Anxiety might be alleviated by regulating gut bacteria

Review of studies suggests a potentially useful link between gut bacteria and mental disorders

May 20, 2019

Science Daily/BMJ

People who experience anxiety symptoms might be helped by taking steps to regulate the microorganisms in their gut using probiotic and non-probiotic food and supplements, suggests a review of studies

Anxiety symptoms are common in people with mental diseases and a variety of physical disorders, especially in disorders that are related to stress.

Previous studies have shown that as many as a third of people will be affected by anxiety symptoms during their lifetime.

Increasingly, research has indicated that gut microbiota -- the trillions of microorganisms in the gut which perform important functions in the immune system and metabolism by providing essential inflammatory mediators, nutrients and vitamins -- can help regulate brain function through something called the "gut-brain axis."

Recent research also suggests that mental disorders could be treated by regulating the intestinal microbiota, but there is no specific evidence to support this.

Therefore a team of researchers from the Shanghai Mental Health Center at Shanghai Jiao Tong University School of Medicine, set out to investigate if there was evidence to support improvement of anxiety symptoms by regulating intestinal microbiota.

They reviewed 21 studies that had looked at 1,503 people collectively.

Of the 21 studies, 14 had chosen probiotics as interventions to regulate intestinal microbiota (IRIFs), and seven chose non-probiotic ways, such as adjusting daily diets.

Probiotics are living organisms found naturally in some foods that are also known as "good" or "friendly" bacteria because they fight against harmful bacteria and prevent them from settling in the gut.

The researchers found that probiotic supplements in seven studies within their analysis contained only one kind of probiotic, two studies used a product that contained two kinds of probiotics, and the supplements used in the other five studies included at least three kinds.

Overall, 11 of the 21 studies showed a positive effect on anxiety symptoms by regulating intestinal microbiota, meaning that more than half (52%) of the studies showed this approach to be effective, although some studies that had used this approach did not find it worked.

Of the 14 studies that had used probiotics as the intervention, more than a third (36%) found them to be effective in reducing anxiety symptoms, while six of the remaining seven studies that had used non-probiotics as interventions found those to be effective -- a 86% rate of effectiveness.

Some studies had used both the IRIF (interventions to regulate intestinal microbiota) approach and treatment as usual.

In the five studies that used treatment as usual and IRIF as interventions, only studies that had conducted non-probiotic ways got positive results, that showed a reduction in anxiety symptoms.

Non-probiotic interventions were also more effective in the studies that used IRIF alone. In those studies only using IRIF, 80% were effective when using non-probiotic interventions, while only 45% were found to be effective when using probiotic ways.

The authors say one reason that non-probiotic interventions were significantly more effective than probiotic interventions was possible due to the fact that changing diet (a diverse energy source) could have more of an impact on gut bacteria growth than introducing specific types of bacteria in a probiotic supplement.

Also, because some studies had involved introducing different types of probiotics, these could have fought against each other to work effectively, and many of the intervention times used might have been too short to significantly increase the abundance of the imported bacteria.

Most of the studies did not report serious adverse events, and only four studies reported mild adverse effects such as dry mouth and diarrhoea.

This is an observational study, and as such, cannot establish cause. Indeed, the authors acknowledge some limitations, such as differences in study design, subjects, interventions and measurements, making the data unsuitable for further analysis.

Nevertheless, they say the overall quality of the 21 studies included was high.

The researchers conclude: "We find that more than half of the studies included showed it was positive to treat anxiety symptoms by regulation of intestinal microbiota.

"There are two kinds of interventions (probiotic and non-probiotic interventions) to regulate intestinal microbiota, and it should be highlighted that the non-probiotic interventions were more effective than the probiotic interventions. More studies are needed to clarify this conclusion since we still cannot run meta-analysis so far."

They also suggest that, in addition to the use of psychiatric drugs for treatment, "we can also consider regulating intestinal flora to alleviate anxiety symptoms."

https://www.sciencedaily.com/releases/2019/05/190520190110.htm

Transplanting gut bacteria alters depression-related behavior, brain inflammation in animals

Knowledge of stress biology may eventually yield bacterial treatments for psychiatric disorders

May 6, 2019

Science Daily/Children's Hospital of Philadelphia

Scientists have shown that transplanting gut bacteria, from an animal that is vulnerable to social stress to a non-stressed animal, can cause vulnerable behavior in the recipient. The research reveals details of biological interactions between the brain and gut that may someday lead to probiotic treatments for human psychiatric disorders such as depression.

