Tag Archives: neurotransmitter

From the Zombie Files: Ampulex dementor, obesity, and brains. What’s the connection?

One of the central concepts of The Symbiont Factor is that there are times in nature that organisms can take control of another organism’s nervous system, rendering it “a zombie”. This isn’t a zombie in the Hollywood sense, just a host organism that no longer is singularly in control of itself due to the effects of other organisms that “hijack” its nervous system.

In this case, a new organism has been discovered, a fearsome looking wasp in Thailand. This wasp hunts cockroaches, and injects a neurotoxin into them. This makes the cockroach lose active control of its legs so that it cannot escape, and the wasp can eat it slowly while it is still alive. Nature really has some gruesome stories, doesn’t it?

In our own bodies, we have a colony of trillions of bacteria. The late Prof Eshel Ben-Jacob performed experiments and wrote articles documenting how large bacterial colonies were able to act with logic, more as multicellular¬† organisms. Like multicellular organisms, their activities have a goal: survival. In the case of our microbiome, it is beginning to appear that their ability to alter our nervous system function and our brain activity is not randomized. There is a bi-directional influence at work: as an example, the bacteria that thrive on a fatty diet make us crave fatty foods, and those that thrive on sweets make us crave sweets. If we eat the fatty foods or sweets, it of course preferentially benefits the organisms that thrive on it. This is why there seems to be a “tipping point” in gaining weight such that our energy level drops and our appetite changes, facilitating weight gain. The actual organisms that help us lose weight and stay lean have been identified (Akkermansia mucinophilia is one example), as have those that make us gain weight. Their effect is significant enough that they have been called “obesogens”. It isn’t a single organism but a pattern of demographic shift-more of these/less of those-that results in weight gain or loss.

The changes to brain function, sensory sensitivity (ie what smells tasty to you), mood and behavior shift (a stress microbiome!) make us just a little like a zombie too in some cases. Certainly our behavior and our function is the result of the activity of trillions of symbiont organisms as well as our own decision-making. In effect “we” are composed of many organisms!

Relevant links (many are in the bibliography of The Symbiont Factor: http://tinyurl.com/p3b9o9d):

http://www.treehugger.com/natural-sciences/terrifying-new-dementor-wasp-species-named-evil-spirits-harry-potter.html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995701/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380304/

http://www.ncbi.nlm.nih.gov/pubmed/26047662

http://www.ncbi.nlm.nih.gov/pubmed/24430437

http://www.ncbi.nlm.nih.gov/pubmed/25968641

http://www.ncbi.nlm.nih.gov/pubmed/25401094

http://iopscience.iop.org/1478-3975/11/5/053009/pdf/1478-3975_11_5_053009.pdf

Top Ten Reasons that the Microbiome Matters:

As I’ve been busily shutting down one clinic to open another, I’ve logged many miles of driving-which has given me time to think about the microbiome as well (really!) Why would the microbiome matter? Here’s my top ten list, as a microbial tribute to David Letterman’s years of late night entertainment:

10. It guides the development of the human brain early in life

9. It influences our moods, desires, behaviors throughout life

8. The microbiome helps develop and guide the immune system

7. Our HPA axis (Hypothalamus, Pituitary, Adrenal) is heavily influenced by the microbiome early in life, which determines our response to stress…

6. The human microbiome can alter the way our brain’s receptors respond to neurotransmitters, changing it significantly.

5. If our microbiome becomes imbalanced (dysbiosis) it can cause inflammation, brain dysfunction, immune dysfunction, changes in appetite, obesity, depression…and many other problems

4. The microbiome is extremely vulnerable to antibiotics from doctors or in (non-organic) meat that we consume. Once species die off and diversity is lost, dysbiosis results

3. Glyphosate, the most commonly used herbicide on the planet, is toxic to gut bacteria (and also mitochondria that supply our cells with energy)

2. Gut bacteria are true symbiont organisms; they aren’t “hitching a ride” but are indeed a part of us that functions more like a vital organ. They are part of why we are alive; death of the microbiome causes disease and aging!

1. The only source of energy that fuels this planet is sunlight, and only plants (true plants, algae, cyanobacteria) can process sunlight into biomass. After that, only bacteria can digest plants to produce energy…so everything from termites to cattle including us can only digest plants because of our gut bacteria. No gut bacteria? very very bad news!

