Impact of maternal obesity and prebiotic supplementation on select maternal milk miRNA levels and correlation to offspring outcomes

2021 ◽  
pp. 1-22
Author(s):  
Dana E. Lowry ◽  
Heather A. Paul ◽  
Raylene A. Reimer

Abstract Breastmilk composition varies with maternal factors including diet, and confers health benefits to the neonate; however, the mechanisms mediating this protection remain incompletely understood. Our aim was to investigate the effects of supplementing a maternal high fat/sucrose (HFS) diet with prebiotic oligofructose (OFS) on milk composition in rats and associations with offspring body composition and gut microbiota. Obese Sprague-Dawley dams consumed a control, HFS, HFS+OFS (10% wt/wt) or HFS diet weight-matched to the HFS+OFS group (HFS-WM) during pregnancy and lactation. Pups were weaned onto a HFS diet on day 21. Milk was collected at weaning and analysed for protein, leptin, and microRNA (miRNA) levels. Milk produced by HFS dams contained less protein than milk from lean controls which was normalized by OFS. Six miRNAs (miR-222, miR-203a, miR-200a, miR-26a, miR-27a, and miR-103) were differentially expressed in milk according to maternal diet. Milk leptin content was positively correlated with maternal body fat and fecal Enterobacteriaceae in male offspring at 24 weeks of age. Milk protein content was inversely associated with maternal body fat and body weight. miR-200a was positively associated with maternal body fat and Enterobacteriaceae in female offspring at 24 weeks of age. Correlations between milk protein and multiple milk miRNAs and offspring body composition and gut microbiota differed by sex. Overall, our results suggest that obesogenic diets and prebiotic supplementation can alter the protein and miRNA levels in breastmilk in rats and these milk components may explain, in part, the influence of these maternal diets on offspring body composition.

2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Camilla Kaae Hojgaard ◽  
Thomas Sønderby Bruun ◽  
Peter Kappel Theil

Abstract The main objective of this study was to evaluate the impact of milk intake, milk composition, and nutrient intake on piglet growth in lactation and body composition at weaning. To evaluate the body composition of piglets, data from one experiment (44 Danish Landrace × Yorkshire × Duroc piglets) were used to develop prediction equations for body pools of fat, protein, ash, and water based on live weight and deuterium dilution space (exp. 1). Furthermore, a total of 294 piglets (Danish Landrace × Yorkshire × Duroc) from 21 sows of second parity were included in a second experiment (exp. 2). In exp. 2, piglet live weight was recorded on days 3, 10, 17, and 25 of lactation. On the same days, the milk intake and body composition were measured, using the deuterium oxide (D2O) dilution technique. Piglet weight gain was highly positively correlated with the intake of milk and the intake of milk constituents each week and on an overall basis having r values ranging from 0.65 to 0.93 (P < 0.001). When evaluating regressions for piglet growth, the milk intake in combination with the milk protein concentration explained 85% and 87% of the total variation in piglet gain in the second and third week of lactation, respectively, whereas milk intake was the only predictor of piglet gain in the first week of lactation explaining 81% of the variation. Fat, protein, and energy retention rates were all highly positively correlated with the daily intake of milk and intake of milk nutrients with r values ranging from 0.76 to 0.94 (P < 0.001). Piglet gain and retention rates were rather weakly correlated with the milk composition with r values ranging from 0.01 to 0.50 (being either negative or positive). Curvilinear response curves were fitted for live weight gain and body fat content at weaning in response to milk protein concentration, showing that live weight gain was slightly greater and body fat content was slightly lower at 4.9% milk protein, but it should be emphasized that the quadratic effects did not reach significance. Body fat content at weaning was positively related with the intake of milk (R2 = 0.44, P < 0.001) and milk fat (R2 = 0.46, P < 0.01). In conclusion, milk intake had a major impact on the piglet growth rate, and milk fat intake greatly influenced the body fat percentage at weaning, whereas milk composition per se only played a minor role for these traits.


2015 ◽  
Vol 31 (10) ◽  
pp. 2073-2092 ◽  
Author(s):  
Helen Castillo-Laura ◽  
Iná S. Santos ◽  
Lenice C. M. Quadros ◽  
Alicia Matijasevich

Abstract This study reviewed the evidence that assessed the association between maternal pre-pregnancy body mass index (BMI) and/or gestational weight gain and offspring body composition in childhood. A systematic review was conducted. Cohort studies, case-control studies and randomized controlled trials measuring offspring body composition by indirect methods were included. Meta-analyses of the effect of pre-pregnancy BMI on offspring fat-free mass, body fat percent, and fat mass were conducted through random-effects models. 20 studies were included, most of which reported a positive association of pre-pregnancy BMI with offspring body fat. Standardized mean differences in body fat percent, fat mass and fat-free mass between infants of women with normal pre-pregnancy BMI and those of overweight/obese women were 0.31 percent points (95%CI: 0.19; 0.42), 0.38kg (95%CI: 0.26; 0.50), and 0.18kg (95%CI: -0.07; 0.42), respectively. Evidence so far suggests that pre-pregnancy maternal overweight is associated with higher offspring adiposity.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
E. Chang ◽  
H. Hafner ◽  
M. Varghese ◽  
C. Griffin ◽  
J. Clemente ◽  
...  

