Overselling the microbiome award - many - for stories about placental vs. oral microbiomes

A few days ago on Twitter I was pointed to a news story about the human microbiome:

There's bacteria in the placenta, similar to those in mouth. But the oral hygiene msg seems hugely premature to me. http://t.co/WfVWfMpCT4

— Ed Yong (@edyong209) May 21, 2014

I looked at the article and definitely agreed with Ed. So I responded

well @edyong209 that is not the only issue w/ that article

— Jonathan Eisen (@phylogenomics) May 21, 2014

And then a mini conversation happened

@phylogenomics Tell me more.
— Ed Yong (@edyong209) May 21, 2014

I think @edyong209 @phylogenomics are right, and besides lots of more testable good reasons to brush your teeth before bed.

— Nick Loman (@pathogenomenick) May 21, 2014

@phylogenomics Is it the implicit assumption that the presence of bacteria in the placenta is a bad thing? Cos that annoyed me too

— Ed Yong (@edyong209) May 21, 2014

well @edyong209 1) is this a living microbiome or just DNA? 2) adaptationism in giving "purpose" 3) no mention of prior work

— Jonathan Eisen (@phylogenomics) May 21, 2014

@phylogenomics @edyong209 Re point 3, from 9 months ago-- http://t.co/o79GA2QbUC
— carlzimmer (@carlzimmer) May 21, 2014

.@phylogenomics @edyong209 given human history and oral health, if impacts pregnancy so much, how are any humans still alive and reproducing
— Dr. SPONCH (@SponchPhD) May 21, 2014

@edyong209 @phylogenomics bacteria are bad everywhere right?
— Vincent J. Lynch (@VinJLynch) May 21, 2014

And I pondered writing up an "overselling the microbiome award" but I got caught up in other things. And then today some people (including Jens Walter) pointed me to this New York Times article about the same topic: Study Sees Bigger Role for Placenta in Newborns’ Health - NYTimes.com. And I decided I had to write something up because too many news stories were not doing a great job with the science here.



So here goes. First, the Science news (UPDATE - NOTE this is the news part of Science magazine, not ScienceNewsOrg) story Ed Yong pointed to originally and the parts I have problems with.

• Sentence 1: Researchers have discovered a small community of bacteria living in a most unlikely place: the placenta, the organ that nourishes a developing fetus through the umbilical cord.  No - not really.  They did not discover this.  They did a more detailed characterization of the community.
• Sentence 2: The finding overturns the conventional wisdom that the placenta is sterile.  No - the study is another piece of evidence that argues against the "conventional wisdom"
• Sentence 3 is OK.
• Sentence 4.  Medical experts have long assumed that any bacteria found in the organ must have been picked up when it passed through the vagina after delivery.  Sure - some "experts" have assumed this.  But there has been growing evidence for many years that this is a bad assumption.  

I could go on and on.  Actually though I won't.  Becuase every news story can have some limitations.  I don't like inaccurate statements but it is a part of life I guess.  But the part that drives me batty in this story is the inclusion of a discussion about oral health.  Here are the two paragraphs that are the crux of my concern (with bold emphasizing the worst parts).

Surprisingly, the mix of bacteria in the placenta looked more like the microbiome in an adult human’s mouth than the vaginal, skin, gut, or other body microbiomes, Aagaard’s team reports today in Science Translational Medicine. The researchers think the microbes may get to the placenta from the mother’s mouth through her bloodstream, perhaps when she brushes her teeth and dislodges them into the blood. That possibility is intriguing, because there’s a well-known correlation between gum disease and preterm birth. Indeed, the array of bacteria in the placenta differed in women who gave birth early, before 37 weeks. 

“This reemphasizes the importance of oral health” during pregnancy, Aagaard says. In fact, women may need to pay attention to their teeth even before they may become pregnant, because the placenta develops early in pregnancy, she says. That may be a challenge for low-income women who can’t afford dental care, Aagaard adds. The team also found a correlation between the composition of the placental microbiome and urinary tract infections, which suggests that such illnesses or antibiotics taken to treat them could alter the microbiome in unhealthy ways.

