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Low birth weight resulting from intrauterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low-birth-weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that 1) IUGR piglets present altered postnatal growth and increased adiposity; 2) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behavior; and 3) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition, and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the 1UGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR. intrauterine growth retardation; metabolic programming; obesity; catch-up growth; adipose tissue development

Early supplementation with oregano essential oil (EO) in milk replacer (MR) may improve growth, immune responses, the microbiota and the metabolome in dairy calves during pre-weaning and in adulthood. Sixteen female dairy calves (3 days of age) were divided in two groups ( n = 8/group): the control group (no EO) and the EO group (0.23 ml of EO in MR during 45 days). After weaning, calves were kept in a feedlot and fed ad libitum . The animals were weighed, and blood and faecal samples were collected on days 3 (T0), 45 (T1) and 370 (T2) to measure the biochemical profile and characterise peripheral blood mononuclear cells (PBMCs; CD4 + , CD8 + , CD14 + , CD21 + and WC1 + ), the metabolome and microbiota composition. The EO group only had greater average daily weight gain during the suckling (EO supplementation) period ( P = 0.030). The EO group showed higher average CD14 + population (monocytes) values, a lower abundance of Ruminococcaceae UCG-014 , Faecalibacterium , Blautia and Alloprevotella and increased abundances of Allistipes and Akkermansia . The modification of some metabolites in plasma, such as butyric acid, 3-indole-propionic acid and succinic acid, particularly at T1, are consistent with intestinal microbiota changes. The data suggest that early EO supplementation increases feed efficiency only during the suckling period with notable changes in the microbiota and plasma metabolome; however, not all of these changes can be considered desirable from a gut health point of view. Additional research studies is required to demonstrate that EOs are a viable natural alternative to antibiotics for improving calf growth performance and health.

Evidence suggests that meat processing and heat treatment may increase cancer risk through exposure to potentially carcinogenic compounds, polycyclic aromatic hydrocarbons (PAHs), and heterocyclic aromatic amines (HAAs). This study aims to investigate the effect of low concentrations of PAHs and HAAs (from 1 to 100 μmol/L/24h and 48h) in colorectal tumor cells (HT-29, HCT116, and LS174T) and to evaluate the effect of PAHs in the presence of inulin in mice. In vitro, the 4-PAHs have no effect on healthy colon cells but decreased the viability of the colorectal tumor cells and activated the mRNA and protein expressions of CYP1A1 and CYP1B1. In vivo, in mice with colitis induced by 3% DSS, the 4-PAHs (equimolar mix at 50,100, 150 mg/kg.bw, orally 3 times a week for 3 weeks) induced a loss of body weight and tumor formation. Inulin (10 g/L) had no effect on colon length and tumor formation. A significant decrease in the loss of b.w was observed in inulin group as compared to the fiber free group. These results underscore the importance of considering the biological association between low-dose exposure to 4-HAPs and diet-related colon tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

An in vitro trial was carried out to investigate the effects of natural Thymbra capitata essential oil (NEO) and its main compounds [including carvacrol, p-cymene, γ-terpinene given alone or in a synthetic combination (SEO)] on ruminal fermentation and the bacterial community using batch cultures inoculated with ruminal digesta and incubating two different basal diets [high-forage (F) and high-concentrate (C) diet]. After 24 h of incubation, primary fermentation end-products [gas, methane, volatile fatty acids (VFAs) and ammonia] and rumen microbial diversity were determined. NEO reduced the total VFA concentration (P < 0.05) only in the C diet. In contrast, SEO and carvacrol decreased the total VFA concentration (P < 0.05) only in the F diet. Methane production was not affected (P > 0.05) by any of the experimental treatments or diets evaluated. Microbial diversity analysis showed only a moderate effect of carvacrol and SEO on 13 genera, including, mainly, Atopobium and Blautia (involved in subacute ruminal acidosis) or Candidatus Saccharimonas (related to laminitis). In conclusion, T. capitata EO has a limited potential to attain nutritional or environmental benefits, but further research should be carried out to clarify its effects on animal health and microbial food safety., (© 2023. The Author(s).)

This manuscript aimed to optimise the encapsulation of Thymus capitatus essential oil into nanoemulsion. Response Surface Methodology results were best fitted into polynomial models with regression coefficient values of more than 0.95. The optimal nanoemulsion showed nanometer-sized droplets (380 nm), a polydispersity index less than 0.5, and a suitable Zeta potential (-10.3 mV). Stability results showed that nanoemulsions stored at 4 °C were stable with the lowest d 3,2 , PolyDispersity Index (PDI), and pH (day 11). Significant ameliorations in the capacity to neutralise DPPH radical after the encapsulation of the antimicrobial efficacy of thyme essential oil were recorded. S. typhimurium growth inhibition generated by nanoencapsulated thyme essential oil was 17 times higher than by bulk essential oil. The sensory analysis highlighted that the encapsulation of thyme essential oil improved enriched milk's sensory appreciation. Indeed, 20% of the total population attributed a score of 4 and 5 on the scale used for milk enriched with nanoemulsion. In comparison, only 11% attributed the same score to milk enriched with bulk essential oil. The novel nanometric delivery system presents significant interest for agroalimentary industries.

