From Cancer Drugs To Gut Bugs: 10 Medical Trends To Watch In 2016

Former President Jimmy Carter, whose latest brain scans show no sign of the melanoma he was diagnosed with, is a high-profile example of recent advances in treating cancer. (David Goldman/AP)

Former President Jimmy Carter, whose latest brain scans show no sign of the melanoma he was diagnosed with, is a high-profile example of recent advances in treating cancer. (David Goldman/AP) 

By Dr. Michael Misialek
Guest contributor

2016 is the year of the monkey, according to the Chinese calendar, but from my corner of the medical world — as a pathologist who tries to stay current on the medical big picture — it’s looking more like the year of the crab (cancer, that is).

Looking through my microscope, I expect the most striking medical advances next year in the field of cancer treatment. More broadly, here’s what I expect in the year to come, starting with scientific and technological progress and then getting into the health care system.

1. Cancer: Immunotherapy And More

Immunotherapy for cancer exploded in 2015. What is immunotherapy? It’s the technique by which the power of the immune system is harnessed to attack cancer. It’s already used in many cancer treatments, but it tends to be a second-line approach or reserved for advanced disease. In 2016, we’ll see more immunotherapy treatments approved and they will likely become the first-line choice in many cancers.

We can also expect to see more cell-mediated therapies — engineering a patient’s own immune cells to attack cancer — added to the cancer armamentarium. And expect to hear more about epigenetics — using the cancer cell’s genetic programming to push it back toward normalcy.

Recently, the American Association for Cancer Research convened an international immunotherapy conference, which completely sold out. One of the biggest stories to emerge was how chemotherapy resistance can be overcome using engineered proteins. Resistance is an all-too-common problem that dampens the hopes of precision medicine. These proteins, which are smaller than antibodies, will bring immunotherapy to new levels in 2016.

New drug combinations, combining traditional chemotherapy with immunotherapy, will also blossom in 2016. Such approaches are already showing promise in lung cancer, prostate cancer and melanoma. And we can expect new vaccines against cancer to emerge in 2016.

2. Related: ‘Basket Studies,’ A New Approach to Clinical Trials

Traditional drug trials test a drug against a known cancer type. With the precision medicine revolution upon us, it has become evident that many cancers, regardless of type, often share the same genetic mutations. 2015 saw the first trials of using a drug in an off-label manner to target common mutations across cancers of many different organs. Such “basket trials,” I think, will explode in popularity in 2016 in an effort to bring greater patient access to drugs. This new clinical trial paradigm will become commonplace in 2016. Already the American Society of Clinical Oncology is sponsoring its first-ever basket trial, partnering with five drug companies. Expect preliminary results in 2016.

3. Leveraging Our Gut Microbes

A microbiologist points out an isolated E. coli growth on an agar plate. E. coli is a gut microbe that plays a major role in health and disease. (Elaine Thompson/AP)

A microbiologist points out an isolated E. coli growth on an agar plate. E. coli is a gut microbe that plays a major role in health and disease. (Elaine Thompson/AP)

The bacteria in the gut have long been known to play a role in the immune system and metabolism. Now, new research is showing that many diseases may be caused in part by gut microbes, and I expect the coming year to bring a flurry of new uses for these microbes.

One of the fasting-growing applications is the use of fecal transplants to treat the deadly Clostridium difficile infection. Other diseases such as inflammatory bowel disease, irritable bowel syndrome, autoimmune diseases and allergic disease will likely see bacteria-based treatment advances in 2016.

Recently, gut microbes have even been shown to reduce the side effects of chemotherapy. Perhaps most exciting are the ways in which these bacteria are detected. Traditional methods of bacterial culture will become replaced by genetic sequencing of bacterial DNA. Such powerful information is already showing early promise in helping to stem transmission of drug-resistant bacteria within and between hospitals, a major cause of illness and death.

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Research: Could Birth-Canal Bacteria Help C-Section Babies?

