Jin-Fang Hu,Jun Xing＊,Yan-Fang He

1Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,China.

Abstract Currently,the influence of change in the intestinal flora on the human body has become a popular topic for clinical research.Several studies show that the nutritional balance,physiological metabolism,immune protection,and even the occurrence and development of various chronic diseases are related to the change in intestinal flora.This chapter focuses on the changes in the intestinal microflora in pregnant women and the impact on the health of their offspring in order to provide some theoretical basis for clinical guidance.

Keywords:Pregnancy,Overweight,Obesity,Intestinal flora,Chronic disease

Background

In recent years,the prevalence of obesity during pregnancy has been increasing,and development of obesity during pregnancy has also increased.The incidence of gestational hypertension is 2-21 times higher in obese pregnant women than in normal weight pregnant women.The incidence of gestational diabetes is 1.5-20 times higher among obese pregnant women than in normal weight pregnant women.The proportion of postpartum hemorrhage,dystocia and cesarean section also increased correspondingly [1].There are many factors of obesity in pregnancy,such as dietary pattern,lack of exercise,and consciousness solidification;among these,the issue of intestinal flora is of concern.The intestinal flora is closely related to obesity.The intestinal flora can directly participate into the absorption and utilization of lipids.An imbalance in the intestinal flora can lead to increased fat storage via several mechanisms,leading to obesity,which,in turn,aggravates the disorder of intestinal flora;there are several changes in the intestinal flora during pregnancy.With increasing gestational age,the diversity of the intestinal flora will decrease.Here,we aimed to explore the influence of overweight during pregnancy on the intestinal flora as well as the maternal and birth outcome.

Human intestinal microecology and changes in the intestinal flora during pregnancy

A microecological system inhabits the human intestine that has been established at the time of birth and continues to develop with normal biologic growth.There are 1,014 intestinal microflora in the human body,1,000-1,150 bacterial species,and 3.3 million genes that equal to 150 times that of human genes [2,3],Bacteroides and pachytene account for ＞90% of the normal flora,followed by Proteus,while actinomycetes,fusobacteria,verrucosa,cyanobacteria,spirocheta,vadinbe97,etc.account for a small part of the human flora [4].More than 35% of the enzymes used for metabolism in the human body are produced by the normal flora in the intestine [5].The intestinal microflora may also contribute to the development of obesity;further,it has been hypothesized that intestinal microflora may be the mechanism underlying the intergenerational transmission of obesity risk [6,7].The maternal intestinal microbiota may increase the risk of infant obesity via utero programming effects[8]or the vertical transfer of exogenous intestinal microbiota between mothers and infants during birth and breast feeding[9,10].

Pregnancy is a special physiological period for women.During this period,a series of physiological and endocrine changes take place in the body.These effects indirectly affect the intestinal flora,resulting in certain changes in the composition and structure or the abundance of the flora.Koren [11]and other experts have found that during the whole pregnancy,with the increase in gestational age,from early to late pregnancy,the abundance of Proteus and actinomycetes increased,the overall α diversity of intestinal flora decreased,and β diversity increased.The structure of the intestinal microflora in early pregnancy was similar to that in non-pregnant women.This is because the hormone level of pregnant women changes significantly with the growth and development of the fetus,while the microbiota living in the human body changes significantly with environmental factors,such as pH,humidity,and temperature,and the physiological changes in various organs and systems of the mother.However,another study on pregnant women by Diguilo et al.[12]was not repeated.The differences in the results of the intestinal flora study may be related to the differences in the statistical methods,sampling methods,gestational age,amplification regions,etc.Specific conclusions need further verification.

