Marlena Alika Anand

14/09/2022

A study of mice found that dietary sugar alters the gut microbiome, setting off a chain of events that leads to metabolic disease, pre-diabetes, and weight gain.

The findings, published today in Cell, suggest that diet matters, but an optimal microbiome is equally important for the prevention of metabolic syndrome, diabetes, and obesity.

Diet alters microbiome

A Western-style high-fat, high-sugar diet can lead to obesity, metabolic syndrome, and diabetes, but how the diet kickstarts unhealthy changes in the body is unknown.

The gut microbiome is indispensable for an animal's nutrition, so Ivalyo Ivanov, PhD, associate professor of microbiology & immunology at Columbia University Vagelos College of Physicians and Surgeons, and his colleagues investigated the initial effects of the Western-style diet on the microbiome of mice.

After four weeks on the diet, the animals showed characteristics of metabolic syndrome, such as weight gain, insulin resistance, and glucose intolerance. And their microbiomes had changed dramatically, with the amount of segmented filamentous bacteria -- common in the gut microbiota of rodents, fish, and chickens -- falling sharply and other bacteria increasing in abundance.

Microbiome changes alter Th17 cells

The reduction in filamentous bacteria, the researchers found, was critical to the animals' health through its effect on Th17 immune cells. The drop in filamentous bacteria reduced the number of Th17 cells in the gut, and further experiments revealed that it's the Th17 cells that are necessary to prevent metabolic disease, diabetes, and weight gain.

"These immune cells produce molecules that slow down the absorption of 'bad' lipids from the intestines and they decrease intestinal inflammation," Ivanov says. "In other words, they keep the gut healthy and protect the body from absorbing pathogenic lipids."

Sugar vs. fat

What component of the high-fat, high-sugar diet led to these changes? Ivanov's team found that sugar was to blame.

"Sugar eliminates the filamentous bacteria, and the protective Th17 cells disappear as a consequence," says Ivanov. "When we fed mice a sugar-free, high-fat diet, they retain the intestinal Th17 cells and were completely protected from developing obesity and pre-diabetes, even though they ate the same number of calories."

But eliminating sugar did not help all mice. Among those lacking any filamentous bacteria to begin with, elimination of sugar did not have a beneficial effect, and the animals became obese and developed diabetes.

"This suggests that some popular dietary interventions, such as minimizing sugars, may only work in people who have certain bacterial populations within their microbiota," Ivanov says.

In those cases, certain probiotics might be helpful. In Ivanov's mice, supplements of filamentous bacteria led to the recovery of Th17 cells and protection against metabolic syndrome, despite the animals' consumption of a high-fat diet.

Though people do not have the same filamentous bacteria as mice, Ivanov thinks that other bacteria in people may have the same protective effects.

Providing Th17 cells to the mice also provided protection and may also be therapeutic for people. "Microbiota are important, but the real protection comes from the Th17 cells induced by the bacteria," Ivanov says.

"Our study emphasizes that a complex interaction between diet, microbiota, and the immune system plays a key role in the development of obesity, metabolic syndrome, type 2 diabetes, and other conditions," Ivanov says. "It suggests that for optimal health it is important not only to modify your diet but also improve your microbiome or intestinal immune system, for example, by increasing Th17 cell-inducing bacteria."

14/09/2022

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10/09/2022

10/09/2022

It’s Time To Rethink the Origins of Pain

Every person who has ever felt pain has their origin story, and I certainly have mine.

While performing a bench press more than a decade ago when I was in medical school, I heard a loud click and felt my whole body go limp, and the weights came crashing down. As pain gripped my entire body in a vise, I was rushed to emergency room where I got intravenous painkillers and was told the pain would eventually disappear.

But it didn’t. And what I’ve learned about pain since has me seriously questioning how we diagnose and treat it.

I’m a doctor now, and in researching a book on pain, I’ve begun to understand that the reason the acute pain from my back injury turned into unrelenting chronic pain was likely in my brain. What determines the transformation of transient aches into ceaseless agony is not only explained by anatomy but often by psychology. Our perception of pain—and our fear of it—can play a huge role in clinical outcomes. However, far from minimizing people’s experiences, this understanding is opening the door to treatments that might finally (and durably) help the millions living in unending torment.

