Home » Health » Obesity, Metabolic Disease and Pathways to a Cure

Obesity, Metabolic Disease and Pathways to a Cure

What follows is my abridged version of one of the most significant summaries of research into diet and human health.  This article was written by Moises Velasquez-Manoff  for Mother Jones in April of 2013. When you go to the full text of this article you will also find a video and other helpful information.  The focus of this abridgement is to present the key advances in our understanding of diet, obesity and metabolic syndrome.  Omitted are the implications and recommendations with respect to dietary changes. I would recommend that you read the full article at Mother Jones. The URL Web address is below.

Are Happy Gut Bacteria Key to Weight Loss?

by Moises Velasquez-Manoff

[Abridged version for readers of DataDrivenViewPoints.com]

MOTHER JONES – April 22, 2013

http://m.motherjones.com/environment/2013/04/gut-microbiome-bacteria-weight-loss

Highest-Calorie-Foods

In 2004 a curious diabetes specialist in Buffalo, New York, named Dr. Paresh Dandona, fed nine normal-weight volunteers an egg sandwich with cheese and ham, a sausage muffin sandwich, and two hash brown patties to see what effect this had on their bodies.

He found that levels of a C-reactive protein, an indicator of systemic inflammation, shot up “within literally minutes,” and remained elevated for hours. Inflammation is a natural and important part of our immune system response, but inflammation can also cause collateral damage, especially when the response is overwhelming—like in septic shock—or when it goes on too long.

Chronic, low-grade inflammation has long been recognized as a feature of metabolic syndrome, a cluster of dysfunctions that tends to precede full-blown diabetes and that also increases the risk of heart disease, stroke, certain cancers, and even dementia—the top killers of the developed world. The syndrome includes a combination of elevated blood sugar and high blood pressure, low “good” cholesterol, and an abdominal cavity filled with fat, often indicated by a “beer belly.” Could chronic systemic inflammation (CSI), in fact, be a major cause of metabolic syndrome disorder? A fast-food breakfast inflamed, he found, but a high-fiber breakfast with lots of fruit did not. A breakthrough came in 2007 when he discovered that while sugar water, a stand-in for soda, caused inflammation, orange juice—even though it contains plenty of sugar—didn’t.

This time, along with their two-sandwich, two-hash-brown, 910-calorie breakfast, one-third of his volunteers—10 in total—quaffed a glass of fresh OJ. The non-juice drinkers, half of whom drank sugar water, and the other half plain water, had the expected response—inflammation and elevated blood sugar. But the OJ drinkers had neither elevated blood sugar nor inflammation. The juice seemed to shield their metabolism. “It just switched off the whole damn thing,” Dandona says. Other scientists have since confirmed that OJ has a strong anti-inflammatory effect.

What caught Dandona’s attention was increased blood levels of a substance called endotoxin. This molecule comes from the outer walls of certain bacteria. If endotoxin levels rise, our immune system perceives a threat and responds with inflammation. Where had the endotoxin come from? We all carry a few pounds’ worth of microbes in our gut, a complex ecosystem collectively called the microbiota. The endotoxin, Dandona suspected, originated in this native colony of microbes. Somehow, a greasy meal full of refined carbohydrates ushered it from the gut, where it was always present but didn’t necessarily cause harm, into the bloodstream, where it did. But orange juice stopped that translocation cold.

If what some scientists now suspect about the interplay of food and intestinal microbes pans out, it could revolutionize the $66 billion weight loss industry—and help control the soaring $2.7 trillion we spend on health care yearly. “What matters is not how much you eat,” Dandona says, “but what you eat.”

Scientists now suspect that our microbial communities contribute to a number of diseases, from allergic disorders like asthma and hay fever, to inflammatory conditions like Crohn’s disease, to cancer, heart disease, and obesity. As newborns, we encounter our first microbes as we pass through the birth canal. Until that moment, we are 100 percent human. Thereafter, we are, numerically speaking, 10 percent human, and 90 percent microbe. Our microbiome contains at least 150 times more genes, collectively, than our human genome.

The importance of intestinal microbes to our health has grown increasingly evident. Animals raised without microbes essentially lack a functioning immune system. Entire repertoires of white blood cells remain dormant; their intestines don’t develop the proper creases and crypts; their hearts are shrunken; genes in the brain that should be in the “off” position remain stuck “on.” Without their microbes, animals aren’t really “normal.”