Abstract With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c−) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3417
Author(s):  
Jiaqi Cui ◽  
Lin Song ◽  
Rui Wang ◽  
Shuyuan Hu ◽  
Zhao Yang ◽  
...  

Maternal high-fat (HF) diet is associated with offspring metabolic disorder. This study intended to determine whether maternal metformin (MT) administration during gestation and lactation prevents the effect of maternal HF diet on offspring’s skeletal muscle (SM) development and metabolism. Pregnant Sprague-Dawley rats were divided into four groups according to maternal diet {CHOW (11.8% fat) or HF (60% fat)} and MT administration {control (CT) or MT (300 mg/kg/day)} during gestation and lactation: CH-CT, CH-MT, HF-CT, HF-MT. All offspring were weaned on CHOW diet. SM was collected at weaning and 18 weeks in offspring. Maternal metformin reduced plasma insulin, leptin, triglyceride and cholesterol levels in male and female offspring. Maternal metformin increased MyoD expression but decreased Ppargc1a, Drp1 and Mfn2 expression in SM of adult male and female offspring. Decreased MRF4 expression in SM, muscle dysfunction and mitochondrial vacuolization were observed in weaned HF-CT males, while maternal metformin normalized them. Maternal metformin increased AMPK phosphorylation and decreased 4E-BP1 phosphorylation in SM of male and female offspring. Our data demonstrate that maternal metformin during gestation and lactation can potentially overcome the negative effects of perinatal exposure to HF diet in offspring, by altering their myogenesis, mitochondrial biogenesis and dynamics through AMPK/mTOR pathways in SM.


2021 ◽  
Vol 8 ◽  
Author(s):  
Gaëlle Boudry ◽  
Elise Charton ◽  
Isabell Le Huerou-Luron ◽  
Stéphanie Ferret-Bernard ◽  
Sophie Le Gall ◽  
...  

The assembly of the newborn's gut microbiota during the first months of life is an orchestrated process resulting in specialized microbial ecosystems in the different gut compartments. This process is highly dependent upon environmental factors, and many evidences suggest that early bacterial gut colonization has long-term consequences on host digestive and immune homeostasis but also metabolism and behavior. The early life period is therefore a “window of opportunity” to program health through microbiota modulation. However, the implementation of this promising strategy requires an in-depth understanding of the mechanisms governing gut microbiota assembly. Breastfeeding has been associated with a healthy microbiota in infants. Human milk is a complex food matrix, with numerous components that potentially influence the infant microbiota composition, either by enhancing specific bacteria growth or by limiting the growth of others. The objective of this review is to describe human milk composition and to discuss the established or purported roles of human milk components upon gut microbiota establishment. Finally, the impact of maternal diet on human milk composition is reviewed to assess how maternal diet could be a simple and efficient approach to shape the infant gut microbiota.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Nikki Renall ◽  
Benedikt Merz ◽  
Blair Lawley ◽  
Gerald W. Tannock ◽  
Marine Corbin ◽  
...  

