Keenan Eriksson, May 2, 2019
Beyond-Probiotics-3-Powerful-Tools-For-Healing-The-Gut-BiomeThe human microbiome—a collection of bacteria, archaea, fungi and viruses commingling in the gut and intestines—has been linked to a wide range of human health conditions, including digestive health and the prevention of autoimmune diseases. Some research has even identified a possible link between gut health and brain function. Building on this work, a study published yesterday in Nature Microbiology reveals that clinical depression could be affected by the amounts of certain bacteria in the gut.
The research team, led by microbiologist Jeroen Raes of the Catholic University of Leuven in Belgium, found that almost all gut bacteria are able to produce neurotransmitters, which are chemicals like dopamine and serotonin that enable communication between neurons. If these “chemical messengers” are sent to receptors in the brain, they can influence mood and behavior. The researchers also identified two strains of bacteria that are lacking in the guts of people who have been diagnosed with depression.
The study adds to mounting evidence that an association between gut health and the brain exists. However, it does not establish whether poor mental health causes depletion of the bacteria, or if the missing bacteria intensifies symptoms associated with mood disorders. More research is needed to conclusively say that gut bacteria influences mental health, says Mark Lyte, a professor of microbiology at Iowa State University who wasn’t involved in the study.
“The studies are just really starting,” Lyte says. “We do not fully understand what all the genes in all the bacteria do, so don’t make the conclusion that we understand everything about the microbiota in terms of their genetic capacity to make [neurotransmitters]. We only understand a fraction of that.” Scientists recently identified more than 100 new species of bacteria in the human gut, underscoring how much we still have to learn about the functions of the microbiome.
Read more: https://www.smithsonianmag.com/science-nature/scientists-find-possible-link-between-gut-bacteria-and-depression-180971411/#zmsZgLlVWgrCB5Zi.99
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https://medium.com/@the_economist/gut-bacteria-may-offer-a-treatment-for-autism-33e7cb905947
Autism affects people’s social behaviour and communication, and may impair their ability to learn things. All this is well known. Less familiar to most, though, are the gastrointestinal problems associated with the condition. The intestines of children with autism often harbour bacteria different from those in the guts of the neurotypical. As a consequence, such people are more than three times as likely as others are to develop serious alimentary-canal disorders at some point in their lives.
Unfortunate though this is, the upset gut floras of autistic people are seen by some investigators as the key to the condition — and to treating it. Recent research has shown that altering animals’ intestinal bacteria can have dramatic effects on their nervous systems. Ameliorating autism by tinkering with the ecology of the gut might thus be a fruitful line of inquiry.
A study just published in Neuron suggests that it is. In it, Mauro Costa-Mattioli of Baylor College of Medicine, in Texas, and his colleagues demonstrate that introducing a particular bacterium into the guts of mice that display autistic symptoms can abolish some of those symptoms. The bug in question is Lactobacillus reuteri. It is commonly found in healthy digestive systems and helps regulate acidity levels. And it is also easily obtainable for use as a probiotic from health-food shops.
Dr Costa-Mattioli and his team first reported L. reuteri’s effects on autism in 2016, after conducting experiments with obese female mice. These animals have a tendency to give birth to offspring with autistic traits familiar from people — unwillingness to socialise, repetitive behaviour and unwillingness to communicate (in the case of mice, via ultrasonic squeaking). The researchers noted that the guts of both the obese mothers and their young were bereft of L. reuteri. They wondered what effect transplanting these bugs into the animals might have. They found, when they did so to the offspring, that the youngsters’ autism-like traits vanished.
That led to the latest experiments, on mice that have autistic symptoms induced in four other, different ways. Some were genetically edited to be autistic. Some were exposed to valproic acid, a drug used to treat bipolar disorder and migraines that is known to induce autism in fetuses. Some had their guts cleared of all bacteria. And some belonged to a strain called BTBR, individuals of which display autism-like traits that have no known cause.
Martina Sgritta, one of Dr Costa-Mattioli’s colleagues, analysed the bacteria in the guts of all of these animals. She found that, while the genetically engineered mice and the BTBR mice had, as expected, reduced levels of L. reuteri, and those with bacteria-free guts were (obviously) free of the bug altogether, the valproic-acid mice had normal amounts of the bacterium.
This last result was unexpected, but the team carried on regardless. They arranged for between seven and 15 mice of each of the four types to have, starting at the age of three weeks, their drinking water laced with L. reuteri. Equivalent numbers of each type continued to be given ordinary water as a control. During the course of the experiment the mice had their faeces collected regularly, so that their bacteria could be tracked. And, at the age of seven weeks, they were given two sorts of social tests.