Scientists now suspect that our microbial communities contribute to a number of human diseases, from allergic disorders like asthma and hay fever, to inflammatory conditions like Crohn’s disease, to cancer, heart disease, and obesity. As newborns, we encounter our first microbes as we pass through the birth canal. Until that moment, we are 100 percent human. Thereafter, we are, numerically speaking, 10 percent human, and 90 percent microbe. Our microbiome contains at least 150 times more genes, collectively, than our human genome. Sometime in childhood, the bustling community of between 500 and 1,000 species stabilizes.

Our stool is roughly half living bacteria by weight. Every day, food goes in one end and microbes come out the other. The human gut is roughly 26 feet in length. Hammered flat, it would have a surface area of a tennis court. Seventy percent of our immune activity occurs there. The gut has its own nervous system; it contains as many neurons as the spinal cord. About 95 percent of the body’s serotonin, a neurotransmitter usually discussed in the context of depression, is produced in the gut. So the gut isn’t just where we absorb nutrients. It’s also an immune hub and a second brain. And it’s crawling with microbes. They don’t often cross the walls of the intestines into the blood stream, but they nevertheless change how the immune, endocrine, and nervous systems all work on the other side of the intestine wall.

Science doesn’t know exactly what goes wrong with our microbes in disease situations but a loss of intentional microbe diversity appears to correlate with the emergence of illness. Children in the developing world have many more types of microbes than kids in Europe or North America yet develop have fewer allergies and less asthma. In the developed world, children raised in microbially rich environments—with pets, on farms, or attending day care—have a lower risk of allergic disease.

Some studies find that babies born by C-section, deprived of their mother’s vaginal microbes at birth, have a higher risk of celiac disease, Type 1 diabetes, and obesity. Early-life use of antibiotics—which tear through our microbial ecosystems like a forest fire—has also been linked to allergic disease, inflammatory bowel disease, and obesity. Those who study human microbial communities fret that they are undergoing an extinction crisis.

If our microbiota plays a role in keeping us healthy, then how about attacking disease by treating the microbiota? After all, our community of microbes is quite plastic. New members can arrive and take up residence. Old members can get flushed out. Member ratios can shift. So the microbiota represents a huge potential leverage point in our quest to treat, and prevent, chronic disease. In particular, the “forgotten organ,” as some call the microbiota, may hold the key to addressing our single greatest health threat: obesity.

One-third of Americans are now considered overweight, and another third obese. Worldwide, one-fourth of humanity is too heavy, according to the World Health Organization. One-third of Americans are now considered overweight, and another third obese. Worldwide, one-fourth of humanity is too heavy, according to the World Health Organization.

The long-dominant explanation is simply that too little exercise and too many calories equals too much stored fat. The solution: more exercise and a lot more willpower. But there’s a problem with this theory: In the developed world, most of us consume more calories than we really need, but we don’t gain weight proportionally. If you run a daily surplus of just 500 calories you should gain a pound of fat per week, but we either gain weight much more slowly, or don’t gain weight at all.

Some corpulent people, meanwhile, have metabolisms that work fine. Their insulin and blood sugar levels are within normal range. Their livers are healthy, not marbled with fat. And some thin people have metabolic syndrome, often signaled by a beer gut. They suffer from fatty liver, insulin resistance, elevated blood sugar, high blood pressure, and low-grade, systemic inflammation. From a public health perspective, these symptoms are where the real problem lies—not necessarily how well we fit into our jeans.

In one study, mice raised without any intestinal microbes could gorge on food without developing metabolic syndrome or growing obese. But when colonized with their native microbes, these mice quickly became insulin resistant and grew fat, all while eating less food. Another researcher suspected that low-level inflammation might be the cause for this. To prove the principle, he gave mice a low dose of endotoxin, that molecule that resides in the outer walls of certain bacteria. The mice’s livers became insulin resistant; the mice became obese and developed diabetes. A high-fat diet alone produced the same result: Endotoxin leaked into circulation; inflammation took hold; the mice grew fat and diabetic. Then came the bombshell. The mere addition of soluble plant fibers called oligosaccharides, found in things like bananas, garlic, and asparagus, prevented the entire cascade—no endotoxin, no inflammation, and no diabetes. Oligosaccharides are one form of what’s known as a “prebiotic”.