The composition of intestinal microflora and the metabolism of short chain fatty acids (SCFA) are abnormal in pregnant overweight people.The components of SCFA include acetate,acetate,propionate,and butyrate and can affect the metabolism of glucose,lipid,and cholesterol.A long-term high-fat diet leads to an abnormal SCFA metabolism in the intestine,and the content of acetic acid will increase,leading to increased food intake,triglyceridemia,heterotopic deposition of lipids in the liver and skeletal muscle,and insulin resistance.Intestinal flora disorder can inhibit the activities of peroxisome proliferators’activated receptor coativator-1α (PGC-1α) and adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) induced by fasting induced adipose factors (FIAF),increase the activity of lipoprotein lipase(LPL),cause the accumulation of a large number of adipose tissue,promote the expression of inflammatory factors,lead to the occurrence of chronic inflammatory response,damage the function of a large number of endothelial cells in the body,further increasing the vascular permeability and cause vascular.The dysfunction of systolic and diastolic regulation increases the possibility of intravascular thrombosis that is the pathological basis of pregnancy-induced hypertension,preeclampsia,and other diseases.The occurrence of gestational diabetes is also related to chronic inflammation in the body during pregnancy.Excessive weight gain during pregnancy can change the structure of the intestinal flora,increase the number of opportunistic bacteria,and increase the number of Gram-negative bacteria,resulting in the increase of intestinal lipopolysaccharide (LPS) and induction of chronic inflammation.The intestinal flora can participate in the catabolism process of most carbohydrates in the human body and can decompose and ferment monosaccharides,starch,and food fiber for human use.Chronic inflammation in patients with excessive weight gain aggravates the insulin resistance in pregnant women during pregnancy,thus increasing the risk of gestational diabetes.As shown in the Figure 1,obesity,intestinal flora disorder,and chronicinflammatory state of the body form a vicious circle.

The effect of excessive weight gain on the intestinal flora of the mother

The change in the intestinal microecology is considered an important factor in obesity.The global burden of disease pointed out that [13]the structure of the intestinal flora in the intestine of obese individuals changed significantly,and the diversity decreased.Through the interaction with intestinal tissues,intestinal endocrine cells were activated,active factors were released,the barrier effect of intestinal tract was reduced,and the intestinal tract had lower inflammation for a long time,promoting obesity.Compared to that in the healthy population,the intestinal microecological structure in the obese population changed significantly,showing that the relative abundance of Bacteroides decreased and that of pachytene increased,thus enhancing the ability of the obese population to obtain energy from the diet.However,the relative abundance of Bacteroides will increase when obese individuals lose weight by reducing the content of fat or carbohydrate in their diet[14].Ferrer [15]and other researchers investigated the intestinal microflora from obese and lean people and confirmed that the relative abundance of Bacteroides in the intestinal tract of obese people decreased by analyzing the consistent gene sequence of 22mbp,the diversity of 16SrDNA amplification and the expression spectrum of 613 different proteins.An animal experiment by Ley et al.showed that the proportion of F/B in the intestine of obese mice increased[16],while Duca et al.[17]transplanted the high ratio F/B in the intestine of obese rats into the intestine of sterile mice and successfully reproduced the obese phenotype.The above animal experimental data show a certain relationship between obesity and intestinal flora;further,the relationship between F/B in obese individuals may be specific.

Pregnancy is a special physiological period for women.In addition to maintaining their own body metabolism,the daily food eaten by women after pregnancy not only provides nutrients for the growth and development of the fetus in the body,but also affects the short-term and long-term health of the mother and child.Relevant studies have shown that if the weight of pregnant women increases too rapidly during pregnancy,the diversity in the intestinal flora structure will be significantly lower than that in normal pregnant women [13].Stanislawski et al.[18]pointed out through clinical research that the intestinal flora structure of normal pregnant women on the 4th day after delivery was not significantly difference with reasonable weight gain during pregnancy;however,in comparison,the intestinal flora diversity of obese pregnant women before pregnancy decreased significantly after delivery [19].In addition,the diversity in the intestinal flora during late pregnancy is significantly related to excessive weight gain during pregnancy,but not to the age before pregnancy,body mass index,pregnancy,and delivery.Wang Ying [20]and other experts analyzed the fecal samples of 62 pregnant women with different weight gain levels in the third trimester(36.82±2.19 gestational weeks)and discussed the influence of weight gain during pregnancy on the community structure,diversity,and species richness of the intestinal flora.It was found that the intestinal microflora structure of pregnant women with excessive weight growth was changed,the alpha diversity was significantly reduced,and the alistipes spp.abundance was significantly increased in pregnant women with normal weight growth.Alistipes spp.can produce anti metabolite sulfobacin B that can reduce the immune rejection of grafts by inhibiting the production of tumor necrosis factor (TNF) and nuclear transcription fator-kappa B (NF-kB) [21].The experimental research of Stani Slawski [19]and other experts have shown that the abundance of blautia spp.in intestinal flora increased significantly in pregnant women with excessive weight gain during pregnancy,and this bacterium was also confirmed to be related to obesity and type II diabetes in relevant experiments[22].Collado et al.[23]found that the abundance of B.fragilis sp.and bacteroides in the intestinal flora of the overweight pregnant women in the late pregnancy increased significantly,while Bifidobacterium spp.decreased.Another study [24]showed that the abundance of E.coli spp.,C.leptum spp.,and St aphyloccus aureus spp.in the intestinal flora of pregnant women in the second trimester increased with excessive weight gain during pregnancy,while the abundance of akkermansia muciniphi spp.,bifido bacterium spp.,and Bacteroides decreased.The intestinal flora is affected not only by genetic factors,but also by various other factors,such as diet,mood,living environment and lifestyle.Therefore,it is not surprising that different experimental studies have reached different conclusions regarding the impact of intestinal flora on weight gain during pregnancy.