The first test involved putting each experimental mouse into a perspex container from which it could go either into a chamber where there was an empty wire cup or into one where there was a similar cup containing an unfamiliar mouse. Subject mice were left in the container for ten minutes and were monitored to see how long they spent with the empty cup and with the other mouse.
The second test placed a mouse in an arena where another, unfamiliar mouse was already present. An observer, who did not know which mice were controls and which had been given L. reuteri in their water, then noted how often over the course of ten minutes the two mice touched, sniffed, groomed and crawled on one another.
In both tests, all the mice that had had their water laced with L. reuteri, regardless of how their autism had been induced, were more sociable than equivalents that had been drinking unlaced water. In the first, they spent twice as much time with the mouse under the wire cup. In the second, they engaged in many more social interactions with the unfamiliar mouse.
The team’s initial hypothesis had been that the supplementary L. reuteri were somehow changing the gut flora of the mice exposed to them into something more normal. But they weren’t. Indeed, L. reuteri proved able to abolish autistic behaviour even in those mice which had guts otherwise devoid of microbes — as well as in those with valproic-acid-induced autism, which already had normal levels of the bug. That suggests boosting levels of this bacterial species is shaping behaviour all by itself.
Their next hypothesis was that the bacterium was doing this by interacting somehow with oxytocin, a hormone that shapes behaviour and plays a part in the ways in which people and other mammals form social bonds. Dr Costa-Mattioli knew from work published in 2013 that spraying oxytocin into the noses of mice with autistic symptoms helps to ameliorate some of those symptoms. Dr Sgritta therefore ran the experiments again, but this time on autistic mice that had had the oxytocin receptors on the relevant neurons disabled by genetic engineering. In these new experiments, the presence of L. reuteri in drinking water had no effect.
Follow-up examinations of the mice in all these experiments looked at the strengths of connections between nerve cells within part of the brain called the ventral tegmental region. This region regulates, among other things, motivation and reward-related social behaviour. Nerve signals are carried by the movement of ions (electrically charged atoms), so the team were able to measure connection-strength by monitoring the flow of ions at the junctions between nerve cells in this region. Strong connections, with lots of ion flow, indicated that social experiences were rewarding. These were normal in the mice exposed to L. reuteri, which makes sense since animals treated with the bacterium sought out more social experiences. Conversely, weak connections (those with little ion flow) indicated that social experiences were not triggering a reward. Such weak connections were found in animals that had not been exposed to the bacterium.
The researchers suspected that such effects were controlled by signals from the gut that are being transmitted by the vagus nerve, which connects gut and brain. To test this idea they cut that nerve in selected animals. In these animals, subsequent treatment with L. reuteri failed to abolish their autistic symptoms.
The crucial aspect of this work is L. reuteri’s wide availability — an availability approved by regulators such as America’s Food and Drug Administration. This existing approval, which means L. reuteri poses no known health hazard, simplifies the process of organising clinical trials.
Clearly, autism in people is more complicated than a mere willingness to associate with others. And getting too excited about a mouse trial is usually a mistake. But in Dr Costa-Mattioli’s view his results, which have been replicated in part by Evan Elliot’s laboratory in Bar-Ilan University, Israel, would justify embarking on at least preliminary trials intended to determine whether L. reuteri has positive effects on people with autism, and might thus be worth pursuing.
Others agree. Sarkis Mazmanian of the California Institute of Technology works in the same area. He says of these results: “I think the bar is now very low for getting this research moved on to human trials since most people already have these bacteria inside them and we know there are few, if any, safety or toxicity issues.”
The general availability of L. reuteri does, however, bring with it another possibility — that people will conduct their own, “off label” trials, either on themselves or on their children. Dr Mazmanian is cautious about that idea. “I don’t know if there is a barrier to people buying and using this stuff now. It may be strain-specific and the paper does not state which strain or strains were used,” he says.
At the moment, Dr Costa-Mattioli is unwilling to divulge that information. He is expecting to publish another paper soon, though, with more details. In practice, it may be hard to discourage people from testing L. reuteri’s effects themselves. All the more reason to do properly conducted trials quickly.
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-019-0635-4
Yiran Liang†, Jing Zhan†, Donghui Liu, Mai Luo, Jiajun Han, Xueke Liu, Chang Liu, Zheng Cheng, Zhiqiang Zhou and Peng WangEmail authorView ORCID ID profile
†Contributed equallyMicrobiome20197:19
https://doi.org/10.1186/s40168-019-0635-4
© The Author(s). 2019
Published: 11 February 2019
Disruption of the gut microbiota homeostasis may induce low-grade inflammation leading to obesity-associated diseases. A major protective mechanism is to use the multi-layered mucus structures to keep a safe distance between gut epithelial cells and microbiota. To investigate whether pesticides would induce insulin resistance/obesity through interfering with mucus-bacterial interactions, we conducted a study to determine how long-term exposure to chlorpyrifos affected C57Bl/6 and CD-1 (ICR) mice fed high- or normal-fat diets. To further investigate the effects of chlorpyrifos-altered microbiota, antibiotic treatment and microbiota transplantation experiments were conducted.