Cani had essentially arrived at the same place as Dandona with his freshly squeezed orange juice. Junk food caused nasty microbes to bloom, and friendly bugs to decline. Permeability of the gut also increased, meaning that microbial byproducts—like that endotoxin—could more easily leak into circulation and spur inflammation. Simply adding prebiotics—in this case, Bifidobacteria—kept the gut tightly sealed, preventing the entire cascade. Our sweet and greasy diet changes gut permeability and alters the makeup of our microbial organ. Our “friendly” community of microbes becomes pathogenic, leaking noxious byproducts where they don’t belong.

Probiotics are bacteria thought to be beneficial to digestion, like the lactobacilli and other bacteria in some yogurts. In the future probiotics might be bacteria derived from those found in Amazonian Indians, rural Africans, even the Amish—people, in other words, who retain a microbial diversity that the rest of us may have lost.

Ultimately, the strongest evidence to support microbial involvement in obesity may come from a procedure that, on the face of it, has nothing to do with microbes: gastric bypass surgery. The surgery, which involves creating a detour around the stomach, is the most effective intervention for morbid obesity—far more effective than dieting.

Originally, scientists thought it worked by limiting food consumption. But it’s increasingly obvious that’s not how the procedure works. The surgery somehow changes expression of thousands of genes in organs throughout the body, resetting the entire metabolism. In March, Lee Kaplan, director of the Massachusetts General Hospital Weight Center in Boston, published a study in Science Translational Medicine showing a substantial microbial contribution to that resetting.

He began with three sets obese mice, all on a high-fat diet. The first set received a sham operation—an incision in the intestine that didn’t really change much, but was meant to control for the possibility that trauma alone could cause weight loss. These mice then resumed their high fat diet. A second set also received a sham operation, but was put on a calorically restricted diet. The third group received gastric bypass surgery, but was then allowed to eat as it pleased. As expected, both the bypass mice and dieted mice lost weight. But only the bypass mice showed normalization of insulin and glucose levels. Without that normalization, says Kaplan, mice and people alike inevitably regain lost weight.

To test the microbial contribution to these outcomes, Kaplan transplanted the microbiota from each set to germ-free mice. Only rodents colonized with microbes from the bypass mice lost weight, while actually eating more than mice colonized with microbes from the other groups. In humans, some studies show a rebound of anti-inflammatory bacteria after gastric-bypass surgery. Dandona has also noted a decline in circulating endotoxin after the procedure. If we understand the mechanism by which the microbiota shifts, he says, perhaps we can induce the changes without surgery.

NOT EVERYONE ACCEPTS that inflammation drives metabolic syndrome and obesity. And even among the idea’s proponents, no one claims that all inflammation emanates from the microbiota. Moreover, if you accept that inflammation contributes to obesity, then you’re obligated to consider all the many ways to become inflamed. The odd thing is, many of them are already implicated in obesity.

Particulate pollution from tailpipes and factories, linked to asthma, heart disease, and obesity, is known to be a cause of inflammation. So is chronic stress. And risk factors may interact with each other: In macaque troops, the high-ranking females, which experience less stress, can eat more junk food without developing metabolic syndrome than the more stressed, lower-ranking females. Epidemiologists have made similar observations in humans. Poorer people suffer the consequences of lousy dietary habits more than do those who are wealthier. The scientists who study this phenomenon call it “status syndrome.”

Exercise, meanwhile, is anti-inflammatory, which may explain why a brisk walk can immediately improve insulin sensitivity. Exercise may also fortify healthy brown fat, which burns off calories rather than storing them, like white fat does. This relationship may explain how physical activity really helps us lose weight. Yes, exercise burns calories, but the amount is often trivial. Just compensating for that bagel you ate for breakfast—roughly 290 calories—requires a 20-minute jog.

Then there’s the brain. Michael Schwartz, director of the Diabetes and Obesity Center of Excellence at the University of Washington in Seattle, has found that the appetite regulation center of the brain—the hypothalamus—is ofteninflamed and damaged in obese people. He can reproduce this damage by feeding mice a high-fat diet; chronic consumption of junk food, it seems, injures this region of the brain. Crucially, the brain inflammation precedes weight gain, suggesting that the injury might cause, or at least contribute to, obesity. In other words, by melting down our appetite control centers, junk food may accelerate its own consumption, sending us into a kind of vicious cycle where we consume more of the poison wreaking havoc on our physiology.

