Gas-sensing pills sniff out fiber’s effect on the gut

Intestinal gases are more than just an embarrassing problem. Changes in the type of gases are linked to digestive diseases like irritable bowel syndrome, which affects at least 15.8 million people in the United States alone. But doctors and scientists didn’t have an easy, reliable tool for figuring out how gases change in sick people—until now.

Australian scientists have reported the first-ever animal trials of “smart pills”—tiny electronic capsules that measure gases in real-time as they travel safely through the gut. These smart pills could help scientist figure out what diets and drugs affect the gut. And they might help doctors better diagnose people with IBS, inflammatory bowel disease, and even colon cancer.

Doctors have traditionally used breath tests to measure the intestinal gases wafting out of a patient’s mouth, writes Ariel Bogle for Mashable. But when gases waft out, they’re all jumbled together. “The smart pills allow us to identify precisely where the gases are produced and help understand the microbial activity in these areas,” says study author Kourosh Kalantar-zadeh in a press release.

That microbial activity comes from the trillions of bacteria in people’s guts which help digest food, writes John Boyd for IEEE Spectrum. In heathy people, this microbial fermentation produces the usual mix of hydrogen, methane, and carbon dioxide gases. However, a disease like IBS stresses the microbes and changes the relative concentration of gases.

But before doctors could start measuring sick people’s gases, the scientists had to test the pills in pigs. The scientists gave the pills to one group of pigs eating a high-fiber diet and to a second group eating a low-fiber diet. They were expecting that the pigs eating more fiber would have more microbial fermentation, and therefore produce more hydrogen and methane gases.

What they found instead was a “complete surprise,” says Kalantar-zadeh. Instead of the high-fiber diets producing more hydrogen and methane, the low-fiber diet produced four times more hydrogen in the pigs’ small intestines. This suggests that people who have IBS and microbial overgrowth in their small intestine could eat a high-fiber diet to reduce their hydrogen gas. However, the high-fiber diet produced more methane in the pigs’ large intestine as expected—suggesting that a low-fiber diet might better prevent painful bloating.

Starting in the next two months, the scientists will find out if that’s the case in humans. An upgraded version of the capsule with a temperature sensor and more gas sensors will be tested in healthy human volunteers, writes Boyd. Hopefully, the pills will prove both smart and safe, and doctors will soon use them to help millions of people suffering from more than just an embarrassing problem.

Reference:
Kalantar-Zadeh K, Yao CK, Berean KJ, Ha N, Ou JZ, Ward SA, Pillai N, Hill J, Cottrell JJ, Dunshea FR, McSweeney C, Muir JG, & Gibson PR (2016). Intestinal Gas Capsules: A Proof-of-Concept Demonstration. Gastroenterology, 150 (1), 37-9 PMID: 26518389

The ancient Babylonians calculated Jupiter’s position long before NASA

To the ancient Babylonians, the planet Jupiter was more than a bright light in the Mesopotamian night sky: It was the celestial manifestation of their god, Marduk. Jupiter’s location told of Marduk’s plans for them, such as if they would be blessed with a good harvest. It was so important to know Marduk’s plans that Babylonian astronomers developed a sophisticated, surprisingly modern mathematical technique for predicting Jupiter’s location, according to a new study published in the journal Science.

Read more about this technique (which I used myself while doing molecular biology research) in my first-ever blog post for the award-winning science education site, Visionlearning!

Virus factories and hijacked proteins: How could Zika cause microcephaly?

There’s something missing from all the coverage of Zika virus, the mosquito-borne flavivirus that’s spread across 26 countries in the Americas since May 2015. While Zika usually doesn’t cause symptoms in adults, the outbreak coincided with a 20- to 40-fold surge in babies born with microcephaly—a very small head and an increased risk for mental retardation. With good reason, scientists are working hard to better understand and develop a vaccine against this esoteric virus.

But the scientist in me wants to know: Just how could Zika cause microcephaly?

Microcephaly has lots of causes, from genetic problems to alcohol exposure to congenital infections with syphilis bacteria, rubella virus, and Toxoplasma parasites. Microbes can cause birth defects indirectly—like by triggering fever in a pregnant woman—and directly, if the microbe crosses the placenta. Recent case reports have found that Zika virus can slip through the placenta and into the developing fetal brain.

Thanks to several recent case reports, we have a big-picture idea what Zika can do once it’s in the brain. Among infected fetuses and newborns, major brain structures were shrunken or even missing. The eyes and the optic nerves were damaged and shriveled. The remaining nervous tissue had fewer neurons than normal and was studded with immune cell nodules and calcium deposits—signs of inflammation and cell death.

