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Children's intestinal bacteria

A must-read for pregnant women [More detailed than anywhere else] Changes in intestinal bacteria during pregnancy

Children's intestinal bacteria

2024.02.13

If you’ve been pregnant or know someone who has, you may remember that pregnancy dramatically changes your body.
Not only will you experience morning sickness or your belly get bigger, but your physical and mental health will also change dramatically.
Hormonal balance, immune function, and metabolic function are also part of this.

It may be hard to realize it until your belly actually starts to grow, but from the moment you become pregnant, your body and microbiome switch completely into “pregnancy mode.”

Yes, our bodies and bacteria work together to prepare for birth.
Not only do we need to pass on our microbiome to our babies, but we also need to help them grow healthy (1).

Today, I’d like to share what science knows about how your body’s microbiome (bacteria) changes during pregnancy and what you can do to pass on better bacteria to your baby.

I’ve put together this article about everything pregnancy-related, so it’s quite lengthy, so sit back and read it.

Table of Contents

  1. I’ve put together this article about everything pregnancy-related, so it’s quite lengthy, so sit back and read it.
  2. Microbiome and metabolic function during late pregnancy
  3. Pregnancy complications and the microbiome
  4. gestational diabetes mellitus (GDM)
  5. Preeclampsia (PE)
  6. Other
  7. Increase in bifidobacteria and lactic acid bacteria during late pregnancy
  8. Maternal microbiome and baby health
  9. Neurodevelopment
  10. metabolic development

The numbers in parentheses in the text refer to the reference numbers at the bottom of the article.

I’ve put together this article about everything pregnancy-related, so it’s quite lengthy, so sit back and read it.

Due to factors such as the trend toward older women giving birth, an increasing number of couples are trying to conceive.
It is believed that pregnancy is more likely to occur not just by stopping contraception, but also by adjusting lifestyle habits such as diet, sleep, and exercise, and is considered the first step to take before undergoing infertility treatment.

So, does the pre-pregnancy microbiome affect fertility and the health of the pregnant woman and her fetus?

Unfortunately, research in this area is still underdeveloped.
Currently, research is underway to examine the relationship between the vaginal microbiome (1) and the intestinal microbiome (2) and infertility.

There is also research (3) examining the intestinal bacteria of IBD (inflammatory bowel disease) patients during pregnancy. To reveal the secret, IBD patients’ inflammation levels decreased when they became pregnant, and as the pregnancy progressed, the diversity of their intestinal bacteria became closer to that of healthy pregnant women.
This suggests that pregnancy is safe for IBD patients and may even have benefits for their own health.

In any case, it can be said that when discussing the microbiome and the health of pregnant women and their fetuses, the influence of the microbiome before pregnancy must also be taken into account.

Microbiome and metabolic function during late pregnancy

Ruth E. Ley of Cornell University (then chair of the Department of Microbiology at the Max Planck Institute for Biological Studies) began studying the relationship between pregnancy and the microbiome shortly after giving birth.
A paper published in 2012 by her research team (4) became a landmark in the field of research exploring the relationship between pregnancy and the microbiome.

This study of 91 pregnant women in Finland showed that the gut microbiota of women in the third trimester is surprisingly similar to that of patients with metabolic disorders such as diabetes and obesity.
In the third trimester, many pregnant women worry that they will gain weight just by drinking water. However, this may be a mechanism to protect the baby.

However, this change is temporary during pregnancy and may be different from the mechanism of fat accumulation that occurs in obese patients, for example. This is a very interesting paper, so I would like to summarize the main points below.

  • The gut microbiota during early pregnancy (T1) resembles that of healthy non-pregnant women.
  • During the third trimester (T3), the diversity of gut bacteria decreases.
  • T3 increased insulin resistance, hyperglycemia, and elevated inflammatory markers. This low-grade inflammation may alter the composition of gut bacteria and alter the maternal metabolism in preparation for labor.
  • While the differences in gut bacterial composition between pregnant women in T3 were significant, the abundance of bacteria from the phyla Proteobacteria and Actinobacteria (the former is known to be associated with inflammation, and the latter is a group that includes Bifidobacteria) was generally increased. Conversely, the abundance of bacteria from the genus Faecalis, which is known to be associated with anti-inflammatory properties, was decreased.
  • However, the intestinal flora of the newborn child becomes closer to that of the mother’s T1.
  • When the T3 microbiome was transplanted into germ-free mice, they experienced weight gain and hyperglycemia compared with mice transplanted with T1 bacteria.