"In rats that show depressive-type behavior in a laboratory test, we found that stress changes their gut microbiome -- the population of bacteria in the gut," said study leader Seema Bhatnagar, PhD, a neuroscientist in Department of Anesthesiology and Critical Care at Children's Hospital of Philadelphia (CHOP). "Moreover, when we transplanted bacteria from those stress-vulnerable rats into rats that had not been stressed, the recipient animals showed similar behavior."

Bhatnagar added that stress also increased inflammation in the brains of vulnerable rats, and that this inflammation appeared in unstressed rats after they received transplants from vulnerable animals.

The study team published its findings online March 4, 2019 in Molecular Psychiatry.

Bhatnagar leads the Stress Neurobiology Program at CHOP, and many of her co-authors are members of the PennCHOP Microbiome Program, a collaboration between researchers at CHOP and the Perelman School of Medicine at the University of Pennsylvania. The program aims to better understand the communities of microbes inside our bodies and alter their properties to improve human health. Chunyu Zhao, PhD, of that program, performed microbiome data analysis and is a co-author of the paper.

Scientists already know that brain and gut influence each other. In humans, patients with psychiatric disorders have different populations of gut microbes compared to microbes in healthy individuals, with parallel findings also seen in animal models of psychiatric disease. This study investigated mechanisms related to brain inflammation, microbiomes and stress.

"Humans do not all react identically to the same stresses -- some are more vulnerable than others to developing psychiatric disorders, others are more resilient," said Bhatnagar. "Something similar happens in laboratory animals as well."

In rodents, social hierarchies and territoriality are major sources of stress. In the laboratory, researchers model stressors with validated behavioral tools such as a forced swim test or a social defeat test to examine how animals use coping strategies to deal with stress. Rats that cope more passively are more vulnerable to the effects of stress because they also exhibit more anxiety- and depressive-type behaviors, while rats that cope more actively are resilient to the effects of social stress. Based on these assessments, the researchers classified the animals as either vulnerable or resilient.

The study team then analyzed the fecal microbiomes of vulnerable rats, resilient rats, a non-stressed control group, and a placebo group. They found that vulnerable rats had higher proportions of certain bacteria, such as Clostridia, than the other groups.

They then performed fecal transplants from three donor groups -- vulnerable rats, resilient rats or control non-stressed rats -- into naïve rats, animals that had not been stressed. They found that different microbiomes changed depressive-like behavior. Rats receiving transplants from vulnerable rats were more likely to adopt depressive-like behaviors, whereas rats receiving transplants from resilient animals or non-stressed animals did not exhibit any changes in behavior or in neural measures. Patterns of brain inflammatory processes in recipients also resembled those seen in the brains of vulnerable animals, suggesting that immune-modulating effects of gut bacteria such as Clostridia may have promoted that inflammation. However, transplants did not significantly change anxiety-like behavior.

The finding that gut transplants from vulnerable rats increased depressive-type behavior but not anxiety-type behavior in non-stressed recipients may point to different mechanisms. The authors said this difference suggests that depressive-type behaviors are more regulated by the gut microbiome, whereas anxiety-type behaviors are primarily influenced by neural activity changes produced by stress experience.

"Although much more research remains to be done, we can envision future applications in which we could leverage knowledge of microbiome-brain interactions to treat human psychiatric disorders," said Bhatnagar. "People already are taking over-the-counter probiotics as supplements. If we can eventually validate beneficial behavioral effects from specific bacteria, we could set the stage for new psychiatric treatments."

https://www.sciencedaily.com/releases/2019/05/190506163642.htm

Say Hello to a Healthy Gut and Goodbye to Digestive Problems

By Scott Sanders

www.cancerwell.org

<info@cancerwell.org>

Some people can eat whatever they want without any issues. Others have negative reactions to certain foods and diets. If you’re one of many people who experience occasional digestive problems, it’s time to learn about how you can use the food you consume to heal you from the inside out. 

Digestive ailments hit everyone at some point in their lives, and they can be temporary inconveniences or chronic conditions. Who hasn’t had diarrhea, constipation, bloating, vomiting, or an upset stomach at some point? But there are many who suffer from serious conditions like gallstones, celiac disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and more. According to Everyday Health, 20 percent of Americans are affected by GERD, over 25 million have gallstones, and approximately 10 to 15 percent are affected by irritable bowel syndrome. Disruptive stomach conditions can be caused by what you eat, but they can also be treated by what you eat. 

