Tag Archives: Intestine

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.

There are likely two types of Parkinson’s, a new study cautions

Parkinson’s disease is more likely Parkinson’s diseases, according to a new study.

A human brain, preserved in formadehide, with its outer membrane (dura mater) removed. Image credits Flickr / EUSKALANATO.

Researchers from the Aarhus University and Aarhus University Hospital, Denmark, have found evidence that Parkinson’s disease is actually two conditions with very similar symptoms but different sources. The findings could help explain why patients can show widely different evolutions of Parkinson’s, and could help improve our ability to treat the condition in the future.

Treatments tailored for each individual patient and their particular symptoms are likely the way forward, the authors note.

Two in one

“With the help of advanced scanning techniques, we’ve shown that Parkinson’s disease can be divided into two variants, which start in different places in the body,” says lead author Professor Per Borghammer. “For some patients, the disease starts in the intestines and spreads from there to the brain through neural connections. For others, the disease starts in the brain and spreads to the intestines and other organs such as the heart.”

Parkinson’s involves the slow degradation of the brain due to a build-up of alpha-synuclein proteins — which negatively impact nerve cells at high levels. The end result is a decline in the brain’s ability to control our bodies’ movements, leading to stiffness, difficulty maintaining balance, with walking, and eventually to uncontrollable shaking. Symptoms almost universally start off as mild and slowly worsen over time.

In order to understand its biological roots, the team used PET and MRI imaging techniques to examine patients with Parkinson’s at various points of the disease’s progression. The team also examined people who had not yet been diagnosed with Parkinson’s but were at high risk of developing the disease (the paper explains that people diagnosed with REM sleep behaviour syndrome have an increased risk of developing Parkinson’s).

Some of the patients showed damage in their dopamine pathways before their heart or intestines were affected. Others, however, showed damage to nerve pathways in their intestines and heart first, without any sign of trouble in their brains. These findings show that our current understanding of how the condition arises and how it develops is faulty, the authors explain.

“Until now, many people have viewed the disease as relatively homogeneous and defined it based on the classical movement disorders. But at the same time, we’ve been puzzled about why there was such a big difference between patient symptoms. With this new knowledge, the different symptoms make more sense and this is also the perspective in which future research should be viewed,” says Borghammer.

The researchers refer to the two types of Parkinson’s disease as body-first and brain-first. They suggest that studying the composition of bacteria in our intestines (our ‘microflora’) could help us better understand the roots of the ‘body-first’ cases. Studying the ‘brain-first’ one would be “a bigger challenge”, they admit, as it starts off “relatively symptom-free”, making it hard to impossible to identify in its early stages.

The study “Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study” has been published in the journal Brain.

Wooden Figure belly ache.

Cannabis does reduce intestinal inflammation, and now we know why

New research on mice shows that endocannabinoids help prevent — or control — intestinal inflammation. These findings suggest that such compounds might serve the same function in humans.

Wooden Figure belly ache.

Image credits Wolfgang Claussen.

Cannabis users have long reported that the drug helps reduce the symptoms of inflammatory bowel disease (IBD). New research published by a team from the University of Massachusetts Medical School and the University of Bath explored why. Their findings reveal a novel mechanism that governs inflammation of the gut and may result in a new class of drugs to treat diseases that involve intestinal inflammation.

Pot gut

“There’s been a lot of anecdotal evidence about the benefits of medical marijuana, but there hasn’t been a lot of science to back it up,” said Beth A. McCormick, PhD and paper co-author.

“For the first time, we have an understanding of the molecules involved in the process and how endocannabinoids and cannabinoids control inflammation. This gives clinical researchers a new drug target to explore to treat patients that suffer from inflammatory bowel diseases, and perhaps other diseases, as well.”

While reports of marijuana helping alleviate gut inflammation are quite numerous, evidence to explain why aren’t. This study is the first to identify a biological mechanism that underpins this effect, helping to explain why cannabis reduces intestine inflammation for conditions such as ulcerative colitis and Crohn’s disease.

According to the team, gut inflammation is regulated by two distinct processes that each act in turn depending on the conditions in the intestinal environment.

The first process (which was identified in previous research) kick-starts an aggressive immune response in the intestine. This helps our bodies eliminate pathogens, but overzealous immune cells can also damage the lining of the gut by attacking cells indiscriminately.

The second process turns off this inflammation response. The response is spread by special molecules that move across the epithelial cells in the intestine (i.e. the lining) via the same channels that help flush out toxins from the gut.

The key here is that this second process involves a molecule called an endocannabinoid — which is very similar to the cannabinoids found in cannabis. If there aren’t enough endocannabinoids, inflammation won’t shut down and the body’s immune cells run amok on our guts’ lining.

McCormick and colleagues believe that because cannabis use introduces cannabinoids into the body, these molecules might help relieve gut inflammation as the naturally produced endocannabinoids normally would.

“We need to be clear that while this is a plausible explanation for why marijuana users have reported cannabis relieves symptoms of IBD, we have thus far only evaluated this in mice and have not proven this experimentally in humans,” she adds.

However, the team hopes that these findings will result in new drugs to help treat bowel diseases in humans.

The paper “Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis” has been published in the Journal of Clinical Investigation.