Tag Archives: microbiota

Gut bacteriophages associated with improved cognitive function and memory in both animals and humans

A growing body of evidence has implicated gut bacteria in regulating neurological processes such as neurodegeneration and cognition. Now, a study from Spanish researchers shows that viruses present in the gut microbiota can also improve mental functions in flies, mice, and humans.

Credit: CDC.

They easily assimilate into their human hosts — 8% of our DNA consists of ancient viruses, with another 40% of our DNA containing genetic code thought to be viral in origin. As it stands, the gut virome (the combined genome of all viruses housed within the intestines) is a crucial but commonly overlooked component of the gut microbiome.

But we’re not entirely sure what it does.

This viral community is comprised chiefly of bacteriophages, viruses that infect bacteria and can transfer genetic code to their bacterial hosts. Remarkably, the integration of bacteriophages or phages into their hosts is so stable that over 80% of all bacterial genomes on earth now contain prophages, permanent phage DNA as part of their own — including the bacteria inside us humans. Now, researchers are inching closer to understanding the effects of this phenomenon.

Gut and brain

In their whitepaper published in the journal Cell Host and Microbe, a multi-institutional team of scientists describes the impact of phages on executive function, a set of cognitive processes and skills that help an individual plan, monitor, and successfully execute their goals. These fundamental skills include adaptable thinking, planning, self-monitoring, self-control, working memory, time management, and organization, the regulation of which is thought, in part, to be controlled by the gut microbiota.

The study focuses on the Caudovirales and Microviridae family of bacteriophages that dominate the human gut virome, containing over 2,800 species of phages between them.

“The complex bacteriophage communities represent one of the biggest gaps in our understanding of the human microbiome. In fact, most studies have focused on the dysbiotic process only in bacterial populations,” write the authors of the new study.

Specifically, the scientists showed that volunteers with increased Caudovirales levels in the gut microbiome performed better in executive processes and verbal memory. In comparison, the data showed that increased Microviridae levels impaired executive abilities. Simply put, there seems to be an association between this type of gut biome and higher cognitive functions.

These two prevalent bacteriophages run parallel to human host cognition, the researchers write, and they may do this by hijacking the bacterial host metabolism.

To reach this conclusion, the researchers first tested fecal samples from 114 volunteers and then validated the results in another 942 participants, measuring levels of both types of bacteriophage. They also gave each volunteer memory and cognitive tests to identify a possible correlation between the levels of each species present in the gut virome and skill levels.

The researchers then studied which foods may transport these two kinds of phage into the human gut -results indicated that the most common route appeared to be through dairy products.

They then transplanted fecal samples from the human volunteers into the guts of fruit flies and mice – after which they compared the animal’s executive function with control groups. As with the human participants, animals transplanted with high levels of Caudovirales tended to do better on the tests – leading to increased scores in object recognition in mice and up-regulated memory-promoting genes in the prefrontal cortex. Improved memory scores and upregulation of memory-involved genes were also observed in fruit flies harboring higher levels of these phages.

Conversely, higher Microviridae levels (correlated with increased fat levels in humans) downregulated these memory-promoting genes in all animals, stunting their performance in the cognition tests. Therefore, the group surmised that bacteriophages warrant consideration as a novel dietary intervention in the microbiome-brain axis.

Regarding this intervention, Arthur C. Ouwehand, Technical Fellow, Health and Nutrition Sciences, DuPont, who was not involved in the study, told Metafact.io:

“Most dietary fibres are one way or another fermentable and provide an energy source for the intestinal microbiota.” Leading “to the formation of beneficial metabolites such as acetic, propionic and butyric acid.”

He goes on to add that “These so-called short-chain fatty acids may also lower the pH of the colonic content, which may contribute to an increased absorption of certain minerals such as calcium and magnesium from the colon. The fibre fermenting members of the colonic microbiota are in general considered beneficial while the protein fermenting members are considered potentially detrimental.”

It would certainly be interesting to identify which foods are acting on bacteriophages contained within our gut bacteria to influence cognition.

