HMOs Impact the Gut Microbiome of Children and Adults Starting from Low Predicted Daily Doses.

Recent studies suggest that the dietary intake of human milk oligosaccharides (HMOs) provides health benefits from infancy up to adulthood. Thus far, beneficial changes in the adult gut microbiome have been observed at oral doses of 5-20 g/day of HMOs. Efficacy of lower doses has rarely been tested. We assessed four HMO molecular species-2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), and 6'Sialyllactose (6'SL)-at predicted doses from 0.3 to 5 g/day for 6-year-old children and adults (n = 6 each), using ex vivo SIFR® technology (Cryptobiotix, Ghent, Belgium). This technology employing bioreactor fermentation on fecal samples enables us to investigate microbial fermentation products that are intractable in vivo given their rapid absorption/consumption in the human gut. We found that HMOs significantly increased short-chain fatty acids (SCFAs), acetate, propionate (in children/adults), and butyrate (in adults) from predicted doses of 0.3-0.5 g/day onwards, with stronger effects as dosing increased. The fermentation of 6'SL had the greatest effect on propionate, LNnT most strongly increased butyrate, and 2'FL and 3'SL most strongly increased acetate. An untargeted metabolomic analysis revealed that HMOs enhanced immune-related metabolites beyond SCFAs, such as aromatic lactic acids (indole-3-lactic acid/3-phenyllactic acid) and 2-hydroxyisocaproic acid, as well as gut-brain-axis-related metabolites (γ-aminobutyric acid/3-hydroxybutyric acid/acetylcholine) and vitamins. The effects of low doses of HMOs potentially originate from the highly specific stimulation of keystone species belonging to, for example, the Bifidobacteriaceae family, which had already significantly increased at doses of only 0.5 g/day LNnT (adults) and 1 g/day 2'FL (children/adults).

HMOs Exert Marked Bifidogenic Effects on Children's Gut Microbiota Ex Vivo, Due to Age-Related Bifidobacterium Species Composition.

Prebiotics are substrates that are selectively utilized by host microorganisms, thus conferring a health benefit. There is a growing awareness that interpersonal and age-dependent differences in gut microbiota composition impact prebiotic effects. Due to the interest in using human milk oligosaccharides (HMOs) beyond infancy, this study evaluated how HMOs [2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), 6'Sialyllactose (6'SL)] and blends thereof affect the microbiota of 6-year-old children (n = 6) and adults (n = 6), compared to prebiotics inulin (IN) and fructooligosaccharides (FOS). The ex vivo SIFR® technology was used, given its demonstrated predictivity in clinical findings. First, HMOs and HMO blends seemed to maintain a higher α-diversity compared to FOS/IN. Further, while 2'FL/LNnT were bifidogenic for both age groups, 3'SL/6'SL and FOS/IN were exclusively bifidogenic for children and adults, respectively. This originated from age-related differences in microbiota composition because while 3'SL/6'SL stimulated B. pseudocatenulatum (abundant in children), FOS/IN enhanced B. adolescentis (abundant in adults). Moreover, all treatments significantly increased acetate, propionate and butyrate (only in adults) with product- and age-dependent differences. Among the HMOs, 6'SL specifically stimulated propionate (linked to Bacteroides fragilis in children and Phocaeicola massiliensis in adults), while LNnT stimulated butyrate (linked to Anaerobutyricum hallii in adults). Indole-3-lactic acid and 3-phenyllactic acid (linked to immune health) and gamma-aminobutyric acid (linked to gut-brain axis) were most profoundly stimulated by 2'FL and HMO blends in both children and adults, correlating with specific Bifidobacteriaceae. Finally, 2'FL/LNnT increased melatonin in children, while 3'SL remarkably increased folic acid in adults. Overall, age-dependent differences in microbiota composition greatly impacted prebiotic outcomes, advocating for the development of age-specific nutritional supplements. HMOs were shown to be promising modulators in the adult, and particularly the children's microbiota. The observed HMO-specific effects, likely originating from their structural heterogeneity, suggest that blends of different HMOs could maximize treatment effects.

Microbiota Composition of Breast Milk from Women of Different Ethnicity from the Manawatu-Wanganui Region of New Zealand.

