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Category: human microbiome

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The numbers are amazing. Researchers found all these microbes because of state of the art genetic analysis such as 16S rRNA gene sequencing (because most microbes can not be "cultured"). From Science Daily:

Cataloguing 10 million human gut microbial genes: Unparalleled accomplishment

Over the past several years, research on bacteria in the digestive tract (gut microbiome) has confirmed the major role they play in our health. An international consortium has developed the most complete database of microbial genes ever created. The catalogue features nearly ten million genes and will constitute a reference for all research on gut bacteria.

Research on the gut microbiome (all of the bacteria in the digestive tract) has multiplied over the past several years, helped in great part by new sequencing technologies. The gut microbiome, which scientists have labelled a "new organ" that is composed of tens of trillions of bacteria -- ten times as many as the number of cells in the human body -- is directly linked to the immune system and brain. It is a major player in chronic illnesses such as obesity and Type 2 diabetes. However, research in the field depends on access to reference gene databases (or catalogues), which is particularly important when identifying the functions of microbial genes. Few and far between, existing catalogues were created using samples from a limited number of people and geographical origins.

Most of the genes (around six million) are shared by just 1% of the population, making them quite rare. While there is substantial data today regarding the most common genes, future research will focus on determining the importance and role of these rare genes.

Thanks to this catalogue, the most clinically significant genes can be described, most notably those related to illnesses such as Type 2 diabetes, cirrhosis of the liver, cardiovascular diseases and some cancers. It will also provide a more complete picture of imbalances in the gut microbiome (dysbiosis), particularly those caused by medication.

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Much discussion about the link between gut bacteria and liver cancer, as well as the link between inflammation and cancer. Gut microbiome imbalances can cause health harms.

Bottom line: Try to improve your gut microbiome by eating a diet rich in fruits, vegetables, seeds, nuts, legumes, and whole grains.

From the Dec.4, 2014 issue of Nature: Microbiome: The bacterial tightrope

Imbalances in gut bacteria have been implicated in the progression from liver disease to cancer. The team's research, published last year, suggests that gut bacteria — which are part of the microbiome of bacteria and other microorganisms that live in and on the body — can play a crucial part in liver-cancer progression.

There are trillions of microorganisms in the human microbiome — they outnumber their host's cells by around ten to one — and their exact role in health and disease is only now starting to be explored. Studies have found that people with non-alcoholic fatty liver disease have a different composition of bacteria in their gut from healthy individuals2, 3

 Instead, she sees an emerging picture of liver disease and cancer as a process in which various factors — including a high-fat diet, alcoholism, genetic susceptibility and the microbiome — can each contribute to the progression from minor to severe liver damage, and from severe liver damage to cancer.

Flavell's research suggests that the liver has an important role in immune surveillance and helps to maintain bacterial balance in the gut. Specialized cells in the liver and intestines monitor the microbiome by keeping tabs on bacterial by-products as they pass through. These cells can detect infections and help to fight them.

But they can also pick up on subtler changes in the bacterial populations in the gut. When certain types of bacteria become too numerous — a state called dysbiosis — the immune system becomes activated and triggers inflammation, although at a lower level than it would for an infection... Now, research is emerging that suggests that dysbiosis and the immune reaction it provokes can even contribute to cancer.

He thinks that at least part of this mechanism involves disruption in the balance of the various species of bacteria in the gut. An out-of-balance microbiome promotes a constant state of inflammation, which can contribute to cancer progression, Schwabe says. This aligns with the picture that is emerging of cancer, in general, as an inflammatory process: the same immune reactions that help the body to fight infection and disease can also promote unchecked cell growth.

Some of the earliest research on the human microbiome, published in 2006, demonstrated that the balance of gut bacteria in obese people is different from that in people of healthy weight. In particular, obese people tend to have greater numbers of the bacteria that produce DCA (deoxycholic acid) and other secondary bile acids.

