Effects of Probiotic Supplementation during Pregnancy on the Future Maternal Risk of Metabolic Syndrome

Probiotics are live microorganisms that induce health benefits in the host. Taking probiotics is generally safe and well tolerated by pregnant women and their children. Consumption of probiotics can result in both prophylactic and therapeutic effects. In healthy adult humans, the gut microbiome is stable at the level of the dominant taxa: Bacteroidetes, Firmicutes and Actinobacteria, and has a higher presence of Verrucomicrobia. During pregnancy, an increase in the number of Proteobacteria and Actinobacteria phyla and a decrease in the beneficial species Roseburia intestinalis and Faecalibacterium prausnitzii are observed. Pregnancy is a “window” to the mother’s future health. The aim of this paper is to review studies assessing the potentially beneficial effects of probiotics in preventing the development of diseases that appear during pregnancy, which are currently considered as risk factors for the development of metabolic syndrome, and consequently, reducing the risk of developing maternal metabolic syndrome in the future. The use of probiotics in gestational diabetes mellitus, preeclampsia and excessive gestational weight gain is reviewed. Probiotics are a relatively new intervention that can prevent the development of these disorders during pregnancy, and thus, would reduce the risk of metabolic syndrome resulting from these disorders in the mother’s future.


Introduction
Probiotics are live microorganisms that induce health benefits to the host [1]. Prebiotics, such as inulin and fructooligosaccharides, are nondigestible food components that promote the growth of beneficial bacteria in the colon [2], whereas synbiotics are a mixture of live microorganisms with substrates that are selectively utilized by host which can provide even more benefits than prebiotics alone [3].
Recommendations regarding probiotics are complex and varied by country. There is a distinction between probiotics found in food and probiotics that are pharmaceuticals. The scientific criteria regarding the health benefits of probiotics are also becoming increasingly stringent [4]. Taking probiotics is generally safe and well tolerated by pregnant women and their children [5][6][7][8][9]. Nevertheless, side effects such as systemic infections, mild gastrointestinal disturbances and skin complications have been reported [5,10]. According to a study by Homayouni et al., food is a better carrier of probiotics than supplements [11]. Consumption of probiotics can result in both prophylactic and therapeutic effects. They may help to prevent infections, decrease cholesterol levels, promote the synthesis of vitamins and cytokines, and inhibit cancer progression [12]. Probiotics can normalize the composition of the microbiota of the gastrointestinal tract, genitourinary system, and prevent antibiotic-associated diarrhea and travelers' diarrhea [13,14]. The intestinal microflora can be affected by various factors, and the use of probiotics during an infection or antibiotic therapy can improve it [15].
The human gut, mainly in the distal colon, contains approximately 100 trillion gut microflora, including bacteria, archaea, viruses, and eukaryotic microbes [16,17]. The gut microbiota maintains interaction with the host through digestion, metabolism, nutrient extraction, vitamin synthesis, and pathogen protection [17][18][19][20]. Moreover, it has been found that the role of the human microbiome goes beyond the digestive tract, and the brain-gut-microbiota axis has been described [21,22]. It is generally accepted that in healthy adult humans, the gut microbiome is stable at the level of the dominant taxa: Bacteroidetes, Firmicutes and Actinobacteria and a higher presence of Verrucomicrobia (Akkermansia muciniphila) [21,23,24]. A healthy gut microflora was linked to an increase in the diversity and abundance of Bacteroidetes, and a higher ratio of Akkermansia muciniphila to Ruminococcus gnavus [21].
During pregnancy, an increase in the number of Proteobacteria and Actinobacteria phyla and a decrease in the beneficial species Roseburia intestinalis and Faecalibacterium prausnitzii were observed [25,26]. Changes in the composition of the microbiota in pregnancy may be associated with an increase in adipose mass, blood glucose levels, insulin resistance (IR), and the circulation of pro-inflammatory cytokines in the pregnant woman [27].
During pregnancy, women undergo significant anatomical and physiological changes related to the development of the fetus and the preparation for delivery. The diseases that appear during pregnancy usually concern endothelial dysfunction and endocrine disorders. These diseases put the mother at high risk of developing diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and possibly the development of the metabolic syndrome (MS) as a consequence.
