̽��ֱ�� of Cambridge - Jorge Lopez-Tello

Mother’s gut microbiome during pregnancy shapes baby’s brain development

jg533 — Tue, 20 Aug 2024 23:30:03 +0000

Researchers have compared the development of the fetal brain in mice whose mothers had no bacteria in their gut, to those whose mothers were given Bifidobacterium breve orally during pregnancy, but had no other bacteria in their gut.

Nutrient transport to the brain increased in fetuses of mothers given Bifidobacterium breve, and beneficial changes were also seen in other cell processes relating to growth.

Bifidobacterium breve is a ‘good bacteria’ that occurs naturally in our gut, and is available as a supplement in probiotic drinks and tablets.

Obesity or chronic stress can alter the gut microbiome of pregnant women, often resulting in fetal growth abnormalities. ̽��ֱ��babies of up to 10% of first-time mothers have low birth weight or fetal growth restriction. If a baby hasn't grown properly in the womb, there is an increased risk of conditions like cerebral palsy in infants and anxiety, depression, autism, and schizophrenia in later life.

These results suggest that improving fetal development - specifically fetal brain metabolism - by taking Bifidobacterium breve supplements while pregnant may support the development of a healthy baby.

̽��ֱ��results are published today in the journal Molecular Metabolism.

“Our study suggests that by providing ‘good bacteria’ to the mother we could improve the growth and development of her baby while she’s pregnant,” said Dr Jorge Lopez-Tello, a researcher in the ̽��ֱ�� of Cambridge’s Centre for Trophoblast Research, first author of the report.

He added: “This means future treatments for fetal growth restriction could potentially focus on altering the gut microbiome through probiotics, rather than offering pharmaceutical treatments - with the risk of side effects - to pregnant women.”

“ ̽��ֱ��design of therapies for fetal growth restriction are focused on improving blood flow pathways in the mother, but our results suggest we’ve been thinking about this the wrong way - perhaps we should be more focused on improving maternal gut health,” said Professor Amanda Sferruzzi-Perri, a researcher in the ̽��ֱ�� of Cambridge’s Centre for Trophoblast Research and senior author of the report, who is also a Fellow of St John’s College, Cambridge.

She added: “We know that good gut health - determined by the types of microbes in the gut - helps the body to absorb nutrients and protect against infections and diseases.”

̽��ֱ��study was carried out in mice, which allowed the effects of Bifidobacterium breve to be assessed in a way that would not be possible in humans - the researchers could precisely control the genetics, other microorganisms and the environment of the mice. But they say the effects they measured are likely to be similar in humans.

They now plan further work to monitor the brain development of the offspring after birth, and to understand how Bifidobacterium breve interacts with the other gut bacteria present in natural situations.

Previous work by the same team found that treating pregnant mice with Bifidobacterium breve improves the structure and function of the placenta. This also enables a better supply of glucose and other nutrients to the developing fetus and improves fetal growth.

“Although further research is needed to understand how these effects translate to humans, this exciting discovery may pave the way for future clinical studies that explore the critical role of the maternal microbiome in supporting healthy brain development before birth,” said Professor Lindsay Hall at the ̽��ֱ�� of Birmingham, who was also involved in the research.

While it is well known that the health of a pregnant mother is important for a healthy baby, the effect of her gut bacteria on the baby’s development has received little attention.

Reference

Lopez-Tello, J, et al: ‘Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.’ Molecular Metabolism, August 2024. DOI: 10.1016/j.molmet.2024.102004

A study in mice has found that the bacteria Bifidobacterium breve in the mother’s gut during pregnancy supports healthy brain development in the fetus.

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Unborn babies use ‘greedy’ gene from dads to ‘remote-control’ mums into feeding them extra food

Anonymous — Tue, 11 Jul 2023 15:00:32 +0000

̽��ֱ��unborn baby ‘remote controls’ its mother’s metabolism so the two are in a nutritional tug of war. ̽��ֱ��mother’s body wants the baby to survive but needs to keep enough glucose and fats circulating in her system for her own health, to be able to deliver the baby, breastfeed and to reproduce again.

A new study from the ̽��ֱ�� of Cambridge published today examines how the placenta communicates with the mother through the release of hormones so she will accommodate her baby’s growth. ̽��ֱ��placenta is a vital organ that develops with the fetus in pregnant women and other female mammals to support the developing fetus. In pregnant mice, scientists selectively altered the signalling cells in the placenta that tell mothers to allocate nutrients to her developing fetuses.

Professor Amanda Sferruzzi-Perri, Professor in Fetal and Placental Physiology, a Fellow of St John’s College and co-senior author of the paper, said: “It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetus.”

