**2. Maternal environment**

obesity during pregnancy; moreover, due to the adverse effects that this condition has on both the mother's and offspring's health, infant obesity has become a highlight topic of study [2]. It is well known that the physiology during pregnancy differs between obese and normalweight women. Obesity is associated with increased insulin resistance, adverse effects in implantation and placentation processes, growth, development and metabolism alterations

Until now, studies focused on the origins of obesity were oriented towards dietary excesses (processed sugars, fat, and proteins) [4] or host genes [5]. But recent studies have shown changes in gut microbiota associated to different diseases, like obesity, metabolic syndrome, or type I [6] and type II diabetes [7]. The community of microorganisms living in a specific environment is known as microbiota. These microorganisms include bacteria, Archaea, viruses, and some unicellular eukaryotes [8]. The collective genomes of the microorganism that constitute the microbiota are known as microbiome [9]. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotics, and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens [10]. In fact, some of these microorganisms residing in the gut encode proteins involved in functions important for the host's health, such as enzymes required for the hydrolysis of otherwise indigestible dietary compounds, and the synthesis of vitamins [9]. Since the 1990s, our knowledge of the complexity of this ecosystem has increased due to the advances in culture-independent techniques. These new techniques are fast, facilitate high throughput, and identify organisms that are uncultured to date and present in the gut microbiota; recently, by using these techniques, it has been shown that alterations in the gut microbiota composition and function are associated with certain disease states, such as obesity [11]. With the increase in knowledge about gut microbiome functions, it is becoming increasingly more possible to develop novel diagnostic, prognostic, and most important therapeutic strategies

Focused on obesity, it has been shown that certain bacteria metabolize different nutrients more efficiently than others, increasing the absorption of calories from the diet and the amount of energy usable for the host, which contributes to fat deposition [12]. Many studies have been performed in order to link this disease with changes in the composition of the intestinal microbiota [13]. Several studies have shown increased ratio in the proportion of *Firmicutes*/*Bacteroidetes* in genetically obese mice (ob/ob) and obese humans [14, 15]. However, other studies have failed to confirm these findings and showed variable patterns in the composition of the microbiota in obese humans [13]. Within the studies cited above, it is clear that the gut microbiota plays a role in obesity and metabolic disease, but it is difficult to draw definitive conclusions about the importance of certain bacterial groups. It is therefore very important to identify the active bacteria that cause dysbiosis in the gut microbiota in order to design therapeutic strategies for long-term protection against obesity. Quantitative and qualitative alterations in the composition of the gut microbiome could lead to pathological dysbiosis.

The microbiota colonization of the maternal intestine influences offspring's metabolic and immune system development [16]. Besides, although the microbiota-gut-brain axis is not a new concept [17], in the last years there are growing interest in studying the influence of the microbiota

of the fetus, and even impact on the offspring gut microbiota [3].

based on gut microbiota manipulation.

266 Adiposity - Omics and Molecular Understanding

There is evidence for the importance of the prenatal period in the health and development of offspring throughout childhood and adult life [22].

In the periconceptional period, and during pregnancy and lactation is necessary to acquire the total nutrient requirements, which are associated with mother's lifestyles and health [23]. These requirements include specific amounts of iron, vitamins (D, C, and B), calcium, folic acid, essential fatty-acids, and others, which will increase along pregnancy [24]. Furthermore, it has been demonstrated that bad habits like smoking, use of illegal drugs, consumption of caffeine and alcohol, or overweight/underweight are related to conceiving problems [25].

During the first trimester of pregnancy, the mother is under anabolism, increasing maternal fat and nutrients storage to meet the fetus-placental and maternal requirements during gestation and lactation [26]. When a deficit or overabundance of nutrients arrives to the fetus, it has to adapt itself to the new metabolic status, changing its physiology and metabolism constantly [27].

It is noteworthy that due to fetal programing, obesity may become a self-perpetuating problem, because children of obese mothers may themselves be vulnerable to becoming obese and more likely to have offspring who share this vulnerability, but the mechanisms behind this association are not fully elucidated [28].

One hypothesis to explain the influence of the mothers' weight on their children is the transmission of obesogenic microbes from mother to her offspring; in this situation is also very important the etiology of such maternal obesity and others factors like socioeconomic status or environmental factors [29].

On the other hand, a meta-analysis including nine studies has shown an increased risk of stillbirth in obese pregnant women compared to normal-weight pregnant women [30].

It has been demonstrated that a high body mass index (BMI) and an excessive weight gain during pregnancy are associated with disturbances in the maternal gut microbiota, which will influence the development of gut microbiota in the infant [31].

Infant gut microbiota will not be only influenced by mother's BMI, but also by the mode of delivery [32]. A study indicated that excess maternal prepregnancy weight is associated with differences in neonatal acquisition of microbiota during vaginal delivery, enriched in genus *Bacteroides* and depleted in genus *Enterococcus, Acinetobacter, Pseudomonas*, and *Hydrogenophilus* [33].

Subsequent to delivery, it has been shown that the type of feeding is one of the major factors modulating infants gut microbiota and it will be discussed in Section 4.

The establishment of the microbial community allows the maturation of the immune system as it has been demonstrated in germ-free (GF) animal models, where commensal microorganisms are required for the development of a fully functional immune system, which affects many physiological processes within the host [34].

In conclusion, the mother environment influences the offspring phenotype of her offspring, independently of his genotype. So, not only genetics will influence offspring gut microbiota development, but also mother's lifestyle before, during, and after pregnancy.
