altman tests were used to compare the reference and test method outputs (kcal/day)., Results: A total of 304 input cases were collected of daily dietary intake of participants (kcal/day) measured by both reference and test methods. The Bland-Altman analysis had a mean bias of -105 kcal/day (SD 660), with 95% limits of agreement between -1400 and 1189. The regression equation of the plot was Y=-0.3401X+1963, which was significant (P<.001), indicating a tendency for the wristband to overestimate for lower calorie intake and underestimate for higher intake. Researchers observed transient signal loss from the sensor technology of the wristband to be a major source of error in computing dietary intake among participants., Conclusions: This study documents high variability in the accuracy and utility of a wristband sensor to track nutritional intake, highlighting the need for reliable, effective measurement tools to facilitate accurate, precision-based technologies for personal dietary guidance and intervention., (©Sarah M Dimitratos, J Bruce German, Sara E Schaefer. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 22.07.2020.)

Lactation and breastfeeding support the short- and long-term health of both mother and infant, yet the success of these processes depend upon individual and combined factors of the pair. Complications during pregnancy and delivery greatly affect the likelihood that a mother will be capable of breastfeeding for at least the recommended 6 months. Guidelines for women regarding postpartum diet and lifestyle management also fail to reflect the diversity of mother-infant pairs and their circumstances. In our analysis of the literature, we have identified a categorical deficit in modern scientific discourse regarding human lactation; namely, that postpartum involves full-body contribution of resources and thus requires the application of nutrition from a systemic perspective., (Copyright © 2020 Ford, Underwood and German.)

Consumption of mothers' milk is associated with reduced incidence and severity of enteric infections, leading to reduced morbidity in breastfed infants. Fucosylated and sialylated human milk oligosaccharides (HMO) are important for both direct antimicrobial action - likely via a decoy effect - and indirect antimicrobial action through commensal growth enhancement. Bovine milk oligosaccharides (BMO) are a potential source of HMO-mimics as BMO resemble HMO; however, they have simpler and less fucosylated structures. BMO isolated at large scales from bovine whey permeate were modified by the addition of fucose and/or sialic acid to generate HMO-like glycans using high-yield and cost-effective one-pot multienzyme approaches. Quadrupole time-of-flight LC/MS analysis revealed that 22 oligosaccharides were synthesized and 9 had identical composition to known HMO. Preliminary anti-adherence activity assays indicated that fucosylated BMO decreased the uptake of enterohemorrhagic Escherichia coli O157:H7 by human intestinal epithelial Caco-2 cells more effectively than native BMO.

Mammalian milk is a source of antimicrobial compounds such as xanthine oxidase (XO). The interplay of infant saliva, which contains the substrates for XO activity, and human milk containing XO has been recently shown to inhibit the growth of pathogenic bacteria. Based on the complex and protective mechanism observed in human milk, we hypothesized that bovine milk XO operates similarly, thus representing an opportunity to investigate its functionality in broader health implications. We demonstrated that bovine milk-hypoxanthine mixture (0 to 400 μM) inhibited several Gram-negative and -positive bacterial pathogens in a dose-dependent manner. Kinetic experiments revealed that XO catalyzed hypoxanthine reduction (K m , 58.0 μM; V max , 5.1 μmol -1 min -1 mg) resulted in the production of antimicrobial hydrogen peroxide. These results demonstrate that the antimicrobial properties of bovine milk XO are similar to those of human milk XO with significant implications for the development of novel products targeting infant health.

