A deadly gut infection may come down to a sugar in ice cream
arstechnica.com
arstechnica.com
Citation: J. Collins, C. Robinson, H. Danhof, C. W. Knetsch, H. C. van Leeuwen, T. D. Lawley, J. M. Auchtung & R. A. Britton. Nature 2018-01-03 online.
Link: https://www.nature.com/articles/nature25178
DOI: 10.1038/nature25178
Abstract: Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.
I thought it was weird when the information page that came with the pills said "do not exercise while taking this medication and for at least a month afterwards", as well as a long list of side effects.
I took the first dose, and the very next day I started feeling tingly neuropathy in my extremities. I kept taking the medication for a few days while being worried about it, and it started spreading to other parts of my body. I started reading anecdotes online about how Cipro destroyed people's bodies, snapped tendons (especially the achilles tendon, one of the weaker tendons apparently, hence the don't exercise warning), and has side effects that last for years afterwards and getting even more paranoid about it.
Day 7 I start feeling the tingling in my face, and that prompted me to call the doctor. They got me on a non-fluroquinolone for the rest of the 30 days.
I have had periods of neuropathy on and off for years after that, including in my face, for the past four years since. It seems to have become less frequent recently though, finally. Mind you, this is after taking only 7 pills total four years ago.
It's so dangerous, and pretty much every doctor I've told this too since have been surprised that it could cause such problems.
FDA had to issue a warning (unfortunately after I was prescribed), telling doctors not to prescribe it for minor infections, and saying it had potentially permanent serious side effects, involving tendons, muscles, joints, nerves, and central nervous system: https://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
PLEASE make sure you know the risks before taking ciproflaxin.
In this case, they weren't testing a drug, they were testing the deadliness of the bacteria. It doesn't matter _how_ toxic the bacteria is to humans relative to mice, it only matters that the bacteria is more deadly (or less deadly) to the mice when the sugar is present.
So not just that some bug can mess you up, but that some bugs may well prefer certain chemicals in our diet. Eat a particular food and whatever starts growing and pumping out toxins or proteins your immune system has issues with.
Edit: I bet for people in the right field of medicine/research this is interesting but not a big surprise.
A comment is too short to summarize the reasons why, but I would refer interested people to Eliezer Yudkowsky's Inadequate Equilibria ― there is a 50 page dialogue between two humans and an alien visitor on the FDA.
It seems more accurate to say it does both simultaneously, or that it mis-regulates.
It fails to regulate some things that it should have (such as this), and it regulates other things that are better left alone.
And we should expect any noisy estimator to do that in general: there are always going to be both false positives and false negatives.
One thing we should be careful about though is to distinguish between arguments over the relative propensity of either, vs. the relative weighting that should be given to each.
E.g. sometimes people say 'no, the FDA over-regulates rather than under-regulates', when what they really mean is that the find that specific instances of over-regulation to be very harmful, while they think that the examples of under-regulation can be ignored.
I STRONGLY disagree. The FDA is underfunded and only looks into a tiny minority of cases deemed worth their effort. Walk into a "health" food store and look at how many unregulated drugs are on the shelf. They put out fires more often than they prevent them.
In general, the FDA under-regulates dramatically.
I would recommend caution in using Yudkowsky's long-form fictional strawmen to do anything other than analyze his own cognitive biases.
It appears to be another in a long line of entries in the "undergraduate economics solves all the world's problems" genre.
Oops.
Virtually all of the trehalose in food products is synthetic.
From the paper linked in the article:
"Although its usefulness was recognized, trehalose was not produced on an industrial scale until 1994. The conventional method for production, for example, extraction from yeast, had too low a yield andtoo high a cost to be used. In order to implement industrial production of trehalose, we have researchednew enzyme systems and have succeeded in isolating a novel enzyme system from a bacterial strainbelonging to the genus Arthrobacter sp. Q36 that was obtained from soil [1]. The system has been found to consist of two novel enzymes: malto-oligosyltrehalose synthase (or MTSase) and malto-oligosyltre-halose trehalohydorolase (or MTHase). In the first step, MTSase catalyzes the intramolecular transglycosylation of glucose residue at the reducing end of malto-oligosaccharide from α-1, 4 bond to α-1, 1 bond, then malto-oligosyltrehalose is produced. This contains trehalose residue at the end of the saccharide chain. Next, trehalose is liberated from malto-oligosyltrehalose by MTHase. This pathway needs no high-energy sugar derivative such as sugar phosphate or sugar nucleotide. And those enzymes can repeatedly act on α-1, 4 glucan to produce trehalose up to 80 % yield (Fig. 1). The trehalose production scheme that has been developed in our company is shown in Fig. 2. Starch is liquefied by a thermostable α-amylase and is debranched by isoamylase. The formed amylose is converted into trehalose by this system. The system involves two novel enzymes, MTSase and MTHase, which act on amylose or starch to produce trehalose efficiently. By this process, we have succeeded in reducing the production cost of trehalose to approximately one hundredth of its initial cost. The cost was reduced enough to permit a widespread application to many foods such as sweeteners and stabilizers. In addition, trehalose is also expected to be used for various applications in the fields of medicine and cosmetics."
What's problematic is how "Generally Recognized as Safe" (GRAS) has been redefined. Instead of "something that's historically been in food, and hasn't injured people", it's become "anything that isn't clearly toxic in short-term testing".
Because it's very hard to prove negatives like "not harmful". In that there are just too many ways in which stuff can be harmful. So at best, FDA excludes the obviously-toxic stuff, and the rest is assumed safe, until there's evidence that it's not.
And yes, I don't want new stuff in my food. I avoid processed food, and prefer local "organic" (hate the word, but whatever) sources.
I had c. diff (it sucked, a lot) and this really fills in some gaps for me. Before my gut was destroyed by c. diff, I used to eat more ice cream, no doubt containing this sugar. Obviously I can't say for certain, but I can see how this helped the pathogen gain a hold in my gut.
Management has been staying on a relatively high thyroid hormone replacement dose and periodic radioactive iodine scans. Worst case scenario, the scan requires a grueling couple weeks off of my medication and on a low-iodine diet so that any remaining thyroid cells are completely starved and ready to absorb the radioactive dose. Best case, the recombinant thyroid-stimulating hormone, Thyrogen, is available and my insurance is willing to pay for it because it reduces prep to a pre-scan injection.