Differences in the Concentration and Composition of Human Milk Components Are Related to Variation in Milk and Infant Fecal Microbiomes

Abstract Objectives Profiles of human milk oligosaccharides (HMO) and milk/infant fecal microbiota vary globally. However, associations between and among HMO, other milk-borne factors (e.g., lactose, protein), and milk/infant fecal microbiomes have not been well-investigated. Here we tested the hypothesis that variations in milk lactose, protein, and HMO concentrations are associated with variations in the structure of milk and infant fecal microbial communities. Methods Milk/infant fecal samples from 357 maternal-infant dyads collected as part of the INSPIRE study from 11 geographically/culturally diverse sites located in eight countries (Ethiopia, The Gambia, Ghana, Kenya, Peru, Spain, Sweden, and USA) were analyzed. DNA was extracted and bacterial 16S rRNA V1V3 hypervariable region amplified/sequenced for microbiome analysis. HMO, lactose, and protein profiles were generated from HPLC and spectrophotometric assays. Results Milk and infant feces share many of the same abundant bacterial genera, while also containing unique bacterial communities. Community states type (CST) analyses indicate both sample types group into a relatively small number of discrete communities characterized by enrichment of specific taxa (e.g., Streptococcus, Bifidobacterium). Concentrations of milk lactose and protein varied by population/CST. Additionally, variation in the microbial community structure of milk and infant feces was associated with concentrations of total/individual HMO, lactose, and protein. Conclusions Similar to HMO concentrations, milk lactose and protein vary globally. Variations in milk and infant fecal microbial communities are associated with those of milk lactose, protein, and HMO concentrations. Given these results, as well as prior data on the influence of other environmental variables (e.g., pumped vs. direct breastfeeding), additional longitudinal studies are needed to better understand this complex network of maternal-infant-microbe interactions with respect to environmental factors and how differences impact postnatal maternal-infant health. Funding Sources National Science Foundation (award 1,344,288), National Institutes of Health (R01 HD092297), and USDA.

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Bacterial Co-Occurrence Patterns Between Human Milk and Microbial Sites of Breastfeeding Dyads

Current Developments in Nutrition ◽

10.1093/cdn/nzaa054_038 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 966-966

Author(s):

Erin Davis ◽

Mei Wang ◽

Sharon Donovan

Keyword(s):

Human Milk ◽

Community Organization ◽

Fecal Microbiota ◽

Microbial Interactions ◽

Rrna Gene ◽

Ecological Relationships ◽

Funding Sources ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Occurrence Patterns

Abstract Objectives The human milk (HM) microbiota is predicted to originate from the maternal gastrointestinal tract, saliva and breast skin, and infant saliva. Though compositionally distinct, these habitats are strongly associated during breastfeeding. Vertical microbial transmission from mother to infant has been documented, but complex microbial interactions between sites are less clear. Herein, ecological networks between HM bacteria and other microbial sites of breastfeeding dyads were assessed to investigate the origin of the HM microbiota and how it may shape the infant gut microbiota. Methods DNA was extracted from maternal and infant saliva, HM, breast skin, and maternal and infant stool samples collected at 6 weeks postpartum from 33 mother-infant pairs. The V3-V4 region of the 16S rRNA gene was sequenced and taxonomy was assigned using QIIME 2. Co-occurrence patterns among genus-level abundance data were analyzed in CoNet (Cytoscape 3.0). Results Twenty-one significant co-presence relationships were identified between HM and other microbial communities. Associations spanned from six nodes in HM including Corynebacterium, Cutibacterium, Gemella, Rothia, Veillonella, and Actinomyces. Co-presence between Cutibacterium, Veillonella, Actinomyces, and Corynebacterium on skin and HM were identified, supporting breast skin as a principal contributor to the HM microbiota. Interestingly, Bifidobacterium in infant saliva was associated with Gemella and Rothia in HM. The greatest number of relationships existed between HM and infant stool. HM Gemella, Actinomyces, and Corynebacterium were associated with Bacteroides in infant stool; HM Actinomyces was also associated with infant fecal Escherichia-Shigella and Eggerthella. Additional relationships were identified between HM and maternal saliva and fecal microbiota. Conclusions Several unique ecological relationships exist between HM and microbial sites of breastfeeding dyads. Whether these relationships are indicative of proximity, mutualism, or are biomarkers of other host-microbe interactions remains to be determined. These data will be useful to uncover mechanisms driving microbial community organization and potential targets for microbial modulation in this population. Funding Sources National Dairy Council, NIH, The Gerber Foundation, The Doris Kelley Christopher Foundation.

