Some people may wonder how flora can be a family heirloom.
As we all know, a large number of microorganisms are born inside and outside the human body, especially in the mouth, intestines, body surface and reproductive tract, and the types and quantities of microorganisms are quite rich.
Where did the initial flora come from in the early stage of life activities for a baby just born from his mother?
A large number of scientific studies have confirmed that newborns first obtain microorganisms from their mothers, that is, the mothers vertically transfer part of their own flora to their babies at home, which is the so-called "heirloom"-passing on "heirloom". It can be said that this is a priceless treasure given to us by our mother.
Then I want to use a few key words to bring you to understand the mother-infant flora and its intergenerational transmission.
The first key word I want to say is "health". Let's talk about when newborns first came into contact with maternal microorganisms.
This topic has a long history and attracts more attention.
There have been two hypotheses before, one is called "sterile uterine cavity hypothesis", which holds that the uterine cavity of human body is an absolutely sterile environment, and microorganisms should not be detected in fetus, amniotic fluid and meconium.
The other is called "intrauterine colonization hypothesis", which holds that microbial colonization has occurred before delivery, and newborns and newborn babies should be able to detect the existence of microorganisms in their bodies.
There may be some answers to this topic recently. The article published in Nature in August, 2065438+2009 gives such evidence. This article holds that "the uterus is not absolutely sterile".
In this study, a large number of human samples and strict control conditions were used to detect microorganisms in placenta. Although many bacteria detected may come from exogenous pollution in one way or another, microorganisms such as streptococcus may also enter the uterine cavity.
Of course, there are some shortcomings in this study. For example, the placenta is the object of examination, and only a small amount of tissue is used in each sample. If the initial amount of microorganisms is relatively low, it is easy to cause the exogenous signal to be amplified and the detected microbial species to be underestimated.
For this problem, more researchers choose to start with the characteristics of newborns themselves. A special sample type often used to detect the initial flora of newborns is meconium. As the name implies, meconium is the feces of the fetus, which refers to the feces discharged for the first time after the fetus is delivered from the mother. Many studies have detected the presence of bacteria in fetal feces.
In fact, it is not only meconium, but also amniotic fluid, and the structure and composition of microbial flora in amniotic fluid are very similar to meconium.
Our team also found earlier that bacteria and viruses can be detected in the throat and meconium of newborns born a few seconds after cesarean section. Birth, here refers to the bacteria at birth.
Although many studies have reported that bacteria, fungi and viruses can be detected in newborns, the debate may continue.
However, whether born or infected during childbirth, everyone agrees that "newborns get the initial flora from their mothers."
So the next question is that the original flora of the newborn was obtained from the mother? This is my second key word-how to get it.
There used to be a popular saying that "the microorganisms in pregnant women's mouth can descend into the uterine cavity, because some people have detected human oral microorganisms and periodontal pathogens from amniotic fluid." Therefore, people who hold this view believe that it is particularly important for pregnant women to stay healthy during pregnancy.
There is also a view that "microorganisms in the reproductive tract can ascend into the uterine cavity", which is also well understood. After all, the physical distance between the two parts of the body is relatively close and interconnected.
The data of clinical epidemiological investigation also show that the probability of intrauterine infection in women with reproductive tract infection during pregnancy is relatively high.
Another view was put forward only in the last two years.
Published in cell host &; 20 18； The article in the journal Microbe (Cell Host and Microbe) puts forward that "the strains transmitted from mother to baby mainly come from the horizontal transfer of intestinal flora."
The article published in the journal Nature in September 20 19 also shows that "the matching rate of intestinal flora between infants and mothers can even be as high as 70%."
When analyzing our own data, our team also found that whether it is 16S or metagenome, we can see that the flora in the throat secretions and meconium of newborns is the most similar to their mothers' intestinal flora within a few seconds of cesarean delivery.
In addition to the three possible transmission routes mentioned above, a large number of flora transmission will also occur during childbirth, because in the process of natural childbirth, newborns will definitely be contaminated by microorganisms in the maternal reproductive tract.