Dr Miguel Constancia, MRC Investigator based at the Wellcome-MRC Institute of Metabolic Science and co-senior author of the paper, said: “ ̽��ֱ��baby’s remote control system is operated by genes that can be switched on or off depending on whether they are a ‘dad’s’ or ‘mum’s’ gene’, the so-called imprinted genes.

“Genes controlled by the father are ‘greedy’ and ‘selfish’ and will tend to manipulate maternal resources for the benefit of the fetuses, so to grow them big and fittest. Although pregnancy is largely cooperative, there is a big arena for potential conflict between the mother and the baby, with imprinted genes and the placenta thought to play key roles.”

̽��ֱ��findings by researchers from the Centre for Trophoblast Research at Cambridge’s Department of Physiology, Development and Neuroscience and the Medical Research Council Metabolic Diseases Unit, part of the Wellcome-MRC Institute of Metabolic Science, have been published in Cell Metabolism.

̽��ֱ��baby’s genes controlled by the father tend to promote fetal growth and those controlled by the mother tend to limit fetal growth.

Professor Sferruzzi-Perri explained: “Those genes from the mother that limit fetal growth are thought to be a mother’s way of ensuring her survival, so she doesn’t have a baby that takes all the nutrients and is too big and challenging to birth. ̽��ֱ��mother also has a chance of having subsequent pregnancies potentially with different males in the future to pass on her genes more widely.”

Researchers deleted the expression of an important imprinted gene called Igf2, which provides instructions for making a protein called ‘Insulin Like Growth Factor 2’. Similar to the hormone insulin, which is responsible for making and controlling glucose levels in our circulation, the gene promotes fetal growth and plays a key part in the development of fetal tissues including the placenta, liver and brain.

Dr Jorge Lopez-Tello, a lead author of the study based at the ̽��ֱ��’s Department of Physiology, Development and Neuroscience, said: “If the function of Igf2 from the father is switched off in signalling cells, the mother doesn’t make enough amounts of glucose and lipids – fats – available in her circulation. These nutrients therefore reach the fetus in insufficient amounts and the fetus doesn’t grow properly.”

̽��ֱ��scientists found that deleting Igf2 from the placenta’s signalling cells affects the production of other hormones that modulate the way the mother’s pancreas produces insulin, and how her liver and other metabolic organs respond.

“We found Igf2 controls the hormones responsible for reducing insulin sensitivity in the mother during pregnancy. It means the mother’s tissues don’t absorb glucose so nutrients are more available in the circulation to be transferred to the fetus,” said Professor Sferruzzi-Perri.

Babies with Igf2 gene defects can be overgrown or growth-stunted. “Until now, we didn’t know that part of the Igf2 gene’s role is to regulate signalling to the mother to allocate nutrients to the fetus,” added Professor Sferruzzi-Perri.

̽��ֱ��mice studied were smaller at birth and their offspring showed early signs of diabetes and obesity in later life.

Professor Sferruzzi-Perri said: “Our research highlights how important the controlled allocation of nutrients to the fetus is for the lifelong health of the offspring, and the direct role the placenta plays.

“ ̽��ֱ��placenta is an amazing organ. At the end of pregnancy, the placenta is delivered by the mother, but the memories of how the placenta was functioning leaves a lasting legacy on the way those fetal organs have developed and then how they’re going to function through life.”

̽��ֱ��next step is to understand how placental hormones are controlled by Igf2 and what those hormones are doing. Future research could help scientists discover new strategies to target the placenta to improve health outcomes for mums and babies.

Mice are used in research because the organisation of their DNA and their gene expression is similar to humans, with ninety-eight percent of human genes having a comparable gene in the mouse. They have similar reproductive and nervous systems to humans, and suffer from many of the same diseases such as obesity, cancer and diabetes.

Reference
Lopez-Tello, J et al. Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene. Cell Metabolism; 11 July 2023; DOI: 10.1016/j.cmet.2023.06.007

Adapted from a press release from St John’s College Cambridge

A study in mice has found that fetuses use a copy of a gene inherited from their dad to force their mum to release as much nutrition as possible during pregnancy.

It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetus

Amanda Sferruzzi-Perri

Understanding Animal Research

Brown mouse

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Maternal microbiome promotes healthy development of the baby

jg533 — Tue, 28 Jun 2022 08:23:10 +0000

A new study has found that a species of gut bacteria, known to have beneficial effects for health in mice and humans, changes the mother’s body during pregnancy and affects the structure of the placenta and nutrient transport - which impacts the growing baby.

