Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting approximately 16.5% of pregnancies worldwide and causing significant health concerns. GDM is a serious pregnancy complication caused by chronic insulin resistance in the mother and has been associated with the development of neurodevelopmental disorders in offspring. Emerging data support the notion that GDM affects both the maternal and fetal microbiome, altering the composition and function of the gut microbiota, resulting in dysbiosis. The observed dysregulation of microbial presence in GDM pregnancies has been connected to fetal neurodevelopmental problems. Several reviews have focused on the intricate development of maternal dysbiosis affecting the fetal microbiome. Omics data have been instrumental in deciphering the underlying relationship among GDM, gut dysbiosis, and fetal neurodevelopment, paving the way for precision medicine. Microbiome-associated omics analyses help elucidate how dysbiosis contributes to metabolic disturbances and inflammation, linking microbial changes to adverse pregnancy outcomes such as those seen in GDM. Integrating omics data across these different layers-genomics, transcriptomics, proteomics, metabolomics, and microbiomics-offers a comprehensive view of the molecular landscape underlying GDM. This review outlines the affected pathways and proposes future developments and possible personalized therapeutic interventions by integrating omics data on the maternal microbiome, genetics, lifestyle factors, and other relevant biomarkers aimed at identifying women at high risk of developing GDM. For example, machine learning tools have emerged with powerful capabilities to extract meaningful insights from large datasets.

Perinatal nutrition exerts a profound influence on adult metabolic health. This study aimed to investigate whether increased maternal vitamin A (VA) supply can lead to beneficial metabolic phenotypes in the offspring. The researchers utilized mice deficient in the intestine-specific homeobox (ISX) transcription factor, which exhibits increased intestinal VA retinoid production from dietary β-carotene (BC). ISX-deficient dams were fed a VA-sufficient or a BC-enriched diet during the last week of gestation and the whole lactation period. Total retinol levels in milk and weanling livers were 2- to 2.5-fold higher in the offspring of BC-fed dams (BC offspring), indicating increased VA supplies during late gestation and lactation. The corresponding VA-sufficient and BC offspring (males and females) were compared at weaning and adulthood after being fed either a standard or high-fat diet (HFD) with regular VA content for 13 weeks from weaning. HFD-induced increases in adiposity metrics, such as fat depot mass and adipocyte diameter, were more pronounced in males than females and were attenuated or suppressed in the BC offspring. Notably, the BC offspring were protected from HFD-induced increases in circulating triacylglycerol levels and hepatic steatosis. These protective effects were associated with reduced food efficiency, enhanced capacity for thermogenesis and mitochondrial oxidative metabolism in adipose tissues, and increased adipocyte hyperplasia rather than hypertrophy in the BC offspring. In conclusion, maternal VA nutrition influenced by genetics may confer metabolic benefits to the offspring, with mild increases in late gestation and lactation protecting against obesity and metabolic dysregulation in adulthood.NEW & NOTEWORTHY A genetic mouse model, deficient in intestine-specific homeobox (ISX) transcription factor, is used to show that a mildly increased maternal vitamin A supply from β-carotene feeding during late gestation and lactation programs energy and lipid metabolism in tissues and protects the offspring from diet-induced hypertrophic obesity and hepatic steatosis. This knowledge may have implications for human populations where polymorphisms in ISX and ISX target genes involved in vitamin A homeostasis are prevalent.

UNASSIGNED: Plant-based nutritional programming is the concept of exposing fish at very early life stages to a plant-based diet for a short duration to improve physiological responses when exposed to a similar plant-rich diet at a later developmental stage. The mechanisms of action underlying nutritional programming have not been fully deciphered, and the responses may be controlled at multiple levels.
UNASSIGNED: This 22-week study examines gut transcriptional changes after nutritional programming. Triplicate groups of Atlantic salmon were fed with a plant (V) vs. a marine-rich (M, control) diet for 2 weeks (stimulus phase) at the first exogenous feeding. Both stimulus fish groups (M and V fish) were then fed the M diet for 12 weeks (intermediate phase) and lastly fed the V diet (challenge phase) for 6 weeks, generating two dietary regimes (MMV and VMV) across phases. This study used a whole-transcriptome approach to analyse the effects of the V diet at the end of stimulus (short-term effects) and 22 weeks post-first feeding (long-term effects). After the stimulus, due to its developmental stage, the whole intestine was used, whereas, after the challenge, pyloric caeca and middle and distal intestines were examined.
UNASSIGNED: At the stimulus end, genes with increased expression in V fish enriched pathways including regulatory epigenetic responses and lipid metabolism, and genes involved in innate immune response were downregulated. In the middle intestine at the end of the challenge, expression levels of genes of lipid, carbohydrate, and energy metabolism were increased in V fish, while M fish revealed increased expression of genes associated with autoimmune and acute adaptive immune response. The distal intestine of V fish showed increased expression of genes associated with immune response and potential immune tolerance. Conversely, the distal intestine of M fish at challenge revealed upregulation of lipid and carbohydrate metabolic pathways, tissue degeneration, and apoptotic responses. The present study demonstrated nutritional programming-associated changes in the intestinal transcriptome, with altered expression of genes involved in both immune responses and different metabolic processes. While there were limited changes in growth between the groups, the results show that there were transcriptional differences, suggesting a programming response, although the mechanism of this response still requires to be fully elucidated.