The effect of excessive weight gain on the intestinal flora of the offspring

During pregnancy,the intestinal flora of the mother may be transmitted to the offspring via various ways,such as cord blood,placenta,and amniotic fluid [25].The colonization of infant intestinal flora will change with the structural change of the maternal intestinal flora.The intestinal flora of obese pregnant women changes the nutritional environment and metabolic environment of the fetus due to the structural disorder and metabolic function abnormality that affects the weight of the fetus at birth,resulting in increased birth rate,ultimately leading to the risk of coronary heart disease,high blood pressure,diabetes,and other chronic diseases in the offspring during adulthood.Some studies have shown that the number of bifidobacteria and lactobacilli in the intestines of the newborns delivered by the super recombined pregnant women before pregnancy is lower than that in newborns delivered by normal pregnant women before the pregnancy.Many experts have indicated that the intestinal microflora structure of obese pregnant women is significantly different from that of normal weight pregnant women.Collado et al.[26]found that the fecal microflora structure of overweight pregnant women is significantly different from that of normal pregnant women.The results show that in the intestinal microflora of overweight pregnant women,Staphylococcus,Bacteroides,and other microflora occupy a large proportion of Clostridium,Staphylococcus,and mucoprotein Ekman bacteria in the fetal intestine of normal weight pregnant women is relatively small.In addition,some studies have pointed out that delayed lactation is positively correlated with the BMI.Compared to that in normal weight mothers,the incidence of physiological lactation difficulties in obese mothers is high [27],resulting in a shorter lactation period and low breastfeeding rate that changes the intestinal flora of infants.Therefore,some scholars have proposed the hypothesis that excess weight gain in mothers indicates an increased risk of chronic disease in offspring that may be mediated by the sharing of characteristic microbiota between mothers and infants during pregnancy or childbirth[28].At present,there is no consensus about the effect of excess weight gain during pregnancy on the intestinal flora of the offspring;this subject requires further research and exploration.

The influence of overweight during pregnancy on the mother’s health and the pregnancy outcome

In the 1980s,Barker and other scholars proposed the theory of “development essential origins of health and disease” where they pointed out that some serious health problems in the later stage of human life may originate in the early stage of postnatal life,even being traced back to the fetal period[29].Thus,in addition to genetic factors,if physical life experiences adversely affect the early stage of development,such as over nutrition,under nutrition,and poor gestational environment,it will increase the risk of obesity,cardiovascular disease,diabetes and other chronic diseases in adulthood.Therefore,a good start in the early stage of life is crucial for a healthy life.Overweight and obesity in pregnancy are considered important risk factors for chronic diseases.Therefore,a good beginning early in life is vital for the health of the entire life.Overweight and obesity are considered major risk factors of chronic diseases and are widespread across the globe.The proportion of overweight and obese pregnant women is increasing each year.The physical health,weight gain,nutritional status,and life style of mothers during pregnancy are considered the initial factors that affect their and their child’s life and health.