Despite this, the researchers acknowledge that their work does not conclusively prove that phages in the gut can impact cognition and explain that the test scores could have resulted from different bacteria levels in the stomach but suggest it does seem likely. They close by stating more work is required to prove the case.

Your microbiota will be having non-stop sex this Valentine’s Day

Even if you’re alone this Valentine’s Day, there’s no need to worry: some parts of your body will be getting plenty of action. In fact, your body will host a veritable carnival of the sensual in your tummy, as your microbiota will engage in an orgy of sex and swinger’s parties — where they’ll be swapping genes instead of keys.

A medical illustration of drug-resistant, Neisseria gonorrhoeae bacteria. Original image sourced from US Government department: Public Health Image Library, Centers for Disease Control and Prevention. Image in the public domain.

The salacious gene

Imagine you have a severe disease with a very unusual cure: you can treat by making love with someone who then passes on the necessary genes to cure your ailment. It is, as they say, sexual healing. Using sex to protect or heal themselves is precisely what bacteria can do, and it’s a crucial defense mechanism.

In the past, the research community thought bacterial sex (or conjugation, as scientists call it) was a terrible threat for humans, as this ancient process can spread DNA capable of conveying antibiotic resistance to their neighbors. Antibiotic resistance is one of the most pressing health challenges the world is facing, being projected to cause 10 million deaths a year by 2050.

But there’s more to this bacterial sex than meets the eye. Recently, scientists from the University of Illinois at Urbana-Champaign and the University of California Riverside witnessed gut microbes sharing the ability to acquire a life-saving nutrient with one another through bacterial sex. UCR microbiologist and study lead Patrick Degnan says:

“We’re excited about this study because it shows that this process isn’t only for antibiotic resistance. The horizontal gene exchange among microbes is likely used for anything that increases their ability to survive, including sharing vitamin B12.”

For well over 200-years, researchers have known that bacteria reproduce using fission, where one cell halves to produce two genetically identical daughter cells. However, in 1946, Joshua Lederberg and Edward Tatum discovered bacteria could exchange genes through conjugation, an entirely separate act from reproduction.

Conjugation occurs when a donor and a recipient bacteria sidle up to each other, upon which the donor creates a tube, called a pilus that attaches to the recipient and pulls the two cells together. A small parcel of DNA is then passed from the donor to the recipient, providing new genetic information through horizontal transfer.

Ironically, it wasn’t until Lederberg met and fell in love with his wife, Esther Lederberg, that they made progress regarding bacterial sex.

Widely acknowledged as a pioneer of bacterial genetics, Esther still struggled for recognition despite identifying the horizontal transfer of antibiotic resistance and viruses, which kill bacteria known as bacteriophages. She discovered these phages after noticing small objects nibbling at the edges of her bacterial colonies. Going downstream to find out how they got there, she found these viral interlopers hiding dormant amongst bacterial chromosomes after being transferred by microbes during sex.

Later work found that environmental stresses such as illness activated these viruses to replicate within their hosts and kill them. Still, scientists assumed that bacterial sex was purely a defense mechanism.

Esther Ledeberg in her Stanford lab. Image credits: Esther Lederberg.

Promiscuity means longevity

The newly-published study builds on Esther’s work. The study authors felt this bacterial process extended beyond antibiotic resistance. So they started by investigating how vitamin B12 was getting into gut microbial cells, where the cells had previously been unable to extract this vitamin from their environment — which was puzzling as, without vitamin B12, most types of living cells cannot function. Therefore, many questions remained about how these organisms survived without the machinery to extract this resource from the intestine.

The new study in Cell Reports uses the Bacteroidetes species, which comprise up to 80% of the human microbiome in the intestines, where they break down complex carbohydrates for energy.

“The big, long molecules from sweet potatoes, beans, whole grains, and vegetables would pass through our bodies entirely without these bacteria. They break those down so we can get energy from them,” the team explained.

