Current challenges in microbiome research

Scanning electron micrograph of E. Coli bacterium.

Curtis Huttenhower, Rob Knight, Owen White, Jacques Ravel (all members of our SAB), and others recently published a commentary titled "Advancing the Microbiome Research Community" in Cell.  The paper was a 'State of the Microbiome' address and outlined the current challenges and the future outlooks of the microbiome field.

Among the many challenges they outlined include how to design causality studies, and how to attribute causality of phenotypes to specific bacteria, proteins, or metabolites.  The paper also discussed the bioinformatics bottleneck that is occurring in the field, as the necessary expertise required to properly analyze sequencing data is severely lacking.  There also lacks a proper centralized online repository for all sequencing data that is generated.  This sequencing data needs to include metadata that would describe how the data was generated.  Furthermore, the authors describe the need for guidance on how to properly define and comprehensively describe phenotypes, such as inflammatory bowel disease (IBD), in microbiome studies.  Without this standardization, proper comparison between studies can not take place.  Finally, institutional review boards (IRBs) need guidance on how to properly regulate human microbiome studies in order for scientists to properly prepare and carry out their projects.

While the above areas are only a few of the challenges facing the field, each of them reinforces the mission and programs of the AMI.  The MBQC is standardizing techniques and creating rigorously tested analytical protocols by investigating the sources of variation in microbiome testing.  In addition, the AMI is focusing on future data repository efforts.  These are just a few of the areas we hope to serve the field in the coming years.  We believe a nonprofit, specifically the AMI, can help fill these voids and address many of the issues outlined in this paper.

Microbiome and breast cancer

A recent study out of the University of Maryland suggests that post-menopausal women with a more diverse microbiome have a lower risk of getting breast cancer.  The study investigated the fecal microbiomes of 60 healthy women between the ages of 55 and 69 while also testing the estrogen and estrogen metabolites from their urine.  The results showed a correlation between increased urinary metabolites with increased gut microbiome diversity, independent of other variables.

This is important because estrogen that circulates through the body, that isn't broken down and removed by the body, is correlated with an increased risk for breast cancer.  Therefore, decreasing the amount of circulating estrogen, and increasing the rate at which estrogen is removed from the body may result in a lower risk of breast cancer for post-menopausal women.

It is known that as estrogen and its byproducts are naturally processed, they are circulated in and around the gut, which has led scientists to speculate that the gut microbiome may be important to estrogen cycling and removal in the body.  The authors of this paper help support this hypothesis by showing that microbiome diversity effects estrogen removal.

This paper opens the door to some very interesting questions.  Can microbiome diversity be used as a diagnostic for breast cancer risk?  Can the gut microbiome be adjusted to decrease breast cancer risk?  A nice summary of the findings with quotes from the authors was also published by Science Daily.

Caesarean sections, breast feeding, and the microbiome

There is a growing amount of literature on the subject of babies' microbiomes because it is clear that the first few years of life are crucial to the development of the immune system, and poor development can have lasting, life-long consequences.  As we have learned, a healthy microbiome is absolutely critical to a healthy immune system.  Evidence for this connection is vast, but starkly manifests itself in germ-free mice which can not survive long due to autoimmune disease.  So, as the thinking goes, a healthier microbiome as a baby leads to a healthier life.

In any case, a commentary was recently written by AMI Scientific Advisory Board members Maria Gloria Dominguez-Bello, Rob Knight, and a colleague that discusses how delivery mode and infant feeding affect babies' microbiomes.  As it turns out, epidemiological studies on large human populations have correlated Caesarean Section (C-section) delivery to obesity, asthma, celiac disease and type 1 diabetes, which are all autoimmune diseases.  Breast feeding, on the other hand, leads to decreased risk for some of these same diseases.

Research has shown that both C-section and breast feeding have a direct and significant influence on an infant's microbiome.  During vaginal delivery the child's gut is inoculated with the vaginal microbiome, whereas in a C-section the child's gut is associated more with the skin microbiome.  In addtion, breast feeding contains prebiotics that encourage certain bacteria to grow, which selects for a specific infant gut microbiome.  

Interestingly, the authors mention a study that showed the microbiota from the breast milk may actually be different depending on the mode of delivery.  They also comment on a study that showed certain gut bacteria are found in the vaginal microbiomes of pregnant women, as if prepared to inoculate the child.  This is in agreement with another study from Jacques Ravel which I have already blogged about.

It is very important to consider the microbiome when a woman is giving birth and feeding.  If a C-section is required it may be possible to inoculate the child's gut manually, and studies are currently investigating this.  The results of these studies will be the topic of a future blog. 

Pregnancy and the microbiome

There have been a number of studies that discuss the importance of the microbiome transfer between mother and child; however few studies have looked into the changes that occur to the mother's vaginal microbiome during pregnancy.

A new paper published in the journal Microbiome by AMI Scientific Advisory Board member Dr. Jacques Ravel of the University of Maryland School of Medicine presents a longitudinal study of the vaginal microbiome of women during the course of pregnancy and compared that with women who were not pregnant.  The overall findings of the study conclude that there are statistically significant differences in the vaginal bacterial populations between pregnant and non-pregnant women.  Furthermore, the microbiome of pregnant women was more stable in non-pregnant women.

While there is a difference in the microbiome between pregnant and non-pregnant women, the authors stress that this difference in microbiomes may NOT be exclusive to pregnancy; therefore  at this point, not suitable for diagnostic purposes (say determining pregancy).  Furthermore, it is not known if these differences in any way benefit pregnant women or are just the result of different vaginal environments, for example higher estrogen levels in the vagina.

Finally, another paper that was possibly from the same longitudinal study showed no statistical connection between the vaginal microbiomes of women who go into pre-term labor and those who carry their child full term.