To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP.

The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life.

OBJECTIVE: Maternal high-fat diet (HF) programs obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), hypertriglyceridemia, and hyperglycemia associated with increased endocannabinoid system (ECS) in the liver of adult male rat offspring. We hypothesized that maternal HF would induce sex specific ECS changes in the liver of newborn rats, prior to obesity onset, and maternal fish oil (FO) supplementation would reprogram the ECS and lipid metabolism markers preventing liver triglycerides (TG) accumulation.
METHODS: Female rats received a control (CT) (10.9% fat) or HF (28.7% fat) diet 8 weeks prior to mating and during pregnancy. A subgroup of HF dams received 3% FO supplementation in the HF diet (35.4% fat) during pregnancy (HFFO). Serum hormones and liver TG, ECS, lipid metabolism, oxidative stress and autophagy markers were assessed in male and female newborn offspring.
RESULTS: Maternal HF diet increased liver cannabinoid receptor 1 (CB1) in males and decreased CB2 in females, with no effect on liver TG. Maternal FO supplementation reduced liver CB1 regardless of the offspring sex, but reduced TG liver content only in females. FO reduced the liver content of the endocannabinoid anandamide in males, and the content of 2-arachidonoylglycerol in both sexes. Maternal HF increased lipogenic and decreased lipid oxidation markers, and FO induced the opposite regulation in the liver of offspring.
CONCLUSIONS: Prenatal HF and FO differentially modulate liver ECS in the offspring before obesity and MASLD development. These results suggest that maternal nutrition at critical stages of development can modulate the offspring\'s ECS, predisposing or preventing the onset of metabolic diseases.

This study aims to investigate the potential mechanisms underlying the protective effects of myo-inositol (MI) supplementation during suckling against the detrimental effects of fetal energy restriction described in animal studies, particularly focusing on the potential connections with BDNF signaling. Oral physiological doses of MI or the vehicle were given daily to the offspring of control (CON) and 25%-calorie-restricted (CR) pregnant rats during suckling. The animals were weaned and then fed a standard diet until 5 months of age, when the diet was switched to a Western diet until 7 months of age. At 25 days and 7 months of age, the plasma BDNF levels and mRNA expression were analyzed in the hypothalamus and three adipose tissue depots. MI supplementation, especially in the context of gestational calorie restriction, promoted BDNF secretion and signaling at a juvenile age and in adulthood, which was more evident in the male offspring of the CR dams than in females. Moreover, the CR animals supplemented with MI exhibited a stimulated anorexigenic signaling pathway in the hypothalamus, along with improved peripheral glucose management and enhanced browning capacity. These findings suggest a novel connection between MI supplementation during suckling, BDNF signaling, and metabolic programming, providing insights into the mechanisms underlying the beneficial effects of MI during lactation.

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.

Caffeine is a substance with central and metabolic effects. Although it is recommended that its use be limited during pregnancy, many women continue to consume caffeine. Direct and indirect actions of caffeine in fetuses and newborns promote adaptive changes, according to the Developmental Origins of Health and Diseases (DOHaD) concept. In fact, epidemiological and experimental evidence reveals the impact of early caffeine exposure. Here, we reviewed these findings with an emphasis on experimental models with rodents. The similarity of human and rodent caffeine metabolism allows the comprehension of molecular mechanisms affected by prenatal caffeine exposure. Maternal caffeine intake affects the body weight and endocrine system of offspring at birth and has long-term effects on the endocrine system, liver function, glucose and lipid metabolism, the cardiac system, the reproductive system, and behavior. Interestingly, some of these effects are sex dependent. Thus, the dose of caffeine considered safe for pregnant women may not be adequate for the prenatal period.

The present study aims to investigate nutritional programming through early starvation in the European seabass (Dicentrarchus labrax). European seabass larvae were fasted at three different developmental periods for three durations from 60 to 65 dph (F1), 81 to 87 dph (F2), and 123 to 133 dph (F3). Immediate effects were investigated by studying gene expression of npy (neuropeptide Y) and avt (Arginine vasotocin) in the head, while potential long-term effects (i.e., programming) were evaluated on intermediary metabolism later in life (in juveniles). Our findings indicate a direct effect regarding gene expression in the head only for F1, with higher avt mRNA level in fasted larved compared to controls. The early starvation periods had no long-term effect on growth performance (body weight and body length). Regarding intermediary metabolism, we analyzed related key plasma metabolites which reflect the intermediary metabolism: no differences for glucose, triglycerides, and free fatty acids in the plasma were observed in juveniles irrespective of the three early starvation stimuli. As programming is mainly linked to molecular mechanisms, we then studied hepatic mRNA levels for 23 key actors of glucose, lipid, amino acid, and energy metabolism. For many of the metabolic genes, there was no impact of early starvation in juveniles, except for three genes involved in glucose metabolism (glut2-glucose transporter and pk-pyruvate kinase) and lipid metabolism (acly-ATP citrate lyase) which were higher in F2 compared to control. Together, these results highlight that starvation between 81 to 87 dph may have more long-term impact, suggesting the existence of a developmental window for programming by starvation. In conclusion, European seabass appeared to be resilient to early starvation during larvae stages without drastic impacts on intermediary metabolism later in life.