MS is defined as a group of related risk factors that increase the risk of overall mortality and morbidity, as well as the cost and burden of healthcare. MS is an independent risk factor for CVD including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure [28,29]. The criteria for diagnosing MS in women vary depending on the recommendation, and any three of the five criteria constitute a diagnosis of MS [30,31] (Table 1).  [88]. Current and pregestational obesity and excess weight were found to be important predictors of MS in some studies, especially when combined with a fasting glycemia [80,84,89]. Compared with women with manifest diabetes, the rate of MS is delayed by more than ten years in women with glucose intolerance [57]. Obese people's microbiomes are physically and functionally diverse from their healthier counterparts, according to research [90]. Ferrer et al. found that in the gut of obese people, Firmicutes (94.6%) were more numerous than Bacteroidetes (3.2%), whereas the gut of lean people showed a change towards increased Bacteroidetes (18.9%) [91]. Additionally, the intestinal microbiome of an obese person is less diverse than that of lean person [92,93]. This strongly suggests the possibility of using the microbiome in the therapy of obesity. The extended low-grade inflammation which accompanies MS and obesity is associated with the growth of adipose tissue. Currently, adipose tissue is considered as a potent immune and endocrine organ [94]. It consists of endothelial cells, preadipocytes, adipocytes, fibroblasts, and immune cells, including mainly T cells, B cells, macrophages, and neutrophils [95][96][97]. Excessive caloric intake, body weight and diet control the cellular composition of adipose tissue, especially the composition of the immune cells. In response to these stimuli, immune cells of the stromal vascular fraction change from anti-inflammatory subtypes to more pro-inflammatory subtypes [98]. It is known that adipokines secreted by adipose tissue are involved in inflammatory processes. Patients with pre-existing obesity have a greater risk of subclinical inflammation, IR and endothelial dysfunction leading to the development of MS [80]. Some evidence suggests that MS and GDM may have a common genetic basis [99]. Furthermore, GDM and MS appear to have similar pathophysiologic pathways, as evidenced by a link between the risk gene variants TCF7L2 and FTO [100].
Women at a higher risk of developing MS should be identified using antenatal glucose measurements and BMI [85]. Effective treatment of GDM may be a way to avoid the development of cardiovascular complications in the future [85]. The aim of GDM therapy is to maintain normoglycemia and prevent excessive weight gain to reduce maternal and fetal complications. Exercise and nutritional therapy are examples of lifestyle changes. To avoid postprandial hyperglycemia and reduce IR, caloric restriction combined with a low glycemic index diet is recommended [101]. It is important to look for other methods to prevent or support the treatment of the GDM in order to prevent the onset of MS in the future.

The Use of Probiotics in GDM and EGWG
Preventing GDM, rather than treating it, can have a number of benefits, both health and economic. Homayouni et al. suggest that probiotics are a relatively new intervention that can lower glucose levels, prevent GDM, and reduce maternal and fetal complications resulting from it [102]. Several studies have shown that the gut microflora is significantly altered in women with GDM and is similar to that of adults with T2DM [103][104][105]. An increased number of gram-negative bacteria, such as Parabacteroides, Prevotella, Haemophilus, and Desulfovibrio, has been found in the intestines of GDM patients [104,[106][107][108]. However, a study by Mokkala et al. showed that the presence or absence of a specific bacterial species or function did not predict the onset of GDM, nor did it differ depending on the severity of GDM [109], although in the group of women with GDM, a higher number of Ruminococcus obeum was found in late pregnancy [109].
The roles of probiotics in modulating the composition of the intestinal microbiota and reducing the adherence of pathobionts, regulating the permeability of the intestinal epithelium and reducing the inflammatory process has been observed [77]. A randomized study of probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis) showed a reduction of more than 60% in GDM, with an incidence of 13% in the probiotic group compared with 34% in the control group [110]. However, some studies found no significant differences between the probiotic and placebo groups in terms of glycemic control and antioxidant capability [111,112]. Nevertheless, the study by Sahhaf Ebrahimi et al. found that the use of probiotic yogurt improved blood glucose levels as well as glycated hemoglobin (HbA1c) levels [112]. Probiotic supplementation may improve blood glucose control during the third trimester, according to a study conducted in healthy pregnant women [113]. Supplementing with probiotics reduced fasting plasma glucose, serum insulin levels, and IR while increasing insulin sensitivity [7,114,115]. However, other studies have shown no benefit of taking probiotics in reducing the risk of GDM [116][117][118][119][120] or improving glucose metabolism in overweight and obese women [109,119,120]. Studies in women with GDM found no significant differences in fasting glucose levels between a group receiving supplementation of Lactobacillus salivarius and a placebo group [121]. In contrast, a reduction in insulin resistance (HOMA-IR) and β-cell function (HOMA-B) was observed after probiotic administration [7,115,[122][123][124]. Other studies have shown that taking probiotics containing Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum in GDM patients had a beneficial effect on glycemic control, TG levels and very low-density lipoprotein (VLDL) [114,122].