This bacteria was placed in lab dishes mixing those that could extract B12 from the stomach with some that couldn’t. The team then watched in awe while the bacteria formed their sex pilus to transfer genes enabling the extraction of B12. After the experiment, researchers examined the total genetic material of the recipient microbe and found it had incorporated an extra band of DNA from the donor.

Among living mice, something similar happens. When the group-administered two different subgroups of Bacteroidetes to a mouse – one that possessed the genes for transferring B12 and another that didn’t — they found the genes had ‘jumped’ to the receiving donee after five to nine days.

“In a given organism, we can see bands of DNA that are like fingerprints. The recipients of the B12 transporters had an extra band showing the new DNA they got from a donor,” Degnan said.

Remarkably, the team also noted that different species of phages were also transferred during conjugation, exhibiting bacterial subgroup specificity in some cases. These viruses also showed the capacity to alter the genomic sequence of its bacterial host, with the power to promote or demote the life of its microbic vessel when activated.

Sexual activity in our intestines keeps us healthy

Interestingly, the authors note they could not observe conjugation in all subgroups of the Bacteroidetes species, suggesting this could be due to growth factors in the intestine or a possible subgroup barrier within this large species group slowing the process down.

Despite this, Degnan states, “We’re excited about this study because it shows that this process isn’t only for antibiotic resistance.” And that “The horizontal gene exchange among microbes is likely used for anything that increases their ability to survive, including sharing [genes for the transport of] vitamin B12.”

Meaning that bacterial sex doesn’t just occur when microbes are under attack; it happens all the time. And it’s probably part of what keeps the microbiome and, by extension, ourselves fit and healthy.

How giant pandas stay chubby solely on a bamboo diet: fattening gut bacteria

Giant panda enjoying a bamboo shoot meal. Credit: Pixabay.

Although pandas subsist almost entirely on bamboo, plants with very little nutritional value, they are all on the chubby side. While it’s true that the rare mammals compensate for the poor calorie content by eating up to 80 pounds of bamboo per day, a new study has revealed that symbiotic gut bacteria also play a crucial role in fattening pandas and preparing them for when only bamboo leaves are available to chew on.

Like other bears, giant pandas possess the digestive system of a carnivore, but they have evolved to depend almost entirely on various bamboo species. For most of the year, pandas feed on fibrous bamboo leaves, but during the shoot-eating season in late spring and early summer, they get to enjoy newly sprouted bamboo shoots that are rich in protein. It’s no coincidence that during this season they’re also at their chubbiest.

Researchers led by Fuwen Wei at the Institute of Zoology have been studying wild giant pandas living in the Qinling Mountains in central China for decades. Their research showed that the animals have a much higher level of a bacterium called Clostridium butyricum in their gut during the shoot-eating season compared with during the leaf-eating season. 

That’s quite common since many animals experience a seasonal shift in their microbiota as a result of changes in the availability of food. For instance, some monkeys have different gut bacteria in the summer when they eat fresh leaves and fruit compared to the winter, when they mainly feed on tree bark. Humans are no exception — Hazda people, one of the last hunter-gatherer communities left in the world, experience similar shifts in their gut bacteria as the available food changes throughout the year.

In order to investigate whether the Clostridium butyricum was having any effect on the pandas’ metabolism, the researchers performed fecal transplants of panda poop collected from the wild to germ-free mice. The mice were then fed a bamboo-based diet that mimicked what the pandas normally eat for three weeks.

“For endangered and vulnerable wild animals, we can’t really run tests on them directly. Our research created a mouse model for future fecal transplant experiments that can help study wild animals’ gut microbiota,” said first author Guangping Huang, from the Institute of Zoology at the Chinese Academy of Sciences.

The rodents transplanted with the panda feces from the shoot-eating season gained significantly more weight and had more fat than mice transplanted with feces from the leaf-eating season. Both groups of mice consumed the same amount of food, which means the bacteria must be doing something to help the animals gain weight.

On closer inspection, the researchers in China found that a metabolic product of C. butyricum, butyrate, upregulates the expression of a circadian rhythm gene called Per2, which increases lipid synthesis and storage.