This line of research points to the microbiome as one potential link between obesity and liver-cancer risk . And, much like Schwabe's work, Hara's results indicate that several factors converge to promote cancer: in this case, bacteria, diet and carcinogen exposure. Here, too, the ability to stave off the disease seems to depend on maintaining the appropriate microbial balance. Overweight mice and people have a different composition of gut microbiota from their lighter counterparts, and they have higher levels of DCA, too.

However, not everyone is convinced that individual bacterial species are to blame. Some researchers point out that dysbiosis, and therefore cancer risk, involves multiple strains of bacteria. And the bacterial mix can vary from person to person, meaning it is unlikely that scientists can pin all responsibility on a single species.

Others are looking for ways to promote the growth of healthy bacterial strains rather than target the bad ones....There is also some early clinical evidence that specially formulated probiotics — cocktails of good bacteria — can bump the microbiome back into balance. Hylemon and his colleagues gave people with cirrhosis a probiotic containing Lactobacillus bacteria and found that their blood markers of inflammation decreased along with their cognitive dysfunction (a common symptom of cirrhosis)6. Although the study was not designed to evaluate cancer risk, it does show that delivering bacteria to the gut can have positive therapeutic effects on the liver.

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Please note that the study was of people living in the Baltimore, Maryland area - so it is unknown if this would hold true for people living elsewhere. From Medical Xpress;

Virus may affect mental abilities, study reports

People with an algae virus in their throats had more difficulty completing a mental exercise than healthy people, and more research is needed to understand why, US scientists say. A study in the Proceedings of the National Academy of Sciences showed that the virus was present in about half of 92 human subjects studied, and those who had it performed worse on certain basic tasks.

The virus, known as Acanthocystis turfacea Chlorella virus 1, or ATCV-1, also appeared to limit the cognitive abilities of mice.The mice had a harder time navigating a maze and noticing new objects in their surroundings after they were infected.

It remains unclear if the virus was truly driving the drop in mental functioning. Researchers have not yet shown the cause and effect between the virus and the intelligence results."At this point we do not think that this virus should be considered as a threat to individual or public health," said lead researcher Robert Yolken, a virologist at Johns Hopkins University in Baltimore, Maryland. The virus was found by accident while scientists were analyzing microbes in the throats of healthy humans for a different study.

Experts have been studying viruses similar to ATCV-1 for 35 years, said senior author James Van Etten of the University of Nebraska, an expert on algal viruses. Van Etten joined the research four years ago when Johns Hopkins scientists found ATCV-1's DNA sequences in the brain tissue of people who had died with mental disorders such as schizophrenia.

"These viruses are ubiquitous in fresh water ponds and streams throughout the world," Van Etten said. He noted that the virus—previously thought to only infect algae—could make its way into the human body when people swallow water while swimming.There might also be another host in nature, such as mosquito larvae, he said. But the nature of the disease is still in the early stages of analysis.

It is also unknown if the virus's effects on the brain are lasting or temporary. Scientists have long understood that viruses interact with DNA, and further studies could shed more light on the role of the virus on cognition.

"As more studies like this are conducted, I believe we'll find out there's even more interaction between viruses, bacteria and fungi that are either ingested or breathed into our noses and mouths and the overall human condition," said Jordan Josephson, ear nose and throat specialist at Lenox Hill Hospital in New York, who was not involved in the study.

Further information on this study and the virus. From Medical Xpress:

Researchers identify algae-virus DNA in humans

From Newsweek:

American Researchers Discover 'Stupidity Virus'

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Natural ways that may help GERD symptoms without drugs : eating smaller portions, losing weight, not lying down for 2 hours after eating, and avoiding alcohol, cigarettes, and "trigger" foods.From Health Day News:

Could Popular Heartburn Drugs Upset Your 'Good' Gut Bugs?

Heartburn drugs such as Prilosec and Nexium may disrupt the makeup of bacteria in the digestive system, potentially boosting the risk of infections and other problems, a small new study suggests.

According to Harvard Medical School, billions of dollars are spent annually on antacid drugs in an attempt to combat heartburn, ulcers and gastroesophageal reflux disease, also known as GERD. Old standbys such as Maalox and Mylanta have been supplanted by more effective, more expensive drugs, including proton pump inhibitors. These include Prevacid (lansoprazole) and Protonix (pantoprazole) in addition to Prilosec (omeprazole) and Nexium (esomeprazole).