The results showed that chlorpyrifos caused broken integrity of the gut barrier, leading to increased lipopolysaccharide entry into the body and finally low-grade inflammation, while genetic background and diet pattern have limited influence on the chlorpyrifos-induced results. Moreover, the mice given chlorpyrifos-altered microbiota had gained more fat and lower insulin sensitivity.
Our results suggest that widespread use of pesticides may contribute to the worldwide epidemic of inflammation-related diseases.
The gut microbiome consists of all the bacteria living in an individual’s intestinal tract. Without these bacteria, we would not be able to digest and process the food we eat. They live in an extreme environment and are known to have coevolved with hominids. In one study, 33 mammalian gut microbiomes were compared to find that the two main factors which dictate gut microbiome diversity are phylogeny and diet. In the figure below published by Nature in 2017, you can observe that ancestral gut microbiomes were more severely affected by their diets, whereas today the lineage is almost entirely correlated with host phylogeny.
In recent years, there has been a lot of research on human gut microbiomes and how their diversity can affect our health. There are many factors that influence our gut microbiome diversity, such as diet quality, exposure to food and water-borne pathogens, and use of antibiotics (Carrera-Bastos and Fontes-Villalba 2011). We have seen a loss of diversity in Western populations, where antibiotic use is widespread and diets are more homogenous compared to non-industrialized countries such as Malawi and Venezuela, which have been exposed to more pathogens through food and water and subsist on a varied diet (Davenport and Sanders 2017) The loss of gut microbiome diversity can be linked to several diseases and is a growing issue which requires further research.
Comparing gut microbiomes between humans and closely related primates could provide insight to changes in behavior that alter diversity. “In contrast to African apes, humans have lower gut microbiota diversity, increased relative abundances of Bacteroides, and reduced relative abundances of Methanobrevibacter and Fibrobacter” (Davenport E.R and Sanders J.G 2017) These three bacteria are related to carnivory in other mammals, which may explain the evolutionary change in our microbiome to adjust to eating more meat. The difference in gut microbiome species can be vastly different in current humans. In a population studied in Malawi, a lineage of Bacteroidaceae was found which is completely nonexistent in populations from the United States. (Moeller H.A et al 2016) A possible cause of this is the difference in diet between Malawians and Americans. Where people from Malawi have a varied diet, a large portion of the United State consumed processed food on a regular basis. Antibiotic use is also very widespread in more urbanized countries which can lower the diversity of bacteria in an individual for the rest of their life (Francino M.P 2015) Another article states that the difference in microbiomes of US humans and people from Malawi is greater than those between people from Malawi and bonobos (Moeller H.A et al 2014) Compared to apes, where a variety of different bacteria coexisted at low frequencies, individual humans tend to have fewer dominant taxa at greater rates (Moeller H.A et al 2014) This can be seen in the figure published by PNAS in 2014. These findings could point to a major loss in diversity. The possibility that entire lineages of gut bacteria can disappear points to bigger issues. If this continues, we may lose our ability to digest certain types of food.
So how do we go about reversing the effect of improper diet, antibiotics and the other factors in our lives that alter our microbiome? One step would be to eat healthier, whole foods rather than processed foods. Since the bacteria we are discussing reside in the digestive system and live off of the food humans eat, it makes sense that consuming food that is good for the person will also promote more stable levels of gut bacteria. People who consume high protein and low carbohydrate diets tend to have less Roseburia in their bodies, which is also common in people with irritable bowel syndrome (Singh R.K et al 2017) There are also links to microbes that are promoted by consuming red meat and the levels of a compound produced which increases the risk of cardiovascular disease (Singh R.K et al 2017) Besides eating well, lowering use of antibiotics if possible would also help maintain a healthy microbiome. Many antibiotics are unavoidable as they are found in farm animals and crops. However, broad spectrum antibiotics can affect the abundances of 30% of the bacteria in the gut community (Francino M.P 2015) Overall, people should be more aware of the way that their diet and lifestyle choices can harm their gut flora. Further research needs to be done on the direct impact of antibiotics and diet on gut intestinal flora and the diseases caused by lack of diversity.
Works Cited
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Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in the nucleus accumbens and amygdala. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids, and multiple acylcarnitines, and are transferable to germ-free mice by fecal transplant. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors.
Have you ever been on a diet but didn’t hit your goal weight? Your gut bacteria may be part of the explanation.
