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García-Montero, C.; Fraile-Martinez, O.; Rodriguez-Martín, S.; Saz, J.V.; Rodriguez, R.A.; Moreno, J.M.P.; Labarta, J.R.; García-Honduvilla, N.; Alvarez-Mon, M.; Bravo, C.; et al. Prebiotics for Pregnancy and Its Complications. Encyclopedia. Available online: https://encyclopedia.pub/entry/42388 (accessed on 15 April 2024).
García-Montero C, Fraile-Martinez O, Rodriguez-Martín S, Saz JV, Rodriguez RA, Moreno JMP, et al. Prebiotics for Pregnancy and Its Complications. Encyclopedia. Available at: https://encyclopedia.pub/entry/42388. Accessed April 15, 2024.
García-Montero, Cielo, Oscar Fraile-Martinez, Sonia Rodriguez-Martín, Jose V. Saz, Rocio Aracil Rodriguez, Juan Manuel Pina Moreno, Javier Ruiz Labarta, Natalio García-Honduvilla, Melchor Alvarez-Mon, Coral Bravo, et al. "Prebiotics for Pregnancy and Its Complications" Encyclopedia, https://encyclopedia.pub/entry/42388 (accessed April 15, 2024).
García-Montero, C., Fraile-Martinez, O., Rodriguez-Martín, S., Saz, J.V., Rodriguez, R.A., Moreno, J.M.P., Labarta, J.R., García-Honduvilla, N., Alvarez-Mon, M., Bravo, C., De Leon-Luis, J.A., & Ortega, M.A. (2023, March 21). Prebiotics for Pregnancy and Its Complications. In Encyclopedia. https://encyclopedia.pub/entry/42388
García-Montero, Cielo, et al. "Prebiotics for Pregnancy and Its Complications." Encyclopedia. Web. 21 March, 2023.
Prebiotics for Pregnancy and Its Complications
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The term “prebiotics” was first coined by professors Emeritus Marcel Roberfroid and Glenn Gibson in a 1995 publication, where they explained the selective growth of colonic bifidobacterials boosted by the intact fibrous oligosaccharide inulin. They explained prebiotics as “nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health”.

prebiotics pregnancy newborn

1. What Are Prebiotics and What Types Are There?

The term “prebiotics” was first coined by professors Emeritus Marcel Roberfroid and Glenn Gibson in a 1995 publication, where they explained the selective growth of colonic bifidobacterials boosted by the intact fibrous oligosaccharide inulin. They explained prebiotics as “nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health” [1].
Unusable by human cell enterocytes, prebiotics are therefore microbe food, usually consisting of plant dietary fibers with complex carbohydrates (short and long chain β-fructans [fructooligosaccharides, FOS and inulin], lactulose, and galactooligosaccharides, GOS) which can help the host flora, promoting their growth and/or boost supplemented probiotic effects. It is worthy of note that prebiotics can limit the growth of potential pathogenic bacteria as well. In 2008, the definition was refined to “dietary prebiotics”, which were described as “a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health” [2].
This more recent definition is due to the nature of these bioactive components, not only being carbohydrates but also some polyphenols such as flavonols. The classification of prebiotics involves five groups: fructans (FOS and inulin), GOS, resistant starch and glucose-derived oligosaccharides (e.g., polydextrose), pectin-derived oligosaccharides, and non-carbohydrate oligosaccharides entailing polyphenols (e.g., cocoa flavonols). All of these primarily stimulate Lactobacilli and Bifidobacteria, as well as Enterobacteria, Bacteroidetes and Firmicutes [3].
Furthermore, currently the term “synbiotic” is commonly used as well, referring to dietary supplements that contain both pre- and probiotics. In 2019, the ISAPP updated its definition to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host” [4].