Nutrition

Eating whole, unprocessed foods is the best way to heal the gut. Learn to read nutrition labelsto see what ingredients make up your food. Preservatives and additives make your digestive system work harder and cause other health issues. Some foreign ingredients simply shouldn’t be eaten. Buy your food fresh rather than from packages. The more ingredients in the food, the more you should avoid it.

Food Elimination

Digestive conditions and autoimmune diseases generally call for special diets. To see which foods affect you in negative ways, try an elimination diet that removes specific foods for one month. You can start by cutting out the foods that typically cause issues (such as gluten, dairy, corn, soy, sugar, and alcohol) and reintroduce them slowly to see how they affect you. Another option is to cut out one thing at a time to monitor any differences. If you’re willing to stick with a strict diet, the autoimmune protocoldiet helps reduce intestinal inflammation. 

Gut Health

Since your gut processes all of your body’s nutrients, the health of your digestive tract is important to your overall wellbeing. When things are off in your gut, the rest of your body feels off, too. Gut healthcould affect everything from your brain to your skin to your weight-loss efforts. 

Your gut contains both good bacteria and bad bacteria. Known as microbiomes, these microorganisms live inside your digestive tract. The friendly bacteriain your gut include Bifidobacterium, Lactobacillus, Saccharomyces Boulardii, Bacillus Coagulans, and Akkermansia microbes. They protect against harmful microbes, promote digestive health, aid in digestion, improve the immune system, produce vitamins, impact the metabolism, and have other positive effects on intestinal health. 

Disease

The good bacteria may prevent and treat diseases, such as inflammatory conditions, heart disease, and even cancer. Gut health is linked to cancer in many ways. Digestive issues are often due to cancer and side effects of treatments. Constipation, nausea, stomach cramps, weight loss, and digestion problems can occur as a result of pain medication, chemotherapy, or the cancer itself. 

Sometimes, it’s the gut health that helps treat cancer. An immunotherapy called Checkpoint Inhibition can shrink tumors, but studieshave shown that gut health could have something to do with the patient’s response to it. By altering the gut microbiome, patients develop a better response to the immunotherapy. More good bacteria means better immune cells to kill the cancer cells. 

Probiotics

Healthy people who don’t have underlying medical problems may want to consider adding probioticsto their daily routine. Probiotics contain the same helpful microorganisms that are present in our bodies. You can ingest probiotics through supplements or in foods such as yogurt, kefir, kimchi, sauerkraut, tempeh, and kombucha (which also has antioxidants).

Exercise

Let’s not discount the importance of exercise for overall health. A healthy diet can heal your body, but never underestimate the role of physical fitness in a holistic approach to healing digestive ailments. Any form of cardiovascular exercise can help move digestive waste through your system. Yogais a great activity to practice, especially when it comes to reducing bloat.

There is no one-size-fits-all approach to intestinal health and treating digestive disorders. Each body is different. It takes trial and error, listening to your body, and seeing a doctor when natural methods don’t provide results. When the solutions finally do come, you’ll get to relish in the joy of eating again.

Gut feeling: Research examines link between stomach bacteria, PTSD

April 25, 2016

Science Daily/Office of Naval Research

Could bacteria in your gut be used to cure or prevent neurological conditions such as post-traumatic stress disorder (PTSD), anxiety or even depression? Two researchers think that's a strong possibility.

Dr. John Bienenstock and Dr. Paul Forsythe--who work in The Brain-Body Institute at McMaster University in Ontario, Canada--are investigating intestinal bacteria and their effect on the human brain and mood.

"This is extremely important work for U.S. warfighters because it suggests that gut microbes play a strong role in the body's response to stressful situations, as well as in who might be susceptible to conditions like PTSD," said Dr. Linda Chrisey, a program officer in ONR's Warfighter Performance Department, which sponsors the research.

The trillions of microbes in the intestinal tract, collectively known as the gut microbiome, profoundly impact human biology--digesting food, regulating the immune system and even transmitting signals to the brain that alter mood and behavior. ONR is supporting research that's anticipated to increase warfighters' mental and physical resilience in situations involving dietary changes, sleep loss or disrupted circadian rhythms from shifting time zones or living in submarines.

Through research on laboratory mice, Bienenstock and Forsythe have shown that gut bacteria seriously affect mood and demeanor. They also were able to control the moods of anxious mice by feeding them healthy microbes from fecal material collected from calm mice.