So, get out your copy of my book, The Symbiont Factor, and read up on the microbiome, okay? Oh, you don’t have it yet? Be good to your bugs and buy a copy then!

http://tinyurl.com/kh4g8nm

New Video about Gut Bacteria, Probiotics, Brain!

Well, I had some time between patients yesterday, and, having watched just enough cute cat videos and ignored enough political/religious arguments on Facebook-I decided to do something useful and create a video. This short video should help to make sense out of probiotics, gut bacteria, and how they affect us mentally/emotionally. Check out my new video about gut bacteria and probiotics! http://tinyurl.com/oyvvwt2

Brain/Gut/Symbiont function seen as Rock-Paper-Scissors. Or, why you crave french fries and can’t lose weight!

Rock-Paper-Scissors is an ancient Chinese game, often used in modern society instead of flipping a coin. The concept is that each player, on que, puts his hand out flat (paper) or in a Vulcan-like “V” (scissors), or a fist (rock). Each beats the next: scissors cut paper, paper covers rock, rock crushes scissors. It occurred to me that this is quite similar to how symbiont bacteria, the brain, and the gut interact! I’ll explain the short version, then explain more about it. The symbiont bacteria influence the brain, the brain controls the gut (intestines) and the intestines provide a habitat/home for the symbionts. Imbalances in any of these three can therefore affect the next item in the functional triad: Imbalanced symbionts (dysbiosis) can alter brain neurotransmitters, mood, pain perception, cognition, sense of smell, appetite for specific foods and behaviors. Alterations of this type in the brain result in, amongst other things, cravings for specific foods that would benefit the dominant genera of gut symbionts combined with discomfort/lack of satisfaction if those cravings are not met. Here’s a very common example: one pattern of gut bacteria imbalance results in what researchers have termed “obesogens”, dominant populations of bacteria that cause obesity. How do they do that? In part, by altering appetite, olfaction (sense of smell), and frontal lobe processing to create food cravings and increased appetite, specifically for foods that benefit the bacteria-in this case greasy/sweet and fattening foods. Along with this dietary predilection there are behavioral changes that result in lower energy levels, less ambition, and a preference for a sedentary lifestyle that does not burn calories. These behavioral changes have been evaluated in laboratory animals by taking a sterile (no bacteria) animal of normal weight and transferring the gut bacteria from an obese animal to it. The result is a behavioral and appetite/food preference change similar to that which the obese animal had! In other words, the behavior goes with the bacteria. So, what do you do if you want more energy, want to lose weight and get more done? try to work on improving your gut bacteria! Pre and probiotics as well as exercise and dietary changes provide some ways to accomplish this.

Here’s another example of this triad at work: a stressful lifestyle affects the brain’s control of the gut, by altering autonomic function and causing sympathetic (fight-or-flight) dominance. This suppresses the gut digestive process and causes more putrefaction, altering the balance of symbiont populations. Damage to the mucous lining of the intestines and sloughing off of microvilli that normally improve nutrient absorption and house gut bacteria reduce beneficial symbiont populations. What’s the result? As above, weight gain and a cascade of health problems.

The changes to the symbiont bacteria can alter brain function sufficiently to cause depression, anxiety, irritable bowel syndrome, autism, ASD, and altered brain function, personality and pain perception. These are deeply fundamental changes to “who we are” and are representative of the level of influence that the gut symbionts have on our function.

The “rock paper scissors” explanation should also illustrate why researching specific cause-effect/double blind mechanisms are so challenging in this system, as unless the third variable is controlled for (and it often cannot be) the results may be more inconsistent that they would be in a simpler system.

This functional trifecta is one of the reasons why in my clinic, if I recommend an exercise and a dietary change and the patient immediately becomes resistant and “whiney” about making the changes, I record the resistance as a symptom and try to show the patient how their feelings are in fact potential confirmation of this functional system at work!

References:

Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP.

Distrutti E, O’Reilly JA, McDonald C, Cipriani S, Renga B, Lynch MA, Fiorucci S.

PLoS One. 2014 Sep 9;9(9):e106503. doi: 10.1371/journal.pone.0106503. eCollection 2014.

PMID:
25202975
[PubMed – in process]

Free Article

2.

Gut microbiota, the pharmabiotics they produce and host health.