Anorexia nervosa (AN) is a psychiatric disorder affected by psychological, environmental, and biological factors. Individuals with AN avoid high-fat, high-calorie diets and have shown abnormal metabolism of fatty acids (FAs), which are essential for brain and cognitive/neuropsychiatric health. To clarify the relationship between FAs and AN, fasting and postprandial plasma FAs in AN patients and age-matched control women were analyzed via mass-spectrometry. Clinical phenotypes were assessed using Becker Anxiety Inventory and Becker Depression Inventory. AN patients and controls exhibited different FA signatures at both fasting and postprandial timepoints. Lauric acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and alpha-linoleic acid (ALA) were higher in AN than in controls (lauric acid: 15,081.6 ± 14,970.2 vs. 8257.4 ± 4740.2 pmol/mL; ALA at fasting: 2217.7 ± 1587.6 vs. 1087.9 ± 821.2 pmol/mL; ALA at postprandial: 1830.9 ± 1115.6 vs. 1159.4 ± 664.7 pmol/mL. EPA: 33,788.3 ± 17,487.5 vs. 22,860.6 ± 12,642.4 pmol/mL; DPA: 32,664.8 ± 16,215.0 vs. 20,969.0 ± 12,350.0 pmol/mL. FDR-adjusted p -values < 0.05). Food intake and AN status modified the correlations of FAs with body mass index (BMI), depression, and anxiety. Desaturases SCD-18 and D6D showed lower activities in AN compared to controls. Altered FA signature, specifically correlations between elevated n -3 FAs and worsened symptoms, illustrate metabolic underpinnings in AN. Future studies should investigate the mechanisms by which FA dysregulation, specifically elevated n -3 FAs, affects AN risk and outcome.

Scope: The use of human milk products is increasing for high-risk infants. Human milk contains endogenous enzymes that comprise a dynamic proteolytic system, yet biological properties of these enzymes and their activities in response to variations including pH within infants are unclear. Human milk has a neutral pH around 7, while infant gastric pH varies from 2 to 6 depending on individual conditions. This study is designed to determine the specificity of enzyme-substrate interactions in human milk as a function of pH., Methods and Results: Endogenous proteolysis is characterized by incubating freshly expressed human milk at physiologically relevant pH ranging from 2 to 7 without the addition of exogenous enzymes. Results show that the effects of pH on endogenous proteolysis in human milk are protein-specific. Further, specific interactions between cathepsin D and α-lactalbumin are confirmed. The endogenous enzyme cathepsin D in human milk cleaves α-lactalbumin as the milk pH shifts from 7 to 3., Conclusions: This study documents that selective proteolysis activated by pH shift is a mechanism for dynamic interactions between human milk and the infant. Controlled proteolysis can guide the use of human milk products based on individual circumstance., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Personalized diet requires matching human genotypic and phenotypic features to foods that increase the chance of achieving a desired physiological health outcome. New insights and technologies will help to decipher the intricacies of diet-health relationships and create opportunities for breakthroughs in dietary interventions for personal health management., Scope and Approach: This article describes the scientific progress towards personalized diet and points out the need for integrating high-quality data on food. A framework for molecular annotation of food is presented, focusing on what aspects should be measured and how these measures relate to health. Strategies of applying trending technologies to improve personalized diet and health are discussed, highlighting challenges and opportunities for transforming data into insights and actions., Key Findings and Conclusions: The goal of personalized diet is to enable individuals and caregivers to make informed dietary decisions for targeted health management. Achieving this goal requires a better understanding of how molecular properties of food influence individual eating behavior and health outcomes. Annotating food at a molecular level encompasses characterizing its chemical composition and modifications, physicochemical structure, and biological properties. Features of molecular properties in the food annotation framework are applicable to varied conditions and processes from raw materials to meals. Applications of trending technologies, such as omics techniques, wearable biosensors, and artificial intelligence, will support data collection, data analytics, and personalized dietary actions for targeted health management.

Milk is a source of antimicrobial systems such as xanthine oxidoreductase, which has been proposed to modulate the oral and gut microbiota of infants. Heat treatments are applied to milk to ensure its microbial safety, however, the effects of heat on this antimicrobial enzyme are not known. The effects of batch pasteurization (BP), high-temperature short time (HTST), and ultra high temperature (UHT) on kinetics of inactivation of xanthine oxidase and its antimicrobial properties were determined. Xanthine oxidase activity was preserved by HTST (100%). Partial (8%) and nearly complete (95%) enzyme inactivation were observed for BP and UHT milks, respectively. K m values of 100 μM and V max values of 6.85, 5.12, 6.31, and 0.40 μmol/min/mg were determined for xanthine oxidase in raw, BP, HTST, and UHT milks, respectively. These results demonstrate that xanthine oxidase maintains apparent affinity and activity for its substrate when milk is treated by BP and HTST and yet the enzyme is inactivated with UHT. To investigate heat treatment-induced alterations in the biological activity of xanthine oxidase, heat treated milks were compared to raw milk for their ability to inhibit the growth of S. aureus . Raw, BP, and HTST milk xanthine oxidase efficiently inhibited S. aureus growth. However, these antibacterial properties were lost when milk was subjected to UHT. These results demonstrate that HTST and BP preserves bovine milk xanthine oxidase activity compared with UHT and that, the judicious selection of thermal treatments could be exploited to preserve the antimicrobial properties of bovine milk., Competing Interests: Competing interestsThe authors declare no competing interests.

