The Gut Microbiome and the Brain

[Jon_Tradicionali]

I have created this thread for the PWCFS I've noticed with scepticism or confusion towards hypothesis postulating intestinal bacteria as the psychophysiology of CFS.
The ways bacteria can affect the brain is outlined in the study below:

The Gut Microbiome and the Brain

The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.

http://online.liebertpub.com/doi/abs/10.1089/jmf.2014.7000

Something that took me by surprise was the microbiome's connection with the vagus nerve. This is something I'll be looking into further as its immensely interesting due to its connection with other theorists' hypothesis. Comments on this point are especially appreciated.

 

[cman89]

I can see that taking place though. the vagus nerve is the main "gut" nerve, and so the microbes could undesirable affect transmissions of messages from nerve endings to the brain.

 

[cigana]

Do you think of intestinal bacteria as being the root cause, or just part of the subsequent process once the root cause has been put into effect?

 

[Jon_Tradicionali]

Do you think of intestinal bacteria as being the root cause, or just part of the subsequent process once the root cause has been put into effect?

I think it's a subsequent process. All the possibilities go through my mind every single day. It's a part time job hehe.

The root cause candidates are many, how can we figure it out just by reading?

I can only think of Trial and error.

 

[cigana]

I think it's a subsequent process. All the possibilities go through my mind every single day. It's a part time job hehe.

The root cause candidates are many, how can we figure it out just by reading?

I can only think of Trial and error.

Part time job for a lot of us

I agree that it is very prevalent but IMO probably not the root cause. KDM told me that even when you replace all of a PWC's gut flora (by performing a fecal transplant), that although there are small improvements to begin with, those improvements are not maintained because the flora quickly modifies and reverts back to a disturbed state. In KDM's opinion this is because the underlying cause is immune dysfunction, and obviously it is principally the immune system that's keeping the microbiome in check.

Re the trial and error, I think we can bias it in our favour if we prioritise research into immune dysfunction. Because it seems to me that immune dysfunction is
(a) arguably present in every single PWC
(b) present in the entire spectrum of disorders to which MECFS belongs (Autism, Lyme, Gulf war illness)
(c) highly related to the treatments that have good success rates (Ampligen, rituximab, LDN).

Other apsects of the disease don't seem to fullfill all of those requirements so well.

 

[cfsStevew]

its really fascinating the role of gut bacteria and its ability to stimulate efferent nerves...its difficult to know which aspects are playing more or a role - but I suspect point 1 is a issue in a lot of cases...I got this impression from talking to several patients about their reactivity to food due to gut permeability and their immune system reacting, which improved as they recovered...

 

[MeSci]

Re the trial and error, I think we can bias it in our favour if we prioritise research into immune dysfunction. Because it seems to me that immune dysfunction is
(a) arguably present in every single PWC
(b) present in the entire spectrum of disorders to which MECFS belongs (Autism, Lyme, Gulf war illness)
(c) highly related to the treatments that have good success rates (Ampligen, rituximab, LDN).

Other apsects of the disease don't seem to fullfill all of those requirements so well.

Gut dysbiosis is also prevalent in autism - don't know about the other illnesses but worth checking out.

 

[jepps]

http://www.sciencedaily.com/releases/2015/01/150108125953.htm
Could gut microbes help treat brain disorders? Mounting research tightens their connection with the brain

The work of these three researchers raises the possibility that brain disorders, including anxiety, depression and autism, may be treated through the gut, which is a much easier target for drug delivery than the brain. But there is still much more research to be done to understand the gut-microbiome-brain connection, they said.

Mazmanian's lab is also exploring whether the microbiome plays a role in neurodegenerative diseases such as Alzheimer's and Parkinson's.

"There are flash bulbs going off in the dark, suggesting that very complex neurodegenerative disorders may be linked to the microbiome. But once again this is very speculative. These seminal findings, the flash bulbs, are only just beginning to illuminate our vision of the gut-microbiome-brain connection," said Mazmanian.

 

[jepps]

http://www.sciencedaily.com/releases/2014/11/141119142205.htm

Gut microbiota influences blood-brain barrier permeability

The team also showed that the increased 'leakiness' of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this 'leakiness' could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. The precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria.

 

[adreno]

I agree that it is very prevalent but IMO probably not the root cause. KDM told me that even when you replace all of a PWC's gut flora (by performing a fecal transplant), that although there are small improvements to begin with, those improvements are not maintained because the flora quickly modifies and reverts back to a disturbed state. In KDM's opinion this is because the underlying cause is immune dysfunction, and obviously it is principally the immune system that's keeping the microbiome in check.

Isn't it mainly the other way around? That microflora regulates the immune system.

That improvements don't last could be due to diet. For example, if not enough prebiotics are supplied in the diet, then the positive changes won't last, as the beneficial bacteria will be gone.

 

[jepps]

Isn't it mainly the other way around? That microflora regulates the immune system.