̽��ֱ��bacteria, Bifidobacterium breve, is widely used as a probiotic so this study could point to ways of combating pregnancy complications and ensuring a healthy start in life across the population.

̽��ֱ��research involved scientists from the ̽��ֱ�� of Cambridge, the Quadram Institute, and the ̽��ֱ�� of East Anglia and is published today in the journal Cellular and Molecular Life Sciences.

Microbes in our gut, collectively called the gut microbiome, are known to play a key role in maintaining health by combating infections, and influencing our immune system and metabolism. They achieve these beneficial effects by breaking down food in our diet and releasing active metabolites that influence cells and body processes.

Little is known about how these interactions influence fetal development and the baby’s health pre-birth. To address this, Professor Lindsay Hall from the Quadram Institute and ̽��ֱ�� of East Anglia, and Dr Amanda Sferruzzi-Perri and Dr Jorge Lopez-Tello from the ̽��ֱ�� of Cambridge analysed how supplementation with Bifidobacterium bacteria affected pregnancy in mice.

Hall has been studying Bifidobacterium and the microbiome in very early life, previously showing how providing specific probiotics can help premature babies. These bacteria rise in numbers in the microbiome during pregnancy in humans and mice, and alterations in its levels have been linked to pregnancy complications.

Sferruzzi-Perri said: “Pregnancy disorders affect around one in ten pregnant women. This is worrying, as pregnancy complications can lead to health problems for the mother and her baby even after the pregnancy.”

“This study, carried out in mice, identifies the maternal microbiome as a new player in the communication between mother, placenta and fetus. Finding out how this form of communication works and how to improve it may help many women who develop pregnancy complications, as well as helping their developing child.”

‘Germ-free’ mice - lacking any microbes – can be bred to allow comparisons with other mice that have a ‘normal’ microbiome. This can provide valuable insights into the role of the microbiome in health - such studies can’t be carried out in humans.

In this study, the researchers also looked at the effect of feeding germ-free mice the probiotic Bifidobacterium breve.

In the germ-free mice, the fetus did not receive adequate sugar and failed to grow and develop properly. Excitingly, providing Bifidobacterium breve to germ-free mice improved fetal outcomes by restoring fetal metabolism, growth and development to the normal levels.

Lacking the maternal microbiome also hampered the growth of the placenta in a way that would affect fetal growth, and more detailed analysis identified a number of key cell growth and metabolic factors that appear to be regulated by the microbiome and Bifidobacterium breve.

“ ̽��ֱ��placenta has been a neglected organ, despite it being vital for the growth and survival of the fetus. A better understanding of how the placenta grows and functions will ultimately result in healthier pregnancies for mothers and babies,” said Lopez-Tello.

̽��ֱ��researchers also found that the microbiome affected key nutrient transporters, including those for sugars within the placenta that would also influence the growth of the fetus.

“Our findings reveal that the maternal microbiome promotes development of the placenta and growth of the fetus,” said Hall.

“We think that this is linked to the altered profile of metabolites and nutrients, which affects nutrient transport from mother to baby across the placenta. Excitingly it appears that adding in a probiotic Bifidobacterium during pregnancy may help to boost how the placenta functions, which has positive effects on the baby’s growth in the womb.”

These findings are strong indicators of a link between the microbiome of the mother and the development of the baby, but in this first study of its kind there are limitations.

This study focused on one single bacterial species, and whilst this showed that Bifidobacterium breve had positive effects on germ-free mice during pregnancy, this is not a natural situation. Future studies are needed to confirm these effects in a more natural and complex microbiome.

̽��ֱ��study was carried out in mice and cannot automatically be translated into treatments for humans. ̽��ֱ��knowledge provided in this proof-of-concept animal study is critical for guiding future studies in humans - to uncover whether the human maternal microbiome has similar effects. If that is the case, it could provide a relatively simple and low-cost way to help improve pregnancy outcomes with positive benefit for the life-long health of the mother and her child.

̽��ֱ��research was funded by Wellcome and the Biotechnology and Biological Sciences Research Council.

Reference

Lopez-Tello, J et al: ‘Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice.’ Cellular and Molecular Life Sciences, June 2022. DOI: 10.1007/s00018-022-04379-y

Adapted from a press release by the Quadram Institute.

Researchers studying mice have found the first evidence of how a mother’s gut microbes can help in the development of the placenta, and the healthy growth of the baby.

This study, carried out in mice, identifies the maternal microbiome as a new player in the communication between mother, placenta and fetus.”

Amanda Sferruzzi-Perri

Hall Lab, Quadram Institute

Bifidobacterium breve

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