Posts Tagged ‘microbe’


Microbes can produce so much alcohol that people become drunk—and sustain liver damage—without touching any booze.

by Ed Yong

The man’s troubles began in 2004, when, having moved from China to attend college in Australia, he got really drunk. That would hardly have been a noteworthy event, except that the man hadn’t consumed any alcohol—only fruit juice.

The bizarre incident soon turned into a pattern. About once a month, and out of the blue, he’d become severely inebriated without drinking any alcohol. Over time, the episodes became more severe and more frequent. He lost jobs because people suspected him of being a closet drinker. He was frequently hospitalized. In 2011, he returned to China and his mother cared for him while monitoring him with a Breathalyzer. His blood-alcohol levels, she found, would erratically and inexplicably soar to 10 times the legal limit for driving.

In June 2014, at the age of 27, he was admitted to the intensive-care unit of Chinese PLA General Hospital, in Beijing. At one point, so much alcohol was on his breath that he couldn’t sleep through the night. Another time, he threw up and blacked out after chugging some soda water. A CT scan showed that his liver was damaged, inflamed, and riddled with fatty deposits.

The man was diagnosed with a rare condition aptly known as auto-brewery syndrome, in which microbes in a person’s gut ferment carbohydrates into excessive amounts of alcohol. The earliest cases were documented in Japan in the 1950s, and a few dozen more have been reported since, in people all over the world, and even in children as young as 3. The microbial culprits are usually yeasts—the same fungi used to brew beer and wine—and the condition can often be treated with antifungal drugs.

But those drugs didn’t work on the Chinese patient. Baffled, a team of doctors, led by Jing Yuan from the Capital Institute of Pediatrics, analyzed the man’s stool samples and found that the alcohol in his body was being produced not by yeast, but by bacteria. During his first episode in the hospital, Klebsiella bacteria had bloomed so vigorously that it made up 19 percent of the microbes in his gut, and became 900 times more common than in healthy people.

Klebsiella pneumoniae is extremely common in both soils and human bodies. Though usually harmless, it’s also an opportunistic pathogen that can cause severe infections if given the chance. And while Klebsiella is not known for intoxicating its hosts, Yuan’s team found that the patient had two particular strains that can churn out alcohol. Many gut microbes do this, but at such low levels that their boozy by-products are easily removed by the liver. The Klebsiella strains in Yuan’s patient were exceptions: At one point, they produced so much of the stuff that it was as if the man had knocked back 15 shots of whiskey. “We were surprised that bacteria can produce so much alcohol,” Yuan says.

Auto-brewery syndrome is extreme, but it has similarities to other, milder and more prevalent conditions. For example, people with nonalcoholic fatty liver disease (NAFLD) build up fatty deposits in their liver in the style of heavy drinkers, despite touching little or no alcohol. This condition is very common, affecting 30 to 40 percent of American adults; the causes are still unclear and likely varied. Yuan wondered if Klebsiella might be involved, and when she analyzed 43 Chinese people with NAFLD, she found that 61 percent had the same high-alcohol strains as the man with auto-brewery syndrome. By contrast, just 6 percent of people with a healthy liver carry those strains.

To see if those strains were actually causing fatty livers, the team fed them to mice that had been raised in sterile conditions and lacked microbes of their own. Within two months, the rodents had signs of liver disease, inflammation, and scarring, comparable to mice that had been drinking alcohol itself. The same thing happened if the team transplanted the stool from an NAFLD patient into germ-free mice, but not if they first removed the alcohol-making Klebsiella using a virus—a phage—that specifically kills those strains. Although studies in mice should be treated with caution, Yuan nonetheless suggests that these strains could be an important cause of NAFLD, through the alcohol they produce.

Other researchers have suggested this before. In 2000, Anna Mae Diehl from Johns Hopkins University noticed that obese mice often have alcohol on their breath, which goes away after antibiotic treatment. “Intestinal production of ethanol may contribute to the genesis of obesity-related fatty liver,” she speculated. Two groups later showed that alcohol-producing microbes are more common in the guts of people with NAFLD than in those of their healthy peers.