To get an idea how Zika causes inflammation and death, we have to turn to studies in mice and cultured human skin cells. A 1971 study in mice found that the virus penetrated the brain’s neuron and glial cells, forming clot-like structures that the scientists called “virus factories.” These clots were microscopic evidence of the virus hijacking autophagy, the cell’s process for breaking down unwanted garbage proteins. A 2014 study using infected human skin cell cultures found that, like its other flavivirus cousins, Zika steals components needed for autophagy and uses them to replicate itself. Between a hijacked garbage system and microscopic factories churning out millions of viruses, it’s no wonder that cells are dying and the immune system is reacting.

However, a recent letter to the editor of Microbes and Infection proposes an interesting hypothesis for how a hijacked garbage system could lead to microcephaly. In his letter, Canadian microbiologist Jason Tetro proposes that Zika may actually be causing microcephaly by interfering with a cell’s centrosomes—structures important to evenly dividing chromosomes between two dividing cells. Some proteins are involved both in autophagy and in stabilizing these centrosomes. When Zika hijacks autophagy to replicate itself, it may be co-opting these double-duty proteins. Without the proteins, the chromosomes are less likely to be divided equally—leading to the sorts of genetic problems and chromosome abnormalities that most often cause microcephaly.

As for why we’re not seeing even more babies born with microcephaly: The severity of these effects probably relates to how developed the fetus is when it’s infected. Infections early in the pregnancy often have worse effects, because the brain and major organs are just being formed. Later infection usually has subtler effects.

Personally, I’m wondering about these fetuses infected later with Zika. Are we going to see a surge in kids with subtler problems, such as learning disabilities, that won’t be detected until they start school? Or will we be able to get a vaccine out there fast enough that Zika will become another contained tragedy, like thalidomide?

Reference:

Tetro JA (2016). Zika and microcephaly: causation, correlation, or coincidence? Microbes and infection / Institut Pasteur PMID: 26774330

I’m on radio!

… more specifically, I was on Talk 910 radio last Friday, when I was interviewed by Ed Baxter for the Gil Gross show.  We talked about why Cecil the lion was so important scientifically – a point I covered earlier in my article on Cecil for Slate.

The intro to the interview starts at about the 90% mark of the show’s podcast (01:55:19, if you download it), and the interview lasts for about 10 minutes.  Which is funny, because I spent easily 2+ hours reviewing the scientific literature, re-reading my story, and prepping answers for a dozen other questions that were never asked.

But, good experience overall!

E-cigarettes don’t help smokers stop smoking (or smoke less)

Electronic cigarettes don’t help people quit smoking or even smoke less. This conclusion – which further squashes hopes that e-cigarettes might enable America’s 42 million smokers to quit – comes from one of the largest studies of e-cigarette users to date, recently published in the American Journal of Public Health. In 2011, American researchers interviewed 1,000 adult smokers in California. One year later, the researchers found that Californians who either quit smoking or smoked less were less likely to have ever used e-cigarettes. The study’s findings agree with recent research that e-cigarettes do not help smokers quit, and may even make smokers more dependent on the nicotine in cigarettes.

These results arrive in the midst of a massive increase in e-cigarette use. In 2014, 13 out of every 100 high schoolers reported having used e-cigarettes – a ten-fold increase in popularity since just 2011. In 2011, more than 6 out of every 100 American adults reported using e-cigarettes, a doubling from just the previous year. Part of this increasing popularity among adult smokers likely comes from their perception that e-cigarettes help with quitting. Indeed, the researchers reported that the Californian smokers who had tried (and mostly failed) to quit were more likely to have used e-cigarettes. Unfortunately, this study demonstrates that using e-cigarettes and actually quitting – as opposed to intending to quit – were mutually exclusive.

Reference:
Al-Delaimy WK, Myers MG, Leas EC, Strong DR, & Hofstetter CR (2015). E-cigarette use in the past and quitting behavior in the future: a population-based study. American journal of public health, 105 (6), 1213-9 PMID: 25880947

An unusual form of diabetes may be caused by drinking arsenic-contaminated water

Like a careless criminal, even small amounts of toxic arsenic leave telltale fingerprints on victims’ bodies—although these fingerprints are different if the victim as Type 2 Diabetes, scientists report. And arsenic has many potential victims: more than 200 million people worldwide drink freshwater naturally contaminated with small amounts of arsenic. But for the first time, scientists have captured arsenic’s molecular fingerprint in the body fluids of people with and without diabetes from arsenic-contaminated Chihuahua, Mexico. By capturing these molecular fingerprints, the scientists have taken the first step towards reconstructing how arsenic may cause a little-understood form of Type 2 Diabetes.