Long-term use of proton pump inhibitors has been linked to infection with a germ called Clostridium difficile, which causes severe diarrhea, he said. Researchers have also connected the medications to vitamin deficiencies, bone fractures and pneumonia, among other conditions.

In the new study, researchers sought to understand what happens to the trillions of germs in the digestive system when people take omeprazole, the generic name for the drug best known as Prilosec.Ten participants, aged 18 to 57, took 20 or 40 milligrams of the drug a day for 28 days. Researchers analyzed the study participants' stool samples to understand the germs in their guts.

"These microbes have evolved with us to participate in our normal development and metabolism, and perform certain functions that we would not be able to accomplish without their help," DiBaise said. Many scientists believe that people's risk of disease goes up when their normal germ makeup changes, he said.

The researchers found evidence that the medications disrupted the balance of bacteria in the digestive systems of the participants, and the changes lasted for at least a month after they discontinued the drug. It didn't seem to matter whether they took the higher or lower dose, DiBaise said.

DiBaise cautioned that the study doesn't prove that the drug causes users to become more vulnerable to C. difficile infections. However, it shows that the drug "creates a situation in the gut microbial environment that may increase an individual's susceptibility," he said.

What should users do for now? According to DiBaise, proton pump inhibitors are "the most effective medications to treat gastroesophageal reflux disease." If patients don't have the most severe symptoms, he said, other types of heartburn drugs might help. Also recommended: eating smaller portions, losing weight, not lying down for two hours after eating, and avoiding alcohol, cigarettes and "trigger" foods.

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Bottom line: Try to avoid artificial sweeteners!

From Scientific American: Artificial Sweeteners May Have Despicable Impacts on Gut Microbes

I find it ironic that Thanksgiving coincides with American Diabetes Month. In honor of that irony, two recently published studies have suggested a possible link between what you eat, how it impacts the behavior of the microbes living in your gut, and type II diabetes.

Results from a study by researchers in Israel, published in the journal Nature in October, have suggested that consumption of artificial sweeteners—found in over 6,000 food products—can lead to changes in the gut microbiome, and have put forth an explanation for how this alteration might be associated with diseases such as type II diabetes.

Jotham Suez, a PhD candidate and lead author of the study explains, “We asked people who do not regularly consume artificial sweeteners to add them to their diet for one week, and saw that the majority of these subjects had poorer glycemic responses.” And like humans, mice that were given saccharin-spiked water also developed marked glucose intolerance compared to mice drinking sugar water, or water alone.

Their experiment revealed that mice did exhibit different microbiome profiles after consuming artificial sweeteners, just as with the human volunteers who had developed glucose intolerance. And importantly, the humans who did not show glucose intolerance after consuming artificial sweeteners also did not see changes in the community composition of their microbiome.

Consequently, this change in microbial community in mice also modified how the microbiota functioned as a group to regulate metabolism. Pathways that impact the transport of sugar in the body were found to have decreased function after saccharin treatment and, notably, there was an increased abundance of short-chain fatty acids (SCFAs), which are implicated in lipid biosynthesis.

An investigation done by an independent group of researchers in Canada found similar results in a study published in October in the journal PLoS ONE. Although conducted using rats instead of mice, and with a different artificial sweetener (aspartame instead of saccharin) this study also found an increased risk of glucose intolerance. In addition, both studies showed that propionate—a SCFA highly involved in sugar production—is increased in animals consuming artificial sweeteners (although, unfortunately, propionate concentrations in humans weren’t assessed in the Nature study).

But the take home point is this: findings from two independent studies suggest that messing with the microbiome may have despicable consequences. Artificial sweeteners were originally intended to stave off the increasing obesity and metabolic disease epidemic, but instead they may have directly contributed to it.

In other words, consuming artificial sweeteners appears to throw metabolism out of whack by upsetting the critical balance of the biota in the gut—just as how chaos would surely ensue if you were to throw Gru’s minions out of whack.

