Increasing evidence is showing that the gut microbiota can alter the brain and behavior, and thus may play a role in the development of psychiatric and neurodevelopmental disorders, such as autism and schizophrenia.
Animal models are a useful tool to study this mechanism. For example, germ-free (GF) mice, which have never been exposed to microorganisms, are compared with mice exposed to microorganisms, known as conventional colonized mice (CC). Recent studies have reported that GF animals show increased response to stress, as well as reduced anxiety and memory. In most cases, these alterations are restricted to males, in which there are higher incidence rates of neurodevelopmental disorders compared with females.
Mice, like humans, are a social species and are used to study social behavior. A recent study compared GF and CC mice using different sociability tests. GF mice showed impairments in social behavior compared with CC mice, particularly in males. Interestingly, they demonstrate that social deficits can be reversed by bacterial colonization of the GF gut (GFC), achieving normal social behavior.
Microbiota seem to be crucial for social behaviors, including social motivation and preference for social novelty. Microbiota also regulate repetitive behaviors, characteristic of several disorders such as autism and schizophrenia.
Bacterial colonization can change brain function and behavior, suggesting that microbial-based interventions in later life could improve social impairments and be a useful tool to effect the symptoms of these disorders.
This blog was co-authored by Noèlia Fernàndez and Judit Cabana
Real time measurements of intestinal
gases: a novel method to study how food is being digested
Researchers in Wageningen (The
Netherlands), have been able to identify for the first time, how gut microorganisms
process different types of carbohydrates by measuring in real time the intestinal
gases of mice. This is not only a novel method to understand how food is
digested but could also tell us more about the role of gut microorganisms in
The intestinal microbiota is a diverse and
dynamic community of microorganisms which regulate our health status. The
advancement of biomolecular techniques and bioinformatics nowadays allows
researchers to explore the residents of our intestines, revealing what type of microorganisms
are there. However, studying only the microbial composition of an individual
provides limited insights on the mechanisms by which microorganisms can
interact with the rest of our body. For example, far less is understood about
the contribution of the gut microorganisms in the production of intestinal
gases such as hydrogen, methane and carbon dioxide through the breakdown of
food and how these gases affect the biochemical pathways of our bodies.
Intestinal gases consist mostly of
nitrogen, and carbon dioxide, which originate primarily from inhaled air. Hydrogen
and methane though, are produced as by-products of carbohydrate fermentation
(break down), by intestinal microorganisms. However, not all carbohydrates are
digested in the same way. For instance, food with simple sugars can be rapidly absorbed
in the small intestine unlike complex carbohydrates such as fibers, which reach
the colon where they are digested by the colonic microbiota.
Measuring hydrogen in mouse intestines
To study these interactions and gain
knowledge on how microorganisms process carbohydrates, the research team led by Evert van
Schothorst from the Human and Animal Physiology Group of Wageningen University
(WU) in collaboration with the WU-Laboratory of Microbiology fed mice two
different diets with the same nutritional values but with different types of carbohydrates
(1). The first diet contained amylopectin,
a carbohydrate which can be digested readily in the small intestine while the
second diet contained amylose, a slowly digestible carbohydrate that is
digested by intestinal microorganisms in the colon.
Animals fed the easily digestible carbohydrates
showed minimal production of hydrogen whereas the group fed with the complex
carbohydrates presented high levels of hydrogen. Moreover, the two groups were
characterized not only by distinct microbial composition (different types of
bacteria present) but also distinct metabolic profiles (short chain fatty acids),
suggesting that the type of carbohydrate strongly affects microbial composition
The importance of
Hydrogen consumption is essential in any anoxic
(without oxygen) microbial environment to maintain fermentative processes. In
the intestine it can be utilised through three major pathways for the
production of acetate, methane and hydrogen sulphide. These molecules are
critical mediators of gut homeostasis, as acetate is the most predominant short
chain fatty acid produced in mammals with evidence suggesting a role in inflammation and obesity (2). Methane, which is produced by a specific type of microorganisms,
called archaea, has been associated with constipation related diseases, such as
irritable bowel syndrome(3) and also recently with athletes’ performance (4)! Finally hydrogen sulphide
is considered to be a toxic gas, although recent findings support the notion
that it also has neuroprotective effects in neurodegenerative disorders such as Parkinson and Alzheimer diseases (5).
