A Scoping Review of the Relationship Between Maternal BMI and Offspring Incidence of Respiratory Infection: Where Do We Go From Here?

Introduction: Pregnancy complications, including high maternal BMI, are associated with altered early development and child health outcomes. A growing body of work links the prenatal environment, specifically maternal BMI, with respiratory infections in offspring. In this rapid review, the authors review the literature supporting the hypothesis that high maternal BMI during pregnancy is associated with childhood respiratory infection incidence. Methods: The authors employed systematic search criteria in known databases-EMBASE, EMCARE, MEDLINE, CINAHL, and PsychINFO-searching from inception to January 2023. Included were primary research studies that involved (1) human pregnancy, (2) pregravid or gestational overweight or obesity, and (3) childhood respiratory infection with or without hospitalization. Results: Only 7 population-based cohort studies met the criteria, investigating maternal BMI as an exposure and childhood respiratory infection as an outcome (age 6 months to 18 years). Therefore, the authors conducted a qualitative analysis, and outcomes were reported. The authors found that >85% of the albeit few published studies support the hypothesis that maternal BMI may have independent and profound consequences on respiratory infection risk across childhood. Discussion: This area of research needs large-scale, well-controlled studies to better understand the relationship between maternal BMI and childhood respiratory infection. Possible resources such as cohort catalogs and combined databases are discussed. These findings add to the growing evidence that early environmental factors influence lifelong respiratory health. By incorporating a life course approach to infectious disease risk, policy makers can put this research to work and target health vulnerabilities before they arise.

Maternal high-fat diet during pregnancy and lactation affects factors that regulate cell proliferation and apoptosis in the testis of adult progeny.

Context A maternal high-fat diet is thought to pose a risk to spermatogenesis in the progeny. Aims We tested whether a maternal high-fat diet would affect Sertoli cell expression of transcription factors (insulin-like growth factor I (IGF-I); glial-cell line-derived neurotrophic factor (GDNF); Ets variant 5 (ETV5)) and cell proliferation and apoptotic proteins, in the testis of adult offspring. Methods Pregnant rats were fed ad libitum with a standard diet (Control) or a high-fat diet (HFat) throughout pregnancy and lactation. After weaning, male pups were fed the standard diet until postnatal day 160. Males were monitored daily from postnatal day 34 to determine onset of puberty. On postnatal day 160, their testes were processed for morphometry and immunohistochemistry. Key results The HFat diet increased seminiferous-tubule diameter (P P P P P P P P Conclusions A maternal high-fat diet alters the balance between spermatogonia proliferation and spermatid apoptosis. Implications A maternal high-fat diet seems to 'program' adult male fertility.

Parity modulates impact of BMI and gestational weight gain on gut microbiota in human pregnancy.

Dysregulation of maternal adaptations to pregnancy due to high pre-pregnancy BMI (pBMI) or excess gestational weight gain (GWG) is associated with worsened health outcomes for mothers and children. Whether the gut microbiome contributes to these adaptations is unclear. We longitudinally investigated the impact of pBMI and GWG on the pregnant gut microbiome. We show that the gut microbiota of participants with higher pBMI changed less over the course of pregnancy in primiparous but not multiparous participants. This suggests that previous pregnancies may have persistent impacts on maternal adaptations to pregnancy. This ecological memory appears to be passed on to the next generation, as parity modulated the impact of maternal GWG on the infant gut microbiome. This work supports a role of the gut microbiome in maternal adaptations to pregnancy and highlights the need for longitudinal sampling and accounting for parity as key considerations for studies of the microbiome in pregnancy and infants. Understanding how these factors contribute to and shape maternal health is essential for the development of interventions impacting the microbiome, including pre/probiotics.

Intestinal permeability and peripheral immune cell composition are altered by pregnancy and adiposity at mid- and late-gestation in the mouse.