From a poster at the recent Boston meeting of the American Society of Microbiology. (Courtesy Dr. Dominguez-Bello)

From a poster at the recent Boston meeting of the American Society for Microbiology. (Courtesy Dr. Dominguez-Bello)

The usual drill is to wipe the effluvia of birth off of newborn babies, cleaning them up and readying them for snuggling.

But in a fascinating departure, researchers have begun to experiment with the opposite: collecting birth-canal bacteria and wiping them onto babies after birth.

Why in the world? For good reason: to explore whether it might help babies delivered by C-section to restore some of the vaginal bacteria that they would have been exposed to if they’d gone through the birth canal.

Why do that? On the theory that altered bacterial populations could help explain why C-section babies tend to have higher odds of asthma, allergies, obesity and other health risks.

Dr. Maria Gloria Dominguez-Bello, an associate professor in the Human Microbiome Program at the NYU School of Medicine, presented some preliminary results on that research at a recent conference of the American Society for Microbiology here in Boston. Those initial findings suggest that indeed, using gauze to gather a mother’s birth-canal bacteria and then impart them to babies born by C-section does make those babies’ bacterial populations more closely resemble vaginally born babies — though only partially.

Many questions remain. But the research sounded so intriguing — and the intervention so simple, if it gains medical approval — that I asked Dr. Dominguez-Bello to discuss it. Our conversation, edited:

Your poster reports that there were six vaginal births, seven C-sections and four C-sections in which the babies also received the ‘inoculum’ of vaginal bacteria. But it wasn’t clear to me: To what extent did the mothers’ bacteria restore a more normal balance of bacteria in the C-section babies? A little or a lot?

When we analyzed the sharing — how many microbes any site of the baby’s body share with their mom’s vagina — we doubled the number of bacteria that the C-section babies were exposed to. But the vaginal process was six times as much. So the vaginal delivery still exposes the baby to a lot more.

In other words, if we got one bacteria in the C-section baby that is associated with the vagina, we got two in the inoculated C-section but six in the vaginal births. So those C-section babies still don’t have the full exposure of the vaginal babies.

That’s logical because during labor, the baby is rubbing against the mucosa of the birth canal for a long time and bacteria start growing even before the baby is out — growing and colonizing the baby during birth. In half an hour, you get multiplication of bacteria. If the baby gets one cell, an hour later the baby has probably four of those cells and five hours later, it’s exponential.

Also, C-sections involve antibiotics. There is no C-section without antibiotics, and we don’t know what the effect is of that gram of penicillin. If it’s good enough to kill strep B, I’m sure it’s killing a lot more than that community of bacteria.

If your research pans out, using this gauze technique for C-section babies would seem to be such an easy intervention. I imagine there might already be women saying, ‘I want to do that.’ Possibly even, ‘I want to schedule a C-section and do that.’ What would you say to them?

I would say labor is a very complex process and labor is far more than inoculating the baby. And it’s a process that we don’t fully understand — what’s its adaptive value, why is it important? Continue reading

‘Missing Microbes’: How Hard Should You Resist Antibiotics? And Why

(Photo: R. Zimmerman)

(Photo: R. Zimmerman)

The new book “Missing Microbes” posits that our rampant overuse of antibiotics is not just creating antibiotic-resistant “superbugs”; it is contributing to many of our modern maladies, particularly those affecting children: asthma, allergies, diabetes, obesity.

It’s an idea that has lately been gaining attention and adherents. But you’re especially likely to pay attention and be persuaded when you’re hearing about it from a leading authority on the microbial “ecologies” in our bodies that are damaged by antibiotics: Dr. Martin Blaser, director of the Human Microbiome Program at New York University. Dr. Blaser, who wrote “Missing Microbes,” is in town for a microbiology conference and will be on Radio Boston this afternoon. Our conversation, lightly edited:

As you write, antibiotics are prescribed at incredibly high rates in this country. That’s the big picture, and it’s clear that it’s a problem, but what’s the pragmatic translation? The small picture is something more like a baby who’s been screaming for days and a scared parent who needs to know, just how hard should we resist antibiotics, and in what situations?