To the best of our knowledge, this is the first time that food-microbiota interactions have been studied continuously, non-invasively and in real time in a mouse model. Hydrogen is a critical molecule for intestinal health and understanding its dynamics can provide valuable information about intestinal function, and deviations in conditions such as Crohn’s disease or irritable bowel syndrome (IBS).
1. Fernández-Calleja, J.M., et al., Non-invasive continuous real-time in vivo analysis of microbial
hydrogen production shows adaptation to fermentable carbohydrates in mice.
Scientific reports, 2018. 8(1): p.
Perry, R.J., et al., Acetate mediates a
microbiome–brain–β-cell axis to promote metabolic syndrome. Nature, 2016. 534(7606): p. 213
3. Triantafyllou, K., C. Chang, and M. Pimentel, Methanogens, methane and gastrointestinal
motility. Journal of neurogastroenterology and motility, 2014. 20(1): p. 31.
4. Petersen, L.M., et al., Community characteristics of the gut microbiomes of competitive
cyclists. Microbiome, 2017. 5(1):
Y.O., Provotella‐derived hydrogen sulfide, constipation,
and neuroprotection in Parkinson’s disease. Movement Disorders, 2015. 30(8): p.
Breaking news: It has long been assumed that the gut and the brain communicate not only via a slow, hormonal pathway, but that there must be an additional, faster association between gut and brain. Melanie Maya Kelberer and her colleagues from Duke University, NC, now managed to detect this connection. Their paper has just been published in the renowned journal ‘Science’.
By researching a mouse model, they were able to show that the gut and the brain are connected via one single synapse. This is how it works: A cell in the gut (the so-called enteroendocrine cell) transfers its information to a nerve ending just outside the gut. At the connecting nerve ending (the synapse), the neurotransmitter glutamate – the most important excitatory transmitter in the nervous system – passes on the information about our nutrition to small nerve endings of the vagal nerve, which spreads from the brain to the intestines.
By travelling along this vagal nerve, the information from the gut reaches the brainstem within milliseconds. The authors now state that a new name is needed for the enteroendocrine cells, now that they have been shown to be way more than that. The name ‘neuropod cells’ has been suggested. The authors interpret their findings as such, that this rapid connection between the gut and the brain helps the brain to make sense of what has been eaten. Through back-signalling, the brain might also influence the gut. In sum, this finding is an important step towards a better understanding of how the gut and the brain communicate. Findings such as this one help us to find ways to positively influence our brain states and our mental health by our food choices.
Read the original paper here: http://science.sciencemag.org/content/361/6408/eaat5236.long
Kaelberer, M.M., Buchanan, K. L., Klein, M. E., Barth, B. B., Montoya, M. M., Shen, X., and Bohórquez, D. V. (2018), A gut-brain neural circuit for nutrient sensory transduction, Science,
Vol. 361, Issue 6408
We know that high-energy food (rich in refined sugars and fats) is addictive and can lead to an eating addiction and obesity. Addiction is a very severe disorder with chronic and relapsing components. People who suffer from addiction show compulsivity, persistence to seek the reward (food), and high motivation to overconsume in some cases.
To study eating addiction, we have developed a mouse model that shows persistence to eat, high motivation for palatable food and resistance to punishment in obtaining the food. We have tested these three characteristics in several genetically identical animals and selected two extreme groups: Mice that are vulnerable to eating addiction and mice that are resilient to it.
Mice have more than 25,000 genes in their genome, and they can be turned on or turned off (‘expressed’ or ‘not expressed’) depending on certain needs or circumstances.
We are now investigating the activation status of a certain type of genes, the ones encoding the so-called microRNAs that are very important as they are involved in regulating the function of other genes. An alteration in the status of one of these genes can have numerous downstream consequences.
In particular, our studies highlighted several microRNA genes that are involved in multiple brain functions, like synaptic plasticity (variation in the strength of nerve signaling) or neuronal development. Now we will test these alterations in patients to try to find convergent abnormalities.
All this work is being done at the Department of Genetics, Microbiology & Statistics (Universitat de Barcelona) and at the Neuropharmacology lab at the Universitat Pompeu Fabra, both based in Catalonia.
Co-authored by Bru Cormand, Judit Cabana, Noelia Fernàndez
Have you experienced drowsiness after eating a large meal? Has an important presentation made your stomach turn? Seeing a special someone made you feel butterflies in your stomach? If you have (and you most likely have), then you know how strong the connection between the brain and the gut is.
Scientists have found that many chronic metabolic diseases, type 2 diabetes, mood disorders and even neurological diseases, such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders (1). The importance of the association between the gut and the brain is gaining momentum with each new study. However, the way HOW the signaling between these two integral parts of the body exactly works hasn’t been clear until recently.