The potential positive effects of using probiotics may also result from other mechanisms. Reduction of oxidative stress and increased secretion of incretin are considered as potential mechanisms by which probiotics improve glucose metabolism [125][126][127][128]. Bifidobacterium and Lactobacillus are among the most common, non-pathogenic living microorganisms used as probiotics [129]. They have been identified as probiotics that reduce systemic inflammation, regulate immune function, improve intestinal mucosa permeability, and ultimately reduce IR [130][131][132][133]. Bifidobacteria are commensals of humans and animals, they belong to the phylum of Actinobacteria [4]. Lactic acid bacteria are gram-positive bacteria that are traditionally used in the production of yogurt and other fermented dairy products [4]. Similar results were presented by Badehnoosh et al., who showed that taking a probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum (2 × 109 CFU/g each) for 6 weeks improved the glycemic response and markers of inflammation but did not affect pregnancy outcomes [134].
In addition, recent studies indicate that plasma vitamin C levels negatively correlate with the development of MS. It has been suggested that vitamin C supplementation may help reduce oxidative stress and postpone the chronic inflammation associated with the development of MS.
The relative abundance of short-chain fatty acids (SCFA) producing bacteria from the genera Faecalibacterium, Ruminococcus, Roseburia, Coprococcus, Akkermansia, Phascolarctobacterium, and Eubacterium was found to be lower in GDM women, obese and T2DM [104][105][106]108,[135][136][137][138][139][140][141]. SCFA affect the activity of cells of the immune system, as well as their migration to the site of inflammation, showing a significant anti-inflammatory potential [142]. The results of many animal studies show that supplementation with the probiotic Lactobacillus spp. induces the production of SCFA by modulating the intestinal microbiome [141,[143][144][145][146]. Manipulating the composition of the gut microbiome, and thus the level of SCFA, may prove to be a promising method in the treatment of inflammatory diseases [142].
In the peripheral blood of patients with GDM, probiotic intake increases the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), transform growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) and decreases the expression of tumor necrosis factor alpha (TNF-α) [114]. This suggests that probiotics alleviate IR and chronic inflammation through the PPAR pathway [147].
The supplementation of probiotics also results in a considerable decrease in plasma malondialdehyde (MDA) and a significant increase in plasma nitric oxide (NO) and total antioxidant capacity [114]. MDA has cytotoxic, mutagenic and carcinogenic properties [148]. It can also inhibit enzymes related to the cell's defence against oxidative stress [148]. NO is the main factor in endothelial cells responsible for maintaining vascular homeostasis [149].
The studies found that there was no significant difference in reducing GWG in overweight or obese pregnant women between the probiotic group (Lactobacillus rhamnosus and Bifidobacterium lactis) and the placebo group [119,150,151].

The Use of Probiotics in PE
PE is a complicated disorder in pregnancy which occurs after 20 weeks of gestation and affects 2-8% of all pregnancies in the world [152][153][154]. PE is a vascular pregnancy complication with high fetal and maternal mortality and morbidity rates [155,156]. The presence of PE in the past increases the risk of hypertension, ischemic heart disease, venous thromboembolism, kidney disease and CVD, including myocardial infarction, stroke, and heart failure [152,[157][158][159][160][161]. PE is associated with a 4-fold increased risk of future stroke [162]. PE is associated with a 2-7 times higher risk of CVD, especially if PE occurs before 34 weeks of gestation [157,[163][164][165][166]. Research has shown a significant relationship between the occurrence of PE and MS later in life [167][168][169][170][171][172]. PE is connected to MS risk factors, which are modifiable CVD risk factors [164,173,174]. According to research by Heidema et al., obesity, IR, and arterial hypertension are all common within the first year following a pregnancy affected by PE [159]. Moreover, Hooijschuur et al. showed that the incidence of MS was higher in the subgroup of women with PE and small-forgestational-age (SGA) neonate than in women without SGA neonate [164]. It is important to look for new interventions that can reduce the risk of developing PE and consequently, complications for the mother and offspring.
