How To Read a Microbiome Study Like a Scientist

bmahersciwriter (2955569) writes Scientific reports have increasingly linked the bacteria in your gut to health and maladies, often making wild-sounding claims. Did you hear about the mice who were given fecal transplants from skinny humans and totally got skinny! Well, some of the more gut-busting results might not be as solid as they seem. Epidemiologist Bill Hanage offers five critical questions to ask when confronted by the latest microbiome research.

Comments

? what's a

[oldmac31310]

microblome?

Re:? what's a

[i kan reed]

It's a specific environment that hosts multiple species that are evolved to niches exclusively dependent on that environment, but the locality of conditions is so small as to be considered a part of another "bigger" biome.

Human intestines, small tidal pools, fig trees are some common examples.

You spelled it microbLome, which I assume is a mistake on your part since the summary doesn't.

Re:? what's a

[oldmac31310]

on my screen it looks like blome. I was trying - unsuccessfully to be a smart ass. Well, blow me down...

Re:? what's a

[i kan reed]

Do you have some sort of weird font pack?

Odd linux distro, maybe?

Re:? what's a

[oldmac31310]

nope. OS X on a 26" iMac screen, Chrome. Just looks like that. The bold type in the teal bar is the culprit. In fact all instances of the letter i look like l.

Re:? what's a

[reboot246]

Aha! That's the problem. Buy something other than an Apple product. :)

Re:? what's a

[oldmac31310]

Ha, ha. I knew someone had to make an anti Apple comment, even if only in jest.

You mean that...

[gurps_npc]

I can't become skinny by eating a skinny person's fecal matter?

I am going to have to insist on a refund!

Stop laughing, I'm serious!

Re:You mean that...

[geekoid]

Sure you can. You'll get ill and then loose weight from the illness.

Re:You mean that...

[Anonymous Coward]

You might even be able to lose the weight transitively. Watch 2 girls 1 cup, which is simply a documentary on fecal transplant; then see if you lose weight from the resulting vomiting.

Probiotics!

[Anonymous Coward]

All I know is that I definitely have more regular poops when I eat that probiotic yogurt.

Re:Probiotics!

[ColdWetDog]

All I know is that I definitely have more regular poops when I eat that probiotic yogurt.

Yes, it appears that it is indeed, all that you know....

Titles are not sentences PERIOD!

[Anonymous Coward]

more than that for your comment

Not just microbiome studies

[jstave]

Those 5 questions should be asked of pretty much every scientific study done, no matter what the field

Re:Not just microbiome studies

[jfengel]

Yep, came here to say that. And since effectively every daily news story on any science subject fails to answer any of them, it would be a pretty good heuristic to simply ignore all of them.

Newspapers and TV news are designed to sell news today, and to sell you news again tomorrow. Science doesn't turn out news on a daily basis like that. Important results take a very long time from first inkling to confirmation. You won't be able to act on that news today at any rate. Wait until the news comes out in a source like Science News or Scientific American, when it's got at least a few days worth of evaluation and consideration under its belt. Everything that comes out more frequently than that is going to be just plain rubbish the overwhelming majority of the time. And you'll hear about the stuff that isn't rubbish plenty quickly enough.

Re:Not just microbiome studies

[0bject]

:s/scientific study done/religion/g

Re:Not just microbiome studies

[nbauman]

Those 5 questions should be asked of pretty much every scientific study done, no matter what the field

That's the way to write a good science story. Whatever the story is about, you explain the basic questions that the reader should ask.

I despair about ever having people know the difference between association and causation. Nevertheless, it's worth repeating.

Gary Schwitzer's web site http://www.healthnewsreview.or... has more detail http://www.healthnewsreview.or...

Re:Not just microbiome studies

[raymorris]

Pretty strong correlation:
http://gizmodo.com/5977989/int... :)

Home fecal transplant went wrong

[nbauman]

There was an article this week in the New England Journal of Medicine about a guy who tried a home fecal transplant, and wound up in the hospital. He gave himself cytomegalovirus, with very bad gastrointestinal symptoms.

He had a 7-year history of ulcerative colitis. The doctors made recommendations but he declined many of them. Instead, he gave himself a "home brew" fecal microbiota transplant. He used stool from his wife and 10-month-old child. Some people think that stool from children is more "pristine" than stool from adults, and doesn't need testing for infectious disease. Actually, children are a bad source of stool, because they get frequent viral infections, especially if they attend day care.

He finally started following doctors' recommendations and the ulcerative colitis and cytomegalovirus cleared up after a couple of weeks.

Fecal microbiota transplant actually works well for Clostridium difficile, with more than 90% effectiveness, which is great since C. difficile can be fatal and is often antibiotic-resistant. However, in the few studies with ulcerative colitis it didn't work too well and sometimes made it worse.