While Yuan’s team pointed their fingers at Klebsiella, “it was found in only 60 percent of the human subjects they studied with NAFLD,” says Susan Baker at the State University of New York at Buffalo. “Others have identified other likely bacteria as possible culprits.” She cautions against focusing on any specific microbe, and instead considering the entire ecosystem of the body—bacteria, yeasts, viruses, gut cells, immune cells, liver, and all.

Yuan agrees. She notes that NAFLD is a complex and varied condition, and that even if Klebsiella does turn out to be a cause, it would be one of many. It also raises several questions: Why do some strains produce so much alcohol? Where do they come from? What makes them bloom so vigorously in people such as the unfortunate Chinese man who launched this study—genetics, diet, or something else? And perhaps most important, what can be done about them?

Phages might eventually help, as they did in Yuan’s mice. But for her patient with auto-brewery syndrome, simpler measures did the trick. He was treated with an antibiotic and put on a no-sugar, no-carbohydrate diet for three weeks. His intoxication symptoms eventually subsided, and two months later he was released from the hospital.

https://amp.theatlantic.com/amp/article/598414/

Why do some people remain healthy into their 80s and beyond, while others age faster and suffer serious diseases decades earlier? New research led by UCLA life scientists may produce a new way to answer that question—and an approach that could help delay declines in health.

Specifically, the study suggests that analyzing intestinal bacteria could be a promising way to predict health outcomes as we age.

The researchers discovered changes within intestinal microbes that precede and predict the death of fruit flies. The findings were published in the open-source journal Cell Reports.

“Age-onset decline is very tightly linked to changes within the community of gut microbes,” said David Walker, a UCLA professor of integrative biology and physiology, and senior author of the research. “With age, the number of bacterial cells increase substantially and the composition of bacterial groups changes.”

The study used fruit flies in part because although their typical life span is just eight weeks, some live to the age equivalent of humans’ 80s and 90s, while others age and die much younger. In addition, scientists have identified all of the fruit fly’s genes and know how to switch individual ones on and off.

In a previous study, the UCLA researchers discovered that five or six days before flies died, their intestinal tracts became more permeable and started leaking.

In the latest research, which analyzed more than 10,000 female flies, the scientists found that they were able to detect bacterial changes in the intestine before the leaking began. As part of the study, some fruit flies were given antibiotics that significantly reduce bacterial levels in the intestine; the study found that the antibiotics prevented the age-related increase in bacteria levels and improved intestinal function during aging.

The biologists also showed that reducing bacterial levels in old flies can significantly prolong their life span.

“When we prevented the changes in the intestinal microbiota that were linked to the flies’ imminent death by feeding them antibiotics, we dramatically extended their lives and improved their health,” Walker said. (Microbiota are the bacteria and other microorganisms that are abundant in humans, other mammals, fruit flies and many other animals.)

Flies with leaky intestines that were given antibiotics lived an average of 20 days after the leaking began—a substantial part of the animal’s life span. On average, flies with leaky intestines that did not receive antibiotics died within a week.

The intestine acts as a barrier to protect our organs and tissue from environmental damage.

“The health of the intestine—in particular the maintenance of the barrier protecting the rest of the body from the contents of the gut—is very important and might break down with aging,” said Rebecca Clark, the study’s lead author. Clark was a UCLA postdoctoral scholar when the research was conducted and is now a lecturer at England’s Durham University.

The biologists collaborated with William Ja, an assistant professor at Florida’s Scripps Research Institute, and Ryuichi Yamada, a postdoctoral research associate in Ja’s laboratory, to produce an additional group of flies that were completely germ-free, with no intestinal microbes. Those flies showed a very dramatic delay in intestinal damage, and they lived for about 80 days, approximately one-and-a-half times as long as the animal’s typical life span.

Scientists have recently begun to connect a wide variety of diseases, including diabetes and Parkinson’s, among many others, to changes in the microbiota, but they do not yet know exactly what healthy microbiota look like.

“One of the big questions in the biology of aging relates to the large variation in how we age and how long we live,” said Walker, who added that scientific interest in intestinal microbes has exploded in the last five years.

When a fruit fly’s intestine begins to leak, its immune response increases substantially and chronically throughout its body. Chronic immune activation is linked with age-related diseases in people as well, Walker said.

Walker said that the study could lead to realistic ways for scientists to intervene in the aging process and delay the onset of Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease, diabetes and other diseases of aging—although such progress could take many years, he said.

