The glories of the gut? Ask a fat mouse!

So Friday was all about things we should care about…Dr. Rob Knight enlightens on the awesomeness of microbial ecology and microbiome studies and Evan (which will be posted later) regales us with tales of human genomics and structural variation in an effort to convince us the Human is still a pretty nifty animal to study!

But first…Rob

Dr. Rob Knight
University of Colorado, Boulder

Topic: Microbial Ecology and Metagenomics

 “It is important to remember our world is a microbial world.”

Why you should care about microbial community ecology in the context of bioinformatics?

  • Most molecular diversity can be found in microbes
  • 99+% cannot be cultured, we only know then from sequences
  • rRNA is an excellent/uniquely good genetic marker
  • rRNA is found in all species
  • Fast/slow evolving regions
  • We have large preexisting databases which are good for designing universal PCR primers (from conserved regions) The Greengenes database is a really good reference for 16S rRNA.
  • Microbes are ubiquitous and provide key ecosystem services: air quality, water quality, natural ecosystem balance.

So the obsession of the microbiome has dated as far back (or further) to the 1600’s. Van Leeuwenhoek made the observations that…

“…animalcules were in such enormous numbers, that all the water…seemed to be alive” –Van Leeuwenhoek (1683)

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Continuing on with why we should continue to care about microbes:

  • They determine whether tylenol is toxic to your liver.
  • They tell you who to have sex with if you’re a fruit fly
  • They steal genes from your food to help you digest it
“If you haven’t tried the sushi in St. Louis, you really shouldn’t”

 

There are as many E. coli in your gut as there are people on earth, a little freaky but there you have it! E. coli is a classic gut microbe and is incredibly good at living in captivity. E. coli can be as much as 40% different from other E. coli cells.

 

Anotherwards:
“You are not a beautiful unique snowflake but your microbes might be.”
Awww...sad.
Awww…sad.

So now we can ask some questions:

  • How human are we?
  • How can we develop technologies that manipulate our microbiota to improve health
  • How are microbes distributed across our bodies?
  • How do our microbes change over time?
  • Classical studies have been done and continue to be done on mice, how do we translate between humans and mice?

From a bioinformatics perspective we have a wealth of applications we can look at:

  • Homology
  • Sequence alignment
  • Phylogeny
  • Assembly
  • Functional assignments
  • Distance metrics
  • Dimensionality reduction
  • Classification
  • Networks
  • Data visualization

And with sequencing getting cheaper and cheaper by the day, the issue is needing to interpret vast amounts of sequence and tree data.

One of the studies highlighted by Rob was microbial biogeography on the keyboard where few microbes survive. They wanted to answer a variety of questions including if there was a Wallace line between the keys G & H. They found that each individual has a unique skin community. They used QIIME to integrate analysis of 100’s of samples!

QIIME analysis of keyboards
QIIME analysis of keyboards

So the QIIME workflow in short…

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In terms of next generation sequencing they were using 454…which prompted this quote from Rob:
“Why is it called 454?…
Because that’s the temperature you burn bills at when you start sequencing with it.”
Rob continued to highlight studies conducted by his group and in collaboration with others using QIIME to explore microbiomes…rob5
They looked at specific sites of the human body, they’ve looked at infants born via vaginal versus C-section births, showing the initial microbial colonization of infants and how that microbiome changes over time as we become adults and our microbial communities stabilize.
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The Human Microbiome Project (HMP) only started to cover the true diversity of the human population…
The American Gut project (AMP) took it further, wanting to include more ages and international involvement to assess the human microbiome…starting out as a crowdsourced Indiegogo project! They have now just released data on the first 1080 AMP samples. And their results have  indeed covered a wide gammut of human diversity with samples ranging in age from 0-80+ years of age, and conditions such as obesity from BMI levels ranging from underweight to severely obsese. And their results have been very consistent with previous studies conducted on the microbiome which is exciting.
hey look there's Daniel!
hey look there’s Daniel!
Moving on… Rob talks about how we can tell cause from effect with respect to the human microbiome. We cannot exactly whip out Koch’s postulates and act them out on humans we might have a few…just a few IRB as well as legal and ethical problems with that. BUT, we have a gnotobiotic mice (germ free)! And we can use these mice to look at whether differences in microbiome matter. To quote Rob’s slide:
Do differences in microbiome matter?
Ask a Fat Mouse…”
I highlighted one of these studies in Rob’s faculty highlight so if you’d like to review it, go here.

So what were they finding essentially?

  • There were a lot more firmicutes in obese/obese mice
  • Genetic mutation can be passed by doing a gut community transfer.
  • Gut microbes associated with obesity: the more weight the mice lost the greater the change in microbial community.

Future directions look toward personalized medicine in developing nations and these pilot studies in humanized mice should allow us to look at issues of obesity and malnutrition in the developed and underdeveloped world.

And with that Rob ended Part I…and released us all for coffee
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