I have read and reread the paper (which I note - is not open access - making it hard to the public to actually dig into the paper if they wanted to).  And I see no evidence presented anywhere of the importance of oral health or any causal connection between oral health and the placental microbiome or risks to pregnancies. The claims made about this here in this news story are irresponsible.  Yes, there have been some other studies about dental health and birth issues.  But nothing in this paper.  And to imply otherwise is misleading at best.  And then to go on with "That may be a challenge for low-income women who can’t afford dental care" is really not appropriate.  And to then go on about UTIs and how treating them may "alter the microbiome in unhealthy ways" is also misleading and not supported.  

Where is the critical evaluation of such claims?  Certainly the paper is very interesting.  Among the findings of interest to me: (1) that low amounts of DNA from diverse microbes is found even in the placentas from healthy pregnancies and (2) that in their analysis these microbes were most similar to those from the mouth.  But how we get from those findings (and some others) to "the importance of oral health during pregnancy" and "such illnesses or antibiotics could alter the microbiome in unhelathy ways" is, well, not in the realm of scientific research.  This is in the realm of speculation.  And speculation is fine -IF YOU TELL PEOPLE YOU ARE SPECULATING.  If you don't tell people you are speculating I have another term for it - it is called misleading.  I assume the researchers and reporter did not intend to be misleading but that is the end result of excessive speculation without making it clear what one is doing.

Now this brings me to other articles about this study.  There are many out there.  And most seem to have eaten up this oral health connection without questioning it.  For example, consider the artilce in the New York Times yesterday:Study Sees Bigger Role for Placenta in Newborns’ Health - NYTimes.com by Denise Grady.  Some issues I have with this article:

• Let's start with the title "Study Sees Bigger Role for Placenta in Newborns’ Health."  Well, no - there was nothing in this study that showed any evidence about a new connection between the placenta and newborns' health.  
• NYTimes: "During pregnancy, the authors of the new study suspect, the wrong mix of bacteria in the placenta may contribute to premature births." Sure - they suspect it.  Would have been good to point out they have no evidence for this.
• NYTimes: Although the research is preliminary, it may help explain why periodontal disease and urinary infections in pregnant women are linked to an increased risk of premature birth.  Again, may help explain - sure.  But it also may have no connection whatsoever.  There is no evidence presented in the paper connecting periodontal disease and UTIs and the placental microbiome.  So this is pure speculation.  And it should have been met with some discussion of all the other ways that periodontal disease and UTIs could lead to risk of premature birth.  Like leading to increased inflammation in the mother.  Or affecting blood flow in the mother.  Or other things.  There is actually a TON of research in this area.  Below are some of the factors that affect preterm labor, as listed by the Mayo Clinic - are we now discounting the years and years of work on this and going whole hog into proposing a new cause without any evidence?
• Previous preterm labor or premature birth, particularly in the most recent pregnancy or in more than one previous pregnancy
• Pregnancy with twins, triplets or other multiples
• Certain problems with the uterus, cervix or placenta
• Smoking cigarettes, drinking alcohol or using illicit drugs
• Certain infections, particularly of the genital tract
• Some chronic conditions, such as high blood pressure and diabetes
• Being underweight or overweight before pregnancy, or gaining too little or too much weight during pregnancy
• Stressful life events, such as the death of a loved one
• Domestic violence or any form of abuse during pregnancy
• Multiple miscarriages
• Red blood cell deficiency (anemia), particularly during early pregnancy
• Too much amniotic fluid (polyhydramnios)
• Pregnancy complications, such as preeclampsia
• Vaginal bleeding during pregnancy
• Presence of a fetal birth defect
• Little or no prenatal care
• An interval of less than six months since the last pregnancy
• Also, having a short cervical length or the presence of fetal fibronectin — a substance that acts like a glue between the fetal sac and the lining of the uterus — in your vaginal discharge might be linked to an increased risk of preterm labor. 
• I note - the authors even say in their paper "Although this study is not able to address the relationship between periodontal disease and the placental microbiome, we, as a community of obstetricians, have appreciated for decades the association between periodontal disease and preterm birth". Clearly the paper received more scrutiny that the quotes and the news stories. 
• NYTimes: The new study suggests that babies may acquire an important part of their normal gut bacteria from the placenta. No.  Nothing in this study showed any connection between what is in the placenta and what is in the babies guts.  None.
• NYTimes: If further research confirms the findings, that may be reassuring news for women who have had cesareans. Some researchers have suggested that babies born by cesarean miss out on helpful bacteria that they would normally be exposed to in the birth canal.  Again - there is no evidence that babies pick up microbes from the placenta.  So speculating that this may reassure women who have C- sections is way way way too premature.
• NYTimes: “I think women can be reassured that they have not doomed their infant’s microbiome for the rest of its life,  said Dr. Kjersti Aagaard.  Wow. Now we have gone from "if further research confirms" to just flat out reassuring women who have had C-sections that there are no effects on the microbiome.
• NYTimes: “It didn’t make a whole lot of sense to us,” she said. “It’s not like babies are hanging out in the vagina. They come shooting out pretty fast.” Also, she said, they emerge covered in a waxy substance called vernix, which most likely helps keep bacteria from latching on. Wow.  So babies come shooting out of the vegina and therefore cannot get microbes from the vagina.  This despite the massive amounts of evidence that they in fact do get microbes from the vagina and that C-section born babies get a different community (see for example this).  (UPDATE 5/26 - see UPDATE below with some comments / papers about C-sections vs. vaginal birth and how my use of "massive" here may be an overstatement itself).