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Probiotics in human milk and probiotic supplementation in infant nutrition: a workshop report

British Journal Of Nutrition ◽

10.1017/s0007114514001949 ◽

2014 ◽

Vol 112 (7) ◽

pp. 1119-1128 ◽

Cited By ~ 31

Author(s):

Henrike Bergmann ◽

Juan Miguel Rodríguez ◽

Seppo Salminen ◽

Hania Szajewska

Keyword(s):

Human Milk ◽

Infant Health ◽

Infant Nutrition ◽

Mode Of Delivery ◽

Bacterial Strains ◽

Probiotic Supplementation ◽

Maternal Environment ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Transfer To Milk

Probiotics in human milk are a very recent field of research, as the existence of the human milk microbiome was discovered only about a decade ago. Current research is focusing on bacterial diversity and the influence of the maternal environment as well as the mode of delivery on human milk microbiota, the pathways of bacterial transfer to milk ducts, possible benefits of specific bacterial strains for the treatment of mastitis in mothers, and disease prevention in children. Recent advances in the assessment of early host–microbe interactions suggest that early colonisation may have an impact on later health. This review article summarises a scientific workshop on probiotics in human milk and their implications for infant health as well as future perspectives for infant feeding.

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Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem

The ISME Journal ◽

10.1038/s41396-019-0553-2 ◽

2019 ◽

Vol 14 (2) ◽

pp. 635-648 ◽

Cited By ~ 39

Author(s):

Melissa A. E. Lawson ◽

Ian J. O’Neill ◽

Magdalena Kujawska ◽

Sree Gowrinadh Javvadi ◽

Anisha Wijeyesekera ◽

...

Keyword(s):

Human Milk ◽

Early Life ◽

Infant Health ◽

Gene Clusters ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

H Nmr ◽

Feeding Experiments ◽

Microbe Interactions ◽

Breast Fed

AbstractDiet-microbe interactions play an important role in modulating the early-life microbiota, with Bifidobacterium strains and species dominating the gut of breast-fed infants. Here, we sought to explore how infant diet drives distinct bifidobacterial community composition and dynamics within individual infant ecosystems. Genomic characterisation of 19 strains isolated from breast-fed infants revealed a diverse genomic architecture enriched in carbohydrate metabolism genes, which was distinct to each strain, but collectively formed a pangenome across infants. Presence of gene clusters implicated in digestion of human milk oligosaccharides (HMOs) varied between species, with growth studies indicating that within single infants there were differences in the ability to utilise 2′FL and LNnT HMOs between strains. Cross-feeding experiments were performed with HMO degraders and non-HMO users (using spent or ‘conditioned’ media and direct co-culture). Further 1H-NMR analysis identified fucose, galactose, acetate, and N-acetylglucosamine as key by-products of HMO metabolism; as demonstrated by modest growth of non-HMO users on spend media from HMO metabolism. These experiments indicate how HMO metabolism permits the sharing of resources to maximise nutrient consumption from the diet and highlights the cooperative nature of bifidobacterial strains and their role as ‘foundation’ species in the infant ecosystem. The intra- and inter-infant bifidobacterial community behaviour may contribute to the diversity and dominance of Bifidobacterium in early life and suggests avenues for future development of new diet and microbiota-based therapies to promote infant health.