AbstractDiet is considered one of the key drivers of the world-wide obesity epidemic, and the gut microbiota may play a role in this multifaceted disease due to their mutualistic relationship. This study investigated relationships between habitual dietary intake of New Zealand European and Pacific women and their gut microbiota and body fat content. Pacific (44%) and NZ European (NZE; 56%) women (n = 287) aged 18–45 years were recruited based on body mass index (normal versus obese) and stratified as low (< 35%) or high (≥ 35%) body fat percentage (BF%). Dietary intake was assessed with a 5-day estimated food record and a semi-quantitative food frequency questionnaire, which were used to calculate habitual dietary intake using the National Cancer Institute (NCI) method. BF% was assessed by dual-energy x-ray absorptiometry (DXA). Fasting blood samples were analysed for markers of insulin sensitivity. The DNA from faecal samples was analysed following shotgun sequencing. There were no significant differences in BF% between Pacific and NZE women (p = 0.498). Significant differences in homeostasis model assessment of insulin resistance (HOMA-IR) index were observed between Pacific (3.4 [2.3, 5.9]) and NZE (2.1 [1.5, 3.1], p ≤ 0.001) women, and between; low-BF% (1.9 [1.3, 2.7]) and high-BF% (3.4 [2.5, 5.9], p ≤ 0.001) groups. The highest (27.6g/d [24.9, 30.6]) compared to the lowest tertile (16g/d [13.3, 17.6]) of habitual total dietary fibre (DF) intake was associated with a significantly lower HOMA-IR (2.1 [1.3, 3.1] versus 3.3 [2.1, 5.3] p ≤ 0.001) respectively. Higher DF intake was also associated with significantly lower BF% (β -0.35, p ≤ 0.001), and this relationship became stronger when considering the intake of other macronutrients (β -0.47, p ≤ 0.001). Alpha diversity; observed taxonomic units (OTU's; rs = -0.15, p = 0.011), Pielou's evenness (rs = -0.20, p = 0.001), and Shannon index (rs = -0.22, p ≤ 0.001), were all negatively correlated with BF%. In contrast BF% was positively correlated with the Firmicutes:Bacteroidetes ratio (rs = 0.26, p ≤ 0.001). HOMA-IR index was significantly higher in Pacific and women in the higher BF% group, indicating an increased metabolic disease risk. Higher habitual DF intake was associated with lower BF% and HOMA-IR, suggesting a potential metabolically protective effect. The positive effects of higher DF intake may be associated with microbiota diversity, as higher BF% was associated with reduced alpha diversity and an increased Firmicutes:Bacteroidetes ratio. Further analysis will explore which foods contributed to the higher DF intake, and associations with body composition, microbiota and biomarkers of metabolic health.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1076-1076
Author(s):  
Kartik Shankar ◽  
Ying Zhong ◽  
Ping Kang ◽  
Keshari Thakali ◽  
Brian Piccolo ◽  
...  

Abstract Objectives Maternal diet and body composition are important determinants of offspring obesity risk, which may be mediated via changes in placental function. Here we examined the influence of maternal obesity and diet quality on the placental metabolome using untargeted metabolomics. Methods Placenta were collected from a longitudinal observational study in which maternal anthropometrics, body composition, dietary intake (3 d food records) and other variables were collected every trimester. Untargeted metabolomics of villous placental tissues from normal weight (NW, n = 72), overweight (OW, n = 49), and obese women (OB, n = 29) based on BMI at first trimester, were performed using GC-TOF MS. Differential metabolite features were identified using univariate comparisons (ANOVA/Mann Whitney U tests) and partial least squares discriminant analysis (PLS-DA). Results Principal component analysis did not reveal global shifts in the metabolome with maternal OW or OB. While no differences survived multiple testing corrections (P &lt; 0.05), univariate analysis indicated that OW/OB subjects showed increased abundance of 2-deoxypentitol and decreases in maltotriose and 3-hydroxybutanoic acid relative to NW subjects (un-adjusted P &lt; 0.05). Alterations in a number of non-annotated metabolites were also observed between NW, OW and OB groups. PLS-DA models predicted maternal OB status with ∼80% accuracy in held out samples. Predictive metabolites were enriched for aspartate metabolism and ammonia recycling. The global placental metabolome was significantly associated with maternal diet quality (Healthy Eating Index 2010 score averaged over pregnancy; PC1 ANOVA P &lt; 0.01) which was characterized by differences in 138 metabolites (ANOVA, un-adjusted P &lt; 0.05). Abundance of heptadecanoic acid and glycerol-3-galactoside increased with HEI score. Conclusions Maternal obesity appears to alter amino acid or protein metabolism, whereas diet quality seemed to affect metabolism of fatty acids and BCAA. These results suggest a potential shift in nutrient delivery to the offspring. Funding Sources Supported by USDA-ARS Project 6026–51,000-010–05S.


2019 ◽  
Vol 110 (1) ◽  
pp. 111-120 ◽  
Author(s):  
Elvira Isganaitis ◽  
Sarah Venditti ◽  
Tucker J Matthews ◽  
Carles Lerin ◽  
Ellen W Demerath ◽  
...  

