**5. Dysbiosis and early noncommunicable diseases**

Throughout life, the structure of the intestinal microbiota can be affected by different factors, such as diet, drugs, the host's immune system, and even the intestinal mucosa itself. Changes in the microbiota can be transient or long-lasting. However, most of the time, alterations in multiple factors are required to generate changes in the microbiota that become harmful to health. This is because the microbiota has resilience, also known as the ability to adapt, to some extent, to changes in the availability of nutrients or environmental conditions [57]. However, when negative conditions are maintained over time, for example, when breastfeeding is not provided or when there is an inadequate dietary pattern or lifestyle in the early years of life, a persistent imbalance of bacterial communities is generated, known as dysbiosis [58].

*Could Alterations in the Infant Gut Microbiota Explain the Development of Noncommunicable… DOI: http://dx.doi.org/10.5772/intechopen.105168*

In addition, some elements have been identified that can amplify or drive changes in the microbiota, making the imbalance more evident and leading directly to dysbiosis. Among them are an increase in the richness of bacteriophages with lytic action in the intestinal environment [59] and the secretion of bacteriocins as a bacterial competition strategy in the intestinal ecosystem. Both situations are enhanced when there is some type of stress [60]. For example, oxidative stress also leads to dysbiosis by promoting the increase of specific bacterial communities and causing the activation of the immune system, as well as the development of subclinical inflammation [57]. This, together with the local and systemic effects of imbalanced SCFAs, described in Section 4 of this chapter, links dysbiosis with the pathophysiological processes of some noncommunicable metabolic diseases, such as obesity, T2D, and CVD [58], as is shown in **Figure 1.**

#### **5.1 Obesity**

Different studies have confirmed that there is an imbalance in the intestinal microbiota of obese children when compared to healthy children with normal weight. In general, an increase in the Firmicutes/Bacteroidetes (F/B) ratio has been described in some populations [61]; while in others, no differences have been found at the phylum level [62]. In the systematic review by Indiani *et al*. [63], the results of seven high-quality studies were analyzed and a significant association of Firmicutes with body mass index (BMI) was identified. At the genus and species levels, there is greater consensus regarding the increase in abundance of some Bacteroides species, such as *B. fragilis* [64, 65] and *B. eggerthii* [62]. Other studies have also detected microorganisms such as *Methanobrevibacter smithii, Akkermansia muciniphyla, Desulfovibrionaceae, Bifidobacteriaceae*, and *Enterobacteriaceae* associated with obesity in specific populations, but more studies are needed to increase the evidence of these associations in children [63]. Furthermore, it is generally considered that members of the Bacteroidetes family are the best predictors of the BMI z-score than the phylum analysis [66].

The specific mechanisms by which these associations could explain the early development of obesity from the DOHaD perspective are diverse. In the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort [67], 935 motherinfant dyads were followed from pregnancy through the first 3 years. Their results explain the intergenerational transmission of overweight and obesity, where having an obese mother and being born by cesarean section increases the risk 5 times for obesity at 1 and 3 years. In this model, the abundance of some specific families of Firmicutes, such as Lachnospiraceae, were sequentially associated with the development of obesity. This association increased in children with obese mothers and was even higher in those born by cesarean section.

Bacteria belonging to the phylum Firmicutes are mostly SCFA producers, such as butyrate and acetate. This supports the findings of Riva *et al.* [66], who found a higher production of SCFA in children with obesity, suggesting a higher fermentative activity. Consequently, when this occurs, energy harvest is increased, which favors a positive energy balance, and contributes to overweight and obesity. Despite this, it depends on the type of SCFA. For example, acetate that is absorbed in the intestine can serve as a substrate for de novo lipogenesis in the liver, which contributes to the accumulation of adipose tissue [68] and compromises the integrity of the intestinal barrier, increasing paracellular permeability and inducing inflammation due to bacterial translocation [6]. In contrast, others SCFA, such as butyrate and propionate, which

#### **Figure 1.**

*Perinatal determinants of the first microbiota and effects of protective or harmful interventions for child health through life. BMI: Body mass index, SCFA: Short-chain fatty acids, TMAO: Trimethylamine-n-oxide, T2D: Type 2 diabetes, ACVD: Atheroesclerotic cardiovascular disease.*

are dominant products in eubiosis, have a protective effect against obesity. Among the proposed mechanisms, its role in reducing cholesterol synthesis, improving insulin sensitivity, inducing fatty acid oxidation, and leptin gene expression stand out [69].

In obese Canadian children [70], prebiotic supplementation for 16 weeks was associated with a normalized rate of weight gain, decreased percent body fat, and changes in gut microbiota structure, characterized by the increase of *Bifidobacterium* spp. This highlights the role of the microbiota in obesity and the impact that a high-fiber diet could have on its prevention and treatment in childhood.

*Could Alterations in the Infant Gut Microbiota Explain the Development of Noncommunicable… DOI: http://dx.doi.org/10.5772/intechopen.105168*

#### **5.2 Type 2 diabetes**

There is increasing evidence of the role of the microbiota in the development of type 2 diabetes (T2D) in youth. In a murine study [71], it was found that during pregnancy, maternal gut microbiota provides protection against obesity and diabetes, through mechanisms related to the SCFA receptors GRP41 and GRP43, which are part of the FFAR family of receptors. This axis participates in the prenatal development of the metabolic and neural systems, driving the development of enteroendocrine cells and pancreatic beta cells. In this way, the deficiency in the signaling of this pathway caused sympathetic dysfunction, compromising energy metabolism, and inducing hyperglycemia.

As in children with obesity, adult patients with T2D have heterogeneous results regarding the F/B ratio [72, 73]. In a study conducted in China [74], it was found that when separating patients with T2D according to the presence or absence of chronic complications, the group without chronic complications presented a higher F/B ratio than those with complications, at the expense of increased Proteobacteria in the latter. Furthermore, some opportunistic pathogens have been identified as part of the microbiota of T2D patients, such as *Bacteroides caccae, Clostridium hathewayi, Clostridium ramosum, Clostridium symbiosum, Eggerthella tarda*, *and Escherichia coli* [75]. Thus, in general, in patients with T2D, there is a depletion of butyrate-producing bacteria such as *Prevotella* and *Bifidobacterium*. Also, decreased levels of *Akkermansia muciniphila* have been related to mucosal damage and induction of inflammation by activation of the immune system in the lamina propria [74, 75].

Seeking to integrate the previous observations, different mechanisms have been proposed that link the microbiota with the regulation of glycemia. Among them is the production of SCFA due to its effects already described and the increase in the secretion of incretins such as GLP-1 and its role in the differentiation of enteroendocrine cells. In addition, there is evidence regarding their participation in the metabolism of bile acids (BA) and the consequent induction of local and peripheral signals, and the regulation of adipose tissue by promoting white adipose tissue browning and by acting as a trigger for metabolic inflammation [76].