2. Prebiotics for Healthy Pregnant Women

In a 2018 meta-analysis, little evidence was collected about the efficacy of prebiotics, but in combination with probiotics it was concluded that the risk of preterm birth was not increased or decreased due to the intake of these compounds during pregnancy [5]. Despite this argument, other objectives can be pursued to contrast the benefits of prebiotics in pregnancy compared to not using them.
A primary reason to consider the recommendation to take prebiotics in pregnancy lies in the changes in the nutritional requirements of a pregnant woman. Sheridan et al. explained that gut microbiota is highly altered in this period of a woman’s life, between the first and third trimesters, with an increase in the relative abundances of Proteobacteria and Actinobacteria, along with a decrease of bacterial diversity in general. With a view to promoting a healthy microbiota in this population, they then proposed that these microbial alterations should be addressed by designing more robust human studies with pro- and prebiotics applications [6].
In fact, pregnancy has been categorized by some authors as a “stressor” that reduces barrier function due to elevated serological markers of elevated intestinal permeability (as with zonulin or lipopolysaccharide), and they argue that this should be faced by restoring barrier function with supplements including prebiotics [7]. However, it should be mentioned that microbial changes during pregnancy can also be part of the immunosuppression that occurs in maternal utero to allow paternal antigens and to prevent the rejection of the embryo. To achieve this, the mother should have increased IgA and phagocytic cell concentrations and diminished vaginal pH thanks to Lactobacilli. These favorable changes are in relation to preventing vertical infections at the moment of birth [8]. Thus, it seems important to protect the vaginal microbiota.
In a randomized double-blind placebo-controlled trial with maternal intake FOS programming during the third trimester, there was a significant increase in fecal Bifidobacterium spp. and Bifidobacterium longum in the intervention group at the end of pregnancy [9]. Another randomized controlled trial in Indonesian pregnant women evaluated the administration of milk fortified with prebiotic, probiotic, DHA and micronutrients, observing notable increases in the fecal concentration of the organism used as the probiotic [10]. Therefore, this evidence indicates that probiotic colonization is successful when combined with prebiotics and other micronutrients.
Another randomized controlled trial assessed the effectiveness of synbiotic food in pregnant women for 9 weeks and its impact on insulin levels. Synbiotics containing Lactobacillus sporogenes and inulin showed significant differences with lower serum insulin levels in the intervention group versus the control group [11].
A meta-analysis regarding the safety of pro- and prebiotics use in pregnancy and lactation found that adverse effects were rare and normally related to changes in stool consistency and did not pose risks to the mother’s or child’s health [12]. It is also true that more scientific evidence is needed before drawing any relevant conclusions in the administration of prebiotics in healthy pregnant women. However, this preliminary evidence seems to be encouraging regarding the potential use of prebiotic supplementation in pregnancy. Nevertheless, it would be fruitful to study which groups of women would benefit the most and how to optimize prebiotic formulas and synbiotics in more detail.
Some highlights can be summarized in Figure 1.
Figure 1. The effect of prebiotics on pregnancy.

3. Prebiotics for Pregnancy Complications

Many pregnancies face adversity with hypertension and metabolic problems such as gestational diabetes mellitus, obese pregnancy, or metabolic syndrome. All of these complications may have an impact on maternal health on the mother’s and also on newborn’s health. In fact, these complications have been related to infant allergy, asthma or skin problems, as will be discussed later.
Many studies are in agreement that pro-, prebiotics, and synbiotics have health benefits in terms of preventing adverse pregnancy outcomes. In this line, Sohn and Underwood reviewed that dysbiosis is a key factor involved in increasing the risk of pre-eclampsia, diabetes, infection, preterm labor, and (later) childhood atopy. It has been demonstrated that this maternal dysbiosis goes hand in hand with neonatal dysbiosis, which causes colic in infants. Therefore, the administration of pro- and prebiotics during pregnancy and lactation was recommended as a safe option to optimize these periods of life and prevent adverse outcomes [13].

3.1. Obese Pregnancy

Obesity in pregnancy entails a maternal body max index ≥30. Obese women may suffer from dysbiosis and metabolic impairment, which can cause damage to the fetus or even a miscarriage. This condition can increase the risk of other pregnancy complications such as gestational diabetes mellitus, hypertension, preeclampsia, venous disease, or even venous thromboembolism. The consequences for the fetus can be premature birth, neonatal death, and the increased risk of metabolic disorders in later life.
Wiedmer and Herter-Aeberli narrated the intergenerational cycle of obesity: the mother’s dysbiosis entails shifts in maternal metabolites and the placental microbiome, having implications in fetal programming. The risk of obesity for the child is very high. For this issue, there have been more animal models examining prebiotics use than human studies, which normally only evaluate probiotics. Prebiotic supplementation in preclinical models has demonstrated a clear decreased risk of obesity in the offspring, but more evidence is required [14]. Zhou and Ziao summarized the mice and rat models of maternal prebiotic exposure to GOS, inulin, FOS, oligofructose, caprine milk oligosaccharides, and some derivatives of all of these. The effects observed on offspring included reduced symptoms of allergic asthma, the prevention of food allergies, a lessening in the severity of atopic dermatitis, less fat mass, better immune response, and reduced obesity risk [15].
Prebiotic use has yet to be explored with regard to reducing the obesity risk in children from obese pregnancies, but they may cause an amelioration of maternal metabolic health by the production of probiotic short chain fatty acids. Other authors agree that the future research ought to be focused on intervention strategies combining B vitamin deficiencies and targeting gut dysbiosis in obese mothers through pro- and prebiotics [16].

