Crowd-Sourcing Drug Discovery

“The first challenge that OSDD’s cyber-community assigned itself was to glean more information from the M. tuberculosis genome. It was sequenced in 1998, but researchers had clues to the functions of only a quarter of its 4000 genes. In December 2009, OSDD set out to reannotate all possible genes. Some 500 volunteers got the job done in a mere 4 months. Now OSDD is trying to exploit these data. “The more people you put to work on the problem, the more chances you will have to identify the set of compounds that will likely make it through compound optimization, animal models, preclinical, and, eventually, clinical trials. If you increase your success chances, then your overall costs decrease,” says Marc Marti-Renom of the National Center for Genomic Analysis in Barcelona, Spain.”

FoldIt, GalaxyZoo, now this. Is the next phase of computing networked human computing?

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Friendly bacteria move in mysterious ways : Nature News

“Many yoghurts are loaded with live bacteria, and labelled with claims that consuming these microorganisms can be good for your health. But a study published today shows that such yoghurts have only subtle effects on the bacteria already in the gut and do not replace them.”

Yes, but the paper goes to point out that both in humans and mice, there was an upregulation of polysaccharide metabolism genes in the existing gut microbes. Hm, there are some serious implications there.

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Probiotic-prebiotic combination may ease eczema in kids: Study

“Supplements containing a combination of Lactobacillus salivarius and fructo-oligosaccharide for eight weeks were associated with significant reductions in measures of the severity of eczema, compared with a control group receiving only prebiotics, according to findings published in the British Journal of Dermatology.”

In addition to the usual yogurt bugs, I am starting to see salivarius popping up more frequently. It’s from the mouth, by the way.

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Fortify your poop – Transfaunation

As you know, I’m always looking for practical uses of microbes. One that I stumbled upon a long while back was “transfaunation”, or, seeding one person’s gut with microbes from another’s. Yes, transfering poop microbes from one to another.

Be an adult. Don’t get grossed out. I’ve read some great papers on the process how our guts get colonized after birth. Also, there are some really interesting papers on how our gut microbes (or lack thereof) are involved in various intestinal disorders. And there are some promising papers on how diet affect the bacterial ecology in the gut. [Sorry, I'll link to the papers in a larger gut related set of posts at some point in the future - you can also just search for gut and microbes in my posts.]

Here’s the basic idea. People suffering from the hardy C. diff bacteria are generally prescribed a powerful antibiotic. Problem is, the drugs don’t just kill the invaders; they also wipe out much of the beneficial bacteria in the gut. With these “good” microorganisms out of the way, any C. diff stragglers have a much easier time regrouping for a second bout of illness. If there were some way to respawn the beneficial bacteria in the intestines, such re-infections could be warded off. Some people, like Ruth, turn to expensive probiotic supplements. (At one point she was spending $350 on them every week.) But in certain cases, a patient who has lost nearly all of her good bacteria will find it nearly impossible to get them back. A fecal transplant seems to work as a sort of mega-probiotic, allowing doctors to repopulate a patient’s intestines with the appropriate microorganisms by placing a robust sample directly into her gut.

Slate had a nice article on the subject (quoted above). It’s a serious subject and for many, the only hope to get a better and healthier bacterial gut fauna (hence the term, transfaunation).

My wife’s a vet and she’s not only heard of this procedure, but performed it on animals. It’s not uncommon to jumpstart an animal’s ability to digest grass by grabbing bugs from one animal and putting it in the right place. And, did you know, some animals eat poop on purpose for this very reason – rabbits, capibaras, hamsters, elephants, termites, pandas, koalas, and hippos – to colonize their gut?

And really, folks eat yogurt to populate their gut with good bacteria. Why not poo bacteria as probiotics? I actually think, as we learn more about our gut fauna, this will be come a more accepted course of action for folks with nasty bowel infections, colitis, or inflammatory bowel diseases.

What do you think?

Image of Kristen Paulson’s Anatomy and Guts Embroidery Hoop Art on Etsy (get your own!)

Health benefits and health claims of probiotics: bridging science and marketing – BJN

“Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority. Despite a substantial amount of basic and clinical research on the beneficial effects of probiotics, all of the evaluated claim applications thus far have received a negative opinion. With the restrictions on the use of clinical endpoints, validated biomarkers for gut health and immune health in relation to reduction in disease risk are needed. Clear-cut criteria for design as well as evaluation of future studies are needed. An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.”