That improvements don't last could be due to diet. For example, if not enough prebiotics are supplied in the diet, then the positive changes won't last, as the beneficial bacteria will be gone.

Yes, and as the mucosa consists mainly of glucose, we must feed the mucosa to with glucose, that does not inflame the mucosa, but only heal it. This could be bone broth and healthy starches.

 

[MeSci]

Yes, and as the mucosa consists mainly of glucose, we must feed the mucosa to with glucose, that does not inflame the mucosa, but only heal it. This could be bone broth and healthy starches.

Mucosa consist mainly of glucose? Do you have a link for this? Why should it be fed with glucose?

 

[jepps]

http://perfecthealthdiet.com/category/disease/carbohydrate-deficiency/

Tears, saliva, and mucus of the sinuses, airways, and gastrointestinal tract are all comprised substantially of glycoproteins called mucins. Mucins are primarily composed of sugar; they typically have a number of large sugar chains bound to a protein backbone.

For instance, the main mucin of the gastrointestinal tract, MUC2, is composed of a dimerized protein – each protein weighing 600,000 Daltons individually, so 1.2 million Daltons for the pair – plus about 4 million Daltons of sugar, for a total mass of 5 million Daltons. In the mucus, these large molecules become cross-linked to form “enormous net-like covalent polymers.” (source)

 

[MeSci]

http://perfecthealthdiet.com/category/disease/carbohydrate-deficiency/

That page is about zero-carb diets. I don't think people here are generally on those, and many of us are actually much better on low-sugar/low-grain diets, with a good intake of veg and small amount of fruit. I am one of these.

I think there is a lot of difference between pure/free glucose and glycoproteins, which are widespread in the body. Binding and polymerisation can transform substances into completely different materials. For example, ethylene is a gas, whereas polyethylene is what we know as polythene. It's a polymer of ethylene.

 

[ljimbo423]

Although this is only anecdotal. I have noticed a substantial decrease in anxiety and depression since I started an aggressive gut protocol about 2-3 months ago. It's seems very clear to me that there is a definite gut microbiome- brain connection.

My energy is also way up and my clarity of mind is noticeably better. I have been taking DGL, aloe vera, glutamine, n-acetyl-glucosamine, zinc carnosine, and inulin.

I have also been on a low carb diet for about a year, as well as taking oil of oregano and berberine for dysbiosis. It feels like a lot of hard work is finally paying off! Jim

 

[cigana]

Isn't it mainly the other way around? That microflora regulates the immune system.

Sure gut flora regulates the immune system, but that doesn't mean immune dysfunction is always a result of gut flora. Take HIV for example.

 

[adreno]

Sure gut flora regulates the immune system, but that doesn't mean immune dysfunction is always a result of gut flora. Take HIV for example.

True. And I believe there are several causes for ME/CFS (i.e., subsets) as well.

 

[MeSci]

Although this is only anecdotal. I have noticed a substantial decrease in anxiety and depression since I started an aggressive gut protocol about 2-3 months ago. It's seems very clear to me that there is a definite gut microbiome- brain connection.

My energy is also way up and my clarity of mind is noticeably better. I have been taking DGL, aloe vera, glutamine, n-acetyl-glucosamine, zinc carnosine, and inulin.

I have also been on a low carb diet for about a year, as well as taking oil of oregano and berberine for dysbiosis. It feels like a lot of hard work is finally paying off! Jim

What's DGL?

Energy is the one thing that I haven't been able to improve, but my fat loss and muscle gain has given me more strength, except when I have that frustrating weakness as part of PEM and just have to wait for it to pass. I wonder whether it's a specific component of your supplement regime that has increased your energy.

I tend to think that my energy won't increase until I have fixed whatever is impairing the use of oxygen by mitochondria.

 

[Jon_Tradicionali]

Study linking altered microbiome as a consequence of depression induced HPA deregulation.

"Conclusions & Inferences
The induction of chronic depression alters motor activity and the microbial profile in the colon likely via activation of the HPA. These findings provide a basis for linking the behavioral and gastrointestinal manifestations of IBS."

http://onlinelibrary.wiley.com/doi/...ionid=AE0EC25D7E65A1269D3E17C37ED7BA68.f04t01

 

[MeSci]

Study linking altered microbiome as a consequence of depression induced HPA deregulation.

"Conclusions & Inferences
The induction of chronic depression alters motor activity and the microbial profile in the colon likely via activation of the HPA. These findings provide a basis for linking the behavioral and gastrointestinal manifestations of IBS."

http://onlinelibrary.wiley.com/doi/...ionid=AE0EC25D7E65A1269D3E17C37ED7BA68.f04t01

That is about an animal model of "depression-like behavior in mice" who "demonstrated chronic depression- and anxiety-like behaviors." The 'model' was created via bilateral olfactory bulbectomy. The olfactory bulb is described here.

Knowing what I do about the irrelevance of animal 'models', this one seems particularly far-fetched.