The findings of this paper showed that the microbiome plays a role in efficiently supplying energy to the fetus during pregnancy.
However, if this cooperation between pregnant women and bacteria does not work well, it can lead to various pregnancy complications.

Pregnancy complications and the microbiome

It is known that during pregnancy, the body deliberately lowers its immune system in order to keep the fetus inside.
For this reason, pregnant women must be careful about infectious diseases. In some cases, bacteria and viruses can reach the fetus.

A study in Malawi of 1,391 pregnant women (5) also found that infections such as chorioamnionitis lead to low birth weight babies.

In Japan, what many pregnant women are concerned about more than infectious diseases is probably weight management.
Many people have probably been advised by their doctors that “if you gain too much weight, you will develop gestational diabetes” or “if fat accumulates in the birth canal, it will make labor difficult.”

If the microbiome regulates metabolic functions during pregnancy, then there should be a strong correlation between the composition of bacteria and pregnancy complications.

gestational diabetes mellitus (GDM)

In Japan, around 10% of pregnant women are diagnosed with gestational diabetes mellitus (GDM).
This occurs when the pregnant woman’s body is unable to withstand the process that is supposed to increase the efficiency of energy absorption for the baby.

Several studies have explored the relationship between GDM and the microbiome, observing increases or decreases in specific bacteria and genes. It has also been shown that changes in the microbiome in GDM patients can lead to dopamine deficiency, an imbalance in short-chain fatty acids, and metabolic inflammation.

A very interesting paper published in 2023 (6) combined data from 44 GDM patients with the results of experiments in germ-free mice. It was the work of the laboratory of Omry Koren (currently at Bar-Ilan University), who studied in the laboratory of Ruth Ley.

They suggest that it may be possible to predict or reduce the risk of GDM early in pregnancy based on clinical data and microbiome composition.
They also point out that GDM may be caused not only by bacteria but also by the entire microbiome, including other microorganisms, viruses, metabolic products, etc.

Preeclampsia (PE)

Although there is very little literature on preeclampsia (PE) and the microbiome, some studies have reported that PE patients have a reduced diversity of gut bacteria and an increase in potential pathogens known as opportunistic pathogens (7).

Furthermore, transplantation of the fecal microbiome from PE patients into mice caused increased blood pressure and proteinuria, suggesting that changes in the microbiome are a cause rather than an effect.

Other

Most of the research into the relationship between pregnancy problems and the microbiome has focused on GDM or PE, as mentioned above, but research is also beginning to look into the relationship with premature birth and unexplained miscarriage.

Increase in bifidobacteria and lactic acid bacteria during late pregnancy

A fetus grows in its mother’s womb for 10 months, receiving nutrients from the mother.
When the time comes, mothers don’t just deliver the baby out of their bodies; they also give a gift along with it.

There is growing evidence that changes in the microbiome during pregnancy not only benefit the mother and her developing fetus, but also the baby at birth and after birth.

I’d like to introduce another finding from the laboratory of Omry Koren, mentioned above.
During the third trimester of pregnancy, the composition of the mother’s intestinal bacteria changes significantly. Individual differences become greater and diversity decreases.
However, there are some commonalities. Bacteria such as Bifidobacterium, Blautia, and Collinsella increase. Of these, Bifidobacterium is also a bacterium that increases during pregnancy in mice.

The authors focused on progesterone, a hormone that remains at high levels throughout pregnancy. Could it be that progesterone promotes the growth of bifidobacteria?
The results showed that this hypothesis was a complete hit.
The amount of bifidobacteria increased in the stool of mice that were administered progesterone. What’s more, when progesterone was added to the stool itself and the mice were cultured, the amount of bifidobacteria still increased.
There is no doubt that the increase in progesterone during pregnancy is causing the growth of bifidobacteria.

What does this result mean?

Bifidobacteria are known to be beneficial to human health, and may offer many benefits to pregnant women, including boosting immunity, regulating weight gain, and improving insulin sensitivity and glucose tolerance.

There’s an even more fascinating explanation: Bifidobacteria reach the womb of babies born vaginally, and they’re essential for the digestion of human monosaccharides (HMOs) found in breast milk.