Using plant essential oils (EOs) contributes to the growing number of natural plants' applications in livestock. Scientific data supporting the efficacy of EOs as anti-inflammatory, antibacterial and antioxidant molecules accumulates over time; however, the cumulative evidence is not always sufficient. EOs antioxidant properties have been investigated mainly from human perspectives. Still, so far, our review is the first to combine the beneficial supporting properties of EOs in a One Health approach and as an animal product quality enhancer, opening new possibilities for their utilization in the livestock and nutrition sectors. We aim to compile the currently available data on the main anti-inflammatory effects of EOs, whether encapsulated or not, with a focus on mammary gland inflammation. We will also review the EOs' antioxidant activities when given in the diet or as a food preservative to counteract oxidative stress. We emphasize EOs' in vitro and in vivo ruminal microbiota and mechanisms of action to promote animal health and performance. Given the concept of DOHaD (Developmental Origin of Health and Diseases), supplementing animals with EOs in early life opens new perspectives in the nutrition sector. However, effective evaluation of the significant safety components is required before extending their use to livestock and veterinary medicine.

Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome. The desire to obtain a high degree of certainty and verification of the evidence used for decision-making must be weighed against the costs and necessary duration of research, as well as the long-term costs to human health because of delayed protection of vulnerable early-life stages of human development and, possibly, future generations. Although two-generation toxicology tests may be useful for initial test purposes, other rapidly emerging tools need to be seriously considered from computational chemistry and metabolomics to CLARITY-BPA-type designs, big data and population record linkage approaches that will allow efficient generation of new insight; epigenetic mechanisms may necessitate a set of additional regulatory tests to reveal such effects. As reflected by the Prenatal Programming and Toxicity (PPTOX) VI conference, the current scientific understanding and the timescales involved require an intensified approach to protect against preventable adverse health effects that can harm the next generation and generations to come. While further research is needed, the main emphasis should be on research translation and timely public health intervention to avoid serious, irreversible and perhaps transgenerational harm., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Early-life microbial exposure is of particular importance to growth, immune system development and long-lasting health. Hence, early microbiota composition is a promising predictive biomarker for health and disease but still remains poorly characterized in regards to susceptibility to diarrhoea. In the present study, we aimed to assess if gut bacterial community diversity and composition during the suckling period were associated with differences in susceptibility of pigs to post-weaning diarrhoea. Twenty piglets from 5 sows (4 piglets / litter) were weaned in poor housing conditions to challenge their susceptibility to post-weaning diarrhoea. Two weeks after weaning, 13 pigs exhibited liquid faeces during 2 or 3 days and were defined as diarrhoeic (D) pigs. The other 7 pigs did not have diarrhea during the whole post-weaning experimental periodand were defined as healthy (H) pigs. Using a molecular characterisation of fecal microbiota with CE-SSCP fingerprint, Next Generation Sequencing and qPCR, we show that D and H pigs were mainly discriminated as early as postnatal day (PND) 7, i.e. 4 weeks before post-weaning diarrhoea occurence. At PND 7 H pigs displayed a lower evenness and a higher abundance of Prevotellaceae, Lachnospiraceae, Ruminocacaceae and Lactobacillaceae compared to D pigs. The sPLS regression method indicates that these bacterial families were strongly correlated to a higher Bacteroidetes abundance observed in PND 30 H pigs one week before diarrhoea. These results emphasize the potential of early microbiota diversity and composition as being an indicator of susceptibility to post-weaning diarrhoea. Furthermore, they support the health promoting strategies of pig herds through gut microbiota engineering., Competing Interests: The authors have declared that no competing interests exist.