Bienenstock and Forsythe used a "social defeat" scenario in which smaller mice were exposed to larger, more aggressive ones for a couple of minutes daily for 10 consecutive days. The smaller mice showed signs of heightened anxiety and stress--nervous shaking, diminished appetite and less social interaction with other mice. The researchers then collected fecal samples from the stressed mice and compared them to those from calm mice.

"What we found was an imbalance in the gut microbiota of the stressed mice," said Forsythe. "There was less diversity in the types of bacteria present. The gut and bowels are a very complex ecology. The less diversity, the greater disruption to the body."

Bienenstock and Forsythe then fed the stressed mice the same probiotics (live bacteria) found in the calm mice and examined the new fecal samples. Through magnetic resonance spectroscopy (MRS), a non-invasive analytical technique using powerful MRI technology, they also studied changes in brain chemistry.

"Not only did the behavior of the mice improve dramatically with the probiotic treatment," said Bienenstock, "but it continued to get better for several weeks afterward. Also, the MRS technology enabled us to see certain chemical biomarkers in the brain when the mice were stressed and when they were taking the probiotics."

Both researchers said stress biomarkers could potentially indicate if someone is suffering from PTSD or risks developing it, allowing for treatment or prevention with probiotics and antibiotics.

Later this year, Bienenstock and Forsythe will perform experiments involving fecal transplants from calm mice to stressed mice. They also hope to secure funding to conduct clinical trials to administer probiotics to human volunteers and use MRS to monitor brain reactions to different stress levels.

Gut microbiology is part of ONR's program in warfighter performance. ONR also is looking at the use of synthetic biology to enhance the gut microbiome. Synthetic biology creates or re-engineers microbes or other organisms to perform specific tasks like improving health and physical performance. The field was identified as a top ONR priority because of its potential far-ranging impact on warfighter performance and fleet capabilities.

https://www.sciencedaily.com/releases/2016/04/160425161324.htm

Prebiotics may help to cope with stress

Prebiotic fibers can help to protect beneficial gut bacteria and restore healthy sleep patterns after a stressful event

February 10, 2017

Science Daily/Frontiers

Probiotics are well known to benefit digestive health, but prebiotics are less well understood. Recent study in rats shows that prebiotic fibers may help to protect beneficial gut bacteria and restore healthy sleep patterns after a stressful event.

Probiotics are well known to benefit digestive health, but prebiotics are less well understood. Prebiotics are certain types of non-digestible fibers that probiotic bacteria feed on, such as the fibers found in many plant sources like asparagus, oatmeal, and legumes. Certain bacteria also feed on non-fibers such as the protein lactoferrin, which also acts like a prebiotic and is found in breast milk.

According to a new study published in the online journal, Frontiers in Behavioral Neuroscience by Professor Monika Fleshner, PhD, and her team from the University of Colorado, Boulder, regular intake of prebiotics may promote beneficial gut bacteria and recovery of normal sleep patterns after a stressful episode.

"Acute stress can disrupt the gut microbiome," explained Dr. Agnieszka Mika, a postdoctoral fellow and one of the authors of the study, "and we wanted to test if a diet rich in prebiotics would increase beneficial bacteria as well as protect gut microbes from stress-induced disruptions. We also wanted to look at the effects of prebiotics on the recovery of normal sleep patterns, since they tend to be disrupted after stressful events."

In this experiment, test rats received prebiotic diets for several weeks prior to a stressful test condition and compared with control rats that did not receive the prebiotic-enriched diet. Interestingly, rats that ate prebiotics prior to the stressful event did not experience stress-induced disruption in their gut microbiota, and also recovered healthier sleep patterns sooner than controls.

Given that these experiments were done in rats, are these results relevant for humans? "The stressor the rats received was the equivalent of a single intense acute stressful episode for humans, such as a car accident or the death of a loved one," said Dr. Robert S. Thompson, the lead author of the study. "A next set of studies will be looking exactly at that question -- can prebiotics help humans to protect and restore their gut microflora and recover normal sleep patterns after a traumatic event?"

In the mean time, should we start including prebiotics in our diets to help cope with stress? "So far no adverse effects from prebiotics have been reported," said Dr. Mika, "and they are found widely in many plants, even present in breast milk, and are already commercially available." Healthy gut bacteria and restful sleep could be your benefits.

https://www.sciencedaily.com/releases/2017/02/170210130951.htm