by Sondra Turjeman

The microbiome has been a hot topic for the past several years; you may have heard the claim that the bacteria and other microbes (the “microbiome”) in our body outnumber our own cells. While there is some debate about the actual number, the microbiome is very large, estimated at 39 trillion bacteria cells on average1, and implicated in a number of health functions and day-to-day processes, including food breakdown and vitamin synthesis. Each microbiome is unique to its host, varying in the types and abundances of microbes present, and microbiomes in different parts of the body (e.g. mouth, gut, vaginal, skin, oral) differ greatly. Variation in microbiomes can arise from both internal (e.g. host genetic makeup, health, gender) and external (e.g. diet, hygiene) drivers, with varying implications on host wellbeing.

Dr. Moran Yassour, a new faculty member at the Hebrew University, Jerusalem, affiliated both with the Microbiology & Molecular Genetics Department, Faculty of Medicine and the School of Computer Science and Engineering, studies the infant gut microbiome. Specifically, she is interested in understanding how the newborn gut microbial community is established. About a decade ago, a number of research groups found supporting evidence of significant microbiome differences between infants born vaginally and those born via Cesarean delivery2, yet Yassour explains that the microbiomes of infants born vaginally do not match those of their mothers’ birth canals.

The Yassour Lab is trying to understand why this is the case. To this end, Yassour enrolled 190 mother-partner-infant trios at the time of their admission into the hospital prior to birth (in Boston, USA), collecting samples for each individual from various body niches. Not only did Yassour compare microbiota across individuals and body niches in light of birth method (vaginal birth, planned cesarean delivery, emergency cesarean delivery), but she is now working to identify which specific bacteria and stains drive these differences.

Instead of using the common 16S sequencing method which focuses on one (highly variable) gene, Yassour employed the more advanced and data-heavy method of shotgun metagenomics3. This method involves deep sequencing the entire DNA content (all genes) of all of the various microbes in a given sample. The real challenge is sorting out the sequences and assigning names to the jumbles of letters.

As she describes it, it’s as if one had to piece together the entire contents of a library following an earthquake. All of the pages are scattered on the floor and ripped, and they each must be pieced together, sorted, and returned to the book from which they came. In shotgun genomics, though, the resolution goes beyond the “book”; the goal is to differentiate between different strains of a given bacteria or different editions of the same book. The amount of data generated from a single microbiome using shotgun sequencing is on the order of 10-50 million sequences, and for each individual in the study, multiple samples are collected. Assigning a bacterial identification to each sequence is more than half the battle. In her postdoc, Yassour developed computational tools to classify bacteria from sequencing reads and also to analyze data from the same individual at multiple timepoints while comparing multiple samples from the same family unit.

The data processing step is both tedious and rewarding – Yassour has already uncovered some surprising patterns. When examining infant microbiomes, she found that infants born via emergency cesarean deliveries, meaning they were first exposed to the birth canal and only later delivered surgically, had microbiomes more similar to infants born via planned cesarean delivery than those that passed through the birth canal.

This supports the finding that most infants born vaginally do not share the microbiota of their mother’s birth canal. Yassour hypothesizes that some other source, likely the rectal microbial community, contributes more substantially to the gut microbiomes of infants. If this is the case, then infants born via emergency cesarean delivery would never be exposed to the relevant source microbiome (the rectum) despite their exposure to the birth canal.

Yassour is now building additional cohorts of mother-infant pairs to better understand mother-to-child bacteria inheritance. She is currently enrolling families to three new cohorts, focusing on the Bedouin community in southern Israel, mothers with Inflammatory Bowel Diseases (IBD), and antibiotic resistance transmission to premature infants. Comparisons of microbiota across cohorts (Scandanavian, American, Bedouin) should help Yassour put the rest of the puzzle together.

  1. Scientists bust myth that our bodies have more bacteria than human cells: https://www.nature.com/news/scientists-bust-myth-that-our-bodies-have-more-bacteria-than-human-cells-1.19136
  2. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns: https://www.pnas.org/content/107/26/11971.full  
  3. Characterization of the gut microbiome using 16S or shotgun metagenomics: https://www.frontiersin.org/articles/10.3389/fmicb.2016.00459/full

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