While arsenic has many potential victims, Type 2 Diabetes has many confirmed ones. Roughly one out of fifteen adults—approximately 256 million people worldwide—has Type 2 Diabetes, and the excess glucose in their blood can damage their heart, kidneys, and nerves over time. But while people who drink arsenic-contaminated water are more likely to develop Type 2 Diabetes, scientists have observed that these arsenic-linked diabetics are different from most diabetics. Unlike most diabetics, their cells react normally to insulin, a hormone released by the pancreas that tells the cells to gobble up glucose from the blood. The problem—at least, the problem in arsenic-drinking lab rats which develop rat diabetes—is that the pancreas’s insulin-making cells seem to be poisoned by arsenic.

To figure out if this is true in humans, the scientists studied 176 people in Chihuaha, where the municipal water is contaminated with more than twice the WHO’s safety limit for arsenic. For each person with Type 2 Diabetes, the scientists matched them to another person the same gender, age, body-mass index, and the amount of arsenic in their tap water at home. The people with and without diabetes then donated their urine and blood plasma—body fluids which contain hundreds of known metabolites, the chemical residues of metabolism.

By examining the pattern of these metabolites, the scientists reconstructed how arsenic had changed people’s metabolism. When they looked at the metabolites unique to people who drank arsenic-contaminated water, they found that the people with diabetes had very different types of metabolites than people without diabetes. The diabetics’ different metabolites suggested that arsenic had changed how their bodies metabolize vitamins and amino acids, as well as how they get energy from food. Surprisingly, the metabolite pattern of the arsenic-linked diabetics was also very different from the metabolite patterns of most diabetics—providing the scientists with “a metabolic fingerprint” that hinted at molecular differences between these forms of diabetes.

 

Reference:
Martin, E., Gonzalez-Horta, C., Rager, J., Bailey, K., Sanchez-Ramirez, B., Ballinas-Casarrubias, L., Ishida, M., Gutierrez-Torres, D., Hernandez Ceron, R., Viniegra Morales, D., Baeza Terrazas, F., Jesse Saunders, R., Drobna, Z., Mendez, M., Buse, J., Loomis, D., Jia, W., Garcia-Vargas, G., Del Razo, L., Styblo, M., & Fry, R. (2015). Metabolomic Characteristics of Arsenic-Associated Diabetes in a Prospective Cohort in Chihuahua, Mexico Toxicological Sciences, 144 (2), 338-346 DOI: 10.1093/toxsci/kfu318

Uterine fibroid growth increases with cadmium exposure, but not because cadmium acts like estrogen

Breathing or eating even small amounts of the toxic metal cadmium—a widespread contaminant of cigarettes and seafood—may increase a woman’s risk for developing uterine fibroids, but not in the way scientists previously thought. By the age of 50, at least seven out of ten American women will have developed these benign tumors that can cause infertility and miscarriage. Scientists have long suspected that cadmium encourages fibroid growth by mimicking the natural hormone estrogen. However, new research published this month in Environmental Health Perspectives indicates that cadmium may instead encourage fibroid growth through a molecular pathway involved in a third of all tumors. The North Carolina researchers suggest that treatments targeting this pathway may block cadmium’s dangerous effects, and help limit the growth and damage of uterine fibroids in women.

To figure out how cadmium encourages fibroid growth, the researchers added it to different types of uterus-like cells grown in Petri dishes. When they grew the cells with low concentrations of cadmium—concentrations similar to the cadmium blood levels of more than 70% of Americans—they found that the metal greatly increased the number of cells, similar to how estrogen increases the number of uterus cells. But the similarity stopped there: while estrogen increased cell growth by interacting with estrogen receptors—molecules on a cell’s surface which relay signals to its nucleus, thereby affecting which genes turn on and off—the cadmium did not interact with the estrogen receptors.

So how was cadmium increasing the uterus cells’ growth? The researchers figured out the answer when they looked at other molecules involved in cell signaling—specifically, the MAPK pathway, a series of signal molecules involved in both healthy cell growth and cancerous cell growth. When they exposed the uterus cells simultaneously to cadmium and to chemicals that interfere with the MAPK pathway, they found that cadmium couldn’t increase cell growth. While cadmium didn’t increase cell growth by interacting with estrogen receptors, the researchers suggested that it may act together with estrogen naturally present in a woman’s body (or estrogen-like molecules such as bisphenol A) to increase fibroid growth more than cadmium or estrogen alone could.

Reference:
Gao X, Yu L, Moore AB, Kissling GE, Waalkes MP, & Dixon D (2015). Cadmium and Proliferation in Human Uterine Leiomyoma Cells: Evidence of a Role for EGFR/MAPK Pathways but Not Classical Estrogen Receptor Pathways. Environmental health perspectives, 123 (4), 331-6 PMID: 25343777