Links of note/Science/Strategy/The Narrative

The wacky world of horizontal gene transfer, genomic variants, and what we think are microbial species

Posted on by charlie

“The main difference from eukaryotes is that prokaryotic reproduction is independent of DNA acquisition and recombination. Instead, DNA is obtained from fragmented chromosomes obtained via parasexual means (that is, without reproduction). These mechanisms of DNA exchange are not restricted to gene exchange within species, and therefore traits can and do come from highly divergent organisms. For example, imagine that acacia trees could exchange DNA with lions and that the resulting new tree developed “limbs” that allowed them to attack grazing giraffes. This is in a sense what prokaryotes do all the time.”

I am fascinated by horizontal gene transfer, whereby microbes from different species share genetic information. Species, as we all learn, are defined by not being able to exchange genetic information and produce fertile offspring.

Of course, microbes flaunt this rule.

The prevalence of gene transfer, where bacteria of different species exchange genetic information, blurs the boundaries between “species”. I remember listening to Penny Chisholm talk to Ira Flatow about Parachlorococcus and redefining what we call a species of microbes, which she called “genomic variants.”

The quote above is from a review of an article in Science that examines speciation in marine bacteria. It discusses how the investigators found prevalent horizontal gene transfer. But the cool thing, as I understand it, was that many of the same genes were being captured by bacteria in the same ecological niche.

In short, the environment is selecting for horizontally transferred genes to be conserved. These genes are not transmitted through organisms in the same species, but all of the bacteria are being selected to keep these transferred genes. In short, many of the genes from a population do not have a common ancestor (as in, cells dividing and propagating genes that way).

Even cooler, an analogue has been seen in prokaryotes, in a sense. Darwin’s finches all share genetic information through the usual repeated back-crossing between species, but ” the characters defining their ecological niche appear to be maintained through selection.”

So I guess we are talking about genomic variants, but not necessarily variants with the same ancestor – the ecological niche selects for that genomic variant, which has a collection of genes from the mother cell (ancestor) and from other cells (horizontal gene transfer)

That’s so cool.

via How Bacterial Lineages Emerge.

Links of note/Strategy/The Narrative

Another article on “Patterns of Early Gut Colonization Shape Future Immune Responses of the Host” in PLoS ONE

Posted on by charlie

“In conclusion, a time window exists that enables the artificial colonization of GF mice by a single oral dose of caecal content, which may modify the future immune phenotype of the host. Moreover, delayed microbial colonization of the gut causes permanent changes in the immune system.”

Ok. So there’s mounting evidence that rapid colonization of the gut of neonates is important to immune development. Next step is to translate that into real medical therapies. There are immune and gut diseases that afflict newborns (also, in many cases, newborns are bombarded by antibiotics at this crucial time) – what have we learned to make them healthier and also ensure that their immune system develops properly?

via PLoS ONE: Patterns of Early Gut Colonization Shape Future Immune Responses of the Host.

Links of note/Strategy/The Narrative

New Old Publishing and “The New Value of Text”

Posted on by charlie

“Finally, the text still requires context. As publishers spin up their digital and print-on-demand backlists, more and more is published with less and less context. These efforts amount to land-grabs and rights-squatting, without adding value. Works without TOCs, indexes, author bios, footnotes. Placing work in context is one of publishers’ primary tasks, stretching out to commissioning introductions, assembling background material, supporting biographies and critical studies. Design belongs here too: good book design, appropriate book design, as important now as it has ever been.

“Velocity, depth, breadth. These are the dimensions we can add to books, that are the gifts of a digital age, not gimmicks, glossy presentation and media-catching stunts.”

What I like about James Bridle is that he’s in love with books and is able to bridge the bits and atoms worlds, translating and informing in both directions.

Obsession
One thing about me I don’t talk about much: I have an obsession with writing. And not the kind that you’ve read from me – websites, blogs, and the like. I’ve been actually writing stories, sketching narratives, jotting down snippets on and off for 30 years.

Of course, I’ve been writing online for almost 20 of those years. And, while James (in the article quoted above) does not think that is publishing, I do. Of a sort. On the level of bulletins and pamphlets of old.

At the same time, I absolutely agree with him that it’s not Publishing, capital P.

“P”ublishing
I am of the camp that thinks there’s a need for editors and publishers who, as James says above, provide context. Partly there’s the culling the chaff and bad writing, pointing out what’s valuable and well-written, no different than how we tend towards online publications that eloquently point us to what’s interesting and worth our attention.

But, James points out further that Publishers wrap text in a rich layer of context to enhance the text. So true. So necessary.

My books-in-waiting
I have posted some of my short stories here (see Narratives tab above), but have never felt complete (I have two novels and a few dozen short stories). A large part of me wants to see the stories in print, in a physical book (meh, Kindle?), for folks to flip through, fondle, read without having to know me. Yeah, good old-fashioned traditional Publishing.

Services like LuLu emboldened me to head down the path of just publishing it myself, but I know in my bones that I want an experienced editor to read my book, make it better (this is what editors do), and give it to a Publisher who can give it a design, context, audience access, and have it rub elbows with other books. No I am not looking for fame or fortune, just that I publish a wholesome book that I will be proud of.

I’ve known this all these years, and every time I put my novel or short stories into a book format (and go through the contortions of endless editing, layouts, design decisions), I am reminded that the mechanics and business of Publishing is not going away any time soon. [UPDATE: No sooner had I posted this I saw a tweet that pointed to this article “Publishing is no longer a job or an industry — it’s a button” which takes another tack to say Publishing is dead and Publishing is necessary – well, parts are dead and other parts are necessary. Basically, the same thing James says and I comment on.]

It’s hard work.

And LuLu knows that – check out all the Publishing services they offer á la carte.

What do you think?

Read Jame’s whole article: The New Value of Text | booktwo.org.

 

Another hat-tip to James, I recently made a travel guide for my wife – travel guide, tips, language guide, photos, some fun things, and so forth. I cleaned up and formatted the text, added photos, laid it out, added a TOC (an index would have killed me), personalized it a bit. LuLu was just my printer. And it was great to not really have to worry about the copyrights. Only thing, it cost more to ship it than to print it (I shipped it fast – couldn’t wait to see it). Ugh. Atoms still have to be moved.

And, yes, she liked it.

Innovation/Links of note/Science/Strategy/The Narrative

Gut microbes and immunity: The hygiene hypothesis, peak antibiotics, and the post-Pasteurian Age

Posted on by charlie

“Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that, in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma compared to specific pathogen-free (SPF) mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal—but not adult—GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.”

That’s the abtract from the paper “Gut Microbes Keep Rare Immune Cells in Line” (I think subscription is required, sorry).

There have been a good series of papers and studies into the “hygiene hypothesis” – that exposure to microbes early in life are actually important for the proper evolution of the immune system. This paper is one more example of that – these researchers were able to show what happened to the immune cells in the but of mice that never acquire bacteria, acquire bacteria only as adults, or acquire bacteria as pups.

I sometimes think of the 1850s-1990s as the Pasteurian Age – we were controlling bacteria to create a sterile world based on germ theory, aseptic techniques, public policies, and, of course, antibiotics. Alas, in the past 20 years, we’ve come to the realizations that we’ve reached (to joke a bit here) “peak antibiotics”, and that the only bugs to survive our clean homes and hospitals and antibiotics were Superbugs.

Now, in the past 5-10 years, I feel we are entering a post-Pasteurian Age, where we are gaining a deeper respect for the bacteria and fungi that share our world (and bodies) and that we are slowly thinking of how we can balance the sterile world we want and the microbe-filled world we need.

Great time to be a practical microbiologist, don’t you think?

Links of note/Science

The Impact of a Consortium of Fermented Milk Strains on the Gut Microbiome of Gnotobiotic Mice and Monozygotic Twins

Posted on by charlie

“The results also showed that (i) consumption of an FMP containing five bacterial strains was not associated with a statistically significant change in the proportional representation of resident community members within and between individuals; (ii) the appearance and disappearance of strains comprising the FMP consortium did not exhibit familial patterns in the fecal microbiota; and (iii) B. animalis subsp. lactis CNCM I-2494 was the most prominent assayed member of the consortium represented in the microbiota during the 7-week period of FMP The results also showed that (i) consumption of an FMP containing five bacterial strains was not associated with a statistically significant change in the proportional representation of resident community members within and between individuals; (ii) the appearance and disappearance of strains comprising the FMP consortium did not exhibit familial patterns in the fecal microbiota; and (iii) B. animalis subsp. lactis CNCM I-2494 was the most prominent assayed member of the consortium represented in the microbiota during the 7-week period of FMP consumption. Analyses of the fecal gene repertoire over the course of the 16 weeks of the experiment indicated that (i) variations in the functional features of the (fecal) microbiome were less than the variations in bacterial species composition; (ii) there was no significant difference in the degree of similarity in representation of KEGG orthology group functions for a given co-twin at each time point compared to the degree of similarity that existed between co-twins, whereas individual and twin pair microbiomes were significantly more similar to one another than those from unrelated individuals; and (iii) there were no statistically significant changes in the representation of these functions when the FMP strain consortium was being consumed.”

This is a seminal paper in probiotic research. I have seen a ton of papers on this subject, but none were as thorough as this one. The one concern I had was that there was no control for the FMP (fermented milk product) matrix (I don’t know what to call it, but the fermented milk without the bacteria). I still think there might be a positive effect on the gut microbiome from that matrix.

But, these folks saw similar effects in humans who ate FMP and the mice who had only the bacteria that were found in the FMP, effectively showing what the effect of just the bacteria have on the microbiome.

Still, I’m curious to settle once and for all if there is any beneficial effect of the FMP matrix. My main thought here is that 1) we know that the lactose digesting bacteria help in the stomach (as seen in folks with lactose intolerance), but 2) only one bacterial species from the FMP really seems to make it all the way through the gut. Perhaps the matrix helps the microbiome or signals the microbiome to do something? In this study, it was suggested that the bacteria alone are activating specific microbiome metabolic pathway.

Fascinating stuff. Will need to dig into it more. And I just saw that there are some videos of the authors. Should be interesting.

via The Impact of a Consortium of Fermented Milk Strains on the Gut Microbiome of Gnotobiotic Mice and Monozygotic Twins. (subscription required, unfortunately).

What do you think of this work?

Links of note/Science/The Narrative

International Human Microbe Program Looks Ahead – ScienceInsider

Posted on by charlie

Indeed, Sharp said at the meeting, patients who come to Cleveland Clinic for treatment of inflammatory bowel disease express their own concerns about such approaches, which could include the use of probiotics, the consumption of live microorganisms, to treat intestinal and other maladies. “Many patients are worried about manipulating their gut microbiota,” Sharp said, adding that “they see these kinds of studies through the lens of genetically modified foods. They worry that tampering with the gut microbiome could lead to irreversible effects.”Sharp also urged the microbiome research community, along with funding agencies, to start doing more public outreach to counter the often “grossly misleading” statements made by companies that sell probiotic products, including claims that probiotics can cure cancers and treat autism spectrum disorders. “Most of what people know about this area of research comes from these retailers,” Sharp said. “We should not be relying on these companies to put out the first messages about this area of research.”

This is an interesting article on what’s next for human microbiome research. It lists some of the companies getting involved (great!) and some talk about what will happen to jumpt start a whole new round of funding.

What was surprising to me was how little money was put into the multi-year programs (total $167M). Prehaps I don’t have a feel for what’s a lot of money in research.

Read International Human Microbe Program Looks Ahead – ScienceInsider.

Science/The Narrative

Microbiome sequencing offers hope for diagnostics : Nature News & Comment

Posted on by charlie

“Jonathan Eisen [@phylogenomics], a microbiologist at University of California, Davis, is worried that microbiome research will eventually encounter the same backlash. “Without a doubt we are running into some of the same problems as the Human Genome Project,” he says. “There are many people who have oversold the human microbiome as the cause or cure of everything.” Eisen worries that although numerous connections have been discovered between the microbiome and diseases, it is usually unclear whether the microbes caused the conditions or merely exploited a new environment.“There’s sensitivity about the expected returns,” says David Relman, who studies infectious disease at Stanford University in Palo Alto, California. “We need to be grounded about what it is we’ll be able to gain at what point in time. I think the shorter-term gains may be around diagnostics, and novel ways of classifying both health and disease.”

This article has some great quotes (like above) on caution about the benefits of microbiome sequencing. I also agree with the writer, Ed Yong (@edyong209), that, yes, learning more about the human microbiome is amazing, but we need to not make outlandish claims as to what we will do with that understanding.