The presence of pesticide residues in food is a public health problem. Exposure to these substances in daily life could have serious effects on the intestine-the first organ to come into contact with food contaminants. The present study investigated the impact of a low dose (1 mg/day in oil) of the pesticide chlorpyrifos (CPF) on the community structure, diversity and metabolic response of the human gut microbiota using the SHIME ® model (six reactors, representing the different parts of the gastrointestinal tract). The last three reactors (representing the colon) were inoculated with a mixture of feces from human adults. Three time points were studied: immediately before the first dose of CPF, and then after 15 and 30 days of CPF-oil administration. By using conventional bacterial culture and molecular biology methods, we showed that CPF in oil can affect the gut microbiota. It had the greatest effects on counts of culturable bacteria (with an increase in Enterobacteria, Bacteroides spp. and clostridia counts, and a decrease in bifidobacterial counts) and fermentative activity, which were colon-segment-dependent. Our results suggest that: (i) CPF in oil treatment affects the gut microbiota (although there was some discordance between the culture-dependent and culture-independent analyses); (ii) the changes are "SHIME ® -compartment" specific; and (iii) the changes are associated with minor alterations in the production of short-chain fatty acids and lactate., Competing Interests: The authors declare no conflict of interest.

Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring's birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure., Competing Interests: The authors have declared that no competing interests exist.

Objective: the present study has been conducted to evaluate the impact of the consumption of high MRP formula on changes in the microbiota and the oxidative status, during development, in the colons of intrauterine growth restricted (IUGR) juvenile pigs., Methods: over a 3-week period, fifteen-day old piglets received formula with two different heat treatments. A formula heated at high temperature (HHF, n = 8) and another one heated at a low temperature (LHF, n = 8). After weaning, animals were fed, ad libitum, a solid diet until postnatal day 54 (PND54). The diversity and composition of the major microbiota were analyzed by CE SSCP and qPCR at postnatal day 36 (PND36) and PND54. Protein oxidation levels, glutathione peroxidase (GPX) activity, catalase (CAT), manganese dependent superoxide dismutase (Mn SOD), NFκB and inducible nitric oxide synthase (iNOS) gene expression were measured in the colon at the juvenile stage (PND54)., Results: HHF resulted in a significant decrease in bacterial diversity in the colon at PND36. An increase in the total count of Bifidobacteria, Lactobacillus, Bacteroidetes and Enterobacteria, without major changes in total microbiota was evidenced by qPCR, suggesting qualitative changes in the bacterial population of the HHF group. The imbalance of microbiota observed at PND36 was significantly modified at PND54, when animals received a solid diet. Colon GPX activity (p < 0.05) and gene expression of CAT and iNOS were significantly (p < 0.05) upregulated in the HHF group. No differences in the total protein oxidation and carbonyl score were found in the HHF group. Colon redox enzyme gene expression and pro-inflammatory factor NFκB negatively correlated (p < 0.05) with the bacterial population, suggesting the involvement of certain phyla in controlling the oxidative status of the IUGR piglets, fed on the high AGE formula., Conclusion: during development, consuming a high load MRP formula was associated with a major modification in the diversity and composition of the microbiota. The onset of an IUGR adaptive oxidant defense mechanism was found to counteract the oxidative stress induced by the presence of MRPs in formula.

Purpose: The long-term effects of the development of chronic metabolic diseases such as type 2 diabetes and obesity have been associated with nutritional insults in critical life stages. In this study, we evaluated the effect of a low-protein diet on metabolism in mid-adulthood male rats., Methods: At 90 days of age, Wistar male rats were fed a low-protein diet (4.0 %, LP group) for 30 days, whereas control rats were fed a normal-protein diet (20.5 %, NP group) throughout their lifetimes. To allow for dietary rehabilitation, from 120 to 180 days of age, the LP rats were fed a normal-protein diet. Then, we measured body composition, fat stores, glucose-insulin homeostasis and pancreatic islet function., Results: At 120 days of age, just after low-protein diet treatment, the LP rats displayed a strong lean phenotype, hypoinsulinemia, as assessed under fasting and glucose tolerance test conditions, as well as weak pancreatic islet insulinotropic response to glucose and acetylcholine (p < 0.01). At 180 days of age, after poor-protein diet rehabilitation, the LP rats displayed a slight lean phenotype (p < 0.05), which was associated with a high body weight gain (p < 0.001). Additionally, fat pad accumulation, glycemia and insulinemia, as well as the pancreatic islet insulinotropic response, were not significantly different between the LP and NP rats (p > 0.05)., Conclusions: Taken together, the present data suggest that the effects of dietary restriction as a stressor in adulthood are reversible with dietary rehabilitation, indicating that adulthood is not a sensitive or critical time window for metabolic programming.