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Amazing persistence of the restroom microbial community.From NPR news:

What Microbes Lurked In The Last Public Restroom You Used?

The invisible world of the bathroom isn't pretty — unless you're a microbe. After scanning the microbial zoo of four public restrooms recently, a team of researchers found a diverse swarm of characters that persisted for months despite regular cleaning of the facilities. The goal of the study, published in the December issue of Applied and Environmental Microbiology, was to better understand how communities of bacteria and viruses can shift in these very public places across a couple of months.

To get their down-and-dirty readings, the researchers selected four bathrooms at San Diego State University... They checked two women's restrooms and two men's restrooms (a high-traffic and a low-traffic bathroom for each gender). The bathrooms were thoroughly cleaned at the study's start with bleach solution, which killed any existing germ communities.Then, during the following hours, days, weeks and months of human use, the researchers periodically swabbed soap dispensers, floors and toilet seats in all four restrooms for microbe samples. 

Within one hour of sterilization, the bathrooms were completely recolonized with microbes — just as plants rapidly arrive and populate a newly emerged island. Fecal bacteria dominated, including on toilet seats and on soap dispensers — about 45 percent of the bacteria there were of fecal origin.

In all, the scientists found genetic traces of more than 77,000 distinct types of bacteria and viruses. (At least some of those species were likely dead or dormant, the scientists add; genetic testing detects them all, whatever their status.)

Patterns of regrowth and succession, as some species waned and others replaced them, were surprisingly similar from bathroom to bathroom; within just five hours the population mix in each room stabilized.

When the team tried growing cultures from different surfaces in each room, they found one set of live bacteria in overwhelming abundance: Staphylococcus. Staph's persistence in these studies points to its power as a potential pathogen, Gilbert says. Various versions are common on human skin and inside the nose and other orifices; they generally cause no problems, or trigger only minor skin infections. But staph infections can be serious, or even kill, if the bacteria get into bloodstream, joints, bones, lungs or heart. 

Gilbert notes that none of the live Staph strains detected in the San Diego bathrooms showed signs of being antibiotic resistant. They were instead relatively harmless "skin bugs that happened to have lost their skin," he says. The team did find genes from MRSA hiding on the floor, as well as traces of some troublemaker viruses, including HPV and herpes virus.

Interestingly, although restrooms that were left open for use for up to two months were cleaned regularly with soap and water, the communities of microbes found there remained relatively unchanged for the full eight weeks of the study.

No need to be scared or grossed out by that finding, Gilbert says..."All human environments contain pathogens — your bedroom, the phone you're talking on, even the bugs inside of you could turn pathogenic at any time," Gilbert tells Shots. "But we desperately need them in our lives." Having a healthy community of good — or even just neutral — microbes can crowd out the bad ones. As we've learned from using broad-spectrum antibiotics in the human body, "sterilization is not necessarily good," he says. "Bacteria come back right away, and they might come back perturbed."

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Amazing how long the bacteria persisted in the air. From Science Daily:

Hand dryers can spread bacteria in public toilets, research finds

Modern hand dryers are much worse than paper towels when it comes to spreading germs, according to new research. Scientists from the University of Leeds have found that high-powered 'jet-air' and warm air hand dryers can spread bacteria in public toilets. Airborne germ counts were 27 times higher around jet air dryers in comparison with the air around paper towel dispensers.

The study shows that both jet and warm air hand dryers spread bacteria into the air and onto users and those nearby.

The research team, led by Professor Mark Wilcox of the School of Medicine, contaminated hands with a harmless type of bacteria called Lactobacillus, which is not normally found in public bathrooms. This was done to mimic hands that have been poorly washed.

Subsequent detection of the Lactobacillus in the air proved that it must have come from the hands during drying. The experts collected air samples around the hand dryers and also at distances of one and two metres away. Air bacterial counts close to jet air dryers were found to be 4.5 times higher than around warm air dryers and 27 times higher compared with the air when using paper towels. Next to the dryers, bacteria persisted in the air well beyond the 15 second hand-drying time, with approximately half (48%) of the Lactobacilli collected more than five minutes after drying ended. Lactobacilli were still detected in the air 15 minutes after hand drying.