Background: Proteins in human milk are essential and known to support the growth, development, protection, and health of the newborn. These proteins are highly modified by glycans that are currently being recognized as vital to protein structure, stability, function, and health of the intestinal mucosa. Although milk proteins have been studied, the quantitative changes in milk proteins and their respective site-specific glycosylation are unknown., Objective: This study expanded the analytical tools for milk proteins and their site-specific glycosylation and applied these tools to a large cohort to determine changes in individual protein concentrations and their site-specific N-glycosylation across lactation., Design: A tandem mass spectrometry method was applied to 231 breast-milk samples from 33 mothers in Davis, California, obtained during 7 different periods of lactation. Dynamic changes in the absolute abundances of milk proteins, as well as variation in site-specific N-glycosylation of individual proteins, were quantified., Results: α-Lactalbumin, β-casein, k-casein, and α-antitrypsin were significantly increased from colostrum to transitional milk (4.37 ± 1.33 g/L to 6.41 ± 0.72 g/L, 2.25 ± 0.86 g/L to 2.59 ± 0.78 g/L, 1.33 ± 0.44 g/L to 1.60 ± 0.39 g/L, and 0.09 ± 0.10 g/L to 0.11 ± 0.04 g/L, respectively; P < 0.002). α-Lactalbumin (37%), β-casein (9%), and lysozyme (159%) were higher in mature milk than in colostrum. Glycans exhibited different behavior. Fucosylated glycans of lactoferrin and high-mannose, undecorated, fucosylated, sialylated, and combined fucosylated + sialylated glycans of secretory immunoglobulin A increased during lactation even when the concentrations of the parent proteins decreased., Conclusions: Proteins in healthy mothers vary dynamically through lactation to support the development of infants. Individual milk proteins carried unique glycan modifications that varied systematically in structure even with site specificity. The role of glycosylation in human milk proteins will be important in understanding the functional components of human milk. This trial was registered at clinicaltrials.gov as NCT01817127., (Copyright © American Society for Nutrition 2019.)

Consumptions of fruit seed oils and meals could potentially improve cardiovascular health by reducing plasma total cholesterol and low-density lipoprotein (LDL). The study objective was to compare the effectiveness of expeller-pressed and solvent-extracted grape, tomato, pomegranate seed oils, and defatted pomegranate meals in lowering plasma and hepatic cholesterol using hamster models. Hamsters were fed with fruit seed oils (FSO), defatted pomegranate seed meals (PDM), or control diets. After a 3-week feeding period, plasma total triglycerides of treatment diets were significantly lower. FSO also reduced total, very-low-density lipoprotein- (VLDL), and LDL-cholesterols, while PDM only lowered VLDL-cholesterols. Decreases in low-density and high-density lipoproteins (LDL/HDL) ratios were also observed in most treatments. In liver, triglycerides, total, and free cholesterol levels did not vary between control and treatments. There were no significant differences in lipid modulating properties between solvent-extracted and expeller-pressed oils. In conclusion, partial replacements of saturated fat in high-fat diets with tomato, pomegranate, and grape seed oils could effectively reduce plasma triglyceride levels and improve HDL/LDL ratios.

