Human milk contains a diverse community of bacteria. The growing appreciation of commensal microbes and increasing availability of high-throughput technology has set the stage for a theory-driven ...approach to the study of milk microbiota, and translation of this knowledge to improve maternal and child health. We recently profiled the milk microbiota of healthy Canadian mothers and applied theory-driven causal modeling, finding that mode of breast milk feeding (nursing directly at the breast vs. pumping and feeding breast milk from a bottle) was significantly associated with milk microbiota composition. This observation could reflect an increased exposure to pumps and/or a decreased exposure to the infant mouth. Either way, it provides evidence for the retrograde mechanism of milk inoculation. Here, we discuss the implications of this research and related controversies, and raise new questions about the origins and function of milk bacteria.
In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of ...synbiotics. The panel updated the definition of a synbiotic to "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host". The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.
Breastfeeding has many established health benefits, but its impact on asthma development is uncertain. Breastfeeding appears to have a positive and dose-dependent impact on respiratory health, ...particularly during early childhood and in high-risk populations; however, the strength and causality of these associations are unclear. It is challenging to compare results across studies due to methodological differences and biological variation. Resolving these inconsistencies will require well-designed, prospective studies that accurately capture asthma diagnoses and infant feeding exposures (including breastfeeding duration, exclusivity, and method of feeding), account for key confounders, evaluate dose effects, and consider effect modification and reverse causality. Mechanistic studies examining human milk bioactives and their impact on lung health and asthma development are beginning to emerge, and these will be important in establishing the causality and mechanistic basis of the observed associations between breastfeeding and asthma. In this review, we summarize current evidence on this topic, identify possible reasons for disagreement across studies, discuss potential mechanisms for a causal association, and provide recommendations for future research.
Reactive oxygen species (ROS) have been identified as signaling molecules in various pathways regulating both cell survival and cell death. Autophagy, a self-digestion process that degrades ...intracellular structures in response to stress, such as nutrient starvation, is also involved in both cell survival and cell death. Alterations in both ROS and autophagy regulation contribute to cancer initiation and progression, and both are targets for developing therapies to induce cell death selectively in cancer cells. Many stimuli that induce ROS generation also induce autophagy, including nutrient starvation, mitochondrial toxins, hypoxia, and oxidative stress. Some of these stimuli are under clinical investigation as cancer treatments, such as 2-methoxyestrodial and arsenic trioxide. Recently, it was demonstrated that ROS can induce autophagy through several distinct mechanisms involving Atg4, catalase, and the mitochondrial electron transport chain (mETC). This leads to both cell-survival and cell-death responses and could be selective toward cancer cells. In this review, we give an overview of the roles ROS and autophagy play in cell survival and cell death, and their importance to cancer. Furthermore, we describe how autophagy is mediated by ROS and the implications of this regulation to cancer treatments.
Pre-school children spend an average of two-hours daily using screens. We examined associations between screen-time on pre-school behavior using data from the Canadian Healthy Infant Longitudinal ...Development (CHILD) study.
CHILD participant parents completed the Child Behavior Checklist (CBCL) at five-years of age. Parents reported their child's total screen-time including gaming and mobile devices. Screen-time was categorized using the recommended threshold of two-hours/day for five-years or one-hour/day for three-years. Multiple linear regression examined associations between screen-time and externalizing behavior (e.g. inattention and aggression). Multiple logistic regression identified characteristics of children at risk for clinically significant externalizing problems (CBCL T-score≥65).
Screen-time was available for over 95% of children (2,322/2,427) with CBCL data. Mean screen-time was 1·4 hours/day (95%CI 1·4, 1·5) at five-years and 1·5 hours/day (95%CI: 1·5, 1·6) at three-years. Compared to children with less than 30-minutes/day screen-time, those watching more than two-hours/day (13·7%) had a 2·2-point increase in externalizing T-score (95%CI: 0·9, 3·5, p≤0·001); a five-fold increased odd for reporting clinically significant externalizing problems (95%CI: 1·0, 25·0, p = 0·05); and were 5·9 times more likely to report clinically significant inattention problems (95%CI: 1·6, 21·5, p = 0·01). Children with a DSM-5 ADHD T-score above the 65 clinical cut-off were considered to have significant ADHD type symptoms (n = 24). Children with more than 2-hours of screen-time/day had a 7·7-fold increased risk of meeting criteria for ADHD (95%CI: 1·6, 38·1, p = 0·01). There was no significant association between screen-time and aggressive behaviors (p>0.05).