Human breastmilk components, the microbiota and immune modulatory proteins have vital roles in infant gut and immune development. In a population of breastfeeding women (n = 78) of different ethnicities (Asian, Maori and Pacific Island, New Zealand European) and their infants living in the Manawatu-Wanganui region of New Zealand, we examined the microbiota and immune modulatory proteins in the breast milk, and the fecal microbiota of mothers and infants. Breast milk and fecal samples were collected over a one-week period during the six to eight weeks postpartum. Breast milk microbiota differed between the ethnic groups. However, these differences had no influence on the infant's gut microbiota composition. Based on the body mass index (BMI) classifications, the mother's breast milk and fecal microbiota compositions were similar between normal, overweight and obese individuals, and their infant's fecal microbiota composition also did not differ. The relative abundance of bacteria belonging to the Bacteroidetes phylum was higher in feces of infants born through vaginal delivery. However, the bacterial abundance of this phylum in the mother's breast milk or feces was similar between women who delivered vaginally or by cesarean section. Several immune modulatory proteins including cytokines, growth factors, and immunoglobulin differed between the BMI and ethnicity groups. Transforming growth factor beta 1 and 2 (TGFß1, TGFß2) were present in higher concentrations in the milk from overweight mothers compared to those of normal weight. The TGFß1 and soluble cluster of differentiation 14 (sCD14) concentrations were significantly higher in the breast milk from Maori and Pacific Island women compared with women from Asian and NZ European ethnicities. This study explores the relationship between ethnicity, body mass index, mode of baby delivery and the microbiota of infants and their mothers and their potential impact on infant health.

Adherence to the Traditional Mediterranean Diet and Human Milk Composition: Rationale, Design, and Subject Characteristics of the MEDIDIET Study.

Introduction: Knowledge about how a lactating woman's diet influences the composition of her breast milk is still very limited. In particular, no study has evaluated the role of adherence to the Mediterranean diet on human milk characteristics. Aim: We carried out an observational study to investigate the influence of mother adherence to a Mediterranean diet on her breast milk composition. Methods: Between 2012 and 2014, 300 healthy mothers, who exclusively breastfed their babies, were enrolled from five centers across Italy. During a visit to the hospital center 6 weeks after childbirth these women were asked to provide a sample of their freshly expressed breast milk and to answer a series of questions on personal characteristics and lifestyle factors. The application of a validated food frequency questionnaire allowed the collection of detailed dietary habits. Milk was collected and then stored until chemical analyses were performed. The study has been registered (Trial Registration: Dutch Trial register NTR3468). Descriptive analyses on baseline characteristics of mothers and babies were carried out on the participants, overall and stratified by center. Results: The participants had a mean age of 33 years (SD = 4.06), and a pre-pregnancy BMI of 22.3 Kg/m2 (SD = 3.22). Forty-seven percent gave birth to their first child, 40% to the second 13% to the third or subsequent child. Babies had a mean birth weight of 3,324 g (DS = 389), and a mean length of 51 cm (SD = 1.94). Fifty-three percent were males. Conclusion: The present work provides the general description and the characteristics of mothers and babies included in the MediDiet study.

Human Milk Composition and Dietary Intakes of Breastfeeding Women of Different Ethnicity from the Manawatu-Wanganui Region of New Zealand.

Human milk is nutrient rich, complex in its composition, and is key to a baby's health through its role in nutrition, gastrointestinal tract and immune development. Seventy-eight mothers (19⁻42 years of age) of Asian, Maori, Pacific Island, or of European ethnicity living in Manawatu-Wanganui, New Zealand (NZ) completed the study. The women provided three breast milk samples over a one-week period (6⁻8 weeks postpartum), completed a three-day food diary and provided information regarding their pregnancy and lactation experiences. The breast milk samples were analyzed for protein, fat, fatty acid profile, ash, selected minerals (calcium, magnesium, selenium, zinc), and carbohydrates. Breast milk nutrient profiles showed no significant differences between the mothers of different ethnicities in their macronutrient (protein, fat, carbohydrate, and moisture) content. The breast milk of Asian mothers contained significantly higher levels of polyunsaturated fatty acids (PUFAs), omega-3 (n-3) and omega-6 (n-6) fatty acids, docosahexaenoic acid (DHA), and linoleic acids. Arachidonic acid was significantly lower in the breast milk of Maori and Pacific Island women. Dietary intakes of protein, total energy, saturated and polyunsaturated fat, calcium, phosphorus, zinc, iodine, vitamin A equivalents, and folate differed between the ethnic groups, as well as the number of serves of dairy foods, chicken, and legumes. No strong correlations between dietary nutrients and breast milk components were found.

Transcriptional analysis of adipose tissue during development reveals depot-specific responsiveness to maternal dietary supplementation.

Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specific uncoupling protein (UCP)1 and rapid fat growth. The extent to which this adaptation may vary between anatomical locations remains unknown, or whether the process is sensitive to maternal dietary supplementation. We, therefore, conducted a data mining based study on the major fat depots (i.e. epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and omental) (that do not possess UCP1) of young sheep during the first month of life. Initially we determined what effect adding 3% canola oil to the maternal diet has on mitochondrial protein abundance in those depots which possessed UCP1. This demonstrated that maternal dietary supplementation delayed the loss of mitochondrial proteins, with the amount of cytochrome C actually being increased. Using machine learning algorithms followed by weighted gene co-expression network analysis, we demonstrated that each depot could be segregated into a unique and concise set of modules containing co-expressed genes involved in adipose function. Finally using lipidomic analysis following the maternal dietary intervention, we confirmed the perirenal depot to be most responsive. These insights point at new research avenues for examining interventions to modulate fat development in early life.