In the later stages of pregnancy, a mother’s intestinal bacteria begin to prepare so that the baby, once separated from the umbilical cord, can absorb nutrients properly from breast milk.
And of course, bifidobacteria will also help build your baby’s immune system.
Bacteria such as Blautia and Collinsella, which were not confirmed in the mouse experiments, must also be increasing for their own reasons.

Changes in the microbiome are not limited to intestinal bacteria.
The bacterial composition in the vagina, where a baby comes out, also changes significantly. While there are significant differences depending on the country and race in which you live, and it is difficult to generalize, research has shown that lactobacillus bacteria become significantly more prevalent, resulting in a decrease in diversity (8, 9).

Lactobacillus bacteria acidify the surrounding environment by producing lactic acid. This prevents other bacteria from multiplying, protecting the baby from infection as it passes through the birth canal.
It’s not that bacterial diversity has decreased in anticipation of childbirth; rather, diversity is deliberately narrowed, allowing the bacteria best suited to the baby’s birth to dominate.

Maternal microbiome and baby health

A mother’s microbiome has other effects on her unborn baby.

Neurodevelopment

Helen E. Vuong and her colleagues at the University of California, San Diego, conducted experiments using mice and demonstrated that the maternal gut microbiota plays a major role in fetal neural development.(10) This result was predicted to affect fetal behavior.

The following year, a large-scale cohort study(11) conducted by a research team led by Peter Vuillermin of Deakin University in Australia proved this prediction to be correct.
The study, which involved 213 mothers and 215 children, found a correlation between the diversity of mothers’ gut bacteria in the third trimester of pregnancy and their children’s scores on the Child Behavior Checklist (CBCL) at the age of two.
However, as only 20 of the 215 children failed the checklist at the age of two, further large-scale cohort studies are needed.

metabolic development

Other studies have also shown effects on metabolic systems, including short-chain fatty acids produced by intestinal bacteria (12).
Since this is a Japanese study, I hope you will also refer to the Japanese summary.
Intake of dietary fiber during pregnancy promotes the development of the fetus’s metabolic functions and makes the child less susceptible to obesity after birth.

Preventing allergies

Another study (13) suggests that the bacterium Prevotella copri may reduce the risk of food allergies.
This bacterium, which is often demonized because it is believed to be linked to conditions such as insulin resistance, may actually be protecting unborn babies.
This is a good example of the irrationality of treating a particular bacterium as a villain.

All of these studies assume that the mother’s microbiome is transferred to the baby during birth.
In other words, the transmission of microorganisms through vaginal birth (natural birth).

The conventional wisdom is that babies growing in the womb are sterile and only encounter bacteria when they pass through the birth canal.
However, recent research has shown that the uterus may not be sterile either (14). On the other hand, there is also a strong belief that babies are sterile until they are born (15).

Does a multiparous mother’s microbiome favor a second child?

One study using pigs found that the composition of the microbiome changed more rapidly with increasing birth frequency (16).
If babies benefit from their mother’s microbiome while still in the womb, then it may be that second and subsequent children are more likely to benefit from it.

Lifestyle habits during pregnancy and your baby’s health

If the microbiome during pregnancy is so important for your baby, is there anything we can do to make it a little better?

The conclusion is that it seems possible to some extent.
It is often said that you should adjust your lifestyle during pregnancy, but if the microbiome is included as one of the reasons for this, could it lead to increased motivation?

Diet and the Microbiome During Pregnancy

Our bodies are made up of what we eat.
This phrase, which is repeated in all fields, certainly represents one aspect of the truth.

To what extent does what we eat affect our microbiome?
There’s still some debate about whether diet can positively alter the microbiome, and the same is true for diet during pregnancy.

But given that a mother’s microbiome is transferred to her baby during birth, there could be some dietary advice for mothers who want to prepare their microbiome as best as possible during pregnancy.

There are a few limited studies that have looked at diet during pregnancy and its impact on the microbiome of both the pregnant woman and her baby.
Among them, a paper (17) comprehensively summarizing seven studies on intestinal bacteria examines the effects of high-fat diets and dietary fiber intake on intestinal bacteria.
Other studies have focused on omega-3 fatty acids and polyphenols (18), as well as the intake of dairy products, seafood, and fruit (19).