Have you ever been on the subway and seen something that you did not quite recognize, something mysteriously unidentifiable?

Well, there is a good chance scientists do not know what it is either.

Researchers at Weill Cornell Medical College released a study on Thursday that mapped DNA found in New York’s subway system — a crowded, largely subterranean behemoth that carries 5.5 million riders on an average weekday, and is filled with hundreds of species of bacteria (mostly harmless), the occasional spot of bubonic plague, and a universe of enigmas. Almost half of the DNA found on the system’s surfaces did not match any known organism and just 0.2 percent matched the human genome.

“People don’t look at a subway pole and think, ‘It’s teeming with life,’ ” said Dr. Christopher E. Mason, a geneticist at Weill Cornell Medical College and the lead author of the study. “After this study, they may. But I want them to think of it the same way you’d look at a rain forest, and be almost in awe and wonder, effectively, that there are all these species present — and that you’ve been healthy all along.”

Dr. Mason said the inspiration for the study struck about four years ago when he was dropping off his daughter at day care. He watched her explore her new surroundings by happily popping objects into her mouth. As is the custom among tiny children, friendships were made on the floor, by passing back and forth toys that made their way from one mouth to the next.

“I couldn’t help thinking, ‘How much is being transferred, and on which kinds of things?’ ” Dr. Mason said. So he considered a place where adults can get a little too close to each other, the subway.

Thus was the project, called PathoMap, born. Over the past 17 months, a team mainly composed of medical students, graduate students and volunteers fanned out across the city, using nylon swabs to collect DNA, in triplicate, from surfaces that included wooden benches, stairway handrails, seats, doors, poles and turnstiles.

In addition to the wealth of mystery DNA — which was not unexpected given that only a few thousand of the world’s genomes have been fully mapped — the study’s other findings reflected New York’s famed diversity, both human and microbial.

The Bronx was found to be the most diverse borough in terms of microbial species. Brooklyn claimed second place, followed by Manhattan, Queens and Staten Island, where researchers took samples on the Staten Island Railway.

On the human front, Dr. Mason said that, in some cases, the DNA that was found in some subway stations tended to match the neighborhood’s demographic profile. An area with a high concentration of Hispanic residents near Chinatown in Manhattan, for example, yielded a large amount of Hispanic and Asian genes.

In an area of Brooklyn to the south of Prospect Park that roughly encompassed the Kensington and Windsor Terrace neighborhoods, the DNA gathered frequently read as British, Tuscan, and Finnish, three groups not generally associated with the borough. Dr. Mason had an explanation for the finding: Scientists have not yet compiled a reliable database of Irish genes, so the many people of Irish descent who live in the area could be the source of DNA known to be shared with other European groups. The study produced some less appetizing news. Live, antibiotic-resistant bacteria were discovered in 27 percent of the collected samples, though among all the bacteria, only 12 percent could be associated with disease. Researchers also found three samples associated with bubonic plague and two with DNA fragments of anthrax, though they noted that none of those samples showed evidence of being alive, and that neither disease had been diagnosed in New York for some time. The presence of anthrax, Dr. Mason said, “is consistent with the many documented cases of anthrax in livestock in New York State and the East Coast broadly.”

The purpose of the study was not simply to satisfy scientific curiosity, the authors said. By cataloging species now, researchers can compare them against samples taken in the future to determine whether certain diseases, or even substances used as bioterrorism weapons, had spread.

City and transit officials did not sound grateful for the examination.

“As the study clearly indicates, microbes were found at levels that pose absolutely no danger to human life and health,” Kevin Ortiz, a spokesman for the Metropolitan Transportation Authority, said in an email. And the city’s health department called the study “deeply flawed” and misleading.

Dr. Mason responded by saying he and his team had simply presented their complete results.

“For us to not report the fragments of anthrax and plague in the context of a full analysis would have been irresponsible,” he said. “Our findings indicate a normal, healthy microbiome, and we welcome others to review the publicly available data and run the same analysis.”

http://www.nytimes.com/2015/02/06/nyregion/among-the-new-york-city-subways-millions-of-riders-a-study-finds-many-mystery-microbes.html?hp&action=click&pgtype=Homepage&module=mini-moth&region=top-stories-below&WT.nav=top-stories-below

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.