We’re starting with perhaps the most difficult question. But you see, in the United States, in order to get antibiotics, you need a prescription. And that means it’s really up to the doctor. And because everyone has thought that antibiotics are ‘free,’ there has been a tendency by both doctors and parents to over-prescribe them and to over-want them. But once you start assigning a cost to them, then the situation changes. And so for parents, I advise them that when their child is sufficiently sick, that they should seek medical attention, and they should try to ensure that the doctor — and that’s shorthand for doctor, nurse, nurse practitioner, physician’s assistant — that the doctor do a careful exam. And then if the doctor says your child does not need an antibiotic, that parent should be relieved. Not thinking, ‘Why is my child deprived?’

But isn’t it so often unclear whether antibiotics are actually needed?

It is unclear, and in fact we know that most of the upper respiratory and ear infections that children have are caused by viruses that don’t even respond to antibiotics. As I write in my book, in the U.S. in 2010, there were 258 million courses of antibiotics prescribed. That’s five courses for every six people. So point number one is that that’s a lot. Point number two is that there’s enormous regional variation — variation that cannot be explained based on variation in the prevalence of different bacterial infections. So that means that it’s a function of how medicine is practiced. And the practice of medicine involves both the doctors and the patients. Both are parties. And what I point out is that in Sweden, where the people are at least as healthy as we are, at every age they’re using 40 percent of the antibiotics that we’re using. And that means, across the board, that 60 percent of the antibiotics are unnecessary. And that’s at every age, not just in childhood –though it’s especially important in childhood at every age. Continue reading

What A Difference A High-Fat Day Makes — To Your Gut Bugs

Stop reading right here if you just want to eat your holiday roast in peace. But if the familiar caveats about weight and cholesterol don’t work for you anymore, and you’re looking for a whole new reason for restraint among the rich holiday treats, here it is: High-fat eating wreaks changes in the microbes that inhabit your gut with such dramatic rapidity that even a single day can make a difference.

That finding is just out in the journal Nature, in a study titled “Diet rapidly and reproducibly alters the human gut microbiome.”

(Wikimedia Commons)

(Wikimedia Commons)

“This is the first time we’ve seen, I would say, a dramatic effect on the gut microbiome in response to diet in humans over a very short time frame,” said the paper’s senior author, Harvard microbiologist Peter Turnbaugh.

Just to review recent news from the sizzling, newish field of microbiomics: You are basically a walking, talking mountain of microbes. Well, not quite, but your bugs do outnumber you. The trillions of bacteria and viruses and fungi that live in your body outnumber your own cells by an estimated 10 to 1, and their genes outnumber your genes by probably hundreds to one.

Now for the Nature study: Turnbaugh and his colleagues put 10 human subjects on either a plant-based diet (think developing country, lentils and rice) or an animal-based diet (think Atkins, or a Western diet on steroids, with 70 percent fat and 30 percent protein). The researchers analyzed the participants’ gut microbes and found that within a day, they changed.

It’s not as if the whole set of microbes were replaced by a new set, Turnbaugh said, but the abundance of some microbes changed, and their activity — judged by which genes were “turned on” — changed rapidly. In meat-eaters, the microbes tended toward breaking down protein, while in plant-eaters, the bugs were more geared toward carbohydrate fermentation.

The biggest surprise came from one particular bacterium, Bilophila wadsworthia, which has been linked in animal studies to Irritable Bowel Disease. Turnbaugh’s team found that on the animal-based diet, those B. wadsworthia microbes increased more dramatically than others.

So “it all points to the idea that — just as had been previously seen in animals — in humans, eating certain diets that are high in the right types of fats may lead to expansions of these microbes that are potentially pathogenic,” he said.

More broadly, are we entering an era of thinking differently about how our diets affect us? Will we soon be thinking about how they change not just our waistlines and cholesterol levels but also our microbiomes? Continue reading