Professor Wilcox said: "Next time you dry your hands in a public toilet using an electric hand dryer, you may be spreading bacteria without knowing it. You may also be splattered with 'bugs' from other people's hands.

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Exciting research in a new area - our trillions of viruses or virome. From the new research it looks like some of the viruses are beneficial to us and help keep us healthy. It's time to stop thinking of all viruses (and bacteria) as bad, but instead that some viruses are necessary for good health. From Science Daily:

Natural Gut Viruses Join Bacterial Cousins in Maintaining Health and Fighting Infections

Microbiologists at NYU Langone Medical Center say they have what may be the first strong evidence that the natural presence of viruses in the gut -- or what they call the 'virome' -- plays a health-maintenance and infection-fighting role similar to that of the intestinal bacteria that dwell there and make up the "microbiome."

In a series of experiments in mice that took two years to complete, the NYU Langone team found that infection with the common murine norovirus, or MNV, helped mice repair intestinal tissue damaged by inflammation and helped restore the gut's immune defenses after its microbiome had been wiped out by antibiotic therapy. In a report on their work to be published in the journal Nature online Nov. 19, researchers say they also found that MNV bolstered the immune system in fighting off tissue damage.

"Our research offers compelling data about the mutually supportive relationship between viruses and bacteria in the mouse gut and lays the groundwork for further research on precisely how the virome supports the immune system, which likely applies to humans, as well," says senior study investigator Ken Cadwell, PhD, an assistant professor at NYU Langone.

"We have known for a long time that people get infected all the time with viruses and bacteria, and they don't get sick," says Cadwell. "Now we have scientific evidence that not every viral infection is bad, but may actually be beneficial to health, just as we know that many bacterial infections are good for maintaining health."

According to Cadwell, until now, scientists have had mostly trace genetic evidence of a virome's existence, but none to confirm its normal presence in the gut or to clarify whether it plays a harmful, neutral, or helpful role.

What the NY Times had to say about this new area of research:

Viruses as a Cure

When we talk about viruses, usually we focus on the suffering caused by Ebola, influenza, and the like. But our bodies are home to trillions of viruses, and new research hints that some of them may actually be keeping us healthy.

“Viruses have gotten a bad rap,” said Ken Cadwell, an immunologist at New York University School of Medicine. “They don’t always cause disease.” Dr. Cadwell stumbled by accident onto the first clues about the healing power of viruses. At the time, he was studying the microbiome, the community of 100 trillion microbes living in our bodies. Scientists have long known that the microbiome is important to our health.

Kristine Wylie, a research instructor of pediatrics at Washington University School of Medicine who was not involved in the research, speculated that in real life, certain viruses might be important partners with the microbiome. “It isn’t hard to imagine that the viral exposures we get as children are important to our development,” she said.

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Share your microbiota with a kiss! From Science Daily:

Up to 80 million bacteria sealed with a kiss

As many as 80 million bacteria are transferred during a 10 second kiss, according to research published in the open access journal Microbiome. The study also found that partners who kiss each other at least nine times a day share similar communities of oral bacteria.

The ecosystem of more than 100 trillion microorganisms that live in our bodies -- the microbiome -- is essential for the digestion of food, synthesizing nutrients, and preventing disease. It is shaped by genetics, diet, and age, but also the individuals with whom we interact. With the mouth playing host to more than 700 varieties of bacteria, the oral microbiota also appear to be influenced by those closest to us.

Researchers from Micropia and TNO in the Netherlands studied 21 couples, asking them to fill out questionnaires on their kissing behaviour including their average intimate kiss frequency. They then took swab samples to investigate the composition of their oral microbiota on the tongue and in their saliva.

The results showed that when couples intimately kiss at relatively high frequencies their salivary microbiota become similar. On average it was found that at least nine intimate kisses per day led to couples having significantly shared salivary microbiota.