The article found two other cases of people who got infections from fecal transplant.

http://www.nejm.org/doi/full/1...

case records of the massachusetts general hospital
Case 25-2014 — A 37-Year-Old Man with Ulcerative Colitis and Bloody Diarrhea
Elizabeth L. Hohmann, M.D., Ashwin N. Ananthakrishnan, M.D., M.P.H., and Vikram Deshpande, M.D.
N Engl J Med 2014; 371:668-675
August 14, 2014DOI: 10.1056/NEJMcpc1400842

A 37-year-old man with ulcerative colitis was admitted to the hospital because of abdominal cramping, diarrhea, hematochezia, fever to a peak temperature of 38.8C, and drenching night sweats. Several weeks earlier, he had performed home fecal transplantation.

Re:Home fecal transplant went wrong

[DigiShaman]

Brings new meaning to the phrase "eat shit and die".

Re:Home fecal transplant went wrong

[Anonymous Coward]

And the winner of the "what three words should never be used together in a sentence" contest is....

> home decal transplantation

Re:Home fecal transplant went wrong

[Guppy]

While the clinical picture and timing suggests the possibility, it's far from certain that this was a primary infection stemming from his home fecal transplant. I would have liked to see an analysis of anti-CMV IgM titers, although in this case it's also possible that his case was recognized too long afterwards to determine whether or not it was an actual primary infection.

Re:Home fecal transplant went wrong

[Anonymous Coward]

People also seem to miss that fecal transplants are often suppositories. I doubt these people were swallowing homemade shit pills.

Then again, the stories I've heard from older attendings about *their* attendings performing fecal transplants on unsuspecting patients with refractory alimentary issues via personally-created pills... ah, well, no one had heard of "informed consent" back in the day.

Heh.

Depends

[theshowmecanuck]

Are they skinny because they have a tapeworm? If so, it really should work.

Re:Depends

[gurps_npc]

Most doctors do not believe that tapeworms cause you to lose weight - at least not until you surgically remove them.

Tapeworms eat your nutrients, but they don't make the matter vanish. The tapeworm grows by X ounces for every X ounce you 'lose'.

They do however, cause multiple health issues. (Unlike certain other parasites that some believe trigger helpful immune responses).

Re:Depends

[Thud457]

"fecal transplant" is a concept I could have quite happily gone to my grave without learning. Thank you Dr. Gregory House.

Wait ... What?

[Virtucon]

Dammit I've been taking rat poop ever since that study was released? Are you telling me now I did all that for nothing? I wish you'd make up your minds!

Re:Wait ... What?

[iggymanz]

eating poop can definitely make you lose weight.....by catching cholera or similar

Re:Wait ... What?

[Virtucon]

Too extreme then?

Pretty Standard Questions

[Anonymous Coward]

1. Statistical Significance
2 and 3 more or less boil down to the same thing.
4. Broader Research Impact
5. Reproducibility.

Re:Pretty Standard Questions

[Anonymous Coward]

Statistical Significance
-this is a meaningless concept as commonly used. It only makes sense if your null hypothesis is predicted by theory. If the null hypothesis is "two groups have the same average" the procedure is nothing but a convoluted way of disproving a strawman argument. I guarantee you people are driving the intelligent out of your field by doing that stuff.

Ask about everything

[troll -1]

Those questions should be asked of asked of all health claims including the benefits of vitamin C, fish oil, anti oxidants, and crystal therapy. It's amazing the amount of crap people believe where the evidence is either insufficient or the research flawed.

Re:Ask about everything

[crmarvin42]

The really frustrating part is when people who will rant against drug companies and a supposed lack of testing (which could not be further from the truth) will in the same breath rave about the latest dietary supplement (for which no testing is actually required, and over which the FDA has little legal oversight).

The food supplements industry is largely unregulated in the US due to an impressive mis-information campaign back in the 1980's which resulted in a special section of the regulations for dietary supplements. Animal feed is more tightly regulated than feed supplements. Feed additives have to prove, to the satisfaction of the FDA, that they are effective for a specific purpose. No similar requirement exists for dietary supplements.

Re:Ask about everything

[Anonymous Coward]

This is essentially everything since the 1980s. Name one unequivocally successful nutrient or drug treatment for anything since then.

Re:Ask about everything

[jfengel]

The Faustian bargain there is that they're not supposed to be expressing any specific purposes. If you're categorizing your product as a "supplement" you have to avoid making specific health claims. It generally says so, right on the package, via the incantation "This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease".