“This is the first time we established a causal relationship between a panda’s gut microbiota and its phenotype,” said Huang. “We’ve known these pandas have a different set of gut microbiota during the shoot-eating season for a long time, and it’s very obvious that they are chubbier during this time of the year.”

Identifying which microorganisms in the panda’s gut play crucial roles in their health is highly important for conservation. There are only a few thousands giant pandas left in the wild, and captured pandas need to be fed the right diet to prepare them for rewilding. The research may also benefit humans, as many diseases that afflict us can be treated with probiotics.

The findings appeared in the journal Cell Reports.

How ancient gut microbes might have shaped human evolution

Humans are, in fact, mostly microbes. There are over 100 trillion microbes living inside the human body, which outnumber our human cells ten to one. Most of these microbes live inside the gut, particularly in the large intestine, and are collectively known as the ‘microbiome’. According to a new study, the microbiome may have played a critical role in our ancestors’ quest to spread across the world, allowing them to survive in new geographical areas.

“In this paper, we begin to consider what the microbiomes of our ancestors might have been like and how they might have changed,” Rob Dunn of the North Carolina State University and lead author of the new study said in a statement. “Such changes aren’t always bad and yet medicine, diet, and much else makes more sense in light of a better understanding of the microbes that were part of the daily lives of our ancestors.”

Dunn and colleagues analyzed data gathered by other studies, comparing the microbiota among humans, apes, and other non-human primates.

The bacteria in the microbiome help digest our food, regulate our immune system, protect against other bacteria that cause disease, and produce vitamins including B vitamins B12, thiamine and riboflavin, and Vitamin K, which is needed for blood coagulation. It was only in the late-1990s that the existence of the microbiome was generally recognized.

The new study’s results suggest an extraordinary variation in the composition and function of human gut microbes depending on a person’s lifestyle and geographical location. It would mean that our gut microbes have had to adapt to new environmental conditions and likely did so quickly.

When our ancestors migrated to a new region, they not only encountered novel climates and habitats, but also new kinds of foods and diseases.

By having an adaptive microbiome, these ancestors could digest novel foods that they encountered in a local region while also increasing their resilience against new diseases.

As such, the authors concluded in the journal Frontiers in Ecology and Evolution that microbial adaptation might have been critical to facilitating the spread of humans in a range of environments.

Such microbial adaptations were easily transmitted from human to human thanks to the tight-knit social structure. Yet, our ancestors not only shared microbes among themselves, but they also outsourced them into food through fermentation.

By fermenting food, human ancestors virtually extended their guts outside of their bodies as microbes allowed digestion to begin externally.

Fermentation allowed humans to store food for long periods of time and stay in one place, facilitating larger communities. Fermented foodstuff also re-inoculated the consumers, ensuring that in time their microbiota became more similar to each other compared to individuals living in other groups. So, in many ways, the story of human evolution is very much intertwined with that of microbes.

“We outsourced our body microbes into our foods. That could well be the most important tool we ever invented. But it is a hard tool to see in the past and so we don’t talk about it much,” says Dunn. “Stone artifacts preserve but fish or beer fermented in a hole in the ground doesn’t”.

The authors caution that their hypothesis needs to be validated by further studies, preferably performed by an interdisciplinary team made of paleoanthropologists, medical researchers, ecologists and more.

“We are hoping the findings will change some questions and that other researchers will study the consequences of changes in the human microbiome,” says Dunn. “Hopefully the next decade will see more focus on microbes in our past and less on sharp rocks.”

What’s the link between autism and gut bacteria?

No matter how lonely you might feel, rest assured you’re never by yourself. Millions of microorganisms live in relative peace and harmony inside our guts, collectively comprising the “gut microbiota”. More and more research suggests that abnormalities in this microbiota can impact virtually all organs — and that includes the brain, too. And, according to a new study, treating the gut’s microflora could be key to easing autism symptoms.

Credit: Pixabay.