Brantsaeter et al. showed that consumption of milk-based probiotic products was associated with a reduced risk of overall PE, with the association most prominent in severe PE [175]. Probiotic consumption has been linked to lower blood pressure in nonpregnant women, according to clinical intervention trials using milk-based probiotic supplements [176,177]. The results of a study by Nordqvist et al. showed that consumption of probiotic milk in late pregnancy was associated with a reduced risk of PE, and consumption in early pregnancy was associated with a reduced risk of preterm delivery [178]. On the other hand, a 2018 Cochrane review of maternal oral probiotic supplementation did not find appreciable benefit or harm to neonates as a result of supplementation of pregnant women at low risk of preterm birth [179]. Furthermore, the study by Yeganegi et al. showed that Lactobacillus rhamnosus influences the lipopolysaccharide (LPS) response in placental trophoblast cells, which may affect the inflammatory response important in the pathophysiology of PE development [180]. However, a 2021 Cochrane review showed that probiotics can be harmful by increasing the risk of hypertensive disorders in pregnancy including PE [116]. The authors report that the best variables to predict the occurrence of MS in women with prior PE are early-onset PE, SGA newborn and measurement of systolic blood pressure [164].

The Use of Probiotics in Obesity and Lipid Disorders
The influence of obesity on the development of the MS is unquestionable, and the prevention of excessive weight gain may reduce the risk of complications in the future. Diets high in saturated fat and fructose affect the composition of the gut flora [181]. The resulting dysbiosis leads to a cascade of events including increased intestinal barrier permeability, bacterial translocation, and activation of hepatic receptor-induced inflammation [182]. One proposed mechanism pertains to the production of endogenous alcohol and acetaldehyde [183][184][185].
Probiotics containing Lactobacillus paracasei can impact adipose tissue mass by modulating the activity of angiopoietin-like protein 4, a circulating lipoprotein lipase (LPL) inhibitor that controls TG deposition into adipocytes, which can help prevent obesity and metabolic disorders [186].
The beneficial effect of weight reduction was obtained during Lactobacillus gasseri (SBT2055) supplementation in overweight and obese people [187,188]. Daily consumption of 200 g of yogurt containing Lactobacillus gasseri (108 CFU/g) for 12 weeks significantly reduced abdominal obesity. BMI, waist and hip circumferences, and body fat mass were also significantly decreased from the baseline, but discontinuation of the probiotic for 4 weeks weakened these effects [187]. Additionally, in studies conducted by Ilmonen et al., supplementation with probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis showed a reduction in maternal central adiposity at 6 months postpartum [189].
Lactobacillus plantarum (PL62) as a probiotic has been shown in two mouse trials to produce conjugated linoleic acid (CLA), which has been linked to weight loss [190,191]. In a study on mice by Bagarolli et al. the effects of probiotics (Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium bifidum) on the intestinal microflora, changes in insulin permeability, sensitivity and signaling in a high-fat diet (HFD) were investigated [192,193]. Probiotic-treated mice receiving a HFD gained significantly less weight and had reduced food consumption and also reduced fasting blood glucose and serum insulin compared with animals that did not receive probiotics [28]. The administration of probiotics in mice fed HFD improved leptin sensitivity [192,194,195]. The study showed that the administration of probiotics to obese animals was able to reduce Toll-like receptor 4 (TLR4) activation, downstream c-Jun N-terminal kinases (JNK) phosphorylation and the subsequent insulin receptor substrate-1 (IRS1Ser307) phosphorylation [192]. The probiotic administration had no effect on TLR4 signalling in mice with a normal body weight [192]. TLR4 is a LPS receptor that plays an important role in the regulation of immunological responses to infection [196]. As one of the components of the outer membrane of Gramnegative bacteria, LPS is considered an endotoxin that may contribute to the development of inflammation and IR [197,198]. The relative levels of TNF-α and Interleukin 6 (IL-6) transcripts in the liver, muscle and blood of probiotic-treated mice were significantly lower than in the control group [192]. When compared to untreated mice, treatment with probiotics boosted the predominance of Firmicutes and Actinobacteria while decreasing the presence of Bacteroidetes [192]. Obese animals also had a higher frequency of Bacteroidetes and a lower number of Firmicutes and Actinobacteria [192]. In obese animals, probiotic therapy resulted in the continuing presence of Bacteroidetes, an increase in the prevalence of Actinobacteria, and a decrease in Firmicutes compared with the control group [192]. An increased number of bacteria from the taxonomic family Lachnospiraceae has been associated with the development of diabetes in obese mice [18,199]. Probiotic administration has beneficial effects on the host, including increased adipose tissue lipolysis. Anorexigenic peptides, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), are secreted as a result, leading to an enhanced glucose tolerance and greater energy utilization [200][201][202]. In addition, treatment with probiotics decreased the expression of the main molecules involved in intestinal microflora inflammation and bacterial translocation, nucleotide-binding oligomerization domain-containing protein 1 (NOD-1) and CD-14 [192]. Treatment with probiotics significantly reduced the adipocyte surface area in obese mice, but the values were still outside the norm [192].