It is clear that the gastrointestinal tract influences metabolism and immune function. Most studies to date have used male test subjects, with a focus on effects of obesity and dietary challenges. Despite significant physiological maternal adaptations that occur across gestation, relatively few studies have examined pregnancy-related gut function. Moreover, it remains unknown how pregnancy and diet can interact to alter intestinal barrier function. In this study, we investigated the impacts of pregnancy and adiposity on maternal intestinal epithelium morphology, in vivo intestinal permeability, and peripheral blood immunophenotype, using control (CTL) and high-fat (HF) fed non-pregnant female mice and pregnant mice at mid- (embryonic day (E)14.5) and late (E18.5) gestation. We found that small intestine length increased between non-pregnant mice and dams at late-gestation, but ileum villus length, and ileum and colon crypt depths and goblet cell numbers remained similar. Compared to CTL-fed mice, HF-fed mice had reduced small intestine length, ileum crypt depth and villus length. Goblet cell numbers were only consistently reduced in HF-fed non-pregnant mice. Pregnancy increased in vivo gut permeability, with a greater effect at mid- versus late-gestation. Non-pregnant HF-fed mice had greater gut permeability, and permeability was also increased in HF-fed pregnant dams at mid but not late-gestation. The impaired maternal gut barrier in HF-fed dams at mid-gestation coincided with changes in maternal blood and bone marrow immune cell composition, including an expansion of circulating inflammatory Ly6Chigh monocytes. In summary, pregnancy has temporal effects on maternal intestinal structure and barrier function, and on peripheral immunophenotype, which are further modified by HF diet-induced maternal adiposity. Maternal adaptations in pregnancy are thus vulnerable to excess maternal adiposity, which may both affect maternal and child health.

Diet-induced obesity alters intestinal monocyte-derived and tissue-resident macrophages and increases intestinal permeability in female mice independent of tumor necrosis factor.

Macrophages are essential for homeostatic maintenance of the anti-inflammatory and tolerogenic intestinal environment, yet monocyte-derived macrophages can promote local inflammation. Proinflammatory macrophage accumulation within the intestines may contribute to the development of systemic chronic inflammation and immunometabolic dysfunction in obesity. Using a model of high-fat diet-induced obesity in C57BL/6J female mice, we assessed intestinal paracellular permeability by in vivo and ex vivo assays and quantitated intestinal macrophages in ileum and colon tissues by multicolor flow cytometry after short (6 wk), intermediate (12 wk), and prolonged (18 wk) diet allocation. We characterized monocyte-derived CD4-TIM4- and CD4+TIM4- macrophages, as well as tissue-resident CD4+TIM4+ macrophages. Diet-induced obesity had tissue- and time-dependent effects on intestinal permeability, as well as monocyte and macrophage numbers, surface marker phenotype, and intracellular production of the cytokines IL-10 and tumor necrosis factor (TNF). We found that obese mice had increased paracellular permeability, in particular within the ileum, but this did not elicit recruitment of monocytes nor a local proinflammatory response by monocyte-derived or tissue-resident macrophages in either the ileum or colon. Proliferation of monocyte-derived and tissue-resident macrophages was also unchanged. Wild-type and TNF-/- littermate mice had similar intestinal permeability and macrophage population characteristics in response to diet-induced obesity. These data are unique from reported effects of diet-induced obesity on macrophages in metabolic tissues, as well as outcomes of acute inflammation within the intestines. These experiments also collectively indicate that TNF does not mediate effects of diet-induced obesity on paracellular permeability or intestinal monocyte-derived and tissue-resident intestinal macrophages in young female mice.NEW & NOTEWORTHY We found that diet-induced obesity in female mice has tissue- and time-dependent effects on intestinal paracellular permeability as well as monocyte-derived and tissue-resident macrophage numbers, surface marker phenotype, and intracellular production of the cytokines IL-10 and TNF. These changes were not mediated by TNF.

Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies.

Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.

Associations between exposure to adverse childhood experiences and biological aging: Evidence from the Canadian Longitudinal Study on Aging.