Increased screen-time in pre-school is associated with worse inattention problems.
Breastmilk contains a complex community of bacteria that may help seed the infant gut microbiota. The composition and determinants of milk microbiota are poorly understood. Among 393 mother-infant ...dyads from the CHILD cohort, we found that milk microbiota at 3–4 months postpartum was dominated by inversely correlated Proteobacteria and Firmicutes, and exhibited discrete compositional patterns. Milk microbiota composition and diversity were associated with maternal factors (BMI, parity, and mode of delivery), breastfeeding practices, and other milk components in a sex-specific manner. Causal modeling identified mode of breastfeeding as a key determinant of milk microbiota composition. Specifically, providing pumped breastmilk was consistently associated with multiple microbiota parameters including enrichment of potential pathogens and depletion of bifidobacteria. Further, these data support the retrograde inoculation hypothesis, whereby the infant oral cavity impacts the milk microbiota. Collectively, these results identify features and determinants of human milk microbiota composition, with potential implications for infant health and development.
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•Milk microbiota variability is affected by maternal factors and other milk components•Some factors have phylum-specific effects•Some variations in milk microbiota are sex-specific•Feeding method (at the breast versus pumped) was strongly associated with milk microbiota
Moossavi et al. examine human milk microbiota in the CHILD birth cohort and use causal modeling to describe sex-specific associations with maternal, infant, and early-life factors. A strong association with feeding method (i.e., pumped versus directly at the breast) suggests some milk bacteria originate from the infant oral cavity.
Previous studies on the differences in gut microbiota between exclusively breastfed (EBF) and non-EBF infants have provided highly variable results. Here we perform a meta-analysis of seven ...microbiome studies (1825 stool samples from 684 infants) to compare the gut microbiota of non-EBF and EBF infants across populations. In the first 6 months of life, gut bacterial diversity, microbiota age, relative abundances of Bacteroidetes and Firmicutes, and predicted microbial pathways related to carbohydrate metabolism are consistently higher in non-EBF than in EBF infants, whereas relative abundances of pathways related to lipid metabolism, vitamin metabolism, and detoxification are lower. Variation in predicted microbial pathways associated with non-EBF infants is larger among infants born by Caesarian section than among those vaginally delivered. Longer duration of exclusive breastfeeding is associated with reduced diarrhea-related gut microbiota dysbiosis. Furthermore, differences in gut microbiota between EBF and non-EBF infants persist after 6 months of age. Our findings elucidate some mechanisms of short and long-term benefits of exclusive breastfeeding across different populations.
The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is ...increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding.
We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing.
We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia-Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity.
These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.
Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to ...determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects.
We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.
From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m
; 95% confidence interval CI -1.10 to 0.36;
9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06;
0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.
Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners.
PROSPERO-CRD42015019749.
Secretory immunoglobulin A (SIgA) in human milk plays a central role in complex maternal-infant interactions that influence long-term health outcomes. Governed by genetics and maternal microbial ...exposure, human milk SIgA shapes both the microbiota and immune system of infants. Historically, SIgA-microbe interactions have been challenging to unravel due to their dynamic and personalized nature, particularly during early life. Recent advances have helped to clarify how SIgA acts beyond simple pathogen clearance to help guide and constrain a healthy microbiota, promote tolerance, and influence immune system development. In this review, we highlight these new findings in the context of the critical early-life window and propose outstanding areas of study that will be key to harnessing the benefits of SIgA to support healthy immune development during infancy.
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