The connection between the gut microbiome and the brain is known as the microbiome–gut–brain axis. This connection is of important interest to researchers because individuals suffering from neurological and developmental conditions, such as Alzheimer’s disease and Autism Spectrum Disorders, also suffer from chronic gastrointestinal symptoms.  One 2014 study published in the journal Pediatrics, for instance, found that children with autism are about four times more likely to experience gastrointestinal (GI) distress than are their typically developing peers.

If abnormal gut bacteria may be amplifying autism symptoms, would a healthy microbiome improve symptoms? In a recent study, researchers at Arizona State University and Northern Arizona University attempted to answer this question.

For their study, they recruited 18 children with Autism Spectrum Disorder who also had chronic gastrointestinal problems. The participants followed a 10-week treatment consisting of antibiotics, a bowel cleanse, and then a high dose of microbiota fecal transfer (MTT).

According to the results, eight weeks after the treatment, 80% of the patients experienced reductions in gastrointestinal symptoms and slow, but significant improvements in their autism-related symptoms.

Two years later, the patients still experienced a 58% improvement in gastrointestinal symptoms as measured by the Gastrointestinal Symptom Rating Scale. Some of the symptoms that showed improvement include abdominal pain, indigestion, diarrhea, and constipation.

These results could be considered quite spectacular seeing how all of the patients claimed they hadn’t had normal gastrointestinal tract functioning since infancy. Meanwhile, the severity of autism symptoms dropped by 47%. At the beginning of the study, 83% of the children were classified as “severe” on the autism spectrum. However, two years post-treatment, only 17% of children fell under this classification. Most shocking of all, 44% of the participants had scores below the Autism Spectrum Disorder diagnostic cut-off point, the authors wrote in the journal Scientific Reports.

“Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future,” the authors wrote.

Another study published this month by a team led by Dr. Katerina Johnson of Oxford University’s Department of Experimental Psychology found that both gut microbiome composition and diversity were related to differences in personality, including sociability and neuroticism.

“This suggests that the gut microbiome may contribute not only to the extreme behavioural traits seen in autism but also to variation in social behaviour in the general population. However, since this is a cross-sectional study, future research may benefit from directly investigating the potential effect these bacteria may have on behaviour, which may help inform the development of new therapies for autism and depression,” Johnson said.

It’s not clear what could drive this association but having different populations of digestive tract bacteria and patterns of gene expression have been previously identified as potential factors.

There are still a lot of unanswered questions considering the field is still in its infancy, yet growing rapidly. Just the idea that microbes could influence the brain was unthinkable a few years ago and the pace of research has accelerated over the past few years. Just imagine the possibilities: in the future, it could be possible that ASD symptoms are remedied with bacterial metabolites; there might even be probiotics for autism.

More research is warranted in order to tease out the connection between gut bacteria and autism/behavioral changes. Studies so far on the subject have been mostly small and uncontrolled — and it’s not clear what they mean, given that researchers are still trying to establish the ingredients of a healthy microbiome. This, hopefully, will change in the future as more interest and funding is awarded to investigate this association that cannot be ignored any longer.

Credit: Pixabay.

Drinking red wine (in moderation) improves gut health

Credit: Pixabay.

Credit: Pixabay.

A new study found that people who drank red wine had more bacterial diversity in their guts — which is seen as a sign of better gut health — compared to non-drinkers. Red wine drinkers also showed lower levels of obesity and ‘bad’ cholesterol.

Researchers at King’s College London studied the association between gut microbiome and general health in a group of 916 British female twins who either drank beer, cider, red wine, white wine, or spirits. Additionally, there were three other cohorts in the UK, the U.S., and the Netherlands, bringing the total study participants to over 4,000.

Gut bacteria + red wine = <3

People tend to see bacteria as harmful and potentially dangerous to our health — but that is not necessarily so.

The gut microbiota (also called the gut microbiome, and previously called the gut flora) is the name given to the microbe population living in our intestine. Our gut is home to trillions of microorganisms from hundreds of different species, totaling 3 million genes — 150 times more than human genes. Each one of us carries around 2% of our overall body weight in bacteria

Increasingly, the gut microbiome has been shown to be important in a number of diseases, including your weight, general health, and even mental health.