CVD and associated metabolic diseases are linked to chronic inflammation, which can be modified by diet. The objective of the present study was to determine whether there is a difference in inflammatory markers, blood metabolic and lipid panels and lymphocyte gene expression in response to a high-fat dairy food challenge with or without milk fat globule membrane (MFGM). Participants consumed a dairy product-based meal containing whipping cream (WC) high in saturated fat with or without the addition of MFGM, following a 12 h fasting blood draw. Inflammatory markers including IL-6 and C-reactive protein, lipid and metabolic panels and lymphocyte gene expression fold changes were measured using multiplex assays, clinical laboratory services and TaqMan real-time RT-PCR, respectively. Fold changes in gene expression were determined using the Pfaffl method. Response variables were converted into incremental AUC, tested for differences, and corrected for multiple comparisons. The postprandial insulin response was significantly lower following the meal containing MFGM ( P < 0·01). The gene encoding soluble epoxide hydrolase ( EPHX2 ) was shown to be more up-regulated in the absence of MFGM ( P = 0·009). Secondary analyses showed that participants with higher baseline cholesterol:HDL-cholesterol ratio (Chol:HDL) had a greater reduction in gene expression of cluster of differentiation 14 ( CD14 ) and lymphotoxin β receptor ( LTBR ) with the WC+MFGM meal. The protein and lipid composition of MFGM is thought to be anti-inflammatory. These exploratory analyses suggest that addition of MFGM to a high-saturated fat meal modifies postprandial insulin response and offers a protective role for those individuals with higher baseline Chol:HDL.

Human milk is a dynamic protein-protease system that delivers bioactive peptides to infants. The pH of milk changes from the mother's mammary gland to the infant's digestive tract. Although the release of human milk peptides has been studied during in vivo or in vitro digestion, these models did not explicitly vary nor observe the effect of pH. The objective of this research was to determine the effect of pH on the proteolysis of human milk. Using high-resolution accurate-mass Orbitrap mass spectrometry, profiles of endogenous human milk peptides before and after incubation at various pH levels have been mapped. Over 5000 peptides were identified. Comparative analyses classified 74 peptides that were consistently found independent of pH alterations, and 8 peptides that were released only at pH 4 or 5 (typical infant gastric pH). Results documented that the proteolysis of milk proteins, particularly β-casein, polymeric immunoglobulin receptor, and α-lactalbumin, is pH-dependent., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2-11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments., Competing Interests: J. Bruce German and David A Mills are co-founders of Evolve Biosystems, a company focused on diet-based manipulation of the gut microbiota. Evolve Biosystems played no role in the design, execution, interpretation, or publication of this study. This conflict does not alter our adherence to PLOS ONE policies on sharing data and materials.

The evolution of lactation and the composition, structures, and functions of milk's biopolymers illustrates that the Darwinian pressure on lactation selected for gene products with considerable structural complexity and diverse functions within the digestive system. For example, complex sugar polymers - oligosaccharides - possess unique properties in guiding the growth of intestinal bacteria that are not possible by feeding their simple sugars. The proteins of milk are diverse with some exhibiting enzymatic activities towards other milk components rendering those components both more digestible but also releasing biologically active products. Thus, research into milk's biopolymers has been most enlightening when milk was investigated for the formation and disassembly of its structures and for the functions within the infant. To date however, the most complex structure in mammalian milk, the fat globule, has not been effectively examined beyond its simple composition. The globules of milk are heterogeneous in size, composition, and function. With new research tools, scientists are beginning to understand the mechanisms that control the assembly of globules in the mammary gland and the disassembly within the infant., (© 2019 Nestlé Nutrition Institute, Switzerland/S. Karger AG, Basel.)

Aging populations experience a decline in adaptive immune system function also known as immunosenesence. Protein nutrition has been shown to stimulate and strengthen the immune system, and such approaches are needed for this growing segment of the population. A controlled, randomized, double blind pilot study was conducted to compare two different protein sources (soy and dairy) as nutritional supplementation to enhance vaccine response. Our objective was to examine the immune stimulating effects of dairy protein subjected to ultraviolet radiation (UV-C) radiation treatment process instead of pasteurization. Participants were 21 healthy individuals over 60 years of age who consumed 6 g of the dairy protein or a comparison, soy isoflavone protein, twice a day for 8 weeks. DTaP vaccine administered at week 4. Non-parametric t -tests revealed a significant increase in Tetanus antibodies in the dairy group compared to the soy group at week 8. These findings suggest additional benefits of UV-C treated unheated dairy protein as a solution to counteract immunosenescence, but warrant further study in elderly and other populations that might benefit from immune system stimulation.