Not sure what to make of this other than the comment that ‘clear-cut criteria’ will be needed to actually turn claims into science.

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Ecology drives a global network of gene exchange connecting the human microbiome : Nature : Nature Publishing Group

“Horizontal gene transfer — the exchange of genetic material between different species or lineages — is an important factor in bacterial evolution. A study of human microbiome data comprising more than 2,000 full bacterial genomes shows that this environment is a hotbed of horizontal gene transfer: pairs of bacteria isolated from the human body are 25-fold more likely to share transferred DNA than pairs from other environments. Thus microbial ecology — rather than phylogeny or geography — is the most important driver of the patterns of horizontal gene exchange. Further analysis revealed 42 unique antibiotic-resistance genes that had been transferred between human and agricultural isolates, and 43 transfers across national borders.”

This paper sets me spinning due to it being about microbes, microbes on humans, human microbial ecology, and horizontal gene transfer. The other thing that is intriguing about this paper is the mention of unique antibiotic-resistance genes.

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Vampire-like Predatory Bacteria Could Become A Living Antibiotic : Discover Magazine

“What’s the news: If bacteria had blood, the predatory microbe Micavibrio aeruginosavorus would essentially be a vampire: it subsists by hunting down other bugs, attaching to them, and sucking their life out. For the first time, researchers have sequenced the genome of this strange microorganism, which was first identified decades ago in sewage water. The sequence will help better understand the unique bacterium, which has potential to be used as a “living antibiotic” due to its ability to attack drug-resistant biofilms and its apparent fondness for dining on pathogens.”

Absolutely awesome. And if there’s one bug that does this, there must be many many more.

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Host response: Probiotic ingestion alters mood : Nature Reviews Microbiology

“There is growing evidence that the intestinal microbiota interacts with the host central nervous system (CNS) to modify stress responses and anxiety behaviour; this is the so-called gut–brain axis. Bravo et al.Lactobacillus rhamnosus JB-1 can alter the transcript level for receptors of the neurotransmitter GABA (γ-aminobutyric acid) in the CNS in a region-dependent manner.”

Yet one more data point on the bugs-gut story.

[This is not an open access article. Boo. Hiss.]

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PLoS ONE: Barcoded Pyrosequencing Reveals That Consumption of Galactooligosaccharides Results in a Highly Specific Bifidogenic Response in Humans

“Prebiotics are selectively fermented ingredients that allow specific changes in the gastrointestinal microbiota that confer health benefits to the host. However, the effects of prebiotics on the human gut microbiota are incomplete as most studies have relied on methods that fail to cover the breadth of the bacterial community. The goal of this research was to use high throughput multiplex community sequencing of 16S rDNA tags to gain a community wide perspective of the impact of prebiotic galactooligosaccharide (GOS) on the fecal microbiota of healthy human subjects.”

I’ve seen a ton of papers on “probiotics”, but I think this is the first I’ve heard of “prebiotics”. There is mounting data about the effect of gut bugs on our own systems, and there is a growing set of data on how our diet affects our gut bugs. A wee Google search shows that there’s been a lot of papers data on specific foods that selectively promote the growth of specific gut bugs.

Hm, this is really interesting. It all seems to be coming together. My suggestion: if you’re a grad student or a post-doc in biology, human gut microbiology and ecology is gonna be a big topic in the near future. It’s gonna change the face of medicine.

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Rediscovering Bits of 1890s

“”Laurie Cox, a graduate student who works in the lab, held up the test tube with the 100-year-old bacterium. She explained that they can determine if the spores are alive by their growth, which should be visible within 24 hours. “I think it’s really interesting and amazing to be able to culture bacteria that’s over 100 years old and to see what we can do with it,” she said. Dr. Blaser said they will attempt to sequence the genome and compare it with a modern organism to see how things have changed. “We’ve had 70 years of antibiotics, so the question is, have there been new changes in the bacterial genome from the time of that organism,” he said on Tuesday. “It’s an opportunity to compare our ancient organisms with our modern ones.”"

Really cool. I wonder how many old vials are stored away with interesting bacterial samples.

[via @bruces and @paleofuture]

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