People exposed to adverse childhood experiences (ACEs) suffer from an increased risk of chronic disease and shorter lifespan. These individuals also tend to exhibit accelerated reproductive development and show signs of advanced cellular aging as early as childhood. These observations suggest that ACEs may accelerate biological processes of aging through direct or indirect mechanisms; however, few population-based studies have data to test this hypothesis. We analysed ACEs and biological aging data from the Canadian Longitudinal Study on Aging (CLSA; n = 23,354 adults aged 45-85) and used the BioAge R package to compute three indices of biological aging from blood-chemistry and organ-function data: Klemera-Doubal method (KDM) biological age, phenotypic age (PA), and homeostatic dysregulation (HD). Adults with ACEs tended to be biologically older than those with no ACEs, although the observed effect-sizes were small (Cohen's d<0.15), with the exception of neglect (d=0.35 for KDM and PA). Associations were similar for men and women and tended to be smaller for older as compared to midlife participants. Subtypes of ACEs perceived as being more severe (e.g., being pushed or kicked, experiencing forced sexual activity, witnessing physical violence) and more frequent and diverse exposures were associated with relatively larger effect-sizes. These findings support the hypothesis that ACEs contribute to accelerated biological aging, although replication is needed in studies with access to prospective records of ACEs and cellular-level measurements of biological aging. Furthermore, future work to better understand the degree to which associations between ACEs and biological aging are moderated by specific life-course pathways, and mediated by lifestyle and socioeconomic factors is warranted.

Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism†.

Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal hepatic development. We also determined whether paternal obesity indirectly affects the in utero environment by disrupting maternal metabolic adaptations to pregnancy. Male mice fed a standard chow or high fat diet (60%kcal fat) for 8-10 weeks were time-mated with female mice to generate pregnancies and offspring. Glucose tolerance was evaluated in dams at mid-gestation (embryonic day (E) 14.5) and late gestation (E18.5). Hypoxia, angiogenesis, endocrine function, macronutrient transport, and ER stress markers were evaluated in E14.5 and E18.5 placentae and/or fetal livers. Maternal glucose tolerance was assessed at E14.5 and E18.5. Metabolic parameters were assessed in offspring at ~60 days of age. Paternal obesity did not alter maternal glucose tolerance but induced placental hypoxia and altered placental angiogenic markers, with the most pronounced effects in female placentae. Paternal obesity increased ER stress-related protein levels (ATF6 and PERK) in the fetal liver and altered hepatic expression of gluconeogenic factors at E18.5. Offspring of obese fathers were glucose intolerant and had impaired whole-body energy metabolism, with more pronounced effects in female offspring. Metabolic deficits in offspring due to paternal obesity may be mediated by sex-specific changes in placental vessel structure and integrity that contribute to placental hypoxia and may lead to poor fetal oxygenation and impairments in fetal metabolic signaling pathways in the liver.

The intestine and the microbiota in maternal glucose homeostasis during pregnancy.

It is now well established that, beyond its role in nutrient processing and absorption, the intestine and its accompanying gut microbiome constitute a major site of immunological and endocrine regulation that mediates whole-body metabolism. Despite the growing field of host-microbe research, few studies explore what mechanisms govern this relationship in the context of pregnancy. During pregnancy, significant maternal metabolic adaptations are made to accommodate the additional energy demands of the developing fetus and to prevent adverse pregnancy outcomes. Recent data suggest that the maternal gut microbiota may play a role in these adaptations, but changes to maternal gut physiology and the underlying intestinal mechanisms remain unclear. In this review, we discuss selective aspects of intestinal physiology including the role of the incretin hormone, glucagon-like peptide 1 (GLP-1), and the role of the maternal gut microbiome in the maternal metabolic adaptations to pregnancy. Specifically, we discuss how bacterial components and metabolites could mediate the effects of the microbiota on host physiology, including nutrient absorption and GLP-1 secretion and action, and whether these mechanisms may change maternal insulin sensitivity and secretion during pregnancy. Finally, we discuss how these pathways could be altered in disease states during pregnancy including maternal obesity and diabetes.

Gut microbiota-based vaccination engages innate immunity to improve blood glucose control in obese mice.