Generally in very, very tiny print. In much larger print, they'll hint strongly that it's good for something (often, something fairly vacuous). It's on the FDA to judge when it crosses the line into a medical claim, and they don't have anywhere near the kind of manpower it takes to evaluate the multi-billion-dollar market. It took an outside organization to sue the makers of Airborne, via the FTC, for false advertising rather than a violation of the more specific FDA rules.

So yeah, there are rules about dietary supplements, but they're badly flouted. They walk right up to the line, or even cross right over it, and rely on people's gullibility to make the jump to believe that these worthless products do anything.

Re:Ask about everything

[HornWumpus]

Boner pills. The FDA kind, not the snake oil kind.

Re:Ask about everything

[Anonymous Coward]

Thanks, I am looking for good examples to emulate. To my (currently basic) knowledge you are correct about sildenafil, I will study that.

Re:Ask about everything

[Anonymous Coward]

On looking into it, the erection-inducing activity of sidenafil was discovered on accident sometime between 1992-1994 by researchers working with cGMP analogues based on evidence cGMP was downstream of nitrovasodilators. Nitrates were known to cause vasodilation in the 1800s, cGMP was first detected endogenously in the 1960s, and the relationship between nitrates and cGMP was first reported in the 1970s.

So, the discovery of this treatment was
1) Accidental
2) Independent of any theory or evidence presented after 1980.

Re:Ask about everything

[Anonymous Coward]

I will take the current scenario over the only other option: full blown regulation where I would need a goddamn prescription to get vitamin C powder. Do you know it now costs over a billion dollars to bring a drug to market and this is a key reason why there are no new antibiotics in the R&D pipeline?

The only regulations I want for supplements that they have comprehensively-labeled, unadulterated ingredients, and truth in claims (well, insofar as that is ever possible with biomedical research). I don't want melamine in my whey protein, but I don't care too much about advertising. "Red Bull gives you wings" isn't something for the government to regulate.

People need to take responsibility for their own health and do their own due diligence about what they put in their bodies, whether it's apples, supplements, or heroin.

Re:Ask about everything

[Anonymous Coward]

In more detail, starting in the 1300s various alchemists figured out ways to purify nitric acid. In the mid-1800s it was accidentally (while cleaning up a spill) discovered that soaking cloth in the purified nitric acid made it combustible. Soon after nitroglycerin was synthesized as an explosive and it was noted that tasting it caused headaches in pretty much everyone. Homeopaths then started recommending its use to cure headaches and within a few decades (late 1800s) it was being used as a vasodilator by normal doctors.

In the 1950s chemists were using chromatography to purify compounds from homogenized mammal tissue and discovered cAMP, later in the 1960s cAMP and cGMP were detected using chromatography and radiolabled phosphate in mammal urine. In the 1970s researchers treated homogenized mammal tissues with various agents and measured cGMP formation with radioimmunoassay competition studies, by treating the tissue homogenates with various compounds it was eventually realized that many that increased cGMP levels were nitric oxide donors, followed by the realization that nitric oxide itself would accomplish this.

Based on this, in the 1990s Pfizer set out to develop cGMP analogues meant to inhibit the conversion of cGMP to GMP with the goal of treating angina, etc. The most potent in vitro inhibitor was sildenifil. During human trials of this it did not appear a good drug for angina but some people reported erections as a side effect.

Summary:
The only unequivocally effective drug since the 1980s (that I know of so far) was discovered as the result of alchemists, accident, homeopaths, chemists, and accident. No biomedical theory or methods were necessary. No strawman NHST p-value "analysis" was used.

Re: Ask about everything

[crmarvin42]

FDA regulations are use based. If you are taking vitamin C as a way to meet your daily requirement for vitamin c, then there is no health claim and your purchasing experience wouldn't change. However, the vitamin c seller would need to convince the FDA as to their supplements efficacy of disease prevention, which is BS anyway. The FDA oversight wouldn't do much to vitamin availability (the strawman the afore mentioned misinformation campaign used to drum up support for thei dietary supplement exclusions), but it would keep the "Magic" (read bullshit) pills Dr Oz keeps pushing off of the market in the first place. It would also cause other known BS like herbal supplements that lack any of the advertised herb, or the homeopathic sugar pills to be pulled due to a demonstrable lack of efficacy.

Re:Ask about everything

[david_thornley]

A friend of mine, who worked for the FDA, insisted on taking any herbal stuff as teas. She said that was somewhat regulated, while a pill claiming to be a herbal dietary supplement could contain pretty much anything.

Re:Ask about everything

[crmarvin42]

Probably because herbal tea is food and therefore falls under the more comprehensive oversight and rules that cover all foods. She is correct that dietary supplements can contain pretty much anything.

Re: Ask about everything

[Anonymous Coward]

Okay, I'll simplify it for you: I don't care what you want to put in your body. I expect the same respect from you.