I’m now a doctor, and our traditional approach in medicine has been to find mechanical and anatomic explanations for chronic pain; I was told from the MRI of my back that I had abnormalities so profound for a young person (I was just 20 years old), I had become the dreaded “interesting case” discussed at the radiology department’s weekly conference. My bones were degenerating, and I had multiple damaged discs in my spine. Without any visible scars or deformities that were outwardly apparent, the MRI scans were the only evidence for what turned my acute injury into never-ending torment.

Chronic pain is usually defined as pain that affects someone frequently for three months or more, and mine exceeded that defined period by many years. I was reluctant to take painkillers and focused all of my energies on physical therapy. My pain has improved over time, but my origin story—the injury and the resulting abnormalities that showed up on the MRI—has had little to do with the pain I felt years afterward. “The classic idea is that if the injury is bad enough, it will stay on,” Vania Apkarian, one of the world’s leading pain researchers, told me. “But the injury itself has no value.”

MRIs, while reliable indicators of injury, are not reliable indicators of pain. A review of studies that involved scanning images from about 3,000 people with no symptoms of back pain found that in 20-year-olds without any back pain, 37 percent had disc degeneration, and 30 percent had disc bulges. These abnormalities should cause pain, but for these people, they didn’t. These abnormalities that show up in medical scans only increase with age, as 96 percent of 80-year-olds had disk degeneration and 84 percent had bulges. Even in people whose backs hurt, MRI abnormalities have shown absolutely no correlation with their pain—in other words, an MRI doesn’t help us figure out what hurts and what doesn’t. These data upended my narrative.

This is a really big deal: millions of people in the U.S., alone get MRIs and CT scans for back pain, which is the most common cause of disability around the world. Most of these tests are inappropriate since guidelines now recommend against the routine use of imaging for people with back pain. Yet a recent study showed that only 5 percent of MRIs ordered by clinicians for back pain were appropriate, and of those who received MRIs, 65 percent received potentially harmful advice emanating from the scans—including calls for back surgery.

Spine surgery is one of the most commonly performed procedures in the United States and around the world, but it can have devastating effects: in one study of people who had chronic back pain, of the people who had spine fusion surgery, only 26 percent returned to work compared with 67 percent of people who didn’t have surgery. The people who chose surgery were more likely to develop complications and permanent disability than the people who didn’t. I could have been one of those people: when I took my MRI films to Ather Enam, a renowned surgeon, he told me that an operation might leave my back worse off. “I could do the surgery, but a spine that’s been touched by a surgeon is never the same again,” he said.

So if anatomy doesn’t explain why pain turns chronic, what does? Turns out that at least part of the cause was in my head.

One of the major reasons why pain becomes immortal in our bodies is how we feel in our minds. People who fear being in pain or are anxious about it are up to twice as likely to develop chronic pain after undergoing an operation. A study from Finland published this April showed that the presence of psychological distress significantly affected the presence or absence of back pain in those with degenerated spines. In fact, one small study showed that past traumatic events such as being robbed, bullied or sexually assaulted, were the strongest predictors of back pain turning chronic in the study’s 84 participants; even the early fear of pain becoming permanent becomes a self-fulfilling prophecy.

Although in clinical medicine and societal discourse, mind and body, sensation and emotion, biology and psychology, are often considered as distinct, human nature begs to differ. In fact, these dichotomies collapse most dramatically when it comes to pain. As acute pain turns chronic, Apkarian’s research shows it activates parts of the brain more responsible for emotions than physical sensations.

A recent clinical trial published in the Journal of the American Medical Association: Psychiatry indicates the power of therapies that target how we feel about hurting. In the study, led by Yoni Ashar and Tor Wager, the scientist who discovered the neurologic signature of pain in the brain, patients with chronic low back either received usual care mostly involving pain medications and physical therapy, were told they were getting a placebo (which can be quite effective for back pain) or received pain reprocessing therapy, which teaches people that the brain actively constructs chronic pain in the absence of an active injury and that simply reframing the threat pain represents can reduce or eliminate it. Such therapy defangs chronic pain of its sharpest weapon—fear. The results were quite remarkable: Of those people who received pain processing therapy twice-weekly for a month, 52 percent were pain-free at one year, compared with 27 percent of those receiving placebo and 16 percent receiving usual care. Patients also experienced improvements in disability, anger, sleep and depression.

