Posts tagged microbiome
Articles and news from the latest research reports.
How gut bacteria ensure a healthy brain – and could play a role in treating depression
One of medicine’s greatest innovations in the 20th century was the development of antibiotics. It transformed our ability to combat disease. But medicine in the 21st century is rethinking its relationship with bacteria and concluding that, far from being uniformly bad for us, many of these organisms are actually essential for our health.
Nowhere is this more apparent than in the human gut, where the microbiome – the collection of bacteria living in the gastrointestinal tract – plays a complex and critical role in the health of its host. The microbiome interacts with and influences organ systems throughout the body, including, as research is revealing, the brain. This discovery has led to a surge of interest in potential gut-based treatments for neuropsychiatric disorders and a new class of studies investigating how the gut and its microbiome affect both healthy and diseased brains.
The microbiome consists of a startlingly massive number of organisms. Nobody knows exactly how many or what type of microbes there might be in and on our bodies, but estimates suggest there may be anywhere from three to 100 times more bacteria in the gut than cells in the human body. The Human Microbiome Project, co-ordinated by the US National Institutes of Health (NIH), seeks to create a comprehensive database of the bacteria residing throughout the gastrointestinal tract and to catalogue their properties.
The lives of the bacteria in our gut are intimately entwined with our immune, endocrine and nervous systems. The relationship goes both ways: the microbiome influences the function of these systems, which in turn alter the activity and composition of the bacterial community. We are starting to unravel this complexity and gain insight into how gut bacteria interface with the rest of the body and, in particular, how they affect the brain.
Do Gut Bacteria Rule Our Minds?
It sounds like science fiction, but it seems that bacteria within us — which outnumber our own cells about 100-fold — may very well be affecting both our cravings and moods to get us to eat what they want, and often are driving us toward obesity.
In an article published this week in the journal BioEssays, researchers from UC San Francisco, Arizona State University and University of New Mexico concluded from a review of the recent scientific literature that microbes influence human eating behavior and dietary choices to favor consumption of the particular nutrients they grow best on, rather than simply passively living off whatever nutrients we choose to send their way.
Bacterial species vary in the nutrients they need. Some prefer fat, and others sugar, for instance. But they not only vie with each other for food and to retain a niche within their ecosystem — our digestive tracts — they also often have different aims than we do when it comes to our own actions, according to senior author Athena Aktipis, PhD, co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF.
While it is unclear exactly how this occurs, the authors believe this diverse community of microbes, collectively known as the gut microbiome, may influence our decisions by releasing signaling molecules into our gut. Because the gut is linked to the immune system, the endocrine system and the nervous system, those signals could influence our physiologic and behavioral responses.
“Bacteria within the gut are manipulative,” said Carlo Maley, PhD, director of the UCSF Center for Evolution and Cancer and corresponding author on the paper. “There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not.”
Fortunately, it’s a two-way street. We can influence the compatibility of these microscopic, single-celled houseguests by deliberating altering what we ingest, Maley said, with measurable changes in the microbiome within 24 hours of diet change.
“Our diets have a huge impact on microbial populations in the gut,” Maley said. “It’s a whole ecosystem, and it’s evolving on the time scale of minutes.”
There are even specialized bacteria that digest seaweed, found in humans in Japan, where seaweed is popular in the diet.
Research suggests that gut bacteria may be affecting our eating decisions in part by acting through the vagus nerve, which connects 100 million nerve cells from the digestive tract to the base of the brain.
“Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good,” said Aktipis, who is currently in the Arizona State University Department of Psychology.
In mice, certain strains of bacteria increase anxious behavior. In humans, one clinical trial found that drinking a probiotic containing Lactobacillus casei improved mood in those who were feeling the lowest.
Maley, Aktipis and first author Joe Alcock, MD, from the Department of Emergency Medicine at the University of New Mexico, proposed further research to test the sway microbes hold over us. For example, would transplantation into the gut of the bacteria requiring a nutrient from seaweed lead the human host to eat more seaweed?
The speed with which the microbiome can change may be encouraging to those who seek to improve health by altering microbial populations. This may be accomplished through food and supplement choices, by ingesting specific bacterial species in the form of probiotics, or by killing targeted species with antibiotics. Optimizing the balance of power among bacterial species in our gut might allow us to lead less obese and healthier lives, according to the authors.
“Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating,” the authors wrote.
The authors met and first discussed the ideas in the BioEssays paper at a summer school conference on evolutionary medicine two years ago. Aktipis, who is an evolutionary biologist and a psychologist, was drawn to the opportunity to investigate the complex interaction of the different fitness interests of microbes and their hosts and how those play out in our daily lives. Maley, a computer scientist and evolutionary biologist, had established a career studying how tumor cells arise from normal cells and evolve over time through natural selection within the body as cancer progresses.
In fact, the evolution of tumors and of bacterial communities are linked, points out Aktipis, who said some of the bacteria that normally live within us cause stomach cancer and perhaps other cancers.
“Targeting the microbiome could open up possibilities for preventing a variety of disease from obesity and diabetes to cancers of the gastro-intestinal tract. We are only beginning to scratch the surface of the importance of the microbiome for human health,” she said.
Your gut’s what you eat, too
As the saying goes, you are what you eat. But new evidence suggests that the same may also be true for the microbes in your gut.
A Harvard study shows that, in as little as a day, diet can alter the population of microbes in the gut — particularly those that tolerate bile — as well as the types of genes expressed by gut bacteria.
“What we are really excited about is we and others have shown in animal models that diet can rapidly have major effects on the microbes that are in the gut,” said Peter Turnbaugh, a Bauer Fellow at the Center for Systems Biology in the Faculty of Arts and Sciences. He is senior author of the paper, which appeared in Dec. 11 edition of the journal Nature.
“But it still wasn’t clear how fast the microbes in the human gut respond to changes in diet, and to what degree those changes would be similar in different people. This study is really the first time we’ve seen that, over the course of days, a new diet can reshape the microbial community, and that those changes are consistent and reversible.”
Pregnant mother’s stress affects baby’s gut and brain
Pregnant women may pass on the effects of stress to their fetus by way of bacterial changes in their vagina, suggests a study in mice. It may affect how well their baby’s brain is equipped to deal with stress in adulthood.
The bacteria in our body outnumber our own cells by about 10 to 1, with most of them found in our gut. Over the last few years, it has become clear that the bacterial ecosystem in our body – our microbiome – is essential for developing and maintaining a healthy immune system.
Our gut bugs also help to prevent germs from invading our bodies, and help to absorb nutrients from food.
A baby gets its first major dose of bacteria in life as it passes through its mother’s birth canal. En route, the baby ingests the mother’s vaginal microbes, which begin to colonise the newborn’s gut.
Chris Howerton, then at the University of Pennsylvania in Philadelphia, and his colleagues wanted to know if this initial population of bacteria is important in shaping a baby’s neurological development, and whether that population is influenced by stress during pregnancy.
Stressful pregnancy
The first step was to figure out what features of the mother’s vaginal microbiome might be altered by stress, and then see if any of those changes were transmitted to the offspring’s gut.
To do this, the team exposed 10 pregnant mice to a different psychologically stressful experience, such as exposing them to fox odour, keeping their cages lit at night, or temporarily restraining them every day for what would be the equivalent of the first trimester of their pregnancy. Another 10 pregnant mice were housed normally during the same time.
The team took samples of their vaginal bacteria throughout the pregnancy and again just after the mice had given birth. These samples were genetically sequenced to see what types of bacteria were present.
The microbiomes of the stressed mice were remarkably different to those of the unstressed mice after they had each given birth. There were more types of bacteria present, and the proportion of one common gut bacteria, Lactobacillus, was significantly reduced.
Like mother, like pup
To see whether these changes had been passed on to the pups, a few days after birth the pups’ nascent gut bacteria was removed from their colon and sequenced. Sure enough, the same bacterial patterns were seen in the pups of stressed mothers.
By analysing tissue from the pups’ hypothalamus – a brain area involved in hormone control, behaviour and sleep, among other things – the team was able to infer which genes were affected by the stress-induced changes in each mother’s microbiome.
They found that the expression of 20 genes was affected by the decrease in Lactobacillus, including genes related to the production of new neurons and the growth of synaptic connections in the brain.
These genetic outcomes in the brain are probably a result of a different suite of nutrients and metabolites circulating in the “stressed” pup’s blood, thanks to the altered gut flora they inherited. Indeed, when the team analysed the blood of the pups of the stressed mothers, they found that there were fewer molecules present necessary for the formation of essential neurotransmitters – chemicals that transmit signals to the brain. Furthermore, there were lower levels of a molecule thought to protect the brain from harmful oxidative stress.
"These changes are significant and are likely to be important for determining how the brain initially develops and how it will respond in the future to things like stress or changes in the environment," says Tracy Bale, Howerton’s supervisor during the research and director of the University of Pennsylvania lab.
As well as changing the nutrients available, the microbiome could also affect the brain via the immune system or by innervating the nerves in the gut that connect to it. “These three mechanisms aren’t mutually exclusive. It’s likely that they all play a role,” says Howerton.
Human angle
If the same effects are seen in humans, there may be a straightforward solution. “We can easily manipulate the bacteria we have inside of us,” says Howerton. For example, if a certain cocktail of bacteria is found to be beneficial to the newborns of stressed mothers, we could give it to them right after birth, he suggests. This approach could also benefit babies born via C-section, who do not pass through their mother’s birth canal, or those born to mothers whose gut bacteria has been disrupted as a result of antibiotic use during pregnancy.
Bale is now investigating the link between bacteria and brain development in pregnant women who have been through several traumatic experiences to analyse the effects on their babies’ gut bacteria. She also intends to follow their children’s behaviour as they grow up.
Resource rationale
"This is a remarkable trans-disciplinary study in how it bridged multiple organ systems to illuminate a complex question," says Catherine Hagan from the University of Missouri in Columbia. She says that more work needs to be done to show a causal link. "Mice are not tiny people – people are not big mice – more data is needed to understand how stress in mothers affects brain development in children," she says. "That said, mice and people have enough in common that this study provides a rationale for allocating resources to address such a concern."
"At the end of the day, most of what makes you ‘you’, and what drives your quality of life, comes down to the brain," says Bale. "It’s this very important, vulnerable tissue that is susceptible to many perturbations. If the microbiome is proven to be one of these driving forces, then it’s essential we know just how factors in our environment can change it and can reprogram the brain."
(Source: newscientist.com)