OBJECTIVE: Obesity and diabetes increase circulating levels of microbial components derived from the gut microbiota. Individual bacterial factors (i.e., postbiotics) can have opposing effects on blood glucose. METHODS: We tested the net effect of gut bacterial extracts on blood glucose in mice using a microbiota-based vaccination strategy. RESULTS: Male and female mice had improved glucose and insulin tolerance five weeks after a single subcutaneous injection of a specific dose of a bacterial extract obtained from the luminal contents of the upper small intestine (SI), lower SI, or cecum. Injection of mice with intestinal extracts from germ-free mice revealed that bacteria were required for a microbiota-based vaccination to improve blood glucose control. Vaccination of Nod1-/-, Nod2-/-, and Ripk2-/- mice showed that each of these innate immune proteins was required for bacterial extract injection to improve blood glucose control. A microbiota-based vaccination promoted an immunoglobulin-G (IgG) response directed against bacterial extract antigens, where subcutaneous injection of mice with the luminal contents of the lower SI elicited a bacterial extract-specific IgG response that is compartmentalized to the lower SI of vaccinated mice. A microbiota-based vaccination was associated with an altered microbiota composition in the lower SI and colon of mice. Lean mice only required a single injection of small intestinal-derived bacterial extract, but high fat diet (HFD)-fed, obese mice required prime-boost bacterial extract injections for improvements in blood glucose control. CONCLUSIONS: Subversion of the gut barrier by vaccination with a microbiota-based extract engages innate immunity to promote long-lasting improvements in blood glucose control in a dose-dependent manner.

Associations of Adverse Childhood Experiences with Frailty in Older Adults: A Cross-Sectional Analysis of Data from the Canadian Longitudinal Study on Aging.

INTRODUCTION: Frailty in older adults, characterized by a decline in multiple physiological systems and increasing vulnerability to loss of independence, disability, and death, is a public health priority in developed countries. Etiology of frailty extends across the lifespan and may begin in early life, but empirical evidence for this association is scarce. In this study, we examined whether adverse childhood experiences (ACEs) are associated with frailty in later life. METHODS: We conducted a cross-sectional analysis of data for a population-based sample of 27,748 adults aged 45-85 years from the Canadian Longitudinal Study on Aging. The frailty index (FI) was computed with 76 health-related characteristics of physical and cognitive performance, self-rated health, chronic conditions, visual and hearing ability, activities of daily living, and well-being. Self-reported exposure to ACEs included physical, emotional, and sexual abuse, neglect, and witnessing intimate partner violence prior age of 16 and parental death, divorce, and living with a family member with mental illness prior age of 18. Generalized linear regression models with gamma error distribution and identity link function, adjusted for age and sex, were used to examine associations of each ACE type and the number of ACE types (0, 1, 2, or 3+) reported by an individual with FI. All models were adjusted for income, education, smoking, and alcohol consumption in sensitivity analysis. RESULTS: Individuals exposed to ACEs had elevated levels of FI (mean = 0.13, SD = 0.09) than those unexposed, with the largest difference observed for neglect (B [95% CI]: 0.05 [0.04, 0.06]) and the smallest for parental death and divorce (0.015 [0.01,0.02]). The ACE count was associated with frailty in a graded manner, with the FI difference reaching 0.04 [0.037, 0.044] for participants exposed to 3+ ACE types. The association between ACEs and frailty tended to be stronger for women than men and for men aged 45-64 years than older men. CONCLUSIONS: Our study supports previous studies showing that exposure to ACEs is associated with frailty in adults. Our findings suggest that screening for ACEs involving childhood maltreatment may be useful for identifying individuals at risk of frailty and prevention of ACEs may have long-term benefits for healthy aging.

Effects of Obesity-Associated Chronic Inflammation on Peripheral Blood Immunophenotype Are Not Mediated by TNF in Female C57BL/6J Mice.