Excessive weight gain during pregnancy will affect the health of two generations because it will affect both the mother and her children;it also has the potential of affecting the third future generation.Excessive weight gain during pregnancy can not only increase the pregnancy-related complications and long-term risk of chronic diseases,but also cause a series of health problems,such as long-term obesity and type 2 diabetes in the offspring,thus leading to obesity and the transmission of chronic diseases from one generation to the next generation.The fat in pregnant women with excessive weight gain during pregnancy is not sensitive to insulin and can thus cause insulin resistance,reduce the effect of islet β cells,and increase the probability of gestational diabetes mellitus due to abnormal glucose tolerance.Pregnant women with excessive weight gain during pregnancy have an increased incidence of complications,such as pregnancy-induced hypertension.Some studies have shown that the incidence of pregnancy-induced hypertension in obese women is 3-40 times higher than that in normal-weight women[30].The number of pregnant women with hyperlipidemia during pregnancy was significantly higher than that of normal pregnant women.In recent years,studies have shown that fat accumulation can cause dysfunction of the vascular endothelial cells,thus reducing the secretion of prostacyclin,resulting in the production of peroxidase,making the occurrence of vasoconstriction and platelet aggregation,and ultimately causing placental abruption [31].In addition,the large accumulation of fat in the vulva and the pelvis causes a relatively narrow birth canal and weakens the contraction of abdominal and diaphragm muscles;the parturient is more likely to have prolonged labor,dystocia,and delayed delivery,and the chances of cesarean section rate are also relatively increased.In addition,overweight pregnant women are believed to secrete more leptin that can inhibit the start of natural labor and contraction of the uterine smooth muscle mediated by oxytocin,leading to uterine atony.In addition,pregnant women with excessive weight gain during pregnancy are more likely to retain the excess weight after childbirth or gain more weight with postpartum centripetal adipose tissue further increasing;this leads to increased risk of complications during pregnancy and raises the chances of postpartum long-term risk of diabetes,hypertension,and cardiovascular disease.

Owing to factors,such as physical obesity and excessive nutrition,pregnant women with excessive weight gain in pregnancy will be heavier,give birth to children who weigh more,and the incidence of long-term obesity of their offspring will also increase.A meta-analysis of the relationship between maternal obesity during pregnancy and obesity in infants showed that the proportion of infants born to mothers with obesity was 33%higher than that of those born to normal weight mothers [32].If a 10-13-year-old is overweight,he/she is 65% likely to become overweight as an adult [33].Overweight children have a higher prevalence of hypertension,sleep apnea,coronary artery disease,and type 2 diabetes after adulthood.Placenta is the basis of nutrient and blood exchange between mothers and infants that plays a role of material transport.The placenta can participate in the transportation of oxygen,nutrients,and other substances between the two under the influence of mother and infant hormones.If the weight of pregnant women increases too rapidly during the pregnancy,the excess triglyceride in the plasma will pass through the placenta to the fetal body that will affect the balance of the fetal environment and increase the incidence of obesity and even giant children.

In conclusion,excessive weight gain in pregnant women is a serious public health problem in worldwide.Excessive weight gain during pregnancy will not only affect the perinatal outcome of the mother and child,but also affect their long-term health,even the health of the next generation.Thus,there is a need to actively seek the correct clinical management and intervention methods for weight management during pregnancy to effectively reduce adverse pregnancy outcomes and long-term chronic diseases.The imbalance in the intestinal microflora of obese pregnant affects infants and impairs their health even in later life in terms of imbalance in the intestinal microflora.This results in a serious metabolic imbalance cycle that affects human health and warrants global attention.Women of childbearing age need to maintain a healthy weight,avoid excessive weight gain during pregnancy,develop healthy and reasonable eating habits,and perform sufficient physical activity.In addition,pregnant women can also intervene and regulate the imbalance in their gut bacteria with appropriate supplementation of probiotics to avoid excessive weight gain in infants.However,the research on probiotics is not comprehensive at present,and several clinical experiments are needed.In the future,epidemiological investigation and microbiological study of human and animal models are needed on the intervention of intestinal flora and prediction of overweight in children to lower the risk of overweight and related chronic diseases in children.