Of course there’s a genetic contribution to obesity. But even here, inflammation rears its head. Some studies suggest that gene variants that increase aspects of immune firepower are over-represented among obese individuals. In past environments, these genes probably helped us fight off infections. In the context of today’s diet, however, they may increase the risk of metabolic syndrome.

Biologically simple, processed foods may cultivate a toxic microbial community, not unlike the algal blooms that result in oceanic “dead zones.” In fact, scientists really do observe a dead zone of sorts when they peer into the obese microbiota. Microbes naturally form communities. In obese people, not only are anti-inflammatory microbes relatively scarce, diversity in general is depleted, and community structure degraded. Microbes that, in ecological parlance, we might call weedy species—the rats and cockroaches of your inner world—scurry around unimpeded. What’s the lesson? Junk food may produce a kind of microbial anarchy. Opportunists flourish as the greater structure collapses. Cooperative members get pushed aside. And you, who both contain and depend on the entire ecosystem, pay the price.

[This abridged version is provided for public use. See https://datadrivenviewpoints.com/fair-use-notice/]

Advertisements

27 Comments

  1. dalo2013 says:

    Fascinating article.

  2. avwalters says:

    Thanks, now I’ll go read the long version.

  3. jayden says:

    Then more friends can talk about this problem

  4. There’s certainly a great deal to learn about this issue. I really like all the points you made.

  5. Obesity is now declared a disease! If so, it is a disease of affluence and most people afflicted by it, are obsessed about the difficulty of losing weight, whereas I believe the solution is quite simple. As a kid I grew up in New Zealand during the 2nd world war, when food was scarce and rationed. I remember only 2 kids at primary school who were overweight. One lived on a farm and ate dairy and other foods which were obviously not rationed or at least, were hard to ration by the authorities. The other had no interest in physical activity, but loved eating, particularly fatty fried food. Overweight adults were a rarity, as they are still in poorer societies.

    Today, in the 1st World, the majority of adults are overweight, many grossly and hideously obese. During my frequent business trips to the USA in the nineties, I was taken once to dinner by an obese company representative to Ur Cooks in Houston, Texas, where we selected our own steaks, cooked them and added cooked vegetables. The concept was ideal for feeding yourself a healthy nutritious meal. My host selected an enormous steak about 2 inches thick, covering most of his plate, cooked it and added copious vegetables that almost fell off his plate. I selected the smallest steak available – still large in my view, added vegetables, ate my meal, feeling I probably could have eaten more, but pleasantly satisfied.

    The answer to obesity is common sense. If you are overweight, don’t be so greedy, but select nutritious food of a quantity that doesn’t make you feel (and look like) like a stuffed pig.

    Most obese people blame everyone but themselves – they have tried everything, they say – their genes are wrong (if so, you are lucky, you have an efficient metabolism and don’t need much food to remain functioning and healthy – would have been great in the ‘hunter/gatherer’ days) – they love sweet things – fast food is so tasty (lots of salt and fat!).

    Has old fashioned, self discipline just gone out the window? For goodness sake, stop putting it in your mouth! You don’t need a fad diet. In the blog on this site, ‘Lose Weight’, ( See http://fitnessforum.us), I specify how to live a life that will banish obesity – you will live longer and enjoy the years much more – simply resolve yourself NOW – only you can do it and it is simple.

  6. DataHeart says:

    Both Mr. Keenan and his commercial weight loss website are good examples of the simplistic thinking that attracts people afflicted with obesity but which has not been at all successful in curbing the epidemic. Some of the information on the website is scientifically out of date as well, in my opinion. What may help some people loose weight doesn’t mean that treatment is a cure or that it treats the underlying causes. Clearly, calorie deprevation (wich includes most weight loss diets) will result in some weight loss, but it isn’t sustainable for most people, especially those who are obese. Eating healthier foods, taking smaller portion sizes and moderate exercise are all great pieces of advice, but this doesn’t explain why prior generations didn’t require such special instructions. It doesn’t explain why there are some obese individuals even in societies where food scarcity is consistent or thin people who eat copius amounts of food without gaining weight. It doesn’t explain why some overweight individual have none of the poor health outcomes associated with obesity while some thin indivuduals do have similar health outcomes.

