Human microbiome program?

Because of the importance of beneficial / commensal microbes in human biology, there have been growing efforts to characterize the microbes in various body locations – gut, mouth, lungs, skin, etc. But the efforts so far have simply given a tantalizing taste of how interesting and important these microbes are. So here comes this meeting. Organized by NIH (specifically, Francis Collins at NHGRI), this workshop is geared to discuss the possibility that studies of the human microbiome will be included in the next list of “NIH Roadmap” programs. More on the NIH Roadmap some other time.

Basically, the general idea is – do we need an big scale, organized program to tackle the human microbiome.? To get us in the mood, we had talks by many of the pioneers/leaders in the field (e.g., David Relman, Jeff Gordon, Jim Tiedje) as well as discussion of the NIH Roadmap program. I personally did not need any convincing but it was good to hear some of the ideas presented. In the end, I think there is no doubt that a large scale Human Microbiome Program is needed and would be very beneficial.

In addition to the 10 trillion human cells, there are 100 trillion bacterial cells in a body. Our metagenome may be 100x the human genome.
2010-10-30: Space Standard Microbiome. Venter suggests NASA should replace the microbiome (bacteria species) of astronauts with a standardized, synthetic one to improve survivability of space flight.
2012-06-15: 0.3% Human

Where the human genome carries some 22K protein-coding genes, the human microbiome contributes some 8M protein-coding genes responsible for human survival: 360x more.

The microbiome is one of the most fascinating areas in biology:

in many mammals a microbial community ferments various sweats, oozes and excretions into distinctive scents that reveal age, health and much more to knowing noses in a select social circle.

That’s right, microbes are posting status updates to each other through smells, sharing with other microbes what they’ve learned about host animals.
2012-12-08: American Gut looks amazing. I will of course participate. Since you are only 10% human (the rest is bacteria), even if you do 23andme you don’t really know yourself at all. $99 for 1 bacterial DNA kit, $180 for 2. There are also higher levels, up to the $25k ultra-deep sequencing of your microbiome sample aimed at generating as many individual bacterial genomes as possible.
2015-03-03: a nice summary of The American Gut project

2016-10-01: Poop Bot. As usual, onion’s satire is leading the way:

you can tell the most about someone by sampling their microbiome, and “the sewage system is the great aggregator.” Gross, sure, but Ratti is studying waste to understand everything from heroin use to antibiotic-resistant bacteria—and all with the help of a sewer-slurping robot named Luigi.

2017-09-05: Microbiome 99% unknown

A survey of DNA fragments circulating in the blood suggests the microbes living within us are vastly more diverse than previously known. In fact, 99% of that DNA has never been seen before. The “vast majority” of it belonged to a phylum called proteobacteria, which includes, among many other species, pathogens such as E. coli and Salmonella. Previously unidentified viruses in the torque teno family, generally not associated with disease but often found in immunocompromised patients, made up the largest group of viruses.

2018-10-03: SynBioBeta 2018

In 15 years, brain interfaces will be as common as the cell phone. The radical experiment that has been run over the past 100 years shifting the microbiome of infants and provoking a wide array of immune disorders (allergies, asthma, diabetes)

2019-08-07: Microbiome Friendships?

Now that it is clear that social behavior plays a role in shaping the gut microbiome, the next question is whether microbiomes have had a meaningful impact on our social worlds. Scientists still do not have an answer, but they are tantalized by the possibilities, which could have implications for understanding the evolution of sociality.

2019-12-04: Microbiomes Affect Fear

microbiomes can influence the fear responses of their hosts, possibly by releasing compounds that affect the brain’s neuroanatomy and function.

2022-02-22: Space microbiome

Humans aren’t the only organisms that we have to consider when evaluating the impacts of space travel. While we are traveling on spaceships, microbes are traveling on us. Microgravity has been shown to alter bacterial growth patterns and kinetics, and radiation increases the frequency of mutations—in both cases creating opportunities for increased antimicrobial resistance—all in an environment where astronauts immune systems are compromised. The ISS has a complex microbiome that we fundamentally alter, and that in turn alters us. It’s important to be able to understand the genetic basis of antimicrobial resistance in space. A team of researchers carried out a study with the goal of addressing this question. A considerable number of AMR genes were found in several different locations for Kalamiella piersonii—a microbe potentially involved in causing urinary tract infections. Worryingly, “the potentially very pathogenic microbe E. bugandensis was found in location 2 (forward side panel wall of the Waste and Hygiene Compartment) in flight 1, presenting more than 40 ARGs.” They were also able to detect specific types of potential drug resistance for several microbes within the Pantoea species—which provided a higher level of resolution into observations made in their past analysis.

2023-01-19: person-to-person transmission

Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did.

2023-05-04: Using dental plaque to reconstruct the oral microbiome

Reconstructing an oral microbiome—a soup of 100s of different bacterial species, and millions of individual bacteria—from degraded ancient DNA is “like throwing together pieces of many puzzles and trying to solve them with the pieces mixed up and some pieces missing entirely”.

It took 3 years to adapt DNA sequencing tools and computer programs to work with the much shorter fragments of DNA found in ancient samples. Drawing on dental calculus from 46 ancient skeletons—including a dozen Neanderthals and modern humans who died between 30k and 150 years ago, Warinner identified DNA from 10s of extinct or previously unknown oral bacteria.
Identified as a type of bacterium called a chlorobium, its modern relatives use photosynthesis to survive on small amounts of light and live in anaerobic conditions, such as stagnant water. They aren’t found in modern mouths and appear to have vanished from ancient humans 10 ka BP. This chlorobium might have entered the mouths of ancient people because they drank water in or near caves. Or it might once have been a normal part of some people’s ancient oral microbiome, surviving on faint light penetrating the cheek.

2023-06-08: Sample handling ruins many studies

The authors have tried all sorts of sample-handling variations, and it looks like they have had trouble finding any that don’t change the composition of the microbial samples themselves. Both papers investigated the 2 commercially available stool sample kits (OMNIgene and Zymo), and found that the latter was much more sensitive to temperature variations on storage. And both kits changed the absolute levels of various bacteria types: the OMNIgene-preserved samples had significantly higher amounts of Bacteroidetes species as compared to preservative-free controls, while the Zymo-preserved ones had significantly lower amounts. The second paper also finds that the method used for cell disruption can significantly affect the ribosomal RNA reads used to characterize the bacterial species as well.

Researchers in the field should also be measuring total bacterial load in their samples and monitoring that for signs of variability in their sample handling and people should standardize on 25 PCR cycles, because that can also change things. These effects can help explain the widely varying literature results in human microbiome studies.

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