Although not a microbiome-related study, I would like to introduce a very significant research paper (20) published in July 2023 by the Koshin Eco-Child Research Unit Center (Yamagata Zentaro et al.) at Yamanashi University. (Click here for the Japanese summary.)

The study, titled “The relationship between maternal dietary fiber intake during pregnancy and development at age 3,” involved approximately 76,000 mother-child pairs participating in the Ministry of the Environment’s National Survey on Children’s Health and the Environment (Eco-Chil Survey).

The results showed that children born to mothers who consumed less dietary fiber during pregnancy tended to be more likely to have developmental delays in communication skills, fine motor skills, problem-solving skills, and personal and social skills at the age of three compared to children born to mothers who consumed more dietary fiber.

It is not difficult to speculate that these results are closely related to the influence of the microbiome, including gut bacteria. These results complement the research by Peter Vuillermin and colleagues at Deakin University mentioned above.

A research group at Yamanashi University published similar results on protein intake in January of the same year (21). (Click here for the Japanese summary.)

Ultimately, it may be that the important thing is to eat a well-balanced diet.
Science simply states observed facts. What to do with them can only be decided based on a broad perspective and whether or not you can believe it.
It would be best to listen to this with the attitude that if there is something you can do for your baby, then you should pay a little more attention to your diet.

Other factors include the influence of the pregnant woman’s own microbiome and differences due to the method of delivery.

Many women today are concerned about staying slim, which has led to problems with pregnant women being too thin. It’s also recommended that women gain weight within an appropriate range during pregnancy.
Focusing solely on the microbiome and ignoring other factors will result in missing the forest for the trees. The optimal diet varies greatly from person to person, and will even change over time for the same person. The goal should always be to maintain a healthy diet, whether pregnant or not.

By the way, I lost weight due to morning sickness, gained weight rapidly in the middle of my pregnancy, and then stopped gaining weight during the later stages of morning sickness, so I didn’t reach my target weight gain. Perhaps because of this (I had read several papers that suggested this), my daughter was born just barely underweight, and I spent a while feeling guilty and hated myself (and then, after giving birth, my appetite suddenly increased, which was a bit of a surprise).

No matter how much knowledge you have, pregnancy is not going to go as planned. I recommend taking it easy and not stressing yourself out.

Other lifestyle habits

Research into lifestyle habits other than diet has yet to progress.

Prebiotics and probiotics are representative health foods, and although their health benefits are heavily advertised, many studies have shown that opinions are divided on their effectiveness.
The same is true for the effects during pregnancy, and a paper summarizing the research (19) (22) also found no clear correlation.

A study (23) of 1,440 pregnant women on the relationship between probiotics and pregnancy complications such as gestational diabetes and preeclampsia also pointed out that probiotics do not reduce the risk of gestational diabetes, and may even increase the risk of preeclampsia.
In response to this, the UK non-profit organization Cochrane has issued a warning against the use of probiotics during pregnancy. (Cochrane Update 2021: Probiotics Use in Pregnancy for the Prevention of Gestational Diabetes – The ObG Project)

Research is divided on the impact of a mother’s prenatal BMI and weight gain during pregnancy on her baby.
Smoking is considered a contraindication during pregnancy, but it also appears to have a negative impact on the microbiome.

And then there’s medication. Many people are very careful about taking medication during pregnancy, but a lot of research is progressing on the use of antibiotics, stomach medicines, laxatives, diabetes medications, prebiotics, probiotics, and more.
Medications may be necessary to protect the health of pregnant women and their fetuses. While exposure to the fetus and its impact on the microbiome certainly must be carefully considered, there are many medications that can be taken during pregnancy.
It’s important to take medications with the utmost caution, and in consultation with your doctor. I, too, found magnesium oxide (a laxative) and acetaminophen (analgesic and fever reducer) helpful during my pregnancy.