Embracing the complexity of pain, especially chronic pain, can open the door to new and innovative ways to ensure that even if we hurt, we don’t suffer. Therapies like pain reprocessing therapy embrace pain for what the science reveals it to be—as much an emotional and traumatic construct as a physical sensation. Such a holistic embrace of pain’s nature, far from making us not take it seriously, should spur efforts even further to make sure everyone in agony receives kindness and respect, as well as access to more than pills and surgical procedures on their path to healing.

09/09/2022

The Weight Game: How Body-Size Bias Can Hold Back Health Science

In December 1994 then former U.S. surgeon general C. Everett Koop launched a national weight-loss campaign at a White House press conference, stating that obesity had become the country’s second-largest cause of death, “resulting in about 300,000 lives lost each year.”
This marked the beginning of a long, influential life for the statistic. Pundits and scientists alike began citing the number to highlight the gravity of the “obesity epidemic.” It was leveraged in Food and Drug Administration approval hearings for weight-loss medications with questionable safety profiles. One drug, dexfenfluramine (Redux), was later pulled from the market for damaging patients’ heart valves. Another, sibutramine (Meridia), was removed for increasing the risk of heart attacks and strokes.
After a decade the number had ballooned to nearly 400,000 deaths attributed to high weight, with predictions that it would soon reach half a million—about 20 percent of all annual American deaths. But by 2005 these seemingly staggering numbers were overturned. The statistic slayer was Katherine Flegal, then a senior scientist at the Centers for Disease Control and Prevention and now one of the most cited epidemiologists in her field.
Hoping to better understand the relationship between body size and mortality, Flegal led a study that ultimately revealed something many scientists—and certainly the public—did not expect: the annual deaths related to obesity tallied to just more than 100,000. More interesting still, people considered clinically “overweight” had a longer life expectancy than those who fell in the “normal” weight category. (So if you added the overweight and obese categories together like in previous studies, the total was under 26,000 deaths).
Her work should not have caused such a stir. It was consistent with other research and backed by the CDC (it even received a 2006 Charles C. Shepard Science Award, one of the agency’s most prestigious honors). Yet the study was met with a firestorm of doubt and criticism.
“People were preemptively contacting journalists saying that our article was rubbish,” Flegal says. “Our findings produced controversy because someone wanted a controversy.”
In this short documentary, Retro Report partners with Scientific American to examine how biases about body size can influence the questions scientists investigate and what information people accept as true.
Myths, assumptions and biases are persistent and well documented in the contentious realm of obesity research. Flegal says they are bolstered by societal weight stigma and the financial interests of the pharmaceutical and weight-loss industries. “The whole area of body weight and obesity has become very, very difficult to study objectively,” she explains. “There’s so much emotion, so many interests that are involved.”
As an example of the stubbornness of ingrained beliefs about obesity, the infamous “300,000 deaths” statistic still lives on today despite the lack of supporting evidence. In the past year alone it has appeared in opinion pieces from the Hill, the Washington Post and a variety of local newspapers. (Most have cited a Web page by the West Virginia health department’s Health Statistics Center that has not been updated since 2003). It has also been referenced recently in top medical journals, health manuals and even a congressional bill. Plus, it is a favorite of weight-loss centers across the country.
“People are just more comfortable with a larger number—they prefer it to be larger,” Flegal suspects. “I don’t think discomfort itself should be a factor in science, but I think it has more of an effect than we might realize.”
Bias muddies the process of science. And in nutrition science and medicine, that bias can often equate to the idea that thinner is better, skinnier is healthier. And when results seem to contradict that preconceived notion, the findings are often qualified by the phrase “obesity paradox.”
“You can report the same findings about obesity 100 times, and it can be called ‘unexpected’ every single time,” Flegal says. “It’s like, well, at what point would you change your mind and say this might be the expected result?”
So far this so-called paradox has been documented in several conditions, including heart disease, lung cancer, type 2 diabetes and stroke, among others. But the label of “obesity paradox” can often lead to disbelief around such results even though they present an opportunity to learn something new, says Bette Caan, a cancer researcher at Kaiser Permanente, who stumbled onto her own “paradox” in breast cancer.
“It’s human nature for people to find evidence that supports their belief,” Caan says. “We need to study where the data takes us.” Her own “unexpected findings” led to a discovery that could impact breast cancer patients across the nation: retaining muscle during treatment is far more important to survival than avoiding weigh gain.