Your microbiome and artificial sweeteners

 ‘Artificial sweeteners induce glucose intolerance by altering the gut microbiota’

My colleagues and family pointed out a paper about the apparent effects of non-caloric artificial sweeteners in decreasing glucose tolerance that was published recently in Nature. I am not a dietician but the results interested me primarily because 1) I drink diet soda on occasion and 2) the key the the effect appears to be mediated by the microbiome.

Non-caloric artificial sweeteners (saccharin, sucralose and aspartame), consumed at levels approved of for human consumption, appeared to decrease glucose tolerance, a condition associated with type II diabetes, obesity and metabolic syndrome. This is a concern as many of us do not realize when we are using these sweeteners (diet sodas and diet desserts). The effect was caused by the microbiome, the bacteria that inhabit the gut.  They also found that a significant shift took place in individual humans given normal doses of artificial sweeteners in as little as 7 days.

Artificial sweeteners induce glucose intolerance in mice.

Artificial sweeteners induce glucose intolerance B) Oral glucose tolerance test (area under the two-hour blood glucose response curve) in normal-chow-fed mice drinking commercial NAS (non-caloric artificial sweeteners) for 11 weeks before (N=20) and after antibiotics: ciprofloxacin and metronidazole (‘antibiotics A’, N = 10); or vancomycin (‘antibiotics B’, N= 5).

One of the most striking findings, for me,  is shown above. Giving antibiotics to these mice significantly eliminated this glucose intolerance (shown as the height of the y axis here). This implies that bacteria are mediating the response. They also found that simply donating the microbes of  mice who had been fed the high artificial sweeteners in their diet would cause glucose intolerance in the recipient organisms. The actual cause (outside of being microbial) is not yet known but the population shifts observed during consumption of these artificial sweeteners was similar to shifts associated with obesity. The researchers suggested that the bacteria that are encouraged to take up residence by non-caloric artificial sweeteners may be changing the way sugar is processed (more turned into fat cells) or may change insulin regulation in the blood of individuals.

Notably, in the human trial of 7 days, 4 of the 7 participants experienced dramatic shifts in microbiome and a decrease in glucose tolerance but 3/7 were non-responders. Medicine and nutritional advice may have to be tailored to individuals microbiome or genomes in the future. The latter may explain the variable results in artificial sweetener outcomes in the past.

You can hear my discussion with James Coleman on First@Five here:

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Science News June 5th 2014: Bee Brains and Bacteria Brewing Biofuels

On June 5th I will be on First@Five with James Coleman talking about these news stories:

Bee Brains Build Cognitive Maps

Shout out to Moira, Rick and Jason.

What happens when bees get lost?

Imagine you were knocked out on the block to your house. When you woke up, say, on the other side of town, you wouldn’t naturally get up and travel in the same direction that you were going before, would you? Bees will do that by orienting according to the sun and the time they believe it to be. However, when they don’t find their hive after the appropriate travel time they do something that you do. They establish their location and the correct direction according to local landmarks and their remembered map of the territory. This is according to a new paper published in PNAS by Auckland University, Massey University (my colleague Dr. Mat Pawley), Rutgers and the Free University of Berlin scientists collaborating to look into the evidence for a “metric cognitive map” in the brains of insects.

Bee path  Similar flight speed and accuracy of bees with (red) and without (blue) clock-shifting. Credit: James F. Cheeseman
Read more at: http://phys.org/news/2014-06-bees-cognitive.html#jCp

The work was done in an interesting way; bees were sedated, moved, woken up and tracked according to radar. What they did first, orienting according to the sun, really isn’t the surprise here. The remarkable thing, according to those who did the work, is the evidence that after not arriving home, the bees are able to decide where they are on a map in their minds. This indicates that they have previously memorized the terrain and the location of their hives relative to various positions. This assertion, a metric (relating angles and distances) cognitive map including landmarks means bees have a longer lasting memory and a complexity of brain function that we have not previously attributed to organisms that don’t have spinal cords. If insects as simple as bees (with orders of magnitude fewer neurons than a mouse or rat) can have complex maps in their brains then more is going on than we previously realized and a new chapter in our thoughts on the minds of the smallest creeping and crawling creatures on the planet is about to begin.

Another take:

http://phys.org/news/2014-06-LostBeesSignbees-cognitive.html

Paper:

http://www.pnas.org/content/early/2014/05/29/1408039111.full.pdf+html

Solo Bacteria to Brew Biofuels

How many times will I tout the amazing qualities of our invisible microbial counterparts? Bacteria can do just about anything you can put a chemistry set to and they have been doing it for billions of years. If you think you are not surrounded by useful bacterial byproducts go look up the source of xanthan gum (hint: this common food additive does not come from a tree).

The subject of todays praise is biofuels. Bacteria have been used for producing biofuels such as ethanol for a long time now. However, the processing that comes before their final fermentative steps have been time consuming and expensive (enzymatic processes and breaking up the plant materials). If a single bacterial strain could produce the enzymes to break down the plants AND turn the byproducts into ethanol, that would save steps, time and money in the biofuel production game and money makes all the difference. A huge advance in this field has recently been brought to fruition by Professor Janet Westpheling at the University of Georgia. For the first time a single organism has been modified to handle the entire process single handedly and at high temperatures. She is calling it 2nd Generation CBP (Caldicellulosiruptor bescii P) and it seems we are due for a revolution in biofuels production as a result. For more details of her work see here:

Press release: http://www.sciencedaily.com/releases/2014/06/140602155855.htm

Paper:

http://www.pnas.org/content/early/2014/05/29/1402210111.full.pdf+html?with-ds=yes

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Science News: GMO’s in New Zealand, Robot ethics and the flight of the Kiwi

I was on First@Five this morning with James Coleman talking about this science news:  

The ancestors of the Kiwi were not immigrants from Australia. The Kiwi, once thought to have been related most closely through common ancestry to the Australian Emu has just been informed that it’s ancient uncle is more likely the now extinct, Elephant bird of Madagascar. The elephant bird is another flightless ratite but this one is 2.3 meters tall and by all accounts a formidable species. The work, by the Australian Centre for Ancient DNA was published in the journal Science and was based on DNA extracted from fossils in Museum of New Zealand, Te Papa Tongarewa.

Genetically Modified Organisms : ZFN-1 and TALEs are two technologies in the toolkit of modern geneticists that allow for specific and targeted modification of the DNA without the need to introduce new or foreign DNA into the existing genetic material of an organism. Because this does not produce “transgenic” organisms that have combinations of DNA from previously separate organisms, ‘SCION a Crown Research Institute planned to use these technologies to develop new pine tree strains. The EPA had determined that organisms that had undergone these procedures did not constitute new, genetically modified organisms under the Hazardous Substances and New Organisms Act (1996).  Specifically the HSNO states new organisms have been modified by in vitro techniques or genes have have been modified by in vitro techniques. The sustainability council had asked the high court to rule on these technologies and the high court has over ruled the EPA decision. For more information and expert opinion gathered by the Science Media Centre see here. 

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War Robot Ethics. A Linda Johansson of Sweden’s KTH Royal Institute of Technology has written a thesis suggesting that it is time that we start considering what the ethics of war will be if the primary combatants are robots. Are robots to be held responsible for decisions that they make in the context of war? Despite traditional views of programming, robots today are programmed over time by hundreds of people and also have the capacity to “learn” and are therefore not as predictable as more conventional machines. She also raises issues regarding the place in combat of drone operators in the Laws of War (LOW). You can read more of her papers here.

The subject reminded me of Dr. Daniel Wilson’s book “How to survive a robot uprising: Tips on defending yourself against the coming rebellion.” You can see his instructional video on the subject here. Good luck!

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Science News: May 20th 2014, The Longitude Prize and the Odón Device

I will be on James Coleman on May 21st talking about The Longitude prize and the Odón device.
The Longitude prize is a 10 Million pound purse that has been established cooperatively between the UK’s Technology Strategy Board and NESTA in order to encourage innovation around a major challenge in science by anyone (maybe you).

Today the announcement was made and 6 possible challenges have been set for the public to choose between. Once the public has decided which challenge they want the prize to be set for the race will be on. Awarding this prize will probably take years if the last Longitude prize is any indication (see the link to the history of the prize below).

The 6 potential challenges are:

 

1)   Paralysis, restore movement for those who have been paralyzed.

2)   Dementia, allows those with dementia to live independently for longer.

3)   Water, solve the delsalination problem.

4)   Food, come up with the next food innovation.

5)   Antibiotics, how can we identify the appropriate antibiotics to use cheaply, safely, quickly and easily.

6)   Flight, invent 0 carbon emission flight.

 

You can learn more about the challenges on the longitude prize website.

The history of the Longitude prize as well as John Harrison’s winning device can be found on Wikipedia.

 

The inspiring New York Times write up of the Argentinian car mechanic who invented the Odón Device can be found here. The youtube video that inspired Jorge Odón can be viewed here: https://www.youtube.com/watch?v=uL1ovAYtKuQ

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Science News: May 14th 2014 Resveratrol & Self healing plastics…

Wednesday morning the 14th I am speaking to James Coleman on First@Five, RadioLive.  For those who might want more information about these science stories there are links and details included here.

The first story we discussed had to do with the newest finding for a specific antioxidant found in wine and chocolate, resveratrol. Essentially, in a large scale (783 people) study published in JAMA internal medicine found that in adults over 65 in the Chianti region of Italy, levels of this antioxidant in urine had no effect over a nine year period on major health outcomes such as cause of death, cancer, inflammation or heart disease. The moral of the story? Drink wine and eat chocolate in moderation but don’t expect that doing so is necessarily going to add years to your life, at least not because of resveratrol. For those interested in reading more about the antioxidant, resveratrol you can follow these links:

http://www.reuters.com/article/2014/05/12/us-health-wine-study-idUSKBN0DS1IW20140512

For a nice interactive graphic that includes this and other popular health supplements with varying amounts of scientific support see here:

http://www.informationisbeautiful.net/play/snake-oil-supplements/

A team of scientists from Illinois led by Dr. Scott White, have developed a regenerating plastic: a material that can fill itself in when damage occurs. The technique mimics biological systems, vessels in the material carry separate polymerizing materials that interact only where damage has taken place, filling the hole in a two step process. The hope is that in the future materials will constantly regenerate when damaged. For more on this story see the links below. The video is highly recommended in this case. Seeing is believing!

http://news.illinois.edu/news/14/0508plastic_ScottWhite_JeffryMoore_NancySottos.html

Example at 2:41 in video.
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Science news: WHO Report on Antibiotic Resistance & the Restorative Powers of Young Blood

The World Health Organization has recently released a report on the global incidence of antibiotic resistance in pathogens (summary). Antibiotic resistance is on the rise globally. This is a call to action for reporting from individual nations so that we understand what we are dealing with as well as a warning to us all: We are looking at a post-antibiotic era where infections that arise from simple injuries could be resistant to our antibiotics and therefore life threatening to any one of us.

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Part of the issue and something that needs attention is the issue of “Peak Antibiotics”. Early on, we found many new antibiotics and we stock piled these cure-alls rapidly. Since 1990 we have not found any new major types of antibiotics. By overusing a set of now common antibiotics we have given the bacteria lots of opportunities to adapt, evolve and share the natural capacities for resistance that exist in nature. More than that, by continuing to expose bacteria to low levels of antibiotics we have increased the selection pressure for resistance to the drugs that we have. In a way, we are all responsible. Be sure not to ask for antibiotics you don’t need. Physicians need to resist prescribing antibiotics that are not necessary. Agriculture and government need to accept their involvement as well: invest in research and take action to prevent unnecessary antibiotic use.

7 bacteria of concern & their resistance frequencies in New Zealand, compared to the world:

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Of course, on RadioLive when James asked what we can do to fight antibiotic resistant bacteria, I mentioned bacteriophage therapy.

Young Blood:

To me, it sounds like something out of a science fiction movie or a vampire thriller, a team from Stanford released a paper this week in Nature Medicine that the blood of young mice effects the brain of an older mouse in ways that reverse some of the effects of aging. This was seen in the behavior of these older mice, improving their learning and memory. They were able to pinpoint some of the specific gene expression patterns that changed in the hippocampus of these mice as well. The hippocampi are a pair of small regions in the brain that are responsible for translating short-term memories into long-term memories. It also plays a role in spatial memory and navigation. In order to do this, the researchers actually tied the blood flow of mice of the same age together or mice of different ages. The approach is called parabiotic (para = beside, biotic = life) and while I had never heard of it before, this experimental approach has been implemented in animal research since at least the 1980s.   There is a nice post about parabionts hereImage

It’s a “para-mice”! Oh, never mind. (image from http://www.denigma.de/data/entry/open-distributed-science-for-aging-research)

This work followed on from a 2011 Nature paper where these authors announced that simply transfusing blood from young mice to old mice was sufficient to reverse the effects of aging on the generation of new neurons in the brain. We all know that blood contains red and white blood cells, but when these are removed the golden substance that remains, the blood plasma, has as many as 700 specific factors in it including a suite of clotting factors, and a forest of other small proteins. The function of many of these is unknown. In this 2011 study, a few small peptides were implicated in this miraculous regeneration but the effects on the mice were limited to behavioral evidence of improved memory.

The researchers involved have started a company and are looking forward to starting clinical trials for human treatment.

Find more information in the press release at science daily headlines:

http://www.sciencedaily.com/releases/2014/05/140505094906.htm

For more information about the WHO report see the summary and SMC:

http://www.sciencemediacentre.co.nz/2014/05/02/who-antibiotic-resistance-report-in-the-news/

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Meet Fabio!

Meet Fabio!

Meet Fabio. This is “Big Jess’s” phage from last year. When we took these electron microscopy images of our phages we had purified and amplified that phages so that we would have a pure sample of each new phage. However, not all copies of the same phage will look the same. in A) Fabio is a large T4 style tailed phage (http://en.wikipedia.org/wiki/Caudovirales), of the order caudovirales. in B) this phage Fabio appears to have injected his DNA (observe the contractile tail). His phage head or capsid has collapsed in on itself. Very different looking entity but these images are both of the same bacteriophage.

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The first time I heard about bacteriophages.

I was in an Advanced Placement Biology class in Morgan Hill California and our teacher, the treasured, Mr. Hemeon (surfer, musician, general biology-aficionado and all-rounder) had encouraged us each to do science fair projects on something we found interesting. My crappy tri-fold cardboard monstrosity was sadly typical of my standard homework effort in those days, a hopeless last minute doodle with cut out construction paper letters proclaiming my interest: Buoyancy! This was a project inspired not by the natural world but by my budding holiday hobby: SCUBA diving. In all likelihood this was actually a sad attempt to alert my crush in that class, Scott Sharper*, that I had a “cool” hobby. I don’t remember if Scott was impressed, but I do remember distinctly that Mr. Hemeon was not. I don’t even remember standing by my poor excuse for a science fair project but I do remember my class-mate’s Bacteriophage poster.

ImageBacteriophage image credit.

What was this? First off, the large image in the center, that bacteriophage was like something out of Deep Space Nine or The Navigator. This “bacteriophage” was clearly some comedian’s idea of a microbial-jackalope: a cross between a spacecraft and a spider. It was scary looking!

I shook my chemically induced blond curls at the student standing in front of this obvious fiction in total disbelief. What’s more, there was this totally unbelievable monster number just underneath this obvious monstrosity. My classmate proudly informed me that these “phages” were the most abundant entities on the planet and that we were literally covered with these creepy things all the time.

An estimated 10^31 of them on the planet.” He proclaimed.

“How do you even say a number like that?” I muttered, quietly folding up my tribute to buoyancy! and shoving it under a table.

Mr. Hemeon was delighted by my classmate. I think my primary reaction to the whole thing was a stymied disbelief followed by annoyance followed by a lapse into forgetfulness, but this would only last for a short time. I never took microbiology as an undergraduate. Despite this terrible error I was lucky enough to stumble into an undergraduate job in the laboratory of one of the greatest microbiologists of our time, Professor John Roth.**

While a fledgling experimentalist in his laboratory I had the audacity to confess that I had no idea what a “lysogen” was. Luckily for me, John did not throw me out for my ignorance. He had a post-doc in the lab sit with me after lab meeting to explain that bacteriophages could quietly set up shop in the chromosome of a bacterium, rather than undergoing their normal lytic life cycle and building huge numbers of copies of themselves before rupturing the cell. This kindly post-doc explained to me that bacteriophages are ubiquitous in nature and that as microbiologists, we must constantly be vigilant against our strains becoming lysogens. Perhaps it wasn’t then, in that dusty lab meeting room, perhaps it was a bit later, but it wouldn’t be long before I was hooked on microbiology.

You see, microbial life is all around us. It’s like Obi-Wan said:

The microbes are what gives a microbiologist her power. They partake of the energy created by all living things. They surround us and penetrate us. They bind the galaxy together.

Well, it was something like that***.

This next week we will begin the phage hunt in B. Nat. Sci. I am excited. I know these students have all taken my virus lectures in Biology of Cells at Massey so they are better acquainted with our prey than I was in Roth’s Lab. There are so many phages out there in the soil, numbers so high, I still can not possibly say them out loud. Plenty for us to find a few in the next month.

This is really why, after all of the Star Trek, Star Wars, Dr. Who and Red Dwarf:

Science really is better than science fiction…

* Name altered (a bit) to protect the innocent from embarrassing googlisms.