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Variation in Human Milk Composition Is Related to Differences in Milk and Infant Fecal Microbial Communities

Microorganisms ◽

10.3390/microorganisms9061153 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1153

Author(s):

Ryan M. Pace ◽

Janet E. Williams ◽

Bianca Robertson ◽

Kimberly A. Lackey ◽

Courtney L. Meehan ◽

...

Keyword(s):

Microbial Community ◽

Human Milk ◽

Microbial Communities ◽

Geographical Variation ◽

Milk Composition ◽

Published Data ◽

Community Structures ◽

Microbial Community Structures ◽

Infant Feces ◽

Human Milk Oligosaccharide

Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, as well as the associations among these factors and microbial community structures in milk and infant feces. Here, we characterized and contrasted concentrations of milk-borne lactose, protein, and HMOs, and examined their associations with milk and infant fecal microbiomes in samples collected in 11 geographically diverse sites. Although geographical site was strongly associated with milk and infant fecal microbiomes, both sample types assorted into a smaller number of community state types based on shared microbial profiles. Similar to HMOs, concentrations of lactose and protein also varied by geography. Concentrations of HMOs, lactose, and protein were associated with differences in the microbial community structures of milk and infant feces and in the abundance of specific taxa. Taken together, these data suggest that the composition of human milk, even when produced by relatively healthy women, differs based on geographical boundaries and that concentrations of HMOs, lactose, and protein in milk are related to variation in milk and infant fecal microbial communities.

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Free and Total Amino Acids in Human Milk in Relation to Maternal and Infant Characteristics and Infant Health Outcomes: The Ulm SPATZ Health Study

Nutrients ◽

10.3390/nu13062009 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2009

Author(s):

Joris H.J. van Sadelhoff ◽

Linda P. Siziba ◽

Lisa Buchenauer ◽

Marko Mank ◽

Selma P. Wiertsema ◽

...

Keyword(s):

Amino Acids ◽

Health Outcomes ◽

Human Milk ◽

Infant Development ◽

Infant Health ◽

Child Growth ◽

Health Study ◽

Maternal Characteristics ◽

Tract Infections ◽

Total Amino Acids

Free amino acids (FAAs) are important regulators of key pathways necessary for growth, development, and immunity. Data on FAAs in human milk (HM) and their roles in infant development are limited. We investigated the levels of FAAs and total amino acids (TAA, i.e., the sum of conjugated amino acids and FAAs) in HM in relation to infant and maternal characteristics and immunological conditions. FAA and TAA levels in HM sampled at 6 weeks (n = 671) and 6 months (n = 441) of lactation were determined using high-performance liquid chromatography. Child growth was ascertained at 4–5 weeks and at 6–7 months of age. Child allergy and lower respiratory tract infections were assessed in the first years of life. Associations of amino acid (AA) levels in HM with child growth and health outcomes were determined by Spearman correlation and modified Poisson regression, respectively. Free glutamine, glutamate, and serine in 6-week HM positively correlated with infant weight gain in the first 4–5 weeks of age. Maternal pre-pregnancy weight and body mass index (BMI) were negatively correlated with free glutamine and asparagine in 6-week and 6-month HM and positively correlated with the sum of TAAs in 6-month HM, but significance was lost following confounder adjustment. Free glutamine was lower in 6-month HM of mothers with an allergy (either active or non-active). No consistent associations were found between FAAs in HM and child health outcomes. However, potential negative associations were observed between specific FAAs and the risk of food allergy. These results suggest that specific FAAs play a role in infant growth. Moreover, these findings warrant further investigations into the relation of FAAs in HM with infant health outcomes and maternal allergy.