A study by Fabersani et al. showed that the Lactobacillus fermentum (CRL1446) strain induced a decrease in the production of leptin in adipose tissue [94]. In animal studies, this strain has antioxidant, hypoglycemic and hypocholesterolemic properties, making it an interesting alternative in the treatment of obesity, which is characterized by elevated levels of leptin in the serum [203,204].
A study by Le Barz et al. showed that mice fed the high-fat high-sucrose (HFHS) diet and treated with Lactobacillus plantarum (Lb38), Lactobacillus rhamnosus (Lbl02) or Bifidobacterium animalis ssp. lactis (Bfl41) exhibited a significant decrease in weight gain compared with the control group [205]. Lbl02 and Bf141 significantly reduced visceral obesity, and improved insulin sensitivity and glucose tolerance in HFHS-fed mice [205]. The applied probiotics reduced the concentration of pro-inflammatory chemokines (MCP-1 and RANTES) [205]. Long-term administration of Lbl02 and Lb38 significantly lowered the plasma leptin concentration compared with the control group [205]. Lbl02 and Bfl41 showed a tendency to reduce HFHS-induced lipid accumulation in the liver [205]. The gene expression of zonula occludens 1 (zo-1) and occludin, which code for key tight-junction proteins controlling epithelial integrity, was greatly elevated after Lbl02 therapy. Mucins 2 and 3 (muc2 and -3) gene expression was also raised following Lbl02 therapy, implying that the gut barrier could be strengthened by increasing mucus-layer thickness [205]. Thiennimitr et al. showed that probiotics Lactobacillus paracasei (HII01), prebiotic xylooligosaccharide (XOS), and synbiotics reduce intestinal dysbiosis and enteritis, leading to improved metabolic dysfunction in obese insulin-resistant rats [206].
Numerous studies have shown that dysbiosis, small intestinal bacterial overgrowth and increased intestinal permeability have a role in the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), both of which are closely linked to MS [207][208][209][210]. Dysbiosis was manifested in these disorders by an increase in Enterobacteriaceae and Proteobacteria and a decrease in Bacteroidetes [208]. The specific composition of gut microbiota may play a role in both the inflammatory and fibrosis responses in patients with NAFLD [211]. In patients with NASH, an increase in the numbers of Bacteroides has been shown, and a higher degree of fibrosis has been observed in patients with an increased amount of Ruminococcus [212,213].
A meta-analysis showed that treatment with Lactobacillus acidophilus, a mixture of Lactobacillus acidophilus and Bifidobacterium lactis, and Lactobacillus plantarum for 3 to 12 weeks lowered total and low-density lipoprotein (LDL) cholesterol concentrations compared with a placebo [214][215][216]. On the other hand, no effect of Lactobacillus helveticus and Enterococcus faecium on cholesterol concentrations was demonstrated [214]. Studies found no significant differences in LDL cholesterol in women with GDM between a group with supplementation of Lactobacillus salivarius and a placebo group [120]. In a research review by Okesene-Gafa et al. it was observed that taking probiotics may be associated with a slight reduction in TG and total cholesterol [115]. In a study by Babadi et al., probiotic capsules containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum and Lactobacillus fermentum reduced the concentration of TG, VLDL cholesterol, and the total/HDL cholesterol ratio while increasing HDL cholesterol levels [114].
NAFLD is strongly associated with obesity and thus closely related to the elements of MS (abdominal fat distribution, IR, diabetes, dyslipidemia, and hypertension) [217][218][219][220][221][222]. Preventing the development of NAFLD and NASH may contribute to reducing the risk of developing MS in the future.

