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"Donovan, Sharon M."
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Diet Can Impact Microbiota Composition in Children With Autism Spectrum Disorder
2018
Diet is one of the most influential environmental factors in determining the composition of the gastrointestinal microbiota. Microbial dysbiosis in children with Autism Spectrum Disorder (ASD) and the impact of some bacterial taxa on symptoms of ASD has been recognized. Children with ASD are often described as picky eaters with low intake of fiber-rich foods, including fruits and vegetables. However, the impact of diet on the microbiota composition in children with ASD is largely unknown. Herein, fecal samples, 3 day food diaries and the Youth and Adolescence Food Frequency questionnaire (YAQ) were collected from children with ASD (ASD;
= 26) and unaffected controls (CONT;
= 32). Children's ASD symptoms were determined using the Pervasive Developmental Disorder Behavior Inventory Screening Version (PDDBI-SV). Differences in the microbiota composition at the phyla, order, family, and genus level between ASD and CONT were observed. Microbiota composition of children with ASD was investigated in relation to feeding behavior, nutrient and food group intake as well as dietary patterns derived from the YAQ. In children with ASD, two distinct dietary patterns (DP) were associated with unique microbial profiles. DP1, characterized by higher intakes of vegetables, legumes, nuts and seeds, fruit, refined carbohydrates, and starchy vegetables, but lower intakes of sweets, was associated with lower abundance of
, and
. DP2, characterized by low intakes of vegetables, legumes, nuts and seeds and starchy vegetables, was associated with higher
and
and lower
, as well as higher levels of propionate, isobutyrate, valerate, and isovalerate. Peptostreptococcaceae and
predicted social deficit scores in children with ASD as measured by the PDDBI-SV. Diet-associated microbial profiles were related to GI symptoms, but no significant interaction between nutrition and microbiota in predicting social deficit scores were observed. In conclusion, dietary patterns associated with fecal microbiota composition and VFA concentrations in children with ASD were identified. Future studies using a larger sample size and measuring other behaviors associated with ASD are needed to investigate whether dietary intake may be a modifiable moderator of ASD symptoms.
Journal Article
Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity
2016
The immune system of the infant is functionally immature and naïve. Human milk contains bioactive proteins, lipids, and carbohydrates that protect the newborn and stimulate innate and adaptive immune development. This review will focus on the role human milk oligosaccharides (HMO) play in neonatal gastrointestinal and systemic immune development and function. For the past decade, intense research has been directed at defining the complexity of oligosaccharides in the milk of many species and is beginning to delineate their diverse functions. These studies have shown that human milk contains a higher concentration as well as a greater structural diversity and degree of fucosylation than the milk oligosaccharides in other species, particularly bovine milk from which many infant formulae are produced. The commercial availability of large quantities of certain HMO has furthered our understanding of the functions of specific HMO, which include protecting the infant from pathogenic infections, facilitating the establishment of the gut microbiota, promoting intestinal development, and stimulating immune maturation. Many of these actions are exerted through carbohydrate-carbohydrate interactions with pathogens or host cells. Two HMOs, 2'-fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT), have recently been added to infant formula. Although this is a first step in narrowing the compositional gap between human milk and infant formula, it is unclear whether 1 or 2 HMO will recapitulate the complexity of actions exerted by the complex mixture of HMO ingested by breastfed infants. Thus, as more HMO become commercially available, either isolated from bovine milk or chemically or microbially synthesized, it is anticipated that more oligosaccharides will be added to infant formula either alone or in combination with other prebiotics.
Journal Article
SARS‐CoV‐2 and human milk: What is the evidence?
by
Pace, Ryan M.
,
Meehan, Courtney L.
,
Raiten, Daniel J.
in
Adult
,
Antibodies, Viral - analysis
,
Babies
2020
The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed.
Journal Article
Nopal (Opuntia ficus indica) protects from metabolic endotoxemia by modifying gut microbiota in obese rats fed high fat/sucrose diet
2017
Current efforts are directed to reducing the gut dysbiosis and inflammation produced by obesity. The purpose of this study was to investigate whether consuming nopal, a vegetable rich in dietary fibre, vitamin C, and polyphenols can reduce the metabolic consequences of obesity by modifying the gut microbiota and preventing metabolic endotoxemia in rats fed a high fat and sucrose diet. With this aim, rats were fed a high fat diet with 5% sucrose in the drinking water (HFS) for 7 months and then were fed for 1 month with HFS + 5% nopal (HFS + N). The composition of gut microbiota was assessed by sequencing the 16S rRNA gene. Nopal modified gut microbiota and increased intestinal occludin-1 in the HFS + N group. This was associated with a decrease in metabolic endotoxemia, glucose insulinotropic peptide, glucose intolerance, lipogenesis, and metabolic inflexibility. These changes were accompanied by reduced hepatic steatosis and oxidative stress in adipose tissue and brain, and improved cognitive function, associated with an increase in
B
.
fragilis
. This study supports the use of nopal as a functional food and prebiotic for its ability to modify gut microbiota and to reduce metabolic endotoxemia and other obesity-related biochemical abnormalities.