Patterson E, Cryan JF, Fitzgerald GF, Ross RP, Dinan TG, Stanton C.

Proc Nutr Soc. 2014 Sep 8:1-13. [Epub ahead of print]

PMID:
25196939
[PubMed – as supplied by publisher]
3.

Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

Smith CJ, Emge JR, Berzins K, Lung L, Khamishon R, Shah P, Rodrigues DM, Sousa AJ, Reardon C, Sherman PM, Barrett KE, Gareau MG.

Am J Physiol Gastrointest Liver Physiol. 2014 Sep 4. pii: ajpgi.00238.2014. [Epub ahead of print]

PMID:
25190473
[PubMed – as supplied by publisher]
4.

Obese-type Gut Microbiota Induce Neurobehavioral Changes in the Absence of Obesity.

Bruce-Keller AJ, Salbaum JM, Luo M, Blanchard E 4th, Taylor CM, Welsh DA, Berthoud HR.

Biol Psychiatry. 2014 Jul 18. pii: S0006-3223(14)00520-4. doi: 10.1016/j.biopsych.2014.07.012. [Epub ahead of print]

PMID:
25173628
[PubMed – as supplied by publisher]
5.

Enteric Bacterial Metabolites Propionic and Butyric Acid Modulate Gene Expression, Including CREB-Dependent Catecholaminergic Neurotransmission, in PC12 Cells – Possible Relevance to Autism Spectrum Disorders.

Nankova BB, Agarwal R, MacFabe DF, La Gamma EF.

PLoS One. 2014 Aug 29;9(8):e103740. doi: 10.1371/journal.pone.0103740. eCollection 2014.

PMID:
25170769
[PubMed – in process]

Free PMC Article

6.

Altered brain-gut axis in autism: Comorbidity or causative mechanisms?

Mayer EA, Padua D, Tillisch K.

Bioessays. 2014 Oct;36(10):933-9. doi: 10.1002/bies.201400075. Epub 2014 Aug 22.

PMID:
25145752
[PubMed – in process]
7.

Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms.

Alcock J, Maley CC, Aktipis CA.

Bioessays. 2014 Oct;36(10):940-9. doi: 10.1002/bies.201400071. Epub 2014 Aug 8.

PMID:
25103109
[PubMed – in process]
8.

Microbiota-host interactions in irritable bowel syndrome: epithelial barrier, immune regulation and brain-gut interactions.

Hyland NP, Quigley EM, Brint E.

World J Gastroenterol. 2014 Jul 21;20(27):8859-66. doi: 10.3748/wjg.v20.i27.8859.

PMID:
25083059
[PubMed – in process]

Free PMC Article

9.

Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

O’Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF.

Behav Brain Res. 2014 Jul 29. pii: S0166-4328(14)00476-8. doi: 10.1016/j.bbr.2014.07.027. [Epub ahead of print]

PMID:
25078296
[PubMed – as supplied by publisher]
10.

Digesting the emerging role for the gut microbiome in central nervous system demyelination.

Joscelyn J, Kasper LH.

Mult Scler. 2014 Jul 28. pii: 1352458514541579. [Epub ahead of print] Review.

PMID:
25070675
[PubMed – as supplied by publisher]
11.

The impact of microbiota on brain and behavior: mechanisms & therapeutic potential.

Borre YE, Moloney RD, Clarke G, Dinan TG, Cryan JF.

Adv Exp Med Biol. 2014;817:373-403. doi: 10.1007/978-1-4939-0897-4_17.

PMID:
24997043
[PubMed – in process]
12.

Microbiota-gut-brain axis and cognitive function.

Gareau MG.

Adv Exp Med Biol. 2014;817:357-71. doi: 10.1007/978-1-4939-0897-4_16.