Chronic low-grade systemic inflammation in obesity contributes to the development and progression of aspects of metabolic syndrome. In obese male mice, expanded adipose tissue releases proinflammatory cytokines, including TNF, which promotes an increase in immature, proinflammatory, peripheral blood Ly-6Chigh monocytes. The aim of this study was to characterize how TNF alters circulating cellular immunity in female mice with diet-induced obesity. We initially quantified peripheral blood immune cells by flow cytometry in female wild-type C57BL/6J mice after 3-30 wk of allocation to a high-fat (HF) or standard chow diet. We assessed effects of diet and time on neutrophil, monocyte, B cell, NK cell, CD4+ T cell, and CD8+ T cell populations. There was a significant interaction of the effects of diet type and time on the numbers and prevalence of circulating total monocytes and Ly-6Chigh, Ly-6Clow, and Ly-6C- subsets. Circulating monocytes, in particular Ly-6Chigh monocytes, were increased in HF-fed mice compared with chow-fed mice. Ly-6Chigh monocytes from HF-fed mice also had a more immature phenotype yet were highly responsive to the chemotactic ligand CCL2 and had greater intracellular production of TNF. Comparisons of the effects of HF diet feeding in littermate wild-type (TNF+/+) and TNF-/- female mice showed that genetic ablation of TNF did not protect from higher adiposity or an increase in circulating, immature, proinflammatory Ly-6Chigh monocytes during HF diet-induced obesity. These data emphasize the importance of considering biological sex when determining the mechanisms of TNF action in obesity-induced cellular inflammation and in other chronic inflammatory conditions.

Investigating the normalization and normative views of gestational weight gain: Balancing recommendations with the promotion and support of healthy pregnancy diets.

OBJECTIVES: Gestational weight gain (GWG) is increasingly monitored in the United States and Canada. While promoting healthy GWG offers benefits, there may be costs with over-surveillance. We aimed to explore these costs/benefits. METHODS: Quantitative data from 350 pregnant survey respondents and qualitative focus group data from 43 pregnant/post-partum and care-provider participants were collected in the Mothers to Babies (M2B) study in Hamilton, Canada. We report descriptive statistics and discussion themes on GWG trajectories, advice, knowledge, perceptions, and pregnancy diet. Relationships between GWG monitoring/normalization and worry, knowledge, diet quality, and sociodemographics-namely low-income and racialization-were assessed using χ2 tests and a linear regression model and contextualized with focus group data. RESULTS: Most survey respondents reported GWG outside recommended ranges but rejected the mid-20th century cultural norm of "eating for two"; many worried about gaining excessively. Conversely, respondents living in very low-income households were more likely to be gaining less than recommended GWG and to worry about gaining too little. A majority had received advice about GWG, yet half were unable to identify the range recommended for their prepregnancy BMI. This proportion was even lower for racialized respondents. Pregnancy diet quality was associated with household income, but not with receipt or understanding of GWG guidance. Care-providers encouraged normalized GWG, while worrying about the consequences of pathologizing "abnormal" GWG. CONCLUSIONS: Translation of GWG recommendations should be done with a critical understanding of GWG biological normalcy. Supportive GWG monitoring and counseling should consider clinical, socioeconomic, and community contexts.

Fetal meconium does not have a detectable microbiota before birth.

Microbial colonization of the human intestine impacts host metabolism and immunity; however, exactly when colonization occurs is unclear. Although many studies have reported bacterial DNA in first-pass meconium samples, these samples are typically collected hours to days after birth. Here, we investigated whether bacteria could be detected in meconium before birth. Fetal meconium (n = 20) was collected by rectal swab during elective breech caesarean deliveries without labour and before antibiotics and compared to technical and procedural controls (n = 5), first-pass meconium (neonatal meconium; n = 14) and infant stool (n = 25). Unlike first-pass meconium, no microbial signal distinct from negative controls was detected in fetal meconium by 16S ribosomal RNA gene sequencing. Additionally, positive aerobic (n = 10 of 20) and anaerobic (n = 12 of 20) clinical cultures of fetal meconium (13 of 20 samples positive in at least one culture) were identified as likely skin contaminants, most frequently Staphylococcus epidermidis, and not detected by sequencing in most samples (same genera detected by culture and sequencing in 2 of 13 samples with positive culture). We conclude that fetal gut colonization of healthy term infants does not occur before birth and that microbial profiles of neonatal meconium reflect populations acquired during and after birth.

Maternal undernutrition during pregnancy and lactation increases transcription factors, ETV5 and GDNF, and alters regulation of apoptosis and heat shock proteins in the testis of adult offspring in the rat.