New research suggests the mix of microbes in our guts can either help — or hinder — weight-loss efforts.
“We started with the premise that people have different microbial makeups, and this could influence how well they do with dieting,” explains Purna Kashyap, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
As part of the study, Kashyap and his collaborators tracked the progress of people who were enrolled in a lifestyle-intervention program for weight loss. The participants were advised to follow a low-calorie diet, and they were tracked closely for about three months.
“We found that people who lost at least 5 percent of their body weight had a different gut bacteria as compared to those who did not lose 5 percent of their body weight,” Kashyap explains. Their findings are published in the journal Mayo Clinic Proceedings.
The successful dieters had an increased abundance of a bacteria called Phascolarctobacterium, whereas another bacteria, Dialister, was associated with a failure to lose the weight. And, Kashyap says it’s likely that there are other types of bacteria that might influence dieting as well.
So, how might bacteria influence weight loss? It turns out we can get a significant number of calories from our microbes.
Here’s how it works: Consider what happens when you eat an apple. You digest most of it.
“But there’s a certain part of the apple we can’t absorb,” explains Martin Blaser, a professor in the Department of Microbiology at NYU Langone Medical Center. “We don’t have the right enzymes to digest every bit of [the apple], but our bacteria can.”
Think of it this way: The bacteria eat what we can’t.
And, in the process, they produce byproducts that we can digest. So these byproducts become another source of calories for us.
The new study suggests that certain bacteria — or mix of bacteria — may be more efficient at creating “extra” calories for us to digest.
“Somewhere between 5 to 15 percent of all our calories come from that kind of digestion, where the microbes are providing energy for us, that we couldn’t [otherwise] get,” Blaser explains.
This calorie boost could be beneficial if food were scarce. “If times were bad, if we were starving, we’d really welcome it,” Blaser says.
But at a time when many people want to lose weight, these extra calories may be an unwanted gift.
But the study was small — just 26 participants. Now, researchers want to conduct a larger, follow-up study, including dieters from different geographic regions, to see if they can reproduce the results.
“If two studies show the same thing, then we’re on more solid ground,” Blaser says. He was not involved in the research, but agreed to review the findings for NPR. For now, he says these findings are intriguing but preliminary.
Down the road, if the results hold up in a larger group, it could lead to more tailored dieting approaches. “What we would hope to do is to be able to individualize care for people,” Kashyap says. “And we’d also try to develop new probiotics, which we could use to change the microbial makeup.”
Probiotics that are currently on the market would not be effective. The idea is to develop a new product that includes the specific types of bacteria linked to successful dieting.
But it’s not so simple to manipulate the mix of microbes in our guts. Identifying the organism — or organisms — that are thought to be beneficial is just the first step.
Next, the organisms would need to be cultivated and mass-produced in order to create a new probiotic. “Some bacteria are difficult to work with,” so it could be challenging, says Blaser.
So, if it’s possible to produce a probiotic for dieters based on this research, “it’s at least some years off,” Blaser says.
Obesity is a risk factor for osteoarthritis (OA), the greatest cause of disability in the US. The impact of obesity on OA is driven by systemic in ammation, and increased systemic in ammation is now understood to be caused by gut microbiome dysbiosis. Oligofructose, a nondigestible prebiotic ber, can restore a lean gut microbial community pro le in the context of obesity, suggesting a potentially novel approach to treat the OA of obesity. Here, we report that — compared with the lean murine gut — obesity is associated with loss of bene cial Bi dobacteria, while key proin ammatory species gain in abundance. A downstream systemic in ammatory signature culminates with macrophage migration to the synovium and accelerated knee OA. Oligofructose supplementation restores the lean gut microbiome in obese mice, in part, by supporting key commensal micro ora, particularly Bi dobacterium pseudolongum. This is associated with reduced in ammation in the colon, circulation, and knee and protection from OA. This observation of a gut microbiome–OA connection sets the stage for discovery of potentially new OA therapeutics involving strategic manipulation of speci c microbial species inhabiting the intestinal space.
Interesting article that continues the discussion of redeveloping our medical diagnostic and treatment paradigm to include dysbiosis. Technologies such a multiplexing assays give us the ability to quickly gauge the absence or presence of certain complexes that create an environment for disease. Additionally, the introduction of new vocabulary is essential to further discussions and analysis outside of the traditional medical paradigms.
Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study
New research suggests a link between the microbiome and autism spectrum disorder. Using a protocol that involved a fecal microbiota transplant (FMT) resulted in an improvement in both gastrointestinal symptoms but also behavioral improvements. This small study is important as it reproduces the results of other adult studies that have shown an improvement in psychological symptoms following FMT. It provides yet more evidence of a gut-brain connection and should encourage others to explore this important connection.