Ed mentioned some probiotic studies (an area I have been reading a lot about) and that hype pre-dates all the microbiome hype.

My comment: let’s learn all we can about the microbiome. Let’s see what we learn before we make as outlandish claims as we did in the 80s about knowing all about our genome.

Spot, on, Ed. Thanks for calling this out.

Read Microbiome sequencing offers hope for diagnostics : Nature News & Comment.

Links of note/Science/The Narrative

Dangerous C. difficile infections soar in US, but Massachusetts hospitals have cut germ’s spead – The Boston Globe

Posted on by charlie

“A life-threatening germ that causes diarrhea and spreads easily from doctors’ offices to hospitals and nursing homes has climbed to historic highs nationally, federal disease trackers warned Tuesday, as they pointed to efforts in Massachusetts that have helped slow the rate of infections here.”

More on this nasty bug. It’s now getting headlines.

Read this article…

Links of note/Science

A human gut microbial gene catalogue established by metagenomic sequencing : Nature

Posted on by charlie

“Beyond providing the global view of the human gut microbiome, the extensive gene catalogue we have established enables future studies of association of the microbial genes with human phenotypes and, even more broadly, human living habits, taking into account the environment, including diet, from birth to old age. We anticipate that these studies will lead to a much more complete understanding of human biology than the one we presently have.”

I feel kinda cheezy for quoting the very last paragraph of this long and interesting paper. But there is so much to like about it, I didn’t know which to quote.

Basically, these folks sequenced the bacteria on fecal samples from a lot of healthy folks, and folks with IBD (inflammatory bowel disease), ulcerative colitis, obesity, and who were overweight.

They confirmed that each of these states have their own particular microbiome profile. But they also did a ton of metagenomic analysis, even establishing what the “minimal microbiome” is. And in their analysis they describe what this minimal microbiome mean to human health and physiological processes.

Quite fascinating.

And the reason they are building this catalog (3.3 million microbial genes!) is that they will continue studying the subjects who donated the samples. And this is a good addition to the International Human Microbiome Consortium.

And of note, about half the authors of this work are from BGI-Shenzen, the über-sequencing institute, but the rest of the collaborators are from Europe and some from the large European sequencing centers. This reminds me of an article about BGI-Shenzen that discusses how the center is building up amazing collaborations outside of China. This is proof of what those collaborations can yield. We all gain, and it’s so much better than trying to do it alone, for the glory of China.

via A human gut microbial gene catalogue established by metagenomic sequencing : Article : Nature.

Links of note/Science

Genome Sequence of E. coli O104:H4 Leads to Rapid Development of a Targeted Antimicrobial Agent against This Emerging Pathogen – PLoS ONE

Posted on by charlie

“A recent widespread outbreak of Escherichia coli O104:H4 in Germany demonstrates the dynamic nature of emerging and re-emerging food-borne pathogens, particularly STECs and related pathogenic E. coli. Rapid genome sequencing and public availability of these data from the German outbreak strain allowed us to identify an O-antigen-specific bacteriophage tail spike protein encoded in the genome. We synthesized this gene and fused it to the tail fiber gene of an R-type pyocin, a phage tail-like bacteriocin, and expressed the novel bacteriocin such that the tail fiber fusion was incorporated into the bacteriocin structure. The resulting particles have bactericidal activity specifically against E. coli strains that produce the O104 lipopolysaccharide antigen, including the outbreak strain. This O-antigen tailspike-R-type pyocin strategy provides a platform to respond rapidly to emerging pathogens upon the availability of the pathogen’s genome sequence.”

When an outbreak in pathogenic E coli broke out in Germany last summer, scientists were able to sequence the genome in a few hours on a Life Technologies Ion PGM sequencer. This speed gave the public health official insight into what they were dealing with.

This paper linked to below, was able to then take the sequence and rapidly create a strain-specifc bacteriocin-phage bacteriocide. And, based on the submission date, they did this in a few months.

This points to a promising future where we sequence the pathogen the day we discover it and rapidly create targeted bactericides. Cool. And our kids will look back and wonder why were were trying carpet-bomb bacteria with rapidly useless antibiotics. This is the post-antibiotic age.

via PLoS ONE: Genome Sequence of E. coli O104:H4 Leads to Rapid Development of a Targeted Antimicrobial Agent against This Emerging Pathogen.