Journal Article
Dietary supplementation of 3′-sialyllactose or 6′-sialyllactose elicits minimal influence on cognitive and brain development in growing pigs
by
Sutkus, Loretta T.
,
Dilger, Ryan N.
,
Golden, Rebecca K.
in
3′-sialyllactose
,
6′-sialyllactose
,
Baby foods
2024
Sialylated human milk oligosaccharides (HMO), such as 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL), are abundant throughout lactation and at much higher concentrations than are present in bovine milk or infant formulas. Previous studies have suggested that sialylated HMO may have neurocognitive benefits in early life. Recent research has focused on infant formula supplementation with key nutrients and bioactives to narrow the developmental gap between formula-fed and breastfed infants. Herein, we investigated the impact of supplemental 3′-SL or 6′-SL on cognitive and brain development at two time-points [postnatal days (PND) 33 and 61]. Two-day-old piglets (
N
= 75) were randomly assigned to commercial milk replacer
ad libitum
without or with 3′-SL or 6′-SL (added in a powdered form at a rate of 0.2673% on an as-is weight basis). Cognitive development was assessed via novel object recognition and results were not significant at both time-points (
p
> 0.05). Magnetic resonance imaging was used to assess structural brain development. Results varied between scan type, diet, and time-point. A main effect of diet was observed for absolute volume of white matter and 9 other regions of interest (ROI), as well as for relative volume of the pons on PND 30 (
p
< 0.05). Similar effects were observed on PND 58. Diffusion tensor imaging indicated minimal differences on PND 30 (
p
> 0.05). However, several dietary differences across the diffusion outcomes were observed on PND 58 (
p
< 0.05) indicating dietary impacts on brain microstructure. Minimal dietary differences were observed from myelin water fraction imaging at either time-point. Overall, sialyllactose supplementation had no effects on learning and memory as assessed by novel object recognition, but may influence temporally-dependent aspects of brain development.
Journal Article
Experimentally induced colitis impacts myelin development and home-cage behavior in young pigs regardless of supplementation with oral gamma-cyclodextrin-encapsulated tributyrin
by
Sutkus, Loretta T.
,
Dilger, Ryan N.
,
Li, Zimu
in
brain development
,
colitis
,
dextran sodium sulfate
2025
Colitis, a chronic intestinal disorder that causes inflammation of the colonic mucosa, has been linked with structural brain abnormalities. To combat intestinal inflammation, researchers have investigated how nutritional supplementation, such as butyric acid, may ameliorate untoward effects. By encapsulating and using conjugates of butyrate, such as butyrate glycerides (i.e., tributyrin), slower release to the lower portions of the gastrointestinal tract can be achieved. Additionally, butyrate supplementation has been linked with supporting brain function and regulating integrity.
In the present study, a total of 24 intact male pigs were artificially reared and randomly assigned to 1 of 3 treatment conditions: (1) a control milk replacer (CON), (2) control plus oral dextran sodium sulfate (DSS) to induce colitis, or (3) control supplemented with 9.0 mM of gamma-cyclodextrin encapsulated tributyrin (TBCD) plus oral DSS (TBCD+DSS). Pigs were orally administered DSS treatments daily from postnatal day (PND) 14-18. Continuous video recording began on PND 3 and ceased on PND 27 or 28, with videos processed and analyzed for home-cage tracking behavior. On PND 26 or 27, pigs underwent neuroimaging procedures to assess overall brain anatomy (MPRAGE), microstructure (DTI), and myelin (MWF).
Home-cage spatial preference was not altered prior to DSS dosing or during the overall study period. However, TBCD+DSS pigs spent less (p < 0.05) time within quadrant 4 when compared with CON pigs. Across almost all 29 brain regions assessed, absolute volumes were observed to be smaller in the TBCD+DSS group compared with CON and DSS groups. However, once individual volumes were assessed relative to the whole brain, most treatment effects dissipated other than for gray matter volume (p = 0.041). Diffusivity was found to be altered in several regions across treatment groups, thereby indicating differences in fiber organization. In areas like the hippocampus and thalamus, when fractional anisotropy (FA) values were highest for a given treatment, in the other diffusion metrics (mean, radial, axial diffusivity) values were lowest for that same treatment, indicating more organized cellular structure. Several other diffusion trends and differences were observed across various regions. Lastly, myelin water fraction (MWF) values were lowest in DSS-treated groups compared with CON (p < 0.05) for the whole brain and left/right cortices.