We tested whether changes in Sertoli cell transcription factors and germ cell heat shock proteins (HSPs) are linked to the effects of maternal undernutrition on male offspring fertility. Rats were fed ad libitum with a standard diet (CONTROL) throughout pregnancy and lactation or with 50% of CONTROL intake throughout pregnancy (UNP) or lactation (UNL) or both periods (UNPL). After postnatal Day 21, 10 male pups per group were fed a standard diet ad libitum until postnatal Day 160 when testes were processed for histological, mRNA and immunohistochemical analyses. Compared with CONTROL: caspase-3 was increased in UNP and UNPL (P=0.001); Bax was increased in UNL (P=0.002); Bcl-2 (P<0.0001) was increased in all underfed groups; glial cell line-derived neurotrophic factor (P=0.002) was increased in UNP and UNL; E twenty-six transformation variant gene 5 and HSP70 were increased, and HSP90 was diminished in all underfed groups (P<0.0001). It appears that maternal undernutrition during pregnancy and lactation disrupts the balance between proliferation and apoptosis in germ cells, increasing germ cell production and perhaps exceeding the support capacity of the Sertoli cells. Moreover, fertility could be further compromised by changes in meiosis and spermiogenesis mediated by germ cell HSP90 and HSP70.

Biological sex, not reproductive cycle, influences peripheral blood immune cell prevalence in mice.

KEY POINTS: Traditionally the female sex, compared with the male sex, has been perceived as having greater variability in many physiological traits, including within the immune system. We investigated effects of biological sex and the female reproductive cycle on numbers of circulating leukocytes in C57BL/6J mice. We show that biological sex, but not female reproductive cyclicity, has a significant effect on peripheral blood immune cell prevalence and variability, and that sex differences were not consistent amongst common inbred laboratory mouse strains. We found that male C57BL/6J mice, compared with female mice, have greater variability in peripheral blood immunophenotype, and that this was influenced by body weight. We created summary tables for researchers to facilitate experiment planning and sample size calculations for peripheral immune cells that consider the effects of biological sex. ABSTRACT: Immunophenotyping (i.e. quantifying the number and types of circulating leukocytes) is used to characterize immune changes during health and disease, and in response to pharmacological and other interventions. Despite the importance of biological sex in immune function, there is considerable uncertainty amongst researchers as to the extent to which biological sex or the female reproductive cycle influence blood immunophenotype. We quantified circulating leukocytes by multicolour flow cytometry in young C57BL/6J mice and assessed the effects of the reproductive cycle, biological sex, and other experimental and biological factors on data variability. We found that there are no significant effects of the female reproductive cycle on the prevalence of peripheral blood B cells, NK cells, CD4+ T cells, CD8+ T cells, monocytes, or neutrophils. Immunophenotype composition and variability do not significantly change between stages of the female reproductive cycle. There are, however, sex-specific differences in immune cell prevalence, with fewer monocytes, neutrophils, and NK cells in female mice. Surprisingly, immunophenotype is more variable in male mice, and weight is a significant contributing factor. We provide tools for researchers to perform a priori sample size calculations for two-group and factorial analyses. We show that immunophenotype varies between inbred mouse strains, and that using equal sample sizes of male and female mice is not always appropriate for within-sex evaluations of immune cell populations in peripheral blood.

Exposure to high fructose corn syrup during adolescence in the mouse alters hepatic metabolism and the microbiome in a sex-specific manner.