Impact of maternal nutrition on breast-milk composition: a systematic review.

BACKGROUND: It is widely reported that maternal diet influences the nutritional composition of breast milk. The amount of variability in human milk attributable to diet remains mostly unknown. Most original studies that reported a dietary influence on breast-milk composition did not assess diet directly, did not quantify its association with milk composition, or both. OBJECTIVE: To gather the quantitative evidence on this issue, we carried out a systematic PubMed and Medline search of articles published up to January 2015 and filtered the retrieved articles according to predefined criteria. DESIGN: Only studies that provided quantitative information on both maternal diet and milk data, measured in individual healthy mothers of healthy term infants and based on an original observational or experimental design, were included. Exclusion criteria were a focus on supplements, transfer of toxic metals or other contaminants from diet to milk, or on marginally nourished women. RESULTS: Thirty-six publications-including data on 1977 lactating women-that matched our criteria were identified. Seventeen studies investigated dietary effects on fatty acids in breast milk. The rest included studies that focused on a diverse spectrum of other nutritional properties of breast milk. The largest evidence, in terms of number of articles, for any link between maternal diet and a nutritive property of breast milk came from 3 studies that supported the link between fish consumption and high docosahexaenoic acid in breast milk and 2 studies that reported a positive correlation between dietary vitamin C and milk concentrations of this vitamin. CONCLUSIONS: The available information on this topic is scarce and diversified. Most of the evidence currently used in clinical practice to make recommendations is limited to studies that only reported indirect associations.

Functional glycans and glycoconjugates in human milk.

Human milk contains complex carbohydrates that are important dietary factors with multiple functions during early life. Several aspects of these glycostructures are human specific; some aspects vary between lactating women, and some change during the course of lactation. This review outlines how variability of complex glycostructures present in human milk is linked to changing infants' needs.

Chronic intake of fermented floral nectar by wild treeshrews.

For humans alcohol consumption often has devastating consequences. Wild mammals may also be behaviorally and physiologically challenged by alcohol in their food. Here, we provide a detailed account of chronic alcohol intake by mammals as part of a coevolved relationship with a plant. We discovered that seven mammalian species in a West Malaysian rainforest consume alcoholic nectar daily from flower buds of the bertam palm (Eugeissona tristis), which they pollinate. The 3.8% maximum alcohol concentration (mean: 0.6%; median: 0.5%) that we recorded is among the highest ever reported in a natural food. Nectar high in alcohol is facilitated by specialized flower buds that harbor a fermenting yeast community, including several species new to science. Pentailed treeshrews (Ptilocercus lowii) frequently consume alcohol doses from the inflorescences that would intoxicate humans. Yet, the flower-visiting mammals showed no signs of intoxication. Analysis of an alcohol metabolite (ethyl glucuronide) in their hair yielded concentrations higher than those in humans with similarly high alcohol intake. The pentailed treeshrew is considered a living model for extinct mammals representing the stock from which all extinct and living treeshrews and primates radiated. Therefore, we hypothesize that moderate to high alcohol intake was present early on in the evolution of these closely related lineages. It is yet unclear to what extent treeshrews benefit from ingested alcohol per se and how they mitigate the risk of continuous high blood alcohol concentrations.

Molecular and genomic data identify the closest living relative of primates.

A full understanding of primate morphological and genomic evolution requires the identification of their closest living relative. In order to resolve the ancestral relationships among primates and their closest relatives, we searched multispecies genome alignments for phylogenetically informative rare genomic changes within the superordinal group Euarchonta, which includes the orders Primates, Dermoptera (colugos), and Scandentia (treeshrews). We also constructed phylogenetic trees from 14 kilobases of nuclear genes for representatives from most major primate lineages, both extant colugos, and multiple treeshrews, including the pentail treeshrew, Ptilocercus lowii, the only living member of the family Ptilocercidae. A relaxed molecular clock analysis including Ptilocercus suggests that treeshrews arose approximately 63 million years ago. Our data show that colugos are the closest living relatives of primates and indicate that their divergence occurred in the Cretaceous.

Metschnikowia orientalis sp. nov., an Australasian yeast from nitidulid beetles.

A novel species, Metschnikowia orientalis sp. nov., is described for haploid, heterothallic yeasts isolated from nitidulid beetles sampled in flowers in Rarotonga in the Cook Islands, and the Cameron Highlands of Malaysia. As evidenced by analysis of D1/D2 large subunit rDNA sequences, the species is related to Candida hawaiiana, to which it is similar in growth responses. Cylindrical, conjugated asci and acicular ascospores of moderate size are formed. Rudimentary mating reactions were observed with Metschnikowia aberdeeniae and Metschnikowia continentalis, but not with C. hawaiiana. The type strain of M. orientalis is UWOPS 99-745.6(T) (h(+)) (=CBS 10331(T)=NRRL Y-27991(T)) and the designated allotype is UWOPS 05-269.1 (h(-)) (=CBS 10330=NRRL Y-27992).