Your microbiome could be used to identify you

Scientists have long speculated that each individual’s microbiome may be unique and static enough so that it could be used for identification.  This becomes very important for forensic investigations, which we have written about before, and also raises many ethical concerns regarding privacy during microbiome sampling and donation.  Previously, most of the studies on this topic were not exhaustive enough to provide any firm conclusions.  Last week though, Curtis Huttenhower’s group from the Harvard School of public health published a powerful, and statistically robust method for tracing the a microbiome back to its host.  The study was published in the Proceedings of the National Academy of Sciences.

Using the Human Microbiome Project (HMP) database, the scientists used machine learning to construct a test for the most important conserved metagenomics traits after comparing individuals’ microbiomes over time.  The algorithm depended on both 16s rRNA sequences, as well as whole genome sequencing (in addition to derivatives of the whole genome sequencing).  The researchers note that the algorithm is not just looking for microbiome genes that are conserved over time, but rather microbiome genes that are conserved over time and unique amongst the population.  Overall, they found that after a year, their algorithm could accurately identify 86% of people based on their stool samples, with very few false positives.  Other sites on the body, like the skin, were less effective for identification, but it was feasible to use them.

This team definitively proved that a microbiome can be used to identify its host.  They admit that full sequencing if the microbiome is necessary, but regardless, it is possible.  This has all sorts of ethical and privacy concerns associated with it.  For example, microbiome data that is made publically available, though anonymized, could be traced back to its donors.  This could include information like STDs or other diseases.  Another obvious application of this would be in forensics, and it probably wont be long before a case hinges on microbiome evidence.

IBD, Crohn's disease, and the microbiome

There have been several large scale studies that show a definite association between the microbiome and inflammatory bowel diseases like Crohn’s and colitis.  While it is becoming clear that the microbiome plays a pivotal role in these diseases, the exact mechanisms of pathogenesis are not known.  One of the reasons it has been so hard to uncover this link is because of a lack of robust studies, that usually contain small sample sizes.  In response, a team of leading scientists in the field, including multiple scientists from our own scientific advisory board, assembled a brand new cohort, the largest of its kind, to study the disease.  The cohort consisted of 447 children with newly diagnosed, still untreated, Crohn’s disease and 221 healthy children.   They then combined this data with two other cohorts that included adult patients to bring the total number of samples to 1,742.  The first results of this study were published in Cell Host and Microbe, and shed many insights into IBD and its relationship to the microbiome.

In the study the researchers sampled and sequenced the microbiome of the gut mucosa and stool.  From this data, they identified specific bacteria that had higher abundances in diseased patients, like Enterobacteriaceae and Veillonellaceae, and others that had lower than normal abundances, such as Clostridiales and Bacteroidales.  According to the samples, these relative abundances were more pronounced in the mucosal samples, rather than the stool samples, meaning that the mucosa may play a more important role in Crohn’s pathogenesis and diagnosis.  Moreover, children under age 10 did not have large populations of the ‘bad’ bacteria, which were negatively correlated with age.

Another important finding from the study is that antibiotic treatment of the Chrohn’s disease further exacerbated the microbial imbalances (dysbiosis), and caused the bad bacteria to proliferate and the good bacteria to die off.  The researchers are quick to dismiss antibiotics as the cause of the disease, rather hypothesizing that the antibiotics allow for opportunistic bacteria to grow which may cause dysbiosis.  They also encourage further research on the subject and question whether antibiotics should be prescribed to IBD patients.

The researchers used this knowledge of the dysbiosis to create a potential diagnostic for IBD.  They were able to calculate a microbiome diversity index by sampling the mucous for the existence of certain bacteria and for overall microbiome diversity.  The index shows remarkable ability to not only accurately predict the existence of IBD, but also the severity of it.  Also, the researchers showed their microbiome dysbiosis index could be combined with clinical data to better predict the future outcome of the disease.

A final conclusion of the paper is that the gut mucous is a more accurate signal for IBD.  They conclude that stool samples are composed of higher levels of aerobic, oxygen using, bacteria than those in gut, and that stool is not representative of the overall microbiome.

This study is the first to rigorously tackle IBD, specifically, Crohn's disease, and the microbiome.  We now know what bacteria are most highly associated (both positively and negatively) with IBDs, and how this this information can be incorporated into early diagnostic screens.

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.