ABSTRACTBackgroundMaternal obesity is a risk factor for childhood obesity; this is a major public health concern given that ∼40% of pregnant women are either overweight or obese. Whether differences in milk composition in lean compared with obese women contribute to childhood obesity is unclear.ObjectivesWe aimed to analyze relationships between maternal obesity and human milk metabolites, infant body composition, and postnatal weight gain.MethodsThis was a prospective study in which mothers intending to breastfeed exclusively, and their newborn infants, were enrolled at delivery (n = 35 mother–infant pairs). We excluded mothers with diabetes, other medical conditions, or pregnancy complications. Participants were grouped by maternal prepregnancy BMI <25 (lean) or ≥25 kg/m2 (overweight/obese). We analyzed infant body composition by dual-energy X-ray absorptiometry and used untargeted liquid chromatography–gas chromatography–mass spectrometry to measure the milk content of 275 metabolites at 1 and 6 mo postpartum.ResultsAt 1 mo postpartum, 10 metabolites differed between overweight/obese and lean groups with nominal P < 0.05, but none was altered with a false discovery rate <0.25. Many differentially abundant metabolites belonged to the same chemical class; e.g., 4/10 metabolites were nucleotide derivatives, and 3/10 were human milk oligosaccharides. Milk adenine correlated positively with both continuously distributed maternal BMI and with infant adiposity and fat accrual. Analysis of milk composition at 6 mo postpartum revealed 20 differentially abundant metabolites (P < 0.05) in overweight/obese compared with lean women, including 6 metabolites with a false discovery rate of <0.25. At both 1 and 6 mo, human milk abundance of 1,5-anhydroglucitol, which has not previously been described in milk, was positively associated with maternal BMI.ConclusionsMaternal obesity is associated with changes in the human milk metabolome. While only a subset of metabolites correlated with both maternal and infant weight, these point to potential milk-dependent mechanisms for mother–child transmission of obesity. This trial was registered at www.clinicaltrials.gov as NCT02535637.


1986 ◽  
Vol 106 (2) ◽  
pp. 351-367 ◽  
Author(s):  
K. G. Geenty ◽  
A. R. Sykes

SUMMARYIn two experiments Dorset ewes were offered low (LP) or high (HP) herbage allowances during pregnancy to induce light (45–50 kg) or heavy (60–65 kg) post-partum body weights, respectively. During the first 6 weeks of lactation three herbage allowances were offered in a 2 x 3 factorial design: 2 (LL), 5 (ML) and 8 (HL) kg D.M./ewe per day. In the first experiment (Expt 1) lambs were removed and ewes machine-milked twice daily. In the second (Expt 2) they were suckled by two lambs; a further group on the ML allowance (MML) was machine-milked. Ewes were slaughtered during early pregnancy, post-partum and after 6 weeks of lactation for determination of body composition. Diet selection and faecal output were measured during lactation.Absolute level of milk production was not affected by pregnancy nutrition when rearing two lambs and producing 2·0–2–7 kg milk/day or at 30–50% lower milk production when machine-milked. When expressed as g/kg W0·75 per day milk production was 14% greater in LP than in HP ewes. Milk fat content was higher at low allowances and was positively related to rate of body fat mobilization. Milk protein concentration was lower in suckled than in machine-milked ewes (40 ν. 47 g/kg) though total milk protein secreted (g/day) was similar. Milk production was 11–13% greater in ewes bearing twin lambs compared with those bearing singles whether machine-milked or suckling two lambs.Mean intakes during the 6 weeks of lactation were 58, 69 and 73 g DOM/kg W0·75 per day, respectively, for LL, ML and HL groups when machine-milked and 51, 75 and 83 g DOM/kg W0·75/day, respectively, for ewes rearing two lambs. LP ewes consumed 13% (Expt 1) and 17% (Expt 2) more feed (g DOM/kg W0·75/day) during lactation than HP ewes, though in absolute terms (kg D.M./day) there was no difference. The difference in OMD between herbage offered (OMD = 0·77) and consumed ranged from 0 when sheep grazed to a residual herbage mass of 910 kg D.M./ha to + 0·04 when residual herbage was < 1600 kg D.M./ha.All sheep, irrespective of pregnancy nutrition, milk production or herbage allowance, were in negative body energy balance during lactation. Mobilization of body fat during lactation averaged 40 g/day for machine-milked and 150 g/day for suckled ewes and was greatest in HPLL groups (92 and 219 g/day in Expts 1 and 2, respectively). In LP groups body protein loss during pregnancy was 10 and 16 g/day in Expts 1 and 2, respectively, and little further net protein loss occurred during lactation. The maximum rate of body protein loss in HP groups was 30 g/day in ewes rearing two lambs on the low herbage allowance.Maintenance energy requirement during lactation averaged 0·238 MJ ME/kg W per day for ewes in both experiments; efficiency of use (Kl, (t)) of total energy available above maintenance for milk synthesis (namely, milk energy/ME intake - estimated energy requirement for maintenance (MEm + mobilized tissue energy) decreased from 0·84 to 0·51 with increasing rate of tissue energy mobilization. There was a positive relationship between Kl(t) and the proportion of mobilized energy derived from body protein.The overall energy requirement of lactating ewes well-fed during pregnancy was similar to previous estimates (Agricultural Research Council, 1980) but that of sheep undernourished during pregnancy was 10–20% greater.


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