In a controlled kissing experiment to quantify the transfer of bacteria, a member of each of the couples had a probiotic drink containing specific varieties of bacteria including Lactobacillus and Bifidobacteria. After an intimate kiss, the researchers found that the quantity of probiotic bacteria in the receiver's saliva rose threefold, and calculated that in total 80 million bacteria would have been transferred during a 10 second kiss.

The researchers found that while tongue microbiota were more similar among partners than unrelated individuals, their similarity did not change with more frequent kissing, in contrast to the findings on the saliva microbiota.

Commenting on the kissing questionnaire results, the researchers say that an interesting but separate finding was that 74% of the men reported higher intimate kiss frequencies than the women of the same couple. This resulted in a reported average of ten kisses per day from the males, twice that of the female reported average of five per day.

A more humorous write-up of same study and a museum of microbes. From Time:

Here’s How Many Bacteria Spread Through One Kiss

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Another research result from the American Gut Project, an amazing crowdsourced project. While differences were found in the fecal microbiome (microbial community) of adults born by cesarean section vs vaginal delivery, it is unknown whether this has any possible effects on diseases or risks of diseases during adulthood. This study is online as of 8 November 2014, but still In Press. From EBioMedicine:

Diversity and Composition of the Adult Fecal Microbiome Associated with History of Cesarean Birth or Appendectomy: Analysis of the American Gut Project

Adults born by cesarean section appear to have a distinctly different composition of their fecal microbial population. Whether this distinction was acquired during birth, and whether it affects risk of disease during adulthood, are unknown.

Prenatal and early postnatal exposures and events can affect the entire life course. As one example, cesarean birth has been associated with an increased likelihood of asthma and cardiovascular disease in children (Renz-Polster et al., 2005, Thavagnanam et al., 2008 and Friedemann et al., 2012), hypertension in young adults (Horta et al., 2013), and obesity in both children and adults (Pei et al., 2014, Darmasseelane et al., 2014,Blustein et al., 2013 and Mueller et al., 2014). ... As well summarized by Arrieta and colleagues, several studies have noted differences in the neonatal fecal microbiota by route of delivery (Arrieta et al., 2014). ... More recently, with comprehensive analysis based on next generation sequencing of 16S rRNA genes, Dominguez-Bello and colleagues reported that route of delivery was associated with differences in the composition of the microbial populations that initially colonized the offspring. Notably, neonates who were born vaginally were colonized by vagina-associated bacteria, whereas those born by cesarean section were initially colonized by skin-associated bacteria ( Dominguez-Bello et al., 2010).

Early life alteration of the gut microbiota may have a lasting effect. Trasande et al. observed that exposure to antibiotics up to age 6 months was associated with elevated body mass index (BMI) up to age 7 years (Trasande et al., 2013).

The 16S rRNA V4 region was sequenced by the American Gut Project....Of the 1097 participants, cesarean birth was reported as “yes” by 92, “no” by 948, and missing or uncertain by 57. Likewise, appendectomy was reported as “yes” by 155, “no” by 961, and missing or uncertain by 21.

This analysis was primarily motivated by the observation that the composition of the microbiome of neonates differed significantly between those born vaginally and those born by cesarean section (Arrieta et al., 2014 and Dominguez-Bello et al., 2010). With vaginal delivery, the neonatal microbiome resembled the vaginal microbiome, with high relative abundance of Prevotella and especially Lactobacillus taxa. In contrast, cesarean-delivered neonates had a diverse array of taxa resembling the skin microbial community, including Staphylococcus, Streptococcus, Propionibacterineae, Haemophilus, and Acinetobacter ( Dominguez-Bello et al., 2010). Cesarean-delivered neonates and infants typically have a paucity of Bifidobacterium and Bacteroides species ( Arrieta et al., 2014).

In the current analysis, we observed that the fecal microbiome composition differed in adults who reported that they had been delivered by cesarean section. This suggests that a difference by route of delivery may persist into adulthood. Of the taxa noted to be increased in cesarean-delivered neonates and infants ( Arrieta et al., 2014, Penders et al., 2006 and Dominguez-Bello et al., 2010), only Haemophilus and certain Clostridia genera had elevated abundance in the fecal microbiome of cesarean-delivered adults ( Table 3).