What are the factors that affect the colonization of neonatal flora? Only the part obtained from the matrix is mentioned here. Of course, these factors often affect the quality of heirlooms to a great extent.
It is easy for all of us to think of medication during pregnancy, especially antibiotics.
Of course, at present, people pay more attention to this point, and never take antibiotics during pregnancy unless absolutely necessary. Indeed, studies have confirmed that if pregnant women take antibiotics during pregnancy, it will affect the initial flora of newborns.
Compared with drug treatment, it may not be easy for all of us to think of pregnancy diseases.
In previous studies, our team also found that the initial flora of newborns born to pregnant women with gestational diabetes mellitus was significantly different from that of healthy pregnant women. This reminds everyone that the health of pregnant women during pregnancy will shape the initial flora of newborns.
There are many diseases and complications during pregnancy, and I believe there will be similar evidence in the future.
Both of the above points are related to pregnancy. Let's talk about some situations during and after childbirth. The mode of delivery is the most concerned.
The article published in Nature from 2065438 to September 2009 also pointed out that "delivery mode is an important factor affecting the initial flora structure of newborns".
In fact, as early as a few years ago, it was found that the initial flora of newborns in natural delivery and cesarean section was different. Because naturally born newborns will be contaminated by microorganisms when they pass through the maternal birth canal, their flora is more like the maternal birth canal; Cesarean section, on the other hand, lost this opportunity, and their newborn flora may be similar to the skin and body surface they first came into contact with.
Therefore, whether the delivery is natural or cesarean section may determine whether the newborn can obtain a large number of flora in the maternal reproductive tract during delivery.
After talking about the mode of delivery, we can't help but talk about the feeding mode. Some people may say, "That must be different. Breast milk and formula milk have different ingredients. " Yes, indeed, there is a difference between the two. The natural immune factors in breast milk cannot be replaced by any formula milk.
But what I want to say here is that the influence of breast milk and formula milk on the initial flora of newborns is not only nutritional components, but also microorganisms in breast milk and maternal bodies will be continuously transported to newborns during breastfeeding, affecting their initial flora, which is also a factor that cannot be ignored.
What is the relationship between the spread of flora and the health of newborns?
Is it possible that newborns born to healthy women before and during pregnancy will get good flora and be healthier, and vice versa? I think it's quite possible.
Taking gestational diabetes mellitus as an example, our team found in early research that the flora transmitted from pregnant women to newborns is determined by the flora in pregnant women. This consistency is not only reflected in the species and quantity of microorganisms, but also in the interaction between them.
If the flora of pregnant women with gestational diabetes mellitus will change, the initial flora of their newborns will also change, which shows that the initial metabolic ability is weakened and the detection rate of some viruses is greatly improved.
In other words, the health status of pregnant women during pregnancy will affect the mother's own flora, and this influence will be passed on to the newborn.
What kind of flora newborns get will not only affect their health in the early stage of life activities, but also play a long-term role in the future.
Many studies have confirmed that the development of neonatal innate immunity has a great relationship with their early flora structure and composition, and also determines their chances of suffering from allergies, asthma and other diseases in the future.
In other words, the flora of pregnant women and children is also good or bad.
It seems to be a good choice to adjust and shape the initial flora through some explorations and attempts. Let me introduce a few such examples.
There are always some people who have some novel and bold ideas. Some people transferred engineering Escherichia coli into pregnant mice, and they found that it could better stimulate the innate immune development and metabolism of young mice and reduce microbial infection. Of course, such experiments can only stay on animals.
Others choose to work hard on the spread of maternal and child flora during childbirth.
For example, Professor Dominguez-Bello from new york University School of Medicine and Professor Rob Knight from the University of California, San Diego, have made some attempts. They transplanted reproductive tract flora for newborns who had caesarean section.
In some countries and regions, the cesarean section rate is staggering, reaching 50%, far higher than the normal level of 15%. Although there is no evidence of direct causality, there are a large number of clinical epidemiological survey data showing that children undergoing cesarean section are prone to allergies and asthma, even obesity and immune deficiency. Some people suspect that the loss of maternal flora caused by cesarean section has played an unshirkable responsibility.