It was thought for a long time that the only “communication channel” between the gut and the brain was the passive release of hormones stimulated by the consumed nutrients. Hormones entered the bloodstream and slowly notified the brain that the stomach is full of nutrients and calories. This rather slow and indirect way of passing messages takes from minutes to hours.
But now, a recent study (2) has elegantly proven that the gut can message the brain in seconds! Using a rabies virus enhanced with green fluorescence, the scientists traced a signal as it traveled from the intestines to the brainstem of mice, crossing from cell to cell in under 100 milliseconds – faster than the blink of an eye.
The researchers had also noticed that the sensory cells lining the gut were quite similar to the receptors in the nose and on the tongue (3). The effects, however, differ. In the mouth, the taste of fatty acids triggers signals to increase hunger, whereas in the small intestine, fatty acids trigger signals of satiety. This means that the discovered “gut feeling” might be considered as a sixth sense, a way of how the brain is being signaled when the stomach is full.
This new knowledge will help to understand the mechanism of appetite, develop new and more effective appetite suppressants and help those struggling with weight and problematic eating patterns.
REFERENCES (1) Pellegrini C et al (2018) Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases? Acta Neuropathol 136:345. doi:10.1007/s00401-018-1856-5
(2) Kaelberer et al (2018) A gut-brain neural circuit for nutrient sensory transduction. Science 361(6408):eaat5236. doi:10.1126/science.aat5236
(3) Bohórquez and Liddle (2015) The gut connectome: making sense of what you eat. J Clin Invest 125(3):888–890. doi:10.1172/JCI81121
A hot topic these days, that one can hear more and more information about is the microbiota-gut-brain axis, the bidirectional interaction between the intestinal microbiota and the central nervous system nowadays, this has become a hot topic. We are becoming increasingly aware that gut microbiota play a significant role in modulating brain functions, behavior and brain development. Pre- and probiotics can influence the microbiota composition, so the question arises, can we have an impact on our mental health by controlling nutrition and using probiotics?
Burokas and colleagues aimed to investigate this possibility in their study (2017), where the goal was to test whether chronic prebiotic treatment in mice modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior.
In the first part of the study, the researchers fed mice with prebiotics for 10 weeks. They were administered the prebiotics fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), a combination of both, or water. FOS and GOS are soluble fibers that are associated with the stimulation of beneficial bacteria such as bifidobacterium and lactobacillus.
Behavioral testing started from the third week including
the open field test (anxiety – amount of exploratory behavior in a new place),
novel object test (memory and learning – exploration time of a novel object in a familiar context), and
forced swimming test (depression-like behavior – amount of activity in the cylinder filled water).
Meanwhile, plasma corticosterone, gut microbiota composition, and cecal short-chain fatty acids were measured. Taken together, the authors found that the prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic (anti-anxiety) effects. However, there were no major effects observed on cognition, nociception (response to pain stimulus), and sociability; with the exception of blunted aggressive behavior and more prosocial approaches.
In the second part, FOS+GOS or water-treated mice were exposed to chronic psychosocial stress. Behavior, immune, and microbiota parameters were assessed. Under stress, the microbiota composition of water-treated mice changed (decreased concentration of bifidobacterium and lactobacillus), which effect was reversed by treatment with prebiotics.
Furthermore, it was found that three weeks of chronic social stress significantly reduced social interaction, and increased stress indicators (basal corticosterone levels and stress-induced hyperthermia), whereas prebiotic administration protected from these effects.
After stimulation with a T-cell activator lectin (concanavalin A), the stressed, water-treated mice group presented increased levels of inflammatory cytokines (interleukin 6, tumor necrosis factor alpha), whereas in animals with prebiotics had these at normal levels.
Overall, these results suggest a beneficial role of prebiotic treatment in mice for stress-related behaviors and supporting the theory that modifying the intestinal microbiota via prebiotics represents a promising potential for supplement therapy in psychiatric disorders.
REFERENCES Burokas, A., Arboleya, S., Moloney, R. D., Peterson, V. L., Murphy, K., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017). Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice. Biological Psychiatry, 82(7), 472–487. https://doi.org/10.1016/j.biopsych.2016.12.031
Our purpose is to educate and inform you. To make this website more useful on your next visit, we use "cookies" which help us track your interests and activities. By continuing to browse this site you agree to our use of "cookies."