Overall, fiber organization and myelination were observed to be altered by experimentally induced colitis and contrary to expectations, tributyrin supplementation did not ameliorate these effects. Future work is warranted to investigate other protective nutritional mechanisms for colitis.
Journal Article
Longitudinal changes in home food availability and concurrent associations with food and nutrient intake among children at 24–48 months
by
McMath, Arden L
,
Donovan, Sharon M
,
Barton, Jennifer M
in
Assessment and Methodology
,
Availability
,
Babies
2024
To describe changes in home food availability during early childhood, including modified, developmentally sensitive obesogenic scores, and to determine whether home food availability is associated with food and nutrient intakes of children concurrently, over time.
Data were drawn from the STRONG Kids 2 longitudinal, birth cohort to achieve the study objectives. Home food availability was assessed with the Home Food Inventory (HFI) and included 15 food groups (e.g., fruit, vegetables) and 3 obesogenic scores (1 original and 2 modified). Food and nutrient intakes were measured using the Block Food Frequency Questionnaire and included 27 food groups and 18 nutrients (e.g., vitamins A and C, protein). HFI and FFQ were completed by trained researchers or mothers, respectively, at 24, 36, and 48 months. Repeated measures ANOVAs and Spearman correlations were used to achieve the study objectives.
Central Illinois, United States.
468 children at 24, 36 and 48 months of age.
Availability of less nutritious foods and obesogenic foods and beverages increased as children aged, and availability of both nutritious and less nutritious foods were associated with child food and nutrient intake. The 3 obesogenic scores demonstrated similar, positive associations with the intake of energy, saturated fat, added sugars, and kilocalories from sweets.
These findings offer novel insight into changes in home food availability and associations with food and nutrient intake during early childhood. Additional attention is needed examining antecedents (e.g., built environments, purchasing behaviors) and consequences (e.g., child diet quality, weight) of home food availability.
Journal Article
Human and Bovine Milk Oligosaccharides Elicit Improved Recognition Memory Concurrent With Alterations in Regional Brain Volumes and Hippocampal mRNA Expression
2020
Human milk contains a unique profile of oligosaccharides (OS) and preliminary evidence suggests they impact brain development. The objective of this study was to assess the impact of bovine and/or human milk oligosaccharides (2’fucosyllactose [2’FL] and Lacto-N-neotetraose [LNnT]) on cognition, brain development, and hippocampal gene expression. Beginning on postnatal day (PND) 2, male pigs received one of four milk replacers containing bovine milk oligosaccharides (BMOS), human milk OS (HMO), both (BMOS + HMO), or neither (CON). Pigs were tested on the novel object recognition task using delays of 1- or 48-h at PND 22. At PND 32-33, magnetic resonance imaging (MRI) procedures were used to assess structural brain development and hippocampal tissue was collected for analysis of mRNA expression. Pigs consuming only HMO exhibited recognition memory after a 1-h delay and those consuming BMOS + HMO exhibited recognition memory after a 48-h delay. Both absolute and relative volumes of cortical and subcortical brain regions were altered by diet. Hippocampal mRNA expression of GABRB2, SLC1A7, CHRM3, and GLRA4 were most strongly affected by diet. HMO and BMOS had distinct effects on brain structure and cognitive performance. These data suggest different mechanisms underlie their influence on brain development.
Journal Article
Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life: a randomized controlled trial
by
West, Christina E
,
Peerson, Janet M
,
Donovan, Sharon M
in
631/250/1619
,
692/308/2779/777
,
692/700/1720/3187
2017
Background
Human milk is rich in osteopontin (OPN), which has immunomodulatory functions.
Methods
In a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing ~50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group.
Results
The F130 group had increased T-cell proportions compared with the SF (
P
=0.036, average effect size 0.51) and F65 groups (
P
=0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (
P
=0.001, average effect size 0.59) and F130 (
P
=0.006, average effect size 0.50) groups, but were comparable among the formula groups.
Conclusion
OPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at ~50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.
Journal Article
Correction: Experimentally induced colitis impacts myelin development and home-cage behavior in young pigs regardless of supplementation with oral gamma-cyclodextrin-encapsulated tributyrin
by
Sutkus, Loretta T.
,
Dilger, Ryan N.
,
Li, Zimu
in
brain development
,
colitis
,
dextran sodium sulfate
2025
[This corrects the article DOI: 10.3389/fnins.2025.1484497.].
Journal Article