** This is a personal opinion obviously but I am far from alone on this one.

*** Midi-chlorians are obviously microbial. They are mitochondria, or chloroplasts or just bacteria. am I right? Come on! Update: Mitochondrial parasite named after midi-chlorians by an Australian microbiologist.

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Good bugs, the future of medicine –

Welcome to the first instalment of “This Microbial Life”. This is a blog that I have thought about for awhile but not had the impetus to actually start. I will be using it for a couple of different practical purposes. When I am in the media (TV or radio) I would like a place to send people to find more information and a place to put references for my colleagues who want to read journal papers first hand. Those will be published here under the heading “Science, better than science fiction”. The phage hunt class that I run will be doing a bit of blogging and blog commenting and I am hoping that those will blog posts (at least the one’s from me) will be here as well to give my students a model.  Without any further ado, I give you the text of an article I wrote late last year for the NZ Herald. See yah!

Good bugs: The future of medicine

Dr Heather Hendrickson (DRHHNZ)

One of the key science questions of our time is how to beat bacteria in an age where antibiotics are no longer effective. Much like the “peak oil” crisis, the “peak antibiotic” point has likely transpired and, as a society, we are hesitant to even speak about what the medical equivalent of the clean energy revolution will be.

The outlook is both good and bad. The bad news is we can’t beat them. The good news is that beating bacteria is not our only option. Bacterial cells out number the human cells in a healthy body by 10 to one. With a greater understanding of their role in our bodies, we will be able to harness their power to treat disease and promote good health.

Recent studies have suggested that people with more diverse populations of bacteria living in their guts are less prone to obesity, cardiovascular disease and diabetes. In addition, the one out of four individuals with low microbial diversity are more likely to gain weight and gain it more quickly than their high diversity friends.

More than being indicators of our tendencies, microbes may be directly engineering our metabolism or modifying the way our bodies encounter nutrients. In mouse studies, exchanging the microbes of a thin mouse for those from an obese mouse actually increased the mouse’s weight without changing the diet.

In the future, we may be able to treat conditions like obesity and diabetes simply by adjusting the levels and diversity of microbes in our systems, rather than taking drugs. And this is just the beginning. There are hints that our microbes are sending chemical signals that affect our psychological and emotional function as well.

Scientists recently discovered that some soil microbes actually increase our levels of serotonin, a neuro-transmitter found to have a calming effect on temper and to increase intelligence. In the future it may be possible to take an asthma-style inhaler full of friendly uplifting microbes when you are having a bad day – instant warm fuzzies. Or imagine stopping off for a delicious fruit shake from a local stand with a microbial additive that will help you focus in class or get over that disastrous crush on your neighbour.

Another promising area of microbial research will see the return of a form of medicine that saved lives during the first half of the twentieth century from the United States to the Soviet Union and Georgia. Bacteriophages (phages for short) are viruses that seek out and destroy specific bacterial targets in order to replicate themselves. These entities have been the natural parasites of bacteria for billions of years and they are very good at it.

Phage therapy is the application of a cocktail of appropriate phages in order to combat specific bacteria. This is a medical treatment formerly applied to humans that lost wide acceptance in much of Western medicine due to an untrained start. The beauty of phages as medicine is three-fold. They are extremely specific to particular pathogens and can therefore be tailored to suit. They replicate themselves when they destroy their targets, enhancing effectiveness at the infection site. And when the infection is gone, they simply leave the system to be turned over naturally.

Despite these advantages, when antibiotics were found to be safe and effective mid-century phage therapy was dismissed outside of the Soviet block. Cold war era politics kept the lessons of appropriate phage use outside of the mainstream. In the future phage therapy will be approved for use in humans once again. Gone will be the days of taking an antibiotic with broad-spectrum killing of the important and beneficial microorganisms in our bodies. Infections will be handled by taking a small dose of your enemies’ enemy.

Phages can also be useful in fighting serious infections caused by medical implants. Recently, it was found that various phages have co-evolved with animal hosts (including us) to provide a first-responder’s style immune system. In the future, implants – ranging from hearts to hips – could be constructed using biomaterials that have natural adherence sites for beneficial phages.

There is no telling where tinkering with our microbial communities will take us. While some will no doubt continue to make us sick, the vast array of microbes on our planet may turn out to be the undiscovered rainforest of natural cures we have been searching for.

Originally published in the New Zealand Herald and Massey University websites:

http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11156555

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