The human microbiome is a complex and dynamic system of bacteria in the gut that provides instructions for function and growth, including immune system and brain development.[1,2] The first 1000 days of life, which go from conception up to the child’s second birthday, represent a critical window for gut microbiome development.[3]

Different early-life microbial exposures initiate long-lasting effects, predicting potential health outcomes for adult life.[4-7] Disruptions to the microbiota in this phase can lead to increased risks of inflammatory and neurological disorders, autoimmune diseases and obesity.[8]

Maintaining a healthy gut microbiome in pregnancy and infancy can therefore help to reduce the risk of neurodevelopmental disorders in early life and preserve long-term infant health.[9]

Gestational influences: maternal weight and health status

Foetal growth and development are significantly influenced by the in utero environment and foetal-maternal interactions like maternal diet, metabolic status, mode of delivery and the use of antibiotics.[10,11]

A healthy intestinal microbial composition during pregnancy and following delivery plays a crucial role in establishing the initial colonisation of an infant’s gut microbiota.[12] Maternal inflammation during pregnancy is associated with an increased risk of gut dysbiosis in the infant.[13,14]

Gestational diabetes, for instance, leads to a reduction of important microbes that suppress neonatal immunity.[15] Conversely, the abundance of microbial metabolites like short-chain fatty acids (SCFA) regulates immune function and influences the maturation of intestinal epithelial cells.[16-19]

Elevated maternal body mass index (BMI) can affect maternal milk composition by reducing the levels of beneficial Bifidobacteria in the milk during the first six months of lactation.[20-24] An elevated BMI is associated with low SCFA-producing bacteria and consequent lower faecal butyric acid levels, which may predict elevated adiposity in later infancy.[25,26]

High maternal BMI before pregnancy, rather than gestational weight gain, may consequently be a key factor in the risk of intergenerational transmission of infant obesity, which increases with caesarean section (c-section), as obese mothers are more likely to undergo c-section and less likely to breastfeed.[17,27-30,32-35] The resulting gut dysbiosis can increase gut permeability in the infant and directly initiate pathways of non-alcoholic fatty liver disease.[29,36]

In addition, if the mother’s gut microbiota is imbalanced due to an unhealthy diet, this can be transferred to the milk and affect the infant’s gut microbiome during breastfeeding.[8]

Understanding the impact of mother-to-infant transfer of dysbiotic microbes due to maternal diet, rather than just maternal obesity, may help modify an infant’s initial colonisation of bacteria and prevent chronic health conditions later in life.[15,18,37]

Dietary considerations

Healthy eating habits, such as adopting a Mediterranean-style diet while breastfeeding, can help maintain a diverse gut microbiota in newborns.[8,13,38] On the contrary, the widespread use of food additives, increased fat and reduced fibre content in the diet may contribute to transgenerational shifts in microbiome composition and function.[39]

These dietary considerations could drive public health strategies aimed at preserving beneficial microbes in early life and mitigating the long-term health consequences of unhealthy dietary patterns.[40] Nutrition education of the public and professionals is a key element in supporting women to adopt and maintain healthy dietary patterns in order to ultimately improve maternal and child health outcomes.[38]

The nutritional needs of women and the importance of a balanced diet before, during and after pregnancy must be supported by evidence-based professional advice and through motivational strategies for eating behaviour change. This can be achieved by offering practical and food-based demonstrations and by debunking reductive commercial claims commonly marketed as healthy, especially on social media.[38,41,42]

To highlight that a healthy pre-conception diet is associated with effective weight management, reduced risk of pregnancy complications and overall enhanced maternal health, nutrition guidance should also address social, financial and commercial barriers to behavioural change.[38]

Postnatal influences

Mode of delivery

Newborns delivered vaginally receive microbial species from the maternal vaginal area and perianal regions, while those delivered by elective c-section are colonised with bacteria from the maternal skin and oral cavity.[8,35,43-48] Interestingly, infants born by emergency c-section receive both vaginal and skin microbes due to the infiltration of vaginal microbes following foetal membrane rupture.[49]

C-section delivery is, therefore, associated with a deficit of bacteria from the birth canal, which results in a delayed, altered immune initiation, increasing the risk of later immune diseases such as obesity, allergy and asthma.[50-52]

Breastfeeding

A crucial factor in the normal development of infant microbiota, breastfeeding should ideally begin within one hour of birth.[53] Exclusive breastfeeding should ideally last at least until the baby is six months old and then be continued for the first year of life to contribute to both infant and maternal health.[54,55]

