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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The brain’s powers are a little overrated. To keep your body going, you don’t need a functioning brain, but you do need something to provide energy. Enter the gut.
For instance, the processes the enteric nervous system performs also gives it some control over the trillions of microbes that sit in your gut. Many of them are essential for our health, because they help us extract nutrients that we wouldn’t otherwise be able to, and some even fend off infections.
And there’s more. It had been suspected that what happens in the gut could have an impact on the brain. Now we have found too many correlations to ignore the gut-to-brain connection.
Until now, however, these gut-brain connections have been mere correlations. With some help from tapeworms, a new study changes that.
One of the connecting factors between the brain and the gut has been the immune system. Neurological diseases, such as Alzheimer’s and multiple sclerosis, are linked to changes in the immune system, and auto-immune diseases of the gut, such as Crohn’s disease, are linked to mental illnesses.
She split a group of 30 rats in two: those infected with the Hymenolepis diminuta worm and those without. Then, in both groups, she induced a second infection aimed at increasing the production of a brain signaling chemical called IL-1β. The chemical is usually beneficial, but in excess it can cause damage and has been associated with brain disease.
The reason was that mice with tapeworm infection had already had an immune response, which kept the levels of IL-1β low when a second infection came along. Lower levels of IL-1β in the brain ensured the formation and retention of memories, more than in rats without the worms. Those who hadn’t had the infection produced far greater levels of IL-1β.
Cleveland Clinic asked more than 100 of its top experts about the innovations set to reshape healthcare in the coming year. These are their answers — the Top 10 Innovations for 2014.
The microbiota, or mix of microbes, in your intestines exists in a delicate state of balance. Sometimes, antibiotics used for treatment can undo that balance by killing both aggressive and friendly bacteria.
When this happens, hardy C.diff (short for Clostridium difficile) microbes live on — often with disastrous results when they spread infection from person to person. Many gastroenterologists are fighting this problem with a novel approach called fecal microbiota transplantation, a.k.a. human stool transplants.
In this therapy, doctors use a colonoscopy or enema to transfer a liquid suspension made from a healthy person’s fecal matter into a sick person’s colon. The goal is to restore bacterial balance and fight infections and diseases.
Fecal microbiota transplantation could become a primary therapy not only for C.diff infection, but also for inflammatory bowel disease.
C.diff poses such high risks because of how it spreads, particularly in hospitals. It can be transmitted to hands, food, utensils, sheets, countertops and curtains as spores. When passed to another person, these spores lead to intestinal inflammation, diarrhea, nausea, vomiting and abdominal pain. According to the U.S. Centers for Disease Control and Prevention, C. diffinfections have increased to 500,000 cases each year in the United States. That includes 15,000 deaths annually.
Fecal transplantation might help bring those numbers down.
Clinical study results have been positive. Some people who have had multiple C. diff infections have realized benefits from the therapy hours later, have been cured of their symptoms within 24 hours, and have had no further infections.
As research continues, experts expect that fecal microbiota transplantation could become a primary therapy not only for C.diff infection, but also for inflammatory bowel disease. It even holds promise for treating conditions such as rheumatoid arthritis and Parkinson’s disease.
The mucosal surface of the human gastrointestinal (GI) tract is about 200-300 m2 and is colonized by 1013-14 bacteria of 400 different species and subspecies. Savage has defined and categorized the gastrointestinal microflora into two types, autochthonous flora (indigenous flora) and allochthonous flora (transient flora). Autochthonous microorganisms colonize particular habitats, i.e., physical spaces in the GI tract, whereas allochthonous microorganisms cannot colonize particular habitats except under abnormal conditions. Most pathogens are allochthonous microorganisms; nevertheless, some pathogens can be autochthonous to the ecosystem and normally live in harmony with the host, except when the system is disturbed. The prevalence of bacteria in different parts of the GI tract appears to be dependent on several factors, such as pH, peristalsis, redox potential, bacterial adhesion, bacterial cooperation, mucin secretion, nutrient availability, diet, and bacterial antagonism. Because of the low pH of the stomach and the relatively swift peristalsis through the stomach and the small bowel, the stomach and the upper two-thirds of the small intestine (duodenum and jejunum) contain only low numbers of microorganisms, which range from 103 to 104 bacteria/mL of the gastric or intestinal contents, mainly acid-tolerant lactobacilli and streptococci. In the distal small intestine (ileum), the microflora begin to resemble those of the colon, with around 107-108 bacteria/mL of the intestinal contents. With decreased peristalsis, acidity, and lower oxidation-reduction potentials, the ileum maintains a more diverse microflora and a higher bacterial population. Probably because of slow intestinal motility and very low oxidation-reduction potentials, the colon is the primary site of microbial colonization in humans. The colon harbors tremendous numbers and species of bacteria. However, 99.9% of colonic microflora are obligate anaerobes.
The gut houses trillions of microbes. They eat what you eat. Many specialize in fermenting the soluble fiber in legumes, grains, fruits and vegetables. Certain microbial species are adept at colonizing the mucous layer of the gut. Mucus contains antimicrobial substances that keep the microbiota at a slight distance. But it also contains sugars such as those found in breast milk. Some microbes, often the same ones that specialize in fermenting fiber, can use these sugars as sustenance when other food is not available. The by-products of fiber fermentation nourish cells lining the colon. Some by-products pass into the circulation and may calibrate our immune system in a way that prevents inflammatory disorders such as asthma and Crohn’s disease.
Little did I know that I would be friends with a bunch of microbes! All my life I have been taught to “Wash your hands!” “you don’t want to have those nasty germs all over you!” etc., etc. Little did we know that most of those nasty germs were actually friends.
The more as a society that we have cleaned up, we have become sicker and not better. New autoimmune diseases are discovered every week and physicians are at a loss to fix it. All we are told is that we should take drugs to “turn off” our immune response. REALLY!? This is how crazy it has gotten.
Many of my friends, family members and acquaintances now suffer from Crohn’s or IBS, or ADHD, etc. and their only hope is a lifelong drug addiction. Not for me. Understanding our microbiome holds such great hope that it has inspired me to start this website. I hope that it can be a help to others looking for clues and answers that they are not getting through their physicians.
Let me know your story. Let me know what you have found out and post it here. I will promise you that we will share it and research it.