By Claire O’Connell

Gut bugs in pregnancy - a curious development

During pregnancy, a woman experiences all sorts of visible changes to her body. Her belly gets larger, she puts down fat deposits and patches of her skin can even change colour. But what’s not so easy to spot are the changes happening inside the gut. And if a new study is anything to go by, those changes can be profound.

It might not be the most appetising of thoughts but, as a human, your gut is typically home to billions of bacteria. The gut ‘microbiome’ has become something of a hot topic in research in recent years, with people asking whether and how the nature of gut bugs could be linked with the body’s immune system, certain diseases and possibly even obesity.

Part of the drive to better understand what the bugs do is to see how the profile of bacteria can change: studies have looked at whether diet, ageing and illness correlate with changes in the makeup of gut bugs. And now a research group with members in the US, Sweden and Finland has been looking at what happens to gut bugs during a woman’s pregnancy too, with some interesting results.

Again it’s not appetising, but they got stool samples from 91 pregnant women in the first and third trimesters of their pregnancies. Then they analysed the bacterial content of the stools and compared them with data from the patients such as body mass index, diet information, other clinical measurements and whether they had developed a condition called gestational diabetes, which can happen in late pregnancy.

And what did they find? In short, the composition and structure of the gut microbial community - the bacteria that hang out in the gut - changed profoundly between the first and last trimesters of pregnancy. “By the third trimester, each woman’s microbiota has diverged in ways that could not be predicted from the [trimester 1] composition and that were not associated with health status or our diet records,” write the authors in the journal Cell.

Overall, the diversity of bacteria within an individual person’s gut seemed to reduce between the start and the home furlong of pregnancy. And if you look at the bacteria that typically lived in the gut of a woman in the last trimester of pregnancy, you could be forgiven for thinking they had come from someone who is not in the peak of good health. In fact they resembled the kind of profile that you might expect from someone with metabolic syndrome, a state of health that pushes up the risk of heart disease and diabetes. Plus the types of bacteria that seemed to come to the fore in the gut in late pregnancy are also linked with inflammatory conditions.

And interestingly, when the researchers transferred the bacteria (pooled from the samples of five healthy-weight women) into mice that had no microbiome of their own, they found the mice who got trimester-3 bugs put on more fat and became less sensitive to the hormone insulin than the mice who got the trimester-1 gut bugs.

So overall the gut bugs in late pregnancy resemble the gut bugs from a diseased state. Yet the woman is simply pregnant. But in the journal paper that describes the work, the study authors point out that context can matter.

“Dysbiosis [microbial imbalance], inflammation, and weight gain are features of metabolic syndrome, which increases the risk of type 2 diabetes in nonpregnant individuals,” they write. “These same changes are central to normal pregnancy, where they may be highly beneficial, as they promote energy storage in fat tissue and provide for the growth of the fetus.”

Article
Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy

Omry Koren, Julia K. Goodrich, Tyler C. Cullender, Aymé Spor, Kirsi
Laitinen, Helene Kling Bäckhed, Antonio Gonzalez, Jeffrey J. Werner,
Largus T. Angenent, Rob Knight, Fredrik Bäckhed, Erika Isolauri, Seppo
Salminen, Ruth E. Ley

Cell - 3 August 2012 (Vol. 150, Issue 3, pp. 470-480)

http://www.cell.com/abstract/S0092-8674%2812%2900829-X

By Claire O’Connell

When a baby arrives too early, it can cause problems and in some cases it can unfortunately be fatal. Why do some pregnancies end in premature birth? New research in Ireland suggests there could be a process where the mother’s immune system senses DNA from the baby in the mother’s bloodstream.

Pregnancy typically lasts around 38 to 40 weeks in humans (or even a little longer in some cases) and during this time the baby develops and grows in the womb.

But if the pregnancy ends before 37 weeks, the birth is considered pre-term. And pre-term birth is one of the leading causes of infant mortality, according to the authors of a recent paper in the Journal of Immunology.

They set out to look at how the immune system might be involved in triggering preterm birth, and what they suggest is that it could involve the immune system picking up on DNA from the baby in the mother’s bloodstream.

Previous work had shown that in pregnancies which ended in pre-term birth or involved a potentially life-threatening condition called pre-eclampsia, the mother tends to have high levels of DNA from the foetus circulating in her own blood.

This foetal DNA is in a particular state called ‘hypomethylation’, which is important because DNA from microbes is also hypomethylated. And one of the ways in which the body senses microbial DNA is through a molecule called Toll-like receptor (TLR) 9.

Toll-like receptors have become one of the hot areas in immune-system research because they are like buttons that activate segments of the immune system. And when TLR-9 detects hypomethylated DNA from a microbial source in the blood, it switches on an immune response.

Could TLR-9 also sense foetal DNA in the blood and be involved in triggering preterm birth? The experiments, by researchers at Trinity College Dublin and the Coombe Women & Infants University Hospital in Dublin point in that direction.

Their research found that human immune cells growing in the lab could be activated by mouse foetal DNA. And in mice, introducing foetal DNA into the blood was linked with pregnancy complications and foetal loss.

But where does TLR-9 come in? It turned out that if the mice were engineered so that their TLR-9 didn’t work, the foetal DNA had no obvious ill effect on the pregnancy.

That’s all very well, but we can’t engineer humans to not make TLR-9. So it’s encouraging that the scientists also saw similar effects when they blocked the actions of TLR-9 with a drug called chloroquine.

“Our work identifies a process in the mother’s immune system which can trigger pre-term birth,” says researcher Prof Luke O’Neill, director of the Trinity Biomedical Sciences Institute. “If this process can be targeted therapeutically, we might be able to stop women going into labour early, which could save the baby.”

References:
TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal
Loss in Preterm Birth and Preeclampsia.
Scharfe-Nugent A, Corr SC, Carpenter SB, Keogh L, Doyle B, Martin C, Fitzgerald KA, Daly S, O’Leary JJ, O’Neill LA. J Immunol. 2012 Jun 1;188(11):5706-12.