The first epidemiological studies showing a link between low birth weight and chronic diseases in adults did not distinguish the origins of low birth weight. A low birth weight may be the result of a premature birth. It can also be caused by an intrauterine growth restriction (IUGR). A child can be both preterm and IUGR. It is clear now that prematurity is an independent risk factor for programming chronic adult diseases. However, unlike adults born IUGR, adults born prematurely do not have an increased risk to develop metabolic syndrome (dyslipidemia or obesity). An increased risk of neurodevelopmental and psychiatric morbidity and hypertension is found after a premature birth. Mechanisms of chronic diseases programming are multiple: they involve both the cause of prematurity and IUGR such as infection / inflammation or placental insufficiency, but also consequences for therapeutic or nutritional strategies needed to support these children. This chapter describes the possible prevention of perinatal programming of noncommunicable diseases., (© 2016 médecine/sciences – Inserm.)

Introduction: A sedentary lifestyle and high-fat feeding are risk factors for cardiometabolic disorders. This study determined whether moderate exercise training prevents the cardiometabolic changes induced by a high-fat diet (HFD)., Materials and Methods: Sixty-day-old rats were subjected to moderate exercise three times a week for 30 days. After that, trained rats received a HFD (EXE-HFD) or a commercial normal diet (EXE-NFD) for 30 more days. Sedentary animals also received the diets (SED-HFD and SED-NFD). Food intake and body weight were measured weekly. After 120 days of life, analyses were performed. Data were analysed with two-way ANOVA and the Tukey post-test., Results: Body weight gain induced by HFD was attenuated in trained animals. HFD reduced food intake by approximately 30% and increased body fat stores by approximately 75%. Exercise attenuated 80% of the increase in fat pads and increased 24% of soleus muscle mass in NFD animals. HFD induced a hyper-response to glucose injection, and exercise attenuated this response by 50%. Blood pressure was increased by HFD, and the beneficial effect of exercise in reducing blood pressure was inhibited by HFD. HFD increased vagal activity by 65% in SED-HFD compared with SED-NFD rats, and exercise blocked this increase. HFD reduced sympathetic activity and inhibited the beneficial effect of exercise on ameliorating sympathetic activity., Conclusion: Four weeks of moderate exercise at low frequency was able to prevent the metabolic changes induced by a HFD but not the deleterious effects of diet on the cardiovascular system.

Scope: Formula-derived dietary advanced glycation end products (AGEs) may promote programming of inflammation and oxidative stress in the kidney of intrauterine growth retardation (IUGR) piglets., Methods and Results: IUGR piglets received either a low temperature heated formula (n = 8) or a high temperature heated formula (HHF: n = 8) or suckled naturally for 3 wk postnatally. Then they were fed with normal ad libitum regular diet. N(ε)-carboxymethyllysine (CML) was measured in plasma, feces, and formula by HPLC/MS-MS. CML was detected by immunofluorescence in kidney cells. Target renin-angiotensin-apoptotic, pro-inflammatory genes-p62 NF-κB, and soluble receptor of AGE (sRAGE) levels were quantified. Compared with that in controls, free CML and plasma urea increased significantly in the HHF-fed group at PND36 (p < 0.05). CML was detected in the nuclei of renal tubular cells of formula-fed piglets but not in suckled ones. This presence of CML was associated with the activation of the soluble receptor of AGE. AT1, AT2, caspase 3, caspase 8, NF-κB, p62 NF-κB, and total protein oxidation in kidney were higher in HHF-fed group as compared to LHF-fed group (p < 0.05)., Conclusion: Food processes aimed at reducing the concentration of AGEs in infant formula are urgently needed and may be therapeutically relevant for premature and/or IUGR babies., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Intrauterine growth restriction (IUGR) may be accompanied by inadequate thermoregulation, especially in piglets that are not considered to possess any brown adipose tissue (BAT) and are thus entirely dependent on shivering thermogenesis in order to maintain body temperature after birth. Leptin can stimulate heat production by promoting non-shivering thermogenesis in BAT, but whether this response occurs in piglets is unknown. Newborn female piglets that were characterised as showing IUGR (mean birth weight of approximately 0.98 kg) were therefore administered injections of either saline or leptin once a day for the first 5 days of neonatal life. The dose of leptin was 0.5 mg/kg, which is sufficient to increase plasma leptin by approximately tenfold and on the day of birth induced a rapid increase in body temperature to values similar to those of normal-sized 'control' piglets (mean birth weight of ∼1.47 kg). Perirenal adipose tissue was then sampled from all offspring at 21 days of age and the presence of the BAT-specific uncoupling protein 1 (UCP1) was determined by immunohistochemistry and immunoblotting. UCP1 was clearly detectable in all samples analysed and its abundance was significantly reduced in the IUGR piglets that had received saline compared with controls, but was raised to the same amount as in controls in those IUGR females given leptin. There were no differences in gene expression between primary markers of brown and white adipose tissues between groups. In conclusion, piglets possess BAT that when stimulated exogenously by leptin can promote increased body temperature., (© 2014 Society for Endocrinology.)