3.2. Gestational Diabetes

Women with GDM exhibit pancreatic β-cell dysfunction on a background of chronic insulin resistance during pregnancy, along with changes in other systems and organs [17]. This problem normally appears only during pregnancy but can also have metabolic consequences for the offspring. The management of multifactorial disease gestational diabetes mellitus (GDM) is also contemplated from the perspective of dysbiosis. Some authors propose soy oligosaccharides as intestinal modulators involved in the alleviation of insulin resistance and other related pathological events such as oxidative stress in women with GDM [18]. They promote the advantages of certain foods such as soy, which has prebiotics, but also has polyphenols that can form a synergy to enhance its effects [19]. Similarly, the use of synbiotics have also shown notable benefits on the clinical management of GDM. According to a meta-analysis conducted by Zhou et al. [20], this type of intervention has demonstrated significant improvements on glucose and lipid metabolism, as well as having an anti-inflammatory and antioxidant effect on diet controlled GDM patients, reducing the risk of fetal hyperbilirubinemia, fetal macrosomia, and limiting newborn weight. Similarly, a systematic review and meta-analysis also demonstrated that the use of synbiotics ameliorated insulin resistance in GDM women [21]. However, a recent meta-analysis undertaken by Łagowska et al. [22] found that similar benefits were observed when either probiotics or synbiotics were used, this probably resulting from the fact that not all Lactobacillus and Bifidobacterium strains have the ability to ferment certain prebiotics used. Thus, more efficient synbiotic combinations arises as a promising and potential field of research to evaluate in pregnant women, and particularly in GDM patients.

3.3. Hypertension and Preeclampsia

Preeclampsia is a kind of complication characterized by high blood pressure and proteinuria, leading to kidney and multisystem damage. It also entails a danger to the fetus. Gynecological studies regarding a well-functioning vaginal microbiome indicate a benefit of this depending on the gut microbiome. Pro- and prebiotic use stimulate gut-derived metabolites such as butyrate that attenuate inflammation [23]. Other authors have also mentioned the potentiality of pro- and prebiotics in tandem in a context of nutritional interventions to manipulate oral microbiota as well. They found that this microbial ecosystem is also a key to cardiovascular health during gestation, and therefore may aid in the treatment and prevention of hypertensive pregnancy disorders including hypertension and preeclampsia [24]. Conversely, in a recent systematic review and meta-analysis, Movaghar et al. [25] did not find any notable benefits from probiotics or synbiotics administration in women with hypertensive disorders and GDM, although due to the limited number of studies available, further efforts are required.

3.4. Bacterial Vaginosis

Other impairments in vaginal microbiota can provoke the occurrence of chlamydia. This imbalance can be present during pregnancy and cause premature labor or spontaneous miscarriage. This is another reason why an increasing number of scientists and doctors are contemplating the idea of nutritional strategies that help prevent this damage. Synbiotics consumption seems to effectively prevent recurrent urinary tract infections in women [26]. In the case of bacterial vaginosis, they suggest that a combination of probiotics and prebiotics should be applied instead of using antibiotics, which is risky for a pregnant woman. Systematic reviews found that pre/probiotic regimens have even higher cure rates than antibiotics [27]. This would also provide greater protection to the mother and the fetus.

3.5. Perinatal Mental Health

Currently, there are clinical trials exploring the role of gut microbiota modulators on mental health (i.e., Ecologic Barrier© -NCT04951687-) in the general population, suggesting a complex but an evident relationship between the gut and the brain. It is necessary that mental health in postpartum women be addressed. Perinatal mood disorders are common disabling conditions that can be treated through the so-called gut-brain axis. According to systematic reviews, promising limited evidence of lower incidence of anxiety and depressive symptoms in the perinatal period has been reported when supplementing with pro-, pre-, and synbiotics during pregnancy [28][29].