KEY POINTS: The prevalence of obesity and non-alcoholic fatty liver disease in children is dramatically increasing at the same time as consumption of foods with a high sugar content. Intake of high fructose corn syrup (HFCS) is a possible aetiology as it is thought to be more lipogenic than glucose. In a mouse model, HFCS intake during adolescence increased fat mass and hepatic lipid levels in male and female mice. However, only males showed impaired glucose tolerance. Multiple metabolites including lipids, bile acids, carbohydrates and amino acids were altered in liver in a sex-specific manner at 6 weeks of age. Some of these changes were also present in adulthood even though HFCS exposure ended at 6 weeks. HFCS significantly altered the gut microbiome, which was associated with changes in key microbial metabolites. These results suggest that HFCS intake during adolescence has profound metabolic changes that are linked to changes in the microbiome and these changes are sex-specific. ABSTRACT: The rapid increase in obesity, diabetes and fatty liver disease in children over the past 20 years has been linked to increased consumption of high fructose corn syrup (HFCS), making it essential to determine the short- and long-term effects of HFCS during this vulnerable developmental window. We hypothesized that HFCS exposure during adolescence significantly impairs hepatic metabolic signalling pathways and alters gut microbial composition, contributing to changes in energy metabolism with sex-specific effects. C57bl/6J mice with free access to HFCS during adolescence (3-6 weeks of age) underwent glucose tolerance and body composition testing and hepatic metabolomics, gene expression and triglyceride content analysis at 6 and 30 weeks of age (n = 6-8 per sex). At 6 weeks HFCS-exposed mice had significant increases in fat mass, glucose intolerance, hepatic triglycerides (females) and de novo lipogenesis gene expression (ACC, DGAT, FAS, ChREBP, SCD, SREBP, CPT and PPARα) with sex-specific effects. At 30 weeks, HFCS-exposed mice also had abnormalities in glucose tolerance (males) and fat mass (females). HFCS exposure enriched carbohydrate, amino acid, long chain fatty acid and secondary bile acid metabolism at 6 weeks with changes in secondary bile metabolism at 6 and 30 weeks. Microbiome studies performed immediately before and after HFCS exposure identified profound shifts of microbial species in male mice only. In summary, short-term HFCS exposure during adolescence induces fatty liver, alters important metabolic pathways, some of which continue to be altered in adulthood, and changes the microbiome in a sex-specific manner.

Synergies between the Developmental Origins of Health and Disease framework and multiple branches of evolutionary anthropology.

The Developmental Origins of Health and Disease (DOHaD) hypothesis derives from the epidemiological and basic/mechanistic health sciences. This well-supported hypothesis holds that environment during the earliest stages of life-pre-conception, pregnancy, infancy-shapes developmental trajectories and ultimately health outcomes across the lifespan. Evolutionary anthropologists from multiple subdisciplines are embracing synergies between the DOHaD framework and developmentalist approaches from evolutionary biology. Even wider dissemination and employment of DOHaD concepts will benefit evolutionary anthropological research. Insights from experimental DOHaD work will focus anthropologists' attention on biochemical/physiological mechanisms underpinning observed links between growth/health/behavioral outcomes and environmental contexts. Furthermore, the communication tools and wide public appeal of developmentalist health scientific research may facilitate the translation/application of evolutionary anthropological findings. Evolutionary Anthropology, in turn, can increase mainstream DOHaD research's use of evolutionary theory; holistic, longitudinal, and community-based perspectives; and engagement with populations whose environmental exposures differ from those most commonly studied in the health sciences.

Behaviour change interventions: getting in touch with individual differences, values and emotions.

Systematic reviews and meta-analyses suggest that behaviour change interventions have modest effect sizes, struggle to demonstrate effect in the long term and that there is high heterogeneity between studies. Such interventions take huge effort to design and run for relatively small returns in terms of changes to behaviour.So why do behaviour change interventions not work and how can we make them more effective? This article offers some ideas about what may underpin the failure of behaviour change interventions. We propose three main reasons that may explain why our current methods of conducting behaviour change interventions struggle to achieve the changes we expect: 1) our current model for testing the efficacy or effectiveness of interventions tends to a mean effect size. This ignores individual differences in response to interventions; 2) our interventions tend to assume that everyone values health in the way we do as health professionals; and 3) the great majority of our interventions focus on addressing cognitions as mechanisms of change. We appeal to people's logic and rationality rather than recognising that much of what we do and how we behave, including our health behaviours, is governed as much by how we feel and how engaged we are emotionally as it is with what we plan and intend to do.Drawing on our team's experience of developing multiple interventions to promote and support health behaviour change with a variety of populations in different global contexts, this article explores strategies with potential to address these issues.