I could go on and on.  But I won't.  I am pleased the reporter talked to Martin Blaser who puts some damping on the speculation:

Dr. Martin J. Blaser, director of the human microbiome program at NYU Langone Medical Center, and the author of a recently published book, “Missing Microbes,” said that Dr. Aagaard’s study was important, but preliminary, and that it did not provide information that could be used in treating pregnant women. 

Thank you Martin.  But even with this, these articles leave me very frustrated.  The best I can do I guess is give out an award or two. So, for their reporting on the topic I am giving Denise Grady of the New York Times and Jocelyn Kaiser of Science News an Overselling the Microbiome award since they oversell the potential connection between oral health and infant health as mediated by the placenta.  And I am also giving this award to  Kjersti Aagaard, the first author of the paper, for her comments on the topic.

For more examples of "Overselling the Microbiome" awards see my page here.

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UPDATE: Some other news stories where the headline alone is painful

• Bacteria in placentas may provide diagnostic insight
• Friendly bacteria in placenta prepare babies for outside world
• How Bacteria in Placenta Could Help Shape Human Health
• Newborn's Health Influenced Significantly by the Placenta
• Microbes Lurking in Placenta Also Found in Your Mouth
• Bacteria in placentas of healthy women may play role in preterm birth
• Study says mom's mouth could transmit baby's first gut bacteria
• Women's wombs full of good germs, not bacteria-free after all, study finds
• Oral Hygiene May Be Important for a Healthy Pregnancy

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UPDATE 2: Some articles that discussed placental microbes before this story came out

• Human Microbiome May Be Seeded Before Birth - NYTimes by Carl Zimmer August 2013
• Funkhouser LJ, Bordenstein SR (2013) Mom Knows Best: The Universality of Maternal Microbial Transmission. PLoS Biol 11(8): e1001631. doi:10.1371/journal.pbio.1001631
• The Story Behind “Mom Knows Best: The Universality of Maternal Microbial Transmission”
• Yet another thing for which to blame/thank your mother ...

and many more

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UPDATE 3: Paper on placental - mother - infant connection not even mentioned