    Obesity is epidemic today but was not an issue 50 years ago. This suggests that there are significant environmental factors behind the changes. We used to be quite capable of eating excess calories without gaining weight. Now we can gain weight while eating fewer calories. A greater proclavity to gain weight is too recent a development to be the result of genetic changes. Scientists no longer believe that our less active lifestyles is a controling factor. Clearly there is a complexity to the problem not previously appreciated, and complexity is always the result of our limited understanding. So we all need to do what is sensible without overyly subscribing to simplistic explainations or unsupported claims. And we should support calls to increase research in this area of study.

  7. With havin so much content do you ever run into any problems of
    plagorism or copyright infringement? My site has a lot of unique content I’ve either created myself or outsourced but it seems a lot of it is popping it up all over the internet without my permission. Do you know any ways to help reduce content from being ripped off? I’d certainly appreciate
    it.

    • DataHeart says:

      Sorry for the late reply. I was traveling abroad with little internet access.

      Regarding your question, I see that my content is sometimes reposted on other websites without attribution. This is annoying in part because I would like readers to know where they can go do find more of my content. I am not interested in so much in attribution for attributions sake as I am for broadening access to the content I want others to read. In fact, your inquiry reminds me that I need to specify somewhere that everyone is free to repost my content so long as they properly attribute it to my blog site. So my situation may not be similar to yours in that I have no pecuniary interests and you may. As you know, original writings are copyrighted the moment they are posted, and it is easy to prove when content is posted, but enforcing infringement can’t be easy. However, searching for advice on the internet as to how to handle copyright infringement on the Web should be easy. Also, WordPress has a good primer on copyrights somewhere on their Web page. Sorry I can’t be more helpful.

  8. These are really wonderful ideas in concerning blogging. You have touched some nice things here.
    Any way keep up wrinting.

  9. Alex says:

    Hello, i read your blog from time to time and i own a similar one and i
    was just curious if you get a lot of spam feedback? If so how do you protect against it, any plugin or anything you can recommend?
    I get so much lately it’s driving me insane
    so any support is very much appreciated.

    • DataHeart says:

      I haven’t gotten a lot of spam so far. I have marked a few items as spam. I haven’t had this site for a full year yet. How long have you been on WordPress? Maybe spam vollume grows over time.

  10. Hey there are using WordPress for your blog platform? I’m new to the blog world but I’m
    trying to get started and set up my own. Do you require any html coding knowledge to make your own blog?
    Any help would be greatly appreciated!

    • DataHeart says:

      html coding is always useful to know but completely unnecessary to operate a wordpress blog for most users. There are a lot of good user face options that don’t require knowledge of html to incorporate into your blog. Plus there are sites that offer ready made html scripts that you can cut and paste into your blog if you want to.

  11. Its not my first time to goo to see this website, i am browsing
    this site dailly and obtain good data from here everyday.

  12. Hi! This is my 1st comment here so I just wanted to give a quick shout out and tell you I truly enjoy reading through your posts.
    Can you recommend any other blogs/websites/forums that go over the same topics?
    Many thanks!

  13. I wish that more homeowners could become more aware of the
    serious dangers of carbon monoxide poisoning. Each year over twenty people are killed by this odourless, colourless gas
    leaking from faulty gas boilers and many hundreds more suffer health problems because of it.

  14. My spouse and I stumbled over here by a different web
    page and thought I should check things out. I like what I ssee
    so now i’m following you. Look forward to looking at
    your web page yet again.

  15. mobile games says:

    You’ve made some really good points there. I looked on the net for additional
    information about the issue and found most people will go along with your views
    on this web site.

  16. Superb blog you have here but I was curious if you knew of
    any forums that cover the same topics talked about in this article?
    I’d really love to be a part of online community where
    I can get advice from other experienced people that share the same
    interest. If you have any suggestions, please let me know.
    Thanks a lot!

    • DataHeart says:

      My interests are diverse I spend more time reading than discussing. I don’t know of any forums, but if you find one, or better yet start one, I would join it.

  17. Hey! I’m at work surfing around your blog from my new iphone!
    Just wanted to say I love reading your blog and look forward to all your posts!

    Keep up the outstanding work!

  18. Wow, this post is nice, my younger sister is analyzing
    these things, so I am going to let know her.

  19. Kellee says:

    I was suggested this web site by way of my cousin. I am now not sure whether or not this post is written by means off him as nobody else know suh distinctive approximately my difficulty.
    You’re amazing! Thanks!

  20. Good post. I will be facing many of these
    issues as well..

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: