Exposure to 'good bacteria' during pregnancy buffers risk of autism-like syndrome
Study in rats suggests prenatal microbial exposures influence neurodevelopment
May 27, 2020
Science Daily/University of Colorado at Boulder
Giving beneficial bacteria to stressed mothers during the equivalent of the third trimester of pregnancy prevents an autism-like disorder in their offspring, according to a new animal study by University of Colorado Boulder researchers.
The study, published in the journal Brain, Behavior, and Immunity, marks the latest in a series of studies in animals and humans suggesting that exposure to certain immune-modulating microbes can dampen inflammation, positively impacting the brain and central nervous system.
It's among the first studies to suggest that such exposures during pregnancy influence neurodevelopment of a fetus and, while far more research is necessary, could open the door to new prenatal interventions.
"It suggests that you could develop microbial interventions that lower the risk of neurodevelopmental syndromes like autism," said co-author Christopher Lowry, an associate professor in the Department of Integrative Physiology.
In humans, research has long shown that maternal stress during pregnancy prompts systemic inflammation in both the mother and fetus and is a risk factor for autism, said senior author Daniel Barth, a professor of psychology and neuroscience.
In a previous study, Barth found that when rats were stressed and given a drug called terbutaline, which is often administered to women to delay preterm labor, their offspring demonstrated an autism-like syndrome -- including the two hallmark features of social deficits and repetitive behavior. They also developed an epilepsy-like seizure disorder.
"Our fundamental question with this new study was whether we could use an immunoregulatory microbe to prevent the long-term consequences of environmental stressors during pregnancy," said first author Zachariah Smith, a post-doctoral researcher in Barth's lab.
For the study, the researchers exposed rats to mild stressors and gave them terbutaline during what would be the equivalent of the third trimester of pregnancy in humans.
Half were also given a series of injections of a heat-killed preparation of a friendly bacterium known as Mycobacterium vaccae (M. vaccae), shown in previous studies to have lasting anti-inflammatory effects on the brain. A third control group of rats got no treatments.
At two and four months, the pups were given a series of tests assessing, among other things, their degree of social interaction and whether they exhibited repetitive behaviors.
As in the previous study, those whose mothers had been stressed and given terbutaline showed autism-like behaviors. But those who had been immunized with M. vaccae did not.
"Immunization with M. vaccae appears to provide some protection against the negative effects of environmental stressors during development, specifically against Autism Spectrum Disorder (ASD)-like behavior," said Smith.
The inoculation did not appear to protect against development of seizure disorders. But because epilepsy tends to develop later in life, the researchers intend to repeat the experiment with a larger sample size and longer treatment period.
Autism and epilepsy often manifest together in humans, with about 30% of autistic individuals exhibiting epileptic symptoms, such as seizures. Stress-induced inflammation likely plays a role in both, the researchers suspect.
"It could be that if we continue the treatment for longer we could also prevent the development of some cases of epilepsy, but much more research is necessary," said Lowry.
The researchers caution that they are not developing an "autism vaccine" and they are not suggesting that microbial interventions could reverse the disorder in children who already have it. But their study does reinforce the idea that exposure to beneficial microorganisms, sometimes referred to as "old friends," can play a critical role in brain development in utero.
Ultimately, Lowry envisions a day when stressed moms deemed particularly high risk of having a child with a neurodevelopmental disorder could be given a specially formulated probiotic or inoculation to support healthy brain development of their child.
"This is the first maternal intervention that I know of that has been able to prevent an autism-like syndrome, including the behavioral and social aspects," Lowry said. "If this could be replicated in humans, that would be pretty profound."
Meantime, they say, mothers should be cognizant of the potential risks of emotional and environmental stressors, including the drug terbutaline, during pregnancy.
And they should try to expose themselves to beneficial bacteria, through fermented foods like yogurt and sauerkraut and even time spent in nature.
https://www.sciencedaily.com/releases/2020/05/200526173818.htm
Mediterranean diet for one year promotes gut bacteria linked to 'healthy aging'
It may help curb advance of frailty and cognitive decline, suggest researchers
February 17, 2020
Science Daily/BMJ
Eating a Mediterranean diet for a year boosts the types of gut bacteria linked to 'healthy' ageing, while reducing those associated with harmful inflammation in older people, indicates a five-country study, published online in the journal Gut.
As ageing is associated with deteriorating bodily functions and increasing inflammation, both of which herald the onset of frailty, this diet might act on gut bacteria in such a way as to help curb the advance of physical frailty and cognitive decline in older age, suggest the researchers.
Previous research suggests that a poor/restrictive diet, which is common among older people, particularly those in long term residential care, reduces the range and types of bacteria (microbiome) found in the gut and helps to speed up the onset of frailty.
The researchers therefore wanted to see if a Mediterranean diet might maintain the microbiome in older people's guts, and promote the retention or even proliferation of bacteria associated with 'healthy' ageing.
They analysed the gut microbiome of 612 people aged 65 to 79, before and after 12 months of either eating their usual diet (n = 289) or a Mediterranean diet (n = 323), rich in fruits, vegetables, nuts, legumes, olive oil and fish and low in red meat and saturated fats, and specially tailored to older people (NU-AGE diet).
The participants, who were either frail (n=28), on the verge of frailty (n=151), or not frail (n=433) at the beginning of the study, lived in five different countries: France, Italy, Netherlands, Poland, and the UK.
Sticking to the Mediterranean diet for 12 months was associated with beneficial changes to the gut microbiome.
It was associated with stemming the loss of bacterial diversity; an increase in the types of bacteria previously associated with several indicators of reduced frailty, such as walking speed and hand grip strength, and improved brain function, such as memory; and with reduced production of potentially harmful inflammatory chemicals.
More detailed analysis revealed that the microbiome changes were associated with an increase in bacteria known to produce beneficial short chain fatty acids and a decrease in bacteria involved in producing particular bile acids, overproduction of which are linked to a heightened risk of bowel cancer, insulin resistance, fatty liver and cell damage.
What's more, the bacteria that proliferated in response to the Mediterranean diet acted as 'keystone' species, meaning they were critical for a stable 'gut ecosystem,' pushing out those microbes associated with indicators of frailty.
The changes were largely driven by an increase in dietary fibre and associated vitamins and minerals -- specifically, C, B6, B9, copper, potassium, iron, manganese, and magnesium.
The findings were independent of the person's age or weight (body mass index), both of which influence the make-up of the microbiome.
And while there were some differences in the make-up of a person's gut microbiome, depending on country of origin to start with, the response to the Mediterranean diet after 12 months was similar and consistent, irrespective of nationality.
The study findings can't establish a causative role for the microbiome in health, added to which some of the implications are inferred rather than directly measured, say the researchers.
"The interplay of diet, microbiome and host health is a complex phenomenon influenced by several factors," they emphasise.
"While the results of this study shed light on some of the rules of this three-way interplay, several factors such as age, body mass index, disease status and initial dietary patterns may play a key role in determining the extent of success of these interactions," they explain.
Older people may have dental problems and/or difficulty swallowing, so it may be impractical for them to eat a Mediterranean diet, they add. But the beneficial bacteria implicated in healthy ageing found in this study might yet prove useful therapeutic agents to ward off frailty, they suggest.
https://www.sciencedaily.com/releases/2020/02/200217192025.htm
Gut microbes may contribute to depression and anxiety in obesity
Study in mice links gut microbes with signs of negative feelings and brain chemistry
June 17, 2018
Science Daily/Joslin Diabetes Center
Like everyone, people with type 2 diabetes and obesity suffer from depression and anxiety, but even more so. Researchers now have demonstrated a surprising potential contributor to these negative feelings -- and that is the bacteria in the gut or gut microbiome, as it is known.
Studying mice that become obese when put on a high-fat diet, the Joslin scientists found that mice on a high-fat diet showed significantly more signs of anxiety, depression and obsessive behavior than animals on standard diets. "But all of these behaviors are reversed or improved when antibiotics that will change the gut microbiome were given with the high fat diet," says C. Ronald Kahn, M.D., co-Head of the Section on Integrative Physiology and Metabolism at Joslin and the Mary K. Iacocca Professor of Medicine at Harvard Medical School .
"As endocrinologists, we often hear people say that they feel differently when they've eaten different foods," notes Kahn, who is senior author on a paper in Molecular Psychiatry describing the research. "What this study says is that many things in your diet might affect the way your brain functions, but one of those things is the way diet changes the gut bacteria or microbes. Your diet isn't always necessarily just making your blood sugar higher or lower; it's also changing a lot of signals coming from gut microbes and these signals make it all the way to the brain."
His lab has long studied mice that are prone to developing obesity, diabetes and related metabolic diseases when given high-fat diets. Earlier this year, the team showed that at least part of this development is driven by changing bacteria in the gut microbiome. The condition was reversed in mice who were given antibiotics in their drinking water, which altered the microbiome.
In the most recent study, the Joslin scientists followed up by giving mice on a high-fat diet four classic lab animal behavioral tests, which are often employed in screening drugs for anxiety and depression. In each case, mice on high-fat diet showed higher signs of anxiety and depression than mice on a regular diet. However, when the mice were given antibiotics with the high fat diet, their behaviors returned to normal.
One of the ways the researchers showed this was an effect of the microbiome was by transferring gut bacteria from these experimental mice toto germ-free mice, who did not have any bacteria of their own. The animals who received bacteria from mice on a high-fat diet showed began to show increased levels of activity associated with anxiety and obsessive behavior. However, those who received microbes from mice on a high-fat diet plus antibiotics did not, even though they did not receive the antibiotics themselves. "This proves that these behaviors are driven to some significant extent by the gut microbiome," says Kahn.
But what exactly were the microbes doing? The Joslin looked for clues in two areas of the brain, the hypothalamus (which helps to control whole body metabolism) and the nucleus accumbens (which is important in mood and behavior).
"We demonstrated that, just like other tissues of the body, these areas of the brain become insulin resistant in mice on high-fat diets," Kahn says. "And this response to the high fat is partly, and in some cases almost completely, reversed by putting the animals by antibiotics. Again, the response is transferrable when you transfer the gut microbiome from mice on a high-fat diet to germ-free mice. So, the insulin resistance in the brain is mediated at least in part by factors coming from the microbiome."
The Joslin team went on to link the microbiome alterations to the production of certain neurotransmitters -- the chemicals that transfer signals across the brain.
Kahn and his colleagues are now working to identify specific populations of bacteria involved in these processes, and the molecules that the bacteria produce. The eventual goal is to find drugs or supplements that can help to achieve healthier metabolic profiles in the brain.
"Antibiotics are blunt tools that change many bacteria in very dramatic ways," Kahn says. "Going forward, we want to get a more sophisticated understanding about which bacteria contribute to insulin resistance in the brain and in other tissues. If we could modify those bacteria, either by putting in more beneficial bacteria or reducing the number of harmful bacteria, that might be a way to see improved behavior."
Overall, this study highlights how basic research that draws on expertise from multiple fields can lead in unexpected directions, Kahn emphasizes. "Understanding one area of biology, like diabetes and metabolism, can often give new and different perspectives in another field, like psychiatric and behavioral disorders," he says. "Even if that's not what you start out to do!"
https://www.sciencedaily.com/releases/2018/06/180617204413.htm