Just found this paper from a Google Scholar search:  Probiotics Modulate Host-Microbe Interaction in the Placenta and Fetal Gut: A Randomized, Double-Blind, Placebo-Controlled Trial.  Seems like it is of direct relevance.  Abstract is below;

Abstract
Background: Early host-microbe interaction provides important maturational stimuli for the developing immune system. The role of prenatal microbial contact remains elusive. Objectives: Our aim was to investigate whether microbes in placenta or amniotic fluid affect fetal innate immune gene expression during late pregnancy and whether innate immune gene expression profiles in the placenta and the fetal gut may be modulated by dietary supplementation with specific probiotics. Methods: Altogether 43 pregnant women were randomized to receive (1) Bifidobacterium lactis, (2) B. lactis in combination with Lactobacillus rhamnosus GG (LGG) or (3) placebo for 14 days before elective cesarian section at full term in a double-blind clinical trial. Bacteria in amniotic fluid and placenta were detected by quantitative (q)PCR. The expression of Toll-like receptor (TLR)-related genes in the placenta and meconium samples was assessed by qPCR. Gene expression patterns in meconium were interpreted to reflect immune physiology in the fetal gut. Results: The study was completed by 29 mother-infant pairs. Bacterial DNA was detected in all placenta samples. Microbial DNA in amniotic fluid and placenta was associated with changes in TLR-related gene expression in the fetal intestine. Maternal probiotic supplementation significantly modulated the expression of TLR-related genes both in the placenta and in the fetal gut. Conclusions: Microbial contact in utero is associated with changes in fetal intestinal innate immune gene expression profile. Fetal and placental immune physiology may be modulated by maternal dietary intervention using specific probiotics.

This paper was not mentioned or cited as far as I can tell in the current study.

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UPDATE 4: This paper also seems relevant

Microbial contact during pregnancy, intestinal colonization and human disease.  Abstract:

Interaction with colonizing intestinal bacteria is essential for healthy intestinal and immunological development in infancy. Advances in understanding early host–microbe interactions indicate that this early microbial programming begins in utero and is substantially modulated by mode of birth, perinatal antibiotics and breastfeeding. Furthermore, it has become evident that this stepwise microbial colonization process, as well as immune and metabolic programming by the microbiota, might have a long-lasting influence on the risk of not only gastrointestinal disease, but also allergic, autoimmune and metabolic disease, in later life. Modulating early host–microbe interaction by maternal probiotic intervention during pregnancy and breastfeeding offers a promising novel tool to reduce the risk of disease. In this Review, we describe the current body of knowledge regarding perinatal microbial contact, initial intestinal colonization and its association with human disease, as well as means of modulating early host–microbe interaction to reduce the risk of disease in the child.

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UPDATE 5 - more misleading quotes

• From Time's misleadingly named article "The New Way to Predict When Pregnant Women Will Deliver": “By focusing on oral health, we may actually be optimizing the health of the pregnancy and limiting the risk of pre-term birth,” says Aagaard. After paying so much attention to the more obvious ways to make a pregnancy healthy, it may be time to consider the less obvious – and less visible ones
• That quote is just so inappropriate ... uggh

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UPDATE 6: May 24.  Some  Made a Storify with some of the Tweets related to this post. Note - November 2018 replaced with Wakelet. UPDATE 7: May 26 - some other papers of relevance to birth mode and infant microbiomes and placentas

• Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns
• Development of the human infant intestinal microbiota
• Factors influencing the composition of the intestinal microbiota in early infancy
• Vaginal microbiome of reproductive-age women
• Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery
• Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery
• Molecular monitoring of succession of bacterial communities in human neonates

A key question to me I guess is the following - how do differences between the microflora in babies born by C-Section vs. vaginal birth arise if the microbes in placentas have a big role in colonizing infants?  Perhaps the differences between C-section babies and vaginal birth babies are small -- I do not know -- need to dig into this more.