Professor Rob Knight is an international expert on intestinal flora. 20 1 1, his wife had to have a caesarean section for some special reasons. As a well-known scholar in the field of microbiology, Professor Rob Knight didn't think much at that time. He just subconsciously smeared the secretion and flora of his wife's birth canal on his daughter. He hopes that in this way, his daughter can get the microorganisms that should belong to her.
A few years later, in Rob Knight's own words, he thought his daughter was healthy. Of course, this may be just an example. When Professor Rob Knight heard that Dominguez-Bello was going to do such a study, he joined in.
They transplanted vaginal secretions from some pregnant women into their children and found that they could partially restore the flora that these newborns should have obtained. However, the effect of this transplantation needs to be known through a large number of people and long-term follow-up. But this is at least a good start.
Then we also have some thoughts on maternal and infant flora and pregnancy health, mainly caused by a bowl of sugar water.
The gold standard for clinical detection of gestational diabetes mellitus is OGTT experiment. Some people may not know OGTT very well. This experiment is called oral glucose tolerance test. The basic method is as follows: pregnant women come to the hospital in a specific pregnancy week, take high-concentration glucose water first, and then draw blood to test their blood sugar values before and after taking it 1 hour and 2 hours.
There are several problems in this experiment: one is that the high concentration of sugar water makes it difficult for pregnant women to swallow; The second is to draw blood, but also many times; The third is that it takes a long time and the clinical cooperation is low; The most crucial point is that 80%~90% people don't have gestational diabetes, but they have to take so many injections for nothing.
Therefore, when our team studied gestational diabetes mellitus and maternal and infant flora, it was found that some microorganisms in several parts of pregnant women's bodies had a very good correlation with clinical OGTT detection values.
So we thought, can we use these microorganisms as markers to develop some auxiliary diagnosis methods for gestational diabetes?
Therefore, we choose the most convenient oral cavity as the object, select several oral microbes, and construct the models of support vector machine and random forest. It is found that both of them can achieve ideal discriminant effect, and the highest AUC value can even reach more than 90%.
As can be seen from the previous introduction, there are still many problems that we need to explore, at least some effective methods and tools are needed in the analysis of microbial data.
For example, the source of neonatal flora and its transmission route are still controversial.
For some methods, such as the study of flora source, it is usually based on 16S sequence and community similarity, that is, the possible source of neonatal flora is inferred by calculating the flora distance within and between groups.
For example, DC distance is used to study the relationship between placental microflora and oral microflora, and PCOA is used to study the flora source of natural delivery and cesarean section newborns.
Later, some tools specially used to trace the origin of flora appeared one after another, such as early traceability instrument and recent feast. Some mathematical models were introduced to infer the possible source of neonatal flora by calculating the species and abundance of OTU.
However, the resolution of this method and tool often cannot meet the requirements.
There are also some tools that trace the source from the strain level based on metagenome data, such as strain, Constrains, StrainEst, MIDAS and so on.
However, among these tools, if there are tools containing confidential information, the resolution is usually not high, while the tools with high resolution often do not have rich information.
Most importantly, the characteristics of neonatal flora are that the types and quantities of microorganisms are often low, so the existing tools often fail to achieve satisfactory results when analyzing such data for traceability.
Previously, our team also developed some tools for assembling microbial genomes, inGAP-sf, and a tool for assembling and analyzing metagenomes, which involved the contents of some strains.
Then we hope that in the next work, according to some characteristics of neonatal flora, we will develop some tools for strain identification and traceability to serve the study of maternal and infant flora.
Finally, I want to summarize today's content with the key word flora inheritance, which is also the meaning of "heirloom" I mentioned earlier.
I hope that through my previous sharing, we can better understand the mother-infant flora and its intergenerational transmission; I hope it can inspire people to pay more attention to maternal and infant health and think about the relationship between maternal and infant flora and pregnancy health and various pregnancy complications from a new perspective. I also hope that more people can join in the study of maternal and infant flora.
Thank you for your attention!