In general, scientists believe that the higher the number of different bacterial species in a person’s gut, the better the health outcomes. And this is exactly what they found for people who consumed red wine. Those who drank beer, white wine, or spirits did not show a more diverse gut microbiome.

“Although we observed an association between red wine consumption and the gut microbiota diversity, drinking red wine rarely, such as once every two weeks, seems to be enough to observe an effect. If you must choose one alcoholic drink today, red wine is the one to pick as it seems to potentially exert a beneficial effect on you and your gut microbes, which in turn may also help weight and risk of heart disease. However, it is still advised to consume alcohol with moderation,” said Dr. Caroline Le Roy from King’s College London, first author of the study.

The reason why red wine may improve gut health may be due to the many polyphenols it contains. Polyphenols are natural compounds also present in fruits and vegetables which have many beneficial properties — they’re a great source of antioxidants, for instance — and may act as a fuel source for the gut bacteria.

“This is one of the largest ever studies to explore the effects of red wine in the guts of nearly three thousand people in three different countries and provides insights that the high levels of polyphenols in the grape skin could be responsible for much of the controversial health benefits when used in moderation,”Professor Tim Spector from King’s College London said in a statement.

stressed frog

Stress could be as harmful to your gut’s health as junk food

A study on mice performed by researchers at Brigham Young University (BYU) found stress can be as bad for digestion as a diet of low-nutrient fast food.

stressed frog

Credit: Pixabay.

 

The team studied the gut microbiota of these mice. These bacteria live in a relationship that is vital to normal health, although some species are also opportunistic pathogens that can invade the host gut and cause disease. The human body is host to around 100 trillion microbes, meaning they outnumber somatic cells by about 10 to 1.  

Microorganisms start colonizing the gut immediately after birth in mammalian hosts and are followed by a succession of populations until a stable adult microbiota has been established.

Studies on the microbiota, though numerous, can be extremely challenging. Because there are so many different species of microorganisms colonizing the gut, it can be very difficult if not impossible to identify which organisms are beneficial and which are bad for our health, especially since the effects are rooted in an interplay of various bacteria. Most gut bacteria can’t be cultured in a dish, making these types of studies even harder. What we do know for sure is that the microbiota is essential to the health of all mammals.

Sometimes, the intestine-wandering bacteria can affect us in unexpected ways. For instance, when a team at BYU sampled the gut microbiome from female mice subjected to a stress test, the microbiota resembled that of an obese mouse. This surprising finding seems to suggest that stress can have as much of an impact on our metabolism as poor diet. Interestingly enough, male mice didn’t exhibit the same microbiome shift, but they became more anxious and less physically active.

“Stress can be harmful in a lot of ways but this research is novel in that it ties stress to female-specific changes in the gut microbiota,” BYU professor of microbiology and molecular biology Laura Bridgewater said in a statement. “We sometimes think of stress as a purely psychological phenomenon but it causes distinct physical changes.”

These findings, which were reported in a paper in Scientific Reports, logically follow previous findings. For instance, scientists previously found that high levels of the stress hormone cortisol are linked to a higher body mass index (BMI). The higher the BMI, the more likely an individual is overweight or obese.

This sort of metabolic response to stress, though a nuisance to our modern lifestyle, may have provided evolutionary advantages. When faced with a threat, like a predator, glucose levels rise so we have more energy for our ‘flight or fight’ response. However, when glucose rises, so does insulin, which causes fat storage.

As such, these findings suggest that any diet or weight loss routine should also be paired with stress management. Obese people looking to lose weight are advised to relax more often by engaging in calming and pleasurable activities.

“In society, women tend to have higher rates of depression and anxiety, which are linked to stress,” Bridgewater said. “This study suggests that a possible source of the gender discrepancy may be the different ways gut microbiota responds to stress in males versus females.”