However, in low and middle-income countries, only one in two neonates are put to the breast within the first hour of life. Self-reported insufficient milk is the most common reason for introducing commercial milk formula and stopping breastfeeding. This suggests that breastfeeding is not the sole responsibility of women and requires collective societal approaches that take inequities into consideration.[56]

Human milk feeds newborns, helps them adapt to the microbial exposures of the external environment and contributes to metabolism development, gut integrity and maturation of the neuroendocrine system.[52,57,59] Rich in fats, proteins and carbohydrates, breastmilk supports the infant immune system by promoting tolerance to intestinal bacteria and enhancing the production of immune-regulatory cytokines.[52]

Breastmilk protects against respiratory and gastrointestinal infections, decreases the risk of sudden infant death syndrome and helps prevent inflammatory diseases such as dermatitis, asthma, obesity, type 1 diabetes and type 2 diabetes.[60-62]

Reducing early protein intake from infant formula during the first two years of life may help lower the risk of later obesity. This is because high intakes of protein early in life raise insulin levels, increasing insulin-like growth factor 1 (IGF-1), which is responsible for the proliferation of adipose tissue cells that lead to obesity. Infants fed with artificial milk get this protein excess because maternal milk contains five times fewer calories from protein compared to cow’s milk. [63-64]

The complex sugars that constitute human milk oligosaccharides (HMOs) are undigestible prebiotics fermented in the colon to feed Bifidobacteria, which generate SCFA.[65-68]

Due to their defence mechanism action as antiviral and antimicrobial, HMOs are key compounds in maintaining immune homeostasis and reducing infants’ risks of developing diarrhoea and gastroenteritis, as they strengthen gut barrier function, preventing intestinal attacks of viruses and parasites.[69-71]

Overall, Bifidobacteria are less represented in the intestinal microbiota of infants fed with formula compared to breastfed infants, and even supplemented formula does not significantly increase them.[67]

As different feeding patterns impact the initial microbiota and can have long-term effects, dietitians, nutritionists and healthcare professionals have a key role in supporting mothers to breastfeed.[72]

Microbial alterations due to disruptors

Increasing evidence suggests that antibiotic exposure during the first two years of life disrupts microbiome maturation and increases the gut resistome – the collection of antimicrobial resistance genes in the gut – potentially predisposing infants to adverse health outcomes such as eczema, allergic rhinitis, ADHD and inflammatory bowel disease.[73,74]

Moreover, antibiotic misuse during prenatal and postnatal periods can decrease the abundance of Bifidobacteria in the gut, which leads to a drastic reduction in the gut microbial diversity, resulting in an increase of intestinal pathogens.[75,76]

Feeding during and after weaning

Weaning generally occurs from the sixth month of age up to two years, with a dietary shift from a milk-only diet to one that includes other fluids and solid foods.[77] Complementary feeding coincides with the maturation of the gut microbiome.[78-81]

In the first year of life, the microbiota is enriched with bacteria that can utilise lactate, while solid food promotes the growth of bacteria that can use a wider variety of carbohydrates, synthesise vitamins and degrade xenobiotics.[82]

Introducing solid foods before six months may alter infant gut microbiota composition, including reducing the relative abundance of beneficial Bifidobacteria, and has been associated in some studies with a higher risk of respiratory infections.[83]

Bacteria that can digest complex fibres and proteins are the main promoters of the microbiome change.[84] By the first year of life, the development of an infant’s intestinal flora depends on exposure to various environmental factors; by the second year, the type of foods introduced has an important role.[85-87]

An important recommendation is to avoid introducing added sugars during the first two years of life, as maternal and infant sugar intake can alter the infant gut microbiome and may increase the risk of developing hypertension and diabetes later in life.

The main issue with sugar and industrial products rich in sugar and refined flours/fats is that they are not nutrient-dense, being calorie-empty, and therefore they contribute to nutritional deficiencies leading to dyslipidaemia, low HDL cholesterol, abdominal obesity and consequent inflammation. [89-91]

Additionally, added sugar may damage teeth and bones and increase the risk of asthma, depression and ADHD. Hence, the advice during and after weaning is to only consume sugar from fruit and avoid foods and drinks with added sugar, while at the same time favouring vegetables to fruits, to make their taste more acceptable in infants.[89,90]

Conclusion

During the first 1000 days of life, the gut microbiome is shaped by various factors that include maternal health status and diet, delivery mode and breastfeeding. Beneficial bacteria in an infant’s gut lay the foundations for optimal lifelong health status. To protect this delicate and complex system and prevent long-term risks of inflammatory and metabolic disorders, exposure to disruptors such as antibiotics, premature weaning and added sugars should be avoided.

Overall, a more integrated societal approach is required to support mothers with public health strategies that address social, financial and commercial barriers to behavioural change.