PMID:
24997042
[PubMed – in process]

Autism, ASD, the Brain and the Microbiome

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Autism is a rapidly growing problem, affecting 1 in 68 people today. It affects some people more than others, hence the use of the term “autism spectrum.” Autism and ASD have a “cousin” called Asperger’s syndrome. All of these conditions have several features in common, resulting in problems with social situations, communication, perseveration on thoughts or tasks, issues with expressive or receptive communication verbally or with body language, anxiety or becoming overstimulated/overwhelmed and sometimes self-harming. These are viewed as developmental neurologic problems with some genetic/inherited component. It has been found that the human microbiome plays a critical role in assisting the developing brain. Yes, that’s right, no typographic error!-symbiotic bacteria help build the human brain. If they are not present in sufficient numbers and correct species, functional imbalances can result-problems such as autism. The symbiotic bacteria not only help build the brain, but also to run it properly and keep it tuned up for optimum function. The details, pulled from several research studies, are quite specific. The study of the microbiome has progressed so exponentially in the last few years that some of these conclusions can seem very surprising at times. During the first five years of life, the human brain is a firestorm of remodeling activity, with neurons being pared off if not needed and others branching out to form new synapses. This is the time of the most dramatic plasticity, where the brain learns how to control the body and form intelligence, personality and emotional response. Early damage to the resident microbiome, that population of a trillion-member bacterial colony that runs things from behind the scenes, results in a loss of proper brain development. Some of this damage also results from by-products produced by the non-beneficial bacteria that take up residence in the gut if beneficial bacteria are not present (Propionate, for example, that is in much higher concentrations in autistic individuals and has been implicated in autistic dysfunctions at higher levels). Damage is also caused by loss of immune system control (one of the other systems partly governed by bacteria). Without the symbiont bacteria monitoring and programming the immune system, it can cause an inflammatory response that damages the brain, or even an autoimmune response that targets the brain. This immune dysfunction and resultant neuroinflammation is thought to be one of the causative mechanisms behind autism. Another factor causing autism/asd is a problem with forming serotonin (normally the pleasant/feelgood/happy reward neurotransmitter). Serotonin is made from tryptophan, through conversion to 5-HTP and DHEA-s. In an autistic person, the conversion takes a “left turn at Albequerque” and produces cortisol. This is a bad outcome, as cortisol is toxic to brain cells in this scenario and contributes to the damage from neuroinflammation. Part of why the conversion fails turns out to be microbiome related, as research shows that an absent microbiome causes accumulation of tryptophan and 5-htp and lowered levels of serotonin. Another way the microbiome is implicated is the neurotransmitter GABA. This neurotransmitter is inhibitory and is used in the brain to block out/filter stimulations. When it fails, a normal environment is overwhelmingly stimulating to an ASD sufferer, resulting in stress/anxiety or a behavior such as self-harm (cutting, for example) that helps to block out some of the overstimulation with a simpler stimulation such as pain. In this mechanism, pain brings relief! The microbiome modulates GABA receptor activation in a site-specific manner, such that GABA receptors work more in some parts of the brain and less in others. This permits a type of partial gating of activity through control of receptor activation! The net result is reduced stress and anxiety-two of the very things that autism sufferers experience the most when placed in social situations. Researchers have found that genetics play a role in autism, with some children having a genetic predisposition to the condition. The catch is that genetics are variable; gene sequences can be activated or suppressed through a process called epigenetics. The tremendous genetic resources of the microbiome (estimates are from 100-1000 times the number of genes as there are human genes) indicate that the microbiome is an epigenetic entity itself. Certainly the microbiome plays a role in human epigenetics, with the ability to “turn on” certain gene sequences and cause their expression. It is probable that not every child who is genetically prone to autism will actually express the disease due to this process. If the microbiome is imbalanced and damaged, the genes can more easily be expressed. The mechanisms described show that an imbalanced microbiome early in life is a major risk factor for autism, and furthermore that microbiome imbalances later in life perpetuate the symptoms of the condition. Our modern society has inadvertently created a multi-front assault on the human microbiome through the use of antibiotics, herbicides such as RoundUp, pollution, Caesarian childbirth, interrupted or absent breastfeeding, chlorinated drinking water, sugar-laden foods, and a myriad of harmful chemicals in our food. The demise of the microbiome opens a Pandora’s box of disease possibilities as the body’s immune, endocrine, and digestive systems function in an uncoordinated and destructive manner.
References:
http://www.ncbi.nlm.nih.gov/pubmed/24669209
http://www.ncbi.nlm.nih.gov/pubmed/21876150
http://www.ncbi.nlm.nih.gov/pubmed/24286462
http://www.ncbi.nlm.nih.gov/pubmed/24366270
http://www.ncbi.nlm.nih.gov/pubmed/24416709
http://www.ncbi.nlm.nih.gov/pubmed/24466331
http://www.ncbi.nlm.nih.gov/pubmed/24481190