It's specious to allow vitamin powder to be sold under the aegis of meeting an RDA but not in stronger doses for whatever reason the consumer wants to use it for (real or imagined).

I want the herbals, homeopathics, etc, to be available for the same reason I want freedom of speech and freedom of religion (even though I am an atheist). You do not have the moral authority to tell another person what they may or may not ingest. That means I want unfettered access to things that have no established RDA as well as the ability to consume more than the RDA of... whatever.

As I stated before: regulation to ensure the product contains only the labeled, unadulterated ingredients is the limit. I can also conceptually support banning "false claims" but that is a very squishy concept in biomedical terms and is typically advocated as an subterfuge to ban things.

Re: Ask about everything

[crmarvin42]

I don't care what you want to put in your body. I expect the same respect from you.

Wow, you have a very carrying soul [/sarcasm]

Unlike you, the FDA has a statutory obligation to make sure that foods and drugs sold in the US are safe for their intended use. The "intended use" part allows for a surprising amount of wiggle room. How is the FDA to know if you bought vitamins to treat some disease (a drug use) or to make sure you meet the normal RDA (not a drug use)? They can't and don't try. The intended use limit is not on the end user, but the seller. VitaminsRUs cannot advertise that their vitamin pills prevent cancer, but if you believe they will there is nothing the FDA can do to stop you, and they won't even try.

You do not have the moral authority to tell another person what they may or may not ingest.

The FDA is not a moral authority, but a scientific one. They are staffed with experts in various fields necessary to decide which products are safe and effective, and which are not. You appear to feel yourself up to the task of sorting the wheat from the chaff, but most Americans are not. I'm going to go out on a limb here and guess that you consider yourself to be of above average intelligence and education (ironically, the vast majority of people do as well). But think about most of the people you see in a day (neighbors, friends, family, strangers). How many of them would you suspect are similarly equipped to handle sophisticated marketing made to give the appearance of scientific validity despite a demonstrable lack there of? That is why the agency was created (see patent medicines, most of which were simply different forms of cocaine). To protect the largely ignorant populace from unsafe and unproven products.

As I stated before: regulation to ensure the product contains only the labeled, unadulterated ingredients is the limit. I can also conceptually support banning "false claims" but that is a very squishy concept in biomedical terms and is typically advocated as an subterfuge to ban things.

All such regulations require oversight. Verification that companies are obeying the laws that are supposed to govern their actions. The dietary supplement market is exempt from much of this oversight because they lied to the US population and convinced them that the FDA was out to take away their vitamins and make they by prescription only. That would never have happened. I know this because I do regulatory work with the division of the FDA involved in regulating the animal equivalent to dietary supplements, namely Feed Additives. No prescription is needed for an approved feed additive, no consultation with a veterinarian is required, but feed additive manufacturers are required to prove that a new additive is safe and effective. Once approved, anyone can sell that feed additive for the approved use without further involvement of the FDA. A feed additive petition takes about 2 years (on average, with a HUGE SD due to a non-normal distribution) from submission to approval, but once the approval is made no more work is required. In most other countries the requirements are similar, except that approvals are vendor specific (Company A and B both have to register their Vitamin C), and have to be renewed periodically (US system only requires approval once).

Depends on language

[Anonymous Coward]

If it is in English: left to right, top to bottom.

It's funny how excited Republicans are by this!

[Anonymous Coward]

They love the idea of shoving their shit up someone else's ass. They shove their hatred of us down our throats every day, and now their kind wants to also start shoving things up our ass. Oh well. That's their way.

Re:It's funny how excited Republicans are by this!

[Bob the Super Hamste]

I didn't know you rectum and throat were the same thing?

Only two questions are neccessary.

[Anonymous Coward]

Was your "null hypothesis" a strawman, or something you believed was true?
What did the distribution of results look like?

If the answer to the first is strawman and the second is missing, file the paper away as an opinion piece.

Fecal transplant

[Anonymous Coward]

I seem to remember that, in certain cultures, that the doctor/midwife/etc., who assisted in the delivery of an infant, would use a finger to obtain a sample of fecal material, and then insert that into the newly born infant. The idea was to jump-start the infant's intestinal bacterial culture with the correct bacteria, e.g., those from a functioning gut. It's indeterminate where the doctor obtained the sample from, though (himself? mother?).

Re: Fecal transplant

[Anonymous Coward]

Something like 80% of women drop a dookie during labor. So I assume they get the sample from the floor.

Re: It's funny how excited Republicans are by this

[Anonymous Coward]

Rectum? Damn near killed 'im!

Re: It's funny how excited Republicans are by this

[Anonymous Coward]

What is that supposed to mean? I see a lot of Republicans use that before they start into their typical racist rants.