References

  1. Gibson, G.R.; Roberfroid, M.B. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. J. Nutr. 1995, 125, 1401–1412.
  2. Gibson, G.R.; Scott, K.P.; Rastall, R.A.; Tuohy, K.M.; Hotchkiss, A.; Dubert-Ferrandon, A.; Gareau, M.; Murphy, E.F.; Saulnier, D.; Loh, G.; et al. Dietary prebiotics: Current status and new definition. Food Sci. Technol. Bull. Funct. Foods 2010, 7, 1–19.
  3. Davani-Davari, D.; Negahdaripour, M.; Karimzadeh, I.; Seifan, M.; Mohkam, M.; Masoumi, S.J.; Berenjian, A.; Ghasemi, Y. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods 2019, 8, 92.
  4. Swanson, K.S.; Gibson, G.R.; Hutkins, R.; Reimer, R.A.; Reid, G.; Verbeke, K.; Scott, K.P.; Holscher, H.D.; Azad, M.B.; Delzenne, N.M.; et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 687–701.
  5. Jarde, A.; Lewis-Mikhael, A.M.; Moayyedi, P.; Stearns, J.C.; Collins, S.M.; Beyene, J.; McDonald, S.D. Pregnancy outcomes in women taking probiotics or prebiotics: A systematic review and meta-analysis. BMC Pregnancy Childbirth 2018, 18, 14.
  6. Sheridan, P.O.; Bindels, L.B.; Saulnier, D.M.; Reid, G.; Nova, E.; Holmgren, K.; O’Toole, P.W.; Bunn, J.; Delzenne, N.; Scott, K.P. Can prebiotics and probiotics improve therapeutic outcomes for undernourished individuals? Gut Microbes 2014, 5, 74–82.
  7. Camilleri, M. Human Intestinal Barrier: Effects of Stressors, Diet, Prebiotics, and Probiotics. Clin. Transl. Gastroenterol. 2021, 12, e00308.
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  11. Taghizadeh, M.; Asemi, Z. Effects of synbiotic food consumption on glycemic status and serum hs-CRP in pregnant women: A randomized controlled clinical trial. Hormones 2014, 13, 398–406.
  12. Sheyholislami, H.; Connor, K.L. Are Probiotics and Prebiotics Safe for Use during Pregnancy and Lactation? A Systematic Review and Meta-Analysis. Nutrients 2021, 13, 2382.
  13. Sohn, K.; Underwood, M.A. Prenatal and postnatal administration of prebiotics and probiotics. Semin. Fetal Neonatal Med. 2017, 22, 284–289.
  14. Wiedmer, E.B.; Herter-Aeberli, I. The Potential of Prebiotic and Probiotic Supplementation During Obese Pregnancy to Improve Maternal and Offspring’s Metabolic Health and Reduce Obesity Risk-A Narrative Review. Front. Nutr. 2022, 9, 819882.
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  17. Plows, J.F.; Stanley, J.L.; Baker, P.N.; Reynolds, C.M.; Vickers, M.H. The Pathophysiology of Gestational Diabetes Mellitus. Int. J. Mol. Sci. 2018, 19, 3342.
  18. Fei, B.B.; Ling, L.; Hua, C.; Ren, S.Y. Effects of soybean oligosaccharides on antioxidant enzyme activities and insulin resistance in pregnant women with gestational diabetes mellitus. Food Chem. 2014, 158, 429–432.
  19. De Mendonça, E.L.S.S.; Fragoso, M.B.T.; de Oliveira, J.M.; Xavier, J.A.; Goulart, M.O.F.; de Oliveira, A.C.M. Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies. Antioxidants 2022, 11, 129.
  20. Zhou, L.; Ding, C.; Wu, J.; Chen, X.; Ng, D.M.; Wang, H.; Zhang, Y.; Shi, N. Probiotics and synbiotics show clinical efficacy in treating gestational diabetes mellitus: A meta-analysis. Prim. Care Diabetes 2021, 15, 937–947.
  21. Çetinkaya Özdemir, S.; Küçüktürkmen Paşa, B.; Metin, T.; Dinçer, B.; Sert, H. The effect of probiotic and synbiotic use on glycemic control in women with gestational diabetes: A systematic review and meta-analysis. Diabetes Res. Clin. Pract. 2022, 194, 110162.
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  27. Afifirad, R.; Darb Emamie, A.; Golmoradi Zadeh, R.; Asadollahi, P.; Ghanavati, R.; Darbandi, A. Effects of Pro/Prebiotics Alone over Pro/Prebiotics Combined with Conventional Antibiotic Therapy to Treat Bacterial Vaginosis: A Systematic Review. Int. J. Clin. Pract. 2022, 2022, 4774783.
  28. Desai, V.; Kozyrskyj, A.L.; Lau, S.; Sanni, O.; Dennett, L.; Walter, J.; Ospina, M.B. Effectiveness of Probiotic, Prebiotic, and Synbiotic Supplementation to Improve Perinatal Mental Health in Mothers: A Systematic Review and Meta-Analysis. Front. Psychiatry 2021, 12, 622181.
  29. Rackers, H.S.; Thomas, S.; Williamson, K.; Posey, R.; Kimmel, M.C. Emerging literature in the Microbiota-Brain Axis and Perinatal Mood and Anxiety Disorders. Psychoneuroendocrinology 2018, 95, 86–96.
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