Probiotics and the Prevention of the Development of MS
The studies suggest that the intestinal microbiota is a key player in the development of a chronic low-grade inflammatory state associated with MS [206]. The relationship between gut microbiota and the onset of metabolic inflammation related to obesity, IR and T2DM has been demonstrated [223,224]. Metabolic endotoxemia, which is caused primarily by the Gram-negative bacterial membrane component-LPS, is a critical event in the development of these conditions [224,225]. Through metabolic pathways, LPS leads to pro-inflammatory changes (increases in TNF-α, IL-1β and IL-6, leptin and resistin, plasminogen activator inhibitor-1 and C-reactive protein) and induces IR [226].
It has been noted that specific probiotics may, apart from their immunomodulatory and metabolic effects, modulate the intestinal microflora [12]. For these reasons, probiotics may play an important role in immunomodulation to help prevent the low-grade chronic inflammation associated with MS [4,94,226].
Inflammatory reactions in the gut can occur through activation of the TLR pathway, degradation of the IkB kinase, and release of nuclear-kappa B factor (NF-kB), which activates the pro-inflammatory cascade [227,228]. Several probiotic strains such as Lactobacillus rhamnosus or Lactobacillus casei have been shown to be effective in preventing IkB breakdown and thus reducing the release of pro-inflammatory molecules [229,230].
SCFAs such as acetate, propionate, and butyrate can be catabolized by probiotics from complex polysaccharides from the diet [231]. These substances are thought to help with metabolic disorders associated with MS. SCFAs show significant anti-inflammatory potential by reducing IR, and increasing the secretion of the protective GLP-1, which stimulates insulin release and improves β-cell function [142]. A study by Yadav et al. showed that acetate can suppress insulin signaling in adipocytes, inhibiting fat accumulation in adipose tissue [126].
It is important not only to take probiotics, but also other substances which affect probiotics bioavailability. Therefore, further work should pay attention to additional aspects including plasma concentrations of substances such as beta glucans and curcuminoids in pregnant women, which may affect probiotic absorption and increase the well-being of the gut microflora [232,233]. Vitamin C taken with probiotics may multiply their beneficial effect by reducing oxidative stress and postponing the chronic inflammation associated with the development of chronic diseases, including MS [234]. In addition, a proper diet rich in whole grains should be beneficial and could impact the microbiota profile in these patients [232].
Our study has some limitations. This work is not a systematic review and publications covering animal studies were included.

Conclusions
Pregnancy is said to be "a window to future health" as the occurrence of characteristic complications during pregnancy may trigger a vascular or metabolic risk of developing civilization diseases in the future life of the mother.
Even modest reductions in maternal glucose levels in nondiabetic women, especially those at high risk of GDM, may decrease the risk of developing maternal MS in the future. Effective postpartum follow-up of patients diagnosed with GDM is essential since GDM may progress to T2DM and MS, both of which are major public health problems. Pregestational obesity is predictive of progression to MS, while patients with high FPG and insulin requirements during pregnancy are at an increased risk of developing T2DM. Targeting and identifying high-risk individuals might delay and possibly prevent MS and T2DM. Knowledge about eventual interactions between the gut microflora in GDM and the host could be a potential therapeutic approach to improve health outcomes in women with GDM. A synergistic approach involving both probiotic supplementation and lifestyle modification At the present time, there is no consensus regarding the effectiveness of symbiotic or probiotic supplements in GDM management due to limited evidence. Further high-quality studies of longer duration are required to determine the optimal dose, safety and the optimal composition of probiotics used in the group of patients at risk of developing MS. Additional research on the efficacy of probiotics for lipid management is also warranted. At the present time, there is no consensus regarding the effectiveness of symbiotic or probiotic supplements in GDM management due to limited evidence. Further high-quality studies of longer duration are required to determine the optimal dose, safety and the optimal composition of probiotics used in the group of patients at risk of developing MS. Additional research on the efficacy of probiotics for lipid management is also warranted. The development of obesity, NASH and NAFLD may contribute to the onset of MS in the mother in the future.
The occurrence of PE during pregnancy may be an early warning sign of metabolic complications, described in the literature as "a window to future health". Women who have been diagnosed with metabolic disorders in pregnancy should be monitored in the puerperium and later in life for the development of these disorders. In patients with a history of PE, it is worth recommending a lifestyle change, reduction of excess body weight and regular medical examinations, which can prevent them from developing MS. It can be hypothesized that probiotics may reduce the risk of PE by modulating blood pressure and reducing inflammation, and more research is needed to elucidate their mechanisms of action and their safety for mother and child. Attention should be paid to reports on the possibility of increasing the risk of PE by taking probiotics and conducting research with due care.