Reference list

1. Vitale SG, Ferrari F, Ciebiera M, et al. The Role of Genital Tract Microbiome in Fertility: A Systematic Review. Int J Mol Sci. 2022;23(1). doi:10.3390/ijms23010180
2. Komiya S, Naito Y, Okada H, et al. Characterizing the gut microbiota in females with infertility and preliminary results of a water-soluble dietary fiber intervention study. J Clin Biochem Nutr. 2020;67(1):105-111. doi:10.3164/jcbn.20-53
3. Giessen J van der, Binyamin D, Belogolovski A, et al. Modulation of cytokine patterns and microbiome during pregnancy in IBD. Gut. 2020;69(3):473-486. doi:10.1136/gutjnl-2019-318263
4. Koren O, Goodrich JK, Cullender TC, et al. Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy. Cell. 2012;150(3):470-480. doi:10.1016/j.cell.2012.07.008
5. Doyle RM, Harris K, Kamiza S, et al. Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes. PLoS ONE. 2017;12(7):e0180167. doi:10.1371/journal.pone.0180167
6. Pinto Y, Frishman S, Turjeman S, et al. Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis. Gut. 2023;72(5):918-928. doi:10.1136/gutjnl-2022-328406
7. Chen X, Li P, Liu M, et al. Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation. Gut. 2020;69(3):513-522. doi:10.1136/gutjnl-2019-319101
8. Romero R, Hassan SS, Gajer P, et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014;2(1):4. doi:10.1186/2049-2618-2-4
9. MacIntyre DA, Chandiramani M, Lee YS, et al. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci Rep. 2015;5(1):8988. doi:10.1038/srep08988
10. Vuong HE, Pronovost GN, Williams DW, et al. The maternal microbiome modulates fetal neurodevelopment in mice. Nature. 2020;586(7828):281-286. doi:10.1038/s41586-020-2745-3
11. Dawson SL, O’Hely M, Jacka FN, et al. Maternal prenatal gut microbiota composition predicts child behaviour. EBioMedicine. 2021;68:103400. doi:10.1016/j.ebiom.2021.103400
12. Kimura I, Miyamoto J, Ohue-Kitano R, et al. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science. 2020;367(6481):eaaw8429. doi:10.1126/science.aaw8429
13. Vuillermin PJ, O’Hely M, Collier F, et al. Maternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring. Nat Commun. 2020;11(1):1452. doi:10.1038/s41467-020-14552-1
14. Funkhouser LJ, Bordenstein SR. Mom Knows Best: The Universality of Maternal Microbial Transmission. PLOS Biol. 2013;11(8):e1001631. doi:10.1371/journal.pbio.1001631
15. Kennedy KM, Gerlach MJ, Adam T, et al. Fetal meconium does not have a detectable microbiota before birth. Nat Microbiol. 2021;6(7):865-873. doi:10.1038/s41564-021-00904-0
16. Berry ASF, Pierdon MK, Misic AM, et al. Remodeling of the maternal gut microbiome during pregnancy is shaped by parity. Microbiome. 2021;9(1):146. doi:10.1186/s40168-021-01089-8
17. Maher SE, O’Brien EC, Moore RL, et al. The association between the maternal diet and the maternal and infant gut microbiome: a systematic review. Br J Nutr. 2023;129(9):1491-1499. doi:10.1017/S0007114520000847
18. García-Mantrana I, Selma-Royo M, González S, Parra-Llorca A, Martínez-Costa C, Collado MC. Distinct maternal microbiota clusters are associated with diet during pregnancy: impact on neonatal microbiota and infant growth during the first 18 months of life. Gut Microbes. 2020;11(4):962-978. doi:10.1080/19490976.2020.1730294
19. Lundgren SN, Madan JC, Emond JA, et al. Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner. Microbiome. 2018;6(1):109. doi:10.1186/s40168-018-0490-8
20. Miyake K, Horiuchi S, Shinohara R, et al. Maternal dietary fiber intake during pregnancy and child development: the Japan Environment and Children’s Study. Front Nutr. 2023;10:1203669. doi:10.3389/fnut.2023.1203669
21. Miyake K, Mochizuki K, Kushima M, et al. Maternal protein intake in early pregnancy and child development at age 3 years. Pediatr Res. 2023;94(1):392-399. doi:10.1038/s41390-022-02435-8
22. Jarde A, Lewis-Mikhael AM, Moayyedi P, et al. Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2018;18(1):14. doi:10.1186/s12884-017-1629-5
23. Davidson SJ, Barrett HL, Price SA, Callaway LK, Nitert MD. Probiotics for preventing gestational diabetes. Cochrane Database Syst Rev. 2021;(4). doi:10.1002/14651858.CD009951.pub3

No applicable articles.

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