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A Microbial Perspective on the Grand Challenges in Comparative Animal Physiology

mSystems ◽

10.1128/msystems.00146-17 ◽

2018 ◽

Vol 3 (2) ◽

Cited By ~ 4

Author(s):

Kevin D. Kohl

Keyword(s):

Microbial Communities ◽

Vertical Integration ◽

Temporal Integration ◽

Data Sets ◽

Grand Challenges ◽

Animal Physiology ◽

Physiological Processes ◽

Microbe Interactions ◽

Animal Hosts ◽

Host Microbe Interactions

ABSTRACTInteractions with microbial communities can have profound influences on animal physiology, thereby impacting animal performance and fitness. Therefore, it is important to understand the diversity and nature of host-microbe interactions in various animal groups (invertebrates, fish, amphibians, reptiles, birds, and mammals). In this perspective, I discuss how the field of host-microbe interactions can be used to address topics that have been identified as grand challenges in comparative animal physiology: (i) horizontal integration of physiological processes across organisms, (ii) vertical integration of physiological processes across organizational levels within organisms, and (iii) temporal integration of physiological processes during evolutionary change. Addressing these challenges will require the use of a variety of animal models and the development of systems approaches that can integrate large, multiomic data sets from both microbial communities and animal hosts. Integrating host-microbe interactions into the established field of comparative physiology represents an exciting frontier for both fields.

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Parallel changes in gut microbiome composition and function in parallel local adaptation and speciation

10.1101/736843 ◽

2019 ◽

Cited By ~ 2

Author(s):

Diana J. Rennison ◽

Seth M. Rudman ◽

Dolph Schluter

Keyword(s):

Microbial Communities ◽

Local Adaptation ◽

Biotic Interactions ◽

Ecological Speciation ◽

Microbiome Composition ◽

Interacting Species ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

And Function ◽

Host Evolution

AbstractThe processes of local adaptation and ecological speciation are often strongly shaped by biotic interactions such as competition and predation. One of the strongest lines of evidence that biotic interactions drive evolution comes from repeated divergence of lineages in association with repeated changes in the community of interacting species. Yet, relatively little is known about the repeatability of changes in gut microbial communities and their role in adaptation and divergence of host populations in nature. Here we utilize three cases of rapid, parallel adaptation and speciation in freshwater threespine stickleback to test for parallel changes in associated gut microbiomes. We find that features of the gut microbial communities have shifted repeatedly in the same direction in association with parallel divergence and speciation of stickleback hosts. These results suggest that changes to gut microbiomes can occur rapidly and predictably in conjunction with host evolution, and that host-microbe interactions might play an important role in host adaptation and diversification.

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Life on leaves : uncovering temporal dynamics in Arabidopsis' leaf microbiota

10.1101/2021.07.06.450897 ◽

2021 ◽

Author(s):

Juliana Almario ◽

Maryam Mahmoudi ◽

Samuel Kroll ◽

Matthew Agler ◽

Aleksandra Placzek ◽

...

Keyword(s):

Microbial Communities ◽

Photosynthetic Activity ◽

Temporal Dynamics ◽

Growing Season ◽

High Turnover ◽

Microbial Network ◽

Stabilization Phase ◽

Time Patterns ◽

Microbe Interactions ◽

Compositional Changes

Leaves are primarily responsible for the plant′s photosynthetic activity. Thus, changes in the phyllosphere microbiota, which includes deleterious and beneficial microbes, can have far reaching effects on plant fitness and productivity. In this context, identifying the processes and microorganisms that drive the changes in the leaf microbiota over a plant′s lifetime is crucial. In this study we analyzed the temporal dynamics in the leaf microbiota of Arabidopsis thaliana, integrating both compositional changes and changes in microbe-microbe interactions via the study of microbial networks. Field-grown Arabidopsis were used to follow leaf bacterial, fungal and oomycete communities, throughout the plant′s growing season (extending from November to March), over three consecutive years. Our results revealed the existence of conserved time patterns, with microbial communities and networks going through a stabilization phase (decreasing diversity and variability) at the beginning of the plant′s growing season. Despite a high turnover in these communities, we identified 19 "core" taxa persisting in Arabidopsis leaves across time and plant generations. With the hypothesis these microbes could be playing key roles in the structuring of leaf microbial communities, we conducted a time-informed microbial network analysis which showed core taxa are not necessarily highly connected network "hubs" and "hubs" alternate with time. Our study shows that leaf microbial communities exhibit reproducible dynamics and patterns, suggesting it could be possible to predict and drive these microbial communities to desired states.

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